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Mold Toxins Harm Humans and Other Mammals

James Schaller Appeals for Physicians to Read About Water Intrusion Illnesses

A "Best Doctor," "Peoples Choice Award MD," and "Top Doctor" according to physicians and patients, appeals for more mold and bacteria attention in sick patients working or living in sick buildings.

201. Microb Ecol. 2011 Jul;62(1):58-68. Epub 2011 May 7.

Can metal nanoparticles be a threat to microbial decomposers of plant litter in streams?

Pradhan A, Seena S, Pascoal C, Cássio F.

Centre of Molecular and Environmental Biology (CBMA), Department of Biology, University of Minho, Campus of Gualtar, 4710-057, Braga, Portugal.

The extensive use of nanometal-based products increases the chance of their release into aquatic environments, raising the question whether they can pose a risk to aquatic biota and the associated ecological processes. Aquatic microbes, namely fungi and bacteria, play a key role in forested streams by decomposing plant litter from terrestrial vegetation. Here, we investigated the effects of nanocopper oxide and nanosilver on leaf litter decomposition by aquatic microbes, and the results were compared with the impacts of their ionic precursors. Alder leaves were immersed in a stream of Northwest Portugal to allow microbial colonization before being exposed in microcosms to increased nominal concentrations of nanometals (CuO, 100, 200 and 500 ppm; Ag, 100 and 300 ppm) and ionic metals (Cu(2+) in CuCl(2), 10, 20 and 30 ppm; Ag(+) in AgNO(3), 5 and 20 ppm) for 21 days. Results showed that rates of leaf decomposition decreased with exposure to nano- and ionic metals. Nano- and ionic metals inhibited bacterial biomass (from 68.6% to 96.5% of control) more than fungal biomass (from 28.5% to 82.9% of control). The exposure to increased concentrations of nano- and ionic metals decreased fungal sporulation rates from 91.0% to 99.4%. These effects were accompanied by shifts in the structure of fungal and bacterial communities based on DNA fingerprints and fungal spore morphology. The impacts of metal nanoparticles on leaf decomposition by aquatic microbes were less pronounced compared to their ionic forms, despite metal ions were applied at one order of magnitude lower concentrations. Overall, results indicate that the increased release of nanometals to the environment may affect aquatic microbial communities with impacts on organic matter decomposition in streams.

PMID: 21553058 [PubMed - indexed for MEDLINE]

202. Mycorrhiza. 2011 Jul;21(5):443-9. Epub 2011 May 7.

The sterol biosynthesis inhibitor molecule fenhexamid impacts the vegetative compatibility of Glomus clarum.

Cardenas-Flores A, Cranenbrouck S, Draye X, Guillet A, Govaerts B, Declerck S.

Earth and Life Institute, Mycology, Université Catholique de Louvain, Place croix du Sud 3, 1348, Louvain-la-Neuve, Belgium.

The vegetative compatibility of the arbuscular mycorrhizal fungus (AMF) Glomus clarum MUCL 46238 was evaluated after continuous exposure to fenhexamid, a sterol biosynthesis inhibitor (SBI). Three lineages of this AMF were cultured in vitro for five generations in association with Ri T-DNA transformed carrot roots in the presence of 0, 5 or 10 mg l(-1) of fenhexamid. Whatever the AMF generation, fenhexamid at 5 and 10 mg l(-1) had no significant impact on the number of spores produced. However, vegetative compatibility tests (VCT) conducted with spores from the three lineages, in the presence of 10 mg l(-1) of fenhexamid, impacted the anastomosis process. At this concentration, the morphology of the germ tubes was modified. In addition, nitrotetrazolium-trypan blue staining revealed that 10 mg l(-l) of fenhexamid significantly reduced the probability of fusion between the germ tubes regardless of the culture conditions (i.e. absence or presence of fenhexamid) preceding the VCT. Our results demonstrated that spore production was not affected by fenhexamid, while anastomosis between germ tubes was decreased. This suggested that high concentrations, accumulation or repeated application of this SBI fungicide may impact the community structure of AMF in soil.

PMID: 21553021 [PubMed - indexed for MEDLINE]

203. PLoS Genet. 2011 Apr;7(4):e1002059. Epub 2011 Apr 28.

Alkylation base damage is converted into repairable double-strand breaks and complex intermediates in G2 cells lacking AP endonuclease.

Ma W, Westmoreland JW, Gordenin DA, Resnick MA.

Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, United States of America.

DNA double-strand breaks (DSBs) are potent sources of genome instability. While there is considerable genetic and molecular information about the disposition of direct DSBs and breaks that arise during replication, relatively little is known about DSBs derived during processing of single-strand lesions, especially for the case of single-strand breaks (SSBs) with 3'-blocked termini generated in vivo. Using our recently developed assay for detecting end-processing at random DSBs in budding yeast, we show that single-strand lesions produced by the alkylating agent methyl methanesulfonate (MMS) can generate DSBs in G2-arrested cells, i.e., S-phase independent. These derived DSBs were observed in apn1/2 endonuclease mutants and resulted from aborted base excision repair leading to 3' blocked single-strand breaks following the creation of abasic (AP) sites. DSB formation was reduced by additional mutations that affect processing of AP sites including ntg1, ntg2, and, unexpectedly, ogg1, or by a lack of AP sites due to deletion of the MAG1 glycosylase gene. Similar to direct DSBs, the derived DSBs were subject to MRX (Mre11, Rad50, Xrs2)-determined resection and relied upon the recombinational repair genes RAD51, RAD52, as well as on the MCD1 cohesin gene, for repair. In addition, we identified a novel DNA intermediate, detected as slow-moving chromosomal DNA (SMD) in pulsed field electrophoresis gels shortly after MMS exposure in apn1/2 cells. The SMD requires nicked AP sites, but is independent of resection/recombination processes, suggesting that it is a novel structure generated during processing of 3'-blocked SSBs. Collectively, this study provides new insights into the potential consequences of alkylation base damage in vivo, including creation of novel structures as well as generation and repair of DSBs in nonreplicating cells.

PMCID: PMC3084215 PMID: 21552545 [PubMed - indexed for MEDLINE]

204. J Anim Sci. 2011 Oct;89(10):3300-9. Epub 2011 May 6.

Concentrations of airborne endotoxin and microorganisms at a 10,000-cow open-freestall dairy.

Dungan RS, Leytem AB, Bjorneberg DL.

Northwest Irrigation and Soils Research Laboratory, ARS, USDA, Kimberly, ID 83341, USA. robert.dungan@ars.usda.gov

Confined animal production systems produce increased bioaerosol concentrations, which are a potential respiratory health risk to individuals on site and downwind. In this longitudinal study, airborne endotoxin and microorganisms were collected during the spring, summer, and fall at a large, open-freestall dairy in southern Idaho. Compared with the background ambient atmosphere, both endotoxin and culturable heterotrophic bacteria concentrations were up to several-hundred-fold greater 50 m downwind from the facility, then decreased to near background concentrations at 200 m. However, downwind fungi concentrations were not increased above background concentrations. At 50 m downwind, the average inhalable endotoxin concentration ranged from 5 to 4,243 endotoxin units per m⁻³, whereas bacteria concentrations ranged from 10² to 10⁴ cfu per m⁻³ of air. Although the bioaerosol concentrations did not follow a seasonal trend, they did significantly correlate with meteorological factors. Increasing temperature was found to be positively correlated with increasing bacteria (r = 0.15, P < 0.05), fungi (r = 0.14, P < 0.05), and inhalable endotoxin (r = 0.32, P < 0.001) concentrations, whereas an inverse relationship occurred between the concentration and solar radiation. The airborne concentrations at 50 m were also found to be greatest at night, which can likely be attributed to changes in animal activity and wind speed and reduced exposure of the airborne microorganisms to UV radiation.

PMID: 21551347 [PubMed - in process]

205. Mol Biol Cell. 2011 Jul 1;22(13):2384-95. Epub 2011 May 5.

Exposed hydrophobicity is a key determinant of nuclear quality control degradation.

Fredrickson EK, Rosenbaum JC, Locke MN, Milac TI, Gardner RG.

Department of Pharmacology, University of Washington, Seattle, WA 98195, USA.

Protein quality control (PQC) degradation protects the cell by preventing the toxic accumulation of misfolded proteins. In eukaryotes, PQC degradation is primarily achieved by ubiquitin ligases that attach ubiquitin to misfolded proteins for proteasome degradation. To function effectively, PQC ubiquitin ligases must distinguish misfolded proteins from their normal counterparts by recognizing an attribute of structural abnormality commonly shared among misfolded proteins. However, the nature of the structurally abnormal feature recognized by most PQC ubiquitin ligases is unknown. Here we demonstrate that the yeast nuclear PQC ubiquitin ligase San1 recognizes exposed hydrophobicity in its substrates. San1 recognition is triggered by exposure of as few as five contiguous hydrophobic residues, which defines the minimum window of hydrophobicity required for San1 targeting. We also find that the exposed hydrophobicity recognized by San1 can cause aggregation and cellular toxicity, underscoring the fundamental protective role for San1-mediated PQC degradation of misfolded nuclear proteins.

PMCID: PMC3128539 PMID: 21551067 [PubMed - indexed for MEDLINE]

206. Chemosphere. 2011 Sep;84(10):1476-83. Epub 2011 May 8.

Levels of chemical and microbiological pollutants in the vicinity of a waste incineration plant and human health risks: temporal trends.

Vilavert L, Nadal M, Figueras MJ, Kumar V, Domingo JL.

Laboratory of Toxicology and Environmental Health, School of Medicine, IISPV, Universitat Rovira i Virgili, Sant Llorenç 21, 43201 Reus, Catalonia, Spain.

In 2007, a program was initiated to monitor air levels of volatile organic compounds (VOCs) and bioaerosols in the vicinity of a municipal solid waste incinerator (MSWI) (Tarragona, Catalonia, Spain). To investigate the temporal trends of chemical and microbiological pollutants, four 6-monthly campaigns were performed. Air samples were collected at different distances and directions from the facility, as well as in reference sites. In general terms, the concentrations of microbiological agents were very similar to those found in urban zones worldwide. The seasonal evaluation of the results showed higher levels of gram-negative bacteria in winter, contrasting with the increase of the airborne amount of total bacteria in summer. On the other hand, the concentrations of VOCs (mean range: 7.6-18.2 μg m(-3)) were typical of suburban zones. The current exposure to those compounds should not mean additional health risks for the population living nearby.

PMID: 21550630 [PubMed - indexed for MEDLINE]

207. J Asthma. 2011 Jun;48(5):464-9. Epub 2011 May 9.

Environmental risk factors in the first year of life and childhood asthma in the Central South of Chile.

Boneberger A, Haider D, Baer J, Kausel L, Von Kries R, Kabesch M, Radon K, Calvo M.

Unit for Occupational and Environmental Epidemiology, Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, University Hospital of Munich, Munich, Germany.

BACKGROUND: Childhood asthma has a high prevalence in South America--a region of the world currently undergoing a thorough modernization and transition process. Asthma in South America is mainly associated with poor urban environment, which actually may challenge the role of the hygiene hypothesis. We systematically assessed the impact of environmental factors in the first year of life on asthma.
METHODS: A case-control study including 188 asthmatics and 294 hospital-based controls aged 6-15 years was carried out in the Central South of Chile. Parents of study participants completed a computer-assisted interview on environmental factors (such as birth order, day-care attendance, pneumonia infection, regular animal and furry pet contact, and environmental tobacco smoke exposure) in the first year of life and potential confounders. Atopy was assessed using skin prick tests. Multivariate logistic regression models were calculated to assess the association between exposures and asthma, adjusting for potential confounders.
RESULTS: Day-care attendance (OR = 0.31; 95% CI: 0.10, 0.94) and regular farm animal contact (OR = 0.38; 95% CI: 0.17, 0.85) were inversely related to childhood asthma in the logistic regression models. Pneumonia infection (OR = 2.24; 95% CI: 1.21, 4.16) and mold or dampness in the home (OR = 1.87; 95% CI: 1.18, 2.97) in the first year of life were positively associated with asthma.
CONCLUSION: Our results suggest that the hygiene hypothesis is also applicable in the Chilean setting, a South American country in epidemiological transition.

PMID: 21548831 [PubMed - indexed for MEDLINE]

208. BMC Plant Biol. 2011 May 5;11:75.

Arbuscular mycorrhizal symbiosis elicits shoot proteome changes that are modified during cadmium stress alleviation in Medicago truncatula.

Aloui A, Recorbet G, Robert F, Schoefs B, Bertrand M, Henry C, Gianinazzi-Pearson V, Dumas-Gaudot E, Aschi-Smiti S.

UMR INRA 1088/CNRS 5184/UB, Plante-Microbe-Environnement, INRA-CMSE, BP 86510, 21065 Dijon Cedex, France.

BACKGROUND: Arbuscular mycorrhizal (AM) fungi, which engage a mutualistic symbiosis with the roots of most plant species, have received much attention for their ability to alleviate heavy metal stress in plants, including cadmium (Cd). While the molecular bases of Cd tolerance displayed by mycorrhizal plants have been extensively analysed in roots, very little is known regarding the mechanisms by which legume aboveground organs can escape metal toxicity upon AM symbiosis. As a model system to address this question, we used Glomus irregulare-colonised Medicago truncatula plants, which were previously shown to accumulate and tolerate heavy metal in their shoots when grown in a substrate spiked with 2 mg Cd kg(-1).
RESULTS: The measurement of three indicators for metal phytoextraction showed that shoots of mycorrhizal M. truncatula plants have a capacity for extracting Cd that is not related to an increase in root-to-shoot translocation rate, but to a high level of allocation plasticity. When analysing the photosynthetic performance in metal-treated mycorrhizal plants relative to those only Cd-supplied, it turned out that the presence of G. irregulare partially alleviated the negative effects of Cd on photosynthesis. To test the mechanisms by which shoots of Cd-treated mycorrhizal plants avoid metal toxicity, we performed a 2-DE/MALDI/TOF-based comparative proteomic analysis of the M. truncatula shoot responses upon mycorrhization and Cd exposure. Whereas the metal-responsive shoot proteins currently identified in non-mycorrhizal M. truncatula indicated that Cd impaired CO2 assimilation, the mycorrhiza-responsive shoot proteome was characterised by an increase in photosynthesis-related proteins coupled to a reduction in glugoneogenesis/glycolysis and antioxidant processes. By contrast, Cd was found to trigger the opposite response coupled the up-accumulation of molecular chaperones in shoot of mycorrhizal plants relative to those metal-free.
CONCLUSION: Besides drawing a first picture of shoot proteome modifications upon AM symbiosis and/or heavy metal stress in legume plants, the current work argues for allocation plasticity as the main driving force for Cd extraction in aboveground tissues of M. truncatula upon mycorrhization. Additionally, according to the retrieved proteomic data, we propose that shoots of mycorrhizal legume plants escape Cd toxicity through a metabolic shift implying the glycolysis-mediated mobilization of defence mechanisms at the expense of the photosynthesis-dependent symbiotic sucrose sink.

PMCID: PMC3112074 PMID: 21545723 [PubMed - indexed for MEDLINE]

209. Virulence. 2011 May-Jun;2(3):200-7. Epub 2011 May 1.

Aspergillus terreus accessory conidia are multinucleated, hyperpolarizing structures that display differential dectin staining and can induce heightened inflammatory responses in a pulmonary model of aspergillosis.

Deak E, Nelson M, Hernández-Rodríguez Y, Gade L, Baddley J, Momany M, Steele C, Balajee SA.

Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, GA, USA.

In addition to phialidic conidia (PC), A. terreus produces accessory conidia (AC) both in vitro and in vivo. AC are distinct from PC in cell surface architecture, with the AC surfaces displaying more β-glucan, a molecule that can be a trigger for the induction of inflammatory responses. The present study follows β-glucan cell surface presentation throughout the course of germination of both types of conidia, and analyzes the differential capacity of AC and PC to elicit immune responses. Results show that AC display early, increased dectin-1 labeling on their cell surfaces compared to PC, and this differential dectin-1 labeling is sustained on the cell surface from the time of breaking dormancy through early germ tube emergence. Mouse alveolar macrophages showed a stronger inflammatory cytokine/chemokine response when challenged with AC than with PC in both ex vivo and in vivo experiments, correlating with the greater exposure of β-glucan exhibited by AC. Further, histopathologic staining of the lungs from mice challenged with AC demonstrated heightened cell recruitment and increased inflammatory response compared to the lungs of mice challenged with PC. Our study also demonstrates that AC are multinucleate structures with the ability to germinate rapidly, polarizing in multiple directions and producing several hyphal extensions. We present evidence that A. terreus AC are phenotypically distinct from PC and can be potent activators of the innate immune mechanism thus possibly playing a role in this organism's pathogenesis.

PMID: 21543882 [PubMed - indexed for MEDLINE]

210. Antimicrob Agents Chemother. 2011 Jul;55(7):3598-602. Epub 2011 May 2.

Five-minute exposure to caspofungin results in prolonged postantifungal effects and eliminates the paradoxical growth of Candida albicans.

Shields RK, Nguyen MH, Press EG, Clancy CJ.

Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

We studied the impact of brief caspofungin exposures on postantifungal effects (PAFEs) and paradoxical effects for five Candida albicans isolates. In time-kill studies, caspofungin at 4× and 16× the MIC resulted in significant killing of all isolates. Caspofungin at 8 μg/ml resulted in lower levels of killing, and paradoxical effects were evident with 4 isolates. Caspofungin exposures of 5 to 60 min caused prolonged, concentration-dependent killing that approached or exceeded the results seen with time-kill experiments and eliminated paradoxical growth.

PMCID: PMC3122450 PMID: 21537017 [PubMed - indexed for MEDLINE]

211. J Food Sci. 2010 Sep;75(7):T123-5. doi: 10.1111/j.1750-3841.2010.01743.x. Epub 2010 Sep 2.

Assessment of dietary intake of patulin from baby foods.

Bonerba E, Conte R, Ceci E, Tantillo G.

Dipartimento di Sanità Pubblica e Zootecnia, Facoltà di Medicina Veterinaria, Univ. degli Studi di Bari, Strada Provinciale per Casamassima, km 3, 70010 (BA), Italy.

Patulin is a mycotoxin produced by microscopic fungi belonging to the Penicillium and Aspergillus genera, frequently detectable in moldy fruits and their derivatives fruit products. The EC Regulation 1881/06 has imposed the limit for the presence of patulin equal to 10 μg/kg or 10 μg/L in baby food on the basis of a PMTDI of 0.4 μg/kg bw set by the Joint FAO/WHO Expert Committee on Food Additives (JECFA). A total of 120 homogenized baby foods were analyzed to evaluate the exposure of baby and children to patulin through the consumption of these products. None of examined samples has shown a toxin concentration above the limit imposed by the law, however a PAT concentration equal to 9 μg/kg was found in 22 samples, slightly below the fixed limit. The presence of patulin in marketed baby food can be regarded as a parameter indicative of the quality of raw materials used.

PMID: 21535575 [PubMed - indexed for MEDLINE]

212. PLoS One. 2011 Apr 13;6(4):e18777.

Role of germination in murine airway CD8+ T-cell responses to Aspergillus conidia.

Templeton SP, Buskirk AD, Law B, Green BJ, Beezhold DH.

Allergy and Clinical Immunology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, West Virginia, United States of America. STempleton@cdc.gov

Pulmonary exposure to Aspergillus fumigatus has been associated with morbidity and mortality, particularly in immunocompromised individuals. A. fumigatus conidia produce β-glucan, proteases, and other immunostimulatory factors upon germination. Murine models have shown that the ability of A. fumigatus to germinate at physiological temperature may be an important factor that facilitates invasive disease. We observed a significant increase in IFN-γ-producing CD8(+) T cells in bronchoalveolar lavage fluid (BALF) of immunocompetent mice that repeatedly aspirated A. fumigatus conidia in contrast to mice challenged with A. versicolor, a species that is not typically associated with invasive, disseminated disease. Analysis of tissue sections indicated the presence of germinating spores in the lungs of mice challenged with A. fumigatus, but not A. versicolor. Airway IFN-γ(+)CD8(+) T-cells were decreased and lung germination was eliminated in mice that aspirated A. fumigatus conidia that were formaldehyde-fixed or heat-inactivated. Furthermore, A. fumigatus particles exhibited greater persistence in the lungs of recipient mice when compared to non-viable A. fumigatus or A. versicolor, and this correlated with increased maintenance of airway memory-phenotype CD8(+) T cells. Therefore, murine airway CD8(+) T cell-responses to aspiration of Aspergillus conidia may be mediated in part by the ability of conidia to germinate in the host lung tissue. These results provide further evidence of induction of immune responses to fungi based on their ability to invade host tissue.

PMCID: PMC3076443 PMID: 21533200 [PubMed - indexed for MEDLINE]

213. J Anim Sci. 2011 Oct;89(10):3008-15. Epub 2011 Apr 29.

Effects of purified zearalenone on growth performance, organ size, serum metabolites, and oxidative stress in postweaning gilts.

Jiang SZ, Yang ZB, Yang WR, Gao J, Liu FX, Broomhead J, Chi F.

Department of Animal Sciences and Technology, Shandong Agricultural University, Tai'an, Shandong, PR China.

Zearalenone (ZEA), an estrogenic mycotoxin, is produced mainly by Fusarium fungi. Previous studies indicated that acute ZEA exposure induced oxidative stress and damage in multiple organs. Therefore, the present study was designed to investigate the adverse effects of dietary ZEA (1.1 to 3.2 mg/kg of diet) on oxidative stress and organ damage in postweaning gilts. A total of 20 gilts (Landrace × Yorkshire × Duroc) weaned at d 21 with an average BW of 10.36 ± 1.21 kg was used in the study. Gilts were housed in a temperature-controlled room, divided into 4 treatments, and fed a basal diet only (control) or basal diet supplemented with purified ZEA at a dietary concentration of 1 (ZEA1), 2 (ZEA2), or 3 (ZEA3) mg/kg of diet for 18 d ad libitum. The actual ZEA contents (analyzed) were 0, 1.1 ± 0.02, 2.0 ± 0.01, and 3.2 ± 0.02 mg/kg for control, ZEA1, ZEA2, and ZEA3, respectively. Gilts fed different amounts of dietary ZEA grew similarly with no difference (P > 0.05) in feed intake. Vulva size increased linearly over the 18 d of feeding in gilts fed diets containing 1.1 mg of ZEA/kg or greater (P < 0.001). Relative weight of genital organs, liver, and kidney increased linearly (P < 0.05) in a ZEA-dose-dependent manner. Serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, γ-glutamate transferase, urea, and creatinine (P < 0.05), and malondialdehyde concentrations in both serum and liver (P < 0.001) were also increased linearly in a ZEA-dose-dependent manner. However, spleen relative weight (P = 0.002) and activities of total superoxide dismutase and glutathione peroxidase (in both serum and liver (P < 0.05) were decreased linearly as dietary ZEA increased. Results showed that besides genital organs, the liver, kidney, and spleen may also be target tissues in young gilts fed diets containing 1.1 to 3.2 mg of ZEA/kg for 18 d. Increased key liver enzymes in the serum suggest progressive liver damage caused by feeding ZEA, and an increase in oxidative stress in gilts is another potential impact of ZEA toxicity in pigs.

PMID: 21531849 [PubMed - in process]

214. J Photochem Photobiol B. 2011 Jun 2;103(3):243-50. Epub 2011 Apr 12.

Sensitivity of Xanthoria parietina to UV-A: role of metabolic modulators.

Kováčik J, Klejdus B, Stork F, Malčovská S.

Department of Botany, Institute of Biology and Ecology, Faculty of Science, P.J. Šafárik University, Mánesova 23, 041 67 Košice, Slovak Republic. jozkovacik@yahoo.com

Effects of methyl jasmonate (MeJA), salicylic acid (SA) or 2-aminoindane-2-phosphonic acid (AIP) pre-treatments on the sensitivity of Xanthoria parietina exposed to UV-A were studied. UV decreased chlorophylls and stimulated increase in hydrogen peroxide and superoxide level. Accumulation of soluble phenols and flavonoids increased in response to UV treatment. Metabolic modulators had negligible impact on these UV-induced changes. Within free amino acids, AIP (-UV variant) and SA and MeJA (+UV variants) altered their accumulation. AIP had no effect on the amount of phenylalanine. Benzoic and cinnamic acids were elevated by UV and mainly MeJA influenced their accumulations. Among lichen specific metabolites, vulpinic acid and ergosterol increased while usnic acid and atranorin decreased after exposure to UV; accumulation of parietin was not affected. Applied modulators showed a different effect on these lichen metabolites but biosynthetic pathway-specific trend of alteration was visible. Overall, MeJA showed the most pronounced effect among studied parameters. Accumulation of selected phenolics in response to UV-A seems to be an important feature of Xanthoria tolerance. Present finding in the context of phenolic metabolism in non-vascular plants and with respect to limited data about effect of studied modulators on non-vascular plants are discussed.

PMID: 21531571 [PubMed - indexed for MEDLINE]

215. J Invertebr Pathol. 2011 Jul;107(3):179-84. Epub 2011 Apr 21.

Comparative growth kinetics and virulence of four different isolates of entomopathogenic fungi in the house fly (Muscadomestica L.).

Anderson RD, Bell AS, Blanford S, Paaijmans KP, Thomas MB.

Department of Entomology, Penn State University, University Park, PA 16802, USA. rda138@psu.edu

Virulence (speed of kill) of a fungal entomopathogen against a particular host insect depends on biological properties of the specific isolate-host combination, together with factors such as fungal dose. How these intrinsic and extrinsic factors affect the actual pattern and extent of fungal growth invivo is poorly understood. In this study we exposed adult house flies (Muscadomestica L.) to surfaces treated with high and low doses of Beauveriabassiana (isolates BbGHA and Bb5344), Metarhiziumanisopliae (strain MaF52) and M.anisopliae var. acridum (isolate Ma189) and used quantitative real-time PCR with species-specific primers to examine the relationship between fungal growth kinetics and virulence. At the highest dose, all fungal isolates killed flies significantly faster than controls, with BbGHA, Bb5344 and MaF52 roughly equivalent in virulence (median survival time (±SE)=5.0±0.10, 5.0±0.08 and 5.0±0.12days, respectively) and Ma189 killing more slowly (MST=8.0±0.20days). At the lower dose, effective virulence was reduced and only flies exposed to isolates BbGHA and Bb5344 died significantly faster than controls (MST=12±1.36, 15±0.64, 18±0.86 and 21.0±0.0days for BbGHA, Bb5344, MaF52 and Ma189, respectively). Real-time PCR assays revealed that flies exposed to surfaces treated with the high dose of spores had greater spore pickup than flies exposed to the low dose for each isolate. After pickup, a general pattern emerged for all isolates in which there was a significant reduction of recovered fungal DNA 48h after exposure followed by a brief recovery phase, a stable period of little net change in fungal sequence counts, and then a dramatic increase in sequence counts of up to three orders of magnitude around the time of host death. However, while the patterns of growth were similar, there were quantitative differences such that higher final sequence counts were recovered in insects infected with the most lethal isolates and with the higher dose. These results suggest that variation in virulence between isolates, species and doses is determined more by quantitative rather than qualitative differences in fungal growth kinetics.

PMID: 21530533 [PubMed - indexed for MEDLINE]

216. J Insect Physiol. 2011 Jul;57(7):966-71. Epub 2011 Apr 21.

Losing the battle against fungal infection: suppression of termite immune defenses during mycosis.

Avulova S, Rosengaus RB.

Department of Biology, Northeastern University, 134 Mugar Life Sciences Building, 360 Huntington Avenue, Boston, MA 02115-5000, USA.

The dampwood termite, Zootermopsis angusticollis is known to generate humoral immune responses to the entomopathogenic fungus Metarhizium anisopliae. However, little is known about how the termite's cellular immune system reacts to fungal infection. To test the effect of conidia exposure on cellular immunity, we quantified the number and types of hemocytes in the hemolymph of naïve nymphs and compared their circulating counts with those of nestmates exposed to 0, 2×10(3), 2×10(6) or 2×10(8) conidia/ml doses. These termites were then bled and their hemocytes counted on days 1, 2, 3, 4, 7 post-exposure. Our results show, first, that naïve Z. angusticollis nymphs have three different blood cell types tentatively identified as granular hemocytes, prohemocytes and plasmatocytes. In these individuals, plasmatocytes were on average 13.5 and 3.3 times more numerous than granular hemocytes and prohemocytes, respectively. Second, a full factorial general linear analysis indicated that hemocyte type, time elapsed since conidia exposure and conidia dosage as well as all their interactions explained 43% of the variability in hemocyte density. The numbers of prohemocytes and particularly plasmatocytes, but not granular hemocytes, appear to be affected by the progression of disease. The decline in hemocyte numbers coincided with the appearance of hyphal bodies and the onset of "sluggish" termite behavior that culminated in the insect's death. Hemocyte counts of infected males and females were affected to the same extent. Hence, M. anisopliae overtakes the cellular immune responses of Z. angusticollis mainly by destroying the host's most abundant hemocyte types.

PMID: 21530532 [PubMed - indexed for MEDLINE]

217. Ecotoxicol Environ Saf. 2011 Sep;74(6):1685-92. Epub 2011 Apr 29.

Effects of heavy metals on production of thiol compounds and antioxidant enzymes in Agaricus bisporus.

Xu H, Song P, Gu W, Yang Z.

Key Laboratory for Bio-resources and Eco-environment of Education Ministry, College of Life Science, Sichuan University, Chengdu 610064, China.

In a pre-experiment, Agaricus bisporus mycelia grown in PDL medium were found to have a substantial ability to tolerate and accumulate heavy metals. In the study, we investigated changes in the contents of soluble protein and thiol compounds as well as the activities of antioxidant enzymes caused by copper, zinc, lead, and cadmium (nitrate salts) in mycelia of A. bisporus during short-and long-term exposure. Results showed that high-level metal concentrations significantly decrease the contents of soluble protein after long-term exposure, Cu and Zn concentrations significantly increase the thiol compounds levels after long-term exposure, while high-level Cd significantly decrease thiol compounds after long-term exposure. Additionally, SOD activities were significantly increased after long-term exposure to metals, especially to Cd. The CAT activities were enhanced after long-term exposure to low-level Cu and high-level Zn, and enhanced after short-and long-term exposure to high-level Pb. The POD activities were significantly increased after long-term exposure to metals, and increased after short-term exposure to Cd and high-level Pb.

PMID: 21529942 [PubMed - indexed for MEDLINE]

218. Clin J Sport Med. 2011 May;21(3):264-5.

Blood exposure at the 2010 International Federation of Football Association World Cup: time for universal adaptation of universal precautions.

Furin JJ.

Divisions of Global Health Equity and Infectious Diseases, Brigham and Women's Hospital, Boston, Massachusetts; Department of Anthropology, Case Western Reserve University, Cleveland, Ohio, USA.

OBJECTIVE: Injuries involving blood exposure are relatively common in football. The goal of this observational study was to assess the use of universal precautions at the 2010 International Federation of Football Association (FIFA) World Cup. DESIGN: Observational descriptive study of more than 4000 minutes of FIFA World Cup football. SETTING: Televised matches of football in the 2010 FIFA World Cup in the Republic of South Africa. ASSESSMENT OF RISK FACTORS: Injuries with visible blood that were attended to by health care providers were recorded. MAIN OUTCOME MEASURES: Number of injuries with visible blood in which gloves were used by responders.
RESULTS: Twenty-two significant bloody injuries were noted in more than 4000 minutes of play observed. In none of these cases were universal precautions implemented.
CONCLUSIONS: This brief report shows the need for better implementation of universal precautions in football and other team sports.

2011 by Lippincott Williams & Wilkins.

PMID: 21519297 [PubMed - indexed for MEDLINE]

219. Proc Natl Acad Sci U S A. 2011 May 10;108(19):7799-803. Epub 2011 Apr 25.

Nucleosome positioning in a model of active chromatin remodeling enzymes.

Padinhateeri R, Marko JF.

Department of Biosciences and Bioengineering and Wadhwani Research Centre for Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai 400076, India. ranjithp@iitb.ac.in

Accounting for enzyme-mediated active sliding, disassembly, and sequence-dependent positioning of nucleosomes, we simulate nucleosome occupancy over cell-cycle-scale times using a stochastic kinetic model. We show that ATP-dependent active nucleosome sliding and nucleosome removal processes are essential to obtain in vivo-like nucleosome positioning. While active sliding leads to dense nucleosome filling, sliding events alone cannot ensure sequence-dependent nucleosome positioning: Active nucleosome removal is the crucial remodeling event that drives positioning. We also show that remodeling activity changes nucleosome dynamics from glassy to liquid-like, and that remodeling dramatically influences exposure dynamics of promoter regions.

PMCID: PMC3093463 PMID: 21518900 [PubMed - indexed for MEDLINE]

220. Antimicrob Agents Chemother. 2011 Jul;55(7):3546-56. Epub 2011 Apr 25.

Transcriptional profiling of azole-resistant Candida parapsilosis strains.

Silva AP, Miranda IM, Guida A, Synnott J, Rocha R, Silva R, Amorim A, Pina-Vaz C, Butler G, Rodrigues AG.

Department of Microbiology, Faculty of Medicine, University of Porto, Porto, Portugal. atsilva@med.up.pt

Herein we describe the changes in the gene expression profile of Candida parapsilosis associated with the acquisition of experimentally induced resistance to azole antifungal drugs. Three resistant strains of C. parapsilosis were obtained following prolonged in vitro exposure of a susceptible clinical isolate to constant concentrations of fluconazole, voriconazole, or posaconazole. We found that after incubation with fluconazole or voriconazole, strains became resistant to both azoles but not to posaconazole, although susceptibility to this azole decreased, whereas the strain incubated with posaconazole displayed resistance to the three azoles. The resistant strains obtained after exposure to fluconazole and to voriconazole have increased expression of the transcription factor MRR1, the major facilitator transporter MDR1, and several reductases and oxidoreductases. Interestingly, and similarly to what has been described in C. albicans, upregulation of MRR1 and MDR1 is correlated with point mutations in MRR1 in the resistant strains. The resistant strain obtained after exposure to posaconazole shows upregulation of two transcription factors (UPC2 and NDT80) and increased expression of 13 genes involved in ergosterol biosynthesis. This is the first study addressing global molecular mechanisms underlying azole resistance in C. parapsilosis; the results suggest that similarly to C. albicans, tolerance to azoles involves the activation of efflux pumps and/or increased ergosterol synthesis.

PMCID: PMC3122401 PMID: 21518843 [PubMed - indexed for MEDLINE]

221. J Air Waste Manag Assoc. 2011 Apr;61(4):461-8.

An assessment of dust, endotoxin, and microorganism exposure during waste collection and sorting.

Park DU, Ryu SH, Kim SB, Yoon CS.

Department of Environmental Health, Korea National Open University, Seoul, South Korea. pdw545@knou.ac.kr

This study was conducted to assess inhalation exposure to dust, endotoxin, and microorganisms (including viable bacteria, Gram-negative bacteria [GNB], and fungi) during waste collection and sorting; to identify factors affecting this exposure; and to estimate the gastrointestinal exposure to microorganisms. A total of 48 or 49 workers involved in collecting and sorting waste from households or the street were studied. Each worker carried two personal samplers in which filters were placed in the breathing zone for estimation of inhalation exposure. To assess the possibility of gastrointestinal exposure, microorganisms on the workers' faces were collected before and after work and compared with those collected from office workers. Inhalation exposure levels were categorized according to job title, waste type handled, and working conditions and were compared using analysis of variance. Multiple regression models were developed to identify those factors that substantially affected inhalation exposure. The average exposure level to total dust was 0.9 mg/m3 (range = 0.05 to 4.51 mg/m3), and the average exposure to endotoxin was 1123 EU/m3. The average respective exposure levels to bacteria, GNB, and fungi each exceeded 10(4) colony forming units (CFU)/m3. The multiple regression models found several factors that significantly explained the variation in levels of inhalation exposure to endotoxin and microorganisms; namely, sex (dust, bacteria, and GNB), job title (GNB and fungi), collection day (dust, bacteria, and GNB), temperature (endotoxin and GNB), humidity (endotoxin and fungi), and region (endotoxin) were significantly associated with exposure to these agents. In addition, the workers' faces were highly contaminated with microorganisms. In conclusion, inhalation exposure to endotoxin and microorganisms was high during waste collection and sorting, which may place workers at risk of developing various health problems, including respiratory complaints.

PMID: 21516941 [PubMed - indexed for MEDLINE]

222. BMC Ophthalmol. 2011 Apr 21;11:8.

Effectiveness of ophthalmic solution preservatives: a comparison of latanoprost with 0.02% benzalkonium chloride and travoprost with the sofZia preservative system.

Ryan G Jr, Fain JM, Lovelace C, Gelotte KM.

Development Analytics, Pfizer Inc, Eastern Point Road, Groton, CT, USA. jerry.ryan@pfizer.com

BACKGROUND: Although in vitro and in vivo laboratory studies have suggested that benzalkonium chloride (BAK) in topical ophthalmic solutions may be detrimental to corneal epithelial cells, multiple short- and long-term clinical studies have provided evidence supporting the safety of BAK. Despite the conflicting evidence, BAK is the most commonly used preservative in ophthalmic products largely due to its proven antimicrobial efficacy. This study was designed to characterize the antimicrobial performance of two commonly used topical ocular hypotensive agents that employ different preservative systems: latanoprost 0.005% with 0.02% BAK and travoprost 0.004% with sofZia, a proprietary ionic buffer system.
METHODS: Each product was tested for antimicrobial effectiveness by European Pharmacopoeia A (EP-A) standards, the most stringent standards of the three major compendia, which specify two early sampling time points (6 and 24 hours) not required by the United States Pharmacopeia or Japanese Pharmacopoeia. Aliquots were inoculated with between 10(5) and 10(6) colony-forming units of the test organisms: Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Candida albicans and Aspergillus brasiliensis. Sampling and enumeration were conducted at protocol-defined time points through 28 days.
RESULTS: BAK-containing latanoprost met EP-A criteria by immediately reducing all bacterial challenge organisms to the test sensitivity and fungal challenges within the first six hours while the preservative activity of travoprost with sofZia did not. Complete bacterial reduction by travoprost with sofZia was not shown until seven days into the test, and fungal reduction never exceeded the requisite 2 logs during the 28-day test. Travoprost with sofZia also did not meet EP-B criteria due to its limited effectiveness against Staphylococcus aureus. Both products satisfied United States and Japanese pharmacopoeial criteria.
CONCLUSIONS: Latanoprost with 0.02% BAK exhibited more effective microbial protection than travoprost with sofZia using rates of microbial reduction, time to no recovery for all challenges and evaluation against EP-A criteria as measures. The rapid and complete reduction of all microbial challenges demonstrates that antimicrobial activity of latanoprost with 0.02% BAK exceeds that of travoprost with sofZia preservative system in these products and provides a more protective environment in the event of contamination and subsequent exposure to microorganisms during use.

PMCID: PMC3107821 PMID: 21510881 [PubMed - indexed for MEDLINE]

223. J Assoc Physicians India. 2010 Oct;58:633-4.

Pseudallescheria boydii lung infection in an immunocompetent adult, difficulties in diagnosis and management.

Soman R, Mahashur AA, Naphade D, Rodrigues C, Bhaduri A, Nagnur PK, Warrier A.

P D Hinduja National Hospital & Medical Research Centre, V S Marg, Mahim, Mumbai-411016.

Pseudallescheria boydii and its asexual state Scedosporium apiospermum is a well known opportunistic pathogen among immunocompromised patients. However it is rare in immunocompetent patients. The optimum management of this infection is still not clear. The new azoles may show better efficacy than amphotericin B and additional surgery may play a pivotal role. We report a case of Pseudallescheria boydii lung infection in an immunocompetent patient who had an old tuberculous cavity and presumed inhalational exposure. The case highlights difficulties in diagnosis which complicates the selection of antifungal agent/s and the need for aggressive surgical debridement.

PMID: 21510115 [PubMed - indexed for MEDLINE]

224. J Vis Exp. 2011 Apr 7;(50). pii: 2585. doi: 10.3791/2585.

Microarray analysis for Saccharomyces cerevisiae.

Tighe S, Hunter T, Reed P, Murray J.

Vermont Genetics Network, The University of Vermont, USA.

In this protocol, gene expression in yeast (Saccharomyces cerevisiae) is changed after exposure to oxidative stress induced by the addition of hydrogen peroxide (H₂O₂), an oxidizing agent. In the experiment, yeast is grown for 48 hours in 1/2X YPD broth containing 3X glucose. The culture is split into a control and treated group. The experiment culture is treated with 0.5 mM H₂O₂ in Hanks Buffered Saline (HBSS) for 1 hour. The control culture is treated with HBSS only. Total RNA is extracted from both cultures and is converted to a biotin-labeled cRNA product through a multistep process. The final synthesis product is taken back to the UVM Microarray Core Facility and hybridized to the Affymetrix yeast GeneChips. The resulting gene expression data are uploaded into bioinformatics data analysis software.

PMID: 21505409 [PubMed - indexed for MEDLINE]

225. Antimicrob Agents Chemother. 2011 Jul;55(7):3564-6. Epub 2011 Apr 18.

Failure of posaconazole therapy in a renal transplant patient with invasive aspergillosis due to Aspergillus fumigatus with attenuated susceptibility to posaconazole.

Kuipers S, Brüggemann RJ, de Sévaux RG, Heesakkers JP, Melchers WJ, Mouton JW, Verweij PE.

Department of Medical Microbiology, Radboud University Nijmegen Medical Center, P.O. Box 9101, 6500 HB Nijmegen, Netherlands. s.kuipers@mmb.umcn.nl.

We report the case of a kidney transplant recipient with invasive aspergillosis due to Aspergillus fumigatus resistant to voriconazole and intermediately susceptible to posaconazole who failed posaconazole therapy. Plasma posaconazole concentrations indicated an unfavorable ratio of the area under the concentration-time curve over the MIC. Posaconazole should be used with caution for invasive aspergillosis caused by strains with attenuated posaconazole susceptibility, as drug exposure may be inadequate, resulting in therapeutic failure.

PMCID: PMC3122456 PMID: 21502625 [PubMed - indexed for MEDLINE]

226. J Environ Monit. 2010 May;12(5):1187-94.

Fungal spores from Pleosporales in the atmosphere of urban and rural locations in Portugal.

Oliveira M, Delgado L, Ribeiro H, Abreu I.

Environment, Society and Education Group, Geology Centre, University of Porto & Biology Department, Faculty of Sciences, University of Porto, Edifício FC4, Rua do Campo Alegre, s/n, 4169-007 Porto, Portugal.

Fungal spores are a significant fraction of the atmospheric bioparticles (bioaerosols) and many species are capable of inducing the production of specific immunoglobulin E (IgE), aggravating the clinical symptoms of allergic respiratory diseases in sensitized individuals. The aim of this work was to evaluate the distribution of potentially allergenic Pleosporales spores in two locations with different urbanization indexes, characterizing its seasonal pattern. The seasonal distribution of several spore types belonging to the Pleosporales (Alternaria, Drechslera, Epicoccum, Paraphaeosphaeria, Pithomyces, Pleospora and Stemphylium) in Amares (rural area) and Porto (urban area) was continually studied from January 2005 to December of 2007, using Hirst-type volumetric spore traps. Alternaria was the most abundant fungal spore type found in the atmosphere of Amares and Porto. This fungal type, together with Drechslera, Epicoccum, Pithomyces and Stemphylium, was mainly present during summer. Nevertheless, Leptosphaeria, Pleospora and Venturia spores were detected during winter and spring, while Paraphaeosphaeria spores were also observed during summer and autumn. These different seasonal patterns were responsible for the expansion of the exposure period for the Alt a 1 allergen. The concentration of the studied spore types was higher in the rural area than in the urban one, with exception for Pleospora and Drechslera. According to the correlations with meteorological factors, the selected fungal spores can be divided into two groups: (i) Alternaria, Drechslera, Epicoccum, Pithomyces and Stemphylium presented positive correlations with temperature and negative correlations with relative humidity and rainfall; (ii) Leptosphaeria, Paraphaeosphaeria, Pleospora and Venturia presented a contrary behavior. Usually, the occurrence of the Alt a 1 allergen has been associated with the presence of airborne Alternaria spores; the present work follows the seasonal distribution of other fungal spore species known to contain this molecule. The widespread occurrence of Alt a 1 plays an important role in the incidence and aggravation of allergic disorders.

PMID: 21491687 [PubMed - indexed for MEDLINE]

227. Bioorg Med Chem Lett. 2011 May 15;21(10):2890-3. Epub 2011 Mar 30.

SAR studies of pyridazinone derivatives as novel glucan synthase inhibitors.

Zhou G, Ting PC, Aslanian R, Cao J, Kim DW, Kuang R, Lee JF, Schwerdt J, Wu H, Herr RJ, Zych AJ, Yang J, Lam S, Wainhaus S, Black TA, McNicholas PM, Xu Y, Walker SS.

Department of Chemical Research, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. gang.zhou@merck.com

A novel series of pyridazinone analogs has been developed as potent β-1,3-glucan synthase inhibitors through structure-activity relationship study of the lead 5-[4-(benzylsulfonyl)piperazin-1-yl]-4-morpholino-2-phenyl-pyridazin-3(2H)-one (1). The effect of changes to the core structure is described in detail. Optimization of the sulfonamide moiety led to the identification of important compounds with much improved systematic exposure while retaining good antifungal activity against the fungal strains Candida glabrata and Candida albicans.

Published by Elsevier Ltd.

PMID: 21489787 [PubMed - indexed for MEDLINE]

228. Lett Appl Microbiol. 2011 Jul;53(1):14-21. doi: 10.1111/j.1472-765X.2011.03058.x. Epub 2011 May 12.

Role of insulin in Cr(VI)-mediated genotoxicity in Neurospora crassa.

Gaddameedi RR, Burgula S, Sairam M, Singh SS.

Department of Biochemistry, Osmania University, Hyderabad, India.

AIMS: Chromium (III) is an insulinomimetic agent whose biological and/or environmental availability is frequently in the form of Cr(VI), which is known to be toxic. Wall-less mutant of Neurospora crassa (FGSC stock no. 4761) is known to possess insulin receptor in its cell membrane and hence is a good model for Cr toxicity studies. This study explores the toxicity of Cr(VI) and the possible consequences on simultaneous exposure to insulin in N. crassa. METHODS AND RESULTS: Comet assay of N. crassa cells treated with 100 μmol l⁻¹ Cr(VI) showed up to 50% reduction in comet tail lengths when incubated simultaneously with 0.4 U insulin. Fluorescence measurement in Cr(VI)-treated cells using DCFH-DA showed six- to eightfold increase in free radical generation, which was reduced to fourfold by 0.4 U insulin. Annexin-V/PI Flow cytometry analysis indicated necrotic cell death up to 28.7 ± 3.6% and 68.6 ± 2.5% on Cr(VI) exposure at concentrations 100 and 500 μmol l⁻¹ which was reduced by 68.3 ± 3.2% and 48.9 ± 3.6%, respectively, upon addition of insulin.
CONCLUSION: Insulin-mediated protection from DNA damage by Cr(VI) is because of scavenging of free radicals liberated during exposure to Cr(VI). SIGNIFICANCE AND IMPACT OF THE STUDY: Overall, Cr(VI) toxicity depends upon available insulin, indicating that Cr(VI) toxicity may be a serious issue in insulin-deficient individuals with diabetes.

PMID: 21488912 [PubMed - indexed for MEDLINE]

229. Proc Natl Acad Sci U S A. 2011 Apr 26;108(17):7271-6. Epub 2011 Apr 12.

A mathematical model for adaptive prediction of environmental changes by microorganisms.

Mitchell A, Pilpel Y.

Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.

Survival in natural habitats selects for microorganisms that are well-adapted to a wide range of conditions. Recent studies revealed that cells evolved innovative response strategies that extend beyond merely sensing a given stimulus and responding to it on encounter. A diversity of microorganisms, including Escherichia coli, Vibrio cholerae, and several yeast species, were shown to use a predictive regulation strategy that uses the appearance of one stimulus as a cue for the likely arrival of a subsequent one. A better understanding of such a predictive strategy requires elucidating the interplay between key biological and environmental forces. Here, we describe a mathematical framework to address this challenge. We base this framework on experimental systems featuring early preparation to either a stress or an exposure to improvement in the growth medium. Our model calculates the fitness advantage originating under each regulation strategy in a given habitat. We conclude that, although a predictive response strategy might by advantageous under some ecologies, its costs might exceed the benefit in others. The combined theoretical-experimental treatment presented here helps assess the potential of natural ecologies to support a predictive behavior.

PMCID: PMC3084127 PMID: 21487001 [PubMed - indexed for MEDLINE]

230. JAMA. 2011 Apr 13;305(14):1400-1.

Research provides new insights on how hygiene affects asthma and allergies.

Hampton T.

PMID: 21486968 [PubMed - indexed for MEDLINE]

231. J Evol Biol. 2011 Jun;24(6):1307-16. doi: 10.1111/j.1420-9101.2011.02264.x. Epub 2011 Apr 11.

The expression of virulence during double infections by different parasites with conflicting host exploitation and transmission strategies.

Ben-Ami F, Rigaud T, Ebert D.

Department of Zoology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel. frida@post.tau.ac.il

In many natural populations, hosts are found to be infected by more than one parasite species. When these parasites have different host exploitation strategies and transmission modes, a conflict among them may arise. Such a conflict may reduce the success of both parasites, but could work to the benefit of the host. For example, the less-virulent parasite may protect the host against the more-virulent competitor. We examine this conflict using the waterflea Daphnia magna and two of its sympatric parasites: the blood-infecting bacterium Pasteuria ramosa that transmits horizontally and the intracellular microsporidium Octosporea bayeri that can concurrently transmit horizontally and vertically after infecting ovaries and fat tissues of the host. We quantified host and parasite fitness after exposing Daphnia to one or both parasites, both simultaneously and sequentially. Under conditions of strict horizontal transmission, Pasteuria competitively excluded Octosporea in both simultaneous and sequential double infections, regardless of the order of exposure. Host lifespan, host reproduction and parasite spore production in double infections resembled those of single infection by Pasteuria. When hosts became first vertically (transovarilly) infected with O. bayeri, Octosporea was able to withstand competition with P. ramosa to some degree, but both parasites produced less transmission stages than they did in single infections. At the same time, the host suffered from reduced fecundity and longevity. Our study demonstrates that even when competing parasite species utilize different host tissues to proliferate, double infections lead to the expression of higher virulence and ultimately may select for higher virulence. Furthermore, we found no evidence that the less-virulent and vertically transmitting O. bayeri protects its host against the highly virulent P. ramosa.

PMID: 21481055 [PubMed - indexed for MEDLINE]

232. Mol Med Report. 2011 Mar-Apr;4(2):357-62. doi: 10.3892/mmr.2011.427. Epub 2011 Jan 18.

Gefitinib induces mitochondrial-dependent apoptosis in Saccharomyces cerevisiae.

Wu J, Min R, Wu M, Chen W.

Department of Pharmaceutical Engineering, School of Medicine and Pharmaceutics, Jiangnan University, Wuxi, Jiangsu 214122, P.R. China. wujing@jiangnan.edu.cn

Gefitinib, a selective inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase, has been clinically demonstrated to be effective in certain cancer cell types. In the present study, using the yeast Saccharomyces cerevisiae as a model, gefitinib-induced apoptotic cell death was demonstrated. Gefitinib inhibited yeast cell proliferation and ultimately led to cell death in a time- and dose-dependent manner. Furthermore, when cells were exposed to 15 µM gefitinib, typical apoptotic markers, including phosphatidylserine exposure, DNA fragmentation, reactive oxygen species production and decrease in mitochondrial membrane potential, were observed. The Δcyc3 strain deleted in cyt c heme lyase and the rho⁰ mutant strain lacking mtDNA-delayed cell death, provided further evidence that the yeast cell death process involved the mitochondria. Thus, these findings suggest that gefitinib induces apoptosis in yeast cells through a mitochondrial-dependent pathway.

PMID: 21468577 [PubMed - indexed for MEDLINE]

233. Hybridoma (Larchmt). 2011 Feb;30(1):29-36.

Production and characterization of IgM monoclonal antibodies against hyphal antigens of Stachybotrys species.

Nayak AP, Green BJ, Janotka E, Blachere FM, Vesper SJ, Beezhold DH, Schmechel D.

Stachybotrys is a hydrophilic fungal genus that is well known for its ability to colonize water-damaged building materials in indoor environments. Personal exposure to Stachybotrys chartarum allergens, mycotoxins, cytolytic peptides, and other immunostimulatory macromolecules has been proposed to exacerbate respiratory morbidity. To date, advances in Stachybotrys detection have focused on the identification of unique biomarkers that can be detected in human serum; however, the availability of immunodiagnostic reagents to Stachybotrys species have been limited. In this study, we report the initial characterization of monoclonal antibodies (MAbs) against a semi-purified cytolytic S. chlorohalonata preparation (cScp) derived from hyphae. BALB/c mice were immunized with cScp and hybridomas were screened against the cScp using an antigen-mediated indirect ELISA. Eight immunoglobulin M MAbs were produced and four were specifically identified in the capture ELISA to react with the cScp. Cross-reactivity of the MAbs was tested against crude hyphal extracts derived from 15 Stachybotrys isolates representing nine Stachybotrys species as well as 39 other environmentally abundant fungi using a capture ELISA. MAb reactivity to spore and hyphal antigens was also tested by a capture ELISA and by fluorescent halogen immunoassay (fHIA). ELISA analysis demonstrated that all MAbs strongly reacted with extracts of S. chartarum but not with extracts of 39 other fungi. However, four MAbs showed cross-reactivity to the phylogenetically related genus Memnoniella. fHIA analysis confirmed that greatest MAb reactivity was ultrastructurally localized in hyphae and phialides. The results of this study further demonstrate the feasibility of specific MAb-based immunoassays for the detection of S. chartarum.

PMCID: PMC3119332 [Available on 2012/2/1] PMID: 21466283 [PubMed - indexed for MEDLINE]

234. Infect Control Hosp Epidemiol. 2011 Apr;32(4):315-22.

The network approach for prevention of healthcare-associated infections: long-term effect of participation in the Duke Infection Control Outreach Network.

Anderson DJ, Miller BA, Chen LF, Adcock LH, Cook E, Cromer AL, Louis S, Thacker PA 2nd, Sexton DJ.

Duke Infection Control Outreach Network, Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA. dja@duke.edu

OBJECTIVE: To describe the rates of several key outcomes and healthcare-associated infections (HAIs) among hospitals that participated in the Duke Infection Control Outreach Network (DICON).
DESIGN AND SETTING: Prospective, observational cohort study of patients admitted to 24 community hospitals from 2003 through 2009.
METHODS: The following data were collected and analyzed: incidence of central line-associated bloodstream infections (CLABSIs), ventilator-associated pneumonia (VAP), catheter-associated urinary tract infections (CAUTIs), and HAIs caused by methicillin-resistant Staphylococcus aureus (MRSA); employee exposures to bloodborne pathogens (EBBPs); physician EBBPs; patient-days; central line-days; ventilator-days; and urinary catheter-days. Poisson regression was used to determine whether incidence rates of these HAIs and exposures changed during the first 5 and 7 years of participation in DICON; nonrandom clustering of each outcome was controlled for. Cost saved and lives saved were calculated on the basis of published estimates.
RESULTS: In total, we analyzed 6.5 million patient-days, 4,783 EBPPs, 2,948 HAIs due to MRSA, and 2,076 device-related infections. Rates of employee EBBPs, HAIs due to MRSA, and device-related infections decreased significantly during the first 5 years of participation in DICON (P< .05 for all models; average decrease was approximately 50%); in contrast, physician EBBPs remained unchanged. In aggregate, 210 CLABSIs, 312 cases of VAP, 332 CAUTIs, 1,042 HAIs due to MRSA, and 1,016 employee EBBPs were prevented. Each hospital saved approximately $100,000 per year of participation, and collectively the hospitals may have prevented 52-105 deaths from CLABSI or VAP. The 7-year analysis demonstrated that these trends continued with further participation.
CONCLUSIONS: Hospitals with long-term participation in an infection control network decreased rates of significant HAIs by approximately 50%, decreased costs, and saved lives.

PMID: 21460482 [PubMed - indexed for MEDLINE]

235. J Dent Educ. 2011 Apr;75(4):544-8.

Underreporting of bloodborne exposures in a dental school clinic.

Cuny E, Hoover TE, Kirk JS.

Arthur A. Dugoni School of Dentistry, University of the Pacific, 2155 Webster Street, San Francisco, CA 94115, USA. ecuny@pacific.edu

This study explored the rate of underreporting of bloodborne exposures among dental students in a U.S. dental school during the final two years of clinical practice. It also explored the reasons students cite for failing to report bloodborne exposures. Surveys of the dental students found that senior students reported only 43 percent of the exposure incidents they experienced in their final year of clinical education and that the rate of reporting declined from the junior year to the senior year. We subsequently undertook an educational campaign to raise awareness among the students regarding the importance of reporting exposure incidents. Surveys were repeated for the next two years at the end of each academic year. The following year, the senior class indicated they had reported 79 percent of the experienced exposure incidents. This was not only a significant improvement over the previous year, but also demonstrated an improvement in reporting from their junior year to senior year, reversing the previously noted trend for exposure reporting to drop off in the senior year.

PMID: 21460275 [PubMed - indexed for MEDLINE]

236. Yeast. 2011 Apr;28(4):265-78. doi: 10.1002/yea.1837. Epub 2011 Jan 16.

Sensitive detection of chemical-induced genotoxicity by the Cypridina secretory luciferase reporter assay, using DNA repair-deficient strains of Saccharomyces cerevisiae.

Ochi Y, Sugawara H, Iwami M, Tanaka M, Eki T.

Molecular Genetics Laboratory, Division of Bioscience and Biotechnology, Department of Environmental and Life Sciences, Toyohashi University of Technology, Aichi, Japan.

Yeast-based reporter assays are useful for detecting various genotoxic chemicals. We established a genotoxicity assay using recombinant strains of Saccharomyces cerevisiae, each containing a reporter plasmid with the secretory luciferase gene from Cypridina noctiluca, driven by a DNA damage-responsive promoter of the yeast RNR3 gene. This system detected the genotoxicity of methyl methanesulphonate (MMS) as sensitively as conventional yeast-based reporter assays, using the β-galactosidase gene in a concentration-dependent manner; it also detects four other genotoxic chemicals, allowing us to monitor DNA damage easily by skipping the cell extraction process for the assay. We examined Cypridina luciferase levels induced by MMS and three antitumour agents using a set of BY4741-derived deletion mutants, each defective in a DNA repair pathway or DNA damage checkpoint. Luciferase activities were particularly enhanced in mutant strains with mms2 Δ and mag1 Δ by exposure to MMS, rad59 Δ and mlh1 Δ to camptothecin and mms2 Δ and mlh1 Δ to mitomycin C, respectively, compared with their parent strains. Enhanced reporter activities were also found in some DNA repair mutants with cisplatin. These observations suggest that this Cypridina secretory luciferase reporter assay using yeast DNA repair mutants offers convenient and sensitive detection of the potential genotoxicity of numerous compounds, including antitumour drugs and studying the mechanisms of DNA damage response in yeast.

PMID: 21456053 [PubMed - indexed for MEDLINE]

237. Eur J Clin Microbiol Infect Dis. 2011 Nov;30(11):1321-4. Epub 2011 Apr 1.

Emerging infectious endocarditis due to Scedosporium prolificans: a model of therapeutic complexity.

Fernandez Guerrero ML, Askari E, Prieto E, Gadea I, Román A.

Division of Infectious Diseases and Haematology (Department of Medicine), Instituto de Investigaciones Sanitarias Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Spain, Aveda. Reyes Católicos 2, 28040 Madrid, Spain. mlfernandez@fjd.es

Scedosporium prolificans is an emerging agent for severe infections. Although among the dematiaceous fungi Scedosporium is the most frequently isolated in blood cultures, Scedosporium endocarditis is rarely reported. We show herein a patient with acute leukaemia who developed S. prolificans endocarditis. Twelve cases were found in an extensive review of the English literature. In six cases (46%), there was predisposing heart conditions such as a prosthetic valve or an intracavitary device. Only 4 patients (31%) were immunocompromised hosts with haematologic neoplasia, solid-organ transplantation or acquired immunodeficiency syndrome (AIDS). Exposure to Scedosporium was observed in immunocompetent patients who developed infection while in the community. Scedosporium endocarditis occurred on both sides of the heart. Systemic and pulmonary emboli and other metastatic complications were seen in all of these patients. The overall mortality was 77% and, specifically, all of the immunocompromised hosts and 6 out of 7 patients with mitral or aortic valve endocarditis died. Patients with right-sided endocarditis associated with a removable intracardiac device exhibited a better prognosis. Scedosporium endocarditis, although still rare, is an emerging infection with an ominous prognosis. At the present time, valve replacement or the removal of cardiac devices plus combined antifungal treatment may offer the best possibility of cure.

PMID: 21455664 [PubMed - in process]

238. Clin Infect Dis. 2011 May;52(9):1108-1115.

Central line-associated bloodstream infection in hospitalized children with peripherally inserted central venous catheters: extending risk analyses outside the intensive care unit.

Advani S, Reich NG, Sengupta A, Gosey L, Milstone AM.

Department of Pediatrics, Division of Pediatric Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

BACKGROUND: Increasingly, peripherally inserted central venous catheters (PICCs) are placed for prolonged intravenous access. Few data exist regarding risk factors for central line-associated bloodstream infection (CLABSI) complicating PICCs in hospitalized children, especially children hospitalized outside the intensive care unit (ICU).
METHODS: We identified all children with a PICC inserted at The Johns Hopkins Hospital (Baltimore, MD) from 1 January 2003 through 31 December 2009 and used Poisson regression models to identify risk factors for PICC-associated CLABSIs.
RESULTS: A total of 2592 PICCs were placed in 1819 children. One hundred sixteen CLABSIs occurred over 44,972 catheter-days (incidence rate [IR], 2.58 cases per 1000 catheter-days; 95% confidence interval [CI], 2.07-3.00 cases per 1000 catheter-days). Independent predictors of CLABSI in the entire cohort included PICC dwell time of > 21 days (IR ratio [IRR], 1.53; 95% CI, 1.05-2.26), parenteral nutrition as indication for insertion (IRR, 2.24; 95% CI, 1.31-3.84), prior PICC-associated CLABSI (IRR, 2.48; 95% CI, 1.18-5.25), underlying metabolic condition (IRR, 2.07; 95% CI, 1.14-3.74), and pediatric ICU exposure during hospitalization (IRR, 1.80; 95% CI, 1.18-2.75). Risk factors for CLABSI in children without PICU exposure included younger age, underlying malignancy and metabolic conditions, PICCs inserted in the lower extremity, and a prior PICC-associated CLABSI.
CONCLUSIONS: Prolonged catheter dwell time, pediatric ICU exposure, and administration of parenteral nutrition as the indication for PICC insertion are important predictors of PICC-associated CLABSI in hospitalized children. A careful assessment of these risk factors may be important for future success in preventing CLABSIs in hospitalized children with PICCs.

PMCID: PMC3070870 [Available on 2012/5/1] PMID: 21454298 [PubMed - indexed for MEDLINE]

239. Ecotoxicol Environ Saf. 2011 May;74(4):593-9. Epub 2011 Mar 30.

Effects of atrazine, agricultural runoff, and selected effluents on antimicrobial activity of skin peptides in Xenopus laevis.

Gibble RE, Baer KN.

College of Pharmacy, Department of Toxicology, The University of Louisiana at Monroe, 700 University Avenue, Monroe, LA 71209-0470, USA.

Atrazine (technical and formulation), agricultural runoff containing atrazine, and treated sewage and landfill effluents were evaluated for their potential to modulate antimicrobial activity of Xenopus laevis skin secretions against the chytrid fungus, Batrachochytrium dendrobatidis. This chytrid fungus is implicated in several localized mass mortality events, yet the cause of the susceptibility of amphibians to this newly emergent pathogen is unknown. Antimicrobial peptides secreted from dermal glands are thought to provide critical protection against this pathogen. Chronic exposure of X. laevis larvae to agricultural runoff decreased protein content of collected secretions, while treated wastewater effluents increased protein content. However, the in vitro bioactivity was decreased in treatments with both increased and decreased protein. No differences were observed in protein or bioactivity following laboratory exposures of technical atrazine or a typical atrazine formulation (AAtrex(®) 4L/Top Surf(®)). These findings demonstrate that exposure of an amphibian model to agricultural runoff or effluent from municipal sewage treatment plants and landfills alters peptide production and in vitro activity of protective peptides. Although evidence suggests peptide production and bioactivity is a critical part of amphibian resistance to pathogens such as the chytrid fungus, the implications of observed effects for immunity and infection are not clear.

PMID: 21453969 [PubMed - indexed for MEDLINE]

240. Parasitol Res. 2011 Sep;109(3):823-31. Epub 2011 Mar 31.

Larvicidal potential of silver nanoparticles synthesized using fungus Cochliobolus lunatus against Aedes aegypti (Linnaeus, 1762) and Anopheles stephensi Liston (Diptera; Culicidae).

Salunkhe RB, Patil SV, Patil CD, Salunke BK.

School of Life Sciences, North Maharashtra University, Post Box-80, Jalgaon 425001, Maharashtra, India.

Larvicides play a vital role in controlling mosquitoes in their breeding sites. The present study was carried out to establish the larvicidal activities of mycosynthesized silver nanoparticles (AgNPs) against vectors: Aedes aegypti and Anopheles stephensi responsible for diseases of public health importance. The AgNPs synthesized by filamentous fungus Cochliobolus lunatus, characterized by UV-Vis spectrophotometry, Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy, and transmission electron microscopy. The characterization studies confirmed the spherical shape and size (3-21 nm) of silver nanoparticles. The efficacy of mycosynthesized AgNPs at all the tested concentrations (10, 5, 2.5, 1.25, 0.625, and 0.3125 ppm) against second, third, and fourth instar larvae of A. aegypti (LC(50) 1.29, 1.48, and 1.58; LC(90) 3.08, 3.33, and 3.41 ppm) and against A. stephensi (LC(50) 1.17, 1.30, and 1.41; LC(90) 2.99, 3.13, and 3.29 ppm) were observed, respectively. The mortality rates were positively correlated with the concentration of AgNPs. Significant (P < 0.05) changes in the larval mortality was also recorded between the period of exposure against fourth instar larvae of A. aegypti and A. stephensi. The possible larvicidal activity may be due to penetration of nanoparticles through membrane. Toxicity studies carried out against non-target fish species Poecilia reticulata, the most common organism in the habitats of A. aegypti and A. stephensi showed no toxicity at LC50 and LC90 doses of the AgNPs. This is the first report on mosquito larvicidal activity of mycosynthesized nanoparticles. Thus, the use of fungus C. lunatus to synthesize silver nanoparticles is a rapid, eco-friendly, and a single-step approach and the AgNps formed can be potential mosquito larvicidal agents.

PMID: 21451993 [PubMed - indexed for MEDLINE]

241. J Nanosci Nanotechnol. 2011 Jan;11(1):503-6.

A simplified fabrication process of Fresnel zone plates with controlling proximity effect correction.

Jeon SC, Kim DS, Kim KN, Kim KM, Seo CH, Yoo JJ, Lee DK.

National NanoFab Center (NNFC), KAIST, Daejeon 305-806, Korea.

Fresnel zone plates (FZPs) for soft X-ray microscopy with an energy range of 284 eV to 540 eV are designed and fabricated in a simple method. An adequate aspect ratio of the resist mold for electroplating was obtained by the proximity effect correction technology for an incident electron beam on a single thick layer resist. Without additional complicated reactive ion etching, a sufficient electro plating mold for nickel structures was fabricated. The overall fabrication procedures which involve a mix-and-match overlay technique for electron beam lithography and an optic exposure system that centers the membrane on the nanostructures, and hybrid silicon etching technology in junction with deep anisotropy and a KOH wet method in order to release the backside Si substrates of the Si3N4 membranes with no deformation of FZPs are introduced. High quality nanostructures with minimum outermost zone widths of 50 nm and diameters of 120 microm were fabricated with simplified fabrication process and with cost-effective.

PMID: 21446485 [PubMed]

242. Mikrobiol Z. 2011 Jan-Feb;73(1):29-35.

[Influence of ionizing radiation on activity of enzymes of antioxidant defense of Paecilomyces lilaclvus (Thom) Samson].

[Article in Ukrainian]

Tuhaĭ TI.

The level of activity of antioxidant protection enzymes (superoxide dismutase, catalase and peroxidase) under exposure to ionizing radiation and without it in strain Paecilomyces lilacinus, showing radioadaptive properties, and in control one has been investigated. It has been established that the researched strains are characterized by the high level activity of superoxide dismutase (200-800 AU/mg protein), extracellular and intracellular catalase (0.02-40 mmol min(-1) mg(-1) protein) and peroxidase (0.2-4 mmol min(-1) mg(-1) protein). Ionizing radiation was the inducer of significant changes in antioxidant enzyme activity of the control strain (from the lack of influence to the change of activity by an order) and showed considerably less influence on their activity in the strain, showing radioadaptive properties (the activity changes by 40-50%). The complex response of antioxidant enzymes in investigated strains under the exposure to ionizing radiation has been revealed.

PMID: 21442950 [PubMed - indexed for MEDLINE]

243. Prep Biochem Biotechnol. 2011 Apr;41(2):138-53.

Zingipain, A cysteine protease from Zingiber ottensii Valeton rhizomes with antiproliferative activities against fungi and human malignant cell lines.

Karnchanatat A, Tiengburanatam N, Boonmee A, Puthong S, Sangvanich P.

Institute of Biotechnology and Genetic Engineering, Chulalongkorn University, Bangkok, Thailand. i_am_top@hotmail.com.com

The objective of this study was to investigate the activity of a protein identified as cysteine protease, purified from Zingiber ottensii Valeton rhizomes, in terms of antiproliferation against fungi, bacteria, and human malignant cell lines. By means of buffer extraction followed by (NH(4))(2)SO(4) precipitation and ion-exchange chromatography, the obtained dominant protein (designated F50) was submitted to non-denaturing and reducing sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), where a single band and three bands were revealed from eletrophoretic patterns, respectively. It could be concluded at this point that the F50 was potentially a heterotrimer or heterodimer composed of either two small (∼13.8 and ∼15.2 kD) subunits or these two together with a larger (∼32.5 kD) one. In-gel digestion was carried out for the most intense band from reducing SDS-PAGE, and to the resulting material was applied liquid chromatography (LC)-mass spectroscopy (MS)/MS. The main F50 subunit was found to contain fragments with 100% similarity to zingipain-1, a cysteine protease first discovered in Zingiber officinale. The activity corresponding to the identified data, cysteine protease, was then confirmed in the F50 by azocasein assay and a positive result was obtained. The F50 then was further investigated for antiproliferation against three plant pathogenic fungi species by disk diffusion test, four bacterial species by direct exposure in liquid culture and dish diffusion tests, and five human malignant cell lines by tissue culture assay. It was found that a dose of 23.6 µg F50/0.3 cm(2) of paper disk exhibited the best inhibitory effect against Collectotrichum cassiicola, while lesser effects were found in Exserohilum turicicum and Fusarium oxysporum, respectively. No inhibitory effect against bacterial proliferation was detected in all studied bacterial strains. However, relatively strong antiproliferative effects were found against five human cell lines, with IC50 values ranging from 1.13 µg/mL (hepatoma cancer; HEP-G2) to 5.37 µg/mL (colon cancer; SW620). By periodic acid-Schiff's staining and phenol-sulfuric acid assay, the F50 was determined as a glycoprotein containing 26.30 ± 1.01% (by weight) of carbohydrate. Thus, a new glycoprotein with protease activity was successfully identified in Zingiber ottensii rhizome. The glycoprotein also contained antiproliferative activity against some plant pathogenic fungi and human cancer cell lines.

PMID: 21442550 [PubMed - indexed for MEDLINE]

244. Adv Dent Res. 2011 Apr;23(1):56-60.

Effect of traditional Chinese medicinal herbs on Candida spp. from patients with HIV/AIDS.

Liu X, Han Y, Peng K, Liu Y, Li J, Liu H.

Department of Traditional Chinese Medicine and Oral Medicine, Peking University, Beijing, China. songxiaoliu@yahoo.com.cn

As an opportunistic infection, candidiasis is common among individuals infected with HIV. About 90% of patients develop oral and/or oropharyngeal candidiasis in various stages of AIDS. Triazole antifungal agents, such as fluconazole and itraconazole, are considered to be first-choice agents for treatment and prevention because of their relatively low side effects and high effectiveness on mucosal infections. However, with prolonged exposure to azoles, drug resistance becomes a challenge for clinicians and patients alike. In traditional Chinese medicine, more than 300 herbs have been discovered to have "pesticidal" activities, and some of these have been used as antifungal agents in clinical practice for many years. Crude extracts from a number of medicinal herbs have been shown to exhibit antifungal activities in vitro. These include cortex moutan, cortex pseudolaricis, rhizoma alpiniae officinarum, rhizoma coptidis, clove and cinnamon, anemarrhena cortex phellodendri, ramulus cinnamomi, and Chinese gall. The effective anti-Candida principals were identified to be berberine, palmatine, allincin, pseudolaric acid A and B, magnolol, honokiol, and galangin. Thus, traditional Chinese medicinal herbs provide abundant choices for the treatment of refractory candidiasis commonly seen in HIV/AIDS patients. However, there remains a need for further screening of effective extracts and for study of the antifungal mechanisms involved. Importantly, ahead of clinical application, the safety of these compounds must be firmly established.

PMID: 21441482 [PubMed - indexed for MEDLINE]

245. Occup Environ Med. 2011 Nov;68(11):849-55. Epub 2011 Mar 24.

Airborne cultivable microflora and microbial transfer in farm buildings and rural dwellings.

Normand AC, Sudre B, Vacheyrou M, Depner M, Wouters IM, Noss I, Heederik D, Hyvärinen A, Genuneit J, Braun-Fahrländer C, von Mutius E, Piarroux R; GABRIEL-A Study Group.

Collaborators: Kovacs K, Morass B, Horak E, Bu G, Sitaridis N, Genuneit J, Weber J, Mutius E, Debinska A, Danielewicz H, Sozanska B, Waser M, Braun-Fahrla C.

Department of Parasitology and Mycology, Assistance Publique-Hoˆpitaux de Marseille, Marseille, France. acecilenor@hotmail.com

OBJECTIVES: Exposure to environments rich in microorganisms such as farms has been shown to protect against the development of childhood asthma and allergies. However, it remains unclear where, and how, farm and other rural children are exposed to microbes. Furthermore, the composition of the microbial flora is poorly characterised. We tested the hypothesis that farm children are exposed indoors to substantial levels of viable microbes originating from animal sheds and barns. We also expected that environmental microbial flora on farms and in farm homes would be more complex than in the homes of rural control children.
METHODS: Dust samples were collected using passive samplers in the bedrooms of the following groups of children in rural Bavaria, Germany: (i) those living on farms (n=144), (ii) those regularly exposed to farm environments but not living on farms (n=149) and (iii) those never visiting farms (n=150). For farm children, additional samples were collected in animal sheds and barns. All samples were subjected to fungal and bacterial culturing.
RESULTS: Detectable levels of microorganisms were more often found in samples taken from farm dwellings than from other homes. Farm dwellings also showed higher microbial levels. Microbial counts of farm dwelling samples correlated with the counts in corresponding animal sheds and barns.
CONCLUSIONS: Microorganisms are transported from animal sheds and barns into farm dwellings. Therefore, children living in these environments are exposed when indoors and when visiting animal sheds and barns. Indoor exposure may also contribute to the protective effect of the farm environment.

PMID: 21441175 [PubMed - indexed for MEDLINE]

246. J Hosp Infect. 2011 Jul;78(3):226-30. Epub 2011 Mar 25.

Environmental and clinical epidemiology of Aspergillus terreus: data from a prospective surveillance study.

Rüping MJ, Gerlach S, Fischer G, Lass-Flörl C, Hellmich M, Vehreschild JJ, Cornely OA.

Department I of Internal Medicine, University of Cologne, Cologne, Germany.

Aspergillus terreus may be resistant to amphotericin B and is associated with significant morbidity and mortality in immunocompromised patients. Local incidence is influenced by the density of airborne Aspergillus spp. spores which may in turn depend on meteorological factors. Once-weekly environmental samples were collected prospectively inside and outside the University Hospital of Cologne, Germany (UHC) and haematological patients were screened for nasal Aspergillus spp. colonisation and monitored for invasive fungal disease (IFD). RAPD (rapid amplification of polymorphic DNA)-polymerase chain reaction (PCR) and amphotericin B susceptibility testing were performed on all A. terreus isolates. A total of 4919 colony-forming units (cfu) were isolated (2212 indoors, 2707 outdoors). Further identification revealed A. fumigatus (73.5%), A. niger (4.3%), A. flavus (1.7%), A. terreus (0.2%) and non-Aspergillus fungi (20.3%). RAPD-PCR did not reveal clonal relationships between the A. terreus isolates. All A. terreus isolates displayed complete resistance to amphotericin. The B. Aspergillus spp. conidia exposure was lowest in June and highest in November inside and outside UHC. Conidia load correlated with the season and the relative humidity, with increasing spore counts during dry periods. One out of 855 nasal swabs was positive for A. niger. The patient did not develop IFD. A. terreus is unlikely to be a relevant pathogen at the UHC. Results from RAPD-PCR suggested a wide epidemiological variety of strains rather than a common source of contamination. Nasal swab surveillance cultures for early detection of Aspergillus spp. colonisation were not useful in identifying patients who may develop IFD. The risk of IFD at the UHC may increase in autumn and during dry periods.

PMID: 21440331 [PubMed - indexed for MEDLINE]

247. Int J Biol Macromol. 2011 Jul 1;49(1):37-43. Epub 2011 Mar 31.

Immobilization of Aspergillus oryzae β galactosidase on zinc oxide nanoparticles via simple adsorption mechanism.

Husain Q, Ansari SA, Alam F, Azam A.

Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh 202002, India. qayyumbiochem@gmail.com

The present study demonstrates the immobilization of Aspergillus oryzae β galactosidase on native zinc oxide (ZnO) and zinc oxide nanoparticles (ZnO-NP) by simple adsorption mechanism. The binding of enzyme on ZnO-NP was confirmed by Fourier transform-infrared spectroscopy and atomic force microscopy. Native ZnO and ZnO-NP showed 60% and 85% immobilization yield, respectively. Soluble and immobilized enzyme preparations exhibited similar pH-optima at pH 4.5. ZnO-NP bound β galactosidase retained 73% activity at pH 7.0 while soluble and ZnO adsorbed enzyme lost 68% and 53% activity under similar experimental conditions, respectively. There was a marked broadening in temperature-activity profile for ZnO-NP adsorbed β galactosidase; it showed no difference in temperature-optima between 50°C and 60°C. Moreover, ZnO-NP adsorbed β galactosidase retained 53% activity after 1h incubation with 5% galactose while the native ZnO- and soluble β galactosidase exhibited 35% and 28% activity under similar exposure, respectively. Native ZnO and ZnO-NP adsorbed β galactosidase retained 61% and 75% of the initial activity after seventh repeated use, respectively. It was noticed that 54%, 63% and 71% milk lactose was hydrolyzed by soluble, ZnO adsorbed and ZnO-NP adsorbed β galactosidase in batch process after 9h while whey lactose was hydrolyzed to 61%, 68% and 81% under similar experimental conditions, respectively. In view of its easy production, improved stability against various denaturants and excellent reusability, ZnO-NP bound β galactosidase may find its applications in constructing enzyme-based analytical devices for clinical, environmental and food technology.

PMID: 21439994 [PubMed - indexed for MEDLINE]

248. Sci Total Environ. 2011 May 1;409(11):2005-9.

Airborne fungal volatile organic compounds in rural and urban dwellings detection of mould contamination in 94 homes determined by visual inspection and airborne fungal volatile organic compounds method.

Moularat S, Hulin M, Robine E, Annesi-Maesano I, Caillaud D.

Département Energie Santé Environnement, Division Santé, Laboratoire de Recherche et d'Innovation pour l'Hygiène des Bâtiments, 77447 Marne-la-Vallée, France. stephane.moularat@cstb.fr

Moulds can both degrade the materials and structures they colonise and contribute to the appearance of symptoms and diseases in the inhabitants of contaminated dwellings. Only few data have compared the levels of contamination in urban and rural environments and the results are not consistent. The aim of this study was to use a fungal contamination index, based on the detection of specific Microbial Volatile Organic Compounds (MVOC), to determine the exposure to moulds of individuals living in urban and rural dwellings. For this purpose, 94 dwellings (47 in an urban setting in Clermont-Ferrand and 47 in rural areas of the Auvergne region, France) were studied. By demonstrating marked disparities between the proportion of visible contamination (19%) and that of active, visible and/or hidden contamination (59%) and the fact that almost all visible contamination was identified by MVOC, we were able to show that use of the index seemed relevant to confirm the actual presence of fungal contamination in a dwelling. Furthermore, it was possible to demonstrate a relationship between moulds and the presence of water on surfaces (condensation, infiltrations, water damage, etc.). A higher proportion of positive fungal contamination index in rural homes was observed compared to the proportion in urban ones (68% versus 49%; p<0.05).

PMID: 21439610 [PubMed - indexed for MEDLINE]

249. Biochem J. 2011 Jun 15;436(3):537-46.

Effects on antigen-presenting cells of short-term interaction with the human host defence peptide β-defensin 2.

Morgera F, Pacor S, Creatti L, Antcheva N, Vaccari L, Tossi A.

Department of Life Sciences, University of Trieste, Trieste 34127, Italy.

β-Defensins are antimicrobial peptides that exert their host-defence functions at the interface between the host and microbial biota. They display a direct, salt- and medium-sensitive cidal activity, in vitro, against a broad spectrum of bacteria and fungi, and there is increasing evidence that they also play a role in alerting and enhancing cellular components of innate and adaptive immunity. Their interaction with biological membranes plays a central role in both of these types of activities. In the present study, we have investigated the interaction of fluorescently labelled hBD2 (human β-defensin 2) with monocytes, macrophages and iDCs (immature dendritic cells), observing a differential capacity to be rapidly internalized into these cells. Complementary microscopy techniques [TEM (transmission electron microscopy), optical microscopy and IR microspectroscopy] were used to explore the functional and biological implications of these interactions on iDCs. Short-term exposure to the peptide resulted in significant alterations in membrane composition and re-organization of the endomembrane system, with the induction of degranulation. These events may be associated with the antigen-presenting activities or the chemotaxis of iDCs, which appears to occur via both CCR6 (CC chemokine receptor 6)-dependent and -independent mechanisms.

PMID: 21434867 [PubMed - indexed for MEDLINE]

250. Parasitol Res. 2011 Sep;109(3):751-8. Epub 2011 Mar 19.

Survival of anopheline eggs and their susceptibility to infection with Metarhizium anisopliae and Beauveria bassiana under laboratory conditions.

Luz C, Mnyone LL, Russell TL.

Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, CP 131, 74001-970 Goiânia, GO, Brazil. wolf@iptsp.ufg.br

The viability of Anopheles gambiae sensu stricto and Anopheles arabiensis (Diptera: Culicidae) eggs over time and the ovicidal activity of Beauveria bassiana (Ascomycota: Cordycipitaceae) and Metarhizium anisopliae (Ascomycota: Clavicipitaceae) were investigated. Eggs were incubated in soil or leaf litter for up to 12 weeks at 26°C and 75%, 86% or >98% relative humidity (RH). Eggs were treated topically with M. anisopliae ICIPE-30 or B. bassiana I93-825 conidia in either water or oil-in-water formulations. Survival of eggs whether treated or not with fungus was similar, and untreated eggs generally did not survive longer than 2 weeks regardless of the substrate or humidity tested. After a minimal 5-day exposure, M. anisopliae at 5 × 10(6) conidia/cm(2) clearly reduced the number of larvae. The efficacy of the fungus increased when it was oil-in-water formulated, and eclosion was completely prevented regardless of the conidial concentration (10(5)-10(7) conidia/cm(2)) after a 10-day exposure in soils at >98% RH. Treatment of eggs with B. bassiana, however, failed to reduce the number of eclosing larvae. This is the first demonstration of the ovicidal activity by M. anisopliae against either A. gambiae s. s. or A. arabiensis and the results underline the potential of this fungus against anopheline mosquitoes.

PMID: 21424402 [PubMed - indexed for MEDLINE]

251. Antimicrob Agents Chemother. 2011 Jun;55(6):2506-14. Epub 2011 Mar 21.

Loss of heterozygosity of FCY2 leading to the development of flucytosine resistance in Candida tropicalis.

Chen YN, Lo HJ, Wu CC, Ko HC, Chang TP, Yang YL.

Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan, Republic of China.

As fluconazole resistance becomes an emerging issue for treating infections caused by Candida tropicalis, searching for alternative becomes a prominent task. In the present study, 97 clinical isolates of C. tropicalis were tested for the susceptibilities to flucytosine (5FC) with the Etest method. Although only one isolate was resistant to 5FC, 30 susceptible isolates could produce resistant progeny after exposure to the drug. Interestingly, 22 of these 30 clinical isolates had a heterozygous G/T at the 145th position on FCY2, encoding purine-cytosine permease, whereas their progeny recovered from within the inhibitory ellipses had homozygous T/T, resulting in null alleles for both copies of the gene and produced only truncated proteins, effecting the 5FC resistance. Furthermore, we found that two major fluconazole-resistant clinical clones, diploid sequence type 98 (DST98) and DST140, had a homozygous G/G at the 145th position, and neither was able to produce 5FC-resistant progeny within the inhibitory ellipses. Hence, strains of C. tropicalis containing heterozygous alleles may develop 5FC resistance readily, whereas those with homozygous G/G wild-type alleles can be treated with 5FC. Subsequently, a combination of 5FC and another antifungal drug is applicable for treating infections of C. tropicalis.

PMCID: PMC3101439 PMID: 21422221 [PubMed - indexed for MEDLINE]

252. Int J Antimicrob Agents. 2011 Jun;37(6):567-71. Epub 2011 Mar 21.

Effects of enrofloxacin on the human intestinal microbiota in vitro.

Chen T, Yuan J, Feng X, Wei H, Hua W.

Department of Laboratory Animal Science, College of Basic Medicine, Third Military Medical University, Chongqing 400038, China.

An anaerobic, continuous-flow culture method has been developed to assess the effects of different levels of enrofloxacin (ENR) on the human intestinal microbiota. Chemostats containing human faecal flora were exposed to 1.25, 12.5 and 125 μg/mL ENR. Before and during drug exposure, samples aspirated from culture vessels were analysed using viable cell counting and denaturing gradient gel electrophoresis (DGGE). In addition, the colonisation resistance (CR) of the microbiota to Candida albicans SC5314 was evaluated. When exposed to 1.25 μg/mL ENR, total counts of aerobic bacteria, anaerobic bacteria, Lactobacillus, enterococci, Escherichia coli and Bacteroides fragilis were similar to the control group, except for Bifidobacterium; when exposed to 12.5 μg/mL and 125μg/mL ENR, numbers of categorised microorganisms changed significantly, except for B. fragilis. DGGE indicated that although 1.25 μg/mL ENR had little effect on the total number of microbiota, several bands representing dominant bacteria disappeared. The bands disappeared more quickly when exposed to 12.5 μg/mL and 125 μg/mL ENR. In addition to their influence on microbial diversity, different levels of ENR reduced the CR of the intestinal microbiota to C. albicans SC5314.

PMID: 21420834 [PubMed - indexed for MEDLINE]

253. J Cataract Refract Surg. 2011 Apr;37(4):763-6.

In vitro efficacy of a povidone-iodine 0.4% and dexamethasone 0.1% suspension against ocular pathogens.

Pelletier JS, Miller D, Liang B, Capriotti JA.

Ocean Ophthalmology Group, North Miami Beach, Miami, Florida, USA. jessepelletier@yahoo.com

PURPOSE: To assess the efficacy of a povidone-iodine 0.4%-dexamethasone 0.1% suspension against bacterial, fungal, and Acanthamoeba clinical isolates. SETTING: Bascom Palmer Eye Institute, McKnight Research Building, Miami, Florida, USA. DESIGN: Experimental study.
METHODS: One hundred milliliters of 10(4) colony-forming units/mL of ocular isolates of methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, Serratia marcescens, Candida albicans, Fusarium solani, and Acanthamoeba castellanii were inoculated into 100 μL of a povidone-iodine 0.4%-dexamethasone 0.1% suspension in a 96-well microtiter plate incubated at room temperature. Organism viability was assessed at 15, 30, and 60 seconds by removing 10 μL aliquots and streaking onto a 5.0% sheep blood agar plate (fungi and bacteria) and agar-agar (Acanthamoeba) using a 0.001 calibrated loop. The plates were then incubated at 35 °C and monitored for up to 7 days. Isolates were inoculated into 200 μL of trypticase soy broth as controls. The number of colonies was counted and compared with controls to determine the kill rate.
RESULTS: A 99.9% kill was observed for MRSA, P aeruginosa, S marcescens, and C albicans after 15 seconds of exposure and for F solani after 60 seconds. Acanthamoeba castellanii cyst viability was not inhibited by exposure to the povidone-iodine and dexamethasone suspension. Organism growth was achieved on all control broth.
CONCLUSIONS: Povidone-iodine 0.4%-dexamethasone 0.1% suspension killed all bacterial and candida isolates within 15 seconds of exposure. It killed Fusarium isolates at 60 seconds but was ineffective against Acanthamoeba cysts. FINANCIAL DISCLOSURE: Drs. Pelletier and Miller have no financial or proprietary interest in any material or method mentioned. Additional disclosures are found in the footnotes.

Published by Elsevier Inc.

PMID: 21420603 [PubMed - indexed for MEDLINE]

254. J Agric Food Chem. 2011 May 11;59(9):5087-92. Epub 2011 Mar 28.

Characterization, antimicrobial activity, and mechanism of a high-performance (-)-epigallocatechin-3-gallate (EGCG)-CuII/polyvinyl alcohol (PVA) nanofibrous membrane.

Sun LM, Zhang CL, Li P.

School of Life Sciences and Technology, Tongji University, Shanghai, People's Republic of China.

(-)-Epigallocatechin-3-gallate (EGCG) exhibited strong antimicrobial activity. However, the easy oxidation of EGCG has limited its application. To increase the antimicrobial activity and stability of EGCG, the EGCG-Cu(II) complex was formed by chelating copper ions and then electronspun into polyvinyl alcohol (PVA) nanofibers. Electronspun nanofibrous membranes were investigated by Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM), which showed that the average fiber diameter was 210 nm. Minimal inhibitory concentrations (MICs) of EGCG-Cu(II)/PVA membranes were tested against the tested strains. The bactericidal activity of EGCG-Cu(II) was suppressed by ethylenediaminetetraacetic acid (EDTA). Cell killing was accompanied by the leakage of intracellular proteins, indicating that the cytoplasmic membrane was badly damaged after exposure to the EGCG-Cu(II)/PVA membrane. We observed the process of cell damage by SEM. On the basis of experimental evidence and theoretical analyses, the mechanism proposed that copper ions played a cooperative role in the bactericidal process of EGCG. To evaluate the antimicrobial activity of the EGCG-Cu(II)/PVA membrane, we developed a rapid detection method by labeling cells with water-soluble CdTe quantum dots.

PMID: 21417240 [PubMed - indexed for MEDLINE]

255. Biol Pharm Bull. 2011;34(2):243-8.

Neoechinulin a impedes the progression of rotenone-induced cytotoxicity in PC12 cells.

Akashi S, Kimura T, Takeuchi T, Kuramochi K, Kobayashi S, Sugawara F, Watanabe N, Arai T.

Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, Tokyo University of Science; 2641 Yamazaki, Noda, Chiba 278–8510, Japan.

Neoechinulin A, an indole alkaloid from marine fungi, can protect PC12 cells from the cytotoxicity of 1-methyl-4-phenylpyridinium (MPP(+)), a Parkinson disease-inducing neurotoxin, by ameliorating downstream events resulting from mitochondrial complex I inactivation. However, the cytoprotective mechanisms remained unclear. In this study, by using rotenone, another parkinsonian-inducing neurotoxin targeting mitochondrial complex I, we investigated the cytoprotective mechanism of neoechinulin A. Rotenone-induced cell death was associated with accelerated glucose consumption, and excess glucose supplementation in the culture medium almost completely suppressed cell death, suggesting that glucose deficiency in the medium is critical for triggering cell death in this model. Co-treatment with neoechinulin A, but not neoechinulin A pre-treatment before rotenone exposure, significantly impeded cell death by rotenone. Although the presence of neoechinulin A did not affect the accelerated glycolytic turnover in rotenone-treated cells, it paradoxically decreased ATP levels in the cells, suggesting increased ATP consumption. Although the link between the decreased ATP levels and cytoprotection is not clear at present, it suggests that neoechinulin A may ameliorate rotenone toxicity by activating a cytoprotective machinery that requires ATP.

PMID: 21415535 [PubMed - indexed for MEDLINE]

256. Bioresour Technol. 2011 May;102(10):5905-11. Epub 2011 Feb 24.

Response of compost maturity and microbial community composition to pentachlorophenol (PCP)-contaminated soil during composting.

Zeng G, Yu Z, Chen Y, Zhang J, Li H, Yu M, Zhao M.

College of Environmental Science and Engineering, Hunan University, Changsha 410082, PR China. zgming@hnu.cn

Two composting piles were prepared by adding to a mixture of rice straw, vegetables and bran: (i) raw soil free from pentachlorophenol (PCP) contamination (pile A) and (ii) PCP-contaminated soil (pile B). It was shown by the results that compost maturity characterized by water soluble carbon (WSC), TOC/TN ratio, germination index (GI) and dehydrogenase activity (DA) was significantly affected by PCP exposure, which resulted in an inferior degree of maturity for pile B. DGGE analysis revealed an inhibited effect of PCP on compost microbial abundance. The bacteria community shifts were mainly consistent with composting factors such as temperature, pH, moisture content and substrates. By contrast, the fungal communities were more sensitive to PCP contamination due to the significant correlation between fungal community shifts and PCP removal. Therefore, the different microbial community compositions for properly evaluating the degree of maturity and PCP contamination were suggested.

PMID: 21414773 [PubMed - indexed for MEDLINE]

257. Clin Pharmacol Ther. 2011 May;89(5):702-7. Epub 2011 Mar 16.

Safety and pharmacokinetics of multiple-dose anidulafungin in infants and neonates.

Cohen-Wolkowiez M, Benjamin DK Jr, Piper L, Cheifetz IM, Moran C, Liu P, Aram J, Kashuba AD, Capparelli E, Walsh TJ, Hope WW, Smith PB.

Department of Pediatrics, Duke University, Durham, North Carolina, USA. michael.cohenwolkowiez@duke.edu

Candida infections are common and often fatal in infants and neonates. Anidulafungin has excellent activity against Candida species, but the pharmacokinetics (PK) and safety of the drug in infants and neonates are unknown. The object of our study was to determine the PK and safety of anidulafungin in infants and neonates at risk for invasive candidiasis. Intravenous anidulafungin (1.5 mg/kg/day maintenance dose) was administered to 15 infants and neonates over 3 to 5 days. Plasma samples were collected after the first dose and again after the third to fifth doses. The pharmacokinetic parameters of the drug were determined by noncompartmental analysis. Safety was assessed using National Cancer Institute common toxicity criteria. The study showed that drug exposure levels were similar between neonates and infants; the median areas under the concentration-time curve (range) was 75 (30-109) µg·h/ml and 98 (55-278) µg·h/ml (P = 0.12) for neonates and infants, respectively. No drug-related serious adverse events were observed. The study results indicate that neonates and infants receiving 1.5 mg/kg/day have anidulafungin exposure levels similar to those in children receiving similar weight-based dosing and in adult patients receiving 100 mg/day.

PMCID: PMC3124385 PMID: 21412233 [PubMed - indexed for MEDLINE]

258. Nanotechnology. 2011 Apr 29;22(17):175101. Epub 2011 Mar 16.

Transmission electron microscopy for elucidating the impact of silver-based treatments (ionic silver versus nanosilver-containing coating) on the model yeast Saccharomyces cerevisiae.

Despax B, Saulou C, Raynaud P, Datas L, Mercier-Bonin M.

Université de Toulouse, UPS, INPT, LAPLACE, 118 route de Narbonne, F-31062 Toulouse cedex 9, France.

After exposure to ionic silver or nanosilver-containing plasma coating, the same visual aspect of scanning transmission electron microscopy (STEM) images was observed for the model yeast Saccharomyces cerevisiae. The main common feature was the presence of electron-dense nodules all over the cell. However, high resolution TEM (HRTEM), STEM, energy dispersive x-ray microanalysis spectroscopy (EDS) and electron microdiffraction revealed some striking differences. Regarding ionic silver exposure, the formation of electron-dense nodules was related to the Ag(+) reactivity towards sulfur-containing compounds to form clusters with Ag(2)S-like structures, together with the production of a few silver nanocrystals, mainly at the cell wall periphery. For nanosilver-based treatment, some sulfur-containing silver clusters preferentially located at the cell wall periphery were detected, together with nodules composed of silver, sulfur and phosphorus all over the cell. In both silver-based treatments, nitrogen and silver signals overlapped, confirming the affinity of silver entities for proteinaceous compounds. Moreover, in the case of nanosilver, interactions of silver with phosphorus-containing subcellular structures were indicated.

PMID: 21411917 [PubMed - indexed for MEDLINE]

259. Ecotoxicol Environ Saf. 2011 Jul;74(5):1434-43. Epub 2011 Mar 15.

Cytological stress and element uptake in moss and lichen exposed in bags in urban area.

Spagnuolo V, Zampella M, Giordano S, Adamo P.

Dipartimento di Biologia Strutturale e Funzionale, Università di Napoli Federico II, Complesso Universitario Monte S. Angelo, Via Cintia 4, I-80126 Napoli, Italy. valeria.spagnuolo@unina.it

In this study cytological ultrastructure, total content of C, N and S, and cellular location of major and trace elements (K, Ca, Mg, Cu, Pb and Zn) were investigated in the moss Hypnum cupressiforme and in the lichen Pseudevernia furfuracea exposed in bags for a spring-summer 12-weeks period in the urban area of Naples city. In the moss, severe ultrastructural damages, such as membrane interruptions and dehydration, developed after exposure supporting the occurrence of a dead biomonitor. In the lichen, the post-exposure stress marks, such as the development of lysosome-like vesicles and concentric bodies, or the production of melanin, were overall compatible with life. With exposure, N, S, major and trace element contents all increased in both biomonitors, while C remained substantially unchanged. Copper and Pb were mainly retained in extracellular and particulate forms. Intracellular concentration of Zn consistently increased in both biomonitors, irrespective of their vitality. In transplants, cellular location of elements can better reflect the form in which they occur in the environment.

PMID: 21411142 [PubMed - indexed for MEDLINE]

260. Digestion. 2011;83 Suppl 1:1-6. Epub 2011 Mar 10.

Flavor perception in human infants: development and functional significance.

Beauchamp GK, Mennella JA.

Monell Chemical Senses Center, Philadelphia, PA 19104, USA. beauchamp@monell.org

BACKGROUND: Foods people consume impact on their health in many ways. In particular, excess intake of salty, sweet and fatty foods and inadequate intake of fruits and vegetables have been related to many diseases including diabetes, hypertension, cardiovascular disease and some cancers. The flavor of a food determines its acceptability and modulates intake. It is thus critical to understand the factors that influence flavor preferences in humans. AIM: To outline several of the important factors that shape flavor preferences in humans.
METHODS: We review a series of studies, mainly from our laboratories, on the important role of early experiences with flavors on subsequent flavor preference and food intake. RESULTS AND CONCLUSIONS: Some taste preferences and aversions (e.g. liking for sweet, salty and umami; disliking for bitter) are innately organized, although early experiences can modify their expression. In utero events may impact on later taste and flavor preferences and modulate intake of nutrients. Both before and after birth, humans are exposed to a bewildering variety of flavors that influence subsequent liking and choice. Fetuses are exposed to flavors in amniotic fluid modulating preferences later in life and flavor learning continues after birth. Experience with flavors that are bitter, sour or have umami characteristics, as well as volatile flavors such as carrot and garlic, occurs through flavorings in breast milk, infant formula and early foods. These early experiences mold long-term food and flavor preferences which can impact upon later health.

PMCID: PMC3202923 [Available on 2012/3/1] PMID: 21389721 [PubMed - indexed for MEDLINE]

261. Oecologia. 2011 Aug;166(4):1029-41. Epub 2011 Mar 13.

Individual and combined effects of multiple pathogens on Pacific treefrogs.

Romansic JM, Johnson PT, Searle CL, Johnson JE, Tunstall TS, Han BA, Rohr JR, Blaustein AR.

Department of Zoology, Oregon State University, Corvallis, OR 97331, USA. jmromansic@gmail.com

In nature, individual hosts often encounter multiple pathogens simultaneously, which can lead to additive, antagonistic, or synergistic effects on hosts. Synergistic effects on infection prevalence or severity could greatly affect host populations. However, ecologists and managers often overlook the influence of pathogen combinations on hosts. This is especially true in amphibian conservation, even though multiple pathogens coexist within amphibian populations, and several pathogens have been implicated in amphibian population declines and extinctions. Using an amphibian host, Pseudacris regilla (Pacific treefrog), we experimentally investigated interactive effects among three pathogens: the trematode Ribeiroia sp. (hereafter, Ribeiroia), the fungus Batrachochytrium dendrobatidis (hereafter, BD), and the water mold Achlya flagellata. We detected no effects of A. flagellata, but did find effects of Ribeiroia and BD that varied depending on context. Low doses of Ribeiroia caused relatively few malformations, while higher Ribeiroia doses caused numerous deformities dominated by missing and reduced limbs and limb elements. Exposure to low doses of BD accelerated larval host development, despite there being no detectable BD infections, while exposure to higher BD doses caused infection but did not alter developmental rate. Hosts exposed to both Ribeiroia and BD exhibited the highest mortality, although overall evidence of interactive effects of multiple pathogens was limited. We suggest further research on the influence of multi-pathogen assemblages on amphibians, particularly under a variety of ecological conditions and with a wider diversity of hosts and pathogens.

PMID: 21400194 [PubMed - indexed for MEDLINE]

262. Arerugi. 2011 Feb;60(2):207-13.

[A case of bronchial asthma caused by occupational exposure to trichophyton].

[Article in Japanese]

Hoshi R, Nakagome K, Aoki H, Takaku Y, Yamaguchi T, Soma T, Nishihara F, Komiyama K, Hagiwara K, Kanazawa M, Nagata M.

Allergy Center, Saitama Medical University, Japan.

A case involved a 39-year-old female nurse in a health-care facility for elderly individuals requiring long-term care, who presented with insufficient control of bronchial asthma. Although she did not have tinea, she had opportunities for contact with patients who did. Careful interview of history suggested a relationship between asthma exacerbation and workplace, so we measured the specific IgE antibody to Trichophyton and confirmed a positive result. As occupational exposure to Trichophyton was considered as a cause of asthma exacerbations, avoidance of Trichophyton as well as anti-asthma treatment was conducted and symptoms improved. Identification and avoidance of specific allergens is essential for successful long-term management of asthma. However, measurement of specific IgE antibody to Trichophyton is not routinely performed, although this fungus could induce not only tinea, but also asthma. The possibility that occupational exposure to trichophyton could exacerbate asthma symptoms needs to be kept in mind, particularly in the case of nurses who may be in contact with elderly individuals with tinea.

PMID: 21399401 [PubMed - indexed for MEDLINE]

263. Int J Biochem Cell Biol. 2011 Jun;43(6):897-904. Epub 2011 Mar 10.

Fumonisin B1 inhibits mitochondrial respiration and deregulates calcium homeostasis--implication to mechanism of cell toxicity.

Domijan AM, Abramov AY.

Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.

Fumonisin B(1) (FB(1)) is a neurodegenerative mycotoxin produced by Fusarium verticiloides mould that contaminates maize worldwide. FB(1) toxicity has been connected with deregulation of sphingolipid metabolism, but the mechanism of cytotoxicity remains controversial. In cell cultures of rat primary astrocytes and human neuroblastoma (SH-SY5Y), we found that FB(1) inhibits mitochondrial complex I, which leads to a decrease in the rate of mitochondrial and cellular respiration, depolarisation of the mitochondrial membrane, induction of reactive oxygen species (ROS) production in mitochondria and deregulation of calcium signalling. Despite the increase in ROS production, the intracellular level of glutathione (GSH) was significantly increased. After 24h of FB(1) exposure, no cell death was observed. Thus, mitochondria appear to be the primary target of FB(1), which leads to sustained deregulation of calcium homeostasis and presumably to cell death.

PMID: 21397036 [PubMed - indexed for MEDLINE]

264. J Mol Biol. 2011 May 6;408(3):432-48. Epub 2011 Mar 15.

Destabilization and recovery of a yeast prion after mild heat shock.

Newnam GP, Birchmore JL, Chernoff YO.

School of Biology and Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332-0230, USA.

Yeast prion [PSI(+)] is a self-perpetuating amyloid of the translational termination factor Sup35. Although [PSI(+)] propagation is modulated by heat shock proteins (Hsps), high temperature was previously reported to have little or no effect on [PSI(+)]. Our results show that short-term exposure of exponentially growing yeast culture to mild heat shock, followed by immediate resumption of growth, leads to [PSI(+)] destabilization, sometimes persisting for several cell divisions after heat shock. Prion loss occurring in the first division after heat shock is preferentially detected in a daughter cell, indicating the impairment of prion segregation that results in asymmetric prion distribution between a mother cell and a bud. Longer heat shock or prolonged incubation in the absence of nutrients after heat shock led to [PSI(+)] recovery. Both prion destabilization and recovery during heat shock depend on protein synthesis. Maximal prion destabilization coincides with maximal imbalance between Hsp104 and other Hsps such as Hsp70-Ssa. Deletions of individual SSA genes increase prion destabilization and/or counteract recovery. The dynamics of prion aggregation during destabilization and recovery are consistent with the notion that efficient prion fragmentation and segregation require a proper balance between Hsp104 and other (e.g., Hsp70-Ssa) chaperones. In contrast to heat shock, [PSI(+)] destabilization by osmotic stressors does not always depend on cell proliferation and/or protein synthesis, indicating that different stresses may impact the prion via different mechanisms. Our data demonstrate that heat stress causes asymmetric prion distribution in a cell division and confirm that the effects of Hsps on prions are physiologically relevant.

PMCID: PMC3095851 [Available on 2012/5/6] PMID: 21392508 [PubMed - indexed for MEDLINE]

265. Environ Toxicol. 2011 Mar 7. doi: 10.1002/tox.20698. [Epub ahead of print]

Inflammatory cytokine gene expression in THP-1 cells exposed to Stachybotrys chartarum and Aspergillus versicolor.

Pei R, Gunsch CK.

Department of Civil and Environmental Engineering, Duke University, Box 90287, Durham, North Carolina 27708-0287, United States.

Very little is known about the mechanisms that occur in human cells upon exposure to fungi as well as their mycotoxins. A better understanding of toxin-regulated gene expression would be helpful to identify safe levels of exposure and could eventually be the basis for establishing guidelines for remediation scenarios following a water intrusion event. In this research, cytokine mRNA expression patterns were investigated in the human monocytic THP-1 cell line exposed to fungal extracts of various fragment sizes obtained from Stachybotrys chartarum RTI 5802 and/or Aspergillus versicolor RTI 3843, two common and well-studied mycotoxin producing fungi. Cytokine mRNA expression was generally upregulated 2-10 times following a 24 h exposure to fungal extracts. Expression of the proinflammatory interleukin-1β, interleukin-8, and tumor necrosis factor-α genes increased while the anti-inflammatory gene interleukin-10 also increased albeit at very low level, suggesting that negative feedback regulation mechanism of production of proinflammatory cytokines initiated upon 24 h of incubation. In addition, submicron size extracts of A. versicolor caused significant death of THP-1 cells, whereas extracts of S. chartarum caused no cell death while the mixture of the two fungi had an intermediate effect. There was no general correlation between gene expression and fragment sizes, which suggests that all submicron fragments may contribute to inflammatory response. © 2011 Wiley Periodicals, Inc. Environ Toxicol, 2011.

PMID: 21384497 [PubMed - as supplied by publisher]

266. PLoS Pathog. 2011 Feb;7(2):e1001302. Epub 2011 Feb 24.

The bZIP transcription factor MoAP1 mediates the oxidative stress response and is critical for pathogenicity of the rice blast fungus Magnaporthe oryzae.

Guo M, Chen Y, Du Y, Dong Y, Guo W, Zhai S, Zhang H, Dong S, Zhang Z, Wang Y, Wang P, Zheng X.

Department of Plant Pathology, College of Plant Protection, Nanjing Agricultural University, and Key Laboratory of Monitoring and Management of Crop Diseases and Pest Insects, Ministry of Agriculture, Nanjing, China.

Saccharomyces cerevisiae Yap1 protein is an AP1-like transcription factor involved in the regulation of the oxidative stress response. An ortholog of Yap1, MoAP1, was recently identified from the rice blast fungus Magnaporthe oryzae genome. We found that MoAP1 is highly expressed in conidia and during invasive hyphal growth. The Moap1 mutant was sensitive to H₂O₂, similar to S. cerevisiae yap1 mutants, and MoAP1 complemented Yap1 function in resistance to H₂O₂, albeit partially. The Moap1 mutant also exhibited various defects in aerial hyphal growth, mycelial branching, conidia formation, the production of extracellular peroxidases and laccases, and melanin pigmentation. Consequently, the Moap1 mutant was unable to infect the host plant. The MoAP1-eGFP fusion protein is localized inside the nucleus upon exposure to H₂O₂, suggesting that MoAP1 also functions as a redox sensor. Moreover, through RNA sequence analysis, many MoAP1-regulated genes were identified, including several novel ones that were also involved in pathogenicity. Disruption of respective MGG_01662 (MoAAT) and MGG_02531 (encoding hypothetical protein) genes did not result in any detectable changes in conidial germination and appressorium formation but reduced pathogenicity, whereas the mutant strains of MGG_01230 (MoSSADH) and MGG_15157 (MoACT) showed marketed reductions in aerial hyphal growth, mycelial branching, and loss of conidiation as well as pathogenicity, similar to the Moap1 mutant. Taken together, our studies identify MoAP1 as a positive transcription factor that regulates transcriptions of MGG_01662, MGG_02531, MGG_01230, and MGG_15157 that are important in the growth, development, and pathogenicity of M. oryzae.

PMCID: PMC3044703 PMID: 21383978 [PubMed - indexed for MEDLINE]

267. Proc Natl Acad Sci U S A. 2011 Mar 22;108(12):4944-9. Epub 2011 Mar 7.

Holliday junction-containing DNA structures persist in cells lacking Sgs1 or Top3 following exposure to DNA damage.

Mankouri HW, Ashton TM, Hickson ID.

Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, United Kingdom.

The Sgs1-Rmi1-Top3 "dissolvasome" is required for the maintenance of genome stability and has been implicated in the processing of various types of DNA structures arising during DNA replication. Previous investigations have revealed that unprocessed (X-shaped) homologous recombination repair (HRR) intermediates persist when S-phase is perturbed by using methyl methanesulfonate (MMS) in Saccharomyces cerevisiae cells with impaired Sgs1 or Top3. However, the precise nature of these persistent DNA structures remains poorly characterized. Here, we report that ectopic expression of either of two heterologous and structurally unrelated Holliday junction (HJ) resolvases, Escherichia coli RusA or human GEN1(1-527), promotes the removal of these X-structures in vivo. Moreover, other types of DNA replication intermediates, including stalled replication forks and non-HRR-dependent X-structures, are refractory to RusA or GEN1(1-527), demonstrating specificity of these HJ resolvases for MMS-induced X-structures in vivo. These data suggest that the X-structures persisting in cells with impaired Sgs1 or Top3 contain HJs. Furthermore, we demonstrate that Sgs1 directly promotes X-structure removal, because the persistent structures arising in Sgs1-deficient strains are eliminated when Sgs1 is reactivated in vivo. We propose that HJ resolvases and Sgs1-Top3-Rmi1 comprise two independent processes to deal with HJ-containing DNA intermediates arising during HRR in S-phase.

PMCID: PMC3064375 PMID: 21383164 [PubMed - indexed for MEDLINE]

268. J Biosci Bioeng. 2011 Jun;111(6):706-10. Epub 2011 Mar 5.

Enhanced plumbagin production in elicited Plumbago indica hairy root cultures.

Gangopadhyay M, Dewanjee S, Bhattacharya S.

Medicinal Plant Laboratory, Department of Botany, Bose Institute, 93/1 APC Road, Kolkata 700009, India. moumita_gangopadhyay@yahoo.co.uk

Elicitation of Plumbago indica hairy roots with yeast carbohydrate fraction, chitosan, manganese chloride, copper chloride and methyl jasmonate exhibited significant elevation (~1.2 to 2 fold) of plumbagin production in shake flask culture as compared with control. Chitosan and methyl jasmonate elicitation also caused simultaneous plumbagin leaching into culture media. Three days' exposure of chitosan (200 mg l(-1)) and methyl jasmonate (80 μM) together synergized total plumbagin yield to its maximum 11.96 ± 0.76 mg g(-l) DW in shake flask culture. In bioreactor cultivation, a significant raise in fresh root biomass was recorded on day 20 as compared with control shake flask culture. Three days' exposure of chitosan (200 mg l(-1)) and methyl jasmonate (80 μM) with 20 days old bioreactor-culture significantly improved total plumbagin production to 13.16 ± 1.72 mg g(-l) DW with simultaneous plumbagin leaching into bioreactor media.

PMID: 21382748 [PubMed - indexed for MEDLINE]

269. Dent Mater. 2011 May;27(5):e81-6. Epub 2011 Mar 3.

Cytotoxicity of orthodontic materials assessed by survival tests in Saccharomyces cerevisiae.

Limberger KM, Westphalen GH, Menezes LM, Medina-Silva R.

Imunology and Microbiology Lab, Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.

The aim of this study was to assess the cytotoxicity of orthodontic materials (brackets, wires, resin, elastomers and silver solder) using Saccharomyces cerevisiae as a model organism. The induction of cytotoxicity was assessed by two different tests using the wild-type S. cerevisiae strain FF18733: (1) direct exposure to orthodontic materials in YPD broth, and (2) exposure to artificial commercial saliva pre-treated with orthodontic materials. Only the silver solder was tested in mutant S. cerevisiae strains to investigate the origin of the observed cytotoxicity. Colony forming units per mL counts were carried out in all experiments and compared to controls to detect significant survival differences. The results showed that only the silver solder induced significant cytotoxicity, which might have occurred via oxidative stress, although this mechanism is not completely understood. Moreover, S. cerevisiae proved to be a reliable and useful model microorganism for evaluating the cytotoxicity of clinical materials.

PMID: 21376384 [PubMed - indexed for MEDLINE]

270. Int J Hyg Environ Health. 2011 Jun;214(3):205-9. Epub 2011 Mar 2.

Determinants of stimulated peripheral blood cytokine production among farming women.

Lampi J, Roponen M, Hyvärinen A, Hirvonen MR, Larsson L, Nevalainen A, Pekkanen J.

Department of Environmental Health, National Institute for Health and Welfare, Kuopio, Finland. jussi.lampi@thl.fi

Farming environment and environmental exposure to microbial agents have been suggested to promote favorable development of immune system in children and protect against allergic diseases. However, effects of farm exposure on adult immune responses are less clear. Aim of the present study was to examine associations of farm related factors and measured microbial exposure with stimulated production of interferon-gamma (IFN-γ) and interleukin-4 (IL-4) in peripheral blood samples among farming women. Whole peripheral blood samples were obtained from 112 women living on farms and stimulated with phorbol myristate acetate/ionomycin, lipopolysaccharide and staphylococcal enterotoxin B. Following 24h stimulation, protein levels of IFN-γ and IL-4 in the supernatants were measured by ELISA. From house dust, concentrations of 3-hydroxy fatty acids (C10:0-C14:0, marker for Gram-negative bacteria), muramic acid (Gram-positive bacteria) and ergosterol (fungal biomass) were analyzed with GC-MS/MS and viable microbes by culturing. Information on farm related factors and allergic diseases were collected from self-administered questionnaires. We found that household pets or other current or childhood farm-related factors had only few associations with stimulated cytokine production among studied farming women. Similarly, no strong associations were observed between markers of microbial exposure measured in house dust and cytokine levels. Atopic sensitization, allergic rhinitis and recent respiratory infections were, however, associated with reduced IFN-γ production. Our results suggest that the capacity of the studied environmental factors to modulate immune system is relatively weak in adulthood.

PMID: 21371936 [PubMed - indexed for MEDLINE]

271. J Dent Educ. 2011 Mar;75(3):421-7.

Knowledge, attitudes, and practice regarding infection control measures among dental students in Central India.

Singh A, Purohit BM, Bhambal A, Saxena S, Singh A, Gupta A.

Department of Public Health Dentistry, People's College of Dental Sciences & Research Centre, Bhopal, India. drabhinav.singh@gmail.com

A questionnaire study was conducted among 245 dental students from Bhopal city, Central India, to determine their level of knowledge, attitudes, and practice regarding infection control measures and if any correlation exists among the knowledge, attitudes, and practice scores. The self-administered questionnaire consisted of three parts: knowledge, attitudes, and practice. Analysis of Variance (ANOVA) was used to compare mean of knowledge, attitudes, and practice scores and Kendall's test to compute the correlation between knowledge, attitudes, and practice scores. A p value of ≤0.05 was considered significant for all statistical analyses. We found that 61.2 percent of the dental students had not been vaccinated with hepatitis B. Use of face mask, gloves, eyewear, and protective clothing as standard infection control measures was practiced only by two students. Mean knowledge, attitude, and practice scores were 3.75 (1.01), 3.40 (0.75), and 3.35 (1.04), respectively. Significant linear correlation was seen between attitude and practice scores (r=0.20, p≤0.01). The level of knowledge and practice of infection control measures was poor among dental students. The attitude towards infection control measures was positive, but a greater compliance was needed. We recommend rigorous training on infection control measures prior to graduation and mandatory hepatitis B immunization of students before exposure to clinical practice.

PMID: 21368266 [PubMed - indexed for MEDLINE]

272. Proc Natl Acad Sci U S A. 2011 Mar 15;108(11):4316-21. Epub 2011 Feb 28.

Requirement for kinase-induced conformational change in eukaryotic initiation factor 2alpha (eIF2alpha) restricts phosphorylation of Ser51.

Dey M, Velyvis A, Li JJ, Chiu E, Chiovitti D, Kay LE, Sicheri F, Dever TE.

Laboratory of Gene Regulation and Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.

As phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) on Ser51 inhibits protein synthesis, cells restrict this phosphorylation to the antiviral protein kinase PKR and related eIF2α kinases. In the crystal structure of the PKR-eIF2α complex, the C-terminal lobe of the kinase contacts eIF2α on a face remote from Ser51, leaving Ser51 ∼ 20 Å from the kinase active site. PKR mutations that cripple the eIF2α-binding site impair phosphorylation; here, we identify mutations in eIF2α that restore Ser51 phosphorylation by PKR with a crippled substrate-binding site. These eIF2α mutations either disrupt a hydrophobic network that restricts the position of Ser51 or alter a linkage between the PKR-docking region and the Ser51 loop. We propose that the protected state of Ser51 in free eIF2α prevents promiscuous phosphorylation and the attendant translational regulation by heterologous kinases, whereas docking of eIF2α on PKR induces a conformational change that regulates the degree of Ser51 exposure and thus restricts phosphorylation to the proper kinases.

PMCID: PMC3060252 PMID: 21368187 [PubMed - indexed for MEDLINE]

273. Curr Infect Dis Rep. 2011 Apr;13(2):159-68.

Chronic rhinosinusitis as a multifactorial inflammatory disorder.

Lee S, Lane AP.

Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Chronic rhinosinusitis (CRS) is a prevalent health condition characterized by sinonasal mucosal inflammation lasting at least 12 weeks. Heterogeneous in clinical presentation, histopathology, and therapeutic response, CRS represents a spectrum of disease entities with variable pathophysiology. Increased knowledge of cellular and molecular derangements in CRS suggests potential etiologies and targets for therapy. Microbial elements including fungi, staphylococcal enterotoxin, and biofilms have been implicated as inflammatory stimuli, along with airborne irritants and allergens. Defects in innate immunity have gained increased attention as contributors to the chronic inflammatory state. A combination of host susceptibility and environmental exposure is widely believed to underlie CRS, although direct evidence is lacking. Presently, without precise disease definitions and identifiable universal triggers, CRS pathogenesis is broadly described as multifactorial. Current research is beginning to unravel complex and diverse effects of chronic inflammation on sinonasal mucosal homeostasis, but dysfunctional pathways of inflammatory regulation and resolution require further elucidation.

PMID: 21365379 [PubMed]

274. Genes Dev. 2011 Mar 1;25(5):434-9.

Synthetic circuit identifies subpopulations with sustained memory of DNA damage.

Burrill DR, Silver PA.

Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.

Comment in Cell Cycle. 2011 Aug 1;10(15):2410-1.

Differential responses to stimuli can affect how cells succumb to disease. In yeast, DNA damage can create heterogeneous responses. To delineate how a response contributes to a cell's future behavior, we constructed a transcription-based memory circuit that detects DNA repair to isolate subpopulations with heritable damage responses. Strongly responsive cells show multigenerational effects, including growth defects and iron-associated gene expression. Less-responsive cells exhibit increased mutation frequencies but resume wild-type behavior. These two subpopulations remain distinct for multiple generations, indicating a transmissible memory of damage. Collectively, this work demonstrates the efficacy of using synthetic biology to define how environmental exposure contributes to distinct cell fates.

PMCID: PMC3049284 PMID: 21363961 [PubMed - indexed for MEDLINE]

275. Chin J Integr Med. 2011 Mar;17(3):218-23. Epub 2011 Feb 27.

Effects of inotodiol extracts from inonotus obliquus on proliferation cycle and apoptotic gene of human lung adenocarcinoma cell line A549.

Zhong XH, Wang LB, Sun DZ.

Department of Pathology, Jilin Medical College, Jilin, 132013, China. xhzhong0611@yahoo.com.cn

OBJECTIVE: To observe the proliferation inhibition, apoptosis, and cell proliferation cycle of human lung carcinoma cell line A549 treated with Inotodiol extracts from Inonotus obliquus and explore the possibility of Inotodiol extracts from Inonotus obliquus as a new tumor chemopreventive drug.
METHODS: Human lung cancer cell line A549 was treated with different concentrations of Inotodiol, the effects of Inotodiol on cell apoptosis, the expression of Ki-67, Bcl-2, Bax, and p53 and cell cycle were detected by TUNEL assay, immunohistochemistry, and flow cytometry assay respectively.
RESULTS: Inotodiol extracts had antiproliferation effect on human lung carcinoma cell line A549. The expression of Ki-67 decreased with the increase of Inotodiol concentration and exposure time (P<0.05), in a dose-dependent and time-dependent manner. The typical characteristics of the apoptosis of A549 cells treated with Inotodiol were observed, and the apoptotic rate of A549 cell at 48 h was the highest by TUNEL assay. Inotodiol arrested A549 cells in the S phase, and apoptotic peak was observed by flow cytometry. Immunocytochemistry indicated that the expression of Bcl-2 protein decreased, while the expression of p53 and Bax proteins increased in A549 cells treated with Inotodiol, compared with the control cells (P<0.05).
CONCLUSION: Inotodiol can inhibit proliferation and induce the apoptosis of A549 cells, and its molecular mechanism may be associated with the up-regulating expression of p53 and bax proteins and down-regulating expression of Bcl-2 protein, which arrested A549 cells in S phase.

PMID: 21359924 [PubMed - indexed for MEDLINE]

276. Braz Oral Res. 2011 Jan-Feb;25(1):23-7.

Effectiveness of 2% peracetic acid for the disinfection of gutta-percha cones.

Salvia AC, Teodoro GR, Balducci I, Koga-Ito CY, Oliveira SH.

Department of Biosciences and Oral Diagnosis, São José dos Campos Dental School, Univ. Estadual Paulista, São José dos Campos, SP, Brazil.

The aim of this study was to evaluate the effectiveness of 2% peracetic acid for the disinfection of gutta-percha cones contaminated in vitro with Escherichia coli, Staphylococcus aureus, Streptococcus mutans, Candida albicans and Bacillus subtilus (in spore form). Two hundred and twenty-five gutta-percha cones were contaminated with standardized suspensions of each microorganism and incubated at 37°C for 24 h. The cones were divided into 10 experimental groups (n = 15), according to the microorganism tested and disinfection testing times. The disinfection procedure consisted of immersing each cone in a plastic tube containing the substance. The specimens remained in contact with the substance for 1 or 2.5 minutes. Afterwards, each cone was transferred to a 10% sodium thiosulphate solution (Na(2)S(2)O(3)) to neutralize the disinfectant. Microbial biofilms adhering to the cones were dispersed by agitation. Aliquots of 0.1 ml of the suspensions obtained were plated on Sabouraud dextrose agar, or brain and heart infusion agar, and incubated at 37°C for 24 h. The results were expressed in colony forming units (CFU/ml) and the data were submitted to the Wilcoxon Signed Rank Test (level of significance at 0.05). A significant reduction was observed, after 1 minute of exposure, in the test solution for C. albicans (p = 0.0190), S. aureus (p = 0.0001), S. mutans (p = 0.0001), B. subtilis (p = 0.0001), and E. coli (p = 0.0001). After 2.5 minutes of exposure, 100% of the microbial inocula were eliminated. It was concluded that the 2% peracetic acid solution was effective against the biofilms of the tested microorganisms on gutta-percha cones at 1 minute of exposure.

PMID: 21359448 [PubMed - indexed for MEDLINE]

277. J Environ Monit. 2011 Apr;13(4):1082-7. Epub 2011 Feb 25.

Pre-sampling contamination of filters used in measurements of airborne (1 → 3)-β-D-glucan based on glucan-specific Limulus amebocyte lysate assay.

Shogren ES, Park JH.

National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505, USA.

Air sampling for (1 → 3)-β-D-glucan may be a good method for assessing inhalation exposure to airborne fungi. Pre-sampling contamination of filter media used for sampling (1 → 3)-β-D-glucan may lead to substantial exposure measurement errors. Using the Limulus amebocyte lysate assay, we tested for pre-sampling levels of (1 → 3)-β-D-glucan on three types of filters-mixed cellulose ester (MCE)[1 brand], glass fiber (GF)[1 brand], and polycarbonate (PC)[5 brands]. Levels of (1 → 3)-β-D-glucan on MCE filters exceeded 4586.1 pg per filter. Levels on GF filters averaged 135.3 (± 28.9) pg per filter (range = 94.8-160.4 pg per filter) and levels on PC filters averaged 152.4 (± 236.1) pg per filter (range = non-detectable-1760.7 pg per filter). Efforts to clean MCE and GF filters were unfeasible or unsuccessful. Sonicating PC filters for two hours in ethanol, followed by a wash in pyrogen-free water, effectively eliminated measured levels of (1 → 3)-β-D-glucan on four brands of PC filters, as compared to untreated PC filters. This pretreatment process did not appear to physically damage the PC filters. Air sampling results highlighted the potentially problematic contamination of untreated PC filters. Ensuring that sampling media are free of (1 → 3)-β-D-glucan before sampling is crucial to accurately measure levels of (1 → 3)-β-D-glucan exposure, especially in environments where levels of (1 → 3)-β-D-glucan are low.

PMID: 21359295 [PubMed - indexed for MEDLINE]

278. Can J Microbiol. 2011 Mar;57(3):204-10.

Curcumin as a promising anticandidal of clinical interest.

Neelofar K, Shreaz S, Rimple B, Muralidhar S, Nikhat M, Khan LA.

Department of Biosciences, Jamia Millia Islamia, New Delhi 110025, India.

Curcumin, an important Asian spice, is part of many Indian food preparations. This work evaluates the antifungal activity of curcumin against 14 strains of Candida (10 clinical and 4 standard). Curcumin displayed antifungal properties against all tested Candida strains, with minimum inhibitory concentrations (MICs) varying from 250 to 2000 µg·mL⁻¹. The in vitro effect of curcumin on growth, sterol content, proteinase secretion, and H+ extrusion by plasma membrane ATPase was investigated for 2 standard strains Candida albicans ATCC 10261 and Candida glabrata ATCC 90030 and compared with the effect of fluconazole. At MIC, curcumin inhibited H+ extrusion in 2 species of Candida by 42% and 32% in the absence of glucose and by 28% and 18% in the presence of glucose. Respective inhibition of H+ extrusion caused by the MIC of fluconazole was 85% and 89% in the absence of glucose and 61% and 66% in its presence. Ergosterol content decreased by 70% and 53% for the 2 strains following exposure to curcumin at MIC; comparative values for fluconazole at MIC were 93% and 98%. Curcumin and fluconazole decreased proteinase secretion by 49% and 53%, respectively, in C. albicans and by 39% and 46%, respectively, in C. glabrata. In conclusion, curcumin is found to be active against all tested clinical and standard strains but is less effective than fluconazole. Antifungal activity of curcumin might be originating from alteration of membrane-associated properties of ATPase activity, ergosterol biosynthesis, and proteinase secretion.

PMID: 21358761 [PubMed - indexed for MEDLINE]

279. Mol Plant. 2011 Jul;4(4):688-96. Epub 2011 Feb 28.

Phytochromes regulate SA and JA signaling pathways in rice and are required for developmentally controlled resistance to Magnaporthe grisea.

Xie XZ, Xue YJ, Zhou JJ, Zhang B, Chang H, Takano M.

High-Tech Research Center, Shandong Academy of Agricultural Sciences, Jinan 250100, PR China. xzhxie2010@163.com

Old leaves of wild-type rice plants (Oryza sativa L. cv. Nipponbare) are more resistant to blast fungus (Magnaporthe grisea) than new leaves. In contrast, both old and new leaves of the rice phytochrome triple mutant (phyAphyBphyC) are susceptible to blast fungus. We demonstrate that pathogenesis-related class 1 (PR1) proteins are rapidly and strongly induced during M. grisea infection and following exogenous jasmonate (JA) or salicylic acid (SA) exposure in the old leaves, but not in the new leaves of the wild-type. In contrast, the accumulation of PR1 proteins was significantly attenuated in old and new leaves of the phyAphyBphyC mutant. These results suggest that phytochromes are required for the induction of PR1 proteins in rice. Basal transcription levels of PR1a and PR1b were substantially higher in the wild-type as compared to the phyAphyBphyC mutant, suggesting that phytochromes also are required for basal expression of PR1 genes. Moreover, the transcript levels of genes known to function in SA- or JA-dependent defense pathways were regulated by leaf age and functional phytochromes. Taken together, our findings demonstrate that phytochromes are required in rice for age-related resistance to M. grisea and may indirectly increase PR1 gene expression by regulating SA- and JA-dependent defense pathways.

PMID: 21357645 [PubMed - indexed for MEDLINE]

280. J Immunol. 2011 Apr 1;186(7):4375-87. Epub 2011 Feb 25.

The danger signal, extracellular ATP, is a sensor for an airborne allergen and triggers IL-33 release and innate Th2-type responses.

Kouzaki H, Iijima K, Kobayashi T, O'Grady SM, Kita H.

Division of Allergic Diseases, Department of Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA.

The molecular mechanisms underlying the initiation of innate and adaptive proallergic Th2-type responses in the airways are not well understood. IL-33 is a new member of the IL-1 family of molecules that is implicated in Th2-type responses. Airway exposure of naive mice to a common environmental aeroallergen, the fungus Alternaria alternata, induces rapid release of IL-33 into the airway lumen, followed by innate Th2-type responses. Biologically active IL-33 is constitutively stored in the nuclei of human airway epithelial cells. Exposing these epithelial cells to A. alternata releases IL-33 extracellularly in vitro. Allergen exposure also induces acute extracellular accumulation of a danger signal, ATP; autocrine ATP sustains increases in intracellular Ca(2+) concentration and releases IL-33 through activation of P2 purinergic receptors. Pharmacological inhibitors of purinergic receptors or deficiency in the P2Y2 gene abrogate IL-33 release and Th2-type responses in the Alternaria-induced airway inflammation model in naive mice, emphasizing the essential roles for ATP and the P2Y(2) receptor. Thus, ATP and purinergic signaling in the respiratory epithelium are critical sensors for airway exposure to airborne allergens, and they may provide novel opportunities to dampen the hypersensitivity response in Th2-type airway diseases such as asthma.

PMCID: PMC3062674 [Available on 2012/4/1] PMID: 21357533 [PubMed - indexed for MEDLINE]

281. Appl Environ Microbiol. 2011 Apr;77(8):2676-84. Epub 2011 Feb 25.

Contribution of the gas1 gene of the entomopathogenic fungus Beauveria bassiana, encoding a putative glycosylphosphatidylinositol-anchored beta-1,3-glucanosyltransferase, to conidial thermotolerance and virulence.

Zhang S, Xia Y, Keyhani NO.

Genetic Engineering Research Center, College of Bioengineering, Chongqing University, Chongqing, China.

Beauveria bassiana is a mycoinsecticide alternative to chemicals for use in biological pest control. The fungus-insect interaction is also an emerging model system to examine unique aspects of the development, pathogenesis, and diversity of fungal lifestyles. The glycoside hydrolase 72 (GH72) family includes β-1,3-glucanosyltransferases that are glycosylphosphatidylinositol (GPI)-anchored cell wall-modeling enzymes affecting fungal physiology. A putative B. bassiana GPI-anchored β-1,3-glucanosyltransferase (Bbgas1) was isolated and characterized. B. bassiana targeted gene knockouts lacking Bbgas1 were affected in Congo red and salt sensitivity but displayed minor growth defects in the presence of sorbitol, SDS, or calcofluor white. Lectin and antibody mapping of surface carbohydrates revealed increased exposure of carbohydrate epitopes, including β-1,3-glucans, in the ΔBbgas1 strain. Transmission electron micrographs revealed localized destabilization of the cell wall in ΔBbgas1 conidia, in which fraying of the outer cell wall was apparent. Heat shock temperature sensitivity profiling showed that in contrast to the wild-type parent, ΔBbgas1 conidial spores displayed decreased germination after 1 to 4 h of heat shock at temperatures >40°C, and propidium iodide exclusion assays revealed decreased membrane stability in the knockout strain at temperatures >50°C. The ΔBbgas1 knockout showed reduced virulence in Galleria mellonella insect bioassays in both topical and intrahemocoel-injection assays. B. bassiana ΔBbgas1 strains complemented with the complete Bbgas1 open reading frame were indistinguishable from the wild-type parent in all phenotypes examined. The Bbgas1 gene did not complement the phenotype of a Saccharomyces cerevisiae β-1,3-glucanosyltransferase Δgas1 mutant, indicating that this family of enzymes likely possess discrete cellular functions.

PMCID: PMC3126355 PMID: 21357429 [PubMed - indexed for MEDLINE]

282. Food Microbiol. 2011 May;28(3):484-91. Epub 2010 Oct 27.

Combination treatment of alkaline electrolyzed water and citric acid with mild heat to ensure microbial safety, shelf-life and sensory quality of shredded carrots.

Rahman SM, Jin YG, Oh DH.

Department of Food Science and Biotechnology, Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon, Gangwon 200-701, Republic of Korea. ehsan_bau@yahoo.com

The objective of this study was to determine the synergistic effect of alkaline electrolyzed water and citric acid with mild heat against background and pathogenic microorganisms on carrots. Shredded carrots were inoculated with approximately 6-7 log CFU/g of Escherichia coli O157:H7 (932, and 933) and Listeria monocytogenes (ATCC 19116, and 19111) and then dip treated with alkaline electrolyzed water (AlEW), acidic electrolyzed water (AcEW), 100 ppm sodium hypochlorite (NaOCl), deionized water (DaIW), or 1% citric acid (CA) alone or with combinations of AlEW and 1% CA (AlEW + CA). The populations of spoilage bacteria on the carrots were investigated after various exposure times (1, 3, and 5 min) and treatment at different dipping temperatures (1, 20, 40, and 50 °C) and then optimal condition (3 min at 50 °C) was applied against foodborne pathogens on the carrots. When compared to the untreated control, treatment AcEW most effectively reduced the numbers of total bacteria, yeast and fungi, followed by AlEW and 100 ppm NaOCl. Exposure to all treatments for 3 min significantly reduced the numbers of total bacteria, yeast and fungi on the carrots. As the dipping temperature increased from 1 °C to 50 °C, the reductions of total bacteria, yeast and fungi increased significantly from 0.22 to 2.67 log CFU/g during the wash treatment (p ≤ 0.05). The combined 1% citric acid and AlEW treatment at 50 °C showed a reduction of the total bacterial count and the yeast and fungi of around 3.7 log CFU/g, as well as effective reduction of L. monocytogenes (3.97 log CFU/g), and E. Coli O157:H7 (4 log CFU/g). Combinations of alkaline electrolyzed water and citric acid better maintained the sensory and microbial quality of the fresh-cut carrots and enhanced the overall shelf-life of the produce.

PMID: 21356455 [PubMed - indexed for MEDLINE]

283. Chem Biol Interact. 2011 Apr 25;190(2-3):139-47. Epub 2011 Feb 25.

Effects of low molecular weight fungal compounds on inflammatory gene transcription and expression in mouse alveolar macrophages.

Rand TG, Dipenta J, Robbins C, Miller JD.

Department of Biology, Saint Mary's University, Halifax, NS, Canada B3H 3C3.

The inflammatory potential and molecular mechanisms underscoring inflammatory responses of lung cells to compounds from fungi that grow on damp building materials is poorly understood in vitro. In this study we evaluated the effect of pure fungal compounds on potentiating acute inflammatory response in primary mouse alveolar macrophages (AMs) and tested the hypothesis that AM responses to low molecular weight fungal compounds exhibit temporal and compound specificity that mimic that observed in the whole lung. Transcriptional responses of 13 inflammation/respiratory burst-associated genes (KC=Cxcl1, Cxcl2, Cxcl5, Cxcl10, Ccl3, Ccl112, Ccl20, IL-1β, Il-6, ifi27 Tnfα, iNOS and Blvrb) were evaluated in mouse AMs exposed to a 1ml (10(-8)mol) dose of either pure atranone C, brevianimide, cladosporin, curdlan, LPS, neoechinulin A & B, sterigmatocystin or TMC-120A for 2h, 4h and 12h PE using customized reverse transcription (RT)-PCR based arrays. Multianalyte ELISA was used to measure expression of 6 pro-inflammatory cytokines common to the transcriptional assays (Cxcl1, Cxcl10, Ccl3, IL1β, Ifn-λ and Tnf-α) to determine whether gene expression corresponded to the transcription data. Compared to controls, all of these compounds induced significant (≥2.5-fold or ≤-2.5-fold change at p≤0.05) time- and compound-specific transcriptional gene alterations in treatment AMs. The highest number of transcribed genes were in LPS treatment AMs at 12h PE (12/13) followed by neoechinulin B at 4h PE (11/13). Highest fold change values (>30) were associated with KC, Cxcl2, Cxcl5 and IL1β genes in cells exposed to LPS. Compound exposures also induced significant (p≤0.05) time- and compound-specific pro-inflammatory responses manifest as differentially elevated Cxcl1, Cxcl10, Ccl3, Ifn-λ and Tnf-α concentrations in culture supernatant of treatment AMs. Dissimilarity in transcriptional responses in AMs and our in vivo model of lung disease is likely attributable to whole lung vs. isolated cell responsive and dose differences between the two studies. The results not only indicate that low molecular weight compounds from fungi that grow in damp built environments are potently pro-inflammatory in vitro, it further highlights the important role AMs play in innate lung defence, and against exposure to low molecular weight fungal compounds. These observations further support our position that exposure to low molecular weight compounds from indoor-associated fungi may provoke some of the inflammatory health effects reported from humans in damp building environments. They also open up a hypothesis building process that could explain the rise of non-atopic asthma associated with fungi.

PMID: 21356202 [PubMed - indexed for MEDLINE]

284. Indian J Biochem Biophys. 2010 Dec;47(6):383-7.

Cadmium-induced oxidative stress in Saccharomyces cerevisiae.

Muthukumar K, Nachiappan V.

Department of Biochemistry, School of Life Sciences, Bharathidasan University Tiruchirappalli 620 024, India.

The present study was undertaken to determine the effect of cadmium (Cd) on the antioxidant status of the yeast Saccharomyces cerevisiae. S. cerevisiae serves as a good eukaryotic model system for the study of the molecular mechanisms of oxidative stress. We investigated the adaptative response of S. cerevisiae exposed to Cd. Yeast cells could tolerate up to 100 microM Cd and an inhibition in the growth and viability was observed. Exposure of yeast cells to Cd showed an increase in malondialdehyde and glutathione. The activities of catalase, superoxide dismutase and glutathione peroxidase were also high in Cd-exposed cells. The incorporation of Cd led to significant increase in iron, zinc and inversely the calcium, copper levels were reduced. The results suggest that antioxidants were increased and are involved in the protection against macromolecular damage during oxidative stress; presumably, these enzymes are essential for counteracting the pro-oxidant effects of Cd.

PMID: 21355423 [PubMed - indexed for MEDLINE]

285. Fungal Biol. 2011 Mar;115(3):302-9. Epub 2011 Jan 13.

Metergoline-induced cell death in Candida krusei.

Kang K, Wong KS, Fong WP, Tsang PW.

Biochemistry Programme, School of Life Sciences, The Chinese University of Hong Kong, Hong Kong, China.

Metergoline possesses potent antifungal activity against Candida krusei, a notorious yeast species that is inherently resistant to the common antifungal agents. In an attempt to elucidate the action mechanisms of metergoline, the present study was designed to investigate its effects on a number of classical markers of apoptosis in C. krusei. The results showed that transient exposure (2h) to metergoline led to a massive intracellular accumulation of reactive oxygen species (ROS) and depolarization of mitochondrial membrane potential in a concentration-dependent fashion. Analyses of the treated fungal cells after prolonged incubation (12h) with metergoline by flow cytometry and fluorescence microscopy clearly demonstrated phosphatidylserine externalization, the presence of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling-positive cells and fungal cells undergoing necrosis. Taken together, our data provide evidence that metergoline elicited cell death process in C. krusei through elevation of the intracellular ROS level and perturbation of mitochondrial homeostasis, followed by damage of nucleus and eventual cell demise.

PMID: 21354537 [PubMed - indexed for MEDLINE]

286. Int J Antimicrob Agents. 2011 Apr;37(4):380-4. Epub 2011 Feb 25.

Possible role of azole and echinocandin lock solutions in the control of Candida biofilms associated with silicone.

Cateau E, Berjeaud JM, Imbert C.

UMR CNRS 6008, Université de Poitiers, 6 rue de la Milètrie, BP 199, 86034 Poitiers Cedex, France. estelle.cateau@chu-poitiers.fr

Until now, management of candidiasis related to implanted devices has remained problematic. The aim of this study was to investigate antifungal lock strategies against Candida albicans and Candida glabrata biofilms in vitro. Three antifungal agents were used against eight C. albicans and six C. glabrata clinical strains isolated from infected catheters. Caspofungin and micafungin, both echinocandins, as well as the azole posaconazole were tested. An in vitro model of Candida biofilm on 100% silicone catheters was used. Efficacy of the antifungal lock was tested against biofilms aged 12h and 5 days following exposure to caspofungin (5mg/L and 25mg/L), micafungin (5mg/L and 15 mg/L) and posaconazole (10mg/L) for 12h. Persistence of antibiofilm activity was investigated 1-3 days following drug elimination. Antifungal lock was considered effective in the event of a significant decrease (P<0.001) in the metabolic activity of the biofilm yeast. The results showed that micafungin had significant inhibitory effectiveness against young and mature C. albicans and C. glabrata biofilms. Moreover, this activity appeared to persist for up to 3 days. Caspofungin displayed similar activity against all C. albicans biofilms, but the activity was less persistent for C. glabrata biofilms. Posaconazole was less effective against C. albicans biofilms, but its activity was sustained. Echinocandin lock therapy could significantly enhance the management of candidiasis in patients with indwelling catheters by combating biofilms and enabling device maintenance in situ.

PMID: 21353488 [PubMed - indexed for MEDLINE]

287. Toxicon. 2011 Apr;57(5):817-25. Epub 2011 Feb 23.

Toxigenicity of enniatins from Western Australian Fusarium species to brine shrimp (Artemia franciscana).

Tan DC, Flematti GR, Ghisalberti EL, Sivasithamparam K, Barbetti MJ.

School of Plant Biology, Faculty of Natural and Agricultural Sciences, The University of Western Australia, Crawley, Western Australia 6009, Australia.

The high prevalence (14 of 24 isolates) of enniatin-producing isolates from Western Australian Fusarium species isolated from pasture legumes associated with sheep feed refusal and rat deaths, and the high toxicity of their crude extracts to brine shrimp (Artemia franciscana) from a previous study warranted further investigation of this class of mycotoxin. Crude extracts from Fusarium acuminatum, Fusarium avenaceum, Fusarium tricinctum and Fusarium sambucinum, along with enniatins A, A1, B and B1 purified from a Western Australian strain of F. acuminatum using semi-preparative HPLC, were bioassayed using brine shrimp. All Fusarium isolates produced both enniatins B and B1, except for F. tricinctum WAC 8019, and 11 of the 17 isolates produced enniatin A1. Overall, all of the F. avenaceum isolates produced high amounts of enniatins, in particular enniatin B. One isolate of F. acuminatum (WAC 5715) and of F. tricinctum (WAC 11486) also produced high amounts of both enniatins B and B1. Only F. acuminatum WAC 5715 produced enniatin A among the tested isolates. All four purified enniatins A, A1, B, B1, individually and in combination, caused brine shrimp toxicity after 6 h of exposure, implicating that this emerging class of mycotoxin as a cause of the acute toxicity to brine shrimp observed. The mixture of all four enniatins was the most toxic to brine shrimp compared to purified individual enniatins, where the relative toxicity order was B > B1 > A1 > A. Enniatin B was the individual most toxic enniatin with some bioactivity at 5 μg/mL and almost 100% brine shrimp death at 50 μg/mL after 24 h of exposure. This study is the first report to confirm the acute toxicity of enniatins A, A1, B and B1 to brine shrimp, and also highlights the need for further investigation of the potential toxicity of these cyclic hexadepsipeptides to animals and humans.

PMID: 21352844 [PubMed - indexed for MEDLINE]

288. Parasit Vectors. 2011 Feb 26;4:24.

Transmission of Beauveria bassiana from male to female Aedes aegypti mosquitoes.

García-Munguía AM, Garza-Hernández JA, Rebollar-Tellez EA, Rodríguez-Pérez MA, Reyes-Villanueva F.

Laboratorio de Entomología Médica, Facultad de Ciencias Biológicas, Universidad Autónoma de Nuevo León, Pedro de Alba S/N Ciudad Universitaria, Apdo. Postal 109-F, 66450, San Nicolás de los Garza, Nuevo León, México.

BACKGROUND: Resistance to chemical insecticides plus high morbidity rates have lead to rising interest in fungi as candidates for biocontrol agents of mosquito vectors. In most studies fungal infections have been induced by exposure of mosquitoes to various surfaces treated with conidia. In the present study eight Mexican strains of Beauveria bassiana were assessed against Aedes aegypti by direct exposure of females to 6 × 10(8) conidia ml (-1) on a filter paper, afterwards, the transmission of the least and most virulent isolates was evaluated by mating behavior from virgin, fungus-contaminated male to females, to examine this ethological pattern as a new approach to deliver conidia against the dengue vector.
METHODS: In an exposure chamber with a filter paper impregnated with 6 × 10(8) conidia ml (-1) of the least and most virulent strains of B. bassiana, 6-8 day old males of A. aegypti were exposed for 48 hours, and then transferred individually (each one was a replicate) to another chamber and confined with twenty healthy females of the same age. Clean males were used in controls. Survival, infection by true mating (insemination) or by mating attempts (no insemination) and fecundity were daily registered until the death of last female. Data analysis was conducted with proc glm for unbalanced experiments and means were separated with the Ryan test with SAS.
RESULTS: All strains were highly virulent with LT(50) ranging from 2.70 (± 0.29) to 5.33 (± 0.53) days. However the most (Bb-CBG2) and least virulent (Bb-CBG4) isolates were also transmitted by mating behavior; both killed 78-90% of females in 15 days after being confined with males that had previously been exposed for 48 hours to fungi. Of these mortality rates, 23 and 38% respectively, were infections acquired by copulations where insemination occurred. The LT(50) for sexually-infected females were 7.92 (± 0.46) and 8.82 (± 0.45) days for both strains, while the one in control was 13.92 (± 0.58). Likewise, fecundity decreased by 95% and 60% for both Bb-CBG2 and Bb-CBG4 isolates in comparison with control. The role of mating attempts in this delivery procedure of B. bassiana is discussed.
CONCLUSIONS: This is the first report about transmission of B. bassiana by mating behavior from virgin, fungus-contaminated males to females in A. aegypti. Fungal infections acquired by this route (autodissemination) infringed high mortality rates (90%) in mated or approached females. However, prior to releasing virgin, fungus-contaminated males to spread B. basasiana among females of A. aegypti, this novel alternative needs further investigations.

PMCID: PMC3051917 PMID: 21352560 [PubMed - indexed for MEDLINE]

289. Int J Evol Biol. 2010 Apr 11;2010:602457.

Elastase Activity in Aspergillus fumigatus Can Arise by Random, Spontaneous Mutations.

Alvarez-Pérez S, Blanco JL, López-Rodas V, Flores-Moya A, Costas E, García ME.

Departamento Sanidad Animal, Facultad de Veterinaria, Universidad Complutense de Madrid (UCM), 28040 Madrid, Spain.

Aspergillus fumigatus Fresenius has the capacity to degrade elastin (the principal protein of the lungs) and it is considered that elastase activity (EA) is among the most important pathogenicity factors of this mold. In particular, there is a strong correlation between EA in A. fumigatus and invasive aspergillosis. However, EA is not universal in this mold, and it is unknown whether the capacity to degrade elastin is the consequence of physiological mechanisms and/or genetic changes (putative adaptive mutations) induced after the exposure to this substrate or, on the contrary, it is due to random spontaneous mutations that occur under nonselective conditions. In order to discriminate between these possibilities, a Luria-Delbrück fluctuation analysis was carried out on an elastase-negative (EA(-)) A. fumigatus strain, using as selective factor a culture medium containing elastin as the sole source of nitrogen. Here we show that the EA(-) → EA(+) transformation in A. fumigatus appears by rare, random mutations before the exposure of the strain to selective conditions. This work represents the first experimental evidence of pathogenicity factor acquisition in mycelial fungi by preselective mutation.

PMCID: PMC3042605 PMID: 21350652 [PubMed]

290. J Perinatol. 2011 May;31(5):335-8. Epub 2011 Feb 24.

Breastmilk cultures and infection in extremely premature infants.

Schanler RJ, Fraley JK, Lau C, Hurst NM, Horvath L, Rossmann SN.

Division of Neonatal-Perinatal Medicine, Cohen Children's Medical Center of New York at North Shore, North Shore University Hospital, Manhasset, NY 11030, USA. schanler@nshs.edu

Comment in J Perinatol. 2011 May;31(5):301.

OBJECTIVE: As expressed mother's milk (MM) is known to be colonized by microbial species, it is occasionally considered as a source of infection in premature infants, prompting some clinicians to obtain milk bacterial culture results before infant feeding. To determine whether serial microbial cultures of MM predict infection in premature infants. STUDY DESIGN: Milk microbial flora was determined by plate counts from aliquots of MM obtained from 161 mothers of infants born <30 weeks gestation (n = 209). Pathogens isolated from the same infant were tabulated. RESULT: Milk samples (n = 813) yielded 1963 isolates. There were no relationships between microbial counts and maternal age, ethnicity, education, skin-to-skin contact and infant infection. In 64 infants, milk and pathological isolates had presumptively the same Gram-positive organism, yet the odds of infection before or after exposure to milk containing that Gram-positive organism were not significant (1.18; 95% confidence interval=0.51, 2.76). In eight infants, milk and pathological isolates had presumptively the same Gram-negative organism, which appeared sporadically in milk, either before or after isolation in the infant.
CONCLUSION: Results of initial milk cultures do not predict subsequent culture results. Random milk cultures, even if obtained at any time during hospitalization, are not predictive of infection in premature infants. The sporadic nature of the appearance of certain isolates, however, suggests common exposure of both mother and infant. Routine milk cultures do not provide sufficient data to be useful in clinical management.

PMID: 21350430 [PubMed - indexed for MEDLINE]

291. PLoS Genet. 2011 Feb 10;7(2):e1001299.

Srf1 is a novel regulator of phospholipase D activity and is essential to buffer the toxic effects of C16:0 platelet activating factor.

Kennedy MA, Kabbani N, Lambert JP, Swayne LA, Ahmed F, Figeys D, Bennett SA, Bryan J, Baetz K.

Ottawa Institute of Systems Biology, Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Canada.

During Alzheimer's Disease, sustained exposure to amyloid-β₄₂ oligomers perturbs metabolism of ether-linked glycerophospholipids defined by a saturated 16 carbon chain at the sn-1 position. The intraneuronal accumulation of 1-O-hexadecyl-2-acetyl-sn-glycerophosphocholine (C16:0 PAF), but not its immediate precursor 1-O-hexadecyl-sn-glycerophosphocholine (C16:0 lyso-PAF), participates in signaling tau hyperphosphorylation and compromises neuronal viability. As C16:0 PAF is a naturally occurring lipid involved in cellular signaling, it is likely that mechanisms exist to protect cells against its toxic effects. Here, we utilized a chemical genomic approach to identify key processes specific for regulating the sensitivity of Saccharomyces cerevisiae to alkyacylglycerophosphocholines elevated in Alzheimer's Disease. We identified ten deletion mutants that were hypersensitive to C16:0 PAF and five deletion mutants that were hypersensitive to C16:0 lyso-PAF. Deletion of YDL133w, a previously uncharacterized gene which we have renamed SRF1 (Spo14 Regulatory Factor 1), resulted in the greatest differential sensitivity to C16:0 PAF over C16:0 lyso-PAF. We demonstrate that Srf1 physically interacts with Spo14, yeast phospholipase D (PLD), and is essential for PLD catalytic activity in mitotic cells. Though C16:0 PAF treatment does not impact hydrolysis of phosphatidylcholine in yeast, C16:0 PAF does promote delocalization of GFP-Spo14 and phosphatidic acid from the cell periphery. Furthermore, we demonstrate that, similar to yeast cells, PLD activity is required to protect mammalian neural cells from C16:0 PAF. Together, these findings implicate PLD as a potential neuroprotective target capable of ameliorating disruptions in lipid metabolism in response to accumulating oligomeric amyloid-β₄₂.

PMCID: PMC3037409 PMID: 21347278 [PubMed - indexed for MEDLINE]

292. N Engl J Med. 2011 Feb 24;364(8):769-70.

Barnyard microbes and childhood asthma.

Gern JE.

Comment on N Engl J Med. 2011 Feb 24;364(8):701-9.

PMID: 21345107 [PubMed - indexed for MEDLINE]

293. N Engl J Med. 2011 Feb 24;364(8):701-9.

Exposure to environmental microorganisms and childhood asthma.

Ege MJ, Mayer M, Normand AC, Genuneit J, Cookson WO, Braun-Fahrländer C, Heederik D, Piarroux R, von Mutius E; GABRIELA Transregio 22 Study Group.

Collaborators: Apprich S, Bauer J, Boznanski A, Braun-Fahrländer C, Büchele G, Cookson W, Cullinan P, Danielewicz H, Dębińska A, Depner M, Ege M, Frey U, Fuchs O, Genuneit J, Heederik D, Horak E, Hyvärinen A, Illi S, Kabesch M, Kovacs K, Kosmęda A, Kneifel W, Latzin P, Lauener R, Loss G, MacNeill SJ, Mayer M, Morass B, Normand AC, Noss I, Pershagen G, Piarroux R, Renz H, Rintala H, Rochat MK, Schwaiger K, Sitaridis N, Sozanska B, Strachan D, Strunz-Lehner C, Sudre B, von Mutius E, Waser M, Weber J, Wouters I.

University Children's Hospital Munich, Munich, Germany. markus.ege@med.uni-muenchen.de

Comment in N Engl J Med. 2011 May 19;364(20):1972-3; author reply 1973. N Engl J Med. 2011 Feb 24;364(8):769-70. N Engl J Med. 2011 May 19;364(20):1972; author reply 1973.

BACKGROUND: Children who grow up in environments that afford them a wide range of microbial exposures, such as traditional farms, are protected from childhood asthma and atopy. In previous studies, markers of microbial exposure have been inversely related to these conditions.
METHODS: In two cross-sectional studies, we compared children living on farms with those in a reference group with respect to the prevalence of asthma and atopy and to the diversity of microbial exposure. In one study--PARSIFAL (Prevention of Allergy-Risk Factors for Sensitization in Children Related to Farming and Anthroposophic Lifestyle)--samples of mattress dust were screened for bacterial DNA with the use of single-strand conformation polymorphism (SSCP) analyses to detect environmental bacteria that cannot be measured by means of culture techniques. In the other study--GABRIELA (Multidisciplinary Study to Identify the Genetic and Environmental Causes of Asthma in the European Community [GABRIEL] Advanced Study)--samples of settled dust from children's rooms were evaluated for bacterial and fungal taxa with the use of culture techniques.
RESULTS: In both studies, children who lived on farms had lower prevalences of asthma and atopy and were exposed to a greater variety of environmental microorganisms than the children in the reference group. In turn, diversity of microbial exposure was inversely related to the risk of asthma (odds ratio for PARSIFAL, 0.62; 95% confidence interval [CI], 0.44 to 0.89; odds ratio for GABRIELA, 0.86; 95% CI, 0.75 to 0.99). In addition, the presence of certain more circumscribed exposures was also inversely related to the risk of asthma; this included exposure to species in the fungal taxon eurotium (adjusted odds ratio, 0.37; 95% CI, 0.18 to 0.76) and to a variety of bacterial species, including Listeria monocytogenes, bacillus species, corynebacterium species, and others (adjusted odds ratio, 0.57; 95% CI, 0.38 to 0.86).
CONCLUSIONS: Children living on farms were exposed to a wider range of microbes than were children in the reference group, and this exposure explains a substantial fraction of the inverse relation between asthma and growing up on a farm. (Funded by the Deutsche Forschungsgemeinschaft and the European Commission.).

PMID: 21345099 [PubMed - indexed for MEDLINE]

294. Mol Cell Biol. 2011 May;31(9):1921-33. Epub 2011 Feb 22.

Pathways for Holliday junction processing during homologous recombination in Saccharomyces cerevisiae.

Ashton TM, Mankouri HW, Heidenblut A, McHugh PJ, Hickson ID.

Center for Healthy Aging, Department of Cellular and Molecular Medicine, Panum Institute 18.1, University of Copenhagen, DK-2200 Copenhagen, Denmark.

The Saccharomyces cerevisiae Rmi1 protein is a component of the highly conserved Sgs1-Top3-Rmi1 complex. Deletion of SGS1, TOP3, or RMI1 is synthetically lethal when combined with the loss of the Mus81-Mms4 or Slx1-Slx4 endonucleases, which have been implicated in Holliday junction (HJ) resolution. To investigate the causes of this synthetic lethality, we isolated a temperature-sensitive mutant of the RMI1 strain, referred to as the rmi1-1 mutant. At the restrictive temperature, this mutant phenocopies an rmi1Δ strain but behaves like the wild type at the permissive temperature. Following a transient exposure to methyl methanesulfonate, rmi1-1 mutants accumulate unprocessed homologous recombination repair (HRR) intermediates. These intermediates are slowly resolved at the restrictive temperature, revealing a redundant resolution activity when Rmi1 is impaired. This resolution depends on Mus81-Mms4 but not on either Slx1-Slx4 or another HJ resolvase, Yen1. Similar results were also observed when Top3 function was impaired. We propose that the Sgs1-Top3-Rmi1 complex constitutes the main pathway for the processing of HJ-containing HRR intermediates but that Mus81-Mms4 can also resolve these intermediates.

PMCID: PMC3133222 PMID: 21343337 [PubMed - indexed for MEDLINE]

295. Environ Sci Technol. 2011 Mar 15;45(6):2186-93. Epub 2011 Feb 22.

Microbial transformation of triadimefon to triadimenol in soils: selective production rates of triadimenol stereoisomers affect exposure and risk.

Garrison AW, Avants JK, Jones WJ.

National Exposure Research Laboratory, Ecosystems Research Division, US Environmental Protection Agency, Athens, Georgia, United States. garrison.wayne@epa.gov

The microbial transformation of triadimefon, an agricultural fungicide of the 1,2,4-triazole class, was followed at a nominal concentration of 50 μg/mL over 4 months under aerobic conditions in three different soil types. Rates and products of transformation were measured, as well as enantiomer fractions of parent and products. The transformation was biotic and enantioselective, and in each soil the S-(+)-enantiomer reacted faster than the R-(-) one. Rates of the first-order reactions were 0.047, 0.057, and 0.107 d(-1) for the three soils. The transformation involves reduction of the prochiral ketone moiety of triadimefon to an alcohol, resulting in triadimenol, which has two chiral centers and four stereoisomers. The abundances of the four product stereoisomers were different from each other, but abundance ratios were similar for all three soil types. Triadimenol is also a fungicide; the commercial product is composed of two diastereomers of unequal amounts (ratio of about 4.3:1), each having two enantiomers of equal amounts. However, the triadimenol formed by soil transformation of triadimefon exhibited no such stereoisomer profile. Instead, different production rates were observed for each of the four triadimenol stereoisomers, resulting in all stereoisomer concentrations being different from each other and very different from concentration/abundance patterns of the commercial standard. This result is important in risk assessment if the toxicity of the environmental transformation product were to be compared to that of the commercial triadimenol. Because triadimenol stereoisomers differ in their toxicities, at least to fungi and rats, the biological activity of the triadimenol formed by microbes or other biota in soils depends on the relative abundances of its four stereoisomers. This is an exposure and risk assessment issue that, in principle, applies to any chiral pesticide and its metabolites.

PMID: 21341686 [PubMed - indexed for MEDLINE]

296. Gig Sanit. 2010 Sep-Oct;(5):22-4.

[Ambient air pollution with flour dust at the sites of baking and macaroni enterprises].

[Article in Russian]

Tepikina LA, Safiulin AA, Shipulina ZV, Volokhova LT, Kariakina AB, L'vova LS.

Ambient air pollution with flour dust (FD) and microorganisms, including microscopic fungi, was studied; the single concentrations of FD under emission plumes were 0.12-0.17 mg/m3; the total content of mould, field, and storage fungi was 700 +/- 30, 671 +/- 19, and 29 +/- 3, respectively. The maximum allowable concentrations for FD were ascertained; the equal ones were the maximum single concentration of 1.0; the daily average concentration was 0.4 mg/m3; hazard class IV; the limiting hazard index was their resorptive activity.

PMID: 21341487 [PubMed - indexed for MEDLINE]

297. Rev Soc Bras Med Trop. 2011 Jan-Feb;44(1):40-2.

[Clinical and mycological evaluation of onychomycosis among Brazilian HIV/AIDS patients].

[Article in Portuguese]

Cambuim II, Macêdo DP, Delgado M, Lima Kde M, Mendes GP, Souza-Motta CM, Lima DM, Fernandes MJ, Magalhães OM, Queiroz LA, Neves RP.

Departamento de Micologia, Universidade Federal de Pernambuco, Recife, PE.

INTRODUCTION: Onychomycosis is common in immunocompromised patients, but emerging species have been verified, thereby modifying the epidemiological profile of this mycosis. Thus, the aim of this study was to evaluate clinical and mycological profile of onychomycosis among HIV/AIDS patients.
METHODS: Clinical samples were collected and processed for direct examination, and cultures were maintained at a temperature of 30 °C and 37 °C for 15 days.
RESULTS: Out of 100 patients, 32 had onychomycosis. The etiological agents isolated were Candida albicans, C. parapsilosis, C. tropicalis, C. guilliermondii, Trichophyton rubrum, T. mentagrophytes, Fusarium solani, Scytalidium hialinum, S. japonicum, Aspergillus niger, Cylindrocarpon destructans and Phialophora reptans.
CONCLUSIONS: Onychomycosis in HIV/AIDS patients presents various clinical manifestations and may be caused by emerging fungi. The peculiarities presented by different fungal agents justify the need for identification to species level, with the purpose of guiding better therapeutic approaches and minimizing these patients' exposure to conditions presenting a risk of disseminated infection.

PMID: 21340406 [PubMed - indexed for MEDLINE]

298. Food Sci Technol Int. 2010 Jun;16(3):266-76. Epub 2010 Aug 12.

Biomonitoring of Fusarium spp. mycotoxins: perspectives for an individual exposure assessment tool.

Cano-Sancho G, Marin S, Ramos AJ, Sanchis V.

Food Technology Department, University of Lleida, Rovira Roure 191, 25198 Lleida, Spain.

Fusarium species are probably the most prevalent toxin-producing fungi of the northern temperate regions and are commonly found on cereals grown in the temperate regions of America, Europe and Asia. Among the toxins formed by Fusarium we find trichothecenes of the A-type or B-type, zearalenone, fumonisins or nivalenol. The current exposure assessment consists of the qualitative and/or quantitative evaluation based on the knowledge of the mycotoxin occurrence in the food and the dietary habits of the population. This process permits quantifying the mycotoxin dietary intake through deterministic or probabilistic methods. Although these methods are suitable to assess the exposure of populations to contaminants and to identify risk groups, they are not recommended to evaluate the individual exposition, due to a low accuracy and sensitivity. On the contrary, the use of biochemical indicators has been proposed as a suitable method to assess individual exposure to contaminants. In this work, several techniques to biomonitor the exposure to fumonisins, deoxynivalenol, zearalenone or T-2 toxin have been reviewed.

PMID: 21339143 [PubMed - indexed for MEDLINE]

299. J Dairy Sci. 2011 Mar;94(3):1409-19.

Dry matter and nutritional losses during aerobic deterioration of corn and sorghum silages as influenced by different lactic acid bacteria inocula.

Tabacco E, Righi F, Quarantelli A, Borreani G.

Dipartimento di Agronomia, Selvicoltura e Gestione del Territorio, University of Torino, 10095-Grugliasco (TO), Italy.

The economic damage that results from aerobic deterioration of silage is a significant problem for farm profitability and feed quality. This paper quantifies the dry matter (DM) and nutritional losses that occur during the exposure of corn and sorghum silages to air over 14 d and assesses the possibility of enhancing the aerobic stability of silages through inoculation with lactic acid bacteria (LAB). The trial was carried out in Northern Italy on corn (50% milk line) and grain sorghum (early dough stage) silages. The crops were ensiled in 30-L jars, without a LAB inoculant (C), with a Lactobacillus plantarum inoculum (LP), and with a Lactobacillus buchneri inoculum (LB; theoretical rate of 1 × 10(6) cfu/g of fresh forage). The pre-ensiled material, the silage at silo opening, and the aerobically exposed silage were analyzed for DM content, fermentative profiles, yeast and mold count, starch, crude protein, ash, fiber components, 24-h and 48-h DM digestibility and neutral detergent fiber (NDF) degradability. The yield and nutrient analysis data of the corn and sorghum silages were used as input for Milk2006 to estimate the total digestible nutrients, net energy of lactation, and milk production per Mg of DM. The DM fermentation and respiration losses were also calculated. The inocula influenced the in vitro NDF digestibility at 24h, the net energy for lactation (NE(L)), and the predicted milk yield per megagram of DM, whereas the length of time of air exposure influenced DM digestibility at 24 and 48 h, the NE(L), and the predicted milk yield per megagram of DM in the corn silages. The inocula only influenced the milk yield per megagram of DM and the air exposure affected the DM digestibility at 24h, the NE(L), and the milk yield per megagram of DM in the sorghum silages. The milk yield, after 14 d of air exposure, decreased to 1,442, 1,418, and 1,277 kg/Mg of DM for C, LB, and LP corn silages, respectively, compared with an average value of 1,568 kg of silage at opening. In the sorghum silages, the milk yield, after 14 d of air exposure, decreased to 1,226, 1,278, and 1,250 kg/Mg of DM for C, LB, and LP, respectively. When the estimated milk yield per megagram of harvested DM of corn and sorghum silage were related to mold count, it was shown that the loss of potential milk production occurred when the mold count exceeded 4 log cfu/g of silage, and it was almost halved when the mold count reached values greater than 8 log cfu/g of silage. Inoculation with L. buchneri, at a rate of 1 × 10(6) cfu/g of fresh forage, enhanced the stability of the silage after exposure to air, and, consequently, contributed to maintaining the nutritional value of the harvested forage over time, for air exposure up to 7 d.

PMID: 21338806 [PubMed - indexed for MEDLINE]

300. Eukaryot Cell. 2011 Apr;10(4):578-87. Epub 2011 Feb 18.

Evolution of mating within the Candida parapsilosis species group.

Sai S, Holland LM, McGee CF, Lynch DB, Butler G.

UCD School of Biomolecular and Biomedical Science, University College Dublin, Belfield, Dublin 4, Ireland.

Candida orthopsilosis and Candida metapsilosis are closely related to Candida parapsilosis, a major cause of infection in premature neonates. Mating has not been observed in these species. We show that ∼190 isolates of C. parapsilosis contain only an MTLa idiomorph at the mating-type-like locus. Here, we describe the isolation and characterization of the MTL loci from C. orthopsilosis and C. metapsilosis. Among 16 C. orthopsilosis isolates, 9 were homozygous for MTLa, 5 were homozygous for MTLα, and 2 were MTLa/α heterozygotes. The C. orthopsilosis isolates belonged to two divergent groups, as characterized by restriction patterns at MTL, which probably represent subspecies. We sequenced both idiomorphs from each group and showed that they are 95% identical and that the regulatory genes are intact. In contrast, 18 isolates of C. metapsilosis contain only MTLα idiomorphs. Our results suggest that the role of MTL in determining cell type is being eroded in the C. parapsilosis species complex. The population structure of C. orthopsilosis indicates that mating may occur. However, expression of genes in the mating signal transduction pathway does not respond to exposure to alpha factor. C. parapsilosis is also nonresponsive, even when the GTPase-activating protein gene SST2 is deleted. In addition, splicing of introns in MTLa1 and MTLa2 is defective in C. orthopsilosis. Mating is not detected. The alpha factor peptide, which is the same sequence in C. parapsilosis, C. orthopsilosis, and C. metapsilosis, can induce a mating response in Candida albicans. It is therefore likely either that mating of C. orthopsilosis takes place under certain unidentified conditions or that the mating pathway has been adapted for other functions, such as cross-species communication.

PMCID: PMC3127640 PMID: 21335529 [PubMed - indexed for MEDLINE]

301. Food Chem Toxicol. 2011 Jul;49(7):1477-83. Epub 2011 Feb 17.

A study of anti-cancer effects of Funalia trogii in vitro and in vivo.

Rashid S, Unyayar A, Mazmanci MA, McKeown SR, Banat IM, Worthington J.

Biomedical Sciences Research Institute, University of Ulster, Cromore Road, Coleraine, Co-Londonderry BT52 1SA, United Kingdom.

Extracts of natural products have been used for many years for health benefits. We report on an in vitro and in vivo study into the anti-tumour efficacy of an aqueous extract of the mycelial form of basidiomycete, Funalia trogii. A variety of biological assays were used to show that a 4h exposure of HT29, LNCaP, PC3, MCF-7 and MDA-MB-231 tumour cells to extract (0.5-5.0 mg/ml) resulted in significant cytotoxicity. In a clonogenic assay, IC50 values were found to range from 0.4-0.72 mg/ml; exposing fibroblast cells to the extract resulted in no cell kill. The extract resulted in significant cell kill in proliferating endothelial cells but had no toxicity to quiescent cells, this is useful in targeting tumour tissue since endothelial cells in tumours proliferate more rapidly that those found in other parts of the body. When tumours grown in immune compromised mice were injected intratumourally with extract (5 mg/ml twice a week for two weeks), a 9 day tumour growth delay was observed. The results indicate that the mycelial extract of F. trogii has a promising anti-tumour property.

PMID: 21333711 [PubMed - indexed for MEDLINE]

302. J Endod. 2011 Mar;37(3):398-402.

Fiber post etching with hydrogen peroxide: effect of concentration and application time.

de Sousa Menezes M, Queiroz EC, Soares PV, Faria-e-Silva AL, Soares CJ, Martins LR.

Department of Operative Dentistry and Dental Materials, School of Dentistry, Federal University of Uberlândia, Uberlândia, Minas Gerais, Brazil. murilomenezes@foufu.ufu.br

INTRODUCTION: Etching is necessary to expose the fibers and enable both mechanical and chemical bonding of the resin core to the fiber post. This study evaluated the effect of concentration and application time of hydrogen peroxide on the surface topography and bond strength of glass fiber posts to resin cores.
METHODS: Fiber posts were etched with 24% or 50% hydrogen peroxide for 1, 5, or 10 min (n = 10). Posts without any treatment were used as a control. After etching, the posts were silanated and adhesive resin was applied. The posts were positioned into a mold to allow a self-cured resin core to be inserted. The post/resin assembly was serially sectioned into five beams that were subjected to a tensile bond strength test. Data were subjected to two-way ANOVA and Tukey test (α = 0.05). The surface topography was analyzed using scanning electronic microscopy.
RESULTS: Non-etched post presents a relatively smooth surface without fiber exposure. Application of hydrogen peroxide increased the surface roughness and exposed the fibers. All experimental conditions yielded similar bond strength values that were higher than those obtained in the control group.
CONCLUSION: Both 24% and 50% hydrogen peroxide exposure increased the bond strength of resin to the posts, irrespective of the application time.

PMID: 21329829 [PubMed - indexed for MEDLINE]

303. Int Immunopharmacol. 2011 Aug;11(8):939-47. Epub 2011 Feb 15.

Fungal cell wall agents suppress the innate inflammatory cytokine responses of human peripheral blood mononuclear cells challenged with lipopolysaccharide in vitro.

Stopinšek S, Ihan A, Wraber B, Terčelj M, Salobir B, Rylander R, Simčič S.

Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Zaloška 4, 1000 Ljubljana, Slovenia. sanja.stopinsek@mf.uni-lj.si

Exposure to high levels of fungi might lead to diseases, such as airway inflammation, hypersensitivity pneumonitis and allergy. To comprehend the mechanisms behind the exposure to fungi and a disease, we examined the in vitro innate inflammatory cytokine response of human peripheral blood mononuclear cells (PBMC) challenged by fungal cell wall agents (FCWAs), i.e., soluble and particulate (1→3)-β-D-glucan-curdlan (BGS and BGP), zymosan (ZYM) and chitosan (CHT) in the absence or presence of lipopolysaccharide (LPS). We also studied FCWA effects on the mRNA expression of dectin-1, TLR2, TLR4 and mannose receptor (MR) by real-time RT-PCR. Our results demonstrated that BGP strongly induced the secretion of TNF-α, IL-6, IL-10 and IL-12; BGS, ZYM and CHT were weaker, but still significant cytokine inducers. We showed that BGS significantly augmented the LPS-induced in vitro secretion of TNF-α. On the other hand, BGP, ZYM and CHT suppressed the LPS-induced production of all cytokines. At the mRNA level, the dectin-1, TLR2 and TLR4 expressions were significantly reduced by all FCWAs in the absence of LPS and even more in the presence of LPS. While we demonstrated that the innate inflammatory cytokine response of PBMC induced by CHT was mediated by MR, the MR mRNA expression was significantly reduced by CHT. On the contrary, BGS significantly enhanced the MR mRNA expression. In conclusion, a long-term and massive exposure to LPS and FCWA (e.g., organic dust) may cause an important disruption of normal immune response and allow development and/or persistence of various immunopathological events.

PMID: 21329777 [PubMed - in process]

304. Environ Monit Assess. 2011 Nov;182(1-4):361-73. Epub 2011 Feb 16.

Decrease in air pollution load in urban environment of Bratislava (Slovakia) inferred from accumulation of metal elements in lichens.

Guttová A, Lackovičová A, Pišút I, Pišút P.

Institute of Botany, Slovak Academy of Sciences, Dúbravská cesta 9, 845 23 Bratislava, Slovakia. anna.guttova@savba.sk

The study illustrates the response of epiphytic lichens to changing atmospheric conditions in Central Europe, where the emission of air pollutants has significantly decreased from 1990, in the area in and around Bratislava City. Variation in concentrations of seven metal elements (Cu, Cd, Cr, Mn, Ni, Pb and Zn) in the thalli of Evernia prunastri, Hypogymnia physodes and Parmelia sulcata is assessed. Samples of these species were exposed in lichen bags in 39 sites throughout the territory of the city (more than 300 km(2)) during the period December 2006-February 2007. The samples were analyzed by AAS for metal element contents prior to and after exposure. The decrease in air pollution (for all studied elements by more than 90%) corresponded to a decrease in the accumulation of elements in lichen thalli, e.g. the contents of Pb decreased by 69% and of Cd by 34% on average. The results show also variations in accumulation between with different lichen species. The background values of metal element contents in thalli of H. physodes growing in situ were measured in semi-natural sites in Slovakia. It is suggested that these can be used as a reference in large-scale monitoring studies in Central Europe. Analysis of compatible data from the current study, and the study performed at the end of 1990s shows a significant decrease of metal elements in the air pollution load.

PMID: 21327486 [PubMed - indexed for MEDLINE]

305. Plant Cell Rep. 2011 Jun;30(6):1067-76. Epub 2011 Feb 16.

Phytochelatin synthase of Thlaspi caerulescens enhanced tolerance and accumulation of heavy metals when expressed in yeast and tobacco.

Liu GY, Zhang YX, Chai TY.

College of Life Science, Graduate University of Chinese Academy of Sciences, Yuquan Rd 19, Beijing 100049, China.

Phytochelatin synthase (PCS) is key enzyme for heavy metal detoxification and accumulation in plant. In this study, we isolated the PCS gene TcPCS1 from the hyperaccumulator Thlaspi caerulescens. Overexpression of TcPCS1 enhanced PC production in tobacco. Cd accumulation in the roots and shoots of TcPCS1 transgenic seedlings was increased compared to the wild type (WT), while Cd translocation from roots to shoots was not affected under Cd treatment. The root length of the TcPCS1 transgenic tobacco seedlings was significantly longer than that of the WT under Cd stress. These data indicate that TcPCS1 expression might increase Cd accumulation and tolerance in transgenic tobacco. In addition, the malondialdehyde content in TcPCS1 plants was below that of the wild type. However, the antioxidant enzyme activities of superoxide dismutase, peroxidase and catalase were found to be significantly higher than those of the WT when the transgenic plant was exposed to Cd stress. This suggests that the increase in PC production might enhance the Cd accumulation and thus increase the oxidative stress induced by the cadmium. The production of PCs could cause a transient decrease in the cytosolic glutathione (GSH) pool, and Cd and lower GSH concentration caused an increase in the oxidative response. We also determined TcPCS1 in Thlaspi caerulescens was regulated after exposure to various concentrations of CdCl(2) over different treatment times. Expression of TcPCS1 leading to increased Cd accumulation and enhanced metal tolerance, but the Cd contents were restrained by adding zinc in Saccharomyces cerevisiae transformants.

PMID: 21327392 [PubMed - indexed for MEDLINE]

306. Scand J Work Environ Health. 2011 Jul;37(4):349-56. doi: 10.5271/sjweh.3151. Epub 2011 Feb 16.

Chacinero's lung - hypersensitivity pneumonitis due to dry sausage dust.

Morell F, Cruz MJ, Gómez FP, Rodriguez-Jerez F, Xaubet A, Muñoz X.

Servicio de Neumología, Hospital Vall d'Hebron, 08035 Barcelona, Spain.

OBJECTIVE: Hypersensitivity pneumonitis (HP) comprises a large group of diseases that occur secondary to inhalation of a variety of antigens. This report describes a little-known cause of HP, previously unreported in the English literature.
METHODS: Five patients (three women) with a mean age of 41 years who fulfilled the criteria for HP due to exposure to dry sausage dust were studied. The clinical findings, immunologic testing, results of the specific inhalation challenge, and follow-up are described.
RESULTS: Three patients developed an acute form of disease and two patients a subacute form. A diffuse micronodular centrolobular pattern was seen on high-resolution computer tomography scanning of four patients. A restrictive pattern was identified on pulmonary function testing of four patients and decreased lung diffusion of carbon monoxide (DLCO) among three. In bronchoalveolar lavage specimens from three patients, lymphocytosis was 17%, 40%, and 40%, with a CD4/CD8 ratio of <0.6. Specific immunoglobin G (IgG) antibodies to Penicillium frequentans and Aspergillus fumigatus were positive for three patients. Performed on three patients, the specific inhalation challenge was positive for dry sausage dust extract in two cases and Penicillium frequentans in the third. Resolution of clinical, radiologic, spirometry, and DLCO alterations occurred among the three patients who avoided exposure following the diagnosis.
CONCLUSIONS: A short patient series affected by a little-known cause of occupational HP is described. Penicillium frequentans may be the causative agent in some cases, but other fungi were found that could also be implicated in the etiology of this disease.

PMID: 21327319 [PubMed - indexed for MEDLINE]

307. Afr Health Sci. 2010 Jun;10(2):172-6.

Indoor air mycoflora of residential dwellings in Jos metropolis.

Ayanbimpe GM, Wapwera SD, Kuchin D.

Department of Medical Microbiology, University of Jos, Plateau State Nigeria. ayang@unijos.edu.ng

BACKGROUND: The quality of air in the environment where one lives or works can have potential effects on human health. There are strong indications that in many parts of the world, our homes, schools and workplaces are heavily contaminated with air-borne molds and other biological contaminants. OBJECTIVES: This study was carried out to assess the level of fungal contamination of indoor air, health related experiences of residents, and the prevalent fungi species in the homes.
METHODS: The investigation was done between May 2005 and January 2006, using structured questionnaires and the agar plate exposure. 150 houses from 14 locations were examined.
RESULTS: 380 fungi belonging to 10 species were isolated, Chaetomium globosum (17%), Aspergillus fumigatus (14%), Stachybotrys alternans (14%) and Alternaria alternata (14%) being the predominant isolates.
CONCLUSION: The indoor air quality of residential dwellings in Jos is poor. Rate of isolation of fungi was not significantly different in the wet and dry periods of the year and residential density affected the occurrence of fungal contaminants. Residents are displeased with fungal presence in their homes and the associated health implications. There is need for proper attention to the quality of the indoor environment.

PMCID: PMC2956288 PMID: 21326971 [PubMed - indexed for MEDLINE]

308. Thorax. 2011 May;66(5):396-401. Epub 2011 Feb 16.

Lung function decline in relation to mould and dampness in the home: the longitudinal European Community Respiratory Health Survey ECRHS II.

Norbäck D, Zock JP, Plana E, Heinrich J, Svanes C, Sunyer J, Künzli N, Villani S, Olivieri M, Soon A, Jarvis D.

Department of Medical Science, Uppsala University and Occupational and Environmental Medicine, University Hospital, SE-751 85 Uppsala, Sweden. dan.norback@medsci.uu.se

BACKGROUND: There are few longitudinal studies that have examined the association of lung function decline with indoor mould and dampness. Lung function decline in relation to dampness and mould in the home has studied in adults over a 9 year period.
METHODS: Spirometry was performed twice in participants in the European Respiratory Health Survey (ECRHS I and II) who were initially examined aged 20-45 years, in 1990-1995 and 9 years later (n=6443). Information on their current home was collected twice by interview. Dampness (water damage or damp spots) and indoor mould, ever and in the last 12 months, were assessed. A dampness score and a mould score were calculated. In addition, 3118 homes at 22 centres were inspected directly at follow-up for the presence of dampness and mould.
RESULTS: Dampness and mould were common. Overall, 50.1% reported any dampness and 41.3% any indoor mould in either ECRHS I or ECRHS II. Women with dampness at home had an additional decline in forced expiratory volume in 1 s (FEV(1)) of -2.25 ml/year (95% CI -4.25 to -0.25), with a significant trend in increased lung function decline in relation to the dampness score (p=0.03). The association in women was significant when excluding those with asthma at baseline. Observed damp spots in the bedroom was associated with a significant additional decline in FEV(1) of -7.43 ml/year (95% CI -13.11 to 1.74) in women.
CONCLUSION: Dampness and indoor mould growth is common in dwellings, and the presence of damp is a risk factor for lung function decline, especially in women.

PMID: 21325663 [PubMed - indexed for MEDLINE]

309. PLoS One. 2011 Feb 2;6(2):e16675.

Effects of an infectious fungus, Batrachochytrium dendrobatidis, on amphibian predator-prey interactions.

Han BA, Searle CL, Blaustein AR.

Odum School of Ecology, University of Georgia, Athens, Georgia, United States of America. han@uga.edu

The effects of parasites and pathogens on host behaviors may be particularly important in predator-prey contexts, since few animal behaviors are more crucial for ensuring immediate survival than the avoidance of lethal predators in nature. We examined the effects of an emerging fungal pathogen of amphibians, Batrachochytrium dendrobatidis, on anti-predator behaviors of tadpoles of four frog species. We also investigated whether amphibian predators consumed infected prey, and whether B. dendrobatidis caused differences in predation rates among prey in laboratory feeding trials. We found differences in anti-predator behaviors among larvae of four amphibian species, and show that infected tadpoles of one species (Anaxyrus boreas) were more active and sought refuge more frequently when exposed to predator chemical cues. Salamander predators consumed infected and uninfected tadpoles of three other prey species at similar rates in feeding trials, and predation risk among prey was unaffected by B. dendrobatidis. Collectively, our results show that even sub-lethal exposure to B. dendrobatidis can alter fundamental anti-predator behaviors in some amphibian prey species, and suggest the unexplored possibility that indiscriminate predation between infected and uninfected prey (i.e., non-selective predation) could increase the prevalence of this widely distributed pathogen in amphibian populations. Because one of the most prominent types of predators in many amphibian systems is salamanders, and because salamanders are susceptible to B. dendrobatidis, our work suggests the importance of considering host susceptibility and behavioral changes that could arise from infection in both predators and prey.

PMCID: PMC3032789 PMID: 21311771 [PubMed - indexed for MEDLINE]

310. Environ Health Perspect. 2011 Jun;119(6):794-800. Epub 2011 Feb 10.

Widely used pesticides with previously unknown endocrine activity revealed as in vitro antiandrogens.

Orton F, Rosivatz E, Scholze M, Kortenkamp A.

Centre for Toxicology, School of Pharmacy, University of London, London, United Kingdom. francesorton@gmail.com

BACKGROUND: Evidence suggests that there is widespread decline in male reproductive health and that antiandrogenic pollutants may play a significant role. There is also a clear disparity between pesticide exposure and data on endocrine disruption, with most of the published literature focused on pesticides that are no longer registered for use in developed countries.
OBJECTIVE: We used estimated human exposure data to select pesticides to test for antiandrogenic activity, focusing on highest use pesticides.
METHODS: We used European databases to select 134 candidate pesticides based on highest exposure, followed by a filtering step according to known or predicted receptor-mediated antiandrogenic potency, based on a previously published quantitative structure-activity relationship (QSAR) model. In total, 37 pesticides were tested for in vitro androgen receptor (AR) antagonism. Of these, 14 were previously reported to be AR antagonists ("active"), 4 were predicted AR antagonists using the QSAR, 6 were predicted to not be AR antagonists ("inactive"), and 13 had unknown activity, which were "out of domain" and therefore could not be classified with the QSAR ("unknown").
RESULTS: All 14 pesticides with previous evidence of AR antagonism were confirmed as antiandrogenic in our assay, and 9 previously untested pesticides were identified as antiandrogenic (dimethomorph, fenhexamid, quinoxyfen, cyprodinil, λ-cyhalothrin, pyrimethanil, fludioxonil, azinphos-methyl, pirimiphos-methyl). In addition, we classified 7 compounds as androgenic.
CONCLUSIONS: Due to estimated antiandrogenic potency, current use, estimated exposure, and lack of previous data, we strongly recommend that dimethomorph, fludioxonil, fenhexamid, imazalil, ortho-phenylphenol, and pirimiphos-methyl be tested for antiandrogenic effects in vivo. The lack of human biomonitoring data for environmentally relevant pesticides presents a barrier to current risk assessment of pesticides on humans.

PMCID: PMC3114813 PMID: 21310686 [PubMed - indexed for MEDLINE]

311. Occup Environ Med. 2011 Oct;68(10):771-6. Epub 2011 Feb 9.

Tumour necrosis factor G-308A polymorphism modifies the effect of home dampness on childhood asthma.

Tsai CH, Tung KY, Chen CH, Lee YL.

Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei 100, Taiwan.

OBJECTIVES: Environmental exposure at home, such as dampness, has been shown to have adverse effects on respiratory health. However, few studies explored the association between home dampness and genetic polymorphisms on childhood asthma. The aim of the study is to evaluate the effects of home dampness and tumour necrosis factor-α gene (TNF-α) on asthma in Taiwanese children.
METHODS: The authors investigated 3810 schoolchildren in Taiwan Children Health Study from 14 communities. Children's exposure and disease status were measured from a parental questionnaire. Multiple logistic regression models were fitted to estimate the effects of home dampness exposure and TNF-α genotypes on the prevalence of asthma and wheeze.
RESULTS: Mildewy odour at home was significantly associated with increased prevalence of lifetime wheeze (OR=1.36, 95% CI 1.05 to 1.77, p for trend=0.04). The effects of water stamp on the wall at home were associated with lifetime asthma and lifetime wheeze. Children with water stamp on the wall at home and TNF-308 A allele had increased risks on lifetime asthma, active asthma and lifetime wheeze. TNF-α showed significant interactive effects with mildewy odour on lifetime asthma (p for interaction=0.01), and with water stamp on the wall at home on lifetime wheeze (p for interaction=0.04). Under stratification by TNF-308 genotypes, we found that the frequency of water stamp on the wall was associated with increased risks of all asthma subcategories and lifetime wheeze among TNF-308 GA or AA genotypes (p for trend<0.05).
CONCLUSIONS: Home dampness is a risk factor for asthma and wheeze among children, especially for those with the TNF-308 A allele.

PMID: 21307151 [PubMed - indexed for MEDLINE]

312. Cleft Palate Craniofac J. 2011 Nov;48(6):757-61. Epub 2011 Feb 8.

Incidence of cleft pathology in greater new orleans before and after hurricane katrina.

Goenjian HA, Chiu ES, Alexander ME, St Hilaire H, Moses M.

Background : Reports after the 2005 Hurricane Katrina have documented an increase in stress reactions and environmental teratogens (arsenic, mold, alcohol). Objective : To assess the incidence of cleft pathology before and after the hurricane, and the distribution of cleft cases by gender and race. Methods : Retrospective chart review of cleft lip with or without cleft palate (CL/P) and cleft palate (CP) cases registered with the Cleft and Craniofacial Team at Children's Hospital of New Orleans, the surgical center that treated cleft cases in Greater New Orleans between 2004 and 2007. Live birth data were obtained from the Louisiana State Center for Health Statistics. Results : The incidence of cleft cases, beginning 9 months after the hurricane (i.e., June 1, 2006) was significantly higher compared with the period before the hurricane (0.80 versus 1.42; p = .008). Within racial group comparisons showed a higher incidence among African Americans versus whites (0.42 versus 1.22; p = .01). The distribution of CL/P and CP cases by gender was significant (p = .05). Conclusion : The increase in the incidence of cleft cases after the hurricane may be attributable to increased stress and teratogenic factors associated with the hurricane. The increase among African Americans may have been due to comparatively higher exposure to environmental risk factors. These findings warrant further investigation to replicate the results elsewhere in the Gulf to determine whether there is a causal relationship between environmental risk factors and increased cleft pathology.

PMID: 21303264 [PubMed - in process]

313. Curr Opin Allergy Clin Immunol. 2011 Apr;11(2):137-43.

The indoor environment and its effects on childhood asthma.

Ahluwalia SK, Matsui EC.

Division of Allergy and Immunology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

PURPOSE OF REVIEW: Indoor pollutants and allergens cause asthma symptoms and exacerbations and influence the risk of developing asthma. We review recent studies regarding the effects of the indoor environment on childhood asthma.
RECENT FINDINGS: Exposure to some indoor allergens and second hand smoke are causally related to the development of asthma in children. Many recent studies have demonstrated an association between exposure to indoor pollutants and allergens and airways inflammation, asthma symptoms, and increased healthcare utilization among individuals with established asthma. Genetic polymorphisms conferring susceptibility to some indoor exposures have also been identified, and recent findings support the notion that environmental exposures may influence gene expression through epigenetic modification. Recent studies also support the efficacy of multifaceted environmental interventions in childhood asthma. SUMMARY: Studies have provided significant evidence of the association between many indoor pollutants and allergens and asthma morbidity, and have also demonstrated the efficacy of multifaceted indoor environmental interventions in childhood asthma. There is also a growing body of evidence suggesting that some indoor pollutants and allergens may increase the risk of developing asthma. Future studies should examine mechanisms whereby environmental exposures may influence asthma pathogenesis and expand the current knowledge of susceptibility factors for indoor exposures.

PMID: 21301330 [PubMed - indexed for MEDLINE]

314. Antimicrob Agents Chemother. 2011 May;55(5):2265-75. Epub 2011 Feb 7.

Evaluations of shorter exposures of contact lens cleaning solutions against Fusarium oxysporum species complex and Fusarium solani species complex to simulate inappropriate usage.

Ramani R, Chaturvedi V.

Mycology Laboratory, Wadsworth Center, New York State Department of Health, 120 New Scotland Ave., Albany, NY 12201-2002, USA.

An outbreak of Fusarium keratitis in contact lens users resulted in withdrawal of ReNu with MoistureLoc solution, although the exact cause of the outbreak remains enigmatic. We evaluated current and discontinued multipurpose cleaning solutions (MPSs; MoistureLoc, Equate, MultiPlus, and OptiFree Express) against plankton- and biofilm-derived cells of Fusarium oxysporum species complex (FOSC) and F. solani species complex (FSSC). The methods included a traditional assay based on CFU counts and a novel flow cytometry (FC) assay based on percent cell subpopulation (PCS) stained with two fluorochromes (Sytox Red and 5-chloromethylfluorescein diacetate). The tests were done with the respective manufacturers' recommended cleaning regimens (240 to 360 min) and under shorter exposures (15 to 60 min) to simulate inappropriate usage by the customers. FC assay measured PCS, which was available rapidly, in 5 to 7 h, whereas 24 to 48 h was needed for CFU counts, and there was good correlation between the two methods (r2=0.97). FC assays allowed identification of injured fungal cells, which are likely to be missed with growth assays. In general, a time- and inoculum-dependent survival pattern was seen for both FOSC and FSSC cells, and biofilm-derived cells were more resistant than plankton-derived cells. MultiPlus and Equate produced 100% sterilization of fungi even under shorter exposures. However, biofilm FOSC and FSSC cells survived for up to 4 h in MoistureLoc solution and up to 6 h in OptiFree Express solution under shorter exposure times. This finding was enigmatic, as OptiFree Express is not associated with any outbreak of Fusarium keratitis. This study provides additional support for possible roles that improper lens cleaning regimens and fungal biofilms could play as predisposing factors for Fusarium keratitis.

PMCID: PMC3088191 PMID: 21300826 [PubMed - indexed for MEDLINE]

315. Med Mycol. 2011 Aug;49(6):594-601. Epub 2011 Feb 7.

The evaluation of in vitro pharmacodynamic properties of amphotericin B, voriconazole and caspofungin against A. fumigatus isolates by the conventional and colorimetric time-kill assays.

Kiraz N, Oz Y, Dag I.

Department of Microbiology, Faculty of Cerrahpasa Medicine, Istanbul University, Istanbul, Turkey.

Aspergillus fumigatus is an opportunistic pathogen responsible for life-threatening infections in immuncompromised patients. Data about the in vitro pharmacodynamics of antifungals against A. fumigatus are limited. In the present study, we investigated the fungicidal activities, at concentrations of 1, 4 and 16 times the minimum inhibitory concentration (MIC), of caspofungin (CAS), amphotericin B (AMB) and voriconazole (VORI) against eight A. fumigatus isolates through the use of time kill and 2,3-Bis [2-methoxy-4-nitro-5-(sulfenylamino) carbonyl-2H-tetrazolium-hydroxide] (XTT) reduction tests. By the conventional time kill test, AMB was fungicidal (≥99.9% reduction in colony forming units; CFU) for all isolates at 4-16 MICs after 48 h incubation. The fungicidal effect for VORI was determined at 4 × MIC for one isolate and at 16 × MIC for four isolates at 48 h of exposure. CAS was also fungicidal at 1 × MIC for one isolate and at 4-16 MICs for two isolates at 48 h. While the percentage of median killing of AMB was found by the time-kill method with XTT as 99% at 4 × MIC and 99.28% at 16 × MIC, that of VORI was 94.5% at 4 × MIC and 92.88% at 16 × MIC after 48 h of incubation. However, a significant increase was observed compared to initial inoculum size with CAS after 48 h. Since the XTT method measures all cellular viability in media, it may give more reliable results about pharmacodynamics of antifungal agents against Aspergillus spp. than the time kill test.

PMID: 21299374 [PubMed - indexed for MEDLINE]

316. J Mol Biol. 2011 Apr 1;407(3):354-67. Epub 2011 Feb 3.

The N-terminal unstructured domain of yeast ODC functions as a transplantable and replaceable ubiquitin-independent degron.

Gödderz D, Schäfer E, Palanimurugan R, Dohmen RJ.

Institute for Genetics, University of Cologne, Zülpicher Strasse 47, D-50674 Cologne, Germany.

Ornithine decarboxylase (ODC), a homodimeric enzyme with a rate-limiting function in polyamine biosynthesis, is subject to a feedback control involving its selective proteolysis. Targeting of ODC monomers to the proteasome is mediated by ODC antizyme (OAZ), the expression of which is induced by high levels of polyamines. Here, we report our analysis of the N-terminal degron in Saccharomyces cerevisiae ODC and the mechanism of its antizyme-dependent targeting. This ∼45-residue domain of ODC [termed ODC degradation signal (ODS)] is essential for degradation of ODC. Extensive mutagenesis indicated that it is not a specific sequence within ODS that is important but, rather, its unstructured nature. Consistent with this conclusion, ODS could be functionally replaced by an unrelated unstructured domain. We show that increasing the distance of ODS to the rest of the ODC protein reduced the dependence on Oaz1 for targeting, indicating that exposure of ODS is critical for its function. Disruption of ODC dimers by introducing interface mutations, in contrast, was insufficient for targeting. Binding of Oaz1 to ODC monomers is thus required to activate ODS. Fusion of ODS to the N terminus of Ura3 was sufficient to convert it into a ubiquitin-independent substrate of the proteasome. By contrast, ODS failed to destabilize maltose-binding protein or dihydrofolate reductase, indicating that this degron only operates in an appropriate structural context that enables rapid unfolding.

PMID: 21295581 [PubMed - indexed for MEDLINE]

317. Astrobiology. 2011 Jan-Feb;11(1):65-73. Epub 2011 Feb 6.

Damage escape and repair in dried Chroococcidiopsis spp. from hot and cold deserts exposed to simulated space and martian conditions.

Billi D, Viaggiu E, Cockell CS, Rabbow E, Horneck G, Onofri S.

Dipartimento di Biologia, Università di Roma "Tor Vergata ," Roma, Italy. billi@uniroma2.it

The cyanobacterium Chroococcidiopsis, overlain by 3 mm of Antarctic sandstone, was exposed as dried multilayers to simulated space and martian conditions. Ground-based experiments were conducted in the context of Lichens and Fungi Experiments (EXPOSE-E mission, European Space Agency), which were performed to evaluate, after 1.5 years on the International Space Station, the survival of cyanobacteria (Chroococcidiopsis), lichens, and fungi colonized on Antarctic rock. The survival potential and the role played by protection and repair mechanisms in the response of dried Chroococcidiopsis cells to ground-based experiments were both investigated. Different methods were employed, including evaluation of the colony-forming ability, single-cell analysis of subcellular integrities based on membrane integrity molecular and redox probes, evaluation of the photosynthetic pigment autofluorescence, and assessment of the genomic DNA integrity with a PCR-based assay. Desiccation survivors of strain CCMEE 123 (coastal desert, Chile) were better suited than CCMEE 134 (Beacon Valley, Antarctica) to withstand cellular damage imposed by simulated space and martian conditions. Exposed dried cells of strain CCMEE 123 formed colonies, maintained subcellular integrities, and, depending on the exposure conditions, also escaped DNA damage or repaired the induced damage upon rewetting.

PMID: 21294638 [PubMed - indexed for MEDLINE]

318. Microbiology. 2011 May;157(Pt 5):1416-27. Epub 2011 Feb 3.

Role of sphingosine-1-phosphate (S1P) and S1P receptor 2 in the phagocytosis of Cryptococcus neoformans by alveolar macrophages.

McQuiston T, Luberto C, Del Poeta M.

Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, USA.

The pathogenic fungus Cryptococcus neoformans is a major cause of morbidity and mortality in immunocompromised individuals. Infection of the human host occurs through inhalation of infectious propagules following environmental exposure. In the lung, C. neoformans can reside in the extracellular environment of the alveolar spaces or, upon phagocytosis, it can survive and grow intracellularly within alveolar macrophages (AMs). In previous studies, we found that sphingosine kinase 1 (SK1) influenced the intracellular residency of C. neoformans within AMs. Therefore, with this study we aimed to examine the role of the SK1 lipid product, sphingosine-1-phosphate (S1P), in the AMs-C. neoformans interaction. It was found that extracellular S1P enhances the phagocytosis of C. neoformans by AMs. Using both genetic and pharmacological approaches we further show that extracellular S1P exerts its effect on the phagocytosis of C. neoformans by AMs through S1P receptor 2 (S1P2). Interestingly, loss of S1P2 caused a dramatic decrease in the mRNA levels of Fcγ receptors I (FcγRI), -II and -III. In conclusion, our data suggest that extracellular S1P increases antibody-mediated phagocytosis through S1P2 by regulating the expression of the phagocytic Fcγ receptors.

PMCID: PMC3140583 [Available on 2012/5/1] PMID: 21292747 [PubMed - indexed for MEDLINE]

319. Anim Reprod Sci. 2011 Feb;123(3-4):187-91. Epub 2011 Jan 14.

Effects of maternal and dietary selenium (Se-enriched yeast) on the expression of p34(cdc2) and CyclinB1 of germ cells of their offspring in goats.

Ren Y, Wang Q, Shi L, Yue W, Zhang C, Lei F.

College of Animal Science and Technology, Shanxi Agricultural University, Taigu 030801, PR China.

The aim of the study was to evaluate the effect of selenium on the expression of p34(cdc2) and CyclinB1 (two components of MPF regulating cell cycle) of germ cells of their offspring in goats. A herd of 119 Taihang Black Goats, which was randomly divided into 4 treatments, received experimental diet with different Se levels (from Se-enriched yeast) for 174d. The four treatments, fed with a basal diet, were supplemented with 0 (control), 0.5, 2 and 4 mgkg⁻¹ DM Se. Testis samples were collected from the young male goats of each treatment group at the end of the study (30d after weaning) for mRNA expression using real-time PCR and for protein expression by immunohistochemistry assay. Results show that a significant decrease was observed in mRNA expression of p34(cdc2) and CyclinB1 in the testis of Se-deficient (Group 1) and Se-excess (Group 4) animals compared with that in Groups 2 and 3. However, no significant changes were found in mRNA expression of p34(cdc2) between Se-deficient (Group 1) and Se-excess (Group 4). Also the immunohistochemistry assay detected similar results of protein expression of these two genes. These results suggest, that maternal and dietary Se-induced oxidative stress can modulate the mRNA and protein expression of the cell cycle related genes (p34(cdc2) and CyclinB1) in the testis of their offspring. In addition, Se deficiency and Se excess could prevent the completion of the cell cycle.

PMID: 21288666 [PubMed - indexed for MEDLINE]

320. Malar J. 2011 Feb 2;10:24.

First report of the infection of insecticide-resistant malaria vector mosquitoes with an entomopathogenic fungus under field conditions.

Howard AF, N'Guessan R, Koenraadt CJ, Asidi A, Farenhorst M, Akogbéto M, Knols BG, Takken W.

Laboratory of Entomology, Wageningen University and Research Centre, P.O. Box 8031, 6700 EH Wageningen, The Netherlands. afv.howard@gmail.com

BACKGROUND: Insecticide-resistant mosquitoes are compromising the ability of current mosquito control tools to control malaria vectors. A proposed new approach for mosquito control is to use entomopathogenic fungi. These fungi have been shown to be lethal to both insecticide-susceptible and insecticide-resistant mosquitoes under laboratory conditions. The goal of this study was to see whether entomopathogenic fungi could be used to infect insecticide-resistant malaria vectors under field conditions, and to see whether the virulence and viability of the fungal conidia decreased after exposure to ambient African field conditions.
METHODS: This study used the fungus Beauveria bassiana to infect the insecticide-resistant malaria vector Anopheles gambiae s.s (Diptera: Culicidae) VKPER laboratory colony strain. Fungal conidia were applied to polyester netting and kept under West African field conditions for varying periods of time. The virulence of the fungal-treated netting was tested 1, 3 and 5 days after net application by exposing An. gambiae s.s. VKPER mosquitoes in WHO cone bioassays carried out under field conditions. In addition, the viability of B. bassiana conidia was measured after up to 20 days exposure to field conditions.
RESULTS: The results show that B. bassiana infection caused significantly increased mortality with the daily risk of dying being increased by 2.5 × for the fungus-exposed mosquitoes compared to the control mosquitoes. However, the virulence of the B. bassiana conidia decreased with increasing time spent exposed to the field conditions, the older the treatment on the net, the lower the fungus-induced mortality rate. This is likely to be due to the climate because laboratory trials found no such decline within the same trial time period. Conidial viability also decreased with increasing exposure to the net and natural abiotic environmental conditions. After 20 days field exposure the conidial viability was 30%, but the viability of control conidia not exposed to the net or field conditions was 79%.
CONCLUSIONS: This work shows promise for the use of B. bassiana fungal conidia against insecticide-resistant mosquitoes in the field, but further work is required to examine the role of environmental conditions on fungal virulence and viability with a view to eventually making the fungal conidia delivery system more able to withstand the ambient African climate.

PMCID: PMC3045381 PMID: 21288359 [PubMed - indexed for MEDLINE]

321. Occup Med (Lond). 2011 Mar;61(2):121-6. Epub 2011 Jan 31.

Occupational asthma in professional cleaning work: a clinical study.

Mäkelä R, Kauppi P, Suuronen K, Tuppurainen M, Hannu T.

Occupational Medicine, Finnish Institute of Occupational Health, Topeliuksenkatu 41 a A, FI-00250 Helsinki, Finland.

BACKGROUND: Several epidemiological studies have reported an increased risk of asthma among professional cleaners. To date, however, no analysis of large patient series from clinic of occupational medicine has been published. AIMS: To describe the cases of occupational asthma (OA) diagnosed at the Finnish Institute of Occupational Health (FIOH) during the period 1994-2004 in workers employed in professional cleaning work.
METHODS: OA was diagnosed according to patient history, lung function examinations and specific challenge tests with measurements of the forced expiratory volume in 1 second and peak expiratory flow values.
RESULTS: Our series comprised 20 patients, all female, with a mean age of 48.8 years (range 27-60 years). The mean duration of cleaning work before the onset of the respiratory symptoms was 14.3 years (range 1-36 years), and the mean duration of cleaning work before the FIOH examinations was 18.6 years (range 3-38 years). OA was triggered by chemicals in 9 cases (45%) and by moulds in 11 cases (55%). The chemicals were cleaning chemicals (wax-removing substances containing ethanolamines in five cases and a cleaning agent containing chloramine-T in one case) and chemicals used in the industrial processes at workplaces (three cases). Of the moulds, the most frequently associated with OA was Aspergillus fumigatus (nine cases).
CONCLUSIONS: OA was attributed not only to cleaning chemicals but also to other chemicals used in work environments. Moulds are presented as a new cause of OA in cleaners.

PMID: 21285030 [PubMed - indexed for MEDLINE]

322. J Environ Pathol Toxicol Oncol. 2010;29(4):293-315.

Postexposure prophylaxis for deadly bloodborne viral infections.

Edlich RF, Gubler K, Wallis AG, Clark JJ, Dahlstrom JJ, Long WB 3rd.

Biomedical Engineering and Emergency Medicine, University of Virginia Health System, Charlottesville, VA, USA. richardedlich@gmail.com

The purpose of this report is to discuss management of operating room personnel who have had occupational exposure to blood and other body fluids that might contain hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), and human T-cell lymphotropic virus type I (HTLV-I). HBV postexposure prophylaxis includes starting hepatitis B vaccine series in any susceptible unvaccinated operating room personnel who sustain an exposure to blood or body fluid during surgery. Postexposure prophylaxis with hepatitis B immune globulin (HBIG) is an important consideration after determining the hepatitis B antigen status of the patient. Ideally, all operating room personnel should be vaccinated with hepatitis B vaccine before they pursue their career in surgery. Immune globulin and antiviral agents (eg, interferon with or without ribavirin) should not be used for postexposure prophylaxis of operating room personnel exposed to patients with HCV; rather, follow-up HCV testing should be initiated to determine if infection develops. Postexposure prophylaxis for HIV involves a basic four-week regimen of two drugs (zidovudine and lamivudine; lamivudine and stavudine; or didanosine and stavudine) for most exposures. An expanded regimen that includes a third drug must be considered for HIV exposures that pose an increased risk for transmission. When developing a postexposure prophylaxis regimen, it is helpful to contact the National Clinicians' Postexposure Prophylaxis Hotline, (888) 448-4911. Prevention should be a major consideration in postexposure prophylaxis with the use of the double-glove hole indication system by all operating room personnel.

PMID: 21284594 [PubMed - indexed for MEDLINE]

323. Cornea. 2011 Jun;30(6):620-3.

Microbiological evaluation of chronic blepharitis among Iranian veterans exposed to mustard gas: a case-controlled study.

Karimian F, Zarei-Ghanavati S, A BR, Jadidi K, Lotfi-Kian A.

Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Labbafinejad Medical Center, Department of Ophthalmology, Tehran, Iran. karimianf@yahoo.com

PURPOSE: To evaluate the microbiological characteristics of eyelid margin flora in chronic blepharitis in mustard gas-exposed individuals and compare the results with those in age- and sex-matched unexposed people.
METHODS: In this comparative case series, 289 patients with ocular manifestations of mustard gas exposure (case) were evaluated for signs of chronic blepharitis. Additionally, microbiological evaluation of eyelid margins was conducted in these patients and compared with results of 100 unexposed patients with chronic blepharitis (control).
RESULTS: One-hundred fifty (52.0%) of 289 mustard gas casualties had signs of chronic blepharitis. Microbiological evaluation revealed higher isolation rates of Staphylococcus epidermidis (78%) and Staphylococcus aureus (57%) in the case in comparison to control group (P < 0.01). Moreover, S. aureus isolated from the cases exhibited greater resistance to common antibiotics compared with control group. Fungi were isolated more frequent in the case compared with controls (30% vs. 4%, P < 0.01), with Cladosporium and Candida species being most common in the case group.
CONCLUSIONS: Exposure to mustard gas seems to alter the microbiological flora of the eyelid margin. Staphylococcus spp., including antibiotic-resistant strains, and fungi were more frequently isolated in these patients. The relationship between microbial culture results and the severity of ocular surface manifestations in mustard gas-injured cases warrant further investigation.

PMID: 21282998 [PubMed - indexed for MEDLINE]

324. Chem Biol Interact. 2011 May 30;191(1-3):32-7. Epub 2011 Jan 27.

Novel alkenal/one reductase activity of yeast NADPH:quinone reductase Zta1p. Prospect of the functional role for the ζ-crystallin family.

Crosas E, Porté S, Moeini A, Farrés J, Biosca JA, Parés X, Fernández MR.

Department of Biochemistry and Molecular Biology, Faculty of Biosciences, Universitat Autònoma de Barcelona, Barcelona, Spain.

ζ-Crystallins are a Zn(2+)-lacking enzyme group with quinone reductase activity, which belongs to the medium-chain dehydrogenase/reductase superfamily. It has been recently observed that human ζ-crystallin is capable of reducing the α,β-double bond of alkenals and alkenones. Here we report that this activity is also shared by the homologous Zta1p enzyme from Saccharomyces cerevisiae. While the two enzymes show similar substrate specificity, human ζ-crystallin exhibits higher activity with lipid peroxidation products and Zta1p is more active with cinnamaldehyde. The presence of Zta1p has an in vivo protective effect on yeast strains exposed to the toxic substrate 3-penten-2-one. Analysis of ZTA1 gene expression indicates an induction under different types of cellular stress, including ethanol and dimethylsulfoxide exposure and by reaching the stationary growth phase. The role of Zta1p in the yeast adaptation to some stress types and the general functional significance of ζ-crystallins are discussed.

PMID: 21276778 [PubMed - indexed for MEDLINE]

325. J Hosp Infect. 2011 Apr;77(4):321-6. Epub 2011 Jan 26.

Intention to comply with post-exposure management among nurses exposed to blood and body fluids in Taiwan: application of the theory of planned behaviour.

Ko NY, Yeh SH, Tsay SL, Ma HJ, Chen CH, Pan SM, Feng MC, Chiang MC, Lee YW, Chang LH, Jang JF.

Department of Nursing, College of Medicine, National Cheng Kung University & Hospital, Taiwan. nyko@mail.ncku.edu.tw

Nurses are at significant risk from occupationally acquired bloodborne virus infections following a needlestick and sharps injury. This study aimed to apply the theory of planned behaviour (TPB) to predict nurses' intention to comply with occupational post-exposure management. A cross-sectional survey was applied to select registered nurses who worked in human immunodeficiency virus (HIV)-designated hospitals. An anonymous, self-administered questionnaire based on the TPB was distributed to 1630 nurses and 1134 (69.5%) questionnaires were returned. From these, a total of 802 nurses (71%) reported blood and body fluid exposure incidents during 2003-2005 and this group was used for analysis. Only 44.6% of the 121 exposed nurses who were prescribed post-exposure prophylaxis (PEP) by infectious disease doctors returned to the clinic for interim monitoring, and only 56.6% of exposed nurses confirmed their final serology status. Structural equation modelling was used to test the TPB indicating perceived behavioural control (the perception of the difficulty or ease of PEP management, β=0.58), subjective norm (the perception of social pressure to adhere to PEP, β=0.15), and attitudes (β=0.12) were significant direct effects on nurses' intention to comply with post-exposure management. The hypothesised model test indicated that the model fitted with the expected relationships and directions of theoretical constructs [χ(2) (14, N=802)=23.14, P=0.057, GFI=0.987, RMSEA=0.039]. The TPB model constructs accounted for 54% of the variance in nurses' intention to comply with post-exposure management. The TPB is an appropriate model for predicting nurses' intention to comply with post-exposure management. Healthcare facilities should have policies to decrease the inconvenience of follow-up to encourage nurses to comply with post-exposure management.

PMID: 21276639 [PubMed - indexed for MEDLINE]

326. FEMS Yeast Res. 2011 Jun;11(4):315-23. doi: 10.1111/j.1567-1364.2011.00722.x. Epub 2011 Feb 21.

Microbial alcohol-conferred hemolysis is a late response to alcohol stress.

Shuster A, Korem M, Jacob-Hirsch J, Amariglio N, Rechavi G, Rosenberg M.

Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, The Maurice and Gabriela Goldschleger School of Dental Medicine, Tel-Aviv University, Ramat-Aviv, Israel.

We have reported previously that growth on alcohol vapors confers hemolytic properties on certain yeast species and strains ['microbial alcohol-conferred hemolysis' (MACH)]. In a recent study, we analyzed the genetic basis of MACH in Saccharomyces cerevisiae using the EUROSCARF mutant collection. The data suggested that intact mitochondrial and respiratory chain functions are critical for the observed alcohol-mediated hemolysis. We proposed that the uncontrolled cellular uptake of alcohol results in yeast 'hyper-respiration', leading to elaboration of hemolytic molecules such as hydrogen peroxide and lytic lipids. In the current study, we have further analyzed the molecular mechanisms involved in the MACH phenomenon in S. cerevisiae, using DNA microarrays. The patterns of regulation were confirmed by quantitative reverse transcriptase PCR. The results presented here lend further support to this hypothesis, based on upregulation of the genes responsible for coping with vast amounts of hydrogen peroxide produced as a byproduct of excessive oxidation of alcohol. These results, taken together, show that alcohol-mediated hemolysis in yeast appears to be related to the overproduction of hemolytic byproducts, particularly hydrogen peroxide, which accumulates during long-term exposure of S. cerevisiae to both ethanol and n-butanol.

PMID: 21276200 [PubMed - indexed for MEDLINE]

327. Radiat Res. 2011 Apr;175(4):501-9. Epub 2011 Jan 28.

Pulmonary injury after combined exposures to low-dose low-LET radiation and fungal spores.

Marples B, Downing L, Sawarynski KE, Finkelstein JN, Williams JP, Martinez AA, Wilson GD, Sims MD.

Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan 48073, USA. brian.marples@beaumont.edu

Exposure to infectious microbes is a likely confounder after a nuclear terrorism event. In combination with radiation, morbidity and mortality from an infection may increase significantly. Pulmonary damage after low-dose low-LET irradiation is characterized by an initial diffuse alveolar inflammation. By contrast, inhaled fungal spores produce localized damage around pulmonary bronchioles. In the present study, we assessed lung injury in C57BL/6 mice after combined exposures to whole-body X radiation and inhaled fungal spores. Either animals were exposed to Aspergillus spores and immediately irradiated with 2 Gy, or the inoculation and irradiation were separated by 8 weeks. Pulmonary injury was assessed at 24 and 48 h and 1, 2, 4, 8, and 24 weeks later using standard H&E-stained sections and compared with sham-treated age-matched controls. Immunohistochemistry for invasive inflammatory cells (macrophages, neutrophils and B and T lymphocytes) was performed. A semi-quantitative assessment of pulmonary injury was made using three distinct parameters: local infiltration of inflammatory cells, diffuse inflammation, and thickening and distortion of alveolar architecture. Radiation-induced changes in lung architecture were most evident during the first 2 weeks postexposure. Fungal changes were seen over the first 4 weeks. Simultaneous combined exposures significantly increased the duration of acute pulmonary damage up to 24 weeks (P < 0.01). In contrast, administration of the fungus 8 weeks after irradiation did not produce enhanced levels of acute pulmonary damage. These data imply that the inhalation of fungal spores at the time of a radiation exposure alters the susceptibility of the lungs to radiation-induced injury.

PMID: 21275606 [PubMed - indexed for MEDLINE]

328. Scand J Immunol. 2011 May;73(5):459-64. doi: 10.1111/j.1365-3083.2011.02521.x.

Deltamethrin Increases Candida albicans infection susceptibility in mice.

Rehman H, Mohan A, Tabassum H, Ahmad F, Rahman S, Parvez S, Raisuddin S.

Department of Medical Elementology and Toxicology, Jamia Hamdard (Hamdard University), New Delhi, India.

Deltamethrin, an alpha-cyano type II synthetic pyrethroid insecticide, is used to control a wide range of insects on a variety of crops and vectors of diseases. Deltamethrin has been previously reported for its immunotoxic effects and therefore its exposure may affect the host resistance to infection and tumour challenge. Effect of exposure of deltamethrin on host resistance to Candida albicans infection was examined in Swiss albino mice. The objective of this study was to investigate the modulatory action of deltamethrin in C. albicans infected mice. The dose of deltamethrin was initially tested and selected from our previous study (18 mg/kg). Percentage of infection in deltamethrin treated animals increased faster when compared to that of the controls. Deltamethrin exposure along with C. albicans infection caused alteration of humoral immune response. The number of colony forming unit in liver and spleen were also found to be significantly increased in the treated group. The results from our present study suggest that deltamethrin exhibits an immunosuppressive effect and has a negative impact on host resistance to C. albicans infection.

PMID: 21272049 [PubMed - indexed for MEDLINE]

329. Dis Aquat Organ. 2010 Nov;92(2-3):175-85.

Minimising exposure of amphibians to pathogens during field studies.

Phillott AD, Speare R, Hines HB, Skerratt LF, Meyer E, McDonald KR, Cashins SD, Mendez D, Berger L.

School of Public Health, Tropical Medicine and Rehabilitation Sciences, James Cook University, Townsville, Queensland 4811, Australia. andrea.phillott@jcu.edu.au

Many of the recent global amphibian mass mortalities, declines and extinctions have been attributed to the emerging infectious disease chytridiomycosis. There have been mass mortalities due to ranaviral disease but no major declines or extinctions. Controlling the transmission and spread of disease is of utmost importance, especially where there is the potential for human involvement. We have reviewed current hygiene guidelines for working with wild frogs, identified potential flaws and recommended those most suitable and effective for the field environment. Our within-site hygiene measures aim to reduce the risk of transmission among individuals. These measures encompass the capture, handling and holding of amphibians, skin disinfection before and after invasive procedures, marking frogs, sealing open wounds and treatment of accessory equipment. Our between-site hygiene measures aim to mitigate the risk of pathogen spread among populations. We have designed a risk calculator to help simplify and standardise the decision-making process for determining the level of risk and appropriate risk mitigation strategies to reduce the risk of increasing pathogen spread above background levels. Calculation of an overall risk score for pathogen spread takes into account the prior activity of field workers, the proposed activity, remoteness of the site, presence of known pathogens and the consequences of increased pathogen spread for amphibians in a given area.

PMID: 21268979 [PubMed - indexed for MEDLINE]

330. Alta RN. 2010 Nov-Dec;66(6):10-1.

Post-exposure management of occupational exposure to blood/body fluids.

College & Association of Registered Nurses of Alberta.

PMID: 21268456 [PubMed - indexed for MEDLINE]

331. Parasit Vectors. 2011 Jan 25;4:8.

The combination of the entomopathogenic fungus Metarhizium anisopliae with the insecticide Imidacloprid increases virulence against the dengue vector Aedes aegypti (Diptera: Culicidae).

Paula AR, Carolino AT, Paula CO, Samuels RI.

Department of Entomology and Plant Pathology, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes RJ CEP 28013-602 Brazil.

BACKGROUND: Dengue fever transmitted by the mosquito Aedes aegypti, is one of the most rapidly spreading insect borne diseases, stimulating the search for alternatives to current control measures. The dengue vector A. aegypti has received less attention than anophelene species, although more than 2.5 billion people are at risk of infection worldwide. Entomopathogenic fungi are emerging as potential candidates for the control of mosquitoes. Here we continue our studies on the pathogenicity of the entomopathogenic fungus Metarhizium anisopliae against adult A. aegypti females. With the aim of further reducing mean survival times of A. aegypti exposed to fungus impregnated surfaces, a sub-lethal concentration of the neonicotinoid insecticide Imidacloprid (IMI) was added to fungal suspensions.
RESULTS: A sub-lethal concentration of IMI that did not significantly alter the daily survival rates or mean survival percentages of mosquitoes was identified to be 0.1 ppm. This sub-lethal concentration was combined with M. anisopliae conidia (1 × 10(9) conidia mL(-1)). Both the combined treatment and the conidia alone were able to reduce the survival of A. aegypti compared with untreated or IMI treated mosquitoes. Importantly, mosquito survival following exposure to the combined treatment for 6 and 12 hrs was significantly reduced when compared with mosquitoes exposed to conidia alone.
CONCLUSIONS: This is the first time that a combination of an insecticide and an entomopathogenic fungus has been tested against A. aegypti. Firstly, the study showed the potential of IMI as an alternative to the currently employed pyrethroid adulticides. Secondly, as an alternative to applications of high concentrations of chemical insecticides, we suggest that adult A. aegypti could be controlled by surface application of entomopathogenic fungi and that the efficiency of these fungi could be increased by combining the fungi with ultra-low concentrations of insecticides, resulting in higher mortality following relatively short exposure times.

PMCID: PMC3037915 PMID: 21266078 [PubMed - indexed for MEDLINE]

332. J Perioper Pract. 2010 Dec;20(12):440-5.

Needlestick an sharps injuries among theatre care professionals.

Al-Benna S.

St Bartholomew's Hospital, West Smithfield, London, EC1A 7BE. sammyalbenna@doctors.org.uk

Health care professionals are exposed to blood and other body fluids in the course of their work: (Al-Benna et al 2008). The World Health Organisation (2003) estimates that 9% of the 35 million healthcare professionals worldwide will experience percutaneous exposure to bloodborne pathogens each year (WHO 2003). In the U.K. about 100,000 sharps injuries occur in NHS hospitals each year (Trim & Elliott 2003). This is 17% of all accidents involving NHS staff (NAO 2003). Four percent of NHS staff sustain from 1 to 6.2 sharps injuries each year. These injuries occur mainly in clinical areas such as wards and theatres, but also in non-clinical areas due to accidental handling of inappropriately discarded sharps (Trim & Elliott 2003, Waterson 2004). Percutaneous injuries involving hollowbore needles remain the most commonly reported occupational exposures in the healthcare setting (HPA 2010). Consequently, workers are at risk of infection with bloodborne viruses including human immunodeficiency virus, hepatitis B virus, hepatitis C virus and bacterial infections (Al-Benna et al 2008).

PMID: 21265403 [PubMed - indexed for MEDLINE]

333. PLoS One. 2011 Jan 10;6(1):e16108.

Entomopathogenic fungus as a biological control for an important vector of livestock disease: the Culicoides biting midge.

Ansari MA, Pope EC, Carpenter S, Scholte EJ, Butt TM.

Pure and Applied Ecology, Swansea University, Swansea, United Kingdom. m.a.ansari@swansea.ac.uk

BACKGROUND: The recent outbreak of bluetongue virus in northern Europe has led to an urgent need to identify control measures for the Culicoides (Diptera: Ceratopogonidae) biting midges that transmit it. Following successful use of the entomopathogenic fungus Metarhizium anisopliae against larval stages of biting midge Culicoides nubeculosus Meigen, we investigated the efficacy of this strain and other fungi (Beauveria bassiana, Isaria fumosorosea and Lecanicillium longisporum) as biocontrol agents against adult C. nubeculosus in laboratory and greenhouse studies. METHODOLOGY/FINDINGS: Exposure of midges to 'dry' conidia of all fungal isolates caused significant reductions in survival compared to untreated controls. Metarhizium anisopliae strain V275 was the most virulent, causing a significantly decrease in midge survival compared to all other fungal strains tested. The LT(50) value for strain V275 was 1.42 days compared to 2.21-3.22 days for the other isolates. The virulence of this strain was then further evaluated by exposing C. nubeculosus to varying doses (10(8)-10(11) conidia m(-2)) using different substrates (horse manure, damp peat, leaf litter) as a resting site. All exposed adults were found to be infected with the strain V275 four days after exposure. A further study exposed C. nubeculosus adults to 'dry' conidia and 'wet' conidia (conidia suspended in 0.03% aq. Tween 80) of strain V275 applied to damp peat and leaf litter in cages within a greenhouse. 'Dry' conidia were more effective than 'wet' conidia, causing 100% mortality after 5 days. CONCLUSION/SIGNIFICANCE: This is the first study to demonstrate that entomopathogenic fungi are potential biocontrol agents against adult Culicoides, through the application of 'dry' conidia on surfaces (e.g., manure, leaf litter, livestock) where the midges tend to rest. Subsequent conidial transmission between males and females may cause an increased level of fungi-induced mortality in midges thus reducing the incidence of disease.

PMCID: PMC3018483 PMID: 21264343 [PubMed - indexed for MEDLINE]

334. Mt Sinai J Med. 2011 Jan-Feb;78(1):78-84. doi: 10.1002/msj.20232.

Climate change, aeroallergens, and pediatric allergic disease.

Sheffield PE, Weinberger KR, Kinney PL.

Departments of Pediatrics and Preventive Medicine, Mount Sinai School of Medicine, New York, NY, USA. perry.sheffield@mssm.edu

The degree to which aeroallergens are contributing to the global increase in pediatric allergic disease is incompletely understood. We review the evidence that links climate change to changes in aeroallergens such as pollen and outdoor mold concentrations and, subsequently, aeroallergen association with pediatric allergic disease. We specifically explore the evidence on both the exacerbation and the development of allergic disease in children related to outdoor pollen and mold concentrations. Pediatric allergic diseases include atopic dermatitis or eczema, allergic rhinitis or hay fever, and some types of asthma in children, typically defined as < 18 years of age. We discuss how the timing of aeroallergen exposure both in utero and in childhood could be associated with allergies. We conclude that the magnitude and type of health impacts due to climate change will depend on improved understanding of the relationship between climatic variables, multiple allergen factors, and allergic disease. Improved public-health strategies such as adequate humidity control, optimum air filtration and ventilation, and improved anticipatory public-health messaging will be critical to adaptation.

PMCID: PMC3075981 PMID: 21259264 [PubMed - indexed for MEDLINE]

335. Mycopathologia. 2011 May;171(5):299-323. Epub 2011 Jan 23.

Fungal proteases and their pathophysiological effects.

Yike I.

Department of Environmental Health Sciences, School of Medicine, Case Western Reserve University, Location code 4940, Room WG19, 2109 Adelbert Rd., Cleveland, OH 44106, USA. ixy@case.edu

Proteolytic enzymes play an important role in fungal physiology and development. External digestion of protein substrates by secreted proteases is required for survival and growth of both saprophytic and pathogenic species. Extracellular serine, aspartic, and metalloproteases are considered virulence factors of many pathogenic species. New findings focus on novel membrane-associated proteases such as yapsins and ADAMs and their role in pathology. Proteases from fungi induce inflammatory responses by altering the permeability of epithelial barrier and by induction of proinflammatory cytokines through protease-activated receptors. Many fungal allergens possess proteolytic activity that appears to be essential in eliciting Th2 responses. Allergenic fungal proteases can act as adjuvants, potentiating responses to other allergens. Proteolytic enzymes from fungi contribute to inflammation through interactions with the kinin system as well as the coagulation and fibrinolytic cascades. Their effect on the host protease-antiprotease balance results from activation of endogenous proteases and degradation of protease inhibitors. Recent studies of the role of fungi in human health point to the growing importance of proteases not only as pathogenic agents in fungal infections but also in asthma, allergy, and damp building related illnesses. Proteolytic enzymes from fungi are widely used in biotechnology, mainly in food, leather, and detergent industries, in ecological bioremediation processes and to produce therapeutic peptides. The involvement of fungal proteases in diverse pathological mechanisms makes them potential targets of therapeutic intervention and candidates for biomarkers of disease and exposure.

PMID: 21259054 [PubMed - indexed for MEDLINE]

336. Arch Microbiol. 2011 May;193(5):323-34. Epub 2011 Jan 23.

Ethanol induces calcium influx via the Cch1-Mid1 transporter in Saccharomyces cerevisiae.

Courchesne WE, Vlasek C, Klukovich R, Coffee S.

Department of Microbiology and Immunology, School of Medicine, University of Nevada, Reno, 89557, USA. wcourchesne@medicine.nevada.edu

Yeast suffers from a variety of environmental stresses, such as osmotic pressure and ethanol produced during fermentation. Since calcium ions are protective for high concentrations of ethanol, we investigated whether Ca(2+) flux occurs in response to ethanol stress. We find that exposure of yeast to ethanol induces a rise in the cytoplasmic concentration of Ca(2+). The response is enhanced in cells shifted to high-osmotic media containing proline, galactose, sorbitol, or mannitol. Suspension of cells in proline and galactose-containing media increases the Ca(2+) levels in the cytoplasm independent of ethanol exposure. The enhanced ability for ethanol to induce Ca(2+) flux after the hypertonic shift is transient, decreasing rapidly over a period of seconds to minutes. There is partial recovery of the response after zymolyase treatment, suggesting that cell wall integrity affects the ethanol-induced Ca(2+) flux. Acetate inhibits the Ca(2+) accumulation elicited by the ethanol/osmotic stress. The Ca(2+) flux is primarily via the Cch1 Ca(2+) influx channel because strains carrying deletions of the cch1 and mid1 genes show greater than 90% reduction in Ca(2+) flux. Furthermore, a functional Cch1 channel reduced growth inhibition by ethanol.

PMID: 21259000 [PubMed - indexed for MEDLINE]

337. FEMS Microbiol Ecol. 2011 May;76(2):342-51. doi: 10.1111/j.1574-6941.2011.01051.x. Epub 2011 Feb 23.

Fusarium oxysporum and its bacterial consortium promote lettuce growth and expansin A5 gene expression through microbial volatile organic compound (MVOC) emission.

Minerdi D, Bossi S, Maffei ME, Gullino ML, Garibaldi A.

Centre of Competence for the Innovation in the Agro-Environmental field, Agroinnova, University of Torino, Grugliasco, Italy. daniela.minerdi@unito.it

Fusarium oxysporum MSA 35 [wild-type (WT) strain] is a nonpathogenic Fusarium strain, which exhibits antagonistic activity to plant pathogenic F. oxysporum isolates. The fungus lives in association with a consortium of ectosymbiotic bacteria. The WT strain, when cured of the bacterial symbionts [the cured (CU) form], is pathogenic, causing wilt symptoms similar to those of pathogenic F. oxysporum f. sp. lactucae. Both WT and CU MSA 35 strains produce microbial volatile organic compounds (MVOCs), but with a different spectrum. In vitro dual culture assays were used to assess the effects of the MVOCs produced by WT and CU strains of F. oxysporum MSA 35 on the growth and expansin gene expression of lettuce seedlings. An increase in the root length (95.6%), shoot length (75.0%) and fresh weight (85.8%) was observed only after WT strain MVOCs exposure. Leaf chlorophyll content was significantly enhanced (68%) in WT strain MVOC-treated seedlings as compared with CU strain volatiles and nontreated controls. β-Caryophyllene was found to be one of the volatiles released by WT MSA 35 responsible for the plant growth promotion effect. Semi-quantitative and quantitative reverse transcription-PCR assays indicated a significant difference in the expansin gene expression level between leaf (6.7-fold) and roots (4.4-fold) exposed to WT strain volatiles when compared with the CU strain volatiles and those that were nonexposed.

PMID: 21255049 [PubMed - indexed for MEDLINE]

338. Folia Microbiol (Praha). 2010 Nov;55(6):593-7. Epub 2011 Jan 21.

Effects of mancozeb and other dithiocarbamate fungicides on Saccharomyces cerevisiae: the role of mitochondrial petite mutants in dithiocarbamate tolerance.

Casalone E, Bonelli E, Polsinelli M.

Department of Animal Biology and Genetics, University of Florence, 50125 Florence, Italy. enrico.casalone@unifi.it

Saccharomyces cerevisiae as model system was used to evaluate the occurrence of resistant mutants and adaptation mechanism to mancozeb (MZ), a widespread fungicide of the dithiocarbamate class with a broad spectrum of action and multiple cell targets. We were unable to isolate mutants resistant to inhibitory concentration of MZ but found an unusually large number of mitochondrial defective petite mutants among cells incubated in the presence of subinhibitory MZ concentration. Similar results were obtained with two other dithiocarbamate fungicides. Comparison of wild type and petite mutants showed that the latter were more resistant to toxic effects of MZ, highlighting the role of mitochondria in MZ-tolerance. The data suggest that petite cells, arising by exposure to sub-inhibitory MZ concentration, are not induced by fungicides but are spontaneous mutants already present in the population before the contact with the fungicide.

PMID: 21253904 [PubMed - indexed for MEDLINE]

339. PLoS One. 2011 Jan 6;6(1):e15976.

Deciphering human heat shock transcription factor 1 regulation via post-translational modification in yeast.

Batista-Nascimento L, Neef DW, Liu PC, Rodrigues-Pousada C, Thiele DJ.

Genomics and Stress Laboratory, Instituto de Tecnologia Química e Biológica, Oeiras, Portugal.

Heat shock transcription factor 1 (HSF1) plays an important role in the cellular response to proteotoxic stresses. Under normal growth conditions HSF1 is repressed as an inactive monomer in part through post-translation modifications that include protein acetylation, sumoylation and phosphorylation. Upon exposure to stress HSF1 homotrimerizes, accumulates in nucleus, binds DNA, becomes hyper-phosphorylated and activates the expression of stress response genes. While HSF1 and the mechanisms that regulate its activity have been studied for over two decades, our understanding of HSF1 regulation remains incomplete. As previous studies have shown that HSF1 and the heat shock response promoter element (HSE) are generally structurally conserved from yeast to metazoans, we have made use of the genetically tractable budding yeast as a facile assay system to further understand the mechanisms that regulate human HSF1 through phosphorylation of serine 303. We show that when human HSF1 is expressed in yeast its phosphorylation at S303 is promoted by the MAP-kinase Slt2 independent of a priming event at S307 previously believed to be a prerequisite. Furthermore, we show that phosphorylation at S303 in yeast and mammalian cells occurs independent of GSK3, the kinase primarily thought to be responsible for S303 phosphorylation. Lastly, while previous studies have suggested that S303 phosphorylation represses HSF1-dependent transactivation, we now show that S303 phosphorylation also represses HSF1 multimerization in both yeast and mammalian cells. Taken together, these studies suggest that yeast cells will be a powerful experimental tool for deciphering aspects of human HSF1 regulation by post-translational modifications.

PMCID: PMC3017095 PMID: 21253609 [PubMed - indexed for MEDLINE]

340. J Biol Chem. 2011 Mar 25;286(12):10744-54. Epub 2011 Jan 20.

New regulators of a high affinity Ca2+ influx system revealed through a genome-wide screen in yeast.

Martin DC, Kim H, Mackin NA, Maldonado-Báez L, Evangelista CC Jr, Beaudry VG, Dudgeon DD, Naiman DQ, Erdman SE, Cunningham KW.

Department of Biology, Johns Hopkins University, Baltimore, Maryland 21218, USA.

The bakers' yeast Saccharomyces cerevisiae utilizes a high affinity Ca(2+) influx system (HACS) to survive assaults by mating pheromones, tunicamycin, and azole-class antifungal agents. HACS consists of two known subunits, Cch1 and Mid1, that are homologous and analogous to the catalytic α-subunits and regulatory α2δ-subunits of mammalian voltage-gated calcium channels, respectively. To search for additional subunits and regulators of HACS, a collection of gene knock-out mutants was screened for abnormal uptake of Ca(2+) after exposure to mating pheromone or to tunicamycin. The screen revealed that Ecm7 is required for HACS function in most conditions. Cycloheximide chase experiments showed that Ecm7 was stabilized by Mid1, and Mid1 was stabilized by Cch1 in non-signaling conditions, suggesting they all interact. Ecm7 is a member of the PMP-22/EMP/MP20/Claudin superfamily of transmembrane proteins that includes γ-subunits of voltage-gated calcium channels. Eleven additional members of this superfamily were identified in yeast, but none was required for HACS activity in response to the stimuli. Remarkably, many dozens of genes involved in vesicle-mediated trafficking and protein secretion were required to prevent spontaneous activation of HACS. Taken together, the findings suggest that HACS and calcineurin monitor performance of the membrane trafficking system in yeasts and coordinate compensatory processes. Conservation of this quality control system in Candida glabrata suggests that many pathogenic species of fungi may utilize HACS and calcineurin to resist azoles and other compounds that target membrane biosynthesis.

PMCID: PMC3060525 [Available on 2012/3/25] PMID: 21252230 [PubMed - indexed for MEDLINE]

341. Environ Health. 2011 Jan 20;10(1):8.

Fungal exposure in homes of patients with sarcoidosis - an environmental exposure study.

Terčelj M, Salobir B, Harlander M, Rylander R.

Clinic of Respiratory Diseases and Allergy, University Medical Centre, Ljubljana, Slovenia. marjeta.tercelj@kclj.si

BACKGROUND: There is increasing evidence that exposure to moulds (fungi) may influence the development of sarcoidosis. To assess the influence of the environmental exposure, a study was undertaken to determine the exposure to fungi in homes of subjects with sarcoidosis.
METHODS: Subjects were patients with clinically established sarcoidosis recruited during the period September 2007 till June 2010. Of these 55 were newly diagnosed and currently under treatment for less than one year, 25 had been treated and had no recurrence and 27 had been treated but had recurrence of the disease. Controls were healthy subjects without any respiratory symptoms (n = 30). Samples of air (about 2.5 m3) were taken in the bedroom of the subjects using a portable pump and cellulose ester filters. The filters were analysed for the content of the enzyme N-acetylhexosaminidase (NAHA) as a marker of fungal cell biomass, using a specific substrate and a fluorescent technique and expressed as NAHA units (U)/m3.
RESULTS: Compared to controls, subjects undergoing treatment of the disease (newly diagnosed or with recurrence) had significantly higher activities of NAHA in their homes than controls (33.6 and 39.9 vs 10.0 U/m3, p < 0.001 and <0.001). Among controls only 5 out of 30 subjects had levels of NAHA above the second quartile value (14 U/m3). In homes of subjects with newly diagnosed disease with treatment less than one year, values above 14 NAHA U/m3 were found among 35 out of 55 and among those with recurrent disease among 18 out of 27.
CONCLUSIONS: The higher activities of NAHA enzyme found in homes of subjects with active and recurrent sarcoidosis suggest that exposure to fungi is related to the risk of sarcoidosis. Further environmental studies to assess the importance of this exposure for subjects with sarcoidosis are warranted. The results suggest that remedial actions in homes with high levels of fungi may be justified.

PMCID: PMC3036600 PMID: 21251285 [PubMed - indexed for MEDLINE]

342. Mucosal Immunol. 2011 Mar;4(2):127-32. Epub 2011 Jan 19.

Key questions to guide a better understanding of host-commensal microbiota interactions in intestinal inflammation.

Sartor RB.

Department of Medicine/Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. rbs@med.unc.edu

Comment on Mucosal Immunol. 2011 Mar;4(2):133-8.

Co-evolution with an extremely complex commensal enteric microbiota has helped shape mammalian mucosal immune responses. A yet incompletely defined subset of intestinal bacteria is required to stimulate chronic, immune-mediated intestinal inflammation, including human Crohn's disease, and intestinal microbiota composition is altered in a characteristic manner by the inflammatory response to create a dysbiotic relationship of protective vs. aggressive bacteria. We pose a number of questions regarding host interactions with the enteric microbiota, including influences of inflammation, host genetics, early environmental exposure, and diet on microbial composition and function, and conversely, the effect of bacterial metabolism, enteric fungi and viruses, and endogenous protective bacterial species on host immune and inflammatory responses. These questions are designed to stimulate research that will promote a better understanding of host-microbial interactions in the intestine and promote targeted novel therapeutic interventions.

PMID: 21248723 [PubMed - indexed for MEDLINE]

343. PLoS One. 2011 Jan 5;6(1):e15943.

Rapid host defense against Aspergillus fumigatus involves alveolar macrophages with a predominance of alternatively activated phenotype.

Bhatia S, Fei M, Yarlagadda M, Qi Z, Akira S, Saijo S, Iwakura Y, van Rooijen N, Gibson GA, St Croix CM, Ray A, Ray P.

Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.

The ubiquitous fungus Aspergillus fumigatus is associated with chronic diseases such as invasive pulmonary aspergillosis in immunosuppressed patients and allergic bronchopulmonary aspergillosis (ABPA) in patients with cystic fibrosis or severe asthma. Because of constant exposure to this fungus, it is critical for the host to exercise an immediate and decisive immune response to clear fungal spores to ward off disease. In this study, we observed that rapidly after infection by A. fumigatus, alveolar macrophages predominantly express Arginase 1 (Arg1), a key marker of alternatively activated macrophages (AAMs). The macrophages were also found to express Ym1 and CD206 that are also expressed by AAMs but not NOS2, which is expressed by classically activated macrophages. The expression of Arg1 was reduced in the absence of the known signaling axis, IL-4Rα/STAT6, for AAM development. While both Dectin-1 and TLR expressed on the cell surface have been shown to sense A. fumigatus, fungus-induced Arg1 expression in CD11c(+) alveolar macrophages was not dependent on either Dectin-1 or the adaptor MyD88 that mediates intracellular signaling by most TLRs. Alveolar macrophages from WT mice efficiently phagocytosed fungal conidia, but those from mice deficient in Dectin-1 showed impaired fungal uptake. Depletion of macrophages with clodronate-filled liposomes increased fungal burden in infected mice. Collectively, our studies suggest that alveolar macrophages, which predominantly acquire an AAM phenotype following A. fumigatus infection, have a protective role in defense against this fungus.

PMCID: PMC3016416 PMID: 21246055 [PubMed - indexed for MEDLINE]

344. PLoS One. 2011 Jan 5;6(1):e15926.

Identification and characterization of Ixodes scapularis antigens that elicit tick immunity using yeast surface display.

Schuijt TJ, Narasimhan S, Daffre S, DePonte K, Hovius JW, Van't Veer C, van der Poll T, Bakhtiari K, Meijers JC, Boder ET, van Dam AP, Fikrig E.

Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America. T.J.Schuijt@amc.uva.nl

Repeated exposure of rabbits and other animals to ticks results in acquired resistance or immunity to subsequent tick bites and is partially elicited by antibodies directed against tick antigens. In this study we demonstrate the utility of a yeast surface display approach to identify tick salivary antigens that react with tick-immune serum. We constructed an Ixodes scapularis nymphal salivary gland yeast surface display library and screened the library with nymph-immune rabbit sera and identified five salivary antigens. Four of these proteins, designated P8, P19, P23 and P32, had a predicted signal sequence. We generated recombinant (r) P8, P19 and P23 in a Drosophila expression system for functional and immunization studies. rP8 showed anti-complement activity and rP23 demonstrated anti-coagulant activity. Ixodes scapularis feeding was significantly impaired when nymphs were fed on rabbits immunized with a cocktail of rP8, rP19 and rP23, a hall mark of tick-immunity. These studies also suggest that these antigens may serve as potential vaccine candidates to thwart tick feeding.

PMCID: PMC3016337 PMID: 21246036 [PubMed - indexed for MEDLINE]

345. J Investig Allergol Clin Immunol. 2010;20(6):490-8.

Guidelines on ambient intramural airborne fungal spores.

Fairs A, Wardlaw AJ, Thompson Jr, Pashley CH.

Aerobiology Unit, Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom.

OBJECTIVES: To generate baseline data for indoor airborne fungal spores in noncomplaint residential properties (with no moisture/mold-related problems) and to identify home characteristics indicative of elevated fungal levels.
METHODS: Air samples were collected onto petroleum jelly-coated slides from living rooms of 100 residential properties in Leicestershire, United Kingdom, using a Burkard continuous recording air sampler. The slides were examined by microscopy to determine fungal spore concentrations (spores/m3 air/day).
RESULTS: Total indoor fungal spore concentrations were approximately 16% of outdoor concentrations. Abundant indoor fungal genera include Cladosporium, Sporobolomyces, Tilletiopsis, and Didymella, all of which followed seasonal patterns of release and detection. No clear association was shown between outdoor-predominant fungi and home characteristics. In contrast, Aspergillus/Penicillium-type (Asp/ Pen-type) spores were common indoors and exceeded outdoor levels, with the highest concentrations detected in properties over 90 years old (P = .006) and terraced properties (P = .003).
CONCLUSION: Asp/Pen-type spores are found in noncomplaint UK residential properties and mostly in old terraced houses. This study provides guidelines on acceptable levels of Asp/Pen-type spores and other abundant indoor fungal taxa that can be comparatively used in clinical evaluations of fungal exposure-related disease.

PMID: 21243933 [PubMed - indexed for MEDLINE]

346. Biochim Biophys Acta. 2011 Apr;1810(4):384-90. Epub 2011 Jan 15.

Ergosta-4,6,8(14),22-tetraen-3-one induces G2/M cell cycle arrest and apoptosis in human hepatocellular carcinoma HepG2 cells.

Zhao YY, Shen X, Chao X, Ho CC, Cheng XL, Zhang Y, Lin RC, Du KJ, Luo WJ, Chen JY, Sun WJ.

Biomedicine Key Laboratory of Shaanxi Province, Northwest University, No.229 Taibai North Road, Xi'an, Shaanxi 710069, China.

BACKGROUND: Mushrooms have been used in Asia as traditional foods and medicines for a long time. Ergosta-4,6,8(14),22-tetraen-3-one (ergone) is one of the well-known bioactive steroids, which exists widely in various medicinal fungi such as Polyporus umbellatus, Russula cyanoxantha, and Cordyceps sinensis. Ergone has been demonstrated to possess cytotoxic activity. However, the molecular mechanisms by which ergone exerts its cytotoxic activity are currently unknown.
METHODS: In the present study, ergone possessed a remarkable anti-proliferative activity toward human hepatocellular carcinoma HepG2 cells. We assayed the cell cycle by flow cytometry using PI staining; investigated the exposure of phosphatidylserine at the outer layer of the cytoplasmic membrane by the FITC-annexin V/PI staining; observed the nuclear fragmentation by Hoechst 33258 staining and studied the protein expression of Bax, Bcl-2, p-53, procaspase-3, -8, -9, PARP and cleaved PARP by Western blotting analysis.
RESULTS: Cells treated with ergone showed typical markers of apoptosis: G2/M cell cycle arrest, chromatin condensation, nuclear fragmentation, and phosphatidylserine exposure. Furthermore, PARP-cleavage; activation of caspase-3, -8, -9; up-regulation of Bax and down-regulation of Bcl-2 were observed in HepG2 cells treated with ergone, which show that both the intrinsic and extrinsic apoptotic pathways are involved in ergone-induced apoptosis in HepG2 cells. Ergosta-4,6,8(14),22-tetraen-3-one induces G2/M cell cycle arrest and apoptosis in HepG2 cells in a caspase-dependent manner.
GENERAL SIGNIFICANCE: In this study, we reported for the first time that ergone-induced apoptosis through activating the caspase. These results would be useful for the further utilization of many medicinal fungi in cancer treatment.

PMID: 21241775 [PubMed - indexed for MEDLINE]

347. Cytokine. 2011 Apr;54(1):43-50. Epub 2011 Jan 15.

Extremely low frequency electromagnetic field exposure does not modulate toll-like receptor signaling in human peripheral blood mononuclear cells.

de Kleijn S, Bouwens M, Verburg-van Kemenade BM, Cuppen JJ, Ferwerda G, Hermans PW.

Laboratory of Pediatric Infectious Diseases, Radboud University Nijmegen Medical Centre, The Netherlands.

The effects of extremely low frequency electromagnetic fields (ELF-EMF) on human health remain unclear. It has been reported that ELF-EMF may modulate the innate immune response to microorganisms in animal models and mammalian cell-lines. With the recently gained insight in innate immune signaling and the discovery of pattern recognition, we aim to study whether ELF-EMF modulates innate inflammatory signaling pathways. We used human peripheral blood mononuclear cells (PBMCs), isolated from blood from healthy volunteers, which we stimulated with specific TLR2 and TLR4 ligands, and with several microorganisms. The cells were subsequently exposed in B(dc)=3 μT to a highly controlled and standardized ELF-EMF signal (20-5000Hz, B(ac)=5 μT, 30 min) and cytokine production was measured at different time points after stimulation. No significant difference in immune response, as reflected by IL-1β, IL-6, TNFα, IL-8 and IL-10 production, could be detected after stimulation with LPS (TLR4 ligand), Pam3Cys (TLR2 ligand) or a panel of heat killed microorganisms: Mycobacterium tuberculosis, Salmonella typhimurium, Candida albicans, Aspergillus fumigatus and Staphylococcus aureus (multiple TLR ligands). We therefore conclude that under our experimental conditions, ELF-EMF does not modulate the innate immune response of human primary cells after TLR stimulation in vitro.

PMID: 21239179 [PubMed - indexed for MEDLINE]

348. J Photochem Photobiol B. 2011 Mar 2;102(3):182-91. Epub 2010 Dec 25.

Low intensity light stimulates nitrite-dependent nitric oxide synthesis but not oxygen consumption by cytochrome c oxidase: Implications for phototherapy.

Ball KA, Castello PR, Poyton RO.

Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309-0347, USA.

Cytochrome c oxidase (Cco) has been reported to be a receptor for some of the beneficial effects of low intensity visible and near-infrared light on cells and tissues. Here, we have explored the role of low intensity light in affecting a newly described function of Cco, its ability to catalyze nitrite-dependent nitric oxide (NO) synthesis (Cco/NO). Using a new assay for Cco/NO we have found that both yeast and mouse brain mitochondrial Cco produce NO over a wide range of oxygen concentrations and that the rate of NO synthesis increases as the oxygen concentration decreases, becoming optimal under hypoxic conditions. Low intensity broad-spectrum light increases Cco/NO activity in an intensity-dependent fashion but has no effect on oxygen consumption by Cco. By using a series of bandpass filters and light emitting devices (LEDs) we have determined that maximal stimulation of Cco/NO activity is achieved by exposure to light whose central wavelength is 590 ± 14 nm. This wavelength of light stimulates Cco/NO synthesis at physiological nitrite concentrations. These findings raise the interesting possibility that low intensity light exerts a beneficial effect on cells and tissues by increasing NO synthesis catalyzed by Cco and offer a new explanation for the increase in NO bioavailability experienced by tissue exposed to light.

PMID: 21237670 [PubMed - indexed for MEDLINE]

349. Biotechniques. 2011 Jan;50(1):58-63.

Fluorescence method for determining the mechanism and speed of action of surface-active drugs on yeast cells.

Kodedová M, Sigler K, Lemire BD, Gášková D.

Charles University, Faculty of Mathematics and Physics, Institute of Physics, Prague, Czech Republic.

New antifungal agents are needed to treat life-threatening fungal infections, particularly with the development of resistance. Surface-active antifungals have the advantages of minimizing host toxicity and the emergence of drug resistance. We have developed a time-dependent drug exposure assay that allows us to rapidly investigate the mechanism of surface-active antifungal drug action. The assay uses a multidrug pump-deficient strain of Saccharomyces cerevisiae and the potentiometric dye 3,3'-dipropylthiacarbocyanine iodide [diS-C₃(3)] and can assess whether cells are depolarized, hyperpolarized, or permeabilized by drug exposure. In this work, we investigated the mechanisms of action of five surface-active compounds: SDS, nystatin, amphotericin B, octenidine dihydrochloride, and benzalkonium chloride. The diS-C₃(3) time-dependent drug exposure assay can be used to identify the mechanisms of action of a wide range of drugs. It is a fast and cost-effective method for screening drugs to determine their lowest effective concentrations.

PMID: 21231924 [PubMed - indexed for MEDLINE]

350. Mol Cells. 2011 Mar;31(3):255-9. Epub 2010 Dec 30.

The S-nitrosylation of glyceraldehyde-3-phosphate dehydrogenase 2 is reduced by interaction with glutathione peroxidase 3 in Saccharomyces cerevisiae.

Lee PY, Bae KH, Jeong DG, Chi SW, Moon JH, Kang S, Cho S, Lee SC, Park BC, Park SG.

Medical Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 305-806, Korea.

Glutathione peroxidases (Gpxs) are the key anti-oxidant enzymes found in Saccharomyces cerevisiae. Among the three Gpx isoforms, glutathione peroxidase 3 (Gpx3) is ubiquitously expressed and modulates the activities of redox-sensitive thiol proteins involved in various biological reactions. By using a proteomic approach, glyceraldehyde-3-phosphate dehydrogenase 2 (GAPDH2; EC 1.2.1.12) was found as a candidate protein for interaction with Gpx3. GAPDH, a key enzyme in glycolysis, is a multi-functional protein with multiple intracellular localizations and diverse activities. To validate the interaction between Gpx3 and GAPDH2, immunoprecipitation and a pull-down assay were carried out. The results clearly showed that GAPDH2 interacts with Gpx3 through its carboxyl-terminal domain both in vitro and in vivo. Additionally, Gpx3 helps to reduce the S-nitrosylation of GAPDH upon nitric oxide (NO) stress; this subsequently increases cellular viability. On the basis of our findings, we suggest that Gpx3 protects GAPDH from NO stress and thereby contributes to the maintenance of homeostasis during exposure to NO stress.

PMID: 21229323 [PubMed - indexed for MEDLINE]

351. Antonie Van Leeuwenhoek. 2011 May;99(4):761-71. Epub 2011 Jan 13.

Glutathione peroxidase3 of Saccharomyces cerevisiae protects phospholipids during cadmium-induced oxidative stress.

Muthukumar K, Rajakumar S, Sarkar MN, Nachiappan V.

Department of Biochemistry, Bharathidasan University, Tiruchirappalli, 620 024, Tamilnadu, India.

The present study was undertaken to determine the role of glutathione peroxidase3 (gpx3) in phospholipid protection in cells. Wild-type (WT) cells showed an overall increase in phospholipids upon 50 μM cadmium (Cd)-treatment, whereas an untreated gpx3Δ strain showed a drastic reduction in overall phospholipids which was further reduced with 50 μM Cd. In WT cells, Cd-exposure increased the short chain fatty acids and decreased the unsaturated fatty acids and the magnitude was high in Cd-treated gpx3Δ cells. Purified recombinant gpx3p showed higher activity with phospholipid hydroperoxides than shorter hydroperoxides. An increase in gpx activity was observed in Cd-treated WT cells and no such alteration was observed in gpx3Δ. WT cells treated with Cd showed an increase in MDA over untreated, while untreated gpx3Δ cells themselves showed a higher level of MDA which was further enhanced with Cd-treatment. Iron, zinc and calcium levels were significantly altered in WT and gpx3Δ cells during Cd-treatment.

PMID: 21229313 [PubMed - indexed for MEDLINE]

352. Rev Argent Microbiol. 2010 Oct-Dec;42(4):254-60.

[Histoplasmosis outbreak in Morón, Buenos Aires Province, Argentina].

[Article in Spanish]

Negroni R, Duré R, Ortiz Nareto A, Arechavala AI, Maiolo EI, Santiso GM, Iovannitti C, Ibarra-Camou B, Canteros CE.

Unidad Micología, Hospital de Infecciosas Francisco J. Muñiz, Ciudad Autónoma de Buenos Aires.

A histoplasmosis outbreak affecting 6 previously healthy Air Force cadets is herein presented. The patients suffered from fever and respiratory symptoms after having cleaned an abandoned hangar soiled with pigeons and bat droppings. They all presented fever, myalgia, tachypnea, and nonproductive cough. Chest X-ray and CT scan studies showed disseminated reticulonodular images affecting both lungs. Hiliar adenomegalies were also observed. All patients achieved a favourable outcome without antifungal treatment. Both serologic tests searching for specificic antibodies (immunodiffusion and counterimmunoelectrophoresis) and histoplasmin skin tests were positive in all cases. Five soil samples mixed with pigeons and bat droppings were collected from the hangar. Suspensions of these samples were inoculated into 20 hamsters by intraperitoneal injection; mycelial phase of H. capsulatum was isolated from liver and spleen cultures. The genetic profile of this strain was compared with 12 isolates obtained from Argentinean patients, and a great degree of homogeneity was observed (> 96% similarity). Although histoplasmosis is endemic in the wet Pampas, this is the first epidemic outbreak reported south of the 34th parallel.

PMID: 21229193 [PubMed - indexed for MEDLINE]

353. FEMS Microbiol Ecol. 2011 Apr;76(1):1-13. doi: 10.1111/j.1574-6941.2010.01030.x. Epub 2011 Jan 11.

Yeasts from an oligotrophic lake in Patagonia (Argentina): diversity, distribution and synthesis of photoprotective compounds and extracellular enzymes.

Brandão LR, Libkind D, Vaz AB, Espírito Santo LC, Moliné M, de García V, van Broock M, Rosa CA.

Departamento de Microbiologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.

Nahuel Huapi (NH) Lake is an oligotrophic temperate lake of glacial origin with high transparency, surrounded by well-developed forests and located at San Carlos de Bariloche, Nahuel Huapi National Park, in Patagonia, Argentina. In this lake, we characterized yeast distribution and diversity along a south-to-north transect and established a relationship between the ability to produce photoprotective compounds (PPCs) (carotenoid pigments and mycosporines) and the occurrence of yeast at different collection points. Subsurface water samples were filtered for yeast isolation. Total yeast counts ranged between 22 and 141 CFU L(-1) , and the highest values corresponded to the most impacted sites. Littoral sites had a low proportion of yeast-producing PPCs and this group prevailed in pelagic sites. This is probably a result of the high transparency of the water and the increased UV exposure. The yeast community from NH Lake showed a high species richness and a uniform distribution of taxa between pelagic and border collection points. Yeasts were identified as belonging to 14 genera and 34 species. Rhodotorula mucilaginosa and Cryptococcus victoriae were the most frequently found species, representing 14.4% and 13.6% of the total yeast isolates, respectively. Most of the yeast isolates demonstrated at least one extracellular enzymatic activity (mainly cellulase and lipase activities), which suggested that these microorganisms are metabolically active in the lake.

PMID: 21223324 [PubMed - indexed for MEDLINE]

354. J Food Prot. 2011 Jan;74(1):140-4.

Efficacy of levulinic acid-sodium dodecyl sulfate against Encephalitozoon intestinalis, Escherichia coli O157:H7, and Cryptosporidium parvum.

Ortega YR, Torres MP, Tatum JM.

Center for Food Safety, University of Georgia, Griffin, Georgia 30223, USA. Ortega@uga.edu

Foodborne parasites are characterized as being highly resistant to sanitizers used by the food industry. In 2009, a study reported the effectiveness of levulinic acid in combination with sodium dodecyl sulfate (SDS) in killing foodborne bacteria. Because of their innocuous properties, we studied the effects of levulinic acid and SDS at various concentrations appropriate for use in foods, on the viability of Cryptosporidium parvum and Encephalitozoon intestinalis. The viability of Cryptosporidium and E. intestinalis was determined by in vitro cultivation using the HCT-8 and RK-13 cell lines, respectively. Two Escherichia coli O157:H7 isolates were also used in the present study: strain 932 (a human isolate from a 1992 Oregon meat outbreak) and strain E 0018 (isolated from calf feces). Different concentrations and combinations of levulinic acid and SDS were tested for their ability to reduce infectivity of C. parvum oocysts (10(5)), E. intestinalis spores (10(6)), and E. coli O157:H7 (10(7)/ml) when in suspension. Microsporidian spores were treated for 30 and 60 min at 20 ± 2°C. None of the combinations of levulinic acid and SDS were effective at inactivating the spores or oocysts. When Cryptosporidium oocysts were treated with higher concentrations (3% levulinic acid-2% SDS and 2% levulinic acid-1% SDS) for 30, 60, and 120 min, viability was unaffected. E. coli O157:H7, used as a control, was highly sensitive to the various concentrations and exposure times tested. SDS and levulinic acid alone had very limited effect on E. coli O157:H7 viability, but in combination they were highly effective at 30 and 60 min of incubation. In conclusion, Cryptosporidium and microsporidia are not inactivated when treated for various periods of time with 2% levulinic acid-1% SDS or 3% levulinic acid-2% SDS at 20°C, suggesting that this novel sanitizer cannot be used to eliminate parasitic contaminants in foods.

PMID: 21219777 [PubMed - indexed for MEDLINE]

355. Eukaryot Cell. 2011 Mar;10(3):435-44. Epub 2011 Jan 7.

Fig1 facilitates calcium influx and localizes to membranes destined to undergo fusion during mating in Candida albicans.

Yang M, Brand A, Srikantha T, Daniels KJ, Soll DR, Gow NA.

School of Life Sciences & Medicine, Institute of Medical Science, University of Aberdeen, Foresterhill, Aberdeen, United Kingdom. n.gow@abdn.ac.uk

Few mating-regulated genes have been characterized in Candida albicans. C. albicans FIG1 (CaFIG1) is a fungus-specific and mating-induced gene encoding a putative 4-transmembrane domain protein that shares sequence similarities with members of the claudin superfamily. In Saccharomyces cerevisiae, Fig1 is required for shmoo fusion and is upregulated in response to mating pheromones. Expression of CaFIG1 was also strongly activated in the presence of cells of the opposite mating type. CaFig1-green fluorescent protein (GFP) was visible only during the mating response, when it localized predominantly to the plasma membrane and perinuclear zone in mating projections and daughter cells. At the plasma membrane, CaFig1-GFP was visualized as discontinuous zones, but the distribution of perinuclear CaFig1-GFP was homogeneous. Exposure to pheromone induced a 5-fold increase in Ca(2+) uptake in mating-competent opaque cells. Uptake was reduced substantially in the fig1Δ null mutant. CaFig1 is therefore involved in Ca(2+) influx and localizes to membranes that are destined to undergo fusion during mating.

PMCID: PMC3067472 PMID: 21216943 [PubMed - indexed for MEDLINE]

356. Aquat Toxicol. 2011 Jan 25;101(2):430-7. Epub 2010 Dec 4.

Estrogenic effects of leachates from industrial waste landfills measured by a recombinant yeast assay and transcriptional analysis in Japanese medaka.

Kamata R, Shiraishi F, Nakajima D, Kageyama S.

Research Center for Environmental Risk, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibaraki 305-8506, Japan. kamata.ryo@nies.go.jp

In Japan, the leachates from 'stable type' landfills for industrial wastes are not controlled, and this has given rise to concerns about the possible pollution of surrounding environmental waters, especially by endocrine disrupting chemicals leaching from plastic and rubber wastes. To accurately assess the estrogenic potential of the landfill leachates by both in vitro and in vivo approaches, we confirmed gene-transcriptional responses in recombinant yeast cells and in Japanese medaka fish to estrogenic compounds, and applied these transcription assays to leachate samples. The yeast carrying the estrogen receptor (ER) of medaka and an ER-mediated response pathway responded to both the natural estrogen, 17β-estradiol (E2), and an industrial compound, bisphenol A (BPA), and the effective concentration of BPA was about 2.0×10(3) times that of E2. Transcripts of all genes coding for precursors of yolk protein, vitellogenin (vtg1 and vtg2), and precursors of egg envelope subunit proteins, choriogenins (chgh and chgl), increased in a concentration dependent manner in the livers of male medaka exposed to BPA or E2, and, except for chgh, reached peaks at exposure times of 48h. Although many fish in control groups did not have vtg transcripts, the incidence of vtg transcriptions also increased in a concentration dependent manner with exposure. The minimum effective concentrations of BPA at 48h were 0.5mg/L for chgh and vtg2, 2mg/L for vtg1 and 4mg/L for chgl, while those of E2 were 10ng/L for chgh and chgl and 30ng/L for vtg1 and vtg2. All leachates sampled at 3 landfill sites exerted in vitro estrogenic action. The E2 equivalent of the most potent leachate was 375ng/L for the yeast ER assay. This leachate sample significantly increased the transcripts of chgh, vtg1 and vtg2, but not chgl, in the medaka. In addition, chemical analysis showed that bisphenol A, 4-tert-octylphenol and 4-nonylphenol were the main contributors to the estrogenicity of the leachates. This study indicated that this type of landfill may adversely affect the reproductive functions of fish living in the surrounding area by leakage of industrial estrogenic compounds.

PMID: 21216354 [PubMed - indexed for MEDLINE]

357. J Hazard Mater. 2011 Feb 28;186(2-3):1541-52. Epub 2010 Dec 15.

Bioaccumulation of the synthetic dye Basic Violet 3 and heavy metals in single and binary systems by Candida tropicalis grown in a sugarcane bagasse extract medium: modelling optimal conditions using response surface methodology (RSM) and inhibition kinetics.

Das D, Charumathi D, Das N.

Environmental Biotechnology Division, School of Biosciences and Technology, VIT University, Vellore 632 014, Tamil Nadu, India.

Single and binary effects of dye Basic Violet 3 and heavy metals, 'namely', Pb(II) and Cd(II), were investigated for their role in dye and heavy metal bioaccumulation by Candida tropicalis that was grown in a sugarcane bagasse extract medium containing 8 g/L, 16 g/L or 24 g/L of sugar. The optimum pH was found to be 4.0 in the single system and 5.0 in the binary system. A central composite design was successfully used to analyse the experimental results. Four numerical correlations that were fitted to a second order quadratic equation were used to estimate optimum combinations predicted by response surface methodology. In the dye-Pb(II) binary system, C. tropicalis was capable of bioaccumulating 49.5% of the dye and 49.6% of the Pb(II), in comparison to 15.9% of the dye and 55.5% of the Cd(II) in the dye-Cd(II) binary system. In these two systems, the pollutants were dispersed at minimum working concentration levels. Competitive inhibition was observed in both the single and binary systems, which was suggested by an increase in the saturation constant, K(s), and a simultaneous decrease in the specific growth rate that was calculated from Lineweaver-Burk plots. Atomic force microscopy images demonstrated changes in yeast cell morphology by exposure to these contaminants in the dye-Pb(II) binary system grown in a bioaccumulation medium.

PMID: 21215516 [PubMed - indexed for MEDLINE]

358. Contact Dermatitis. 2011 Feb;64(2):111-4. doi: 10.1111/j.1600-0536.2010.01837.x.

Contact dermatitis caused by salami skin.

Wantke F, Simon-Nobbe B, Pöll V, Götz M, Jarisch R, Hemmer W.

Floridsdorf Allergy Centre, A-1210 Vienna, Austria Department of Cell Biology/Genetics, University of Salzburg, A-5020 Salzburg, Austria. wantke@faz.at

PMID: 21210826 [PubMed - indexed for MEDLINE]

359. Hum Pathol. 2011 Mar;42(3):449-53. Epub 2011 Jan 3.

Peripheral blood eosinophilia as a clue to the diagnosis of an occult Coccidioides infection.

Simons CM, Stratton CW, Kim AS.

Department of Pathology, Vanderbilt University Medical Center, Nashville, TN 37232, USA. christopher.m.simons@vanderbilt.edu

A marked peripheral blood eosinophilia is an uncommon finding in a complete blood count (CBC). According to Wardlaw and Kay (Eosinophils and Their Disorders. In: Beutler E, Lichtman MA, Coller BS, Kipps TJ, Seligsohn U, editors. Williams Hematology. 6(th) ed. New York: McGraw-Hill, 2001. p. 790-93), the most common causes are infection by helminthic parasites, atopic disease, and, less commonly, primary hypereosinophilic syndromes. Therefore, when eosinophilia is seen in a CBC, it can provide an important clue to the correct diagnosis. We present a case of a patient with a finding of pulmonary nodules in the setting of cancer and a CBC finding of profound peripheral blood eosinophilia. As a result of the high level of clinical suspicion for Coccidioides infection due in part to the eosinophilia, adequate steps were taken in the clinical laboratory not only to correctly diagnosis the patient, but also to protect the laboratory staff from work-related exposure to this easily aerosolizable infectious agent.

PMID: 21208646 [PubMed - indexed for MEDLINE]

360. Photochem Photobiol. 2011 Mar-Apr;87(2):342-9. doi: 10.1111/j.1751-1097.2011.00886.x. Epub 2011 Feb 10.

Ultraviolet-C light for treatment of Candida albicans burn infection in mice.

Dai T, Kharkwal GB, Zhao J, St Denis TG, Wu Q, Xia Y, Huang L, Sharma SK, d'Enfert C, Hamblin MR.

Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, USA.

Burn patients are at high risk of invasive fungal infections, which are a leading cause of morbidity, mortality, and related expense exacerbated by the emergence of drug resistant fungal strains. In this study, we investigated the use of UVC light (254 nm) for the treatment of yeast Candida albicans infection in mouse third degree burns. In vitro studies demonstrated that UVC could selectively kill the pathogenic C. albicans compared with a normal mouse keratinocyte cell line in a light exposure dependent manner. A mouse model of chronic C. albicans infection in non-lethal third degree burns was developed. The C. albicans strain was stably transformed with a version of the Gaussia princeps luciferase gene that allowed real-time bioluminescence imaging of the progression of C. albicans infection. UVC treatment with a single exposure carried out on day 0 (30 min postinfection) gave an average 2.16-log(10)-unit (99.2%) loss of fungal luminescence when 2.92 J cm(-2) UVC had been delivered, while UVC 24 h postinfection gave 1.94-log(10)-unit (95.8%) reduction of fungal luminescence after 6.48 J cm(-2). Statistical analysis demonstrated that UVC treatment carried out on both day 0 and day 1 significantly reduced the fungal bioburden of infected burns. UVC was found to be superior to a topical antifungal drug, nystatin cream. UVC was tested on normal mouse skin and no gross damage was observed 24 h after 6.48 J cm(-2). DNA lesions (cyclobutane pyrimidine dimers) were observed by immunofluorescence in normal mouse skin immediately after a 6.48 J cm(-2) UVC exposure, but the lesions were extensively repaired at 24 h after UVC exposure.

PMCID: PMC3048910 [Available on 2012/3/1] PMID: 21208209 [PubMed - indexed for MEDLINE]

361. Indoor Air. 2011 Apr;21(2):156-64. doi: 10.1111/j.1600-0668.2010.00692.x. Epub 2011 Jan 25.

Association between indoor mold and asthma among children in Buffalo, New York.

Jones R, Recer GM, Hwang SA, Lin S.

New York State Department of Health, Bureau of Environmental and Occupational Epidemiology, Center for Environmental Health, Troy, NY 12180, USA. rrj01@health.state.ny.us

Asthma is a leading chronic disease among children and places a significant burden on public health. Exposure to indoor mold has been associated with asthma symptoms. However, many mold assessments have relied on visual or other identification of damp conditions and mold presence, thus have not examined associations with specific fungal genera. The objective of this case-control study was to examine the relationship between airborne mold concentrations and asthma status among children and to identify the contribution from specific mold genera in air. Participants completed a questionnaire of home environmental conditions and underwent indoor air sampling in the home, from which viable and total-count fungal spores were quantified. The most prevalent fungi in the homes were the allergenic molds Cladosporium (98% and 87% of homes from viable and total count samples, respectively) and Penicillium (91% and 73%). There were no significant differences in mean fungal concentrations between the homes of cases and controls, although the observed rate of exposure to several molds was higher among the cases. Among children who lacked a family history of asthma, cases had significantly higher exposures to viable Aspergillus. Measured humidity levels in the home corresponded with some self-reported indicators of mold and dampness.
PRACTICAL IMPLICATIONS: The results of this study support existing literature that indoor fungal exposures play a role in current asthma status and that some qualitative assessments of mold exposure correspond to fungi present in indoor air.

PMID: 21204984 [PubMed - indexed for MEDLINE]

362. Indoor Air. 2011 Apr;21(2):110-20. doi: 10.1111/j.1600-0668.2010.00685.x. Epub 2011 Feb 1.

Collection efficiencies of an electrostatic sampler with superhydrophobic surface for fungal bioaerosols.

Han T, Nazarenko Y, Lioy PJ, Mainelis G.

Department of Environmental Sciences, Rutgers University, New Brunswick, NJ 08901, USA.

We recently developed an electrostatic precipitator with superhydrophobic surface (EPSS), which collects particles into a 10- to 40-μl water droplet allowing achievement of very high concentration rates (defined as the ratio of particle concentration in the collection liquid vs. the airborne particle concentration per time unit) when sampling airborne bacteria. Here, we analyzed the performance of this sampler when collecting three commonly found fungal spores--Cladosporium cladosporioides, Penicillium melinii, and Aspergillus versicolor--under different operating conditions. We also adapted adenosine triphosphate (ATP)-based bioluminescence for the analysis of collection efficiency and the concentration rates. The collection efficiency ranged from 10 to 36% at a sampling flow rate of 10 l/min when the airborne fungal spore concentration was approximately 10(5)-10(6) spores/m(3) resulting in concentration rates in the range of 1 × 10(5)-3 × 10(5)/min for a 10-μl droplet. The collection efficiency was inversely proportional to the airborne spore concentration and it increased to above 60% for common ambient spore concentrations, e.g., 10(4)-10(5) spores/m(3). The spore concentrations determined by the ATP-based method were not statistically different from those determined by microscopy and allowed us to analyze spore concentrations that were too low to be reliably detected by microscopy. PRACTICAL IMPLICATIONS: The new electrostatic precipitator with superhydrophobic surface (EPSS) collects airborne fungal spores into small water droplets (10 and 40 μl) allowing achievement of concentration rates that are higher than those of most currently available bioaerosol samplers. Biosamplers with high concentration rates enable detection of low ambient aerial bioaerosol concentrations in various environments, including indoors air, and would be useful for improved exposure assessment. A successful adaptation of the adenosine triphosphate (ATP)-based bioluminescence assay for the quantification of fungal spores from a specific species enables fast sample analysis in laboratory investigations. This rapid assay could be especially useful when investigating the performance of biological samplers as a function of multiple operational parameters.

PMID: 21204982 [PubMed - indexed for MEDLINE]

363. FEMS Microbiol Lett. 2011 Feb;315(2):81-6. doi: 10.1111/j.1574-6968.2010.02168.x. Epub 2011 Jan 10.

Visible light during mycelial growth and conidiation of Metarhizium robertsii produces conidia with increased stress tolerance.

Rangel DE, Fernandes EK, Braga GU, Roberts DW.

Department of Biology, Utah State University, Logan, UT, USA.

Light conditions during mycelial growth are known to influence fungi in many ways. The effect of visible-light exposure during mycelial growth was investigated on conidial tolerance to UVB irradiation and wet heat of Metarhizium robertsii, an insect-pathogenic fungus. Two nutrient media and two light regimens were compared. Conidia were produced on (A) potato dextrose agar plus yeast extract medium (PDAY) (A1) under dark conditions or (A2) under continuous visible light (provided by two fluorescent lamps with intensity 5.4 W m(-2)). For comparison, the fungus was also produced on (B) minimal medium (MM) under continuous-dark incubation, which is known to produce conidia with increased tolerance to heat and UVB radiation. The UVB tolerances of conidia produced on PDAY under continuous visible light were twofold higher than conidia produced on PDAY medium under dark conditions, and this elevated UVB tolerance was similar to that of conidia produced on MM in the dark. The heat tolerance of conidia produced under continuous light was, however, similar to that of conidia produced on MM or PDAY in the dark. Conidial yield on PDAY medium was equivalent when the fungus was grown either under continuous-dark or under continuous-light conditions.

PMID: 21204917 [PubMed - indexed for MEDLINE]

364. Lett Appl Microbiol. 2011 Apr;52(4):314-21. doi: 10.1111/j.1472-765X.2010.03000.x. Epub 2011 Jan 17.

Bacterial and fungal communities of wilted Italian ryegrass silage inoculated with and without Lactobacillus rhamnosus or Lactobacillus buchneri.

Li Y, Nishino N.

Department of Animal Science, Graduate School of Natural Science and Technology, Okayama University, Okayama, Japan.

AIMS: To understand the effects of lactic acid bacteria (LAB) inoculation on fermentation products, aerobic stability and microbial communities of silage. METHODS AND RESULTS: Wilted Italian ryegrass was stored in laboratory silos with and without inoculation of Lactobacillus rhamnosus and Lactobacillus buchneri. The silos were opened after 14, 56 and 120 days and then subjected to aerobic deterioration for 7 days. Intensive alcoholic fermentation was found in untreated silage; the sum of ethanol and 2,3-butanediol content at day 14 was about 7 times higher than that of lactic and volatile fatty acids. Alcoholic fermentation was suppressed by L. rhamnosus and L. buchneri inoculation and lactic acid and acetic acid became the dominant fermentation products, respectively. Silages were deteriorated in untreated and L. rhamnosus-inoculated silages, whereas no spoilage was found in L. buchneri-inoculated silage. Enterobacteria such as Erwinia persicina, Pantoea agglomerans and Rahnella aquatilis were detected in untreated silage, whereas some of these bacteria disappeared or became faint with L. rhamnosus treatment. When silage was deteriorated, Lactobacillus brevis and Bacillus pumilus were observed in untreated and L. rhamnosus-inoculated communities, respectively. The inoculated LAB species was detectable in addition to untreated bacterial communities. Saccharomyces cerevisiae and Pichia anomala were the main fungi in untreated and L. rhamnosus-inoculated silages; however, P. anomala was not visibly seen in L. buchneri-inoculated silage either at silo opening or after exposure to air.
CONCLUSION: Inoculation with L. rhamnosus can suppress alcoholic fermentation of wilted grass silage with elimination of enterobacteria at the beginning of fermentation. Addition of L. buchneri may improve aerobic stability, with distinct inhibitory effect observed on P. anomala after silo opening. SIGNIFICANCE AND IMPACT OF THE STUDY: Bacterial and fungal community analyses help us to understand how inoculated LAB can function to improve the fermentation and aerobic stability of silage.

PMID: 21204884 [PubMed - indexed for MEDLINE]

365. Parasite Immunol. 2011 Apr;33(4):217-25. doi: 10.1111/j.1365-3024.2010.01269.x.

MyD88-dependent pathway is essential for the innate immunity to Enterocytozoon bieneusi.

Zhang Q, Feng X, Nie W, Golenbock DT, Mayanja-Kizza H, Tzipori S, Feng H.

Division of Infectious Diseases, Department of Biomedical Sciences, Tufts University Cummings School of Veterinary Medicine, North Grafton, MA 01536, USA.

Enterocytozoon bieneusi is clinically the most significant microsporidian parasite associated with persistent diarrhoea, wasting and cholangitis in 30-50% of individuals with HIV/AIDS, as well as in malnutritional children and in the recipients of immunosuppressive therapy. However, the host immune responses to E. bieneusi have not been investigated until recently because of lack of sources of spores, cell culture system and animal models. In this study, we purified spores from heavily infected human or monkey faeces by serial salt-Percoll-sucrose-iodixanol centrifugation, and the purity of spores was confirmed by FACS and scanning electron microscopy. Exposure of dendritic cells to E. bieneusi spores induced the upregulation of the surface markers and production of pro-inflammatory cytokines. The cytokine production was independent of toll-like receptor 4, but MyD88 dependent, because dendritic cells from MyD88 knockout mice failed to secrete these pro-inflammatory cytokines, whereas dendritic cells from C3H/HeJ (a toll-like receptor 4 mutant) were activated by E. bieneusi and secreted these cytokines. Furthermore, MyD88-deficient mice were susceptible to E. bieneusi infection, in contrast to wild-type mice that resisted the infection. Collectively, the data demonstrate innate recognition of E. bieneusi by dendritic cells and the importance of MyD88-dependent signalling in resisting infection in a murine challenge model.

PMCID: PMC3075804 [Available on 2012/4/1] PMID: 21204848 [PubMed - indexed for MEDLINE]

366. Environ Microbiol. 2011 Jan;13(1):163-71. doi: 10.1111/j.1462-2920.2010.02317.x.

Red but not dead? Membranes of stressed Saccharomyces cerevisiae are permeable to propidium iodide.

Davey HM, Hexley P.

Institute of Biological, Environmental and Rural Sciences, Aberystwyth University, Penglais, Aberystwyth, UK. hlr@aber.ac.uk

Flow cytometric monitoring of propidium iodide (PI) uptake is a well-established and rapid method for monitoring cell death and is used on the basis that the intact membrane of viable cells excludes the propidium ion and that loss of this permeability barrier represents irreparable damage and thus cell death. These assumptions are typically based on analysis of live and killed cells. Here we have identified stress levels that lead to a loss of viability of a proportion of Saccharomyces cerevisiae cells and under these conditions we show that there is a subpopulation of cells that can take up PI during and immediately following exposure to stress but that a short incubation allows repair of the membrane damage such that subsequent exposure to PI does not result in staining. Irrespective of the stress applied, approximately 7% of cells exhibited the ability to repair. These results indicate that the level of damage that the yeast cell membrane can sustain and yet retain the ability to repair is greater than previously recognized and care must therefore be taken in using the terms 'PI-positive' and 'dead' synonymously. We discuss these findings in the context of the potential for such environmental stress-induced, transient membrane permeability to have evolutionary implications via the facilitation of horizontal gene transfer.

PMID: 21199254 [PubMed - indexed for MEDLINE]

367. Genes Cells. 2011 Feb;16(2):217-30. doi: 10.1111/j.1365-2443.2010.01480.x. Epub 2010 Dec 29.

Fission yeast ATF/CREB family protein Atf21 plays important roles in production of normal spores.

Morita T, Yamada T, Yamada S, Matsumoto K, Ohta K.

The Graduate School of Science and Engineering, Saitama University, Saitama 338-8570, Japan.

Activating transcription factor/cAMP response element binding protein (ATF/CREB) family transcription factors play central roles in maintaining cellular homeostasis. They are activated in response to environmental stimuli, bind to CRE sequences in the promoters of stress-response genes and regulate transcription. Although ATF/CREB proteins are widely conserved among most eukaryotes, their characteristics are highly diverse. Here, we investigated the functions of a fission yeast ATF/CREB protein Atf21 to find out its unique properties. We show that Atf21 is dispensable for the adaptive response to several stresses such as nitrogen starvation and for meiotic events including nuclear divisions. However, spores derived from atf21Δ mutants are not as mature as wild-type ones and are unable to form colonies under nutrition-rich conditions. Furthermore, we demonstrate that the Atf21 protein, which is scarce in early meiosis, gradually accumulates as meiosis proceeds; it reaches maximum levels approximately 8 h after nitrogen starvation and is present during germination. These results suggest that Atf21 is expressed and functions long after nitrogen starvation. Given that other well-characterized fission yeast ATF/CREB proteins Atf1 and Pcr1 accumulate and function promptly upon exposure to environmental stresses, we propose that Atf21 is a distinct member of the ATF/CREB family in fission yeast.

PMID: 21199192 [PubMed - indexed for MEDLINE]

368. Anaesthesia. 2010 Sep;65(9):880-4. doi: 10.1111/j.1365-2044.2010.06372.x.

A survey of the management of needlestick injuries from incapacitated patients in intensive care units.

Burrows LA, Padkin A.

Sir Humphry Davy Department of Anaesthesia, University Hospitals Bristol, Bristol, UK. lorns@doctors.org.uk

Comment in Anaesthesia. 2010 Dec;65(12):1226. Anaesthesia. 2010 Dec;65(12):1227. Anaesthesia. 2010 Sep;65(9):875-7. Anaesthesia. 2010 Dec;65(12):1225-6. Anaesthesia. 2011 Jun;66(6):524-5. Anaesthesia. 2010 Dec;65(12):1227-8.

The Human Tissue Act 2004 and Mental Capacity Act 2005 resulted in a change in the management of needlestick injuries sustained from incapacitated patients. It appears unlawful to test for blood-borne viruses without a patient's consent for the sole benefit of the healthcare worker. This survey of intensive care units within England, Wales and Northern Ireland investigated how needlestick injuries from incapacitated patients had been managed within the previous year. Of the 225 intensive care units surveyed, 99 (44%) responded. Sixty-two (62.6%) reported a needlestick injury to a healthcare worker from an incapacitated patient. Thirty-six (64.3%) patients were tested for blood-borne viruses without consent. Sixteen (25.8%) patients tested positive for blood-borne viruses. Only 19 (30.6%) healthcare workers took post-exposure prophylaxis following the injury. These results show that needlestick injuries from incapacitated patients are common and that the majority of patients were tested for blood-borne viruses without consent.

PMID: 21198483 [PubMed - indexed for MEDLINE]

369. Front Biosci (Schol Ed). 2011 Jan 1;3:606-20.

Occupational exposure to microorganisms used as biocontrol agents in plant production.

Madsen AM.

The National Research Centre for the Working Environment, Lersoe Parkalle 105, 2100 Copenhagen OE, Denmark. amm@nrcwe.dk

Exposure to bioaerosols containing fungi and bacteria may cause various deleterious respiratory health effects. Fungi and bacteria are commercially produced and applied to the environment as microbiological pest control agents (MPCAs). Attention has been drawn towards the exposure and health risks due to the use of commercially important MPCAs. As part of a risk evaluation this paper intends to review whether the exposure to MPCAs (Beauveria bassiana, Verticillium lecanii, Trichoderma harzianum, T. viride, T. polysporum, Paecilomyces fumosoroseus, P. lilacinus, Streptomyces griseoviridis, Bacillus subtilis and Ba. thuringiensis) exceeds background exposure levels. The paper is further aimed to focus on the aerosolization of MPCAs in relation to exposure and human inhalation. From the few studies about exposures it is concluded that both people handling MPCAs in occupational settings and residents of an area where MPCAs have been applied may be exposed to MPCAs. The highest exposures to MPCAs are found for people applying MPCAs. In 2 of 12 environments exposure to applied MPCAs were higher than exposure to the total number of bacteria or fungi.

PMID: 21196399 [PubMed - indexed for MEDLINE]

370. Front Biosci (Schol Ed). 2011 Jan 1;3:445-53.

Assessment of airborne microorganisms by real-time PCR: optimistic findings and research challenges.

Oppliger A, Masclaux FG, Niculita-Hirzel H.

Institute for Work and Health, University of Lausanne and Geneva, Switzerland. Anne.Oppliger@hospvd.ch

Most airborne microorganisms are natural components of our ecosystem. Soil, vegetation and animals, including humans, are sources for aerial release of these living or dead cells. In the past, assessment of airborne microorganisms was mainly restricted to occupational health concerns. Indeed, in several occupations, exposure to very high concentrations of non-infectious airborne bacteria and fungi, result in allergenic, toxic or irritant reactions. Recently, the threat of bioterrorism and pandemics have highlighted the urgent need to increase knowledge of bioaerosol ecology. More fundamentally, airborne bacterial and fungal communities begin to draw much more consideration from environmental microbiologists, who have neglected this area for a long time. This increased interest of scientists is to a great part due to the development and use of real-time PCR techniques to identify and quantify airborne microorganisms. Even if the advantages of the PCR technology are obvious, researchers are confronted with new problems. This review describes the methodological state of the art in bioaerosols field and emphasizes the future challenges and perspectives of the real-time PCR-based methods for airborne microorganism studies.

PMID: 21196388 [PubMed - indexed for MEDLINE]

371. Front Biosci (Schol Ed). 2011 Jan 1;3:393-407.

Emission of bacteria and fungi in the air from wastewater treatment plants - a review.

Korzeniewska E.

Department of Environmental Microbiology, Faculty of Environmental Sciences and Fisheries, University of Warmia and Mazury, Olsztyn, Poland. ewa.korzeniewska@uwm.edu.pl

An increase in global population, coupled with intensive development of industry and agriculture, has resulted in the generation and accumulation of large amounts of waste around the world. The spread of pathogenic microorganisms, endotoxins, odours and dust particles in the air is an inevitable consequence of waste production and waste management. Thus, the risk of infections associated with wastewater treatment plants (WWTPs) has become of a particular importance in recent decades. Sewage and unstable sludge contain various pathogens such as viruses, bacteria, and human and animal parasites. These microorganisms can be transmitted to the ambient air in wastewater droplets, which are generated during aeration or mechanical moving of the sewage. Bioaerosols generated during wastewater treatment may therefore pose a potential health hazard to workers of these plants or to habitants of their surroundings. The degree of human exposure to airborne bacteria, fungi, endotoxin and other allergens may vary significantly depending upon the type and the capacity of a plant, kind of the facilities, performed activities and meteorological conditions.

PMID: 21196384 [PubMed - indexed for MEDLINE]

372. Front Biosci (Elite Ed). 2011 Jan 1;3:757-71.

Mold exposure and respiratory health in damp indoor environments.

Park JH, Cox-Ganser JM.

Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Division of Respiratory Disease Studies, Morgantown, West Virginia, USA. gzp8@cdc.gov

Almost all modern buildings experience at least minor, and sometimes serious, water damage during their life span. Excess moisture in buildings becomes a critical factor for mold (fungal) proliferation in nutrient-rich environments. As a result, building occupants may be exposed to increased levels of microbial agents such as fungal spores, cell fragments, cell wall components, or toxins. Such exposures may result in various diseases and symptoms, both respiratory and non-respiratory. Respiratory health complaints are common in damp buildings and have been more thoroughly studied than non-respiratory complaints. Respiratory diseases and symptoms which may be produced by exposure to indoor fungi include asthma development, exacerbation of asthma, hypersensitivity pneumonitis, cough, wheeze, dyspnea (shortness of breath), nasal and throat symptoms, and respiratory infections. In addition to these illnesses, rhinosinusitis and sarcoidosis in water-damaged building occupants are also drawing more scientific attention. In this article, we explore the evidence for adverse effects of fungal exposure on respiratory health in damp indoor environments and potential disease mechanisms related to the exposure.

PMID: 21196349 [PubMed - indexed for MEDLINE]

373. Front Biosci (Elite Ed). 2011 Jan 1;3:562-80.

The possible role of fungal contamination in sick building syndrome.

Straus DC.

Department of Microbiology and Immunology, Texas Tech University Health Sciences Center, Lubbock, Texas 79430, USA. david.straus@ttuhsc.edu

The following is a review of some of the work that we have done since 2007 regarding the importance of molds in the phenomenon of sick building syndrome (SBS). In these studies we first examined mold contamination in air handling units (AHU). Our results showed that Cladosporium sp. were commonly recovered in AHU as growth sites and free spores. They were found mainly on the blower wheel fan blades, the ductwork, and cooling coil fans. Our results showed that the presence of species of molds other than Cladosporium in locations other than the blower wheel blades indicated that the AHU condition was not optimal. In a series of three papers, we examined growth and mycotoxin production by Chaetomium globosum (CG). In these studies we showed that CG produces two potent mycotoxins, chaetoglobosin A (Ch-A) and chaetoglobosin C (Ch-C) when grown on building material. We discovered that these toxins break down when exposed to temperatures in excess of 75 degrees C. We also showed that growth and mycotoxin production by CG is favored at a neutral pH. In another study, we showed that mycotoxins can be detected in body fluids and human tissues from patients exposed to mycotoxin producing molds, and we showed which human tissues or fluids were the most likely to give positive results for detection of these compounds. Finally, we showed that the macrocyclic trichothecene mycotoxins (MTM) produced by Stachybotrys chartarum (SC) are detectable in experimental animals soon after exposure and we described the dynamics of MTM tissue loading.

PMID: 21196335 [PubMed - indexed for MEDLINE]

374. J Microbiol Biotechnol. 2010 Dec;20(12):1630-6.

Response of Saccharomyces cerevisiae to ethanol stress involves actions of protein Asr1p.

Ding J, Huang X, Zhao N, Gao F, Lu Q, Zhang KQ.

Laboratory for Conservation and Utilization of Bio-Resources, and Key Laboratory for Microbial Resources of the Ministry of Education, Yunnan University, Kunming, Yunnan, 650091, China.

During the fermentation process of Saccharomyces cerevisiae, yeast cells must rapidly respond to a wide variety of external stresses in order to survive the constantly changing environment, including ethanol stress. The accumulation of ethanol can severely inhibit cell growth activity and productivity. Thus, the response to changing ethanol concentrations is one of the most important stress reactions in S. cerevisiae and worthy of thorough investigation. Therefore, this study examined the relationship between ethanol tolerance in S. cerevisiae and a unique protein called alcohol sensitive RING/PHD finger 1 protein (Asr1p). A real-time PCR showed that upon exposure to 8% ethanol, the expression of Asr1 was continuously enhanced, reaching a peak 2 h after stimulation. This result was confirmed by monitoring the fluorescence levels using a strain with a green fluorescent protein tagged to the C-terminal of Asr1p. The fluorescent microscopy also revealed a change in the subcellular localization before and after stimulation. Furthermore, the disruption of the Asr1 gene resulted in hypersensitivity on the medium containing ethanol, when compared with the wild-type strain. Thus, when taken together, the present results suggest that Asr1 is involved in the response to ethanol stress in the yeast S. cerevisiae.

PMID: 21193817 [PubMed - indexed for MEDLINE]

375. Eukaryot Cell. 2011 Mar;10(3):398-411. Epub 2010 Dec 30.

Molecular characterization of propolis-induced cell death in Saccharomyces cerevisiae.

de Castro PA, Savoldi M, Bonatto D, Barros MH, Goldman MH, Berretta AA, Goldman GH.

Departamento de Ciências Farmacêuticas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Avenida do Café S/N, Ribeirão Preto, São Paulo, Brazil.

Propolis, a natural product of plant resins, is used by the bees to seal holes in their honeycombs and protect the hive entrance. However, propolis has also been used in folk medicine for centuries. Here, we apply the power of Saccharomyces cerevisiae as a model organism for studies of genetics, cell biology, and genomics to determine how propolis affects fungi at the cellular level. Propolis is able to induce an apoptosis cell death response. However, increased exposure to propolis provides a corresponding increase in the necrosis response. We showed that cytochrome c but not endonuclease G (Nuc1p) is involved in propolis-mediated cell death in S. cerevisiae. We also observed that the metacaspase YCA1 gene is important for propolis-mediated cell death. To elucidate the gene functions that may be required for propolis sensitivity in eukaryotes, the full collection of about 4,800 haploid S. cerevisiae deletion strains was screened for propolis sensitivity. We were able to identify 138 deletion strains that have different degrees of propolis sensitivity compared to the corresponding wild-type strains. Systems biology revealed enrichment for genes involved in the mitochondrial electron transport chain, vacuolar acidification, negative regulation of transcription from RNA polymerase II promoter, regulation of macroautophagy associated with protein targeting to vacuoles, and cellular response to starvation. Validation studies indicated that propolis sensitivity is dependent on the mitochondrial function and that vacuolar acidification and autophagy are important for yeast cell death caused by propolis.

PMCID: PMC3067468 PMID: 21193549 [PubMed - indexed for MEDLINE]

376. Environ Health Perspect. 2011 Jun;119(6):771-7. Epub 2010 Dec 29.

Involvement of N-6 adenine-specific DNA methyltransferase 1 (N6AMT1) in arsenic biomethylation and its role in arsenic-induced toxicity.

Ren X, Aleshin M, Jo WJ, Dills R, Kalman DA, Vulpe CD, Smith MT, Zhang L.

Genes and Environment Laboratory, Division of Environmental Health Sciences, School of Public Health, University of California-Berkeley, Berkeley, California 94720, USA.

BACKGROUND: In humans, inorganic arsenic (iAs) is metabolized to methylated arsenical species in a multistep process mainly mediated by arsenic (+3 oxidation state) methyltransferase (AS3MT). Among these metabolites is monomethylarsonous acid (MMAIII), the most toxic arsenic species. A recent study in As3mt-knockout mice suggests that unidentified methyltransferases could be involved in alternative iAs methylation pathways. We found that yeast deletion mutants lacking MTQ2 were highly resistant to iAs exposure. The human ortholog of the yeast MTQ2 is N-6 adenine-specific DNA methyltransferase 1 (N6AMT1), encoding a putative methyltransferase.
OBJECTIVE: We investigated the potential role of N6AMT1 in arsenic-induced toxicity.
METHODS: We measured and compared the cytotoxicity induced by arsenicals and their metabolic profiles using inductively coupled plasma-mass spectrometry in UROtsa human urothelial cells with enhanced N6AMT1 expression and UROtsa vector control cells treated with different concentrations of either iAsIII or MMAIII.
RESULTS: N6AMT1 was able to convert MMAIII to the less toxic dimethylarsonic acid (DMA) when overexpressed in UROtsa cells. The enhanced expression of N6AMT1 in UROtsa cells decreased cytotoxicity of both iAsIII and MMAIII. Moreover, N6AMT1 is expressed in many human tissues at variable levels, although at levels lower than those of AS3MT, supporting a potential participation in arsenic metabolism in vivo.
CONCLUSIONS: Considering that MMAIII is the most toxic arsenical, our data suggest that N6AMT1 has a significant role in determining susceptibility to arsenic toxicity and carcinogenicity because of its specific activity in methylating MMAIII to DMA and other unknown mechanisms.

PMCID: PMC3114810 PMID: 21193388 [PubMed - indexed for MEDLINE]

377. Recent Pat Antiinfect Drug Discov. 2011 Jan;6(1):38-44.

Heat shock protein inhibitors for the treatment of fungal infections.

Wirk B.

University of Florida, BMT Program, Division of Hematology-Oncology, 1600 SW Archer Road, PO BOX 100278, Gainesville, FL 32610, USA. baldeep.wirk@medicine.ufl.edu

Invasive fungal infections are a leading cause of mortality, especially in immunocompromised patients. Therapy is made difficult by the limited number of antifungal agents currently available which mostly target ergosterol in fungal cell membranes. The paucity of targets allows the development of cross resistance to all drugs with a common target. This highlights the need to develop new therapeutic strategies for fungal disease including agents with novel mechanisms of action. Heat shock protein 90 stabilizes calcineurin which regulates response to stress, allowing for calcineurin dependent stress responses required to survive exposure to antifungal drugs. Heat shock protein 90 inhibition abrogates calcineurin dependent stress responses, changing fungistatic drugs to fungicidal. Targeting a highly conserved protein that has a vital role in many cellular signaling pathways, reduces the potential for emergence of resistance to heat shock proteins inhibitors. This article will review recent patents in novel heat shock protein inhibitor therapy, such as efungumab, which diminish the emergence of antifungal drug resistance and enable greater efficacy of existing antifungals.

PMID: 21192778 [PubMed - indexed for MEDLINE]

378. Clin Vaccine Immunol. 2011 Mar;18(3):380-6. Epub 2010 Dec 29.

Decreased serum antibody responses to recombinant pneumocystis antigens in HIV-infected and uninfected current smokers.

Crothers K, Daly KR, Rimland D, Goetz MB, Gibert CL, Butt AA, Justice AC, Djawe K, Levin L, Walzer PD.

University of Washington School of Medicine, Department of Medicine, Division of Pulmonary and Critical Care Medicine, Harborview Medical Center, 325 Ninth Avenue, Box 359762, Seattle, WA 98104, USA. crothk@uw.edu

Serologic studies can provide important insights into the epidemiology and transmission of Pneumocystis jirovecii. Exposure to P. jirovecii can be assessed by serum antibody responses to recombinant antigens from the major surface glycoprotein (MsgC), although factors that influence the magnitude of the antibody response are incompletely understood. We determined the magnitudes of antibody responses to P. jirovecii in comparison to adenovirus and respiratory syncytial virus (RSV) in HIV-infected and uninfected patients and identified predictors associated with the magnitude of the response. We performed a cross-sectional analysis using serum samples and data from 153 HIV-positive and 92 HIV-negative subjects enrolled in a feasibility study of the Veterans Aging Cohort 5 Site Study (VACS 5). Antibodies were measured using an enzyme-linked immunosorbent assay (ELISA). Independent predictors of antibody responses were determined using multivariate Tobit regression models. The results showed that serum antibody responses to P. jirovecii MsgC fragments were significantly and independently decreased in current smokers. Antibodies to P. jirovecii also tended to be lower with chronic obstructive pulmonary disease (COPD), hazardous alcohol use, injection drug use, and HIV infection, although these results were not statistically significant. These results were specific to P. jirovecii and did not correlate with adenovirus. Antibody responses to RSV were in the inverse direction. Thus, current smoking was independently associated with decreased P. jirovecii antibody responses. Whether smoking exerts an immunosuppressive effect that affects the P. jirovecii antibody response, colonization, or subsequent risk for disease is unclear; prospective, longitudinal studies are needed to evaluate these findings further.

PMCID: PMC3067379 PMID: 21191078 [PubMed - indexed for MEDLINE]

379. J Clin Microbiol. 2011 Mar;49(3):1064-70. Epub 2010 Dec 29.

Unapparent microsporidial infection among immunocompetent humans in the Czech Republic.

Sak B, Brady D, Pelikánová M, Květoňová D, Rost M, Kostka M, Tolarová V, Hůzová Z, Kváč M.

Biology Centre of the Academy of Sciences of the Czech Republic, v.v.i., University of South Bohemia in České Budějovice, České Budějovice, Czech Republic.

In the present population-based study, we determined the prevalences of the most common human-pathogenic microsporidia, Encephalitozoon spp. and Enterocytozoon bieneusi, in asymptomatic healthy people living in the Czech Republic. A total of 382 males and females (ages, 1 to 84 years) living in the Czech Republic, of whom 265 were Czech nationals and 117 were foreign students, were included in a study testing for the presence of microsporidia by use of coprology and molecular methods. Single-species infections with Enterocytozoon bieneusi or an Encephalitozoon sp. were detected for 9 and 136 individuals, respectively. Moreover, coinfections were detected for 14 individuals. Four genotypes of 3 human-pathogenic Encephalitozoon spp. and 7 E. bieneusi genotypes, including 3 novel genotypes, were detected. Some of these were reported in humans for the first time. The highest prevalence was recorded for individuals older than 50 years and for loose, unformed stool samples. These findings clearly show that exposure to microsporidia is common among immunocompetent people and that microsporidiosis is not linked to any clinical manifestation in healthy populations.

PMCID: PMC3067711 PMID: 21191056 [PubMed - indexed for MEDLINE]

380. BMC Biochem. 2010 Dec 28;11:49.

Glyceraldehyde-3-phosphate dehydrogenase is largely unresponsive to low regulatory levels of hydrogen peroxide in Saccharomyces cerevisiae.

Cyrne L, Antunes F, Sousa-Lopes A, Diaz-Bérrio J, Marinho HS.

Centro de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal.

BACKGROUND: The reversible oxidation of protein SH groups has been considered to be the basis of redox regulation by which changes in hydrogen peroxide (H2O2) concentrations may control protein function. Several proteins become S-glutathionylated following exposure to H2O2 in a variety of cellular systems. In yeast, when using a high initial H2O2 dose, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was identified as the major target of S-glutathionylation which leads to reversible inactivation of the enzyme. GAPDH inactivation by H2O2 functions to reroute carbohydrate flux to produce NADPH. Here we report the effect of low regulatory H2O2 doses on GAPDH activity and expression in Saccharomyces cerevisiae.
RESULTS: A calibrated and controlled method of H2O2 delivery - the steady-state titration - in which cells are exposed to constant, low, and known H2O2 concentrations, was used in this study. This technique, contrary to the common bolus addition, allows determining which H2O2 concentrations trigger specific biological responses. This work shows that both in exponential- and stationary-phase cells, low regulatory H2O2 concentrations induce a large upregulation of catalase, a fingerprint of the cellular oxidative stress response, but GAPDH oxidation and the ensuing activity decrease are only observed at death-inducing high H2O2 doses. GAPDH activity is constant upon incubation with sub-lethal H2O2 doses, but in stationary-phase cells there is a differential response in the expression of the three GAPDH isoenzymes: Tdh1p is strongly upregulated while Tdh2p/Tdh3p are slightly downregulated.
CONCLUSIONS: In yeast GAPDH activity is largely unresponsive to low to moderate H2O2 doses. This points to a scenario where (a) cellular redoxins efficiently cope with levels of GAPDH oxidation induced by a vast range of sub-lethal H2O2 concentrations, (b) inactivation of GAPDH cannot be considered a sensitive biomarker of H2O2-induced oxidation in vivo. Since GAPDH inactivation only occurs at cell death-inducing high H2O2 doses, GAPDH-dependent rerouting of carbohydrate flux is probably important merely in pathophysiological situations. This work highlights the importance of studying H2O2-induced oxidative stress using concentrations closer to the physiological for determining the importance of protein oxidation phenomena in the regulation of cellular metabolism.

PMCID: PMC3019127 PMID: 21189144 [PubMed - indexed for MEDLINE]

381. Mol Genet Genomics. 2011 Mar;285(3):185-95. Epub 2010 Dec 28.

DNA repair defects sensitize cells to anticodon nuclease yeast killer toxins.

Klassen R, Wemhoff S, Krause J, Meinhardt F.

Institut für Molekulare Mikrobiologie und Biotechnologie, Westfälische Wilhelms-Universität Münster, 48149 Münster, Germany.

Killer toxins from Kluyveromyces lactis (zymocin) and Pichia acaciae (PaT) were found to disable translation in target cells by virtue of anticodon nuclease (ACNase) activities on tRNA(Glu) and tRNA(Gln), respectively. Surprisingly, however, ACNase exposure does not only impair translation, but also affects genome integrity and concomitantly DNA damage occurs. Previously, it was shown that homologous recombination protects cells from ACNase toxicity. Here, we have analyzed whether other DNA repair pathways are functional in conferring ACNase resistance as well. In addition to HR, base excision repair (BER) and postreplication repair (PRR) promote clear resistance to either, PaT and zymocin. Comparative toxin sensitivity analysis of BER mutants revealed that its ACNase protective function is due to the endonucleases acting on apurinic (AP) sites, whereas none of the known DNA glycosylases is involved. Because PaT and zymocin require the presence of the ELP3/TRM9-dependent wobble uridine modification 5-methoxy-carbonyl-methyl (mcm(5)) for tRNA cleavage, we analyzed toxin response in DNA repair mutants additionally lacking such tRNA modifications. ACNase resistance caused by elp3 or trm9 mutations was found to rescue hypersensitivity of DNA repair defects, consistent with DNA damage to occur as a consequence of tRNA cleavage. The obtained genetic evidence promises to reveal new aspects into the mechanism linking translational fidelity and genome surveillance.

PMID: 21188417 [PubMed - indexed for MEDLINE]

382. PLoS Genet. 2010 Dec 16;6(12):e1001247.

A quantitative systems approach reveals dynamic control of tRNA modifications during cellular stress.

Chan CT, Dyavaiah M, DeMott MS, Taghizadeh K, Dedon PC, Begley TJ.

Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.

Erratum in PLoS Genet. 2011 Feb;7(2). doi: 10.1371/annotation/6549d0b1-efde-4aa4-9cda-1cef43f66b30.

Comment in Nat Methods. 2011 Feb;8(2):108-9.

Decades of study have revealed more than 100 ribonucleoside structures incorporated as post-transcriptional modifications mainly in tRNA and rRNA, yet the larger functional dynamics of this conserved system are unclear. To this end, we developed a highly precise mass spectrometric method to quantify tRNA modifications in Saccharomyces cerevisiae. Our approach revealed several novel biosynthetic pathways for RNA modifications and led to the discovery of signature changes in the spectrum of tRNA modifications in the damage response to mechanistically different toxicants. This is illustrated with the RNA modifications Cm, m(5)C, and m(2) (2)G, which increase following hydrogen peroxide exposure but decrease or are unaffected by exposure to methylmethane sulfonate, arsenite, and hypochlorite. Cytotoxic hypersensitivity to hydrogen peroxide is conferred by loss of enzymes catalyzing the formation of Cm, m(5)C, and m(2) (2)G, which demonstrates that tRNA modifications are critical features of the cellular stress response. The results of our study support a general model of dynamic control of tRNA modifications in cellular response pathways and add to the growing repertoire of mechanisms controlling translational responses in cells.

PMCID: PMC3002981 PMID: 21187895 [PubMed - indexed for MEDLINE]

383. J Radiat Res (Tokyo). 2011;52(1):88-95. Epub 2010 Dec 24.

Current concentration of artificial radionuclides and estimated radiation doses from 137Cs around the Chernobyl Nuclear Power Plant, the Semipalatinsk Nuclear Testing Site, and in Nagasaki.

Taira Y, Hayashida N, Brahmanandhan GM, Nagayama Y, Yamashita S, Takahashi J, Gutevitc A, Kazlovsky A, Urazalin M, Takamura N.

Department of Radiation Epidemiology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

To evaluate current environmental contamination and contributions from internal and external exposure due to the accident at the Chernobyl Nuclear Power Plant (CNPP) and nuclear tests at the Semipalatinsk Nuclear Testing Site (SNTS), concentrations of artificial radionuclides in edible mushrooms, soils and stones from each area were analyzed by gamma spectrometry. Annual effective doses were calculated for each area from the cesium contamination. Calculated internal effective doses of (137)Cs due to ingestion of mushrooms were 1.8 × 10(-1) mSv/year (y) in Gomel city (around CNPP), 1.7 × 10(-1) mSv/y in Korosten city (around CNPP), 2.8 × 10(-4) mSv/y in Semipalatinsk city, and 1.3 × 10(-4) mSv/y in Nagasaki. Calculated external effective doses of (137)Cs were 3.4 × 10(-2) mSv/y in Gomel city, 6.2 × 10(-2) mSv/y in Korosten city, 2.0 × 10(-4) mSv/y in Semipalatinsk city, and 1.3 × 10(-4) mSv/y in Nagasaki. Distribution of radionuclides in stones collected beside Lake Balapan (in SNTS) were (241)Am (49.4 ± 1.4 Bq/kg), (137)Cs (406.3 ± 1.7 Bq/kg), (58)Co (3.2 ± 0.5 Bq/kg), and (60)Co (125.9 ± 1.1 and 126.1 ± 1.1 Bq/kg). The present study revealed that dose rates from internal and external exposure around CNPP were not sufficiently low and radiation exposure potency still exists even though current levels are below the public dose limit of 1 mSv/y (ICRP1991). Moreover, parts of the SNTS area may be still contaminated by artificial radionuclides derived from nuclear tests. Long-term follow-up of environmental monitoring around CNPP and SNTS, as well as evaluation of health effects in the population residing around these areas, may contribute to radiation safety with a reduction of unnecessary exposure of residents.

PMID: 21187665 [PubMed - indexed for MEDLINE]

384. Arch Environ Occup Health. 2010 Oct-Dec;65(4):201-10.

Associations between atmospheric concentrations of spores and emergency department visits for asthma among children living in Montreal.

Raphoz M, Goldberg MS, Garneau M, Héguy L, Valois MF, Guay F.

Department of Geography, Universite du Quebec a Montreal, Montreal, Quebec, Canada.

The authors carried out a time-series study to determine whether short-term increases in the concentrations of spores were associated with emergency department visits from asthma among children 0 to 9 years of age in Montreal, 1994-2004. Concentrations of spores were obtained from one sampling monitor. The authors used parametric Poisson models to model the association between daily admissions to emergency rooms for asthma and ambient exposures to a variety of spores, adjusting for secular trends, changes in weather, and chemical pollutants. For first admissions and exposures to Basidiomycetes, the authors found positive associations at all lags but the concurrent day. For Deuteromycetes and Cladosporium, risks were positive starting at lag 3 days and diminished at lag 6 days. There was little evidence of associations for readmissions, except for Basidiomycetes. The results indicate that Basidiomycetes and Cladosporium spores may be implicated in the exacerbation of asthma among children, most notably in the case of first-time visits to emergency departments, and that the effects appear to be delayed by several days.

PMID: 21186425 [PubMed - indexed for MEDLINE]

385. J Microbiol Methods. 2011 Feb;84(2):317-26. Epub 2010 Dec 23.

Studies on the relationship between pulsed UV light irradiation and the simultaneous occurrence of molecular and cellular damage in clinically-relevant Candida albicans.

Farrell H, Hayes J, Laffey J, Rowan N.

Department of Nursing and Health Science, Athlone Institute of Technology, Co. Westmeath, Ireland.

This constitutes the first study to report on the relationship between pulsed UV light (PL) irradiation and the simultaneous occurrence of molecular and cellular damage in clinical strains of Candida albicans. Microbial protein leakage and propidium iodide (PI) uptake assays demonstrated significant increases in cell membrane permeability in PL-treated yeast that depended on the amount of UV pulses applied. This finding correlated well with the measurement of increased levels of lipid hydroperoxidation in the cell membrane of PL-treated yeast. PL-treated yeast cells also displayed a specific pattern of intracellular reactive oxygen species (ROS) generation, where ROS were initially localised in the mitochondria after low levels of pulsing (UV dose 0.82 μJ/cm(2)) before more wide-spread cytosolic ROS production occurred with enhanced pulsing. Intracellular ROS levels were measured using the specific mitochondrial peroxide stain dihydrorhodamine 123 and the cytosolic oxidation stain dichloroflurescin diacetate. Use of the dihydroethidium stain also revealed increased levels of intracellular superoxide as a consequence of augmented pulsing. The ROS bursts observed during the initial phases of PL treatment was consistent with the occurrence of apoptotic cells as confirmed by detection of specific apoptotic markers, abnormal chromatin condensation and externalisation of cell membrane lipid phosphatidylserine. Increased amount of PL-irradiation (ca. UV does 1.24-1.65 μJ/cm(2)) also resulted in the occurrence of late apoptotic and necrotic yeast phenotypes, which coincided with the transition from mitochondrial to cytosolic localisation of ROS and with irreversible cell membrane leakage. Use of the comet assay also revealed significant nuclear damage in similarly treated PL samples. Although some level of cellular repair was observed in all test strains during sub-lethal exposure to PL-treatments (≤20 pulses or UV dose 0.55 μJ/cm(2)), this was absent in similar samples exposed to increased amounts of pulsing. This study showed that PL-irradiation inactivates C. albicans test strains through a multi-targeted process with no evidence of microbial ability to support cell growth after ≤20 pulses. Implications of our findings in terms of application of PL for contact-surface disinfection are discussed.

PMID: 21185335 [PubMed - indexed for MEDLINE]

386. Toxicon. 2011 Mar 15;57(4):525-39. Epub 2010 Dec 22.

Identification of amino acids critical for the cytotoxicity of Shiga toxin 1 and 2 in Saccharomyces cerevisiae.

Di R, Kyu E, Shete V, Saidasan H, Kahn PC, Tumer NE.

Department of Plant Biology and Pathology, School of Environmental and Biological Sciences, Rutgers University, 59 Dudley Road, New Brunswick, NJ 08901-8502, USA.

Shiga toxins (Stx1 and Stx2) are produced by E. coli O157:H7, which is a leading cause of foodborne illness. The A subunits of Stx1 (Stx1A) and Stx2 (Stx2A) are ribosome inactivating proteins (RIPs) that inhibit translation by removing an adenine from the highly conserved α-sarcin ricin loop (SRL) of the large rRNA. Here, we used mutagenesis in Saccharomyces cerevisiae to identify residues critical for cytotoxicity of Stx1A and Stx2A. The A subunits depurinated the SRL, inhibited translation and caused apoptotic-like cell death in yeast. Single mutations in Asn75, Tyr77, Glu167 and Arg176 reduced the cytotoxicity of both toxins around 10-fold. However, Asn75 and Tyr77 were more critical for the depurination activity of Stx2A, while Arg176 was more critical for the depurination activity of Stx1A. The crystal structures of the two proteins lack electron density for some surface loops, including one which is adjacent to the active site in both molecules. Modeling these loops changed neither the secondary nor the tertiary structures of the rest of the protein. Analysis of solvent accessible surface areas indicated that Asn75 and Tyr77 are more exposed in Stx2A, while Arg176 is more exposed in Stx1A, indicating that residues with higher surface exposure were more critical for enzymatic activity. Double mutations at Glu167 and Arg176 eliminated the depurination activity and cytotoxicity of both toxins. C-terminal deletions of A chains eliminated cytotoxicity of both toxins, but showed functional differences. Unlike Stx1A, cytotoxicity of Stx2A was lost before its ability to depurinate ribosomes. These results identify residues that affect enzymatic activity and cytotoxicity of Stx1A and Stx2A differently and demonstrate that the function of these residues can be differentiated in yeast. The extent of ribosome depurination and translation inhibition did not correlate with the extent of cell death, indicating that depurination of the SRL and inhibition of translation are not entirely responsible for cell death.

PMCID: PMC3055938 [Available on 2012/3/15] PMID: 21184769 [PubMed - indexed for MEDLINE]

387. Sci China Life Sci. 2010 Dec;53(12):1374-98. Epub 2010 Dec 23.

A 60-year journey of mycorrhizal research in China: Past, present and future directions.

He X, Duan Y, Chen Y, Xu M.

School of Life Sciences, Yunnan Normal University, Kunming 650092, China. xhhe@caas.ac.cn

The significance of mycorrhizas (fungal roots in 90% of land plants) in plant nutrient acquisition and growth, element biogeochemical cycling and maintaining of terrestrial ecosystem structures has been globally established for more than 120 years. Great progress in mycorrhizal research in the past 60 years (1950-2009, 1981-2009 in particular) has also been made across China, particularly in the mainland, Hong Kong and Taiwan. For instance, a total of 20 new and approximately 120 records of arbuscular mycorrhizal (AM) fungal species, 30 new and approximately 800 records of ectomycorrhizal (EM) fungal species, a dozen of new and approximately 100 records of orchid mycorrhizal (OM) fungal species have been isolated by morphological observation and/or molecular identification in China since the 1950s. Great accomplishment has also been made in the following area, including fungal species richness and genetic structure, relationships between species composition and plant taxa, effects of mycorrhizal fungi on plant nutrient uptake and growth, resistances to pathogens and interactions with other soil microorganisms, potential of mycorrhizal fungi in phytoremediation and/or land reclamation, alterations of enzymatic activities in mycorrhizal plants, and elevated CO(2) and O(3) on root colonization and species diversity. Unfortunately, the international community cannot easily appreciate almost all Chinese mycorrhizal studies since the vast majority of them have been published in Chinese and/or in China-based journals. The aim of this review is to make a comprehensive exposure of the past and present China's major mycorrhizal research to the whole world, and then to suggest potential directions for the enhancement of future mycorrhizal research within and/or between the Chinese and international mycorrhizal community.

PMID: 21181339 [PubMed - indexed for MEDLINE]

388. SADJ. 2010 Oct;65(9):410, 412-4.

Properties of a new mouthrinse for patients receiving radiation therapy.

Patel M, Ndlovu NN, Owen CP, Veale R.

Department of Clinical Microbiology and Infectious Diseases, National Health Laboratory Services and Faculty of Health Sciences.

INTRODUCTION: Patients receiving radiation therapy due to oral cancer develop complications such as hyposalivation, mucositis, oral infections, dental hypersensitivity and caries. Mouthrinses can alleviate some of these problems. AIMS AND OBJECTIVES: To investigate the in vitro antimicrobial properties and cytotoxicity of an experimental mouthrinse.
METHODS: The mouthrinse contained 30% hexylene glycol (glycerine), 7% potassium nitrate and 0.025% sodium fluoride. The minimal inhibitory concentration (MIC) of these ingredients and the mixture was determined for C. albicans, S. aureus and S. mutans over 24 hours at different concentrations. The MICs of two commercial mouthrinses, Corsodyl and Plax, were also determined using the same organisms. All mouthrinses were then tested to determine the percentage kill over 1, 2, and 3 minutes.
RESULTS: The MICs for hexylene glycol were 10%, 30% and 10% for C. albicans, S. aureus and S. mutons respectively. Potassium nitrate and sodium fluoride had no antimicrobial effects. The MIC of Corsodyl was 0.016 mg/ml for all the test organisms. The MIC for Plax varied from 0.0002 mg/ml to 0.001 mg/ml. The kill rates for all mouthrinses were acceptable, with no statistical differences between them. The experimental mouthrinse was not toxic to human oesophageal SCC cells after 1 minute exposure. At the time of the experiment, the costs of a similar quantity of the experimental mouthrinse, Corsodyl and Plax were R5.24, R30.00 and R10.00 respectively.
CONCLUSIONS: The experimental mouthrinse was cost-effective and proved to have an antimicrobial effect and could be used safely to alleviate oral infections, desensitize teeth, improve oral hygiene and control dental caries in cancer patients after radiation therapy.

PMID: 21180287 [PubMed - indexed for MEDLINE]

389. J Environ Sci (China). 2010;22(8):1225-31.

Microbial community variation in phytoremediation of triazophos by Canna indica Linn. in a hydroponic system.

Xiao H, Cheng S, Wu Z.

State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, the Chinese Academy of Sciences, Wuihan 430072, China. xiaohuiping422@sina.com

Phytoremediation of triazophos (O,O-diethyl-O-(1-phenyl-1,2,4-triazole-3-base) sulfur phosphate, TAP) pollution by Canna indica Lim. in a hydroponic system has been well studied, whereas the microbial mechanism on TAP degradation is still unknown. The variation in microbial community compositions was investigated by analyzing phospholipid fatty acids (PLFAs) profiles in microbes under TAP exposure. The TAP exposure resulted in an increase in proportions of fatty acid 16:0 and decrease in fatty acid 18:2omega9,12c, indicating that TAP may stimulate the reproduction of microorganisms and inhibit the growth of fungi to some degree. Significant correlation was found between the ratio of fungi to bacteria and TAP removal (r2 = 0.840, p < 0.01). In addition, the microbial community in the phytoremediation system with C. indica was dominated by Gram negative bacteria, which possibly contributed to the degradation of TAP. These results indicated that TAP might induce the colonization of bacteria in the hydroponic system planted with C. indica, and lead to a discrimination of microbial community, which might be one of the mechanisms on TAP dissipation in phytoremediation system.

PMID: 21179962 [PubMed - indexed for MEDLINE]

390. Ann Occup Hyg. 2011 Apr;55(3):272-85. Epub 2010 Dec 20.

Airborne microorganisms, endotoxin, and (1→3)-β-D-glucan exposure in greenhouses and assessment of respiratory symptoms among workers.

Adhikari A, Gupta J, Wilkins JR 3rd, Olds RL, Indugula R, Cho KJ, Li C, Yermakov M.

Department of Environmental Health, University of Cincinnati, Cincinnati, OH 45267, USA. atin.adhikari@uc.edu

OBJECTIVES: Greenhouse operations are an important sector of the horticulture industry, also known as the Green Industry. The objectives of this study were (i) to investigate exposure levels to airborne culturable fungi, bacteria (total culturable bacteria and actinomycetes), endotoxin, and (1→3)-β-D-glucan in three Midwest greenhouses during summer and winter using multiple exposure assessment methods; (ii) characterize the load of microorganisms on greenhouse floors and determine potential microbial source strengths of the floors for aerosolizing microbial biocontaminants, and (iii) to estimate the prevalence of rhinitis, wheezing, asthma, and other respiratory symptoms/conditions among greenhouse workers.
METHODS: Stationary inhalable aerosol samples were collected from each greenhouse using Button Inhalable Aerosol Samplers. Control samples were collected from offices and nearby outdoor locations. A microbial source strength tester was used to examine the aerosolization potential of microbial contaminants from greenhouse floors. Additionally, surface samples were collected by sterile cotton swabs. Temperature, relative humidity, and wind velocity were recorded. Airborne culturable fungi, bacteria, and actinomycetes were analyzed in the extracts from field samples by cultivation in nutrient agar media. Endotoxin and (1→3)-β-D-glucan in the extracts from field samples were analyzed by specific kinetic chromogenic Limulus amebocyte lysate assays. The prevalence of respiratory symptoms among greenhouse workers (n = 35) and control subjects (office workers; n = 14) was estimated with a standardized questionnaire. Results and
CONCLUSIONS: The collected data indicate that workers employed in Midwest greenhouses may be exposed to elevated levels of inhalable culturable microorganisms (fungi and bacteria collectively on the order of 10(2)-10(5) CFU m(-3)), endotoxin (10(1)-10(3) EU m(-3)), and (1→3)-β-D-glucan (10(1)-10(2) ng m(-3)). Seasonal variations were observed for some bioaerosol components. The prevalence of self-reported respiratory symptoms was generally higher among greenhouse workers compared to controls; however, the differences were not statistically significant, likely due to the relatively low statistical power of the study.

PMID: 21177263 [PubMed - indexed for MEDLINE]

391. Zhongguo Zhong Yao Za Zhi. 2010 Oct;35(19):2503-7.

[Aflatoxin contamination of Chinese herbal medicine in China and its potential management strategies].

[Article in Chinese]

Cai F, Gao W, Li H, Chen J, Li Z.

The Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China.

The mould phenomenon occurred commonly in the cultivation, processing and storage period of medicinal materials, which may result in production of mycotoxins. Mycotoxin contaminations caused by fungi are major issues related to the quality and safety of Chinese herbal medicine. This review summarized the work published in aflatoxins contamination of Chinese herbal medicine in China through the previous decade. The conclusion to be drawn from this survey is that aflatoxin exposure remains an important aspect of Chinese herbal medicine safety which needs to be paid great attention. We raised some points that should be focused on in future. The strategies of changing environment to suppress growth of toxin-producing fungus, so as to reduce aflatoxins are the most practical and effective ways, while biological control in the field production is a promising approach.

PMID: 21174753 [PubMed - indexed for MEDLINE]

392. Ind Health. 2011;49(2):242-8. Epub 2010 Dec 16.

Exposure level and distribution characteristics of airborne bacteria and fungi in Seoul metropolitan subway stations.

Kim KY, Kim YS, Kim D, Kim HT.

Institute of Industrial and Environmental Medicine, Hanyang University, Seoul, Republic of Korea.

The exposure level and distribution characteristics of airborne bacteria and fungi were assessed in the workers' activity areas (station office, bedroom, ticket office and driver's seat) and passengers' activity areas (station precinct, inside the passenger carriage, and platform) of the Seoul metropolitan subway. Among investigated areas, the levels of airborne bacteria and fungi in the workers' bedroom and station precincts were relatively high. No significant difference was found in the concentration of airborne bacteria and fungi between the underground and above ground activity areas of the subway. The genera identified in all subway activity areas with a 5% or greater detection rate were Staphylococcus, Micrococcus, Bacillus and Corynebacterium for airborne bacteria and Penicillium, Cladosporium, Chrysosporium, Aspergillus for airborne fungi. Staphylococcus and Micrococcus comprised over 50% of the total airborne bacteria and Penicillium and Cladosporium comprised over 60% of the total airborne fungi, thus these four genera are the predominant genera in the subway station.

PMID: 21173524 [PubMed - indexed for MEDLINE]

393. Rev Environ Contam Toxicol. 2011;210:1-34.

Attenuation of chromium toxicity by bioremediation technology.

Mohanty M, Patra HK.

Laboratory of Environmental Physiology, Post Graduate Department of Botany, Utkal University, Bhubaneswar, 751004, Orissa, India. 18.monalisa@gmail.com

Chromium is an important toxic environmental pollutant. Chromium pollution results largely from industrial activities, but other natural and anthropogenic sources also contribute to the problem. Plants that are exposed to environmental contamination by chromium are affected in diverse ways, including a tendency to suffer metabolic stress. The stress imposed by Cr exposure also extends to oxidative metabolic stress in plants that leads to the generation of active toxic oxygen free radicals. Such active free radicals degrade essential biomolecules and distort plant biological membranes. In this chapter, we describe sources of environmental chromium contamination, and provide information about the toxic impact of chromium on plant growth and metabolism. In addition, we address different phytoremediation processes that are being studied for use worldwide, in contaminated regions, to address and mitigate Cr pollution. There has been a long history of attempts to successfully mitigate the toxic effects of chromium-contaminated soil on plants and other organisms. One common approach, the shifting of polluted soil to landfills, is expensive and imposes environmental risks and health hazards of its own. Therefore, alternative eco-friendly bioremediation approaches are much in demand for cleaning chromium-polluted areas. To achieve its cleaning effects, bioremediation utilizes living organisms (bacteria, algae, fungi, and plants) that are capable of absorbing and processing chromium residues in ways which amend or eliminate it. Phytoremediation (bioremediation with plants) techniques are increasingly being used to reduce heavy metal contamination and to minimize the hazards of heavy metal toxicity. To achieve this, several processes, viz., rhizofiltration, phytoextraction, phytodetoxification, phytostabilization, and phytovolatilization, have been developed and are showing utility in practice, or promise. Sources of new native hyperaccumulator plants for use at contaminated sites are needed and constitute a key goal of ongoing phytoremediation research programs. Such new plants are needed to enhance the attractiveness of phytoremediation as an effective, affordable, and eco-friendly technique to achieve successful clean-up of metal-contaminated sites worldwide.

PMID: 21170701 [PubMed - indexed for MEDLINE]

394. Biochim Biophys Acta. 2011 Feb;1813(2):358-66. Epub 2010 Dec 15.

Continuous light exposure causes cumulative stress that affects the localization oscillation dynamics of the transcription factor Msn2p.

Bodvard K, Wrangborg D, Tapani S, Logg K, Sliwa P, Blomberg A, Kvarnström M, Käll M.

Department of Applied Physics, Chalmers University of Technology, 412 96 Göteborg, Sweden. kristofer@chalmers.se

Light exposure is a potentially powerful stress factor during in vivo optical microscopy studies. In yeast, the general transcription factor Msn2p translocates from the cytoplasm to the nucleus in response to illumination. However, previous time-lapse fluorescence microscopy studies of Msn2p have utilized a variety of discrete exposure settings, which makes it difficult to correlate stress levels and illumination parameters. We here investigate how continuous illumination with blue light, corresponding to GFP excitation wavelengths, affects the localization pattern of Msn2p-GFP in budding yeast. The localization pattern was analyzed using a novel approach that combines wavelet decomposition and change point analysis. It was found that the Msn2p nucleocytoplasmic localization trajectories for individual cells exhibit up to three distinct and successive states; i) Msn2p localizes to the cytoplasm; ii) Msn2p rapidly shuttles between the cytoplasm and the nucleus; iii) Msn2p localizes to the nucleus. Many cells pass through all states consecutively at high light intensities, while at lower light intensities most cells only reach states i) or ii). This behaviour strongly indicates that continuous light exposure gradually increases the stress level over time, presumably through continuous accumulation of toxic photoproducts, thereby forcing the cell through a bistable region corresponding to nucleocytoplasmic oscillations. We also show that the localization patterns are dependent on protein kinase A (PKA) activity, i.e. yeast cells with constantly low PKA activity showed a stronger stress response. In particular, the nucleocytoplasmic oscillation frequency was found to be significantly higher for cells with low PKA activity for all light intensities.

PMID: 21167216 [PubMed - indexed for MEDLINE]

395. J Korean Med Sci. 2010 Dec;25(12):1722-6. Epub 2010 Nov 24.

In vitro evaluation of antibiotic lock technique for the treatment of Candida albicans, C. glabrata, and C. tropicalis biofilms.

Ko KS, Lee JY, Song JH, Peck KR.

Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Korea.

Candidaemia associated with intravascular catheter-associated infections is of great concern due to the resulting high morbidity and mortality. The antibiotic lock technique (ALT) was previously introduced to treat catheter-associated bacterial infections without removal of catheter. So far, the efficacy of ALT against Candida infections has not been rigorously evaluated. We investigated in vitro activity of ALT against Candida biofilms formed by C. albicans, C. glabrata, and C. tropicalis using five antifungal agents (caspofungin, amphotericin B, itraconazole, fluconazole, and voriconazole). The effectiveness of antifungal treatment was assayed by monitoring viable cell counts after exposure to 1 mg/mL solutions of each antibiotic. Fluconazole, itraconazole, and voriconazole eliminated detectable viability in the biofilms of all Candida species within 7, 10, and 14 days, respectively, while caspofungin and amphotericin B did not completely kill fungi in C. albicans and C. glabrata biofilms within 14 days. For C. tropicalis biofilm, caspofungin lock achieved eradication more rapidly than amphotericin B and three azoles. Our study suggests that azoles may be useful ALT agents in the treatment of catheter-related candidemia.

PMCID: PMC2995224 PMID: 21165285 [PubMed - indexed for MEDLINE]

396. Rev Mal Respir. 2010 Dec;27(10):1195-220. Epub 2010 Oct 30.

[Allergic diseases in children and farming environment].

[Article in French]

Hulin M, Annesi-Maesano I.

Inserm, U707, EPAR, 75012 Paris, France. hulin@u707.jussieu.fr

INTRODUCTION: Children living in rural areas had lower prevalence of allergies than children from cities, in relation to farming exposure.
STATE OF ART: Exposure to farm animals and consumption of raw milk appear to play an important role in the protection afforded by the agricultural environment, and this at different stages of child development. The mechanisms involved in these effects are still controversial, and recent publications cast doubt on the role of endotoxins initially suggested. It seems that exposure to indoor air pollution, characterized by excessive biocontaminants (mold, allergens…) is a key element in the development of allergic diseases.
PERSPECTIVES: The establishment of cohort studies, a better assessment of exposure to pollution at home but also in farm buildings and the study of gene-environment interactions should improve the knowledge on the protective effect towards allergy of farming environment.
CONCLUSIONS: The farming environment, very specific, could be an important model for better understanding the mechanisms involved in allergic and respiratory diseases. In addition, urbanization and thus reduction of the rural environment, may well explain the increased prevalence of allergies observed in the past 50 years.

PMID: 21163397 [PubMed - indexed for MEDLINE]

397. Cancer Genomics Proteomics. 2010 Nov-Dec;7(6):337-46.

Effects of artesunate on cytokinesis and G₂/M cell cycle progression of tumour cells and budding yeast.

Steinbrück L, Pereira G, Efferth T.

Institute of Pharmacy and Biochemistry, University of Mainz, Staudinger Weg 5, Mainz, Germany.

Artesunate, a semi-synthetic derivative of artemisinin, is an effective and safe anti-malaria drug, which also exhibits activity towards cancer cells. The present investigation studied the effect of artesunate on the mitosis of cancer and yeast cells by fluorescence microscopy and mRNA microarrays with a focus on the mitotic spindle checkpoint. The cytotoxicity of artesunate towards seven cell lines from six different cancer types was determined using the XTT assay. Furthermore, the cell cycle distribution of artesunate-treated cells was investigated by flow cytometry and immunofluorescence. To elucidate the genes mediating the effect of artesunate in the mitotic spindle checkpoint, knockout mutants of Saccharomyces cerevisiae were generated, since yeast knockouts are easier to generate than knockout strains of mammalian cells. Four out of the seven tested cell lines showed a G₂/M arrest upon artesunate exposure. Cells residing in the G₂/M arrest revealed multiple centrosomes, small multiple spindles and multi-nucleated cells, suggesting a defect in cytokinesis. The mitotic spindle checkpoint genes bub1, bub2, bub3, mad1, mad2 and mad3 were individually deleted and the sensitivity of these mutants towards artesunate was determined by monitoring the cell growth. The Δbub3 and Δmad3 mutants showed an increased sensitivity and the Δmad2 mutant a slightly decreased sensitivity to artesunate in comparison to the respective wild type. Bub3, Mad3 and Mad2 are the main regulators of the mitotic spindle checkpoint, suggesting that artesunate may interfere with this control mechanism.

PMID: 21156967 [PubMed - indexed for MEDLINE]

398. Bioelectromagnetics. 2011 Jan;32(1):73-8. doi: 10.1002/bem.20619. Epub 2010 Nov 17.

Extremely low frequency magnetic field effects on metabolite of Aspergillus niger.

Gao M, Zhang J, Feng H.

Yangtze University, Jingzhou, Hubei, China. mxgao0398@163.com

The effect of the extremely low frequency (ELF) magnetic field on citric acid and cellulase production by Aspergillus niger using liquid Charles culture medium was studied during shake flask culture. The cellular suspension was exposed to a magnetic field (t = 4 h, B = 1 mT, and f = 50 Hz). The dependence of yield of citric acid and activity of cellulase on time of exposure and on the value of the magnetic field induction B was measured. Both yield of citric acid and activity of cellulase increased with increasing exposure time and/or induction B, but the quantity of the effect was dependent on the chemical structure of metabolites. The metabolism of citric acid was more sensitive to the magnetic field than that of cellulase. From the measurement of the metabolism dynamics we concluded that the increase in the citric acid and activity of cellulase started immediately after the magnetic field was switched on.

PMID: 21154638 [PubMed - indexed for MEDLINE]

399. Plant Signal Behav. 2010 Dec;5(12):1638-41. Epub 2010 Dec 1.

A suggested model for potato MIVOISAP involving functions of central carbohydrate and amino acid metabolism, as well as actin cytoskeleton and endocytosis.

Ezquer I, Li J, Ovecka M, Baroja-Fernández E, Muñoz FJ, Montero M, Díaz de Cerio J, Hidalgo M, Sesma MT, Bahaji A, Etxeberria E, Pozueta-Romero J.

Instituto de Agrobiotecnología (CSIC/UPNA/Gobierno de Navarra), Mutiloako etorbidea z/g, Nafarroa, Spain.

We have recently found that microbial species ranging from Gram-negative and Gram-positive bacteria to different fungi emit volatiles that strongly promote starch accumulation in leaves of both mono- and di-cotyledonous plants. Transcriptome and enzyme activity analyses of potato leaves exposed to volatiles emitted by Alternaria alternata revealed that starch over-accumulation was accompanied by enhanced 3-phosphoglycerate to Pi ratio, and changes in functions involved in both central carbohydrate and amino acid metabolism. Exposure to microbial volatiles also promoted changes in the expression of genes that code for enzymes involved in endocytic uptake and traffic of solutes. With the overall data we propose a metabolic model wherein important determinants of accumulation of exceptionally high levels of starch include (a) upregulation of ADPglucose-producing SuSy, starch synthase III and IV, proteins involved in the endocytic uptake and traffic of sucrose, (b) down-regulation of acid invertase, starch breakdown enzymes and proteins involved in internal amino acid provision, and (c) 3-phosphoglycerate-mediated allosteric activation of ADPglucose pyrophosphorylase.

PMCID: PMC3115121 PMID: 21150257 [PubMed - indexed for MEDLINE]

400. Am J Public Health. 2011 Jan;101(1):55-62.

The Breathe-Easy Home: the impact of asthma-friendly home construction on clinical outcomes and trigger exposure.

Takaro TK, Krieger J, Song L, Sharify D, Beaudet N.

Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, Canada. ttakaro@sfu.ca

OBJECTIVES: We examined the asthma-control benefit of moving into an asthma-friendly Breathe-Easy home (BEH).
METHODS: We used a quasi-experimental design to compare the asthma outcomes of 2 groups of low-income children and adolescents with asthma: 34 participants who moved into a BEH, and a local matched cohort of 68 participants who had received a previous asthma-control intervention. Both groups received in-home asthma education. BEHs were constructed with moisture-reduction features, enhanced ventilation systems, and materials that minimized dust and off-gassing.
RESULTS: BEH residents' asthma-symptom-free days increased from a mean of 8.6 per 2 weeks in their old home to 12.4 after 1 year in the BEH. The proportion of BEH residents with an urgent asthma-related clinical visit in the previous 3 months decreased from 62% to 21%. BEH caretakers' quality of life increased significantly. The BEH group improved more than did the comparison group, but most differences in improvements were not significant. Exposures to mold, rodents, and moisture were reduced significantly in BEHs.
CONCLUSIONS: Children and adolescents with asthma who moved into an asthma-friendly home experienced large decreases in asthma morbidity and trigger exposure.

PMID: 21148715 [PubMed - indexed for MEDLINE]

401. J Toxicol Sci. 2010 Dec;35(6):929-33.

Air purifiers that diffuse reactive oxygen species potentially cause DNA damage in the lung.

Kawamoto K, Sato I, Yoshida M, Tsuda S.

Several appliance manufacturers have recently released new type air purifiers that can disinfect bacteria, fungi and viruses by diffusing reactive oxygen species (ROS) into the air. In this study, mice were exposed to the outlet air from each of 3 air purifiers from different manufacturers (A, B, C), and the lung was examined for DNA damage, lipid peroxidation and histopathology to confirm the safety of these air purifiers. Neither abnormal behavior during exposure nor gross abnormality at necropsy was observed. No histopathological changes were also observed in the lung. However, significant increase of DNA damage was detected by the comet assay in the lung immediately after the direct exposure for 48 hr to models A and B, and for 16 hr to model B. As for model B, DNA migration was also increased by 2 hr exposure in a 1 m(3) plastic chamber but not by 48 hr exposure in a room (12.6 m(3)). Model C did not cause DNA damage. Lipid peroxidation and 8-hydroxy deoxyguanosine (8-OH-dG) was not increased under the conditions DNA damage was detected by the comet assay. The present results revealed that some models of air purifiers that diffuse ROS potentially cause DNA damage in the lung although the mechanism was left unsolved.

PMID: 21139343 [PubMed - indexed for MEDLINE]

402. Biol Pharm Bull. 2010;33(12):2008-12.

The effects of serine palmitoyltransferase inhibitor, ISP-I, on UV-induced barrier disruption in the stratum corneum.

Mizukoshi K, Oshima H, Matsumoto K, Hirose R, Fujita T.

POLA Chemical Industries, Inc., Yokohama, Japan. k-mizukoshi@pola.co.jp

We examined the effects of ISP-I (myriocin, thermozymocidin) - a potent inhibitor of serine palmitoyltransferase (SPT) which is involved in the ceramide synthetic pathway-on skin barrier function in post-UVB-irradiated hairless mouse skin. Disruption of the skin barrier function after UVB irradiation as represented by the increase in transepidermal water loss (TEWL) was significantly suppressed with ISP-I treatment. In the ISP-I-treated skin, the peak of cell proliferation was observed 24 h earlier than in vehicle-treated skin. In addition, the number of apoptotic cells in ISP-I-treated skin showed a sharp decrease at 48 and 72 h post-irradiation. The number of stratum corneum cell layers was increased in ISP-I-treated skin at 72 h after UVB irradiation; at this time, TEWL in ISP-I-treated skin was lower than that in the vehicle-treated skin. We suggest ISP-I treatment altered cell proliferation and apoptosis after UVB exposure by modulating ceramide synthesis in epidermal cells, resulting in an increase of stratum corneum layers which lessened the effects of irradiation-induced barrier disruption.

PMID: 21139242 [PubMed - indexed for MEDLINE]

403. Int J Radiat Biol. 2011 Feb;87(2):222-30. Epub 2010 Dec 6.

Lethal and mutagenic interactions between γ-rays, cisplatin and etoposide at the cellular and molecular levels.

Lillo O, Bracesco N, Nunes E.

Department of Biophysics, Laboratory of Radiobiology, Faculty of Medicine, Universidad de la República, Montevideo, Uruguay. lucefa@adinet.com.uy

PURPOSE: We analysed the lethal and mutagenic interactions between γ-rays, cisplatin (Pt) and etoposide (E), three agents used in tumour chemoradiotherapy. Corresponding results at cellular and molecular levels could provide additional elements on involved mechanisms and, on antitumour activity and toxicity in combined cancer treatments. MATERIALS AND METHODS: The yeast Saccharomyces cerevisiae SC7K(lys2-3) (auxotrophic for lysine) was used as eukaryotic model. Exponential growing cells were exposed to the mentioned agents, as single and combined treatments. Lethal and mutation interaction equations were determined as a function of doses according to quantitative models. DNA double-strand breaks were evaluated immediately after treatments, through pulsed-field electrophoresis and laser densitometry.
RESULTS: All three agents induced significant mutant frequency. The γ +Pt + E combination determined maximal lethal and mutagenic synergism, followed by γ + Pt and γ + E combinations. Meanwhile, Pt + E combination showed lethal additivity and very low mutagenic synergism. Pt + E double combination determined moderate DNA degradation. DNA degradation after γ-exposure, was similar to that of γ + Pt, γ + E and γ + Pt + E combinations.
CONCLUSIONS: Synergistic lethal and mutagenic interactions indicate crosstalk between non-homologous end joining, homologous recombination and postreplicative repair pathways. Pt + E additivity indicate independence of involved repair pathways. Furthermore, the quantification of interactive events may be an additional suitable tool in tumour therapy planning.

PMID: 21133647 [PubMed - indexed for MEDLINE]

404. BMC Mol Biol. 2010 Dec 3;11:92.

Rrd1 isomerizes RNA polymerase II in response to rapamycin.

Jouvet N, Poschmann J, Douville J, Bulet L, Ramotar D.

Maisonneuve-Rosemont Hospital, Research Center, Department of Immunology and Oncology, University of Montreal, 5415 de l'Assomption, Montreal, Quebec, Canada.

BACKGROUND: In Saccharomyces cerevisiae, the immunosuppressant rapamycin engenders a profound modification in the transcriptional profile leading to growth arrest. Mutants devoid of Rrd1, a protein possessing in vitro peptidyl prolyl cis/trans isomerase activity, display striking resistance to the drug, although how Rrd1 activity is linked to the biological responses has not been elucidated.
RESULTS: We now provide evidence that Rrd1 is associated with the chromatin and it interacts with RNA polymerase II. Circular dichroism revealed that Rrd1 mediates structural changes onto the C-terminal domain (CTD) of the large subunit of RNA polymerase II (Rpb1) in response to rapamycin, although this appears to be independent of the overall phosphorylation status of the CTD. In vitro experiments, showed that recombinant Rrd1 directly isomerizes purified GST-CTD and that it releases RNA polymerase II from the chromatin. Consistent with this, we demonstrated that Rrd1 is required to alter RNA polymerase II occupancy on rapamycin responsive genes.
CONCLUSION: We propose as a mechanism, that upon rapamycin exposure Rrd1 isomerizes Rpb1 to promote its dissociation from the chromatin in order to modulate transcription.

PMCID: PMC3019149 PMID: 21129186 [PubMed - indexed for MEDLINE]

405. BMC Med Educ. 2010 Dec 2;10:89.

Health risks encountered by Dutch medical students during an elective in the tropics and the quality and comprehensiveness of pre-and post-travel care.

Sharafeldin E, Soonawala D, Vandenbroucke JP, Hack E, Visser LG.

Department of Infectious Diseases, Leiden University Medical Center, Leiden, Netherlands.

BACKGROUND: Clinical and research electives abroad offer medical students many unique experiences. However, participating in an unfamiliar health-care setting combined with limited medical experience may place students at risk of illness. To improve pre-and post-travel care, we assessed the health risks and the quality and comprehensiveness of pre-and post-travel care in a cohort of Dutch medical students returning form an elective abroad.
METHODS: All medical students who had performed an elective in the tropics between July 2006 and December 2008 were sent an informative email asking them to complete a web-based questionnaire.
RESULTS: 180 of 242 (74%) students completed the questionnaire. Regarding the risk of bloodborne viral infection: 67% of all students and 32% of junior students engaged in procedures that constitute a risk of exposure to bloodborne viral infection, often in countries with high HIV prevalence rates. None of nine students who experienced possible or certain mucosal or percutaneous exposure to potentially infectious body fluids reported the exposure at the time it occurred and none used PEP. Regarding other health risks: 8 of 40 (20%) students stopped using mefloquine due to adverse effects. This left a sizeable proportion unprotected in countries that are hyperendemic for malaria. Post-travel screening for schistosomiasis, tuberculosis (tuberculin skin test) and carriage of methicillin-resistant Staphylococcus aureus (MRSA) encompassed approximately half of all students who should have been screened.
CONCLUSIONS: Based on the results of this study we have adopted an integral set of measures to reduce the health risks associated with an elective abroad. The pre and post-travel consult has been centralized and standardized as well as the distribution of PEP. In addition we have developed a mandatory module on Global Health for all medical students planning an elective abroad.

PMCID: PMC3014955 PMID: 21126347 [PubMed - indexed for MEDLINE]

406. BMC Ecol. 2010 Dec 1;10:24.

Cytochrome P450 diversity and induction by gorgonian allelochemicals in the marine gastropod Cyphoma gibbosum.

Whalen KE, Starczak VR, Nelson DR, Goldstone JV, Hahn ME.

Biology Department, Woods Hole Oceanographic Institution, Woods Hole, MA 02543, USA.

BACKGROUND: Intense consumer pressure strongly affects the structural organization and function of marine ecosystems, while also having a profound effect on the phenotype of both predator and prey. Allelochemicals produced by prey often render their tissues unpalatable or toxic to a majority of potential consumers, yet some marine consumers have evolved resistance to host chemical defenses. A key challenge facing marine ecologists seeking to explain the vast differences in consumer tolerance of dietary allelochemicals is understanding the biochemical and molecular mechanisms underlying diet choice. The ability of marine consumers to tolerate toxin-laden prey may involve the cooperative action of biotransformation enzymes, including the inducible cytochrome P450s (CYPs), which have received little attention in marine invertebrates despite the importance of allelochemicals in their evolution.
RESULTS: Here, we investigated the diversity, transcriptional response, and enzymatic activity of CYPs possibly involved in allelochemical detoxification in the generalist gastropod Cyphoma gibbosum, which feeds exclusively on chemically defended gorgonians. Twelve new genes in CYP family 4 were identified from the digestive gland of C. gibbosum. Laboratory-based feeding studies demonstrated a 2.7- to 5.1-fold induction of Cyphoma CYP4BK and CYP4BL transcripts following dietary exposure to the gorgonian Plexaura homomalla, which contains high concentrations of anti-predatory prostaglandins. Phylogenetic analysis revealed that C. gibbosum CYP4BK and CYP4BL were most closely related to vertebrate CYP4A and CYP4F, which metabolize pathophysiologically important fatty acids, including prostaglandins. Experiments involving heterologous expression of selected allelochemically-responsive C. gibbosum CYP4s indicated a possible role of one or more CYP4BL forms in eicosanoid metabolism. Sequence analysis further demonstrated that Cyphoma CYP4BK/4BL and vertebrate CYP4A/4F forms share identical amino acid residues at key positions within fatty acid substrate recognition sites.
CONCLUSIONS: These results demonstrate differential regulation of CYP transcripts in a marine consumer feeding on an allelochemical-rich diet, and significantly advance our understanding of both the adaptive molecular mechanisms that marine consumers use to cope with environmental chemical pressures and the evolutionary history of allelochemical-metabolizing enzymes in the CYP superfamily.

PMCID: PMC3022543 PMID: 21122142 [PubMed - indexed for MEDLINE]

407. Philos Trans R Soc Lond B Biol Sci. 2011 Jan 12;366(1561):17-27.

TOR and ageing: a complex pathway for a complex process.

McCormick MA, Tsai SY, Kennedy BK.

Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.

Studies in invertebrate model organisms have led to a wealth of knowledge concerning the ageing process. But which of these discoveries will apply to ageing in humans? Recently, an assessment of the degree of conservation of ageing pathways between two of the leading invertebrate model organisms, Saccharomyces cerevisiae and Caenorhabditis elegans, was completed. The results (i) quantitatively indicated that pathways were conserved between evolutionarily disparate invertebrate species and (ii) emphasized the importance of the TOR kinase pathway in ageing. With recent findings that deletion of the mTOR substrate S6K1 or exposure of mice to the mTOR inhibitor rapamycin result in lifespan extension, mTOR signalling has become a major focus of ageing research. Here, we address downstream targets of mTOR signalling and their possible links to ageing. We also briefly cover other ageing genes identified by comparing worms and yeast, addressing the likelihood that their mammalian counterparts will affect longevity.

PMCID: PMC3001303 [Available on 2012/1/12] PMID: 21115526 [PubMed - indexed for MEDLINE]

408. Chemosphere. 2011 Feb;82(7):963-9. Epub 2010 Nov 23.

Physiological effects of arsenic in the lichen Xanthoria parietina (L.) Th. Fr.

Pisani T, Munzi S, Paoli L, Bačkor M, Loppi S.

Department of Environmental Science "G. Sarfatti", University of Siena, Italy.

The aim of this study was to test in a short term laboratory experiment the accumulation and physiological effects of As in the epiphytic lichen Xanthoria parietina. Arsenic content in treated samples increased progressively with increasing concentration in treatment solutions. Treatment of X. parietina thalli with 0.1, 1, 10 ppm As solutions caused significant decrease of viability, measured as intensity of respiratory activity, and damages to cell membranes, assessed by increase of electric conductivity of rinsing water and lipid peroxidation products. Soluble proteins content decreased and H₂O₂ content increased already at the lowest As concentration tested (0.01 ppm). Photosynthetic efficiency, measured in terms of F(V)/F(M) ratio, decreased significantly only at the highest As concentration (10 ppm). It was concluded that As exposure causes physiological stress both on the mycobiont and the photobiont and that cell membrane damage, expressed in terms of electric conductivity of rinsing water, is the parameter most affected by As treatment.

PMID: 21106219 [PubMed - indexed for MEDLINE]

409. Clin Experiment Ophthalmol. 2011 Mar;39(2):156-63. doi: 10.1111/j.1442-9071.2010.02471.x.

Efficacy and safety assessment of a novel ultraviolet C device for treating corneal bacterial infections.

Dean SJ, Petty A, Swift S, McGhee JJ, Sharma A, Shah S, Craig JP.

University of Auckland, Auckland, New Zealand. simondean@xtra.co.nz

BACKGROUND: A prototype solid-state Ultraviolet-C (UVC) LED device may be useful in the treatment of corneal microbial infections, as UVC is commonly used for eradicating bacteria, fungi and viruses in other settings. This study assessed the efficacy of 265 nm UVC from this LED, on four different bacterial strains, and investigated the consequences of corresponding exposures on human corneal epithelial cells in vitro.
METHODS: Agar plate lawns of Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Streptococcus pyogenes were exposed to a 4.5 mm diameter 265 nm UVC beam at a fixed intensity and distance, for 30, 5, 4, 2 and 1 seconds. Growth inhibition was assessed with a BioRad Gel imager, and the diameter of lucent areas of bacterial inhibition recorded. Human corneal epithelial cells cultured on glass cover-slips were exposed to corresponding doses of UVC from the same device. Live/dead staining was performed and the results quantified.
RESULTS: There was 100% inhibition of growth for all bacteria tested, at all exposure times. A 30-second exposure of human corneal epithelium to UVC gave no statistically significant decrease (P = 0.877) in the ratio of live to dead cells when compared to control cultures.
CONCLUSION: The results confirmed that a 1 second exposure to germicidal UVC from this LED source was sufficient to inhibit microbial proliferation in the four bacterial strains tested in vitro. The literature suggests UVC at this dose could potentially be beneficial in treating corneal surface infections, without causing significant adverse effects, supported by our findings in human corneal epithelium exposed to UVC.

PMID: 21105972 [PubMed - indexed for MEDLINE]

410. Scand J Work Environ Health. 2011 Jul;37(4):332-40. doi: 10.5271/sjweh.3135. Epub 2010 Nov 23.

Moulds in floor dust - a particular problem in mechanically ventilated rooms? A study of adolescent schoolboys under the Danish moulds in buildings program.

Meyer HW, Suadicani P, Nielsen PA, Sigsgaard T, Gyntelberg F.

Department of Occupational and Environmental Medicine, Bispebjerg University Hospital, 2400 Copenhagen NV, Denmark. hmey0004@bbh.regionh.dk

OBJECTIVE: To test the hypothesis that the association between levels of mould in floor dust and prevalence of potentially building-related symptoms may depend on the type of ventilation.
METHODS: This stratified cross-sectional study is part of the Danish moulds in buildings program (DAMIB), including 503 adolescent schoolboys aged 13-17 years at 15 schools. Besides assessing symptom prevalences in questionnaires, we measured numerous potential risk factors in the school buildings.
RESULTS: Stratifying on type of ventilation (natural, exhaust only, or full mechanical ventilation system), the negative effect of high levels of mould in floor dust was more pronounced in rooms with mechanical ventilation system. With a variable combining high level of moulds in floor dust with type of ventilation in the classroom, a significantly increased risk was found for all symptoms in the mechanically ventilated classrooms with high mould concentrations. In multiple logistic regression models, significant odds ratios (OR) ranged from 3.9 [95% confidence interval (95% CI) 1.5-10.1] (nasal congestion) to 17.0 (95% CI 2.1-138) (dizziness).
CONCLUSIONS: The combined effect of moulds in dust and ventilation form might be a result of the higher air flow keeping the dust in the breathing zone for a longer time, thereby increasing the exposure for the occupants of the classrooms. It is important in future indoor air research also to focus on the combination effects of risk factors, including the type of ventilation.

PMID: 21103804 [PubMed - indexed for MEDLINE]

411. J Gen Appl Microbiol. 2010 Oct;56(5):359-68.

Cadmium biosorption by yeast, Candida tropicalis CBL-1, isolated from industrial wastewater.

Rehman A, Sohail Anjum M, Hasnain S.

Department of Microbiology and Molecular Genetics, University of the Punjab, Lahore, Pakistan. rehman@mmg.pu.edu.pk

The present study is aimed at assessing the ability of metal-resistant yeast, Candida tropicalis CBL-1, to uptake metal from liquid medium. The minimum inhibitory concentration of Cd(II) against Candida tropicalis CBL-1 was 2,800 mg/L. The yeast could also tolerate Zn(II) (3,100 mg/L), Hg(II) (2,400 mg/L), Ni(II) (2,200 mg/L), Cr(VI) (2,000 mg/L), Pb(II) (1,100 mg/L), and Cu(II) (2,200 mg/L). The yeast isolate showed typical growth curves but lag and log phases extended in the presence of cadmium. The yeast isolate showed optimum growth at 30ºC and pH 7. The metal processing ability of the isolate was determined in a medium containing 100 mg/L of Cd(II). Candida tropicalis CBL-1, could reduce Cd(II) 59%, 64% and 70% from the medium after 48, 96 and 144 h, respectively. C. tropicalis CBL-1 was also able to remove Cd(II) 46% and 60% from the wastewater after 6 and 12 days, respectively. Cd produced an increase in glutathione and non-protein thiols level by 37% (17.50±0.8-24.0±1.2) and 18% (3.30±0.7- 3.90±0.8) at 100 mg/L concentration, respectively. Metal tolerance and accumulation together with changes in the GSH status and non-protein thiols under Cd exposure were studied in C. tropicalis.

PMID: 21099132 [PubMed - indexed for MEDLINE]

412. Occup Environ Med. 2011 Jul;68(7):467-73. Epub 2010 Nov 23.

Does the use of biofuels affect respiratory health among male Danish energy plant workers?

Schlünssen V, Madsen AM, Skov S, Sigsgaard T.

Department of Environmental and Occupational Medicine, School of Public Health, Aarhus University, Bartholins Allé 2, Bg 1260, 8000 Aarhus C, Denmark. vs@mil.au.dk

OBJECTIVES: To study asthma, respiratory symptoms and lung function among energy plant employees working with woodchip, straw or conventional fuel.
METHODS: Respiratory symptoms in 138 woodchip workers, 94 straw workers and 107 control workers from 85 heating- or combined heating and power plants were collected by questionnaire. Spirometry, metacholine provocation tests and skin prick tests were performed on 310 workers. The work area concentrations of 'total dust' (n=181), airborne endotoxin (n=179), cultivable Aspergillus fumigatus (n=373) and cultivable fungi (n=406) were measured at each plant. Personal exposure was calculated from the time spent on different tasks and average work area exposures.
RESULTS: Median (range) average personal exposures in biofuel plants were 0.05 (0 to 0.33) mg/m³ for 'total' dust and 3.5 (0 to 294) endotoxin units/m³ for endotoxin. Fungi were cultivated from filters (straw plants) or slit samplers (woodchip plants); the average personal exposures were 5.230×10³ (118 to 1.85×10⁴) and 1.03×10³ (364 to 5.01×10³) colony-forming units/m³ respectively. Exposure levels were increased in biofuel plants compared with conventional plants. The prevalence of respiratory symptoms among conventional plant and biofuel plant workers was comparable, except for asthma symptoms among non-smokers, which were higher among straw workers compared with controls (9.4 vs 0%, p<0.05). A trend for increasing respiratory symptoms with increasing endotoxin exposure was seen with ORs between 3.1 (1.1 to 8.8) (work-related nose symptoms) and 8.1 (1.5 to 44.4) (asthma symptoms) for the most exposed group. Associations between fungal exposure and respiratory symptoms were less clear but suggested cultivable fungi to be associated with asthma symptoms and work-related respiratory symptoms. No associations were seen between lung function and the level of endotoxin or fungal exposure.
CONCLUSIONS: Working with biofuel at an energy plant does not generally enhance the prevalence of respiratory symptoms. However, the exposure level to micro-organisms has an impact on the occurrence of respiratory symptoms among biofuel workers.

PMID: 21098831 [PubMed - indexed for MEDLINE]

413. RNA. 2011 Jan;17(1):120-33. Epub 2010 Nov 22.

Cellular stress induces cytoplasmic RNA granules in fission yeast.

Nilsson D, Sunnerhagen P.

Department of Cell and Molecular Biology, Lundberg Laboratory, University of Gothenburg, S-405 30 Göteborg, Sweden.

Severe stress causes plant and animal cells to form large cytoplasmic granules containing RNA and proteins. Here, we demonstrate the existence of stress-induced cytoplasmic RNA granules in Schizosaccharomyces pombe. Homologs to several known protein components of mammalian processing bodies and stress granules are found in fission yeast RNA granules. In contrast to mammalian cells, poly(A)-binding protein (Pabp) colocalizes in stress-induced granules with decapping protein. After glucose deprivation, protein kinase A (PKA) is required for accumulation of Pabp-positive granules and translational down-regulation. This is the first demonstration of a role for PKA in RNA granule formation. In mammals, the translation initiation protein eIF2α is a key regulator of formation of granules containing poly(A)-binding protein. In S. pombe, nonphosphorylatable eIF2α does not block but delays granule formation and subsequent clearance after exposure to hyperosmosis. At least two separate pathways in S. pombe appear to regulate stress-induced granules: pka1 mutants are fully proficient to form granules after hyperosmotic shock; conversely, eIF2α does not affect granule formation in glucose starvation. Further, we demonstrate a Pka1-dependent link between calcium perturbation and RNA granules, which has not been described earlier in any organism.

PMCID: PMC3004053 PMID: 21098141 [PubMed - indexed for MEDLINE]

414. Appl Environ Microbiol. 2011 Jan;77(2):416-26. Epub 2010 Nov 19.

Mechanisms of contact-mediated killing of yeast cells on dry metallic copper surfaces.

Quaranta D, Krans T, Espírito Santo C, Elowsky CG, Domaille DW, Chang CJ, Grass G.

School of Biological Sciences, University of Nebraska, Lincoln, NE 68588, USA.

Surfaces made of copper or its alloys have strong antimicrobial properties against a wide variety of microorganisms. However, the molecular mode of action responsible for the antimicrobial efficacy of metallic copper is not known. Here, we show that dry copper surfaces inactivate Candida albicans and Saccharomyces cerevisiae within minutes in a process called contact-mediated killing. Cellular copper ion homeostasis systems influenced the kinetics of contact-mediated killing in both organisms. Deregulated copper ion uptake through a hyperactive S. cerevisiae Ctr1p (ScCtr1p) copper uptake transporter in Saccharomyces resulted in faster inactivation of mutant cells than of wild-type cells. Similarly, lack of the C. albicans Crp1p (CaCrp1p) copper-efflux P-type ATPase or the metallothionein CaCup1p caused more-rapid killing of Candida mutant cells than of wild-type cells. Candida and Saccharomyces took up large quantities of copper ions as soon as they were in contact with copper surfaces, as indicated by inductively coupled plasma mass spectroscopy (ICP-MS) analysis and by the intracellular copper ion-reporting dye coppersensor-1. Exposure to metallic copper did not cause lethality through genotoxicity, deleterious action on a cell's genetic material, as indicated by a mutation assay with Saccharomyces. Instead, toxicity mediated by metallic copper surfaces targeted membranes in both yeast species. With the use of Live/Dead staining, onset of rapid and extensive cytoplasmic membrane damage was observed in cells from copper surfaces. Fluorescence microscopy using the indicator dye DiSBaC(2)(3) indicated that cell membranes were depolarized. Also, during contact-mediated killing, vacuoles first became enlarged and then disappeared from the cells. Lastly, in metallic copper-stressed yeasts, oxidative stress in the cytoplasm and in mitochondria was elevated.

PMCID: PMC3020553 PMID: 21097600 [PubMed - indexed for MEDLINE]

415. Biochem Biophys Res Commun. 2011 Jan 7;404(1):109-14. Epub 2010 Nov 21.

Cyclic phosphatidic acid influences the expression and regulation of cyclic nucleotide phosphodiesterase 3B and lipolysis in 3T3-L1 cells.

Tsukahara T, Hanazawa S, Murakami-Murofushi K.

Department of Integrative Physiology and Bio-System Control, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan. ttamotsu@shinshu-u.ac.jp

Cyclic phosphatidic acid (cPA) is found in cells from slime mold to humans and has a largely unknown function. We previously reported that cPA significantly inhibited the lipid accumulation in 3T3-L1 adipocytes through inhibition of PPARγ activation. We find here that cPA reduced intracellular triglyceride levels and inhibited the phosphodiesterase 3B (PDE3B) expression in 3T3-L1 adipocytes. PPARγ activation in adipogenesis that can be blocked by treatment with cPA then participates in adipocyte function through inhibition of PDE3B expression. We also found the intracellular cAMP levels in 3T3-L1 adipocytes increased after exposure to cPA. These findings contribute to the participation of cPA on the lipolytic activity in 3T3-L1 adipocytes. Our studies imply that cPA might be a therapeutic compound in the treatment of obesity and obesity-related diseases.

PMID: 21095182 [PubMed - indexed for MEDLINE]

416. J Ethnopharmacol. 2011 Jan 27;133(2):874-80. Epub 2010 Nov 18.

Induction of intercellular adhesion molecule-1 by water-soluble components of Hericium erinaceum in human monocytes.

Kim YS, Jeon JH, Im J, Kang SS, Choi JN, Ju HR, Yun CH, Son CG, Lee CH, Han SH.

Department of Oral Microbiology & Immunology, Dental Research Institute, and BK21 Program, School of Dentistry, Seoul National University, Seoul 110-749, Republic of Korea.

AIM OF THE STUDY: Hericium erinaceum is a medicinal mushroom that has been traditionally used in Asian countries for the treatment of cancers and infectious diseases. Although the immunomodulating activity of H. erinaceum is considered to be responsible for its medicinal activity, its action mechanisms are poorly understood. In the present study, we investigated the capability of water-extracted H. erinaceum (WEHE) to induce the expression of intercellular adhesion molecule-1 (ICAM-1), which regulates the migration of immune cells. MATERIALS AND METHODS: THP-1, a human monocytic cell-line, or human peripheral blood mononuclear cells (PBMC) were stimulated with WEHE (0-30 μg/mL) and subsequently analyzed using flow cytometry to examine the surface expression of ICAM-1 protein. Steady-state levels of ICAM-1 mRNA were estimated using real-time reverse transcription-polymerase chain reaction analysis. Electrophoretic mobility shift assay was conducted to examine transcription factors involved in ICAM-1 transcription.
RESULTS: WEHE induced ICAM-1 expression at both protein and mRNA levels in THP-1 cells in a dose- and time-dependent fashion. A similar pattern of ICAM-1 induction was also observed in CD14(+) monocytes in human PBMC that were stimulated with WEHE. The ICAM-1 expression on THP-1 cells stimulated with WEHE was suppressed by specific inhibitors for extracellular signal-regulated kinases (ERK) and reactive oxygen species (ROS). Additionally, exposure of THP-1 cells to WEHE increased the DNA binding activities of NF-κB, AP-1, SP-1 and STAT-1 transcription factors, all of which are known to be required for ICAM-1 gene expression.
CONCLUSIONS: These results suggest that WEHE induces ICAM-1 expression in human monocytes through ERK- and ROS-dependent signaling pathways, resulting in the subsequent activations of NF-κB, AP-1, SP-1, and STAT-1 transcription factors.

PMID: 21093573 [PubMed - indexed for MEDLINE]

417. Int J Food Microbiol. 2011 Jan 5;144(3):331-6. Epub 2010 Sep 29.

Effects of ozone exposure on the xerophilic fungus, Eurotium amstelodami IS-SAB-01, isolated from naan bread.

Antony-Babu S, Singleton I.

Institute for Research on Environment and Sustainability, School of Biology, Devonshire Building, Newcastle University, NE1 7RU, England, United Kingdom. Sanjay.Antony@nancy.inra.fr

Xerophilic moulds cause contamination and spoilage of low moisture foods. This study examined the effect of ozone fumigation on growth of a Eurotium species isolated from naan bread. Two ozone treatments were used - a low-level long-term exposure (0.4 μmol/mol for 21 days) and high-level short-term exposure (300 μmol/mol for 5 to 120 min). For the low level exposure the combination of different media sucrose concentrations (0, 5, 10 and 20% w/v) with ozone treatment was also assessed. The growth of the isolate was found to be sensitive to low-level ozone fumigation depending on the media sucrose concentration and duration of the exposure. Low-level ozone exposure significantly (p<0.05) reduced the number of asexual spores formed in media with no added sucrose, an effect not observed in media with higher sucrose levels. Electron microscope observations of colonies indicated that ozone exposed cultures produced lower numbers of cleistothecia. High-level ozone exposure for short durations reduced spore viability although 100% reduction in viability was achieved only after 120 min exposure. This work demonstrates that ozone may be used to reduce spore production in Eurotium but that the ozone effect can be mediated by sucrose levels in the growth medium.

PMID: 21093088 [PubMed - indexed for MEDLINE]

418. Mol Microbiol. 2010 Dec;78(5):1259-79. doi: 10.1111/j.1365-2958.2010.07403.x. Epub 2010 Oct 14.

Involvement of the Aspergillus nidulans protein kinase C with farnesol tolerance is related to the unfolded protein response.

Colabardini AC, De Castro PA, De Gouvêa PF, Savoldi M, Malavazi I, Goldman MH, Goldman GH.

Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, São Paulo, Brazil.

Previously, we demonstrated that the Aspergillus nidulans calC2 mutation in protein kinase C pkcA was able to confer tolerance to farnesol (FOH), an isoprenoid that has been shown to inhibit proliferation and induce apoptosis. Here, we investigate in more detail the role played by A. nidulans pkcA in FOH tolerance. We demonstrate that pkcA overexpression during FOH exposure causes increased cell death. FOH is also able to activate several markers of endoplasmic reticulum (ER) stress and the unfolded protein response (UPR). Our results suggest an intense cross-talk between PkcA and the UPR during FOH-induced cell death. Furthermore, the overexpression of pkcA increases both mRNA accumulation and metacaspases activity, and there is a genetic interaction between PkcA and the caspase-like protein CasA. Mutant analyses imply that MAP kinases are involved in the signal transduction in response to the effects caused by FOH.

PMID: 21091509 [PubMed - indexed for MEDLINE]

419. Braz J Med Biol Res. 2010 Dec;43(12):1203-14. Epub 2010 Nov 12.

Proteomic analysis of cytosolic proteins associated with petite mutations in Candida glabrata.

Loureiro Y Penha CV, Kubitschek PH, Larcher G, Perales J, Rodriguez León I, Lopes-Bezerra LM, Bouchara JP.

Instituto de Biologia Roberto Alcântara Gomes, Universidade do Estado do Rio de Janeiro, RJ, Brasil. carlapenha@hotmail.com

The incidence of superficial or deep-seated infections due to Candida glabrata has increased markedly, probably because of the low intrinsic susceptibility of this microorganism to azole antifungals and its relatively high propensity to acquire azole resistance. To determine changes in the C. glabrata proteome associated with petite mutations, cytosolic extracts from an azole-resistant petite mutant of C. glabrata induced by exposure to ethidium bromide, and from its azole-susceptible parent isolate were compared by two-dimensional polyacrylamide gel electrophoresis. Proteins of interest were identified by peptide mass fingerprinting or sequence tagging using a matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometer. Tryptic peptides from a total of 160 Coomassie-positive spots were analyzed for each strain. Sixty-five different proteins were identified in the cytosolic extracts of the parent strain and 58 in the petite mutant. Among the proteins identified, 10 were higher in the mutant strain, whereas 23 were lower compared to the parent strain. The results revealed a significant decrease in the enzymes associated with the metabolic rate of mutant cells such as aconitase, transaldolase, and pyruvate kinase, and changes in the levels of specific heat shock proteins. Moreover, transketolase, aconitase and catalase activity measurements decreased significantly in the ethidium bromide-induced petite mutant. These data may be useful for designing experiments to obtain a better understanding of the nuclear response to impairment of mitochondrial function associated with this mutation in C. glabrata.

PMID: 21085892 [PubMed - indexed for MEDLINE]

420. Rev Soc Bras Med Trop. 2010 Sep-Oct;43(5):584-7.

[Air contamination levels in operating rooms during surgery of total hip and total knee arthroplasty, hemiarthroplasty and osteosynthesis in the surgical center of a Brazilian hospital].

[Article in Portuguese]

Dolinger EJ, Brito DV, Souza GM, Melo GB, Gontijo Filho PP.

Curso de Graduação em Enfermagem, Faculdade de Medicina, Universidade Federal de Uberlândia, Uberlândia, MG. elias.brito@terra.com.br

INTRODUCTION: The air contamination levels during orthopedic surgeries were evaluated.
METHODS: The air of operating rooms (ORs) was examined through exposure to microbiological plates placed near the surgical table for an hour.
RESULTS: values above that recommended (369 CFU/m³) for conventional ORs and ORs with ultraclean air were determined. Contamination was predominantly by Staphylococcus sp (86.9%). In all surgeries a high number of people were present inside the ORs and the doors were opened frequently.
CONCLUSIONS: The contamination levels are above the values accepted by regulatory agencies, representing risk for patients.

PMID: 21085875 [PubMed - indexed for MEDLINE]

421. Postgrad Med. 2010 Nov;122(6):24-8.

Pneumocystis jiroveci dihydropteroate synthase gene mutations among colonized individuals and Pneumocystis pneumonia patients from Spain.

Friaza V, Morilla R, Respaldiza N, de la Horra C, Calderón EJ.

Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla, and CIBER de Epidemiología y Salud Pública, Seville, Spain.

Cotrimoxazole, an association of trimethoprim and sulfamethoxazole, and dapsone, are mainstays for the prophylaxis and treatment of Pneumocystis pneumonia (PcP). The inability to culture Pneumocystis prevents routine susceptibility testing and detection of drug resistance. Instead, molecular techniques have been used to detect Pneumocystis jiroveci dihydropteroate synthase (DHPS) mutations that cause sulfa resistance in other microorganisms. The most frequent DHPS mutations occur at nucleotide positions 165 and 171, which lead to an amino acid change at positions 55 and 57. Several studies suggest that these mutations are associated with the failure of chemoprophylaxis for PcP. The aim was to establish the frequency and characteristics of P jiroveci DHPS mutations among colonized individuals and PcP patients from Spain. A total of 50 colonized individuals and 25 PcP patients were studied. DHPS polymorphisms were identified by restriction fragment length polymorphism assay. The analysis provided a rate of 28% of DHPS gene mutations in our population, with the presence of all possible polymorphisms described. The presence of mutations was higher in PcP patients than in colonized subjects (40% vs 22%), probably because of the chemoprophylaxis used in PcP patients. The comparison between patients with and without DHPS mutations did not show statistical differences due to age, sex, steroid use, sulfa drug exposure, or smoking. A high rate of DHPS mutations in our area of Spain, not only confined to patients previously exposed to sulfa drugs, is shown in this study. As well as PcP patients, colonized individuals who harbor P jiroveci strains with DHPS mutations could play a major role in the transmission cycle of these mutations, representing a reservoir and source of infection for susceptible individuals. Further research is thus warranted to assess the true scope of the problem and to design rational preventive strategies.

PMID: 21084778 [PubMed - indexed for MEDLINE]

422. Microbiology. 2011 Mar;157(Pt 3):747-59. Epub 2010 Nov 16.

Exploring the bZIP transcription factor regulatory network in Neurospora crassa.

Tian C, Li J, Glass NL.

Department of Plant and Microbial Biology, University of California, Berkeley, CA 94720-3102, USA.

Transcription factors (TFs) are key nodes of regulatory networks in eukaryotic organisms, including filamentous fungi such as Neurospora crassa. The 178 predicted DNA-binding TFs in N. crassa are distributed primarily among six gene families, which represent an ancient expansion in filamentous ascomycete genomes; 98 TF genes show detectable expression levels during vegetative growth of N. crassa, including 35 that show a significant difference in expression level between hyphae at the periphery versus hyphae in the interior of a colony. Regulatory networks within a species genome include paralogous TFs and their respective target genes (TF regulon). To investigate TF network evolution in N. crassa, we focused on the basic leucine zipper (bZIP) TF family, which contains nine members. We performed baseline transcriptional profiling during vegetative growth of the wild-type and seven isogenic, viable bZIP deletion mutants. We further characterized the regulatory network of one member of the bZIP family, NCU03905. NCU03905 encodes an Ap1-like protein (NcAp-1), which is involved in resistance to multiple stress responses, including oxidative and heavy metal stress. Relocalization of NcAp-1 from the cytoplasm to the nucleus was associated with exposure to stress. A comparison of the NcAp-1 regulon with Ap1-like regulons in Saccharomyces cerevisiae, Schizosaccharomyces pombe, Candida albicans and Aspergillus fumigatus showed both conservation and divergence. These data indicate how N. crassa responds to stress and provide information on pathway evolution.

PMCID: PMC3081083 [Available on 2012/3/1] PMID: 21081763 [PubMed - indexed for MEDLINE]

423. Anal Bioanal Chem. 2011 Jan;399(2):915-25. Epub 2010 Nov 16.

LC-MS-MS determination of ibuprofen, 2-hydroxyibuprofen enantiomers, and carboxyibuprofen stereoisomers for application in biotransformation studies employing endophytic fungi.

Borges KB, de Oliveira AR, Barth T, Jabor VA, Pupo MT, Bonato PS.

Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, 14040-903, Brazil.

The purpose of this study was the development and validation of an LC-MS-MS method for simultaneous analysis of ibuprofen (IBP), 2-hydroxyibuprofen (2-OH-IBP) enantiomers, and carboxyibuprofen (COOH-IBP) stereoisomers in fungi culture medium, to investigate the ability of some endophytic fungi to biotransform the chiral drug IBP into its metabolites. Resolution of IBP and the stereoisomers of its main metabolites was achieved by use of a Chiralpak AS-H column (150 × 4.6 mm, 5 μm particle size), column temperature 8 °C, and the mobile phase hexane-isopropanol-trifluoroacetic acid (95: 5: 0.1, v/v) at a flow rate of 1.2 mL min(-1). Post-column infusion with 10 mmol L(-1) ammonium acetate in methanol at a flow rate of 0.3 mL min(-1) was performed to enhance MS detection (positive electrospray ionization). Liquid-liquid extraction was used for sample preparation with hexane-ethyl acetate (1:1, v/v) as extraction solvent. Linearity was obtained in the range 0.1-20 μg mL(-1) for IBP, 0.05-7.5 μg mL(-1) for each 2-OH-IBP enantiomer, and 0.025-5.0 μg mL(-1) for each COOH-IBP stereoisomer (r ≥ 0.99). The coefficients of variation and relative errors obtained in precision and accuracy studies (within-day and between-day) were below 15%. The stability studies showed that the samples were stable (p > 0.05) during freeze and thaw cycles, short-term exposure to room temperature, storage at -20 °C, and biotransformation conditions. Among the six fungi studied, only the strains Nigrospora sphaerica (SS67) and Chaetomium globosum (VR10) biotransformed IBP enantioselectively, with greater formation of the metabolite (+)-(S)-2-OH-IBP. Formation of the COOH-IBP stereoisomers, which involves hydroxylation at C3 and further oxidation to form the carboxyl group, was not observed.

PMID: 21079932 [PubMed - indexed for MEDLINE]

424. PLoS Pathog. 2010 Nov 4;6(11):e1001180.

Evolution of linked avirulence effectors in Leptosphaeria maculans is affected by genomic environment and exposure to resistance genes in host plants.

Van de Wouw AP, Cozijnsen AJ, Hane JK, Brunner PC, McDonald BA, Oliver RP, Howlett BJ.

School of Botany, University of Melbourne, Victoria, Australia.

Brassica napus (canola) cultivars and isolates of the blackleg fungus, Leptosphaeria maculans interact in a 'gene for gene' manner whereby plant resistance (R) genes are complementary to pathogen avirulence (Avr) genes. Avirulence genes encode proteins that belong to a class of pathogen molecules known as effectors, which includes small secreted proteins that play a role in disease. In Australia in 2003 canola cultivars with the Rlm1 resistance gene suffered a breakdown of disease resistance, resulting in severe yield losses. This was associated with a large increase in the frequency of virulence alleles of the complementary avirulence gene, AvrLm1, in fungal populations. Surprisingly, the frequency of virulence alleles of AvrLm6 (complementary to Rlm6) also increased dramatically, even though the cultivars did not contain Rlm6. In the L. maculans genome, AvrLm1 and AvrLm6 are linked along with five other genes in a region interspersed with transposable elements that have been degenerated by Repeat-Induced Point (RIP) mutations. Analyses of 295 Australian isolates showed deletions, RIP mutations and/or non-RIP derived amino acid substitutions in the predicted proteins encoded by these seven genes. The degree of RIP mutations within single copy sequences in this region was proportional to their proximity to the degenerated transposable elements. The RIP alleles were monophyletic and were present only in isolates collected after resistance conferred by Rlm1 broke down, whereas deletion alleles belonged to several polyphyletic lineages and were present before and after the resistance breakdown. Thus, genomic environment and exposure to resistance genes in B. napus has affected the evolution of these linked avirulence genes in L. maculans.

PMCID: PMC2973834 PMID: 21079787 [PubMed - indexed for MEDLINE]

425. Antimicrob Agents Chemother. 2011 Feb;55(2):532-8. Epub 2010 Nov 15.

Recent exposure to caspofungin or fluconazole influences the epidemiology of candidemia: a prospective multicenter study involving 2,441 patients.

Lortholary O, Desnos-Ollivier M, Sitbon K, Fontanet A, Bretagne S, Dromer F; French Mycosis Study Group.

Collaborators: Bouges-Michel C, Poilane I, Dunan J, Galeazzi G, Botterel F, Fauchet N, Forget E, Lawrence C, Bonnal C, Botterel F, Bouree P, Eloy O, David MF, Khassis N, Milhaila L, Chachaty E, Chochillon C, Paugam A, Baixench MT, Cornet M, Escande MC, Bougnoux ME, Sterckers Y, Challier S, Dannaoui E, Lavarde V, Datry A, Lmimouni B, Brun S, Fekkar A, Poirot JL, Lacroix C, Moissenet D, Develoux M, Bonacorsi S, Raoux D, Hoinard H.

Institut Pasteur, Unité de Mycologie Moléculaire, Centre National de Référence Mycologie et Antifongiques, Paris, France.

A prospective multicenter surveillance program on yeast bloodstream infections was implemented in the Paris, France, area without restrictions on ward of hospitalization (intensive care unit, hematology, and surgery) or age (adults and children). The present analysis concerns 2,618 isolates collected over 7 years from 2,441 patients. Centralized species identification and antifungal susceptibility testing using the EUCAST methodology were performed. Almost 10% (232/2,441) of the patients had recently (≤30 days) been treated with antifungal drugs. We analyzed the effect of recent exposure to fluconazole (n = 159) or caspofungin (n = 61) on the proportions of the five major Candida species. For both drugs, preexposure was associated with a decreased prevalence of Candida albicans in favor of less drug-susceptible species (C. glabrata and C. krusei for the former and C. parapsilosis and, to a lesser extent, C. glabrata and C. krusei for the latter; P = 0.001). In the multivariate analysis, the risk of being infected with an isolate with decreased susceptibility to fluconazole was independently associated with an age of ≥15 years (odds ratio [OR] = 2.45; 95% confidence interval [CI] = 1.39 to 4.31; P = 0.002) and with recent exposure to fluconazole (OR = 2.17; 95% CI = 1.51 to 3.13; P < 0.001), while the risk of being infected with an isolate with decreased susceptibility to caspofungin was independently associated with an age <15 years (OR = 2.53; 95% CI = 1.43 to 4.48; P = 0.001) and with recent exposure to caspofungin (OR = 4.79; 95% CI = 2.47 to 9.28; P < 0.001). These findings could influence future recommendations for the management of candidemia.

PMCID: PMC3028765 PMID: 21078946 [PubMed - indexed for MEDLINE]

426. BMC Microbiol. 2010 Nov 15;10:289.

A genomic approach highlights common and diverse effects and determinants of susceptibility on the yeast Saccharomyces cerevisiae exposed to distinct antimicrobial peptides.

López-García B, Gandía M, Muñoz A, Carmona L, Marcos JF.

Departamento de Ciencia de los Alimentos, Instituto de Agroquímica y Tecnología de Alimentos (IATA), CSIC, Burjassot, Valencia, Spain.

BACKGROUND: The mechanism of action of antimicrobial peptides (AMP) was initially correlated with peptide membrane permeation properties. However, recent evidences indicate that action of a number of AMP is more complex and involves specific interactions at cell envelopes or with intracellular targets. In this study, a genomic approach was undertaken on the model yeast Saccharomyces cerevisiae to characterize the antifungal effect of two unrelated AMP.
RESULTS: Two differentiated peptides were used: the synthetic cell-penetrating PAF26 and the natural cytolytic melittin. Transcriptomic analyses demonstrated distinctive gene expression changes for each peptide. Quantitative RT-PCR confirmed differential expression of selected genes. Gene Ontology (GO) annotation of differential gene lists showed that the unique significant terms shared by treatment with both peptides were related to the cell wall (CW). Assays with mutants lacking CW-related genes including those of MAPK signaling pathways revealed genes having influence on sensitivity to peptides. Fluorescence microscopy and flow cytometry demonstrated PAF26 interaction with cells and internalization that correlated with cell killing in sensitive CW-defective mutants such as Δecm33 or Δssd1. GO annotation also showed differential responses between peptides, which included ribosomal biogenesis, ARG genes from the metabolism of amino groups (specifically induced by PAF26), or the reaction to unfolded protein stress. Susceptibility of deletion mutants confirmed the involvement of these processes. Specifically, mutants lacking ARG genes from the metabolism of arginine pathway were markedly more resistant to PAF26 and had a functional CW. In the deletant in the arginosuccinate synthetase (ARG1) gene, PAF26 interaction occurred normally, thus uncoupling peptide interaction from cell killing. The previously described involvement of the glycosphingolipid gene IPT1 was extended to the peptides studied here.
CONCLUSIONS: Reinforcement of CW is a general response common after exposure to distinct AMP, and likely contributes to shield cells from peptide interaction. However, a weakened CW is not necessarily indicative of a higher sensitivity to AMP. Additional processes modulate susceptibility to specific peptides, exemplified in the involvement of the metabolism of amino groups in the case of PAF26. The relevance of the response to unfolded protein stress or the sphingolipid biosynthesis, previously reported for other unrelated AMP, was also independently confirmed.

PMCID: PMC2996382 PMID: 21078184 [PubMed - indexed for MEDLINE]

427. Aging Cell. 2011 Feb;10(1):5-9. doi: 10.1111/j.1474-9726.2010.00649.x. Epub 2010 Dec 7.

Some highlights of research on aging with invertebrates, 2010.

Partridge L.

Max Planck Institute for Biology of Ageing, Gleueler Strasse 55a, 50931 Köln, Germany. l.partridge@ucl.ac.uk

This annual review focuses on invertebrate model organisms, which continue to yield fundamental new insights into mechanisms of aging. This year, the budding yeast has been used to understand how asymmetrical partitioning of cellular constituents at cell division can produce a rejuvenated offspring from an aging parent. Blocking of sensation of carbon dioxide is shown to extend fly lifespan and to mediate the lifespan-shortening effect of sensory exposure to fermenting yeast. A new study of daf-16, the key forkhead transcription factor that mediates extension of lifespan by mutants in the insulin-signalling pathway in Caenorhabditis elegans, demonstrates that expression of tissue-specific isoforms with different patterns of response to upstream signalling mediates the highly pleiotropic effects of the pathway on lifespan and other traits. A new approach to manipulating mitochondrial activity in Drosophila, by introducing the yeast NADH-ubiquinone oxidoreductase, shows promise for understanding the role of mitochondrial reactive oxygen species in aging. An exciting new study of yeast and mammalian cells implicates deterioration of the nuclear pore, and consequent leakage of cytoplasmic components into the nucleus, as an important cause of aging in postmitotic tissues. Loss of, or damage to, chromosome-associated histones is also implicated in the determination of lifespan in yeast, worms and fruit flies. The relationship between functional aging, susceptibility to aging-related disease and lifespan itself are explored in two studies in C. elegans, the first examining the role of dietary restriction and reduced insulin signalling in cognitive decline and the second profiling aggregation of the proteome during aging. The invertebrates continue to be a power house of discovery for future work in mammals.

PMCID: PMC3121960 PMID: 21078113 [PubMed - indexed for MEDLINE]

428. Med Mycol. 2011 May;49(4):380-94. Epub 2010 Nov 15.

Exposure to host or fungal PGE₂ abrogates protection following immunization with Candida-pulsed dendritic cells.

Kundu G, Noverr MC.

Department of Immunology & Microbiology, Wayne State University School of Medicine, Detroit, Michigan, USA.

Candida albicans produces an immunomodulatory oxylipin from arachidonic acid that is structurally identical to host prostaglandin E₂ (PGE₂). In terms of host immune responses, PGE₂ can promote Th2 responses, which are non-protective against fungal infections. We investigated the effect of host or fungal PGE₂ on murine bone marrow-derived dendritic cell (DC) cytokine production, and the ability to immunize mice against systemic infection with C. albicans. We used GM-CSF to produce myeloid DCs (GM-DCs) and FLT-3L to enrich for plasmacytoid DCs (FL-DCs). In the presence of hyphae, PGE₂ promoted Th2 cytokine production and suppressed Th1 cytokine production. Immunization with yeast-pulsed DCs but not hyphae-pulsed DCs lead to a reduction in kidney fungal burden during systemic infection, which was most dramatic with FL-DCs. However, exposure to either host or fungal PGE₂ during antigenic stimulation abrogated the ability of yeast-pulsed DCs to protect against infection. The lack of protection was associated with a trend towards reduced Th1 cytokines and increased Th2 cytokines in the spleen. However, the pattern of protection did not completely match cytokine expression. Locally, in FL-DC pulsed mice, reduced Th1 and exacerbated Th2 and Th17 cytokines were only detected in the kidneys of mice that did not show reductions in fungal burden after vaccination. This indicates that host or fungal PGE₂ can shift adaptive responses in favor of the pathogen and that uncontrolled Th17 responses are detrimental during systemic infection.

PMID: 21077736 [PubMed - indexed for MEDLINE]

429. Photochem Photobiol. 2011 Jan-Feb;87(1):250-5. doi: 10.1111/j.1751-1097.2010.00819.x. Epub 2010 Nov 12.

Ultraviolet-C irradiation for prevention of central venous catheter-related infections: an in vitro study.

Dai T, Tegos GP, St Denis TG, Anderson D, Sinofsky E, Hamblin MR.

Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, USA.

Central venous catheters (CVC) are widely used in the United States and are associated with 250,000 to 500,000 CVC-related infections in hospitals annually. We used a catheter made from ultraviolet-C (UVC) transmissive material to test whether delivery of UVC from the lumen would allow inactivation of microorganisms on the outer surface of CVC. When the catheter was exposed to UVC irradiation from a cold cathode fluorescent lamp inside the catheter lumen at a radiant exposure of 3.6 mJ cm(-2) , more than 6-log(10) of drug-resistant Gram-positive bacteria adhered to the outer surface of the catheter were inactivated. Three to 7-log(10) of drug-resistant Gram-negative bacteria and 2.80-log(10) of fungi were inactivated at a radiant exposure of 11 mJ cm(-2).UVC irradiation also offered a highly selective inactivation of bacteria over keratinocytes under exactly comparable conditions. After 11 mJ cm(-2) UVC light had been delivered, over 6-log(10) of bacteria were inactivated while the viability loss of the keratinocytes was only about 57%.

PMCID: PMC3010268 PMID: 21073470 [PubMed - indexed for MEDLINE]

430. Parasite. 2010 Sep;17(3):219-32.

Epidemiology and clinical relevance of Pneumocystis jirovecii Frenkel, 1976 dihydropteroate synthase gene mutations.

Matos O, Esteves F.

Unidade de Protozoários Oportunistas/VIH e Outras Protozooses, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisboa, Portugal. omatos@ihmt.unl.pt

A review was conducted to examine the published works that studied the prevalence of Pneumocystis jirovecii dihydropteroate synthase (DHPS) mutations in patients with P. jirovecii pneumonia (PcP), in develop and developing countries, and that focused the problem of the possible association of these mutations with exposure to sulpha or sulphone drugs and their influence in the PcP outcome. Studies conducted in United States of America presented higher P. jirovecii mutations rates, in comparison with European countries, and in developing countries, lower rates of DHPS mutations were reported, due to limited use of sulpha drugs. A significant association was reported between the use of sulpha or sulphone agents for PcP prophylaxis in HIV-infected patients and the presence of DHPS mutations. However these mutations were also detected in PcP patients who were not currently receiving sulpha or sulphone agents. The outcome and mortality of HIV-infected patients with PcP harbouring DHPS gene mutations were related primarily to the underlying severity of illness and the initial severity of PcP, more than to the presence of mutations.

PMID: 21073145 [PubMed - indexed for MEDLINE]

431. Southeast Asian J Trop Med Public Health. 2010 Jul;41(4):928-35.

Rhinofacial entomophthoramycosis; a case series and review of the literature.

Leopairut J, Larbcharoensub N, Cheewaruangroj W, Sungkanuparph S, Sathapatayavongs B.

Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

Rhinofacial entomophthoramycosis is an uncommon chronic mycotic disease caused by exposure to the organism Conidiobolus coronatus. The authors report a case series of 5 patients with rhinofacial entomophthoramycosis and review the literature. All patients had typical involvement of the rhinofacial area with formation of subcutaneous lesions causing a chronic granulomatous inflammatory response with tissue eosinophilia and Splendore-Hoeppli reaction. Diagnoses were made based on histopathologic examination in all cases and fungi were isolated and identified in one case. The clinicopathologic features and therapeutic management of rhinofacial entomophthoramycosis are described.

PMID: 21073068 [PubMed - indexed for MEDLINE]

432. Surv Ophthalmol. 2011 Jan-Feb;56(1):1-22. Epub 2010 Nov 11.

Microsporidial keratitis: need for increased awareness.

Sharma S, Das S, Joseph J, Vemuganti GK, Murthy S.

L.V. Prasad Eye Institute, Bhubaneswar, Orissa, India. savitri@lvpei.org

Since the devastation of the European silk worm industry in the 19th century, microsporidia have been recognized as important organisms. An enormous literature is available on their biology, phylogeny, classification, disease profile, diagnosis, and treatment; however, it is only recently that ophthalmologists have begun to take note of these organisms. The last two decades have seen several publications related to ocular microsporidiosis, in particular those forms affecting the cornea. Both immunocompetent and immunocompromised patients are at risk of developing corneal infections that may range from self limiting mild keratoconjunctivitis to severe stromal keratitis recalcitrant to medical treatment. Exposure to soil, muddy water, and minor trauma are possible risk factors. Although reliable prevalence data are lacking, recent studies indicate a high prevalence of microsporidial keratoconjunctivitis in the rainy season, especially in India and other countries with similar climates. For instance, a high prevalence has been documented in Singapore. We bring together the information available on ocular microsporidiosis.

PMID: 21071051 [PubMed - indexed for MEDLINE]

433. Cancer Chemother Pharmacol. 2011 Aug;68(2):465-75. Epub 2010 Nov 11.

Prediction of human pharmacokinetics and tissue distribution of apicidin, a potent histone deacetylase inhibitor, by physiologically based pharmacokinetic modeling.

Shin BS, Bulitta JB, Balthasar JP, Kim M, Choi Y, Yoo SD.

College of Pharmacy, Catholic University of Daegu, Gyeongsan-si, Gyeongbuk, Korea.

PURPOSE: The objectives of this study were to develop physiologically based models for the pharmacokinetics (PK) and organ distribution of apicidin in rats and mice and to predict human PK in blood and organs.
METHODS: The PK of apicidin was characterized in rats and mice after i.v. bolus injection, and distribution to various tissues was determined in rats following i.v. infusions at steady state. The developed models were prospectively validated within rat and within mouse and by scaling from rat to mouse using data after multiple i.v. injections. Human PK was predicted by the physiologically based modeling using intrinsic clearance data for humans from in vitro experiments.
RESULTS: The Cl(s) predicted for human (9.8 ml/min/kg) was lower than those found in mice (116.9 ml/min/kg) and rats (61.6 ml/min/kg), and the V(ss) predicted for human (1.9 l/kg) was less than in mice (2.0 l/kg) and rats (2.5 l/kg). Consequently, the predicted t (1/2) was longer in human (2.3 h) than in mice and rats (0.4 and 0.9 h, respectively). The highest concentrations of apicidin were predicted in liver followed by adipose tissue, kidney, lung, spleen, heart, arterial blood, venous blood, small intestine, stomach, muscle, testis, and brain.
CONCLUSIONS: The developed models adequately described the PK of apicidin in rats and mice and were applied to predict human PK. These models may be useful in predicting human blood and tissue concentrations of apicidin under different exposure conditions.

PMID: 21069337 [PubMed - indexed for MEDLINE]

434. Am J Physiol Regul Integr Comp Physiol. 2011 Feb;300(2):R330-9. Epub 2010 Nov 10.

Pathogen-induced heart rate changes associated with cholinergic nervous system activation.

Fairchild KD, Srinivasan V, Moorman JR, Gaykema RP, Goehler LE.

Dept. of Pediatrics, University of Virginia Health System, Hospital Dr., Charlottesville, VA 22908, USA.

The autonomic nervous system plays a central role in regulation of host defense and in physiological responses to sepsis, including changes in heart rate and heart rate variability. The cholinergic anti-inflammatory response, whereby infection triggers vagal efferent signals that dampen production of proinflammatory cytokines, would be predicted to result in increased vagal signaling to the heart and increased heart rate variability. In fact, decreased heart rate variability is widely described in humans with sepsis. Our studies elucidate this apparent paradox by showing that mice injected with pathogens demonstrate transient bradyarrhythmias of vagal origin in a background of decreased heart rate variability (HRV). Intraperitoneal injection of a large inoculum of Gram-positive or Gram-negative bacteria or Candida albicans rapidly induced bradyarrhythmias of sinus and AV nodal block, characteristic of cardiac vagal firing and dramatically increased short-term HRV. These pathogen-induced bradycardias were immediately terminated by atropine, an antagonist of muscarinic cholinergic receptors, demonstrating the role of vagal efferent signaling in this response. Vagal afferent signaling following pathogen injection was demonstrated by intense nuclear c-Fos activity in neurons of the vagal sensory ganglia and brain stem. Surprisingly, pathogen-induced bradycardia demonstrated rapid and prolonged desensitization and did not recur on repeat injection of the same organism 3 h or 3 days after the initial exposure. After recovery from the initial bradycardia, depressed heart rate variability developed in some mice and was correlated with elevated plasma cytokine levels and mortality. Our findings of decreased HRV and transient heart rate decelerations in infected mice are similar to heart rate changes described by our group in preterm neonates with sepsis. Pathogen sensing and signaling via the vagus nerve, and the desensitization of this response, may account for periods of both increased and decreased heart rate variability in sepsis.

PMCID: PMC3043803 [Available on 2012/2/1] PMID: 21068197 [PubMed - indexed for MEDLINE]

435. BMC Complement Altern Med. 2010 Nov 10;10:65.

Liquid and vapour-phase antifungal activities of selected essential oils against Candida albicans: microscopic observations and chemical characterization of Cymbopogon citratus.

Tyagi AK, Malik A.

Applied Microbiology Laboratory, Centre for Rural Development & Technology, Indian Institute of Technology Delhi, New Delhi 110 016, India. amittyagiiitd@gmail.com

BACKGROUND: Use of essential oils for controlling Candida albicans growth has gained significance due to the resistance acquired by pathogens towards a number of widely-used drugs. The aim of this study was to test the antifungal activity of selected essential oils against Candida albicans in liquid and vapour phase and to determine the chemical composition and mechanism of action of most potent essential oil.
METHODS: Minimum Inhibitory concentration (MIC) of different essential oils in liquid phase, assayed through agar plate dilution, broth dilution & 96-well micro plate dilution method and vapour phase activity evaluated through disc volatilization method. Reduction of C. albicans cells with vapour exposure was estimated by kill time assay. Morphological alteration in treated/untreated C. albicans cells was observed by the Scanning electron microscopy (SEM)/Atomic force microscopy (AFM) and chemical analysis of the strongest antifungal agent/essential oil has been done by GC, GC-MS.
RESULTS: Lemon grass (Cymbopogon citratus) essential oil exhibited the strongest antifungal effect followed by mentha (Mentha piperita) and eucalyptus (Eucalyptus globulus) essential oil. The MIC of lemon grass essential oil in liquid phase (288 mg/l) was significantly higher than that in the vapour phase (32.7 mg/l) and a 4 h exposure was sufficient to cause 100% loss in viability of C. albicans cells. SEM/AFM of C. albicans cells treated with lemon grass essential oil at MIC level in liquid and vapour phase showed prominent shrinkage and partial degradation, respectively, confirming higher efficacy of vapour phase. GC-MS analysis revealed that lemon grass essential oil was dominated by oxygenated monoterpenes (78.2%); α-citral or geranial (36.2%) and β-citral or neral (26.5%), monoterpene hydrocarbons (7.9%) and sesquiterpene hydrocarbons (3.8%).
CONCLUSION: Lemon grass essential oil is highly effective in vapour phase against C. albicans, leading to deleterious morphological changes in cellular structures and cell surface alterations.

PMCID: PMC2994787 PMID: 21067604 [PubMed - indexed for MEDLINE]

436. Med Mycol. 2010 Nov;48 Suppl 1:S52-9.

Pharmacological considerations for azole antifungal drug management in cystic fibrosis lung transplant patients.

Billaud EM, Guillemain R, Berge M, Amrein C, Lefeuvre S, Louët AL, Boussaud V, Chevalier P.

Departments of Pharmacology, Hôpital Européen Georges Pompidou, Université Paris Descartes, France. eliane.billaud@egp.aphp.fr

This paper aims to present our experience in the pharmacological approach of the management of azole antifungal drugs in cystic fibrosis lung transplant patients. Cystic fibrosis (CF) lung transplantation is associated with multi-factorial care management, because of immunosuppressive requirements, risk of infections, frequency of gastro-oesophageal reflux disease, hepatic alterations and CF pharmacokinetics (PK) specificities that result in important PK variability. CF is associated with frequent colonization of the airways by filamentous fungi, especially by Aspergillus species. Today the antifungal therapeutic arsenal offers several possibilities for long-term oral therapy including azole drugs (itraconazole, voriconazole and posaconazole). Therefore, nephrotoxic amphotericin B should be avoided. The liver is important in the pharmacological profile of azole drugs, due to metabolic elimination, hepatotoxicity and PK drug-drug interaction (DDI) involving CYP3A4 metabolic inhibition. Targets for such DDI are numerous, but immunosuppressive drugs are of major concern, justifying combined therapeutic drug monitoring (TDM) of both azoles (inhibitors) and immunosuppressants (targets) on an individualized patient basis to adjust the coprescription quantitatively. The risk of long under-dosed periods, frequently addressed in this population, could justify, on a PK basis, the need for combination with an exclusive parenteral antifungal while waiting for azole relevant drug level. High PK variability, the risk of low exposure, therapeutic issues and DDI management in this complex underlying disease justify close monitoring with systematic combined TDM of azole and immunosuppressants, in case of coprescription.

PMID: 21067331 [PubMed - indexed for MEDLINE]

437. Med Mycol. 2010 Nov;48 Suppl 1:S37-44.

Clinical associations and prevalence of Scedosporium spp. in Australian cystic fibrosis patients: identification of novel risk factors?

Blyth CC, Middleton PG, Harun A, Sorrell TC, Meyer W, Chen SC.

Centre for Infectious Diseases and Microbiology, Westmead Hospital, Westmead, NSW, Australia.

Risk factors for the association of Scedosporium in cases of cystic fibrosis (CF) and its clinical implications are poorly understood. Clinical, lung function and laboratory data of adult CF patients in Sydney (April 2008-March 2009) were prospectively analysed for such risk factors. Expectorated sputa were cultured for bacteria and examined for fungi using standard mycological and Scedosporium-selective media, and by an internal transcribed spacer region-targeted multiplex PCR assay. Scedosporium spp. (n = 4 each of Scedosporium prolificans, Scedosporium aurantiacum and Pseudallescheria boydii/ Scedosporium apiospermum complex [non-S. aurantiacum]) were recovered from 12 of 69 (17.4%) patients. Samples of 11 of the patients yielded isolates on Scedosporium- selective media (vs. 6 [8.7%] by non-selective culture) and one additional patient was noted by PCR. Of these patients, 83.3% were co-colonized with other moulds, most frequently Aspergillus fumigatus. Colonization was not associated with best FEV₁/predicted, corticosteroid or antifungal therapies. By univariate analysis, patients with Scedosporium colonization were significantly less likely to be colonized with mucoid Pseudomonas aeruginosa (P = 0.025), while prior therapy with antistaphylococcal penicillins was a risk factor for colonization (P = 0.045). Bacterial colonization and antimicrobial exposure likely influence Scedosporium colonization, which is optimally detected with selective media. Studies are required to confirm independent risk factors for Scedosporium colonization and to determine its impact on lung disease.

PMID: 21067328 [PubMed - indexed for MEDLINE]

438. ACS Appl Mater Interfaces. 2010 Dec;2(12):3654-63. Epub 2010 Nov 10.

Bilayer formation between lipid-encased hydrogels contained in solid substrates.

Sarles SA, Stiltner LJ, Williams CB, Leo DJ.

Center for Intelligent Material Systems and Structures (CIMSS), Department of Mechanical Engineering, and Design, Research, and Education for Additive Manufacturing Systems (DREAMS) Laboratory, Virginia Tech, Blacksburg, Virginia 24061, United States.

Solidified biomolecular networks that incorporate liquid-supported lipid bilayers are constructed by attaching lipid-encased, water-swollen hydrogels contained in oil. Poly(ethylene glycol) dimethacrylate (PEG-DMA) and a free-radical photoinitiator are added to an aqueous lipid vesicle solution such that exposure to ultraviolet light results in solidification of neighboring aqueous volumes. Bilayer formation can occur both prior to photopolymerization with the aqueous mixture in the liquid state and after solidification by using the regulated attachment method (RAM) to attach the aqueous volumes contained within a flexible substrate. In addition, photopolymerization of the hydrogels can be performed in a separate mold prior to placement in the supporting substrate. Membranes formed across a wide range of hydrogel concentrations [0-80% (w/v); MW=1000 g/mol PEG-DMA] exhibit high electrical resistances (1-10 GΩ), which enable single-channel recordings of alamethicin channels and show significant durability and longevity. We demonstrate that just as liquid phases can be detached and reattached using RAM, reconfiguration of solid aqueous phases is also possible. The results presented herein demonstrate a step toward constructing nearly solid-state biomolecular materials that retain fluid interfaces for driving molecular assembly. This work also introduces the use of three-dimensional printing to rapidly prototype a molding template used to fabricate polyurethane substrates and to shape individual hydrogels.

PMID: 21067200 [PubMed - indexed for MEDLINE]

439. G Ital Med Lav Ergon. 2010 Jul-Sep;32(3):249-55.

[Focus on health surveillance of health workers exposed to blood-transmissible biological agents: results and perspectives of a multicenter working group].

[Article in Italian]

Carrer P, Micheloni G, Campagna M, Bacis M, Belotti L, Biggi N, Cologni L, Gattini V, Fostinelli J, Lodi V, Magnavita N, Negro C, Omeri E, Placidi D, Polato R, Puro V, Tonelli F, Porru S.

Dip. Medicina del Lavoro, Sez. Ospedale Sacco, Università degli Studi di Milano, Italy.

The biological risk from exposure to bloodborne pathogens in health care environments represents a frequent and widespread risk, involving a large number of exposed workers. On the basis of the available scientific innovations, the recent legislation regarding health and safety of workers and the experiences of SIMLII guidelines on health surveillance (HS) workers exposed to biological risk, a multicenter study was carried out, involving nine relevant hospitals and about 32 000 healthcare workers (HCW). A review of the literature was performed, with particular reference to the last 10 years. For each hospital, protocols of HS have been examined according to tasks and biological risk from bloodborne viruses (HBV, HDV, HCV, HIV) as well as management of HCW infected with this pathogens. Differences of risk management in the hospitals, in relationship also with recommendations of the literature have been evaluated. The literature supplies important indications for HS management of HCW exposed to bloodborne pathogens, with relevant information also for patient safety. Preventive examinations are in line with the recommendations of literature and similar across the hospitals for HCV and HIV, while they are different for HBV. Periodic surveillance was different for the frequency, among the hospitals and also as compared to national SIMLII guidelines. As for management, no differentiation among the hospitals was detected as referred to different risk of exposure, while differences were observed around definitions of restrictions. Finally, good medical practices to support occupational physicians in the prevention and management of HCWs' exposed to biological risks are suggested.

PMID: 21061704 [PubMed - indexed for MEDLINE]

440. G Ital Med Lav Ergon. 2010 Jul-Sep;32(3):235-9.

[Update on the subject of epidemiology of blood-transmitted occupational infections].

[Article in Italian]

Puro V, De Carli G, Segata A, Piccini G, Argentero PA, Signorini L, Daglio M, Penna C, Marchegiano P, Miniero M, Cinti G, Tavanti L, Maggiore A, Sossai D, Micheloni G; Giuseppe Ippolito Gruppo di Studio Italiano Rischio Occupazionale da HIV.

Istituto Nazionale per le Malattie Infettive "Lazzaro Spallanzani", Roma.

Healthcare workers (HCW) are exposed to many different pathogens, and cases of occupational infection have been reported involving the vast majority of known and emerging agents. The risk is present during all the phases of patient care and manipulation of biologic materials, and the implementation of Standard Precautions--and biosafety level 2 measures in the laboratory--and Transmission-Based Precautions in all health settings represents the necessary preventive intervention required by law. Percutaneous exposures represent an extremely frequent event in healthcare facilities; among the many pathogens acquired through this type of exposure, those of highest concern due to the frequency of exposure are HIV, HBV and HCV. Over the last 10 years, though the risk of exposure is still not negligible, occupational infection with HBV has become a rare event; conversely, the incidence of acute C hepatitis became significantly higher among HCW (1,6 per 100.000 inhabitants) with respect to the general population (0,6), with a seroconversion rate following an occupational exposure between 0,5% and 1,8%; finally, reports of occupational HIV infection have decreased, probably also as a secondary beneficial effect of antiretroviral treatment in patients and post-exposure prophylaxis in HCW. The Studio Italiano Rischio Occupazionale da HIV (SIROH) documented from 1986 to 2009 one occupational HBV case, 6 HIV cases (the last one in 2007) and 32 HCV cases. In Europe, the Directive 2010/32/EU approved on May 10 2010 requires Member State to implement within three years a global strategy to prevent occupational exposures in the healthcare setting, particularly with respect to needlestick and sharp injuries, including the adoption, based on risk assessment, of devices incorporating safety features. In Italy the introduction of these devices, according to data collected by the SIROH, showed the possibility to decrease percutaneous exposures by 75%, an effect sustained over time if supported by information, education and training.

PMID: 21061701 [PubMed - indexed for MEDLINE]

441. J Occup Environ Hyg. 2010 Dec;7(12):693-9.

Culture-independent characterization of bacteria and fungi in a poultry bioaerosol using pyrosequencing: a new approach.

Nonnenmann MW, Bextine B, Dowd SE, Gilmore K, Levin JL.

Department of Occupational Health Sciences, University of Texas Health Science Center at Tyler, Tyler, Texas 75708-3154, USA.

Work in animal production facilities often results in exposure to organic dusts. Previous studies have documented decreases in pulmonary function and lung inflammation among workers exposed to organic dust in the poultry industry. Bacteria and fungi have been reported as components of the organic dust produced in poultry facilities. To date, little is known about the diversity and concentration of bacteria and fungi inside poultry buildings. All previous investigations have utilized culture-based methods for analysis that identify only biota cultured on selected media. The bacterial tag-encoded flexible (FLX) amplicon pyrosequencing (bTEFAP) and fungal tag-encoded flexible (FLX) amplicon pyrosequencing (fTEFAP) are modern and comprehensive approaches for determining biodiversity of microorganisms and have not previously been used to provide characterization of exposure to microorganisms in an occupational environment. This article illustrates the potential application of this novel technique in occupational exposure assessment as well as other settings. An 8-hr area sample was collected using an Institute of Medicine inhalable sampler attached to a mannequin in a poultry confinement building. The sample was analyzed using bTEFAP and fTEFAP. Of the bacteria and fungi detected, 116 and 39 genera were identified, respectively. Among bacteria, Staphylococcus cohnii was present in the highest proportion (23%). The total inhalable bacteria concentration was estimated to be 7503 cells/m³. Among the fungi identified, Sagenomella sclerotialis was present in the highest proportion (37%). Aspergillus ochraceus and Penicillium janthinellum were also present in high proportions. The total inhalable fungi concentration was estimated to be 1810 cells/m³. These estimates are lower than what has been reported by others using standard epifluorescence microscope methods. However, no study has used non-culture-based techniques, such as bTEFAP and fTEFAP, to evaluate bacteria and fungi in the inhalable fraction of a bioaerosol in a broiler production environment. Furthermore, the impact of this bTEFAP and fTEFAP technology has yet to be realized by the scientific community dedicated to evaluating occupational and environmental bioaerosol exposure.

PMID: 21058154 [PubMed - indexed for MEDLINE]

442. J Feline Med Surg. 2010 Dec;12(12):988-90. Epub 2010 Nov 4.

Effects of temperature variations and light exposure on the time to growth of dermatophytes using six different fungal culture media inoculated with laboratory strains and samples obtained from infected cats.

Moriello KA, Verbrugge MJ, Kesting RA.

University of Wisconsin-Madison, School of Veterinary Medicine, 2015 Linden Drive West, Madison, WI 53706, USA. moriellk@svm.vetmed.wisc.edu

In this study, 5/6 commercially available fungal culture media were comparable with respect to first growth, first colour change, and first sporulation when inoculated with three strains of Microsporum canis, one strain of Microsporum gypseum, and one strain of Trichophyton species when incubated at either 25°C or 30°C. Five of six plates showed 100% growth at both temperatures. Five of six plates showed 100% growth when inoculated with naturally infective M canis hairs and spores. One commercial product packaged as a self-sealing incubation plate showed growth in only 65.4% of times and the plates were prone to desiccation. M canis inoculated plates were incubated under four different light exposures (24h of light, 24h of dark, 12h light/12h dark, and room lighting) and no differences in growth or sporulation were noted.

PMID: 21051255 [PubMed - indexed for MEDLINE]

443. Plant Physiol Biochem. 2011 Jan;49(1):88-95. Epub 2010 Oct 20.

Expression, in vivo localization and phylogenetic analysis of a pyridoxine 5'-phosphate oxidase in Arabidopsis thaliana.

Sang Y, Locy RD, Goertzen LR, Rashotte AM, Si Y, Kang K, Singh NK.

Department of Biological Sciences, 101 Rouse Life Sciences Building, Auburn University, AL 36849, USA.

Pyridoxal phosphate (PLP), a vitamin B(6) vitamer, is an essential cofactor for numerous enzymes. Pyridoxine/pyridoxamine phosphate oxidase (PPOX) catalyzes the synthesis of pyridoxal phosphate from pyridoxine phosphate (PNP) and/or pyridoxamine phosphate (PMP). The At5g49970 locus in Arabidopsis thaliana encodes an AtPPOX, a PNP/PMP oxidase. The expression of the AtPPOX gene varied in different tissues of Arabidopsis examined, being up-regulated by light, heat shock, ABA, and ethylene treatments, and down-regulated by exposure to drought and NaCl. Monoclonal antibodies raised against two different domains of AtPPOX recognized different sizes of AtPPOX, suggesting that AtPPOX proteins are produced as splice variants of the AtPPOX gene in Arabidopsis. Phylogenetic analysis of AtPPOX across all domains of life demonstrated that plant AtPPOX homologs have an additional Yjef_N domain preceding the Pyridox_Oxidase domain at the C-terminal end of the protein, while AtPPOX homologs from bacteria, fungi and animals have only Pyridox_Oxidase domain. The presence of the Yjef_N domain in plant AtPPOX homologs suggests that acquisition of this domain, and its fusion with the pyridox_oxidase domain began with the endosymbiotic acquisition of the chloroplast. Bioinformatic analysis suggested that AtPPOX is localized in chloroplast, but the monoclonal antibody could not be used for subcellular localization of this protein. A GFP-AtPPOX fusion construct introduced into the Arabidopsis protoplast confirmed localization of AtPPOX into the chloroplast. An RNAi mutant of AtPPOX showed sensitivity to high light suggesting a role for PPOX in resistance to photooxidative damage, and alteration in root growth in the presence of sucrose suggests a role for PPOX in root development.

PMID: 21051239 [PubMed - indexed for MEDLINE]

444. Biol Pharm Bull. 2010;33(11):1911-4.

Transcriptional activation of putative calmodulin genes am-cam-1 and am-cam-2 from Aquilaria microcarpa, in response to external stimuli.

Kenmotsu Y, Yamamura Y, Ogita S, Katoh Y, Kurosaki F.

Laboratory of Plant Resource Sciences, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyamam, Sugitani, Toyama 930–0194, Japan.

A homology-based cloning strategy yielded two cDNA clones designated Am-cam-1 and Am-cam-2, presumably encoding calmodulin protein from a callus culture derived from the leaf tissues of Aquilaria microcarpa. An appreciable increase in the transcriptional activity of Am-cam-1 was reproducibly observed by exposure of the cell culture to methyl jasmonate, as analyzed by a reverse-transcription polymerase chain reaction. The expression level of the gene also increased when the cells were treated with yeast extract. The transcription of Am-cam-2 was similarly stimulated by the treatment with methyl jasmonate and yeast extract, however, the intensities of the enhanced expression appeared to be lower as compared with that of Am-cam-1. In contrast, Ca(2+)-ionophore A23187 did not show inducing activity for the expression of these two calmodulin genes. These results suggest that Am-cam-1 and Am-cam-2 and their products play important roles in signal transduction processes in methyl jasmonate- and yeast extract-treated cells of A. microcarpa, accompanying the change in the transcriptional activities.

PMID: 21048321 [PubMed - indexed for MEDLINE]

445. Biol Pharm Bull. 2010;33(11):1854-60.

Inhibition of cytokine-induced β cell apoptosis via laccase and its therapeutic advantages for insulin-dependent diabetes mellitus, type 1 diabetes.

Joo SS, Lee do I, Hwang KW.

Division of Marine Molecular Biotechnology, Gangneung-Wonju National University, 120 Gangneung Daehangno, Gangneung, Gangwon 210–702, Republic of Korea.

In pancreatic islets, free radical formation produced upon exposure to proinflammatory cytokines mediates β cell destruction, which ultimately leads to type 1 diabetes (T1D). In this study, we examined whether laccase, a family of the blue copper protein, can be successfully used to prevent β cells from cytokine-mediated apoptosis. Non-obese diabetic (NOD) mice were used for these experiments. In parallel, the RINm5f β cell line was employed as a model system for in vitro experiments. The results demonstrated that laccase effectively scavenged peroxinitrite, which can be formed by nitric oxide, and upregulated the expression of antioxidant enzymes, such as manganese superoxide dismutase (MnSOD) and catalase. Interestingly, laccase balanced pro- (Bax) and anti-apoptotic (Bcl-2) proteins in terms of both the mRNA and protein levels with a downregulation of cytochrome c protein in RINm5f cells. In addition, laccase maintained blood glucose concentrations at a normal level with a simultaneous increase in plasma insulin levels during the spontaneous induction of diabetes in NOD mice. In conclusion, the antioxidant potentials of laccase in scavenging free radicals and upregulation of antioxidant enzymes may exert its pro-survival effect by counteracting the increased intracellular oxidative stress, and, consequently, by inhibiting apoptosis induced by cytokine-mediated activation during the course of T1D.

PMID: 21048311 [PubMed - indexed for MEDLINE]

446. Endocrine. 2010 Oct;38(2):194-8. Epub 2010 Jul 16.

Anti-Saccaromyces Cerevisiae antibodies (ASCA) are elevated in autoimmune thyroid disease ASCA in autoimmune thyroid disease.

Yazıcı D, Aydın SZ, Yavuz D, Tarçın O, Deyneli O, Direskeneli H, Akalın S.

Section of Endocrinology and Metabolism, Marmara University Medical School, Istanbul, Turkey. dilekdy2002@yahoo.com

Environmental factors have been implicated in the development of autoimmune thyroid disease (AITD). Anti-Saccaromyces Cerevisiae Antibodies (ASCA) were shown to be elevated in several autoimmune diseases. The aim of the study was to determine ASCA levels and their relationship with thyroid autoantibodies in patients with AITD. One-hundred and twelve patients with AITD (age 41.1±12.8 years; F/M:96/16) and 103 healthy controls (38.5±10.3 years; F/M:82/21) were included. Twenty-four patients had Graves disease (GD), and 88 had Hashimoto's thyroiditis (HT). ASCA IgA and IgG, TSH, free T4, anti-thyroglobulin, and anti-thyroid peroxidase antibody concentrations were determined. ASCA IgA positivity in patients with GD (16.6%) was similar to patients with HT (13.6%) and was higher than controls (5.8%). No significant difference was present between the frequencies of IgG positivity among GD (12.5%), HT (7.9%), and control groups (5.8%). The mean levels of ASCA IgA and IgG were comparable within the groups. No correlation of ASCA and anti-thyroglobulin and anti-thyroid peroxidase levels was observed. Increased IgA ASCA positivity is observed in patients with GD, suggesting a role of environmental stimuli in its pathogenesis. The role of ASCA in the etiology of AITD needs to be further examined.

PMID: 21046480 [PubMed - indexed for MEDLINE]

447. Antonie Van Leeuwenhoek. 2011 Mar;99(3):567-77. Epub 2010 Nov 3.

Enhanced phospholipase B activity and alteration of phospholipids and neutral lipids in Saccharomyces cerevisiae exposed to N-nitrosonornicotine.

Vijayaraj P, Sabarirajan J, Nachiappan V.

Department of Biochemistry, Bharathidasan University, Tiruchirappalli, 24 Tamilnadu, India.

A tobacco-specific nitrosamine (TSNA), N-nitrosonornicotine (NNN), is a potent carcinogen present in cigarette smoke, and chronic exposure to it can lead to pulmonary cancer. NNN causes changes in phospholipid metabolism and the mechanism is yet to be elucidated. Exposure of Saccharomyces cerevisiae to 50 μM NNN leads to a substantial decrease in phosphatidylserine (PS) by 63%, phosphatidylcholine (PC) by 42% and phosphatidylethanolamine (PE) by 36% with a concomitant increase in lysophospholipids (LPL) by 25%. The alteration in phospholipid content was dependent on increasing NNN concentration. Reduced phospholipids were accompanied with increased neutral lipid content. Here we report for the first time that NNN exposure, significantly increases phospholipase B (PLB) activity and the preferred substrate is PC, a major phospholipid responsible for a series of metabolic functions. Furthermore, NNN also promotes the alteration of fatty acid (FA) composition; it increases the long chain fatty acid (C18 series) in phospholipids specifically phosphatidylethanolamine (PE) and PS; while on the contrary it increases short chain fatty acids in cardiolipin (CL). NNN mediated degradation of phospholipids is associated with enhanced PLB activity and alteration of phospholipid composition is accompanied with acyl chain remodelling. Understanding the altered phospholipid metabolism produced by NNN exposure is a worthwhile pursuit because it will help to understand the toxicity of tobacco smoke.

PMID: 21046464 [PubMed - indexed for MEDLINE]

448. Cell Biol Int. 2011 Apr 1;35(4):335-43.

Kojic acid, a secondary metabolite from Aspergillus sp., acts as an inducer of macrophage activation.

Rodrigues AP, Carvalho AS, Santos AS, Alves CN, do Nascimento JL, Silva EO.

Universidade Federal do Par, Instituto de Cincias Biolgicas, Laboratrio de Biologia Estrutural, Belm, Par, Brazil.

KA (kojic acid) is a secondary metabolite isolated from Aspergillus fungi that has demonstrated skin whitening, antioxidant and antitumour properties among others. However, limited information is available regarding its effects on macrophages, the major cell involved in cell defence. The aim of the present study was to analyse whether KA affects functional properties related to macrophage activation, such as phagocytosis and spreading ability over a substrate. Treatment of resident macrophages with 50 μg/ml KA for 1 h induced both morphological and physiological alterations in cells. Immunofluorescence microscopy revealed enhanced cell spreading and an increase in cell surface exposure, associated with a rearrangement of microtubules, actin filaments and intermediate filaments. KA also potentiated phagocytosis by macrophages, as demonstrated by the increase in phagocytic activity towards yeast, when compared to untreated cells. KA increased the production of ROS (reactive oxygen species), but not NO (nitric oxide) production. Three tests were used to assess cell viability; MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide], NR (neutral red) uptake and PI (propidium iodide) exclusion test, which showed that macrophages maintain their viability following KA treatment. Results indicate that KA can modulate macrophage activation through cytoskeleton rearrangement, increase cell surface exposure, enhance the phagocytic process and ROS production. The study demonstrates a new role for KA as a macrophage activator.

PMID: 21044044 [PubMed - indexed for MEDLINE]

449. Infect Immun. 2011 Jan;79(1):125-35. Epub 2010 Nov 1.

Coevolution of TH1, TH2, and TH17 responses during repeated pulmonary exposure to Aspergillus fumigatus conidia.

Murdock BJ, Shreiner AB, McDonald RA, Osterholzer JJ, White ES, Toews GB, Huffnagle GB.

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109-5642, USA.

Aspergillus fumigatus, a ubiquitous airborne fungus, can cause invasive infection in immunocompromised individuals but also triggers allergic bronchopulmonary aspergillosis in a subset of otherwise healthy individuals repeatedly exposed to the organism. This study addresses a critical gap in our understanding of the immunoregulation in response to repeated exposure to A. fumigatus conidia. C57BL/6 mice were challenged intranasally with A. fumigatus conidia weekly, and leukocyte composition, activation, and cytokine production were examined after two, four, and eight challenges. Approximately 99% of A. fumigatus conidia were cleared within 24 h after inoculation, and repeated exposure to A. fumigatus conidia did not result in hyphal growth or accumulation of conidia with time. After 2 challenges, there was an early influx of neutrophils and regulatory T (T(reg)) cells into the lungs but minimal inflammation. Repeated exposure promoted sustained expansion of the draining lymph nodes, while the influx of eosinophils and other myeloid cells into the lungs peaked after four exposures and then decreased despite continued A. fumigatus challenges. Goblet cell metaplasia and low-level fibrosis were evident during the response. Repeated exposure to A. fumigatus conidia induced T cell activation in the lungs and the codevelopment by four exposures of T(H)1, T(H)2, and T(H)17 responses in the lungs, which were maintained through eight exposures. Changes in CD4 T cell polarization or T(reg) numbers did not account for the reduction in myeloid cell numbers later in the response, suggesting a non-T-cell regulatory pathway involved in dampening inflammation during repeated exposure to A. fumigatus conidia.

PMCID: PMC3019910 PMID: 21041495 [PubMed - indexed for MEDLINE]

450. Clin Exp Allergy. 2011 Feb;41(2):171-8. doi: 10.1111/j.1365-2222.2010.03584.x. Epub 2010 Oct 7.

Role of fungal antigens in eosinophilia-associated cellular responses in nasal polyps: a comparison with enterotoxin.

Okano M, Fujiwara T, Haruna T, Kariya S, Makihara S, Higaki T, Nishizaki K.

Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. mokano@cc.okayama-u.ac.jp

BACKGROUND: Fungi and/or Staphylococcus aureus enterotoxins (SEs) may participate in the pathogenesis of eosinophilic inflammation in cases of chronic rhinosinusitis with nasal polyps (CRSwNP). Objective We sought to determine the effects of fungal antigens on eosinophilia-associated cellular responses in nasal polyps.
METHODS: Dispersed nasal polyp cells (DNPCs) were prepared from 13 patients with CRSwNP. DNPCs were cultured with fungal extracts (Aspergillus, Alternaria and Candida) or SEB for 72 h, after which the levels of IL-5, IL-13 and RANTES were measured within the supernatant. Responses to β-d-glucan, mannan and chitin were also examined.
RESULTS: 38.5%, 69.2% and 30.8% of DNPCs produced IL-5, IL-13 and RANTES, respectively, in response to 200 μg/mL of Aspergillus. 53.8%, 53.8% and 7.7% of DNPCs produced IL-5, IL-13 and RANTES, respectively, in response to 200 μg/mL of Alternaria. 53.8%, 38.5% and 15.4% of DNPCs produced IL-5, IL-13 and RANTES, respectively, in response to 200 μg/mL of Candida. All DNPCs produced these cytokines in response to 0.1 μg/mL of SEB. SEB induced significantly greater cytokine levels than the fungal extracts. No correlation between cytokine production following exposure to each of the fungal extracts or SEB and various clinical features, including nasal polyp eosinophilia and radiological severity of sinusitis was observed. Neither sensitization to fungus nor comorbidity with bronchial asthma was correlated with the fungal extract-induced cytokine production by DNPCs. β-d-glucan, mannan and chitin did not induce significant cytokine production.
CONCLUSIONS: These results suggest that, although DNPCs produce IL-5, IL-13 and RANTES in response to fungal extracts, fungal antigens including major carbohydrates are less capable of inducing eosinophilia-associated cellular responses in nasal polyps than SEB.

PMID: 21039976 [PubMed - indexed for MEDLINE]

451. Subst Use Misuse. 2011;46(4):460-5. Epub 2010 Nov 1.

Use and accidental exposure to hallucinogenic agents reported to the Czech Toxicological Information Centre from 1995 to 2008.

Mrazova K, Navratil T, Pelclova D.

Toxicological Information Centre, Department of Occupational Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, Czech Republic.

Intoxication by hallucinogenic agents is relatively common in the Czech Republic, with most cases of the use of these agents being by adolescents and young people. The objective of the study was to evaluate the number, trends, gender and age of the subjects, and the severity of exposure in intoxication by hallucinogenic plant and mushroom substances, in comparison with synthetic drugs, brought to the attention of the Toxicological Information Centre (TIC) through inquiries over the past 14 years (1995-2008) (from total 3,702 calls concerning the use of both natural and synthetic drugs, 917 calls were due to the use of hallucinogenic plants and mushrooms).

PMID: 21039115 [PubMed - indexed for MEDLINE]

452. Nat Methods. 2010 Dec;7(12):973-5. Epub 2010 Oct 31.

Rapid blue-light-mediated induction of protein interactions in living cells.

Kennedy MJ, Hughes RM, Peteya LA, Schwartz JW, Ehlers MD, Tucker CL.

Department of Neurobiology, Duke University Medical Center, Durham North Carolina, USA.

Dimerizers allowing inducible control of protein-protein interactions are powerful tools for manipulating biological processes. Here we describe genetically encoded light-inducible protein-interaction modules based on Arabidopsis thaliana cryptochrome 2 and CIB1 that require no exogenous ligands and dimerize on blue-light exposure with subsecond time resolution and subcellular spatial resolution. We demonstrate the utility of this system by inducing protein translocation, transcription and Cre recombinase-mediated DNA recombination using light.

PMCID: PMC3059133 PMID: 21037589 [PubMed - indexed for MEDLINE]

453. Fungal Biol. 2010 Nov-Dec;114(11-12):949-54. Epub 2010 Sep 15.

Microsatellite stability in the plant pathogen Botrytis cinerea after exposure to different selective pressures.

Ajouz S, Decognet V, Nicot PC, Bardin M.

INRA, UR407, Plant Pathology Unit, Domaine St Maurice, F-84140 Montfavet, France.

The stability of microsatellite markers was investigated in the spore-producing fungus Botrytis cinerea exposed to four growth conditions. This knowledge is essential in order to differentiate mutations from genetic exchanges or recombination in population genetics studies. It is also important when using strains from collections that need to be regularly propagated on medium. Successive spore generations of four isolates of the fungus were realised in plates on different agar media: a nutrient-rich medium, a nutrient-poor medium, a medium supplemented with the antibiotic pyrrolnitrin and a medium supplemented with the fungicide iprodione. The stability of nine microsatellite markers was studied by comparing the molecular pattern obtained between the wild type parent strains and the final generations obtained. The results showed that, despite the phenotypic changes observed in some generations, no changes were observed in the allele size at nine microsatellite loci whatever the selective pressure endured by the fungus. This is the first study that reveals long-term stability of microsatellite markers of a spore-producing fungus exposed to different stresses.

PMID: 21036339 [PubMed - indexed for MEDLINE]

454. Chin Med J (Engl). 2010 Sep;123(17):2446-50.

Higher concentration of CO₂ and 37°C stabilize the less virulent opaque cell of Candida albicans.

Liu ZH, Li M, Lu XL, She XD, Hu SQ, Chen W, Liu WD.

Department of Medical Mycology, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, Jiangsu 210042, China.

BACKGROUND: Candida albicans (C. albicans) strains can spontaneously switch at a very low frequency from white to opaque phase. The ability to switch reversibly between white and opaque phenotype and contributes to the pathogenicity of C. albicans. White and opaque switching can be induced by various environmental signals. Previous study showed that opaque cells switch en masse to white when transferred in vitro to 37°C, the temperature of their animal host. The objective of the present study was to determine the effect of different concentration of carbon dioxide and temperature on white-opaque switching, and to determine the different anti-candida killing activity of white and opaque form by human monocyte-macrophage cell line THP-1.
METHODS: White-opaque switching and opaque-white switching were assayed. Modified Lee's medium supplemented with phloxine B was used to detect white and opaque forms of C. albicans under 0.03% CO2 at 25°C, 0.03% CO2 at 37°C and 5% CO2 at 37°C. Growth curve of C. albicans was monitored using OD value at 630 nm simultaneously. White and opaque forms of C. albicans and THP-1 cells were cocultured at ratio of 1:10. Colony serial dilutions were used to assay for intracellular candidacidal activity. MTT assay was used to measure the extracellular candidacidal activity.
RESULTS: Phenotype switching was successfully induced in vitro in all three strains of C. albicans. When evaluating white to opaque switching, opaque colony proportion of all colonies was 0.572 ± 0.087, 0.920 ± 0.030 and 0.985 ± 0.026 exposure of white cells to 0.03% CO2 at 25°C, 0.03% CO2 at 37°C and 5% CO2 at 37°C. When evaluating opaque to white switching, opaque colony proportion of all colonies was 0.600 ± 0.114, 0.983 ± 0.003 and 0.998 ± 0.003 exposure of white cells to 0.03% CO2 at 25°C, 0.03% CO2 at 37°C and 5% CO2 at 37°C. No significant difference of white or opaque form growth rate was found among three conditions (P > 0.05). THP-1 mediated extracellular anti-candida activity in white form was (79.80 ± 3.71)% and (56.28 ± 19.12)% at different dilution ratio, which were significantly lower than that in opaque form (100%, P < 0.01). THP-1 mediated intracellular anti-candida activity in white form ((62.98 ± 5.02)%) was significantly lower than that in opaque form ((87.07 ± 1.80)%, P < 0.01).
CONCLUSIONS: Our results showed that opaque form is more vulnerable and less virulent than that in white form. It suggested that higher concentration of CO2 and 37°C in host niches stabilize the less virulent opaque cell of C. albicans, which might have implications for pathogenesis, commensalism and mating.

PMID: 21034563 [PubMed - indexed for MEDLINE]

455. Environ Sci Technol. 2010 Dec 15;44(24):9451-5. Epub 2010 Oct 29.

Effectiveness of UV-C equipped vacuum at reducing culturable surface-bound microorganisms on carpets.

Lutz EA, Sharma S, Casto B, Needham G, Buckley TJ.

Division of Environmental Health Sciences, College of Public Health, The Ohio State University, Columbus, Ohio 43210, United States.

Carpets are both sinks and sources for exposure to chemicals, allergens, and microbes and consequently influence health, including asthma, allergies, and infectious diseases. Asthmatics, children, and the immune-compromised are particularly vulnerable to health risks resulting from exposure to carpet contaminants. To address this risk, a commercial upright vacuum cleaner with an ultraviolet germicidal lamp (λ=253.7 nm, UVC) has been developed for residential and commercial uses. However, its effectiveness in reducing microbial load on real-world carpets has not been previously demonstrated. Accordingly, the purpose of the current study was to evaluate the effectiveness of a UVC-equipped vacuum in reducing the carpet surface-bound microbial load. This was accomplished by comparing the carpet microbial surface load from pre- to post-treatment of 9 ft(2) in-use carpet sections under three treatment scenarios: 1) UVC alone (UV), 2) the beater-bar plus vacuum (BB+Vac), or 3) a combination of all three (COMB). Each treatment was two minutes in duration. Microbial surface loads were measured by pressing contact plates containing Sabourauds Dextrose agar onto the carpet surface. In-use carpets from three locations were tested in place. The treatment effect was evaluated at two levels. First, we considered the mean reduction in CFU from pre- to post-treatment for each 9 ft(2) carpet grid (n = 4 for each treatment). The second level considered each 1 ft(2) section using a paired analysis (n = 40 to 49 for each treatment). A total of 125 pre/post-sample pairs were collected across the three treatments. Results showed that all three treatments were associated with a reduction in carpet microbial load (p < 0.0001). The COMB yielded the largest reduction of 13 CFU/plate (87% reduction) and was approximately the sum of the individual effects of either UVC (6.6 CFU/plate, 60% reduction, p = 0.009) or BB+Vac (7.3 CFU/plate, 78% reduction, p < 0.0001). We therefore conclude that a UVC-equipped vacuum approximately doubles the unit's effectiveness in reducing surface-bound microbial load, thereby holding promise as a means for decreasing indoor infectious disease risk.

PMID: 21033658 [PubMed - indexed for MEDLINE]

456. J Agric Food Chem. 2010 Nov 24;58(22):12014-21. Epub 2010 Oct 28.

GMI, a Ganoderma immunomodulatory protein, down-regulates tumor necrosis factor α-induced expression of matrix metalloproteinase 9 via NF-κB pathway in human alveolar epithelial A549 cells.

Lin CH, Hsiao YM, Ou CC, Lin YW, Chiu YL, Lue KH, Chang JG, Ko JL.

Division of Chest Medicine, Changhua Christian Hospital, Changhua, Taiwan, Republic of China.

Matrix metalloproteinase 9 (MMP-9) has been implicated in airway injury in chronic obstructive pulmonary disease (COPD), lung inflammation, and lung cancer and plays a major role in tumor necrosis factor-α (TNF-α)-stimulated tumor invasion and lung inflammation. MMP-9 activity is promoted by the pro-inflammatory cytokine TNF-α. GMI, cloned from Ganoderma microsporum and purified, is one of the recombinant fungal immunomodulatory proteins. To understand the molecular mechanisms involved in the suppression of TNF-α-mediated tumor invasion and inflammation, GMI modulation of this pathway was investigated in human alveolar epithelial A549 cells in this study. GMI exhibited an inhibitory effect on TNF-α-induced invasion, with GMI treatment and TNF-α exposure presenting the most anti-invasive properties on Boyden chamber assay. GMI reduced TNF-α-induced MMP-9 activities on gelatin zymography assay through inhibition of MMP-9 transcriptional activity. RT-PCR and MMP-9 promoter luciferase analysis revealed that GMI inhibits the transcription of MMP-9 mRNA. Moreover, in vitro and in vivo binding experiments, an electrophoretic mobility shift assay (EMSA), and chromatin immunoprecipitation assay (ChIP) demonstrated that GMI suppresses DNA binding of nuclear factor (NF)-κB transcription factors to MMP-9 promoter. Western blot analysis indicated that GMI blocks the phosphorylation and degradation of IκBα, which in turn leads to suppression of the phosphorylation and nuclear translocation of p65. Thus, overall, our results indicated that GMI mediates antitumor invasion and anti-inflammatory effects through modulation of NF-κB/MMP-9 pathways.

PMID: 21028821 [PubMed - indexed for MEDLINE]

457. Genetics. 2011 Jan;187(1):21-35. Epub 2010 Oct 26.

The DNA polymerase activity of Saccharomyces cerevisiae Rev1 is biologically significant.

Wiltrout ME, Walker GC.

Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 01239, USA.

A cell's ability to tolerate DNA damage is directly connected to the human development of diseases and cancer. To better understand the processes underlying mutagenesis, we studied the cell's reliance on the potentially error-prone translesion synthesis (TLS), and an error-free, template-switching pathway in Saccharomyces cerevisiae. The primary proteins mediating S. cerevisiae TLS are three DNA polymerases (Pols): Rev1, Pol ζ (Rev3/7), and Pol η (Rad30), all with human homologs. Rev1's noncatalytic role in recruiting other DNA polymerases is known to be important for TLS. However, the biological significance of Rev1's unusual conserved DNA polymerase activity, which inserts dC, is much less well understood. Here, we demonstrate that inactivating Rev1's DNA polymerase function sensitizes cells to both chronic and acute exposure to 4-nitroquinoline-1-oxide (4-NQO) but not to UV or cisplatin. Full Rev1-dependent resistance to 4-NQO, however, also requires the additional Rev1 functions. When error-free tolerance is disrupted through deletion of MMS2, Rev1's catalytic activity is more vital for 4-NQO resistance, possibly explaining why the biological significance of Rev1's catalytic activity has been elusive. In the presence or absence of Mms2-dependent error-free tolerance, the catalytic dead strain of Rev1 exhibits a lower 4-NQO-induced mutation frequency than wild type. Furthermore, Pol ζ, but not Pol η, also contributes to 4-NQO resistance. These results show that Rev1's catalytic activity is important in vivo when the cell has to cope with specific DNA lesions, such as N(2)-dG.

PMCID: PMC3018306 PMID: 20980236 [PubMed - indexed for MEDLINE]

458. Chemosphere. 2011 Jan;82(3):340-5. Epub 2010 Oct 25.

Secretion profiles of fungi as potential tools for metal ecotoxicity assessment: a study of enzymatic system in Trametes versicolor.

Lebrun JD, Demont-Caulet N, Cheviron N, Laval K, Trinsoutrot-Gattin I, Mougin C.

INRA, UPR 251 Physico-chimie et Ecotoxicologie des SolS d'Agrosystèmes Contaminés, Route de St Cyr, 78026 Versailles, France. jeremie.lebrun@cemagref.fr

The relationship between the expression of extracellular enzymatic system and a metal stress is scarce in fungi, hence limiting the possible use of secretion profiles as tools for metal ecotoxicity assessment. In the present study, we investigated the effect of Zn, Cu, Pb and Cd, tested alone or in equimolar cocktail, on the secretion profiles at enzymatic and protein levels in Trametesversicolor. For that purpose, extracellular hydrolases (acid phosphatase, β-glucosidase, β-galactosidase and N-acetyl-β-glucosaminidase) and ligninolytic oxidases (laccase, Mn-peroxidase) were monitored in liquid cultures. Fungal secretome was analyzed by electrophoresis and laccase secretion was characterized by western-blot and mass spectrometry analyses. Our results showed that all hydrolase activities were inhibited by the metals tested alone or in cocktail, whereas oxidase activities were specifically stimulated by Cu, Cd and metal cocktail. At protein level, metal exposure modified the electrophoretic profiles of fungal secretome and affected the diversity of secreted proteins. Two laccase isoenzymes, LacA and LacB, identified by mass spectrometry were differentially glycosylated according to the metal exposure. The amount of secreted LacA and LacB was strongly correlated with the stimulation of laccase activity by Cu, Cd and metal cocktail. These modifications of extracellular enzymatic system suggest that fungal oxidases could be used as biomarkers of metal exposure.

PMID: 20980042 [PubMed - indexed for MEDLINE]

459. Curr Microbiol. 2011 Mar;62(3):807-15. Epub 2010 Oct 27.

Cellular responses required for oxidative stress tolerance, colonization, and lesion formation by the necrotrophic fungus Alternaria alternata in citrus.

Lin CH, Yang SL, Chung KR.

Citrus Research and Education Center, IFAS, University of Florida, 700 Experiment Station Road, Lake Alfred, FL 33850, USA.

The pathogenic capability of the tangerine pathotype of Alternaria alternata relies on the production of host-selective ACT toxin. Inoculation of A. alternata in leaves of the citrus quickly induced rapid lipid peroxidation, accumulation of hydrogen peroxide (H(2)O(2)), and cell death, indicative of host defensive response. We previously demonstrated an essential role of the A. alternata AaAP1 gene, encoding a redox-responsive YAP1-like transcription factor, to contribute to fungal pathogenicity. The AaAP1 null mutant fails to incite necrotic lesions. In this study, we show further that the fungal mutant defective at the AaAP1 locus displayed reduced activities for glutathione-S-transferase, glutathione peroxidase, glutathione reductase, and ligninolytic peroxidase, yet retained normal production of ACT toxin. In contrast to the wild-type progenitor and the genetically reverted strain, the mutant strain was unable to detoxify H(2)O(2) effectively and was killed upon exposure to H(2)O(2). The mutant strain induced lower levels of H(2)O(2) accumulation in citrus leaves, compared to those induced by the wild-type or by the genetically reverted strain. Upon exposure to H(2)O(2), A. alternata apparently changed expression of a wide array of the genes regulated by AaAP1. Thus, the impairment of the AaAP1 null mutants to incite necrotic lesions is apparently a consequence of their inability to alleviate the toxicity of ROS, and circumvention of plant defenses is important for the disease process.

PMID: 20978890 [PubMed - indexed for MEDLINE]

460. Eur J Clin Microbiol Infect Dis. 2011 Jan;30(1):1-6. Epub 2010 Oct 27.

Improvement of attention span and reaction time with hyperbaric oxygen treatment in patients with toxic injury due to mold exposure.

Ezra N, Dang K, Heuser G.

Department of Medicine, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.

It is, by now, well established that mold toxins (mycotoxins) can cause significant adverse health effects. In this study, 15 subjects who developed an attention deficit disorder (ADD) and slowing of reaction time at the time of exposure to mold toxins were identified. Deficits in attention span and reaction time were documented not only by taking a careful history, but also by performing a Test of Variables of Attention (TOVA). The TOVA test provides an objective measure of these two variables. It was found that mold-exposed subjects show statistically significant decreases in attention span and significant increases in reaction time to stimuli compared to controls. After ten sessions of hyperbaric oxygen treatment (HBOT), a statistically significant improvement was seen in both measures. This preliminary study suggests promising outcomes in treating mold-exposed patients with hyperbaric oxygen.

PMCID: PMC2998645 PMID: 20978814 [PubMed - indexed for MEDLINE]

461. Clin Med Res. 2011 Jun;9(2):57-65. doi: 10.3121/cmr.2010.958. Epub 2010 Oct 25.

Non-rural point source blastomycosis outbreak near a yard waste collection site.

Pfister JR, Archer JR, Hersil S, Boers T, Reed KD, Meece JK, Anderson JL, Burgess JW, Sullivan TD, Klein BS, Wheat LJ, Davis JP.

Bureau of Communicable Disease and Emergency Response, Wisconsin Division of Public Health, Madison, Wisconsin 53701, USA.

BACKGROUND: Blastomycosis is a potentially fatal infection caused by the fungus Blastomyces dermatitidis. During January 1 through March 5, 2006, twenty-one laboratory confirmed cases of blastomycosis were reported among residents of an endemic area in north-central Wisconsin; a striking increase compared with previous years. The objective of the study was to determine if an observed increase in blastomycosis among residents of an urban area in north-central Wisconsin was caused by a point-source exposure and to identify its source.
METHODS: We compared epidemiologic features, and signs and symptoms of B. dermatitidis infection among 46 historic (1999-2005) and 21 possible outbreak case patients. In addition, a case-control study was conducted to compare risk factors of the outbreak case patients with those of 64 age, gender, and geographically-matched control subjects. We conducted site inspections, evaluated meteorological data, genetically compared outbreak and non-outbreak isolates, and attempted environmental detection of B. dermatitidis using polymerase chain reaction, in vitro isolation, and in vivo isolation by tail vein injection of mice.
RESULTS: The unusual risk profile of this outbreak included: residence within non-rural city limits with limited time spent outdoors and an equivalent gender ratio and young median age among case patients consistent with common source rather than unrelated exposures. Thirteen of fourteen outbreak-associated clinical isolates of B. dermatitidis clustered in the same genetic group by PCR-RFLP analysis. Inspections near the cluster center suggested a yard waste collection site as the probable exposure source. B. dermatitidis nucleic acid was detected in one of 19 environmental samples. Environmental and meteorological conditions and material management practices were identified that may have facilitated growth and dispersal of B. dermatitidis conidia near this residential area.
CONCLUSIONS: Results of our investigation of this large non-rural outbreak of blastomycosis suggest bioaerosol hazards may exist near yard waste collection and composting facilities, especially where pine tree litter is present, in B. dermatitidis endemic areas.

PMCID: PMC3134434 PMID: 20974888 [PubMed - indexed for MEDLINE]

462. Antimicrob Agents Chemother. 2011 Jan;55(1):146-54. Epub 2010 Oct 25.

Profiling the Aspergillus fumigatus proteome in response to caspofungin.

Cagas SE, Jain MR, Li H, Perlin DS.

Public Health Research Institute, University of Medicine and Dentistry of New Jersey UMDNJ, New Jersey Medical School, Newark, NJ 07103, USA.

The proteomic response of Aspergillus fumigatus to caspofungin was evaluated by gel-free isobaric tagging for relative and absolute quantitation (iTRAQ) as a means to determine potential biomarkers of drug action. A cell fractionation approach yielding 4 subcellular compartment fractions was used to enhance the resolution of proteins for proteomic analysis. Using iTRAQ, a total of 471 unique proteins were identified in soluble and cell wall/plasma membrane fractions at 24 and 48 h of growth in rich media in a wild-type drug-susceptible strain. A total of 122 proteins showed at least a 2-fold change in relative abundance following exposure to caspofungin (CSF) at just below the minimum effective concentration (0.12 μg/ml). The largest changes were seen in the mitochondrial hypoxia response domain protein (AFUA_1G12250), the level of which decreased >16-fold in the secreted fraction, and ChiA1, the level of which decreased 12.1-fold in the cell wall/plasma membrane fraction. The level of the major allergen and cytotoxin AspF1 was also shown to decrease by 12.1-fold upon the addition of drug. A subsequent iTRAQ analysis of an echinocandin-resistant strain (fks1-S678P) was used to validate proteins specific to drug action. A total of 103 proteins in the 2 fractions tested by iTRAQ were differentially expressed in the wild-type susceptible strain but not significantly changed in the resistant strain. Of these potential biomarkers, 11 had levels that changed at least 12-fold. Microarray analysis of the susceptible strain was performed to evaluate the correlation between proteomics and genomics, with a total of 117 genes found to be changing at least 2-fold. Of these, a total of 22 proteins with significant changes identified by iTRAQ also showed significant gene expression level changes by microarray. Overall, these data have the potential to identify biomarkers that assess the relative efficacy of echinocandin drug therapy.

PMCID: PMC3019664 PMID: 20974863 [PubMed - indexed for MEDLINE]

463. Mycopathologia. 2011 Jun;171(6):431-4. Epub 2010 Oct 24.

Fusarium sacchari: a cause of exogenous fungal endophthalmitis: first case report and review of literature.

Chander J, Singla N, Gulati N, Sood S.

Department of Microbiology, Government Medical College Hospital, Sector 32, Chandigarh 160030, India. jchander@hotmail.com

A case of exogenous fungal endophthalmitis due to Fusarium sacchari is being reported. It has never been reported in this clinical entity before; hence, to the best of our knowledge, this is first report of F. sacchari as a cause of exogenous fungal endophthalmitis and also the first time when this fungus has been isolated from an Indian patient.

PMID: 20972837 [PubMed - indexed for MEDLINE]

464. Fungal Biol. 2010 Jan;114(1):10-5. Epub 2009 Aug 12.

Metarhizium anisopliae lipolytic activity plays a pivotal role in Rhipicephalus (Boophilus) microplus infection.

Beys da Silva WO, Santi L, Schrank A, Vainstein MH.

Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, P.O. Box 15005, 91501-070 Porto Alegre, RS, Brazil. walterbeys@cbiot.ufrgs.br

Lipases secreted by Metarhizium anisopliae, an important biological control agent, could potentially be involved in the host infection process. Here, we present the activity profile during the host infection process and the effect of lipase activity inhibitor ebelactone B on infection. The previous treatment of spores with lipase activity inhibitor, ebelactone B, completely inhibited lipolytic activity and prevented the infection of the Rhipicephalus (Boophilus) microplus host. The results herein presented prove, for the first time, the importance of lipase activity in M. anisopliae host infection process. The filamentous fungus Metarhizium anisopliae is one of the most important and studied biological agents for the control of several arthropod pests, including the cattle tick Rhipicephalus (Boophilus) microplus. Lipases secreted by M. anisopliae could potentially be involved in the host infection process. This work presents the activity profile during the host infection process and the effect of lipase activity inhibitor ebelactone B on infection. During the course of tick exposure to spores (6-120 h) lipase activity increased from 0.03 ± 0.00 U to 0.312 ± 0.068 U using rho NP palmitate as substrate. In zymograms, bands of lipase activity were detected in ticks treated with spores without inhibitor. The previous treatment of spores with lipase activity inhibitor, ebelactone B, completely inhibited lipolytic activity, at all times specified, and prevented the infection of the R. microplus host. Spores treated with the inhibitor did not germinate on the tick, although this effect was not observed in the culture medium. The results herein presented prove, for the first time, the importance of lipase activity in M. anisopliae host infection process.

PMID: 20965056 [PubMed - indexed for MEDLINE]

465. Amino Acids. 2010 Oct 21. [Epub ahead of print]

Methylglyoxal, glyoxalase 1 and the dicarbonyl proteome.

Rabbani N, Thornalley PJ.

Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, University Hospital, Clifford Bridge Road, Coventry, CV2 2DX, UK.

Methylglyoxal (MG) is a potent protein glycating agent. Glycation is directed to guanidino groups of arginine residues forming mainly hydroimidazolone N (δ)-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) residues. MG-H1 formation is damaging to the proteome as modification is often directed to functionally important arginine residues. MG-H1 content of proteins is quantified by stable isotopic dilution analysis tandem mass spectrometry and also by immunoblotting with specific monoclonal antibodies. MG-glycated proteins undergo cellular proteolysis and release MG-H1 free adduct for excretion. MG-H1 residues have been found in proteins of animals, plants, bacteria, fungi and protoctista. MG-H1 is often the major advanced glycation endproduct in proteins of tissues and body fluids, increasing in diabetes and associated vascular complications, renal failure, cirrhosis, Alzheimer's disease, arthritis, Parkinson's disease and ageing. Glyoxalase 1 and aldo-keto reductase 1B1 metabolise >99% MG to innocuous products and thereby protect the proteome, providing an enzymatic defence against MG-mediated glycation. Proteins susceptible to MG modification with related functional impairment are called the "dicarbonyl proteome" (DCP). DCP includes albumin, haemoglobin, transcription factors, mitochondrial proteins, extracellular matrix proteins, lens crystallins and other proteins. DCP component proteins are linked to mitochondrial dysfunction in diabetes and ageing, oxidative stress, dyslipidemia, cell detachment and anoikis and apoptosis. Biochemical and physiological susceptibility of a protein to modification by MG and sensitivity of biochemical pathways and physiological systems to related functional impairment under challenge of physiologically relevant increases in MG exposure are key concepts. Improved understanding of the DCP will likely have profound importance for human health, longevity and treatment of disease.

PMID: 20963454 [PubMed - as supplied by publisher]

466. Curr Microbiol. 2011 Mar;62(3):739-45. Epub 2010 Oct 21.

Chitosan-EDTA new combination is a promising candidate for treatment of bacterial and fungal infections.

El-Sharif AA, Hussain MH.

Department of Microbiology and Immunology, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt. amanyelsharif@yahoo.com

Chitosan is an attractive preparation widely used as a pharmaceutical excipient. This study aimed to evaluate the antimicrobial activities of chitosan derivatives, EDTA, and the newly developed chitosan-EDTA combination against Gram-negative and Gram-positive bacteria as well as Candida albicans. Antimicrobial activity was studied. Both minimal Inhibitory Concentrations (MIC) and minimal biocidal concentrations (MBC) were determined. Chitosan acetic acid recorded lower MIC values against Enterococcus faecalis, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans than those exhibited by EDTA. EDTA failed to have inhibitory activity against Enterococcus faecalis as well as MBC against any of the studied microorganisms. Chitosan acetic acid's MBC were recorded to all examined species. Checkerboard assay results indicated a synergistic antimicrobial activity of the new combination against Staphylococcus aureus and an additive effect against other microorganisms. Moreover, a short microbial exposure to chitosan-EDTA (20-30 min) caused complete eradication. Due to the continuous emergence of resistant strains, there is an urgent need to discover new antimicrobial agents. Our findings suggest the use of chitosan as an enhancing agent with antibacterial and antifungal properties in combination with EDTA in pharmaceutical preparations.

PMID: 20963418 [PubMed - indexed for MEDLINE]

467. Sci Signal. 2010 Oct 19;3(144):ra75.

Single-cell analysis reveals that insulation maintains signaling specificity between two yeast MAPK pathways with common components.

Patterson JC, Klimenko ES, Thorner J.

Division of Biochemistry and Molecular Biology, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3202, USA.

Eukaryotic cells use multiple mitogen-activated protein kinase (MAPK) cascades to evoke appropriate responses to external stimuli. In Saccharomyces cerevisiae, the MAPK Fus3 is activated by pheromone-binding heterotrimeric guanosine triphosphate-binding protein (G protein)-coupled receptors to promote mating, whereas the MAPK Hog1 is activated by hyperosmotic stress to elicit the high-osmolarity glycerol (HOG) response. Although these MAPK pathways share several upstream components, exposure to either pheromone or osmolyte alone triggers only the appropriate response. We used fluorescence localization- and transcription-specific reporters to assess activation of these pathways in individual cells on the minute and hour time scale, respectively. Dual activation of these two MAPK pathways occurred over a broad range of stimulant concentrations and temporal regimes in wild-type cells subjected to costimulation. Thus, signaling specificity is achieved through an "insulation" mechanism, not a "cross-inhibition" mechanism. Furthermore, we showed that there was a critical period during which Hog1 activity had to occur for proper insulation of the HOG pathway.

PMID: 20959523 [PubMed - indexed for MEDLINE]

468. Arch Environ Contam Toxicol. 2011 Aug;61(2):211-9. Epub 2010 Oct 19.

Effects of cadmium and phenanthrene mixtures on aquatic fungi and microbially mediated leaf litter decomposition.

Moreirinha C, Duarte S, Pascoal C, Cássio F.

Department of Biology, Centre of Molecular and Environmental Biology, University of Minho, Campus de Gualtar, 4710-057, Braga, Portugal.

Urbanization and industrial activities have contributed to widespread contamination by metals and polycyclic aromatic hydrocarbons, but the combined effects of these toxics on aquatic biota and processes are poorly understood. We examined the effects of cadmium (Cd) and phenanthrene on the activity and diversity of fungi associated with decomposing leaf litter in streams. Leaves of Alnus glutinosa were immersed for 10 days in an unpolluted low-order stream in northwest Portugal to allow microbial colonization. Leaves were then exposed in microcosms for 14 days to Cd (0.06-4.5 mg L(-1)) and phenanthrene (0.2 mg L(-1)) either alone or in mixture. A total of 19 aquatic hyphomycete species were found sporulating on leaves during the whole study. The dominant species was Articulospora tetracladia, followed by Alatospora pulchella, Clavatospora longibrachiata, and Tetrachaetum elegans. Exposure to Cd and phenanthrene decreased the contribution of A. tetracladia to the total conidial production, whereas it increased that of A. pulchella. Fungal diversity, assessed as denaturing gradient gel electrophoresis fingerprinting or conidial morphology, was decreased by the exposure to Cd and/or phenanthrene. Moreover, increased Cd concentrations decreased leaf decomposition and fungal reproduction but did not inhibit fungal biomass production. Exposure to phenanthrene potentiated the negative effects of Cd on fungal diversity and activity, suggesting that the co-occurrence of these stressors may pose additional risk to aquatic biodiversity and stream ecosystem functioning.

PMID: 20957352 [PubMed - indexed for MEDLINE]

469. Anal Bioanal Chem. 2011 Mar;399(9):2899-907. Epub 2010 Oct 15.

Development of an analytical procedure for evaluation of the protective behaviour of innovative fungal patinas on archaeological and artistic metal artefacts.

Joseph E, Simon A, Prati S, Wörle M, Job D, Mazzeo R.

Microchemistry and Microscopy Art Diagnostic Laboratory, University of Bologna, 40126 Ravenna, Bologna, Italy. edith.joseph@snm.admin.ch

In the literature, the ability to transform metal compounds into metal oxalates has been reported for different species of fungi. This could be an innovative conservation method for archaeological and artistic metal artefacts. In fact, with a high degree of insolubility and chemical stability even in acid atmospheres (pH 3), metal oxalates provide the surface with good protection. Within the framework of the EU-ARTECH project, different fungal strains have been used to transform existing corrosion patinas on outdoor bronze monuments into copper oxalates, while preserving the physical appearance of these artefacts. Given the promising results obtained with this first attempt, the same approach is now applied within the BAHAMAS (Marie Curie Intra European Fellowship action) project, but extended to other metal substrates, for example iron and silver, which are frequently found in cultural heritage artworks and also encounter several problems of active corrosion. The research is investigating the formation mechanisms and adhesion properties of the newly formed metal oxalates by means of complementary analytical techniques (X-ray diffraction (XRD), FTIR microscopy, Raman microscopy, scanning electron microscopy (SEM-EDS), electrochemical impedance spectroscopy (EIS), colorimetry). For each metal substrate, the most appropriate fungal strain is going to be identified and applied to corroded sheets and the novel fungal treatment compared with those used so far. Treated metal sheets will be monitored during 1-year exposure to different cycles of artificial ageing, to evaluate the corrosion resistance of the fungal patinas obtained. The objective of this contribution is to present the first results achieved so far on naturally corroded bronze sheets during the EU-ARTECH project and the analytical procedure used for the testing of the proposed treatment performances during the BAHAMAS project.

PMID: 20949259 [PubMed - indexed for MEDLINE]

470. J Allergy (Cairo). 2010;2010. pii: 510380. Epub 2010 Jun 16.

The Relationship between Mold Exposure and Allergic Response in Post-Katrina New Orleans.

Rabito FA, Perry S, Davis WE, Yau CL, Levetin E.

Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, 1440 Canal Street SL-18, New Orleans, LA 70112, USA.

Objectives. The study's objective was to examine the relation between mold/dampness exposure and mold sensitization among residents of Greater New Orleans following Hurricane Katrina. Methods. Patients were recruited from the Allergy Clinic of a major medical facility. Any patient receiving a skin prick test for one of 24 molds between December 1, 2005 and December 31, 2008 was eligible for the study. Exposure was assessed using standardized questionnaires. Positive mold reactivity was defined as a wheal diameter >3 mm to any mold genera. Results. Approximately 57% of participants tested positive to any indoor allergen, 10% to any mold. Over half of respondents had significant home damage, 34% reported dampness/mold in their home, half engaged in renovation, and one-third lived in a home undergoing renovation. Despite extensive exposure, and multiple measures of exposure, we found no relationship between mold/dampness exposure and sensitivity to mold allergens. Conclusions. These results along with results of earlier research indicate no excess risk of adverse respiratory effects for residents living in New Orleans after the devastation of Hurricane Katrina.

PMCID: PMC2948940 PMID: 20948880 [PubMed]

471. J Biol Chem. 2010 Dec 17;285(51):40081-7. Epub 2010 Oct 14.

Novel channel enzyme fusion proteins confer arsenate resistance.

Wu B, Song J, Beitz E.

Department of Pharmaceutical and Medicinal Chemistry, Christian-Albrechts-Universität zu Kiel, 24118 Kiel, Germany.

Steady exposure to environmental arsenic has led to the evolution of vital cellular detoxification mechanisms. Under aerobic conditions, a two-step process appears most common among microorganisms involving reduction of predominant, oxidized arsenate (H(2)As(V)O(4)(-)/HAs(V)O(4)(2-)) to arsenite (As(III)(OH)(3)) by a cytosolic enzyme (ArsC; Escherichia coli type arsenate reductase) and subsequent extrusion via ArsB (E. coli type arsenite transporter)/ACR3 (yeast type arsenite transporter). Here, we describe novel fusion proteins consisting of an aquaglyceroporin-derived arsenite channel with a C-terminal arsenate reductase domain of phosphotyrosine-phosphatase origin, providing transposable, single gene-encoded arsenate resistance. The fusion occurred in actinobacteria from soil, Frankia alni, and marine environments, Salinispora tropica; Mycobacterium tuberculosis encodes an analogous ACR3-ArsC fusion. Mutations rendered the aquaglyceroporin channel more polar resulting in lower glycerol permeability and enhanced arsenite selectivity. The arsenate reductase domain couples to thioredoxin and can complement arsenate-sensitive yeast strains. A second isoform with a nonfunctional channel may use the mycothiol/mycoredoxin cofactor pool. These channel enzymes constitute prototypes of a novel concept in metabolism in which a substrate is generated and compartmentalized by the same molecule. Immediate diffusion maintains the dynamic equilibrium and prevents toxic accumulation of metabolites in an energy-saving fashion.

PMCID: PMC3000990 PMID: 20947511 [PubMed - indexed for MEDLINE]

472. Aquat Toxicol. 2011 Jan 17;101(1):72-7. Epub 2010 Sep 16.

Low dose TBT exposure decreases amphipod immunocompetence and reproductive fitness.

Jacobson T, Sundelin B, Yang G, Ford AT.

Department of Applied Environmental Science, Stockholm University, Stockholm, Sweden.

The antifouling agent tributyltin (TBT) is a highly toxic pollutant present in many aquatic ecosystems. Despite of regulations on the usage of TBT, it remains in high concentrations in sediments both in harbors and in off-shore sites. The toxicity of TBT in mollusks is well documented. However, adverse effects in other aquatic organisms, such as crustaceans, are less well known. This study is an effort to assess the effects of environmentally realistic concentrations of TBT on an ecologically important species in Swedish fresh and brackish water ecosystems, the benthic amphipod Monoporeia affinis. Field collected animals were exposed during gonad maturation to TBT (70 and 170 ng/g sediment d wt) for five weeks in static microcosms with natural sediment. Exposure concentrations were chosen to reflect effects at concentrations found in Swedish coastal sediment, but below expected effects on survival. TBT exposure resulted in a statistically significant adverse effect on oocyte viability and a doubling of the prevalence of microsporidian parasites in females, from 17% in the control to 34% in the 170 ng TBT/g sediment d wt exposure. No effects on survival were observed. Borderline significant effects were observed on male sexual maturation in the 70 ng TBT/g d wt exposure and on ecdysteroid levels in the 170 ng/g sediment d wt exposure. Both reproduction and parasite infection effects are of ecological importance since they have the potential to affect population viability in the field. This study gives further evidence to the connection between low dose contaminant exposure and increases in microsporidian parasite infection.

PMID: 20947182 [PubMed - indexed for MEDLINE]

473. Mycologia. 2010 Sep-Oct;102(5):1134-40.

Effect of light exposure on in vitro germination and germ tube growth of eight species of rust fungi.

Buck JW, Dong W, Mueller DS.

University of Georgia, Department of Plant Pathology, Griffin, Georgia 30223, USA. jwbuck@uga.edu

The effects of light on urediniospore germination and germ tube elongation was studied with eight species of rust fungi that infect ornamental plants or row crops. Exposure of six species of fungi to cool white fluorescent light at 400 or 600 micromol s(-1) m(-2) for 24 h significantly reduced germination with largest decreases typically observed at 600 micromol s(-1) m(-2). Germination and germ tube elongation did not recover during 24 h dark incubation after 18 h exposure to fluorescent light at 600 micromol s(-1) m(-2), indicating the effects were not reversible. Germ tube elongation of all fungi was negatively affected by increased length of exposure to fluorescent light. Increased exposure to fluorescent light differentially affected germination of the fungi with Puccinia hemerocallidis, Phakopsora pachyrhizi, Pucciniastrum vaccinii and Puccinia menthae negatively affected and Puccinia sorghi, Puccinia triticina, Puccinia pelargonii-zonalis and Puccinia iridis relatively unaffected in 10 h incubation. Exposure of Ph. pachyrhizi and P. triticina urediniospores to sunlight rapidly reduced germination and germ tube elongation with no germination observed for Ph. pachyrhizi after 2.5 h. Germ tube elongation but not germination of hydrated urediniospores of Ph. pachyrhizi and P. triticina was significantly reduced compared to dry urediniospores exposed to 10 h fluorescent light followed by 24 h dark incubation. Exposure to fluorescent light (all fungi) or sunlight (two fungi) negatively affected urediniospore germ tube elongation. Differences observed in urediniospore germination between fungi suggest some species have co-evolved with their host for differing light conditions. Our data suggests exposure of urediniospores to strong light could inactivate rust fungi on plant surfaces or in the atmosphere.

PMID: 20943512 [PubMed - indexed for MEDLINE]

474. Fungal Biol. 2010 Aug;114(8):637-45. Epub 2010 May 25.

Comparative analysis of the Metarhizium anisopliae secretome in response to exposure to the greyback cane grub and grub cuticles.

Manalil NS, Junior Téo VS, Braithwaite K, Brumbley S, Samson P, Helena Nevalainen KM.

Department of Chemistry and Biomolecular Sciences, Macquarie University, Sydney, NSW 2109, Australia. nchikbal@bio.mq.edu.au

Metarhizium anisopliae is a well-characterized biocontrol agent of a wide range of insects including cane grubs. In this study, a two-dimensional (2D) electrophoresis was used to display secreted proteins of M. anisopliae strain FI-1045 growing on the whole greyback cane grubs and their isolated cuticles. Hydrolytic enzymes secreted by M. anisopliae play a key role in insect cuticle-degradation and initiation of the infection process. We have identified all the 101 protein spots displayed by cross-species identification (CSI) from the fungal kingdom. Among the identified proteins were 64-kDa serine carboxypeptidase, 1,3 beta-exoglucanase, Dynamin GTPase, THZ kinase, calcineurin like phosphoesterase, and phosphatidylinositol kinase secreted by M. ansiopliae (FI-1045) in response to exposure to the greyback cane grubs and their isolated cuticles. These proteins have not been previously identified from the culture supernatant of M. anisopliae during infection. To our knowledge, this the first proteomic map established to study the extracellular proteins secreted by M. ansiopliae (FI-1045) during infection of greyback cane grubs and its cuticles.

PMID: 20943175 [PubMed - indexed for MEDLINE]

475. Fungal Biol. 2010 May-Jun;114(5-6):490-7. Epub 2010 Mar 31.

Use of response surface methodology to optimise environmental stress conditions on Penicillium glabrum, a food spoilage mould.

Nevarez L, Vasseur V, Debaets S, Barbier G.

Université Européenne de Bretagne, France.

Fungi are ubiquitous microorganisms often associated with spoilage and biodeterioration of a large variety of foods and feedstuffs. Their growth may be influenced by temporary changes in intrinsic or environmental factors such as temperature, water activity, pH, preservatives, atmosphere composition, all of which may represent potential sources of stress. Molecular-based analyses of their physiological responses to environmental conditions would help to better manage the risk of alteration and potential toxicity of food products. However, before investigating molecular stress responses, appropriate experimental stress conditions must be precisely defined. Penicillium glabrum is a filamentous fungus widely present in the environment and frequently isolated in the food processing industry as a contaminant of numerous products. Using response surface methodology, the present study evaluated the influence of two environmental factors (temperature and pH) on P. glabrum growth to determine 'optimised' environmental stress conditions. For thermal and pH shocks, a large range of conditions was applied by varying factor intensity and exposure time according to a two-factorial central composite design. Temperature and exposure duration varied from 30 to 50 °C and from 10 min to 230 min, respectively. The effects of interaction between both variables were observed on fungal growth. For pH, the duration of exposure, from 10 to 230 min, had no significant effect on fungal growth. Experiments were thus carried out on a range of pH from 0.15 to 12.50 for a single exposure time of 240 min. Based on fungal growth results, a thermal shock of 120 min at 40 °C or a pH shock of 240 min at 1.50 or 9.00 may therefore be useful to investigate stress responses to non-optimal conditions.

PMID: 20943160 [PubMed - indexed for MEDLINE]

476. Fungal Biol. 2010 Feb-Mar;114(2-3):198-208. Epub 2009 Dec 22.

Ambient pH intrinsically influences Trichoderma conidiation and colony morphology.

Steyaert JM, Weld RJ, Stewart A.

Bio-Protection Research Centre, PO Box 84, Lincoln University, Lincoln 7647, New Zealand. johanna.steyaert@lincoln.ac.nz

Conidiation in Trichoderma has been demonstrated to be favoured by a low ambient pH and more recently PacC (Pac1) mediated pH-regulation has been implicated in the control of conidiation. In this study, ambient pH effects on conidiation were investigated in three isolates (Trichoderma hamatum, Trichoderma atroviride and Trichoderma pleuroticola) exposed to a single blue-light burst or to mycelial injury. Disks of conidiation were observed for T. atroviride in response to a single light exposure, which clearly demonstrates that all cells are potentially competent for photoconidiation. Previous studies have suggested T. hamatum does not conidiate in response to mycelial injury, however, in this study a clear injury response was observed from pH 2.8 to 3.2. T. pleuroticola displayed three distinct pH-dependent colony morphologies from pH 2.8 to 5.2. Conidiation was strictly low pH-dependent on buffered media and observed at all pH values on unbuffered media. The dependence of the conidial phenotype on the buffering state of the medium rather than the pH per se, was unexpected as it has been suggested that conidiation is PacC regulated. Conversely, excretion of an anthraquinone was strictly pH-dependent regardless of the buffering state. These studies highlight the complexity of ambient pH effects on Trichoderma spp. and demonstrate a need to widen the scope of research to multiple species.

PMID: 20943130 [PubMed - indexed for MEDLINE]

477. PLoS One. 2010 Sep 30;5(9). pii: e12820.

Competition on the rocks: community growth and tessellation.

Jettestuen E, Nermoen A, Hestmark G, Timdal E, Mathiesen J.

Physics of Geological Processes, University of Oslo, Oslo, Norway.

Crustose lichen communities on rocks exhibit fascinating spatial mosaics resembling political maps of nations or municipalities. Although the establishment and development of biological populations are important themes in ecology, our understanding of the formation of such patterns on the rocks is still in its infancy. Here, we present a novel model of the concurrent growth, establishment and interaction of lichens. We introduce an inverse technique based on Monte Carlo simulations to test our model on field samples of lichen communities. We derive an expression for the time needed for a community to cover a surface and predict the historical spatial dynamics of field samples. Lichens are frequently used for dating the time of exposure of rocks in glacial deposits, lake retreats or rock falls. We suggest our method as a way to improve the dating.

PMCID: PMC2948004 PMID: 20941362 [PubMed - indexed for MEDLINE]

478. J Dent Res. 2010 Dec;89(12):1476-81. Epub 2010 Oct 12.

Effect of biofilm on the repair bond strengths of composites.

Rinastiti M, Özcan M, Siswomihardjo W, Busscher HJ, van der Mei HC.

Department of Biomedical Engineering, University Medical Center Groningen, and University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.

Composite restorations degrade during wear, but it is unknown how wear affects the composite surface and influences composite-to-composite bonding in minimally invasive repair. Here, it is hypothesized that in vitro exposure of composites to oral biofilm yields clinically relevant degradation of composite surfaces, and its influence on composite-to-composite bonding is determined. Biofilms on composite surfaces in vitro increased their roughness and decreased filler particle exposure, except for a microhybrid composite, similar to effects of clinical wear in palatal appliances. Failure shear stresses after intermediate-adhesive-resin application were significantly lower after aging by in vitro exposure to biofilms, while silica-coating maintained the same failure stress levels as in non-aged composites. Failure modes were predominantly cohesive after silica-coating, while intermediate-adhesive-resin application yielded more adhesive failure. It is concluded that in vitro exposure to oral biofilm is a clinically relevant aging condition, and that silica-coating is to be preferred for the repair of aged composites.

PMID: 20940354 [PubMed - indexed for MEDLINE]

479. J Environ Monit. 2010 Nov;12(11):2161-4. Epub 2010 Oct 11.

Airborne enzyme measurements to detect indoor mould exposure.

Rylander R, Reeslev M, Hulander T.

BioFact Environmental Health Research Centre, Bjorkasv 21, 44391, Lerum, Sweden. envhealth@biofact.se

Mould in buildings constitutes a threat to health. Present methods to determine the moulds comprise counting of spores or determination of viable moulds which give imprecise measures of total mould cell biomass. Analysis of ergosterol and β-glucan as markers of mould cell biomass is expensive and cumbersome. To evaluate if airborne enzyme activity was related to mould in buildings air samples were taken using an impinger technique or cellulose filters in 386 rooms in 141 buildings. The samples were analysed for the activity of N-acetylhexosaminidase (NAHA) and expressed as enzyme units per m(3) (EU per m(3)). The highest value found in a building was used for the classification of the building and was related to the results from the subsequent technical inspection. In buildings without mould damage, the NAHA activity was generally below 20 EU per m(3). In buildings with mould damage, almost all the buildings had activities above 20 EU per m(3) (specificity 85%). At 30 EU per m(3) the specificity was 100%. Measurements of airborne enzyme activity have a high sensitivity and specificity to identify buildings with mould problems. The method can be used in the investigations of building related symptoms or for home exposure characteristics when investigating diseases such as asthma that can be related to mould exposure.

PMID: 20936239 [PubMed - indexed for MEDLINE]

480. Anal Bioanal Chem. 2011 May;400(4):1009-13. Epub 2010 Oct 6.

Microscreening toxicity system based on living magnetic yeast and gradient chips.

García-Alonso J, Fakhrullin RF, Paunov VN, Shen Z, Hardege JD, Pamme N, Haswell SJ, Greenway GM.

Department of Biological Sciences, University of Hull, England, UK. j.garcia-alonso@nhm.ac.uk

There is an increasing demand for easy and cost-effective methods to screen the toxicological impact of the growing number of chemical mixtures being generated by industry. Such a screening method has been developed using viable, genetically modified green fluorescent protein (GFP) reporter yeast that was magnetically functionalised and held within a microfluidic device. The GFP reporter yeast was used to detect genotoxicity by monitoring the exposure of the cells to a well-known genotoxic chemical (methyl methane sulfonate, MMS). The cells were magnetised using biocompatible positively charged PAH-stabilised magnetic nanoparticles with diameters around 15 nm. Gradient mixing was utilised to simultaneously expose yeast to a range of concentrations of toxins, and the effective fluorescence emitted from the produced GFP was measured. The magnetically enhanced retention of the yeast cells, with their facile subsequent removal and reloading, allowed for very convenient and rapid toxicity screening of a wide range of chemicals. This is the first report showing magnetic yeast within microfluidic devices in a simple bioassay, with potential applications to other types of fluorescent reporter yeast in toxicological and biomedical research. The microfluidic chip offers a simple and low-cost screening test that can be automated to allow multiple uses (adapted to different cell types) of the device on a wide range of chemicals and concentrations.

PMID: 20924564 [PubMed - indexed for MEDLINE]

481. Antimicrob Agents Chemother. 2010 Dec;54(12):5062-9. Epub 2010 Oct 4.

Mechanism of antifungal activity of terpenoid phenols resembles calcium stress and inhibition of the TOR pathway.

Rao A, Zhang Y, Muend S, Rao R.

Department of Physiology, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA.

Terpenoid phenols, including carvacrol, are components of oregano and other plant essential oils that exhibit potent antifungal activity against a wide range of pathogens, including Candida albicans, Staphylococcus aureus, and Pseudomonas aeruginosa. To gain a mechanistic view of the cellular response to terpenoid phenols, we used Saccharomyces cerevisiae as a model organism and monitored temporal changes in metabolic activity, cytosolic and vacuolar pH, and Ca(2+) transients. Using a panel of related compounds, we observed dose-dependent Ca(2+) bursts that correlated with antifungal efficacy. Changes in pH were long lasting and followed the Ca(2+) transients. A vma mutant lacking functional vacuolar H(+)-ATPase (V-ATPase) and defective in ion homeostasis was hypersensitive to carvacrol toxicity, consistent with a role for ionic disruptions in mediating cell death. Genomic profiling within 15 min of exposure revealed a robust transcriptional response to carvacrol, closely resembling that of calcium stress. Genes involved in alternate metabolic and energy pathways, stress response, autophagy, and drug efflux were prominently upregulated, whereas repressed genes mediated ribosome biogenesis and RNA metabolism. These responses were strongly reminiscent of the effects of rapamycin, the inhibitor of the TOR pathway of nutrient sensing. The results point to the activation of specific signaling pathways downstream of cellular interaction with carvacrol rather than a nonspecific lesion of membranes, as has been previously proposed.

PMCID: PMC2981246 PMID: 20921304 [PubMed - indexed for MEDLINE]

482. Ecohealth. 2010 Sep;7(3):380-8. Epub 2010 Oct 2.

Immmunological clearance of Batrachochytrium dendrobatidis infection at a pathogen-optimal temperature in the hylid frog Hypsiboas crepitans.

Márquez M, Nava-González F, Sánchez D, Calcagno M, Lampo M.

Centro de Ecología, Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela.

Amphibian declines worldwide have been linked to the fungal disease chytridiomycosis. Its causative agent (Batrachochytrium dendrobatidis, hereafter Bd), however, also infects many nondeclining species. Experimental infections have shown species-specific and temperature-dependent frog responses to Bd infection. Although Bd infection may be eliminated by housing amphibians at temperatures above those tolerated by the fungus, the question of whether frogs can eliminate infection under more favorable conditions remains unanswered. Repeated diagnostics using real-time polymerase chain reaction (rt-PCR) assays of postmetamorphic individuals at 28, 38, 45, 53, and 62 days after exposure demonstrated that Hypsiboas crepitans is able to clear infection within a few weeks at 23°C. Thus, we demonstrate a temperature-independent and likely immunological mechanism for the clearance of Bd in a resistant amphibian species. Future studies are needed to determine the generality of this mechanism among amphibians and to describe the immune factors affecting different outcomes of Bd exposure including resistance to infection, tolerance of infection, and clearance of infection.

PMID: 20890631 [PubMed - indexed for MEDLINE]

483. Fungal Genet Biol. 2011 Feb;48(2):144-53. Epub 2010 Sep 29.

A sterol 14α-demethylase is required for conidiation, virulence and for mediating sensitivity to sterol demethylation inhibitors by the rice blast fungus Magnaporthe oryzae.

Yan X, Ma WB, Li Y, Wang H, Que YW, Ma ZH, Talbot NJ, Wang ZY.

State Key Laboratory for Rice Biology, Institute of Biotechnology, Zhejiang University, Hangzhou 310029, People's Republic of China.

The Magnaporthe oryzae genome contains two homologous CYP51 genes, MoCYP51A and MoCYP51B, that putatively encode sterol 14α-demethylase enzymes. Targeted gene deletion mutants of MoCYP51A were morphologically indistinguishable from the isogenic wild type M. oryzae strain Guy11 in vegetative culture, but were impaired in both conidiation and virulence. Deletion of MoCYP51B did not result in any obvious phenotypic changes compared with Guy11. The Δmocyp51A mutants were also highly sensitive to sterol demethylation inhibitor (DMI) fungicides, while Δmocyp51B mutants were unchanged in their sensitivity to these fungicides. Expression of both MoCYP51A and MoCYP51B was significantly induced by exposure to DMI fungicides. Analysis of intracellular localization of MoCyp51A showed that MoCyp51A was mainly localized to the cytoplasm of hyphae and conidia. Taken together, our results indicate that MoCYP51A is required for efficient conidiogenesis, full virulence and for mediating DMI sensitivity by the rice blast fungus.

PMID: 20887796 [PubMed - indexed for MEDLINE]

484. PLoS One. 2010 Sep 23;5(9):e12957.

Presence of anti-microbial antibodies in liver cirrhosis--a tell-tale sign of compromised immunity?

Papp M, Norman GL, Vitalis Z, Tornai I, Altorjay I, Foldi I, Udvardy M, Shums Z, Dinya T, Orosz P, Lombay B Jr, Par G, Par A, Veres G, Csak T, Osztovits J, Szalay F, Lakatos PL.

2nd Department of Medicine, University of Debrecen, Debrecen, Hungary. drpappm@yahoo.com

BACKGROUND: Bacterial translocation plays important role in the complications of liver cirrhosis. Antibody formation against various microbial antigens is common in Crohn's disease and considered to be caused by sustained exposure to gut microflora constituents. We hypothesized that anti-microbial antibodies are present in patients with liver cirrhosis and may be associated with the development of bacterial infections. METHODOLOGY/PRINCIPAL FINDINGS: Sera of 676 patients with various chronic liver diseases (autoimmune diseases: 266, viral hepatitis C: 124, and liver cirrhosis of different etiology: 286) and 100 controls were assayed for antibodies to Saccharomyces cerevisiae (ASCA) and to antigens derived from two intestinal bacterial isolates (one gram positive, one gram negative, neither is Escherichia coli). In patients with liver cirrhosis, we also prospectively recorded the development of severe episodes of bacterial infection. ASCA and anti-OMP Plus™ antibodies were present in 38.5% and 62.6% of patients with cirrhosis and in 16% and 20% of controls, respectively (p<0.001). Occurrence of these antibodies was more frequent in cases of advanced cirrhosis (according to Child-Pugh and MELD score; p<0.001) or in the presence of ascites (p<0.001). During the median follow-up of 425 days, 81 patients (28.3%) presented with severe bacterial infections. Anti-microbial antibody titers (p = 0.003), as well as multiple seroreactivity (p = 0.036), was associated with infectious events. In logistic regression analysis, the presence of ascites (OR: 1.62, 95%CI: 1.16-2.25), co-morbidities (OR: 2.22, 95%CI: 1.27-3.86), and ASCA positivity (OR: 1.59, 95%CI: 1.07-2.36) were independent risk factors for severe infections. A shorter time period until the first infection was associated with the presence of ASCA (p = 0.03) and multiple seropositivity (p = 0.037) by Kaplan-Meier analysis, and with Child-Pugh stage (p = 0.018, OR: 1.85) and co-morbidities (p<0.001, OR: 2.02) by Cox-regression analysis. CONCLUSIONS/SIGNIFICANCE: The present study suggests that systemic reactivity to microbial components reflects compromised mucosal immunity in patients with liver cirrhosis, further supporting the possible role of bacterial translocation in the formation of anti-microbial antibodies.

PMCID: PMC2944893 PMID: 20886039 [PubMed - indexed for MEDLINE]

485. PLoS One. 2010 Sep 23;5(9):e12955.

Generation of IL-23 producing dendritic cells (DCs) by airborne fungi regulates fungal pathogenicity via the induction of T(H)-17 responses.

Chamilos G, Ganguly D, Lande R, Gregorio J, Meller S, Goldman WE, Gilliet M, Kontoyiannis DP.

Department of Immunology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America.

Interleukin-17 (IL-17) producing T helper cells (T(H)-17) comprise a newly recognized T cell subset with an emerging role in adaptive immunity to a variety of fungi. Whether different airborne fungi trigger a common signaling pathway for T(H)-17 induction, and whether this ability is related to the inherent pathogenic behavior of each fungus is currently unknown. Here we show that, as opposed to primary pathogenic fungi (Histoplasma capsulatum), opportunistic fungal pathogens (Aspergillus and Rhizopus) trigger a common innate sensing pathway in human dendritic cells (DCs) that results in robust production of IL-23 and drives T(H)-17 responses. This response requires activation of dectin-1 by the fungal cell wall polysaccharide b-glucan that is selectively exposed during the invasive growth of opportunistic fungi. Notably, unmasking of b-glucan in the cell wall of a mutant of Histoplasma not only abrogates the pathogenicity of this fungus, but also triggers the induction of IL-23 producing DCs. Thus, b-glucan exposure in the fungal cell wall is essential for the induction of IL-23/T(H)-17 axis and may represent a key factor that regulates protective immunity to opportunistic but not pathogenic fungi.

PMCID: PMC2944889 PMID: 20886035 [PubMed - indexed for MEDLINE]

486. Crit Rev Microbiol. 2010 Nov;36(4):282-98.

Candida tropicalis in human disease.

Ann Chai LY, Denning DW, Warn P.

Department of Medicine, National University Hospital, Singapore.

Candida tropicalis is one of the more common Candida causing human disease in tropical countries; the frequency of invasive disease varies by geography causing 3–66% of candidaemia. C. tropicalis is taxonomically close to C. albicans and shares many pathogenic traits. C. tropicalis is particularly virulent in neutropenic hosts commonly with hematogenous seeding to peripheral organs. For candidaemia and invasive candidiasis amphotericin B or an echinocandin are recommended as first-line treatment, with extended-spectrum triazoles acceptable alternatives. Primary fluconazole resistance is uncommon but may be induced on exposure. Physicians in regions where C. tropicalis is common need to be mindful of this lesser-described pathogen.

PMID: 20883082 [PubMed - indexed for MEDLINE]

487. Ecotoxicology. 2010 Nov;19(8):1626-33. Epub 2010 Sep 30.

An assessment of the potential of the microbial assay for risk assessment (MARA) for ecotoxicological testing.

Fai PB, Grant A.

Department of Animal Biology, Faculty of Sciences, University of Dschang, Dschang, West Region, Cameroon, asangapb@yahoo.com.

Rapid microscale toxicity tests make it possible to screen large numbers of compounds and greatly simplify toxicity identification evaluation and other effect directed chemical analyses of effluents or environmental samples. Tests using Vibrio fischeri (such as Microtox®) detect toxicants that cause non-specific narcosis, but are insensitive to other important classes of contaminants. The microbial assay for risk assessment (MARA) is a 24 h multi-species test that seeks to address this problem by using a battery of ten bacteria and a fungus. But there has been little independent evaluation of this test, and there is no published information on its sensitivity to pesticides. Here, we assess the performance of MARA using a range of toxicants including reference chemicals, fungicides and environmental samples. Mean MARA microbial toxic concentrations and IC(20)s (20% Inhibitory concentrations) indicate the toxicant concentrations affecting the more sensitive micro-organisms, while the mean IC(50) (50% Inhibitory concentration) was found to be the concentration that was toxic to most MARA species. For the two fungicides tested, the yeast (Pichia anomalia) was the most sensitive of the ten MARA species, and was more sensitive than the nine other yeasts tested. The test may be particularly valuable for work with fungicides. Mean MARA IC(50)s were comparable to values for nine other yeast species and the lowest individual IC(50)s for each toxicant were comparable to reported IC(50)s for Daphnia magna, Selenastrum capricornutum and Microtox® bioassays. MARA organisms exhibited more variable sensitivities, with the most sensitive organism being different for different samples, enhancing the likelihood of toxicity detection and giving a toxicity "fingerprint" that may help identify toxicants. The test, therefore, has great potential and would be valuable for ecotoxicological testing of pollutants.

PMID: 20882341 [PubMed - indexed for MEDLINE]

488. Mol Genet Genomics. 2010 Dec;284(6):415-24. Epub 2010 Sep 28.

Global gene expression analysis of Aspergillus nidulans reveals metabolic shift and transcription suppression under hypoxia.

Masuo S, Terabayashi Y, Shimizu M, Fujii T, Kitazume T, Takaya N.

Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8572, Japan.

Hypoxia imposes a challenge upon most filamentous fungi that require oxygen for proliferation. Here, we used whole genome DNA microarrays to investigate global transcriptional changes in Aspergillus nidulans gene expression after exposure to hypoxia followed by normoxia. Aeration affected the expression of 2,864 genes (27% of the total number of genes in the fungus), of which 50% were either induced or repressed under hypoxic conditions. Up-regulated genes included those for glycolysis, ethanol production, the tricarboxylic acid (TCA) cycle, and for the γ-aminobutyrate (GABA) shunt that bypasses two steps of the TCA cycle. Ethanol and lactate production under hypoxic conditions indicated that glucose was fermented to these compounds via the glycolytic pathway. Since the GABA shunt bypasses the NADH-generating reaction of the TCA cycle catalyzed by oxoglutarate dehydrogenase, hypoxic A. nidulans cells eliminated excess NADH. Hypoxia down-regulated some genes involved in transcription initiation by RNA polymerase II, and lowered the cellular mRNA content. These functions were resumed by re-oxygenation, indicating that A. nidulans controls global transcription to adapt to a hypoxic environment. This study is the first to show that hypoxia elicits systematic transcriptional responses in A. nidulans.

PMID: 20878186 [PubMed - indexed for MEDLINE]

489. Int J Mol Med. 2010 Nov;26(5):643-50.

Pleurotus ostreatus inhibits colitis-related colon carcinogenesis in mice.

Jedinak A, Dudhgaonkar S, Jiang J, Sandusky G, Sliva D.

Cancer Research Laboratory, Methodist Research Institute, Indianapolis, IN 46202, USA.

Colorectal cancer is one of the leading causes of cancer deaths in both men and women in the world. However, colon cancer can be prevented to some extent by consumption of edible natural products with chemopreventive properties. Therefore, we investigated, whether edible mushroom Pleurotus ostreatus (PO) has chemopreventive effect on inflammation-associated colon carcinogenesis induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and promoted by dextran sodium sulfate (DSS). PO treatment, at both doses (100 and 500 mg/kg), significantly reduced by 50 and 78% the number of aberrant crypt foci and the multiplicity of colon neoplasms by 43 and 89%, respectively. However, incidence of colon tumors and high grade dysplasia was reduced by 50 and 63% only in the dose 500 mg/kg of PO, respectively. Colon shortening and dysplastic index was significantly reduced by PO treatment in dose-dependent manner. The immunohistochemistry of colons revealed that treatment with PO suppressed expression of cyclin D1, Ki-67, COX-2 and F4/80. In summary, our data suggest that PO may prevent inflammation-associated colon carcinogenesis with exposure to PhIP through combined modulatory mechanisms of inflammation and tumor growth via suppression of COX-2, F4/80, Ki-67 and cyclin D1 expression in mice.

PMID: 20878085 [PubMed - indexed for MEDLINE]

490. Eukaryot Cell. 2010 Nov;9(11):1690-701. Epub 2010 Sep 24.

Identification of a cell death pathway in Candida albicans during the response to pheromone.

Alby K, Schaefer D, Sherwood RK, Jones SK Jr, Bennett RJ.

Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912, USA.

Mating in hemiascomycete yeasts involves the secretion of pheromones that induce sexual differentiation in cells of the opposite mating type. Studies in Saccharomyces cerevisiae have revealed that a subpopulation of cells experiences cell death during exposure to pheromone. In this work, we tested whether the phenomenon of pheromone-induced death (PID) also occurs in the opportunistic pathogen Candida albicans. Mating in C. albicans is uniquely regulated by white-opaque phenotypic switching; both cell types respond to pheromone, but only opaque cells undergo the morphological transition and cell conjugation. We show that approximately 20% of opaque cells, but not white cells, of laboratory strain SC5314 experience pheromone-induced death. Furthermore, analysis of mutant strains revealed that PID was significantly reduced in strains lacking Fig1 or Fus1 transmembrane proteins that are induced during the mating process and, we now show, are necessary for efficient mating in C. albicans. The level of PID was also Ca(2+) dependent, as chelation of Ca(2+) ions increased cell death to almost 50% of the population. However, in contrast to S. cerevisiae PID, pheromone-induced killing of C. albicans cells was largely independent of signaling via the Ca(2+)-dependent protein phosphatase calcineurin, even when combined with the loss of Cmk1 and Cmk2 proteins. Finally, we demonstrate that levels of PID vary widely between clinical isolates of C. albicans, with some strains experiencing close to 70% cell death. We discuss these findings in light of the role of prodeath and prosurvival pathways operating in yeast cells undergoing the morphological response to pheromone.

PMCID: PMC2976293 PMID: 20870881 [PubMed - indexed for MEDLINE]

491. J Environ Manage. 2010 Sep 23. [Epub ahead of print]

Tolerance and growth of 11 Trichoderma strains to crude oil, naphthalene, phenanthrene and benzo[a]pyrene.

Argumedo-Delira R, Alarcón A, Ferrera-Cerrato R, Almaraz JJ, Peña-Cabriales JJ.

Área de Microbiología, Postgrado de Edafología, Colegio de Postgraduados, Carretera México-Texcoco Km 36.5, Montecillo 56230, Estado de México, México.

Petroleum hydrocarbons (PHs) are major organic contaminants in soils, whose degradation process is mediated by microorganisms such as the filamentous fungi Cunninghamella elegans and Phanerochaete chrysosporium. However, little is known about the tolerance and the degradation capability of Trichoderma species when exposed to PH. This research evaluated the tolerance and growth of 11 Trichoderma strains to crude oil (COil), naphthalene (NAPH), phenanthrene (PHE) and benzo[a]pyrene (B[a]P) by using in vitro systems. Petri dishes containing solid mineral minimum medium were separately contaminated with COil, with seven doses of either NAPH or PHE (250, 500, 750, 1000, 2000, and 3000mgL(-1)), and with six doses of B[a]P (10, 25, 50, 75, and 100mgL(-1)). Non-contaminated plates were used as controls. Trichoderma strains were exposed to all the contaminants by triplicate, and the growth of each fungal colony was daily recorded. No significant differences were observed among Trichoderma strains when they were exposed to COil in which the maximum fungal growth was reached at 96h. In contrast, Trichoderma strains showed variations to tolerate and grow under different doses of either NAPH, PHE or B[a]P. Increasing NAPH doses resulted on significant greater fungal growth inhibition than PHE doses. The exposure to B[a]P did not inhibited growth of some Trichoderma strains.

PMID: 20869805 [PubMed - as supplied by publisher]

492. Regul Toxicol Pharmacol. 2011 Feb;59(1):53-63. Epub 2010 Sep 22.

Safety assessment of EPA-rich triglyceride oil produced from yeast: genotoxicity and 28-day oral toxicity in rats.

Belcher LA, MacKenzie SA, Donner M, Sykes GP, Frame SR, Gillies PJ.

DuPont Haskell Global Centers for Health & Environmental Sciences, E.I. duPont de Nemours & Company, 1090 Elkton Road, Newark, DE 19711-3507, USA. leigh.a.belcher@usa.dupont.com

The 28-day repeat-dose oral and genetic toxicity of eicosapentaenoic acid triglyceride oil (EPA oil) produced from genetically modified Yarrowia lipolytica yeast were assessed. Groups of rats received 0 (olive oil), 940, 1880, or 2820 mg EPA oil/kg/day, or fish oil (sardine/anchovy source) by oral gavage. Lower total serum cholesterol was seen in all EPA and fish oil groups. Liver weights were increased in the medium and high-dose EPA (male only), and fish oil groups but were considered non-adverse physiologically adaptive responses. Increased thyroid follicular cell hypertrophy was observed in male high-dose EPA and fish oil groups, and was considered to be an adaptive response to high levels of polyunsaturated fatty acids. No adverse test substance-related effects were observed on body weight, nutritional, or other clinical or anatomic pathology parameters. The oil was not mutagenic in the in vitro Ames or mouse lymphoma assay, and was not clastogenic in the in vivo mouse micronucleus test. In conclusion, exposure for 28 days to EPA oil derived from yeast did not produce adverse effects at doses up to 2820 mg/kg/day and was not genotoxic. The safety profile of the EPA oil in these tests was comparable to a commercial fish oil.

PMID: 20868718 [PubMed - indexed for MEDLINE]

493. PLoS Pathog. 2010 Aug 26;6(8):e1001069.

PKC signaling regulates drug resistance of the fungal pathogen Candida albicans via circuitry comprised of Mkc1, calcineurin, and Hsp90.

LaFayette SL, Collins C, Zaas AK, Schell WA, Betancourt-Quiroz M, Gunatilaka AA, Perfect JR, Cowen LE.

Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.

Fungal pathogens exploit diverse mechanisms to survive exposure to antifungal drugs. This poses concern given the limited number of clinically useful antifungals and the growing population of immunocompromised individuals vulnerable to life-threatening fungal infection. To identify molecules that abrogate resistance to the most widely deployed class of antifungals, the azoles, we conducted a screen of 1,280 pharmacologically active compounds. Three out of seven hits that abolished azole resistance of a resistant mutant of the model yeast Saccharomyces cerevisiae and a clinical isolate of the leading human fungal pathogen Candida albicans were inhibitors of protein kinase C (PKC), which regulates cell wall integrity during growth, morphogenesis, and response to cell wall stress. Pharmacological or genetic impairment of Pkc1 conferred hypersensitivity to multiple drugs that target synthesis of the key cell membrane sterol ergosterol, including azoles, allylamines, and morpholines. Pkc1 enabled survival of cell membrane stress at least in part via the mitogen activated protein kinase (MAPK) cascade in both species, though through distinct downstream effectors. Strikingly, inhibition of Pkc1 phenocopied inhibition of the molecular chaperone Hsp90 or its client protein calcineurin. PKC signaling was required for calcineurin activation in response to drug exposure in S. cerevisiae. In contrast, Pkc1 and calcineurin independently regulate drug resistance via a common target in C. albicans. We identified an additional level of regulatory control in the C. albicans circuitry linking PKC signaling, Hsp90, and calcineurin as genetic reduction of Hsp90 led to depletion of the terminal MAPK, Mkc1. Deletion of C. albicans PKC1 rendered fungistatic ergosterol biosynthesis inhibitors fungicidal and attenuated virulence in a murine model of systemic candidiasis. This work establishes a new role for PKC signaling in drug resistance, novel circuitry through which Hsp90 regulates drug resistance, and that targeting stress response signaling provides a promising strategy for treating life-threatening fungal infections.

PMCID: PMC2928802 PMID: 20865172 [PubMed - indexed for MEDLINE]

494. Nature. 2010 Sep 23;467(7314):479-83.

Damage-induced phosphorylation of Sld3 is important to block late origin firing.

Lopez-Mosqueda J, Maas NL, Jonsson ZO, Defazio-Eli LG, Wohlschlegel J, Toczyski DP.

Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California 94158-9001, USA.

Origins of replication are activated throughout the S phase of the cell cycle such that some origins fire early and others fire late to ensure that each chromosome is completely replicated in a timely fashion. However, in response to DNA damage or replication fork stalling, eukaryotic cells block activation of unfired origins. Human cells derived from patients with ataxia telangiectasia are deficient in this process due to the lack of a functional ataxia telangiectasia mutated (ATM) kinase and elicit radioresistant DNA synthesis after γ-irradiation(2). This effect is conserved in budding yeast, as yeast cells lacking the related kinase Mec1 (ATM and Rad3-related (ATR in humans)) also fail to inhibit DNA synthesis in the presence of DNA damage. This intra-S-phase checkpoint actively regulates DNA synthesis by inhibiting the firing of late replicating origins, and this inhibition requires both Mec1 and the downstream checkpoint kinase Rad53 (Chk2 in humans). However, the Rad53 substrate(s) whose phosphorylation is required to mediate this function has remained unknown. Here we show that the replication initiation protein Sld3 is phosphorylated by Rad53, and that this phosphorylation, along with phosphorylation of the Cdc7 kinase regulatory subunit Dbf4, blocks late origin firing in Saccharomyces cerevisiae. Upon exposure to DNA-damaging agents, cells expressing non-phosphorylatable alleles of SLD3 and DBF4 (SLD3-m25 and dbf4-m25, respectively) proceed through the S phase faster than wild-type cells by inappropriately firing late origins of replication. SLD3-m25 dbf4-m25 cells grow poorly in the presence of the replication inhibitor hydroxyurea and accumulate multiple Rad52 foci. Moreover, SLD3-m25 dbf4-m25 cells are delayed in recovering from transient blocks to replication and subsequently arrest at the DNA damage checkpoint. These data indicate that the intra-S-phase checkpoint functions to block late origin firing in adverse conditions to prevent genomic instability and maximize cell survival.

PMID: 20865002 [PubMed - indexed for MEDLINE]

495. Biochem Soc Trans. 2010 Oct;38(5):1257-64.

Signal integration in budding yeast.

Waltermann C, Klipp E.

Theoretische Biophysik, Humboldt-Universität zu Berlin Invalidenstrasse 42, 10115 Berlin, Germany.

A complex signalling network governs the response of Saccharomyces cerevisiae to an array of environmental stimuli and stresses. In the present article, we provide an overview of the main signalling system and discuss the mechanisms by which yeast integrates and separates signals from these sources. We apply our classification scheme to a simple semi-quantitative model of the HOG (high-osmolarity glycerol)/FG (filamentous growth)/PH (pheromone) MAPK (mitogen-activated protein kinase) signalling network by perturbing its signal integration mechanisms under combinatorial stimuli of osmotic stress, starvation and pheromone exposure in silico. Our findings include that the Hog1 MAPK might act as a timer for filamentous differentiation, not allowing morphological differentiation before osmo-adaptation is sufficiently completed. We also see that a mutually exclusive decision-making between pheromone and osmo-response might not be taken on the MAPK level and transcriptional regulation of MAPK targets. We conclude that signal integration mechanisms in a wider network including the cell cycle have to be taken into account for which our framework might provide focal points of study.

PMID: 20863295 [PubMed - indexed for MEDLINE]

496. Photochem Photobiol. 2010 Nov-Dec;86(6):1259-66. doi: 10.1111/j.1751-1097.2010.00793.x. Epub 2010 Sep 22.

Quantification of cyclobutane pyrimidine dimers induced by UVB radiation in conidia of the fungi Aspergillus fumigatus, Aspergillus nidulans, Metarhizium acridum and Metarhizium robertsii.

Nascimento É, da Silva SH, Marques Edos R, Roberts DW, Braga GU.

Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.

Conidia are responsible for reproduction, dispersal, environmental persistence and host infection of many fungal species. One of the main environmental factors that can kill and/or damage conidia is solar UV radiation. Cyclobutane pyrimidine dimers (CPD) are the major DNA photoproducts induced by UVB. We examined the conidial germination kinetics and the occurrence of CPD in DNA of conidia exposed to different doses of UVB radiation. Conidia of Aspergillus fumigatus, Aspergillus nidulans and Metarhizium acridum were exposed to UVB doses of 0.9, 1.8, 3.6 and 5.4 kJ m(-2). CPD were quantified using T4 endonuclease V and alkaline agarose gel electrophoresis. Most of the doses were sublethal for all three species. Exposures to UVB delayed conidial germination and the delays were directly related both to UVB doses and CPD frequencies. The frequencies of dimers also were linear and directly proportional to the UVB doses, but the CPD yields differed among species. We also evaluated the impact of conidial pigmentation on germination and CPD induction on Metarhizium robertsii. The frequency of dimers in an albino mutant was approximately 10 times higher than of its green wild-type parent strain after exposure to a sublethal dose (1.8 kJ m(-2)) of UVB radiation.

PMID: 20860693 [PubMed - indexed for MEDLINE]

497. Photochem Photobiol Sci. 2011 Mar 2;10(3):381-8. Epub 2010 Sep 22.

Solar disinfection of fungal spores in water aided by low concentrations of hydrogen peroxide.

Polo-López MI, García-Fernández I, Oller I, Fernández-Ibáñez P.

Plataforma Solar de Almería - CIEMAT, P.O. Box 22, 04200, Tabernas, Almería, Spain.

Our previous contribution showed that Fusarium solani spores are inactivated by low amounts of hydrogen peroxide (lower than 50 mg L(-1)) together with solar irradiation in bottles. The purpose of the current study was to evaluate the effectiveness of solar H(2)O(2)/UV-Vis in distilled water and simulated municipal wastewater treatment plant effluent (SE) contaminated with chlamydospores of Fusarium equiseti in a 60 L solar CPC photo-reactor under solar irradiation. This study showed that F. equiseti chlamydospores in distilled and simulated municipal wastewater effluent were inactivated with 10 mg L(-1) of H(2)O(2) in a 60 L CPC photoreactor. F. equiseti chlamysdospore concentration decreased from 325 (±70) CFU mL(-1) to below the detection limit (DL=2 CFU mL(-1)) within five hours of solar exposure in a solar bottle reactor and from 180 (±53) CFU mL(-1) to below the detection limit in distilled water within two hours of solar irradiation in the solar CPC reactor. These results demonstrate that the use of low concentrations of hydrogen peroxide and CPC systems may be a good alternative for disinfection of resistant microorganisms in water.

PMID: 20859602 [PubMed - indexed for MEDLINE]

498. Rev Alerg Mex. 2010 Jan-Feb;57(1):11-7.

[Sensitization to Ficus benjamina prevalence in adult patients with moderate-severe allergic rhinitis].

[Article in Spanish]

Sedó Mejía GA, Weinmann AM, González Díaz SN, Vidaurri Ojeda AC.

Centro Regional de Alergia e Inmunología Clínica, Hospital Universitario Dr. José Eleuterio González, Universidad Autónoma de Nuevo León, Monterrey, México. giosedo1@yahoo.com

BACKGROUND: Allergic rhinitis can be caused by allergens such as house dust mites, pollen, fungi, and animals. A less common cause is allergy to Ficus benjamina. OBJECTIVES: To determine the prevalence of sensitization to Ficus benjamina on patients with moderate-severe allergic rhinitis, and to describe the epidemiologic factors associated to Ficus benjamina sensitization. PATIENTS AND METHOD: It is an observational, transversal, prospective study; patients with persistent moderate-severe allergic rhinitis diagnosis were included; skin tests to the most frequent aeroallergens and to Ficus benjamina were applied to these patients, as well as a questionnaire in order to investigate the degree of exposure to Ficus benjamina.
RESULTS: 89 patients with persistent moderate-severe allergic rhinitis were included. 59% had a Ficus benjamina plant at home or at work, 97% were located outdoors. Nine patients (10.1%) were sensitized to Ficus benjamina. A statistically significant association was found between sensitization to Ficus benjamina and to Felix domesticus, Canis familiaris, and Periplaneta.
CONCLUSIONS: Prevalence of sensitization to Ficus benjamina was similar to that reported in the literature, and it is associated to three or more indoor allergens. Patients with allergic rhinitis should avoid contact with Ficus benjamina because of the risk of acquiring sensitization.

PMID: 20857624 [PubMed - indexed for MEDLINE]

499. Proc Natl Acad Sci U S A. 2010 Oct 5;107(40):17385-90. Epub 2010 Sep 20.

Controlled enzymatic production of astrocytic hydrogen peroxide protects neurons from oxidative stress via an Nrf2-independent pathway.

Haskew-Layton RE, Payappilly JB, Smirnova NA, Ma TC, Chan KK, Murphy TH, Guo H, Langley B, Sultana R, Butterfield DA, Santagata S, Alldred MJ, Gazaryan IG, Bell GW, Ginsberg SD, Ratan RR.

Department of Neurology and Neuroscience, Weill Medical College of Cornell University, The Burke Medical Research Institute, White Plains, NY 10605, USA. rrr2001@med.cornell.edu

Comment in Proc Natl Acad Sci U S A. 2011 Jan 4;108(1):E1-2; author reply E3-4.

Neurons rely on their metabolic coupling with astrocytes to combat oxidative stress. The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) appears important for astrocyte-dependent neuroprotection from oxidative insults. Indeed, Nrf2 activators are effective in stroke, Parkinson disease, and Huntington disease models. However, key endogenous signals that initiate adaptive neuroprotective cascades in astrocytes, including activation of Nrf2-mediated gene expression, remain unclear. Hydrogen peroxide (H(2)O(2)) plays an important role in cell signaling and is an attractive candidate mediator of adaptive responses in astrocytes. Here we determine (i) the significance of H(2)O(2) in promoting astrocyte-dependent neuroprotection from oxidative stress, and (ii) the relevance of H(2)O(2) in inducing astrocytic Nrf2 activation. To control the duration and level of cytoplasmic H(2)O(2) production in astrocytes cocultured with neurons, we heterologously expressed the H(2)O(2)-producing enzyme Rhodotorula gracilis D-amino acid oxidase (rgDAAO) selectively in astrocytes. Exposure of rgDAAO-astrocytes to D-alanine lead to the concentration-dependent generation of H(2)O(2). Seven hours of low-level H(2)O(2) production (∼3.7 nmol·min·mg protein) in astrocytes protected neurons from oxidative stress, but higher levels (∼130 nmol·min·mg protein) were neurotoxic. Neuroprotection occurred without direct neuronal exposure to astrocyte-derived H(2)O(2), suggesting a mechanism specific to astrocytic intracellular signaling. Nrf2 activation mimicked the effect of astrocytic H(2)O(2) yet H(2)O(2)-induced protection was independent of Nrf2. Astrocytic protein tyrosine phosphatase inhibition also protected neurons from oxidative death, representing a plausible mechanism for H(2)O(2)-induced neuroprotection. These findings demonstrate the utility of rgDAAO for spatially and temporally controlling intracellular H(2)O(2) concentrations to uncover unique astrocyte-dependent neuroprotective mechanisms.

PMCID: PMC2951414 PMID: 20855618 [PubMed - indexed for MEDLINE]

500. Appl Environ Microbiol. 2010 Nov;76(22):7526-35. Epub 2010 Sep 17.

Activation of two different resistance mechanisms in Saccharomyces cerevisiae upon exposure to octanoic and decanoic acids.

Legras JL, Erny C, Le Jeune C, Lollier M, Adolphe Y, Demuyter C, Delobel P, Blondin B, Karst F.

UMR 1083 Sciences pour l'Oenologie INRA, SupAgro, Montpellier cedex 1, France. jean-luc.legras@supagro.inra.fr

Medium-chain fatty acids (octanoic and decanoic acids) are well known as fermentation inhibitors. During must fermentation, the toxicity of these fatty acids is enhanced by ethanol and low pH, which favors their entrance in the cell, resulting in a decrease of internal pH. We present here the characterization of the mechanisms involved in the establishment of the resistance to these fatty acids. The analysis of the transcriptome response to the exposure to octanoic and decanoic acids revealed that two partially overlapping mechanisms are activated; both responses share many genes with an oxidative stress response, but some key genes were activated differentially. The transcriptome response to octanoic acid stress can be described mainly as a weak acid response, and it involves Pdr12p as the main transporter. The phenotypic analysis of knocked-out strains confirmed the role of the Pdr12p transporter under the control of WAR1 but also revealed the involvement of the Tpo1p major facilitator superfamily proteins (MFS) transporter in octanoic acid expulsion. In contrast, the resistance to decanoic acid is composite. It also involves the transporter Tpo1p and includes the activation of several genes of the beta-oxidation pathway and ethyl ester synthesis. Indeed, the induction of FAA1 and EEB1, coding for a long-chain fatty acyl coenzyme A synthetase and an alcohol acyltransferase, respectively, suggests a detoxification pathway through the production of decanoate ethyl ester. These results are confirmed by the sensitivity of strains bearing deletions for the transcription factors encoded by PDR1, STB5, OAF1, and PIP2 genes.

PMCID: PMC2976208 PMID: 20851956 [PubMed - indexed for MEDLINE]

501. Int J Hyg Environ Health. 2011 Jan;214(1):1-25. Epub 2010 Sep 18.

Influence of indoor factors in dwellings on the development of childhood asthma.

Heinrich J.

Helmholtz Zentrum München, National Research Center for Environmental Health, Institute of Epidemiology, Munich, Germany. joachim.heinrich@helmholtz-muenchen.de

Asthma has become the most common, childhood chronic disease in the industrialized world, and it is also increasing in developing regions. There are huge differences in the prevalence of childhood asthma across countries and continents, and there is no doubt that the prevalence of asthma was strongly increasing during the past decades worldwide. Asthma, as a complex disease, has a broad spectrum of potential determinants ranging from genetics to life style and environmental factors. Environmental factors are likely to be important in explaining the regional differences and the overall increasing trend towards asthma's prevalence. Among the environmental conditions, indoor factors are of particular interest because people spend more than 80% of their time indoors globally. Increasing prices for oil, gas and other sources of primary energy will further lead to better insulation of homes, and ultimately to reduced energy costs. This will decrease air exchange rates and will lower the dilution of indoor air mass with ambient air. Indoor air quality and potential health effects will therefore be an area for future research and for gaining a better understanding of asthma epidemics. This strategic review will summarize the current knowledge of the effects of a broad spectrum of indoor factors on the development of asthma in childhood in Western countries based on epidemiological studies. In conclusion, several epidemiological studies point out, that indoor factors might cause asthma in childhood. Stronger and more consistent findings are seen when exposure to these indoor factors is assessed by surrogates for the source of the actual toxicants. Measurement-based exposure assessments for several indoor factors are less common than using surrogates of the exposure. These studies, however, mainly showed heterogeneous results. The most consistent finding for an induction of asthma in childhood is related to exposure to environmental tobacco smoke, to living in homes close to busy roads, and in damp homes where are visible moulds at home. The causing agents of the increased risk of living in damp homes remained uncertain and needs clarification. Exposure to pet-derived allergens and house dust mites are very commonly investigated and thought to be related to asthma onset. The epidemiological evidence is not sufficient to recommend avoidance measures against pet and dust mites as preventive activities against allergies. More research is also needed to clarify the potential risk for exposure to volatile and semi-volatile organic compounds due to renovation activities, phthalates and chlorine chemicals due to cleaning.

PMID: 20851050 [PubMed - indexed for MEDLINE]

502. J Pediatr. 2011 Feb;158(2):234-8.e1. Epub 2010 Sep 17.

The impact of environmental and genetic factors on neonatal late-onset sepsis.

Bizzarro MJ, Jiang Y, Hussain N, Gruen JR, Bhandari V, Zhang H.

Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06520-8064, USA.

OBJECTIVE: To assess the genetic contribution to late-onset sepsis in twins in the newborn intensive care unit. STUDY DESIGN: A retrospective cohort analysis of twins born from 1994 to 2009 was performed on data collected from the newborn intensive care units at Yale University and the University of Connecticut. Sepsis concordance rates were compared between monozygotic and dizygotic twins. Mixed-effects logistic regression analysis was performed to determine the impact of selected nongenetic factors on late-onset sepsis. The influence of additive genetic and common and residual environmental effects were analyzed and quantified.
RESULTS: One hundred seventy monozygotic and 665 dizygotic twin pairs were analyzed, and sepsis identified in 8.9%. Mean gestational age and birth weight of the cohort was 31.1 weeks and 1637 grams, respectively. Mixed-effects logistic regression determined birth weight (regression coefficient, -0.001; 95% CI, -0.003 to 0.000; P = .028), respiratory distress syndrome (regression coefficient, 1.769; 95% CI, 0.943 to 2.596; P < .001), and duration of total parenteral nutrition (regression coefficient, 0.041; 95% CI, 0.017 to 0.064; P < .001) as significant nongenetic factors. Further analysis determined 49.0% (P = .002) of the variance in liability to late-onset sepsis was due to genetic factors alone, and 51.0% (P = .001) the result of residual environmental factors.
CONCLUSIONS: Our data support significant genetic susceptibility to late-onset sepsis in the newborn intensive care unit population.

PMCID: PMC3008342 [Available on 2012/2/1] PMID: 20850766 [PubMed - indexed for MEDLINE]

503. J Microbiol Methods. 2010 Nov;83(2):106-10. Epub 2010 Sep 16.

Rapid method for screening enoate reductase activity in yeasts.

Raimondi S, Roncaglia L, Amaretti A, Leonardi A, Buzzini P, Forti L, Rossi M.

Department of Chemistry, University of Modena and Reggio Emilia, Modena, Italy.

Old Yellow Enzymes (OYEs, EC 1.6.99.1) are flavin-dependent oxidoreductases that catalyze the asymmetric reduction of electron-poor alkenes (enoate reductase activity). Since OYEs are involved in detoxification of acrolein, a high-throughput method for selecting yeasts expressing high enoate reductase activity, based on their acrolein resistance, was developed. The screening method was based on the measurement of growth in acrolein-supplemented medium, in 96-well microtiter plate cultures. A quantitative descriptor (Acrolein Resistance Factor=ARF) was firstly designed for quantifying the influence of both acrolein concentration and time of exposure on yeast growth. Besides, the efficiency of bioconversion of ketoisophorone (KIP) was exploited to measure OYE activity. In order to validate the method, ARF was correlated with the bioconversion of KIP on thirty yeast strains, belonging to 7 genera. With only a few exceptions, all strains exhibiting the highest ARF also displayed the maximum OYE activity. The presence of OYE genes in the strains showing OYE activity was confirmed by PCR amplification. Based on the results herein reported, this method should be profitably used as a fast screening procedure aimed at selecting outstanding strains for whole-cell bioconversions and could open many possibilities for the isolation and the biocatalytic exploitation of new OYEs from yeasts.

PMID: 20849886 [PubMed - indexed for MEDLINE]

504. Nat Prod Commun. 2010 Aug;5(8):1183-6.

Cytotoxicity of 9,11-dehydroergosterol peroxide isolated from Ganoderma lucidum and its target-related proteins.

Cui YJ, Guan SH, Feng LX, Song XY, Ma C, Cheng CR, Wang WB, Wu WY, Yue QX, Liu X, Guo DA.

Shanghai University of Chinese Traditional Medicine, Shanghai 201203, PR China.

The cytotoxicty of 9,11-dehydroergosterol peroxide (DHEP) isolated from the fruiting bodies of Ganoderma lucidum on HeLa cells was studied. DHEP treatment for 48 h inhibited the proliferation of HeLa human cervical carcinoma cells with an IC50-value of 8.58 +/- 0.98 microM. Morphological changes of DHEP-treated cells indicated that DHEP induced apoptosis in HeLa cells. To identify the cellular targets of DHEP, two-dimensional electrophoresis analysis was performed to compare the protein expression profiles of DHEP-treated cells with that of control cells. Proteins altered in expressional level after DHEP exposure were identified by MALDI-TOF MS/MS. The cytotoxic effect of DHEP was associated with regulated expression of 6 proteins. Stathmin 1 might be an important target-related protein of DHEP. The regulation of stathmin 1 by DHEP treatment was also confirmed by Western blotting.

PMID: 20839614 [PubMed - indexed for MEDLINE]

505. Braz J Infect Dis. 2010 May-Jun;14(3):291-3.

Acute HIV infection with rapid progression to AIDS.

Silva Mde O, Bastos M, Netto EM, Gouvea NA, Torres AJ, Kallas E, Watkins DI, Altfeld M, Brites C.

Universidade Federal da Bahia, Brazil. oliveiras_m@yahoo.com.br

Acute HIV infection is rarely recognized as the signs and symptoms are normally unspecific and can persist for days or weeks. The normal HIV course is characterized by a progressive loss of CD4+ cells, which normally leads to severe immunodeficiency after a variable time interval. The mean time from initial infection to development of clinical AIDS is approximately 8-10 years, but it is variable among individuals and depends on a complex interaction between virus and host. Here we describe an extraordinary case of a man who developed Pneumocisits jiroveci pneumonia within one month after sexual exposure to HIV-1, and then presented with 3 consecutive CD4 counts bellow 200 cells/mm³ within 3 months, with no other opportunistic disease. Although antiretroviral therapy (AZT+3TC+ATZ/r) was started, with full adherence of the patient, and genotyping indicating no primary antiretroviral resistance mutations, he required more than six months to have a CD4 restoration to levels above 200 cells/mm³ and 10 months to HIV-RNA to become undetectable.

PMID: 20835515 [PubMed - indexed for MEDLINE]

506. Appl Environ Microbiol. 2010 Nov;76(21):7102-8. Epub 2010 Sep 10.

Screening for antifungal peptides and their modes of action in Aspergillus nidulans.

Mania D, Hilpert K, Ruden S, Fischer R, Takeshita N.

Karlsruhe Institute of Technology, Institute for Applied Biosciences, Department of Microbiology, Hertzstrasse 16, D-76187 Karlsruhe, Germany.

Many short cationic peptides have been identified as potent antimicrobial agents, but their modes of action are not well understood. Peptide synthesis on cellulose membranes has resulted in the generation of peptide libraries, while high-throughput assays have been developed to test their antibacterial activities. In this paper a microtiter plate-based screening method for fungi has been developed and used to test nine antibacterial peptides against the model fungus Aspergillus nidulans. Microscopical studies using sublethal peptide concentrations caused defects in polarized growth, including increased branch formation and depolarized hyphae. We characterized the mode of action for one of our target peptides, Sub5 (12 amino acids), which has already been shown to possess pharmacological potential as an antibacterial agent and is able to interact with ATP and ATP-dependent enzymes. The MIC for A. nidulans is 2 μg/ml, which is in the same range as the MICs reported for bacteria. Fluorescein isothiocyanate (FITC)-labeled Sub5 targeted the cytoplasmic membrane, particularly hyphal tips, and entered the cytoplasm after prolonged exposure, independent of endocytosis. Interestingly, Sub5 peptide treatment disturbed sterol-rich membrane domains, important for tip growth, at hyphal tips. A very similar peptide, FITC-P7, also accumulated on the cell membrane but did not have antibacterial or antifungal activity, suggesting that the cytoplasmic membrane is a first target for the Sub5 peptide; however, the antifungal activity seems to be correlated with the ability to enter the cytoplasm, where the peptides might act on other targets.

PMCID: PMC2976221 PMID: 20833782 [PubMed - indexed for MEDLINE]

507. Appl Spectrosc. 2010 Sep;64(9):1054-60.

Characterization of fungal-degraded lime wood by X-ray diffraction and cross-polarization magic-angle-spinning 13C-nuclear magnetic resonance spectroscopy.

Popescu CM, Larsson PT, Tibirna CM, Vasile C.

Romanian Academy P. Poni Institute of Macromolecular Chemistry, Department of Physical Chemistry of Polymers, 41A Gr. Ghica Voda Alley, Ro.700487, Iasi, Romania. mihapop@icmpp.ro

X-ray diffraction, scanning electron microscopy (SEM), and solid-state cross-polarization magic-angle-spinning (CP/MAS) (13)C-NMR spectroscopy were applied to determine changes over time in the morphology and crystallinity of lime wood (Tilia cordata Miller) generated by the soft-rot fungi. Wood samples were inoculated with Trichoderma viride Pers for various durations up to 84 days. Structural and morphological modifications were assessed by comparing the structural features of decayed lime wood samples with references. Significant morphology changes such as defibration or small cavities were clearly observed on the SEM micrographs of lime wood samples exposed to fungi. Following the deconvolution process of the diffraction patterns, the degree of crystallinity, apparent lateral crystallite size, the proportion of crystallite interior chains, and the cellulose fraction have been determined. It was found that all crystallographic data vary with the duration of exposure to fungi. The degree of crystallinity and cellulose fraction tend to decrease, whereas the apparent lateral crystallite size and the proportion of crystallite interior chains increase with prolonged biodegradation processes. The most relevant signals in CP/MAS (13)C-NMR spectra were assigned according to literature data. The differences observed were discussed in terms of lignin and cellulose composition: by fixing the lignin reference signal intensity, the cellulose and hemicelluloses moieties showed a relative decrease compared to the lignin signals in decayed wood.

PMID: 20828443 [PubMed - indexed for MEDLINE]

508. Insect Biochem Mol Biol. 2010 Dec;40(12):883-90. Epub 2010 Sep 6.

Insecticidal properties of Sclerotinia sclerotiorum agglutinin and its interaction with insect tissues and cells.

Hamshou M, Smagghe G, Shahidi-Noghabi S, De Geyter E, Lannoo N, Van Damme EJ.

Laboratory of Agrozoology, Department of Crop Protection, Faculty of Bioscience Engineering, Ghent University, Coupure links 653, B-9000 Ghent, Belgium.

This project studied in detail the insecticidal activity of a fungal lectin from the sclerotes of Sclerotinia sclerotiorum, referred to as S. sclerotiorum agglutinin or SSA. Feeding assays with the pea aphid (Acyrthosiphon pisum) on an artificial diet containing different concentrations of SSA demonstrated a high mortality caused by this fungal lectin with a median insect toxicity value (LC50) of 66 (49-88) μg/ml. In an attempt to unravel the mode of action of SSA the binding and interaction of the lectin with insect tissues and cells were investigated. Histofluorescence studies on sections from aphids fed on an artificial liquid diet containing FITC-labeled SSA, indicated the insect midgut with its brush border zone as the primary target for SSA. In addition, exposure of insect midgut CF-203 cells to 25 μg/ml SSA resulted in a total loss of cell viability, the median cell toxicity value (EC50) being 4.0 (2.4-6.7) μg/ml. Interestingly, cell death was accompanied with DNA fragmentation, but the effect was caspase-3 independent. Analyses using fluorescence confocal microscopy demonstrated that FITC-labeled SSA was not internalized in the insect midgut cells, but bound to the cell surface. Prior incubation of the cells with saponin to achieve a higher cell membrane permeation resulted in an increased internalization of SSA in the insect midgut cells, but no increase in cell toxicity. Furthermore, since the toxicity of SSA for CF-203 cells was significantly reduced when SSA was incubated with GalNAc and asialomucin prior to treatment of the cells, the data of this project provide strong evidence that SSA binds with specific carbohydrate moieties on the cell membrane proteins to start a signaling transduction cascade leading to death of the midgut epithelial cells, which in turn results in insect mortality. The potential use of SSA in insect control is discussed.

PMID: 20826211 [PubMed - indexed for MEDLINE]

509. BMC Infect Dis. 2010 Sep 8;10:264.

Molecular characterization of Histoplasma capsulatum isolated from an outbreak in treasure hunters Histoplasma capsulatum in treasure hunters.

Muñoz B, Martínez MA, Palma G, Ramírez A, Frías MG, Reyes MR, Taylor ML, Higuera AL, Corcho A, Manjarrez ME.

Laboratorio de Micología Médica, Depto, de Investigación en Virología, Instituto Nacional de Enfermedades Respiratorias (INER), Calzada de Tlalpan 4502, Sección XVI, Tlalpan,14080 México, DF, México.

BACKGROUND: In Mexico, primary pulmonary histoplasmosis is the most relevant clinical form of the disease. The geographical distribution of specific strains of Histoplasma capsulatum circulating in Mexico has not been fully established. Outbreaks must be reported in order to have current, updated information on this disease, identifying new endemic areas, manner of exposure to the fungi, and molecular characterization of the causative agents. We report a recent outbreak of histoplasmosis in treasure hunters and the molecular characterization of two isolates obtained from these patients.
METHODS: Six patients admitted to the National Institute of Respiratory Diseases (INER) in Mexico City presented severe respiratory symptoms suggestive of histoplasmosis. They acquired the infection in the Veracruz (VZ) endemic zone. Diagnosis was made by X-ray and Computed tomography (CT), liver function, immunological techniques, and culture. Identification of H. capsulatum isolates was confirmed by using Polymerase chain reaction (PCR) was conducted with a probe from the M antigen, and the isolates were characterized by means of Random amplification of polymorphic DNA (RAPD)-PCR employed the 1253 oligonucleotide and a mixture of oligonucleotides 1281 and 1283. These were compared to eight reference strain isolates from neighboring areas.
RESULTS: X-ray and CT revealed disseminated micronodular images throughout lung parenchyma, as well as bilateral retrocaval, prevascular, subcarinal, and hilar adenopathies, hepatosplenomegaly, and altered liver function tests. Five of the six patients developed disseminated histoplasmosis. Two H. capsulatum strains were isolated. The same band profile was detected in both strains, indicating that both isolates corresponded to the sole H. capsulatum strain. Molecular characterization of the isolates was similar in 100% with the EH-53 Hidalgo human (HG) strain (reference strain integrated into the LAm A clade described for Latin America).
CONCLUSIONS: The two isolates appeared to possess the same polymorphic pattern; they are indistinguishable from each other and from EH-53. It is important to remain updated on recent outbreaks of histoplasmosis, the manner of exposure to the fungi, as well as the molecular characterization of the isolates. The severity of cases indicates that this strain is highly virulent and that it is probably prevalent in Hidalgo and Veracruz states.

PMCID: PMC2944350 PMID: 20825675 [PubMed - indexed for MEDLINE]

510. J Immunotoxicol. 2010 Oct-Dec;7(4):308-17. Epub 2010 Sep 8.

Establishment and comparison of delayed-type hypersensitivity models in the B₆C₃F₁ mouse.

Smith MJ, White KL Jr.

Department of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298, USA.

The objective of these studies was to establish and compare delayed-type hypersensitivity (DTH) models, using keyhole limpet hemocyanin (KLH), sheep red blood cells (SRBC), and Candida albicans as sensitizing antigens, for their capability to assess a DTH response (utilizing footpad swelling as the endpoint) with minimal confounding factors resulting from antigen-specific antibody (Ab) production. The key elements of the DTH are the sensitization dose, time interval between sensitization and challenge [i.e. the challenge interval (CI)], and the challenge dose. Models were established by first determining the challenge dose, or the amount of antigen that produced no greater footpad swelling 24-h post-injection than the trauma induced by injection of physiological saline. Time-course studies determined the CI that produced a peak response for each antigen. Dose-response sensitization studies were conducted to determine the optimum sensitization concentration (i.e. maximum footpad swelling with minimal impact by antigen-specific Ab production). Footpad swelling decreased dose-responsively with increasing KLH sensitization concentration and corresponded to a dose-responsive increase in KLH-specific Ab levels. In the SRBC model, footpad swelling decreased at the high dose (1 x 10⁹ SRBC/mouse), and a corresponding increase in SRBC-specific Ab was observed at this dose level. A dose-responsive increase in footpad swelling was observed in the C. albicans model up to 3 x 10⁷ organisms/mouse, while antigen-specific antibody levels were not different from background (unsensitized) levels following sensitization with any concentration of C. albicans (up to 1.2 x 10⁸ organisms/mouse, the highest concentration tested). Finally, each model was evaluated for its ability to detect immunosuppression following exposure to benzo[a]pyrene (B[a]P), with the C. albicans model demonstrating greater sensitivity than the other models. These results indicate that, of the three models examined here, the C. albicans DTH model may be the most appropriate model for evaluating effects on cell-mediated immunity when conducting immunotoxicological investigations.

PMID: 20825253 [PubMed - indexed for MEDLINE]

511. Environ Toxicol Chem. 2010 Apr;29(4):902-8.

Insights into the development of fungal biomarkers for metal ecotoxicity assessment: case of Trametes versicolor exposed to copper.

Lebrun JD, Trinsoutrot-Gattin I, Laval K, Mougin C.

INRA, UMR 251 Physico-chimie et Ecotoxicologie des SolS d'Agrosystèmes Contaminés, RD 10, 78026 Versailles, France. jlebrun@versailles.inra.fr

The relationship between the physiological state of fungi and the response of their functional system to metals is not known, limiting the use of fungal enzymes as tools for assessing metal ecotoxicity in terrestrial ecosystems. The present study attempts to establish how the development phases modulate the secretion of enzymes in the filamentous fungus Trametes versicolor after exposure to Cu. For that purpose, extracellular hydrolases (acid and alkaline phosphatases, aryl-sulfatase, beta-glucosidase, beta-galactosidase, and N-acetyl-beta-glucosaminidase) and oxidoreductases (laccase, manganese and lignin peroxidases) were monitored in liquid cultures for 2 weeks. Copper was added during either the growth or the stationary phases at 20 or 200 ppm. Results of the present study showed that Cu at the highest concentration modifies the secretion of enzymes, regardless of the development phase to which the fungus was exposed. However, the sensitivity of enzyme responses to Cu depended on the phase development and the type of secreted enzyme. In a general way, the production of hydrolases was decreased by Cu, whereas that of oxidoreductases was highly increased. Furthermore, lignin peroxidase was not detected in control cultures and was specifically produced in the presence of Cu. In conclusion, fungal oxidoreductases may be enzymatic biomarkers of copper exposure for ecotoxicity assessment.

PMID: 20821520 [PubMed - indexed for MEDLINE]

512. Biodegradation. 2011 Apr;22(2):243-52. Epub 2010 Sep 6.

Evaluation of ozone for preventing fungal influenced corrosion of reinforced concrete bridges over the River Nile, Egypt.

Geweely NS.

Department of Botany, Faculty of Science, Cairo University, Giza, 12613, Egypt. ngeweely@yahoo.com

Fungal influenced corrosion (FIC) of some corroded sites in three selected bridges [Embaba bridge (E-bridge), Kasr al-Nile-bridge (K-bridge) and University bridge (U-bridge)] located over the River Nile in Egypt were investigated. Six fungal species, belong to 12 fungal genera, were isolated from the corroded reinforced concrete of the three tested bridges. Fourier transform infrared spectroscopy (FTIR) was screened for the most dominant fungal species (Fusarium oxysporium) which showed in all tested bridges that indicated the presence of amine group accompanied with polysaccharides contents. FIC of the most deteriorated bridge (K-bridge) was documented with FTIR. The association of fungal spores with corrosion products was recorded with scanning electron microscope (SEM). Evaluation of ozone for preventing FIC of the K-bridge was carried out by recording the corrosion rate and the corresponding inhibition efficiency (IE%). No mycelial growth with 100% IE was observed at 3 ppm ozone concentration after 120 min exposure time. With longer duration of ozone exposure, the membrane permeability of F. oxysporium was compromised as indicated by protein and nucleic acid leakages accompanied with lipid and tryptophan oxidation. The total intracellular and extracellular proteins of F. oxysporium were run on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) indicated the increasing of the supernatant protein on the expense of the cellular protein bands with extending ozone exposure time (0-80 min).

PMID: 20820884 [PubMed - indexed for MEDLINE]

513. Allergy Asthma Proc. 2010 Jul-Aug;31(4):317-23.

Reduced clinic, emergency room, and hospital utilization after home environmental assessment and case management.

Barnes CS, Amado M, Portnoy JM.

Section of Allergy/Asthma/Immunology, The Children's Mercy Hospital, Kansas City, Missouri 64108, USA. cbarnes@cmh.edu

Allergists often suspect home environmental conditions are contributors to allergic disease. Case management can be an effective tool in managing asthmatic patients. To describe the impact of home environmental assessments and case management on the medical care utilization of patients with allergic disease the following studies were conducted. This study was designed to retrospectively examine health care utilization of pediatric patients that had a home environmental assessment recommended by a pediatric allergist as part of a comprehensive case management program. Subjects were chosen from pediatric patients who received home assessment after referral for case management by pediatric allergy specialists in a hospital-based clinic as indicated by high emergency room (ER) and hospital utilization. Case management included education, clinic visits, environmental assessment, and a single person responsible for following the subject's care. Home assessment included airborne spore collections, surface collections, and dust collection for evaluation of antigens. There were 25 subjects. Seventy-two percent were asthmatic and 12% were diagnosed with allergic rhinitis. In the year before entering the study these subjects experienced 47 ER visits, 22 hospitalizations, and 279 clinic visits. In the subsequent year they underwent 18 ER visits, 3 hospitalizations, and 172 clinic visits. Penicillium/Aspergillus levels were above 100 spores/m(3) of air in 94% of homes and above 1000 spores/m(3) in 74% of homes. Thirty-six percent of homes had Stachybotrys above 100 spores/m(3). Home environmental assessment and case management may reduce medical care utilization for children suffering from allergic rhinitis and asthma.

PMID: 20819322 [PubMed - indexed for MEDLINE]

514. Appl Environ Microbiol. 2010 Nov;76(21):7004-12. Epub 2010 Sep 3.

Accuracy, precision, and method detection limits of quantitative PCR for airborne bacteria and fungi.

Hospodsky D, Yamamoto N, Peccia J.

Department of Chemical Engineering, Environmental Engineering Program, 9 Hillhouse Avenue, Yale University, New Haven, CT 06520, USA.

Real-time quantitative PCR (qPCR) for rapid and specific enumeration of microbial agents is finding increased use in aerosol science. The goal of this study was to determine qPCR accuracy, precision, and method detection limits (MDLs) within the context of indoor and ambient aerosol samples. Escherichia coli and Bacillus atrophaeus vegetative bacterial cells and Aspergillus fumigatus fungal spores loaded onto aerosol filters were considered. Efficiencies associated with recovery of DNA from aerosol filters were low, and excluding these efficiencies in quantitative analysis led to underestimating the true aerosol concentration by 10 to 24 times. Precision near detection limits ranged from a 28% to 79% coefficient of variation (COV) for the three test organisms, and the majority of this variation was due to instrument repeatability. Depending on the organism and sampling filter material, precision results suggest that qPCR is useful for determining dissimilarity between two samples only if the true differences are greater than 1.3 to 3.2 times (95% confidence level at n = 7 replicates). For MDLs, qPCR was able to produce a positive response with 99% confidence from the DNA of five B. atrophaeus cells and less than one A. fumigatus spore. Overall MDL values that included sample processing efficiencies ranged from 2,000 to 3,000 B. atrophaeus cells per filter and 10 to 25 A. fumigatus spores per filter. Applying the concepts of accuracy, precision, and MDL to qPCR aerosol measurements demonstrates that sample processing efficiencies must be accounted for in order to accurately estimate bioaerosol exposure, provides guidance on the necessary statistical rigor required to understand significant differences among separate aerosol samples, and prevents undetected (i.e., nonquantifiable) values for true aerosol concentrations that may be significant.

PMCID: PMC2976253 PMID: 20817798 [PubMed - indexed for MEDLINE]

515. Eur Respir J. 2011 May;37(5):1050-9. Epub 2010 Sep 3.

Respiratory health in children, and indoor exposure to (1,3)-β-D-glucan, EPS mould components and endotoxin.

Tischer C, Gehring U, Chen CM, Kerkhof M, Koppelman G, Sausenthaler S, Herbarth O, Schaaf B, Lehmann I, Krämer U, Berdel D, von Berg A, Bauer CP, Koletzko S, Wichmann HE, Brunekreef B, Heinrich J.

Institute of EpidemiologyHelmholtz Zentrum München, German Research Centre for Environmental Health, Neuherberg, Germany. joachim.heinrich@helmholtz-muenchen.de

For a long time, exposure to mould and dampness-derived microbial components was considered a risk factor for the development of respiratory diseases and symptoms. Some recent studies suggested that early childhood exposure to mould components, such as (1,3)-β-D-glucan and extracellular polysaccharides (EPSs), may protect children from developing allergy. We investigated the association of exposure to (1,3)-β-D-glucan, EPS and endotoxin with asthma and allergies in 6-yr-old children. This investigation was the follow-up to a nested case-control study among three European birth cohorts. Children from two ongoing birth cohort studies performed in Germany (n = 358) and one in the Netherlands (n = 338) were selected. Levels of (1,3)-β-D-glucan, EPS and endotoxin were measured in settled house dust sampled from children's mattresses and living-room floors when the children were, on average, 5 yrs of age. At the age of 6 yrs, health outcome information was available for 678 children. In the two German subsets, domestic EPS and endotoxin exposure from children's mattresses were significantly negatively associated with physician-diagnosed asthma (OR per interquartile range increase 0.60 (95% CI 0.39-0.92) and 0.55 (95% CI 0.31-0.97), respectively). In addition, EPS exposure was inversely related to physician-diagnosed allergic rhinitis (OR 0.50, 95% CI 0.31-0.81). For the Dutch population, no associations were observed between exposure to microbial agents and respiratory health outcomes. We found inverse associations between domestic exposure to EPS and endotoxin from children's mattresses, and doctor-diagnosed asthma and rhinitis in German, but not in Dutch, school children. The reasons for the differences between countries are not clear.

PMID: 20817706 [PubMed - indexed for MEDLINE]

516. Eur J Pharmacol. 2010 Dec 1;648(1-3):39-49. Epub 2010 Sep 9.

Pachymic acid stimulates glucose uptake through enhanced GLUT4 expression and translocation.

Huang YC, Chang WL, Huang SF, Lin CY, Lin HC, Chang TC.

Institute of Preventive Medicine, National Defense Medical Center, Taipei, Taiwan, ROC. alexha@mail.ndmctsgh.edu.tw

In an effort to investigate the effect and mechanism of Poria cocos on glucose uptake, six lanostane-type triterpenoids were isolated and analyzed. Among them, pachymic acid displayed the most significant stimulating activity on glucose uptake in 3T3-L1 adipocytes. The effect of pachymic acid on the expression profile of glucose transporters in differentiated 3T3-L1 adipocytes was also analyzed. Our results demonstrated that pachymic acid induced an increase in GLUT4, but not GLUT1, expression at both the mRNA and protein levels. The role of GLUT4 was further confirmed using the lentiviral vector-derived GLUT4 short hairpin RNA (shRNA). The stimulating activity of pachymic acid on glucose uptake was abolished when the endogenous GLUT4 expression was suppressed in 3T3-L1 adipocytes. In addition to increased GLUT4 expression, pachymic acid stimulated GLUT4 redistribution from intracellular vesicles to the plasma membrane in adipocytes. Exposure of the differentiated adipocytes to pachymic acid increased the phosphorylation of insulin receptor substrate (IRS)-1, AKT and AMP-activated kinase (AMPK). The involvement of PI3K and AMPK in the action of pachymic acid was further confirmed as PI3K and AMPK inhibitors completely blocked the pachymic acid-mediated activities in adipocytes. In addition, pachymic acid was shown to induce triglyceride accumulation and inhibit lipolysis in differentiated adipocytes. Taken together, we demonstrated the insulin-like activities of this compound in stimulating glucose uptake, GLUT4 gene expression and translocation, and promoting triglyceride accumulation in adipocytes. Our study provides important insights into the underlying mechanism of hypoglycemic activity of P. cocos.

PMID: 20816811 [PubMed - indexed for MEDLINE]

517. Cell Microbiol. 2011 Jan;13(1):62-80. doi: 10.1111/j.1462-5822.2010.01520.x. Epub 2010 Sep 16.

Cell wall integrity and high osmolarity glycerol pathways are required for adaptation of Alternaria brassicicola to cell wall stress caused by brassicaceous indolic phytoalexins.

Joubert A, Bataille-Simoneau N, Campion C, Guillemette T, Hudhomme P, Iacomi-Vasilescu B, Leroy T, Pochon S, Poupard P, Simoneau P.

UMR PaVe no. 77, IFR 149 QUASAV, 2 Bd Lavoisier, F-49045 Angers Cedex, France.

Camalexin, the characteristic phytoalexin of Arabidopsis thaliana, inhibits growth of the fungal necrotroph Alternaria brassicicola. This plant metabolite probably exerts its antifungal toxicity by causing cell membrane damage. Here we observed that activation of a cellular response to this damage requires cell wall integrity (CWI) and the high osmolarity glycerol (HOG) pathways. Camalexin was found to activate both AbHog1 and AbSlt2 MAP kinases, and activation of the latter was abrogated in a AbHog1 deficient strain. Mutant strains lacking functional MAP kinases showed hypersensitivity to camalexin and brassinin, a structurally related phytoalexin produced by several cultivated Brassica species. Enhanced susceptibility to the membrane permeabilization activity of camalexin was observed for MAP kinase deficient mutants. These results suggest that the two signalling pathways have a pivotal role in regulating a cellular compensatory response to preserve cell integrity during exposure to camalexin. AbHog1 and AbSlt2 deficient mutants had reduced virulence on host plants that may, at least for the latter mutants, partially result from their inability to cope with defence metabolites such as indolic phytoalexins. This constitutes the first evidence that a phytoalexin activates fungal MAP kinases and that outputs of activated cascades contribute to protecting the fungus against antimicrobial plant metabolites.

PMID: 20812995 [PubMed - indexed for MEDLINE]

518. Sci Total Environ. 2010 Oct 15;408(22):5565-74.

Visually observed mold and moldy odor versus quantitatively measured microbial exposure in homes.

Reponen T, Singh U, Schaffer C, Vesper S, Johansson E, Adhikari A, Grinshpun SA, Indugula R, Ryan P, Levin L, Lemasters G.

University of Cincinnati, Department of Environmental Health, Cincinnati, OH 45267-0056, USA. Tiina.Reponen@uc.edu

The main study objective was to compare different methods for assessing mold exposure in conjunction with an epidemiologic study on the development of children's asthma. Homes of 184 children were assessed for mold by visual observations and dust sampling at child's age 1 (Year 1). Similar assessment supplemented with air sampling was conducted in Year 7. Samples were analyzed for endotoxin, (1-3)-β-D-glucan, and fungal spores. The Mold Specific Quantitative Polymerase Chain Reaction assay was used to analyze 36 mold species in dust samples, and the Environmental Relative Moldiness Index (ERMI) was calculated. Homes were categorized based on three criteria: 1) visible mold damage, 2) moldy odor, and 3) ERMI. Even for homes where families had not moved, Year 7 endotoxin and (1-3)-β-d-glucan exposures were significantly higher than those in Year 1 (p<0.001), whereas no difference was seen for ERMI (p=0.78). Microbial concentrations were not consistently associated with visible mold damage categories, but were consistently higher in homes with moldy odor and in homes that had high ERMI. Low correlations between results in air and dust samples indicate different types or durations of potential microbial exposures from dust vs. air. Future analysis will indicate which, if any, of the assessment methods is associated with the development of asthma.

PMCID: PMC2972663 PMID: 20810150 [PubMed - indexed for MEDLINE]

519. J Invertebr Pathol. 2010 Nov;105(3):305-11. Epub 2010 Aug 31.

Interactions between imidacloprid and Metarhizium brunneum on adult Asian longhorned beetles (Anoplophora glabripennis (Motschulsky)) (Coleoptera: Cerambycidae).

Russell CW, Ugine TA, Hajek AE.

Department of Entomology, Comstock Hall, Cornell University, Ithaca, NY 14853-2601, USA.

Anoplophora glabripennis (Motschulsky) (Coleoptera: Cerambycidae), a longhorned beetle species native to Asia, has been introduced into several North American and European cities. Currently eradication and preventive measures are limited to identifying and destroying infested trees and protecting uninfested trees with trunk or soil-injections of the systemic insecticide imidacloprid. Because entomopathogenic fungi like Metarhizium brunneum Petch have been identified as virulent against these beetles we conducted several tests to determine the compatibility of the two agents in combination. Radial hyphal growth and the sporulation capacity of M. brunneum on Sabouraud dextrose agar with yeast were not significantly affected by the presence of imidacloprid. In a 2×3 factorial experiment investigating interactions between exposure to imidacloprid and M. brunneum we observed no effect of imidacloprid alone on beetle survival when beetles were given a single dose of 10 or 100 ppm compared to control insects. We observed a significant effect of exposure to M. brunneum, and a significant interaction between imidacloprid and M. brunneum representing a synergistic effect of dual treatment. Beetles exposed to the fungus alone lived significantly longer compared to insects treated with a single dose of 100 ppm imidacloprid (9.5 vs. 6.5d). Consumption of striped maple twigs by beetles exposed to imidacloprid, across concentrations, was reduced 48% compared to control insects, where as consumption by M. brunneum-exposed beetles was reduced by 16% over the first 6-days of the test period. Beetles fed 100 ppm imidacloprid consumed 32% less over the first 3d compared to beetles not exposed to imidacloprid and thereafter consumed as much as beetles not fed 100 ppm imidacloprid. M. brunneum-exposed beetles consumed significantly less food than control insects throughout the test period, and beetles treated with imidacloprid produced significantly fewer conidia compared to beetles not treated with imidacloprid.

PMID: 20807541 [PubMed - indexed for MEDLINE]

520. J Invertebr Pathol. 2010 Nov;105(3):322-8. Epub 2010 Aug 31.

Effects of culture media on hydrophobicity and thermotolerance of Bb and Ma conidia, with description of a novel surfactant based hydrophobicity assay.

Kim JS, Skinner M, Hata T, Parker BL.

Entomology Research Laboratory, Department of Plant and Soil Science, University of Vermont, 661 Spear Street, Burlington, VT 05405-0105, USA. jae-su.kim@uvm.edu

Hypocrealean entomopathogenic fungal conidia are made up of multi-aged groups given their chronological conidiogenesis. Most thermotolerance assays have been conducted using mixed-age conidia. The present work exploited a polysiloxane polyether copolymer (siloxane) (Silwet L-77®) mediated conidial collection method, validated by a hydrophobicity assay. This was done to divide mixed-age conidia into two groups based on hydrophobicity and test their thermotolerance, relying on the relationship of conidial age with hydrophobicity. Beauveria bassiana GHA and ERL1170 and Metarhizium anisopliae ERL1171 and ERL1540 conidia, produced on millet agar, whey permeate agar, and ¼SDAY were subjected to hydrophobicity assays that included data on yield of conidia/unit of surface area. Conidia were also collected using 0.01% siloxane, and those remaining with 0.08% siloxane. Hydrophobicity was correlated with percent conidia collected in the two siloxane solutions and yield, suggesting a relationship between percent conidia collected and conidial age (maturation). The conidial suspensions were exposed to 45°C for 45min, and conidial germination was examined. Overall, conidia which were collected in 0.08% siloxane had lower germination after heat exposure than those collected in the 0.01% solution. Conidia of both fungi produced by incubation on millet or whey permeate for 14d were more hydrophobic and exhibited greater thermotolerance than those produced on ¼SDAY. These results suggest that conidia can be divided into two groups with different thermotolerance by using a siloxane-mediated conidial collection method based on hydrophobicity. This depends on the types of substrates used that could influence conidial maturation.

PMID: 20807540 [PubMed - indexed for MEDLINE]

521. Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi. 2010 Jun 30;28(3):210-3.

[Molluscicidal effect of endophyte LL3026 from Buddleia lindleyana against Oncomelania hupensis].

[Article in Chinese]

Han BX, Chen J, Hao L, Zhou XK, Han FA, Li LG.

College of Pharmacy, Jiangsu University, Zhenjiang 212013, China.

OBJECTIVE: To research the molluscicidal effect, active components, thermal stability and light stability of endophyte LL3026 (Colletotrichum sp.) from Buddleia lindleyana
METHODS: The molluscicidal effect of LL3026 against Oncomelania hupensis was determined as referring to the WHO guidelines for laboratory molluscicidal test, and the control experiments were performed with 1 mg/L niclosamide or dechlorinated tap water. The active components from LL3026 were extracted by different polar solvents. The thermal stability and light stability of its extracellular moiety was examined at different temperature (30-100 degrees C), different time (30-150 min) and different illumination time (1-9 d).
RESULTS: Immersion test showed that the LC50 values for the LL3026 broth were 50.11, 3.43, and 1.55 mg/L for 24, 48, and 72 h, respectively. The ether extract of LL3026 broth showed the best molluscicidal activity compared with other fractions. Treated with 25 mg/L ether extract for 24, 48, and 72 h, the mortality of O. hupensis was 100%. The molluscicidal activity of LL3026 broth had no change at 80 degrees C for 120 min, and the snail mortality was 100%. A 48-h exposure to LL3026 broth which placed in an artificial climate box with 3 600 1x illumination for 9 d resulted in 86.7% snail mortality.
CONCLUSION: The fractions extracted from endophyte LL3026 isolated from B. lindleyana shows molluscicidal effect to O. hupensis.

PMID: 20806507 [PubMed - indexed for MEDLINE]

522. Regul Toxicol Pharmacol. 2010 Dec;58(3):490-500. Epub 2010 Sep 8.

Safety assessment of EPA-rich oil produced from yeast: Results of a 90-day subchronic toxicity study.

MacKenzie SA, Belcher LA, Sykes GP, Frame SR, Mukerji P, Gillies PJ.

DuPont Haskell Global Centers for Health and Environmental Sciences, E. I. duPont de Nemours & Company, 1090 Elkton Road, Newark, DE 19711-3507, USA. susan.a.mackenzie@usa.dupont.com

The safety of eicosapentaenoic acid (EPA) oil produced from genetically modified Yarrowia lipolytica yeast was evaluated following 90 days of exposure. Groups of rats received 0 (olive oil), 98, 488, or 976 mg EPA/kg/day, or GRAS fish oil or deionized water by oral gavage. Rats were evaluated for in-life, neurobehavioral, anatomic and clinical pathology parameters. Lower serum cholesterol (total and non-HDL) was observed in Medium and High EPA and fish oil groups. Lower HDL was observed in High EPA and fish oil males, only at early time points. Liver weights were increased in High EPA and Medium EPA (female only) groups with no associated clinical or microscopic pathology findings. Nasal lesions, attributed to oil in the nasal cavity, were observed in High and Medium EPA and fish oil groups. No other effects were attributed to test oil exposure. Exposure to EPA oil for 90 days produced no effects at 98 mg EPA/kg/day and no adverse effects at doses up to 976 mg EPA/kg/day. The safety profile of EPA oil was comparable to that of GRAS fish oil. These results support the use of EPA oil produced from yeast as a safe source for use in dietary supplements.

PMID: 20804805 [PubMed - indexed for MEDLINE]

523. Mycopathologia. 2011 Apr;171(4):291-8. Epub 2010 Aug 29.

Chemosensitization of aflatoxigenic fungi to antimycin A and strobilurin using salicylaldehyde, a volatile natural compound targeting cellular antioxidation system.

Kim JH, Campbell BC, Mahoney N, Chan KL, Molyneux RJ.

Plant Mycotoxin Research Unit, Western Regional Research Center, USDA-ARS, 800 Buchanan Street, Albany, CA 94710, USA.

Various species of fungi in the genus Aspergillus are the most common causative agents of invasive aspergillosis and/or producers of hepato-carcinogenic mycotoxins. Salicylaldehyde (SA), a volatile natural compound, exhibited potent antifungal and anti-mycotoxigenic activities to A. flavus and A. parasiticus. By exposure to the volatilized SA, the growth of A. parasiticus was inhibited up to 10-75% at 9.5 mM ≤ SA ≤ 16.0 mM, while complete growth inhibition was achieved at 19.0 mM ≤ SA. Similar trends were also observed with A. flavus. The aflatoxin production, i.e., aflatoxin B(1) and B(2) (AFB(1), AFB(2)) for A. flavus and AFB(1), AFB(2), AFG(1), and AFG(2) for A. parasiticus, in the SA-treated (9.5 mM) fungi was reduced by ~13-45% compared with the untreated control. Using gene deletion mutants of the model yeast Saccharomyces cerevisiae, we identified the fungal antioxidation system as the molecular target of SA, where sod1Δ [cytosolic superoxide dismutase (SOD)], sod2Δ (mitochondrial SOD), and glr1Δ (glutathione reductase) mutants showed increased sensitivity to this compound. Also sensitive was the gene deletion mutant, vph2Δ, for the vacuolar ATPase assembly protein, suggesting vacuolar detoxification plays an important role for fungal tolerance to SA. In chemosensitization experiments, co-application of SA with either antimycin A or strobilurin (inhibitors of mitochondrial respiration) resulted in complete growth inhibition of Aspergillus at much lower dose treatment of either agent, alone. Therefore, SA can enhance antifungal activity of commercial antifungal agents required to achieve effective control. SA is a potent antifungal and anti-aflatoxigenic volatile that may have some practical application as a fumigant.

PMID: 20803256 [PubMed - indexed for MEDLINE]

524. Sci Total Environ. 2010 Oct 15;408(22):5489-98. Epub 2010 Aug 30.

Exposure matrices of endotoxin, (1→3)-β-d-glucan, fungi, and dust mite allergens in flood-affected homes of New Orleans.

Adhikari A, Lewis JS, Reponen T, Degrasse EC, Grimsley LF, Chew GL, Iossifova Y, Grinshpun SA.

Department of Environmental Health, University of Cincinnati, Cincinnati, OH 45267-0056, USA.

This study examined: (i) biocontaminant levels in flooded homes of New Orleans two years after the flooding; (ii) seasonal changes in biocontaminant levels, and (iii) correlations between biocontaminant levels obtained by different environmental monitoring methods. Endotoxin, (1→3)-β-d-glucan, fungal spores, and dust mite allergens were measured in 35 homes during summer and winter. A combination of dust sampling, aerosolization-based microbial source assessment, and long-term inhalable bioaerosol sampling aided in understanding exposure matrices. On average, endotoxin found in the aerosolized fraction accounted for <2% of that measured in the floor dust, suggesting that vacuuming could overestimate inhalation exposures. In contrast, the (1→3)-β-d-glucan levels in the floor dust and aerosolized fractions were mostly comparable, and 25% of the homes showed aerosolizable levels even higher than the dust-borne levels. The seasonal patterns for endotoxin in dust and the aerosolizable fraction were different from those found for (1→3)-β-d-glucan, reflecting the temperature and humidity effects on bacterial and fungal contamination. While the concentration of airborne endotoxin followed the same seasonal trend as endotoxin aerosolized from surfaces, no significant seasonal difference was identified for the concentrations of airborne (1→3)-β-d-glucan and fungal spores. This was attributed to the difference in the particle size; smaller endotoxin-containing particles can remain airborne for longer time than larger fungal spores or (1→3)-β-d-glucan-containing particles. It is also possible that fungal aerosolization in home environments did not reach its full potential. Detectable dust mite allergens were found only in dust samples, and more commonly in occupied homes. Levels of endotoxin, (1→3)-β-d-glucan, and fungi in air had decreased during the two-year period following the flooding as compared to immediate measurements; however, the dust-borne endotoxin and (1→3)-β-d-glucan levels remained elevated. No conclusive correlations were found between the three environmental monitoring methods. The findings support the use of multiple methods when assessing exposure to microbial contaminants.

PMID: 20800874 [PubMed - indexed for MEDLINE]

525. Malar J. 2010 Aug 27;9:246.

Tools for delivering entomopathogenic fungi to malaria mosquitoes: effects of delivery surfaces on fungal efficacy and persistence.

Mnyone LL, Kirby MJ, Lwetoijera DW, Mpingwa MW, Simfukwe ET, Knols BG, Takken W, Russell TL.

Biomedical and Environmental Group, Ifakara Health Institute, P,O, Box 53, Off Mlabani Passage, Ifakara, Tanzania. llaurent@ihi.or.tz

BACKGROUND: Entomopathogenic fungi infection on malaria vectors increases daily mortality rates and thus represents a control measure that could be used in integrated programmes alongside insecticide-treated bed nets (ITNs) and indoor residual spraying (IRS). Before entomopathogenic fungi can be integrated into control programmes, an effective delivery system must be developed.
METHODS: The efficacy of Metarhizium anisopliae ICIPE-30 and Beauveria bassiana I93-825 (IMI 391510) (2 × 10(10) conidia m(-2)) applied on mud panels (simulating walls of traditional Tanzanian houses), black cotton cloth and polyester netting was evaluated against adult Anopheles gambiae sensu stricto. Mosquitoes were exposed to the treated surfaces 2, 14 and 28 d after conidia were applied. Survival of mosquitoes was monitored daily.
RESULTS: All fungal treatments caused a significantly increased mortality in the exposed mosquitoes, descending with time since fungal application. Mosquitoes exposed to M. anisopliae conidia on mud panels had a greater daily risk of dying compared to those exposed to conidia on either netting or cotton cloth (p < 0.001). Mosquitoes exposed to B. bassiana conidia on mud panels or cotton cloth had similar daily risk of death (p = 0.14), and a higher risk than those exposed to treated polyester netting (p < 0.001). Residual activity of fungi declined over time; however, conidia remained pathogenic at 28 d post application, and were able to infect and kill 73 - 82% of mosquitoes within 14 d.
CONCLUSION: Both fungal isolates reduced mosquito survival on immediate exposure and up to 28 d after application. Conidia were more effective when applied on mud panels and cotton cloth compared with polyester netting. Cotton cloth and mud, therefore, represent potential substrates for delivering fungi to mosquitoes in the field.

PMCID: PMC2939623 PMID: 20799967 [PubMed - indexed for MEDLINE]

526. J Biomed Opt. 2010 Jul-Aug;15(4):041505.

Effect of long- and short-term exposure to laser light at 1070 nm on growth of Saccharomyces cerevisiae.

Aabo T, Perch-Nielsen IR, Dam JS, Palima DZ, Siegumfeldt H, Glückstad J, Arneborg N.

University of Copenhagen, Department of Food Science, Frederiksberg, Denmark. taa@life.ku.dk

The effect of a 1070-nm continuous and pulsed wave ytterbium fiber laser on the growth of Saccharomyces cerevisiae single cells is investigated over a time span of 4 to 5 h. The cells are subjected to optical traps consisting of two counterpropagating plane wave beams with a uniform flux along the x, y axis. Even at the lowest continuous power investigated-i.e., 0.7 mW-the growth of S. cerevisiae cell clusters is markedly inhibited. The minimum power required to successfully trap single S. cerevisiae cells in three dimensions is estimated to be 3.5 mW. No threshold power for the photodamage, but instead a continuous response to the increased accumulated dose is found in the regime investigated from 0.7 to 2.6 mW. Furthermore, by keeping the delivered dose constant and varying the exposure time and power-i.e. pulsing-we find that the growth of S. cerevisiae cells is increasingly inhibited with increasing power. These results indicate that growth of S. cerevisiae is dependent on both the power as well as the accumulated dose at 1070 nm.

PMID: 20799783 [PubMed - indexed for MEDLINE]

527. Arch Toxicol. 2010 Sep;84(9):663-79. Epub 2010 Aug 27.

Deoxynivalenol: mechanisms of action, human exposure, and toxicological relevance.

Pestka JJ.

Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA. Pestka@msu.edu

The trichothecene mycotoxin deoxynivalenol (DON) is produced in wheat, barley and corn following infestation by the fungus Fusarium in the field and during storage. Colloquially known as "vomitoxin" because of its emetic effects in pigs, DON has been associated with human gastroenteritis. Since DON is commonly detected in cereal foods, there are significant questions regarding the risks of acute poisoning and chronic effects posed to persons ingesting this trichothecene. A further challenge is how to best manage perceived risks without rendering critical food staples unavailable to an ever-expanding world population. In experimental animal models, acute DON poisoning causes emesis, whereas chronic low-dose exposure elicits anorexia, growth retardation, immunotoxicity as well as impaired reproduction and development resulting from maternal toxicity. Pathophysiologic effects associated with DON include altered neuroendocrine signaling, proinflammatory gene induction, disruption of the growth hormone axis, and altered gut integrity. At the cellular level, DON induces ribotoxic stress thereby disrupting macromolecule synthesis, cell signaling, differentiation, proliferation, and death. There is a need to better understand the mechanistic linkages between these early dose-dependent molecular effects and relevant pathological sequelae. Epidemiological studies are needed to determine if relationships exist between consumption of high DON levels and incidence of both gastroenteritis and potential chronic diseases. From the perspective of human health translation, a particularly exciting development is the availability of biomarkers of exposure (e.g. DON glucuronide) and effect (e.g. IGF1) now make it possible to study the relationship between DON consumption and growth retardation in susceptible human populations such as children and vegetarians. Ultimately, a fusion of basic and translational research is needed to validate or refine existing risk assessments and regulatory standards for this common mycotoxin.

PMID: 20798930 [PubMed - indexed for MEDLINE]

528. Occup Environ Med. 2010 Nov;67(11):785-91. Epub 2010 Aug 25.

Fast and specific detection of moderate long-term changes in occupational blood exposures.

Chaillol I, Ecochard R, Denis MA, Iwaz J, Khoueiry P, Bergeret A.

Hospices Civils de Lyon, Service de Biostatistique, Lyon, F-69003, France.

OBJECTIVES: Hospital surveillance systems have been established to monitor occupational blood exposures. We compare short-term monitoring with long-term monitoring of data analysis over 11 years and 21 institutions to identify variations in the number of reported exposures.
METHODS: Short-term monitoring examines the current number of exposures compared to their average over previous years. Long-term monitoring detects trends over several years by various exposure characteristics (place, staff, procedure, etc) through estimating rates of change and using the best linear unbiased predictors (BLUPs) to prevent artefactual trends due to the many categories for each characteristic. Graphical representations of estimated rates help detect change and differences in rates of change.
RESULTS: Annual monitoring allowed detection of significant changes in the number of reported exposures. Long-term monitoring identified moderate trends over time. The BLUP corrected the estimate of each specific annual rate of change and allowed all other rates to reduce the random variability around the mean change for more specificity. League tables showed significant increases or decreases compared to no change. League tables for two-by-two comparisons allowed reliable comparisons between estimates of the rates of change, although with spurious ranking. Funnel plots enabled quick detection of changes in trends within specified confidence intervals. Long-term trends agreed with the dominant type of annual changes over the 11 years but were not as sensitive.
CONCLUSIONS: The two methods have different uses. Both are helpful for assessing short-term sudden and long-term minor changes in number of exposures, possibly reflecting the success or otherwise of introducing specific safety devices or guidelines.

PMID: 20798016 [PubMed - indexed for MEDLINE]

529. Fungal Genet Biol. 2011 Feb;48(2):92-103. Epub 2010 Aug 24.

Comparison of transcriptional and translational changes caused by long-term menadione exposure in Aspergillus nidulans.

Pusztahelyi T, Klement E, Szajli E, Klem J, Miskei M, Karányi Z, Emri T, Kovács S, Orosz G, Kovács KL, Medzihradszky KF, Prade RA, Pócsi I.

Department of Microbial Biotechnology and Cell Biology, Faculty of Science and Technology, University of Debrecen, Egyetem tér 1, H-4032 Debrecen, Hungary. pusztahelyi@yahoo.com

Under long-term oxidative stress caused by menadione sodium bisulfite, genome-wide transcriptional and proteome-wide translational changes were compared in Aspergillus nidulans vegetative cells. The comparison of proteomic and DNA microarray expression data demonstrated that global gene expression changes recorded with either flip-flop or dendrimer cDNA labeling techniques supported proteome changes moderately with 40% and 34% coincidence coefficients, respectively. Enzyme levels in the glycolytic pathway were alternating, which was a direct consequence of fluctuating gene expression patterns. Surprisingly, enzymes in the vitamin B2 and B6 biosynthetic pathways were repressed concomitantly with the repression of some protein folding chaperones and nuclear transport elements. Under long-term oxidative stress, the peroxide-detoxifying peroxiredoxins and cytochrome c peroxidase were replaced by thioredoxin reductase, a nitroreductase and a flavohemoprotein, and protein degradation became predominant to eliminate damaged proteins.

PMID: 20797444 [PubMed - indexed for MEDLINE]

530. FEMS Yeast Res. 2010 Dec;10(8):1035-45. doi: 10.1111/j.1567-1364.2010.00674.x.

Lipid-induced ER stress in yeast and β cells: parallel trails to a common fate.

Pineau L, Ferreira T.

Institut de Physiologie et Biologie Cellulaires, CNRS UMR 6187, Université de POITIERS, Poitiers, France.

Exposure to long-chain saturated fatty acids (SFAs; e.g. palmitate) induces apoptosis in pancreatic β cells, a process that may contribute to the development of type 2 diabetes. Under palmitate treatment, β cells undergo a so-called endoplasmic reticulum (ER) stress that can be counteracted by the unfolded protein response (UPR). The UPR is a coordinated response, which is primarily devoted to helping the ER to cope with the accumulation of misfolded proteins. Sustained SFA exposure may ultimately overwhelm the UPR, resulting in cell death. By contrast, unsaturated fatty acids (e.g. oleate) are much less harmful to the cells and can even alleviate palmitate toxicity. Surprisingly, recent evidences indicate that a simple unicellular eukaryote, the budding yeast Saccharomyces cerevisiae, which is not routinely exposed to high-fat diets, also undergoes ER stress under lipotoxic conditions. This suggests that the mechanisms of SFA toxicity are largely conserved throughout eukaryotes and are not specific of a given cell type. The present review discusses the mechanisms of SFA toxicity in yeast and β cells, with a main emphasis on their potential impacts on ER-membrane organization/function and ER-based processes.

PMID: 20738405 [PubMed - indexed for MEDLINE]

531. Yeast. 2011 Jan;28(1):9-17. doi: 10.1002/yea.1816. Epub 2010 Aug 24.

Slt2 MAPK pathway is essential for cell integrity in the presence of arsenate.

Matia-González AM, Rodríguez-Gabriel MA.

Department of Microbiología II, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain.

Arsenate is a common toxic metalloid found in drinking water worldwide that causes several human diseases. The biochemical action underlying cellular response to arsenate, however, is not yet completely understood. Here we used Saccharomyces cerevisiae as an eukaryotic model system to identify proteins essential for adaptation to arsenate treatment. Previous studies have demonstrated a function for Hog1 MAPK in modulating the cellular response to arsenite. Our results, however, showed that cells deficient in Hog1 did not show increased sensitivity to arsenate, suggesting that perhaps other MAPKs may be involved in the response to this particular arsenic species. Here, we found that Slt2 MAPK and several of its upstream regulators are essential in modulating the response to arsenate, and that Slt2 is phosphorylated after arsenate treatment. Furthermore, whole-genome transcriptional analysis showed that Slt2 is required for the induction of several genes in response to arsenate exposure. Many of these genes are involved in the cellular response to heat, suggesting an overlap between these two stress response pathways, and pointing toward a common response to both arsenate and heat exposure in Saccharomyces cerevisiae. Furthermore, our results support the idea that cellular exposure to arsenate results in induction of cellular signalling pathways different from those induced under arsenite treatment.

PMID: 20737431 [PubMed - indexed for MEDLINE]

532. Yeast. 2011 Jan;28(1):19-25. doi: 10.1002/yea.1817. Epub 2010 Aug 24.

Requirement of glutathione for Sod1 activation during lifespan extension.

Mannarino SC, Vilela LF, Brasil AA, Aranha JN, Moradas-Ferreira P, Pereira MD, Costa V, Eleutherio EC.

Departamento de Bioquímica, Instituto de Química, UFRJ, 21941-909, Rio de Janeiro, Brazil. sergiocantum@gmail.com

It has been shown that the activation of cytosolic superoxide dismutase (Sod1) in Saccharomyces cerevisiae is only dependent on Ccs1, which is responsible for insertion of copper into the enzyme catalytic center, and that glutathione (GSH) is not necessary for this process. In this work, we addressed an important role of GSH in Sod1 activation by a Ccs1-dependent mechanism during oxidative stress and its role in yeast lifespan. Exponential cells of Saccharomyces cerevisiae, treated or not with 0.5 mM menadione for 1 h, were used for evaluation of the effect of a mild oxidative stress pre-treatment on chronological lifespan. The results showed that menadione induced a lifespan extension in the wild-type (WT) strain but this adaptive response was repressed in gsh1 and in sod1 strains. Interestingly, menadione treatment increased SOD1 and CCS1 gene expression in both WT and gsh1 strains. However, while these strains showed the same Sod1 activity before treatment, only the WT presented an increase of Sod1 activity after menadione exposure. Glutathionylation seems to be essential for Sod1 activation since no increase in activity was observed after menadione treatment in grx1 and grx2 null mutants. Our results suggest that GSH and glutathionylation are fundamental to protect Sod1 sulfhydryl residues under mild oxidative stress, enabling Sod1 activation and lifespan extension.

PMID: 20737429 [PubMed - indexed for MEDLINE]

533. Am J Infect Control. 2010 Sep;38(7):546-51.

Secular trends of candidemia in a tertiary care hospital.

Sampaio Camargo TZ, Marra AR, Silva CV, Cardoso MF, Martino MD, Camargo LF, Correa L.

Hospital Israelita Albert Einstein, São Paulo, Brazil. zinsly@terra.com.br

BACKGROUND: Candidemias account for 8% to 15% of hospital-acquired bloodstream infections. They have been associated with previous exposure to antimicrobials and are considered high-morbidity infections with high treatment costs. This study characterizes candidemias in a tertiary care hospital and assesses their incidence rates, clinical and microbiological features, and use of antifungals.
METHODS: We assessed hospital-acquired candidemias in the period from January 1997 to July 2007 in a high-complexity private hospital.
RESULTS: There were 151 cases of candidemia in 147 patients. The incidence rate was 0.74 episodes/1000 admissions. The mean age of the patients was 60 years (standard deviation +/- 24.9), and the mean length of hospital stay before the blood culture identified candidemia was 40.9 days (standard deviation +/- 86.3). The in-hospital mortality rate was 44.2%. C albicans was isolated in 44% (n = 67) of the cases, and no difference in mortality rates was found between species (Candida albicans vs C non-albicans, P = .6). The average use of antifungals in the period was 104.0 defined daily dose/1000 patient-days.
CONCLUSION: We found a high mortality rate associated to candidemia events and an increasingly important role of Candida non-albicans. New approaches to health care-related infection control and to defining prophylactic and preemptive therapies should change this scenario in the future.

PMID: 20736114 [PubMed - indexed for MEDLINE]

534. J Ind Microbiol Biotechnol. 2011 Jun;38(6):687-96. Epub 2010 Aug 24.

Single-cell analysis of S. cerevisiae growth recovery after a sublethal heat-stress applied during an alcoholic fermentation.

Tibayrenc P, Preziosi-Belloy L, Ghommidh C.

Université Montpellier 2-UMR IATE, Place Eugène Bataillon, CC023, 34095 Montpellier Cedex 05, France. pierretibayrenc@yahoo.fr

Interest in bioethanol production has experienced a resurgence in the last few years. Poor temperature control in industrial fermentation tanks exposes the yeast cells used for this production to intermittent heat stress which impairs fermentation efficiency. Therefore, there is a need for yeast strains with improved tolerance, able to recover from such temperature variations. Accordingly, this paper reports the development of methods for the characterization of Saccharomyces cerevisiae growth recovery after a sublethal heat stress. Single-cell measurements were carried out in order to detect cell-to-cell variability. Alcoholic batch fermentations were performed on a defined medium in a 2 l instrumented bioreactor. A rapid temperature shift from 33 to 43 °C was applied when ethanol concentration reached 50 g l⁻¹. Samples were collected at different times after the temperature shift. Single cell growth capability, lag-time and initial growth rate were determined by monitoring the growth of a statistically significant number of cells after agar medium plating. The rapid temperature shift resulted in an immediate arrest of growth and triggered a progressive loss of cultivability from 100 to 0.0001% within 8 h. Heat-injured cells were able to recover their growth capability on agar medium after a lag phase. Lag-time was longer and more widely distributed as the time of heat exposure increased. Thus, lag-time distribution gives an insight into strain sensitivity to heat-stress, and could be helpful for the selection of yeast strains of technological interest.

PMID: 20734106 [PubMed - indexed for MEDLINE]

535. Protoplasma. 2010 Dec;247(3-4):233-56. Epub 2010 Aug 24.

From signal transduction to autophagy of plant cell organelles: lessons from yeast and mammals and plant-specific features.

Reumann S, Voitsekhovskaja O, Lillo C.

Centre for Organelle Research, University of Stavanger, 4021 Stavanger, Norway. sigrun.reumann@uis.no

Autophagy is an evolutionarily conserved intracellular process for the vacuolar degradation of cytoplasmic constituents. The central structures of this pathway are newly formed double-membrane vesicles (autophagosomes) that deliver excess or damaged cell components into the vacuole or lysosome for proteolytic degradation and monomer recycling. Cellular remodeling by autophagy allows organisms to survive extensive phases of nutrient starvation and exposure to abiotic and biotic stress. Autophagy was initially studied by electron microscopy in diverse organisms, followed by molecular and genetic analyses first in yeast and subsequently in mammals and plants. Experimental data demonstrate that the basic principles, mechanisms, and components characterized in yeast are conserved in mammals and plants to a large extent. However, distinct autophagy pathways appear to differ between kingdoms. Even though direct information remains scarce particularly for plants, the picture is emerging that the signal transduction cascades triggering autophagy and the mechanisms of organelle turnover evolved further in higher eukaryotes for optimization of nutrient recycling. Here, we summarize new research data on nitrogen starvation-induced signal transduction and organelle autophagy and integrate this knowledge into plant physiology.

PMID: 20734094 [PubMed - indexed for MEDLINE]

536. Proc Natl Acad Sci U S A. 2010 Sep 21;107(38):16715-20. Epub 2010 Aug 23.

Physical interaction between VIVID and white collar complex regulates photoadaptation in Neurospora.

Chen CH, DeMay BS, Gladfelter AS, Dunlap JC, Loros JJ.

Department of Genetics, Dartmouth Medical School, Hanover, NH 03755, USA.

Photoadaptation, the ability to attenuate a light response on prolonged light exposure while remaining sensitive to escalating changes in light intensity, is essential for organisms to decipher time information appropriately, yet the underlying molecular mechanisms are poorly understood. In Neurospora crassa, VIVID (VVD), a small LOV domain containing blue-light photoreceptor protein, affects photoadaptation for most if not all light-responsive genes. We report that there is a physical interaction between VVD and the white collar complex (WCC), the primary blue-light photoreceptor and the transcription factor complex that initiates light-regulated transcriptional responses in Neurospora. Using two previously characterized VVD mutants, we show that the level of interaction is correlated with the level of WCC repression in constant light and that even light-insensitive VVD is sufficient partly to regulate photoadaptation in vivo. We provide evidence that a functional GFP-VVD fusion protein accumulates in the nucleus on light induction but that nuclear localization of VVD does not require light. Constitutively expressed VVD alone is sufficient to change the dynamics of photoadaptation. Thus, our results demonstrate a direct molecular connection between two of the most essential light signaling components in Neurospora, VVD and WCC, illuminating a previously uncharacterized process for light-sensitive eukaryotic cells.

PMCID: PMC2944764 PMID: 20733070 [PubMed - indexed for MEDLINE]

537. Antimicrob Agents Chemother. 2010 Nov;54(11):4758-64. Epub 2010 Aug 23.

Impact of cyp51A mutations on the pharmacokinetic and pharmacodynamic properties of voriconazole in a murine model of disseminated aspergillosis.

Mavridou E, Bruggemann RJ, Melchers WJ, Verweij PE, Mouton JW.

Department of Medical Microbiology, Radboud University Nijmegen Medical Center, Nijmegen, Netherlands.

The in vivo efficacy of voriconazole against 4 clinical Aspergillus fumigatus isolates with MICs ranging from 0.125 to 2 mg/liter (CLSI document M38A) was assessed in a nonneutropenic murine model of disseminated aspergillosis. The study involved TR/L98H, M220I, and G54W mutants and a wild-type control isolate. Oral voriconazole therapy was started 24 h after intravenous infection of mice and was given once daily for 14 consecutive days, with doses ranging from 10 to 80 mg/kg of body weight, using survival as the endpoint. Survival for all isolates was dependent on the voriconazole dose level (R(2) value of 0.5 to 0.6), but a better relationship existed for the area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC/MIC ratio) or the AUC for the free, unbound fraction of the drug divided by the MIC (fAUC/MIC ratio) (R(2) value of 0.95 to 0.98). The 24-h fAUC/MIC ratio showed a clear relationship to effect, with an exposure index for amount of free drug required for 50% of maximum effectiveness (fEI(50)) of 11.17 at day 7. Maximum effect was reached at values of around 80 to 100, comparable to that observed for posaconazole and A. fumigatus. Mice infected with an isolate having a MIC of 2 mg/liter required an exposure that was inversely correlated with the increase in MIC compared to that of the wild-type control, but due to nonlinear pharmacokinetics, this required only doubling of the voriconazole dose. The efficacy of voriconazole for isolates with high MICs for other triazoles but voriconazole MICs within the wild-type population range was comparable to that for the wild-type control. Finally, we used a grapefruit juice-free murine model of aspergillosis and concluded that this model is appropriate to study pharmacokinetic/pharmacodynamic relationships of voriconazole.

PMCID: PMC2976127 PMID: 20733046 [PubMed - indexed for MEDLINE]

538. Crit Care. 2010;14(4):R159. Epub 2010 Aug 24.

Evaluation of pathogen detection from clinical samples by real-time polymerase chain reaction using a sepsis pathogen DNA detection kit.

Yanagihara K, Kitagawa Y, Tomonaga M, Tsukasaki K, Kohno S, Seki M, Sugimoto H, Shimazu T, Tasaki O, Matsushima A, Ikeda Y, Okamoto S, Aikawa N, Hori S, Obara H, Ishizaka A, Hasegawa N, Takeda J, Kamihira S, Sugahara K, Asari S, Murata M, Kobayashi Y, Ginba H, Sumiyama Y, Kitajima M.

Department of Laboratory Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki City, Nagasaki 852-8501, Japan. kyana-ngs@umin.ac.jp

INTRODUCTION: Sepsis is a serious medical condition that requires rapidly administered, appropriate antibiotic treatment. Conventional methods take three or more days for final pathogen identification and antimicrobial susceptibility testing. We organized a prospective observational multicenter study in three study sites to evaluate the diagnostic accuracy and potential clinical utility of the SeptiFast system, a multiplex pathogen detection system used in the clinical setting to support early diagnosis of bloodstream infections.
METHODS: A total of 212 patients, suspected of having systemic inflammatory response syndrome (SIRS) caused by bacterial or fungal infection, were enrolled in the study. From these patients, 407 blood samples were taken and blood culture analysis was performed to identify pathogens. Whole blood was also collected for DNA Detection Kit analysis immediately after its collection for blood culture. The results of the DNA Detection Kit, blood culture and other culture tests were compared. The chosen antimicrobial treatment in patients whose samples tested positive in the DNA Detection Kit and/or blood culture analysis was examined to evaluate the effect of concomitant antibiotic exposure on the results of these analyses.
RESULTS: SeptiFast analysis gave a positive result for 55 samples, while 43 samples were positive in blood culture analysis. The DNA Detection Kit identified a pathogen in 11.3% (45/400) of the samples, compared to 8.0% (32/400) by blood culture analysis. Twenty-three pathogens were detected by SeptiFast only; conversely, this system missed five episodes of clinically significant bacteremia (Methicillin-resistant Staphylococcus aureus (MRSA), 2; Pseudomonas aeruginosa, 1; Klebsiella spp, 1; Enterococcus faecium, 1). The number of samples that tested positive was significantly increased by combining the result of the blood culture analysis with those of the DNA Detection Kit analysis (P = 0.01). Among antibiotic pre-treated patients (prevalence, 72%), SeptiFast analysis detected more bacteria/fungi, and was less influenced by antibiotic exposure, compared with blood culture analysis (P = 0.02).
CONCLUSIONS: This rapid multiplex pathogen detection system complemented traditional culture-based methods and offered some added diagnostic value for the timely detection of causative pathogens, particularly in antibiotic pre-treated patients. Adequately designed intervention studies are needed to prove its clinical effectiveness in improving appropriate antibiotic selection and patient outcomes.

PMCID: PMC2945143 PMID: 20731880 [PubMed - indexed for MEDLINE]

539. ACS Nano. 2010 Aug 24;4(8):4776-84.

High-resolution functional epoxysilsesquioxane-based patterning layers for large-area nanoimprinting.

Pina-Hernandez C, Guo LJ, Fu PF.

The University of Michigan, 1301 Beal Avenue, Ann Arbor, Michigan 48109, USA.

Epoxysilsesquioxane (SSQ)-based materials have been developed as patterning layers for large-area and high-resolution nanoimprinting. The SSQ polymers, poly(methyl-co-3-glycidoxypropyl) silsesquioxanes (T(Me)T(Ep)), poly(phenyl-co-3-glycidoxypropyl) silsesquioxanes (T(Ph)T(Ep)), and poly(phenyl-co-3-glycidoxypropyl-co-perfluorooctyl) silsesquioxanes (T(Ph)T(Ep)T(Fluo)), were precisely designed and synthesized by incorporating the necessary functional groups onto the SSQ backbone. The materials possess a variety of characteristics desirable for NIL, such as great coatability, high modulus, good mold release, and excellent dry etch resistance. In particular, the presence of epoxy functional groups allows the resists to be solidified within seconds under UV exposure at room temperature, and the presence of the fluoroalkyl groups in the SSQ resins greatly facilitate mold release after the imprint process. In addition, the absence of metal in the resins makes the materials highly compatible with applications involving Si CMOS integrated circuits fabrication.

PMID: 20731453 [PubMed]

540. Accid Anal Prev. 2010 Nov;42(6):1744-50.

Analysis of needlestick injuries among nursing students in Hong Kong.

Cheung K, Ho SC, Ching SS, Chang KK.

School of Nursing, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong. hskin@inet.polyu.edu.hk

BACKGROUND: Research has shown that nursing personnel are exposed to the serious risk of contracting bloodborne diseases from needlestick and sharps injuries (NSIs). Only a few studies have examined the problem among nursing students. In Hong Kong, there is an equal lack of research in this area.
METHODS: A review of accident reports in one university was employed to determine the injury rate, causation, and epidemiological profile of NSIs. Descriptive statistics, prevalence, incidence density, cumulative incidence, and Fisher's exact test were used to analyze the data.
RESULTS: From January 2002 to December 2006, there were a total of 51 reported cases of NSIs (43 needlestick injuries and 8 sharps injuries). The annual prevalence of NSIs in four academic years from 2002-2003 to 2005-2006 ranged from 0.6 to 1.6 cases while the incidence rate was one new case per 100 nursing students per academic year. The cumulative incidence of NSIs for year-one, year-two and year-three students were 0, 0.03 and 0.004 respectively. The majority of needlestick injuries (n=25; 58.14%) were from contaminated needles. Procedures involved in the needlestick injuries were giving injection (n=22; 51.16%), collecting urine specimen (n=5; 11.63%), removal of urinary catheter (n=4; 9.30%), and checking blood glucose using glucometer (n=3; 6.98%). Giving injection (n=5; 62.50%) also accounted for the highest percentage of sharps injuries. Specific activities that were identified were opening the needle cap, opening ampoules, inserting the needle and mixing dirty and clean material in one kidney dish.
CONCLUSIONS: Results showed that nursing students are at high risk of occupational exposure to bloodborne pathogens because of NSIs. A hierarchy control involving engineering, administrative and personal behavioral activities is recommended to reduce the occurrence of NSIs among nursing students.

PMID: 20728625 [PubMed - indexed for MEDLINE]

541. Autoimmun Rev. 2010 Dec;10(2):94-102. Epub 2010 Aug 20.

The immune response in Coccidioidomycosis.

Borchers AT, Gershwin ME.

Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, Davis, CA 95616, United States.

With the increasing use of biologics, clinical rheumatologists are becoming very well acquainted with opportunistic infections, including tuberculosis, histoplasmosis and Coccidiomycosis. In the great valleys of California as well as several other hot spots in the Southern areas of the United States and select pockets in South America, valley fever, also known as Coccidiomycosis, is an endemic infection. The vast majority of patients are asymptomatic following exposure, but are at risk for clinical disease in the case of immunosuppression. Additionally, although 60% of patients with infections are completely asymptomatic, nearly all patients have immunological evidence of exposure. Within some communities in the central valley of California, sero conversion approaches 100%, fortunately the vast majority remain asymptomatic. In this review we will place the context of the immune response to Coccidiomycosis in perspective and discuss not only the lymphoid response, but also recent data on antigenic analysis and bioinformatics of Coccidioides. This information is significant not only for a better understanding of Coccidiomycosis, but will also have utility in the management of patients within areas of the world who are treated with the biologics for autoimmune disease.

PMID: 20728582 [PubMed - indexed for MEDLINE]

542. Diagn Microbiol Infect Dis. 2010 Sep;68(1):60-5.

Prevalence of dihydropteroate synthase genotypes before and after the introduction of combined antiretroviral therapy and their influence on the outcome of Pneumocystis pneumonia in HIV-1-infected patients.

Alvarez-Martínez MJ, Miró JM, Valls ME, Mas J, de la Bellacasa JP, Sued O, Solé M, Rivas PV, de Lazzari E, Benito N, García F, Agustí C, Wilson PE, Gatell JM, Jiménez de Anta MT, Meshnick SR, Moreno A.

Hospital Clínic-IDIBAPS (Institut d'Investigació August Pi i Sunyer), Universitat de Barcelona, Barcelona, Spain.

The objective of this study was to determine whether the prevalence of Pneumocystis jirovecii dihydropteroate synthase (DHPS) gene mutations has changed since the introduction of combined antiretroviral therapy (cART) and whether the mutations are associated with poor outcome in Spanish HIV-1-infected patients with Pneumocystis pneumonia (PcP). We studied 167 PcP episodes in HIV-1-infected patients diagnosed during the pre-cART (1989-1995) and cART (2001-2004) periods. Molecular genotyping of DHPS was successfully performed in 98 patients (43 pre-cART and 55 cART). Seventeen patients (17/98, 17%; 95% confidence interval [CI], 10-25%) had mutations in the DHPS gene: 14 patients (14/43, 33%; 95% CI, 19-49%) from the pre-cART period and 3 patients (3/55, 5.5%; 95% CI, 1.3-16%) from the cART period (P < 0.01). In the multivariate analysis, the pre-cART period, previous PcP prophylaxis with sulfa drugs, and homosexuality as an HIV risk factor were found to be associated with a higher risk of presenting DHPS mutations. Overall, 95% of patients were treated with trimethoprim and sulfamethoxazole (TMP-SMX). In-hospital mortality was similar in patients with (out) mutations (6% versus 11%, P = 0.84). DHPS gene mutations were more common during the pre-cART period and were associated with previous sulfa exposure and homosexuality. However, their presence did not worsen prognosis of PcP. The response to TMP-SMX with therapeutic doses was successful in most cases.

PMID: 20727472 [PubMed - indexed for MEDLINE]

543. OMICS. 2010 Oct;14(5):575-86. Epub 2010 Aug 20.

Weak organic acid stress triggers hyperphosphorylation of the yeast zinc-finger transcription factor War1 and dampens stress adaptation.

Frohner IE, Gregori C, Anrather D, Roitinger E, Schüller C, Ammerer G, Kuchler K.

Medical University Vienna, Max F. Perutz Laboratories, Department of Medical Biochemistry, Vienna, Austria.

Exposure of Saccharomyces cerevisiae to weak organic acids such as sorbate, propionate, or benzoate rapidly induces the plasma membrane ABC transporter Pdr12, requiring the Zn(II)(2)Cys(6) zinc-finger transcription factor War1. Weak acid stress rapidly triggers War1 phosphorylation but its role for War1 function is not clear yet. Here, we provide new insights into sorbate-induced phosphorylation of War1. A War1 zinc-finger mutant is still hyperphosphorylated in response to sorbate stress, indicating that War1 phosphorylation occurs independently of DNA recruitment. To map and identify phosphoresidues, War1 purified from stressed and unstressed cells was subjected to semiquantitative phosphopeptide mass spectrometry analysis. Remarkably, we show that weak acid stress causes a dramatic hyperphosphorylation of several already prephosphorylated residues. WAR1 alleles harboring combinations of mutations identified phosphoresidues were generated, some of which display altered gel mobility. Certain mutational combinations almost completely abolish stress-induced gel-shift, suggesting alternative phosphorylation. Surprisingly, PDR12 expression levels are similar in these mutants, demonstrating that War1 phosphorylation is not required for PDR12 induction. Strikingly, absence of hyperphosphorylation in response to stress leads to a faster stress adaptation, suggesting that phosphorylation might play a role in stabilizing War1 activity on the promoter elements, hence changing the dynamics and kinetics of the stress response.

PMID: 20726777 [PubMed - indexed for MEDLINE]

544. J Food Sci. 2010 Aug 1;75(6):M377-82.

Localization, growth, and inactivation of Salmonella Saintpaul on jalapeño peppers.

Liao CH, Cooke PH, Niemira BA.

Eastern Regional Research Center, U.S. Dept. of Agriculture, Wyndmoor, PA 19038, USA.

Consumption of Salmonella-contaminated jalapeño peppers has been implicated in one of the largest foodborne illness outbreaks in the summer of 2008. The objective of this study was to investigate representative groups of native microflora and the distribution, growth, and inactivation of experimentally-inoculated Salmonella Saintpaul on jalapeño peppers. Two genetically modified strains of Salm. Saintpaul producing either green- or red-fluorescent protein were constructed and used in the study. Microbiological analyses showed that jalapeño peppers contained an average of 5.6 log units of total aerobic count and 3.5, 1.8, and 1.9 log units, respectively, of enterobacteriaceae, lactic acid bacteria, and yeast/mold per gram of tissue. Strains typical of Pseudomonas accounted for 8.3% of total aerobic count, and 0.2% of which exhibited pectolytic activity. On inoculated peppers, a vast majority (>90%) of Salm. Saintpaul was recovered from stem/calyx and only a small proportion recovered from fleshy pods. Growth of Salm. Saintpaul on peppers was indicated by an increase in the population of 3 log units after incubation of samples at 20 degrees C for 48 h. Fluorescent Salm. Saintpaul aggregates could be readily detected on stem/calyx using stereofluorescence imaging microscopy and scanning electron microscopy. Data presented showed that Salm. Saintpaul could survive for at least 8 wk on peppers stored at 4 degrees C. Immersion of inoculated peppers in 200 ppm of sodium hypochlorite, acidified sodium chlorite, or peroxy acetic acid for 10 min could reduce the number of Salm. Saintpaul on stem/calyx by 1.5 to 1.7 and that on flesh by 2.1 to 2.4 log units. Practical Application: Consumption of Salmonella-contaminated jalapeño peppers has been implicated in foodborne illness outbreaks. The vast majority of Salmonella Saintpaul recovered from inoculated jalapeño peppers (>90%) was from stem/calyx. Salmonella increased by 3 log units during storage at 68 degrees F (20 degrees C) for 48 h. Salmonella could survive for at least 8 wk on peppers stored at 4 degrees C. Immersion of inoculated peppers in 200 ppm of sodium hypochlorite, acidified sodium chlorite, or peroxyacetic acid for 10 min reduced Salmonella on stem/calyx by 1.5 to 1.7 log units, compared with reductions of 2.1 to 2.4 log units on flesh. These results highlight the need to consider the stem/calyx as the most likely area for contamination of jalapeño peppers, and to process this commodity accordingly to minimize exposure and cross-contaminations.

PMID: 20722940 [PubMed - indexed for MEDLINE]

545. J Food Sci. 2010 Aug 1;75(6):E372-8.

Development and evaluation of a fluidized bed system for wheat grain disinfection.

Dhillon B, Wiesenborn D, Dhillon H, Wolf-Hall C.

Dept. of Agricultural and Biosystems Engineering, North Dakota State Univ., Fargo, ND 58108-6050, USA.

Durum wheat grain from the field is naturally contaminated with bacteria, yeast, and mold. The reduction in aerobic plate count (APC) and yeast and mold count (YMC) is often necessary before processing wheat. Gaseous ozone, ozonated water, and acetic acid solution are nontraditional antimicrobial agents for grains and are safe for humans and the environment. Better disinfection may be possible by applying antimicrobial agents to grain in a fluidized state. Fluidization increases the exposure of grain surfaces, resulting in uniform and quick contact of grain with antimicrobial agents. Therefore, a fluidized bed was developed with automated spraying system (to spray treatment waters), and a port for gaseous ozone injection. The pressures and velocities within the fluidized bed system were measured to characterize the system. The treatments used on fluidized grain were: distilled water (control), gaseous ozone (6 ppm), ozonated water (23 mg/L), gaseous ozone + ozonated water (6 ppm, 23 mg/L), acetic acid solution (0.5%), acetic acid + ozonated water (0.5%, 26 mg/L), and gaseous ozone + acetic acid + ozonated water (6 ppm, 0.5%, 26 mg/L). The last of these treatments was most effective with 1.7 and 3.3 log reduction in APC and YMC, respectively. This combined treatment can be used to replace the chlorinated water that industry uses during tempering of grain. Ozonated water alone resulted in a 0.3 log reduction in both APC and YMC. Gaseous ozone alone did not cause a significant reduction in APC and YMC.

PMID: 20722922 [PubMed - indexed for MEDLINE]

546. J Public Health Manag Pract. 2010 Sep-Oct;16(5 Suppl):S11-20.

Housing interventions and control of asthma-related indoor biologic agents: a review of the evidence.

Krieger J, Jacobs DE, Ashley PJ, Baeder A, Chew GL, Dearborn D, Hynes HP, Miller JD, Morley R, Rabito F, Zeldin DC.

Chronic Disease and Injury Prevention Section, Public Health-Seattle and King County, Seattle, Washington 98104, USA. james.krieger@kingcounty.gov

Subject matter experts systematically reviewed evidence on the effectiveness of housing interventions that affect health outcomes, primarily asthma, associated with exposure to moisture, mold, and allergens. Three of the 11 interventions reviewed had sufficient evidence for implementation: multifaceted, in-home, tailored interventions for reducing asthma morbidity; integrated pest management to reduce cockroach allergen; and combined elimination of moisture intrusion and leaks and removal of moldy items to reduce mold and respiratory symptoms. Four interventions needed more field evaluation, 1 needed formative research, and 3 either had no evidence of effectiveness or were ineffective. The 3 interventions with sufficient evidence all applied multiple, integrated strategies. This evidence review shows that selected interventions that improve housing conditions will reduce morbidity from asthma and respiratory allergies.

PMID: 20689369 [PubMed - in process]

547. Rev Lat Am Enfermagem. 2010 May-Jun;18(3):368-72.

Biological risk in nursing care provided in family health units.

Cardoso AC, De Figueiredo RM.

Departamento de Enfermagem, Universidade Federal de São Carlos, Brazil.

There is very frequent exposure to potentially contaminated material in procedures performed by nursing professionals. This exploratory and descriptive study characterizes the potential risk of biological exposure in procedures performed by nursing professionals in ten Family Health units in São Carlos-SP, Brazil. We observed 238 procedures involving potential risk of contact with biological material, in which more than 90% involved the use of needles. The average rates of adherence to standard precautions were: 27.9% hand washing prior to procedures; 41.4% use of gloves; and 88.8% adequate disposal of piercing and cutting instruments. These professionals are subject to risks similar to those which hospital workers are also subjected, because they have a high risk of blood exposure and the frequency with which they handle needles is very high.

PMID: 20721425 [PubMed - indexed for MEDLINE]

548. Cancer Sci. 2010 Nov;101(11):2375-83. doi: 10.1111/j.1349-7006.2010.01680.x.

Huaier aqueous extract inhibits proliferation of breast cancer cells by inducing apoptosis.

Zhang N, Kong X, Yan S, Yuan C, Yang Q.

Department of Breast Surgery Obstetrics and Gynecology, Qilu Hospital, Shandong University, School of Medicine, Ji'nan, Shandong, China.

Aqueous extract of Trametes robiniophila murr (Huaier) has been commonly used in China for cancer complementary therapy in recent years; however, the mechanisms of its anticancer effects are largely unknown. In the present study, we aim to investigate its inhibitory effect on both MCF-7 and MDA-MB-231 cells, and explore the possible mechanisms of its anticancer effect. Cell viability and motility were measured by MTT and invasive assays, migration and scratch assays in vitro, respectively. The distribution of cell cycle, PI-Annexin-V staining and Rhodamine 123 assay were analyzed by flow cytometry, and western blot were used to test the apoptotic pathways. We found that Huaier extract could strongly inhibit cell viability of MCF-7 and MDA-MB-231 cells in a time- and dose-dependent manner; however, MDA-MB-231 cells showed more susceptibility to the treatment. Furthermore, cell invasiveness and migration were also suppressed with exposure to Huaier extract. We also indicated that Huaier could induce G0/G1 cell-cycle arrest, p53 accumulation and activation selectively in MCF-7 cells. Inspiringly, the PI-Annexin-V staining assay and western blot analysis confirmed cell apoptosis executed by caspase-3. Decreased mitochondrial membrane potential by Rhodamine 123 assay and down-regulation of Bcl-2 and up-regulation of BCL2-associated X protein (BAX) indicated that Huaier induced apoptosis through the mitochondrial pathway. Caspase activation during Huaier-induced apoptosis was confirmed by pan-caspase inhibitor, Z-VAD-fmk. As expected, the inhibitor decreased Huaier-induced apoptosis in both cell lines. Based on our findings, Huaier can induce cell apoptosis in both ER-positive and ER-negative breast cancer cell lines and is an effective complementary agent for breast cancer treatment.

PMID: 20718753 [PubMed - indexed for MEDLINE]

549. Med Mycol. 2011 Feb;49(2):143-9. Epub 2010 Aug 18.

Developing a safe antifungal treatment protocol to eliminate Batrachochytrium dendrobatidis from amphibians.

Martel A, Van Rooij P, Vercauteren G, Baert K, Van Waeyenberghe L, Debacker P, Garner TW, Woeltjes T, Ducatelle R, Haesebrouck F, Pasmans F.

Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium. an.martel@ugent.be

Batrachochytrium dendrobatidis is one of the most pathogenic microorganisms affecting amphibians in both captivity and in nature. The establishment of B. dendrobatidis free, stable, amphibian captive breeding colonies is one of the emergency measures that is being taken to save threatened amphibian species from extinction. For this purpose, in vitro antifungal susceptibility testing and the development of efficient and safe treatment protocols are required. In this study, we evaluated the use of amphotericin B and voriconazole to treat chytridiomycosis in amphibians. The concentration at which the growth of five tested B. dendrobatidis strains was inhibited was 0.8 μg/ml for amphotericin B and 0.0125 μg/ml for voriconazole. To completely eliminate a mixture of sporangia and zoospores of strain IA042 required 48 h of exposure to 8 μg/ml of amphotericin B or 10 days to 1.25 μg/ml of voriconazole. Zoospores were killed within 0.5 h by 0.8 μg/ml of amphotericin B, but even after 24 h exposure to 1.25 μg/ml of voriconazole they remained viable. Amphotericin B was acutely toxic for Alytes muletensis tadpoles at 8 μg/ml, whereas toxic side effects were not noticed during a seven-day exposure to voriconazole at concentrations as high as 12.5 μg/ml. The voriconazole concentrations remained stable in water during this exposure period. On the basis of this data, experimentally inoculated postmetamorphic Alytes cisternasii were sprayed once daily for 7 days with a 1.25 μg/ml solution of voriconazole in water which eliminated the B. dendrobatidis infection from all treated animals. Finally, treatment of a naturally infected colony of poison dart frogs (Dendrobatidae) using this protocol, combined with environmental disinfection, cleared the infection from the colony.

PMID: 20718611 [PubMed - indexed for MEDLINE]

550. J Asthma. 2010 Sep;47(7):754-61.

Quantification of airborne Aspergillus allergens: redefining the approach.

Vermani M, Vijayan VK, Kausar MA, Agarwal MK.

Department of Respiratory Allergy and Applied Immunology, University of Delhi, Delhi, India.

BACKGROUND: Airborne Aspergillus species are significant environmental components involved in the pathogenesis and persistence of allergic respiratory diseases. The detection and quantification of airborne allergens is important to elucidate the clinical implications of environmental exposure of patients suffering with allergic asthma and/or allergic rhinitis.
OBJECTIVE: The authors report a simple volumetric approach to measure atmospheric concentration of four common airborne species of Aspergillus-A. flavus, A. fumigatus, A. niger, and A. tamarii.
METHODS: As particulate aeroallergens may also exist in amorphous form in addition to morphologically identifiable fungal spores/hyphae, a volumetric technique using membrane filters was developed for simultaneous quantification of (a) viable Aspergillus counts, i.e., colony-forming units (cfu)/m(3), and (b) actual Aspergillus allergen content (ng/m(3)) in the air. Further, immunochemically quantified airborne Aspergillus allergens were compared with their corresponding colony counts.
RESULTS: The average monthly aerial counts of the four Aspergillus species recorded during the sampling year were A. flavus: 0.25-15.2 cfu/m(3); A. fumigatus: 1.25-15.6 cfu/m(3); A. niger: 0.75-16.0 cfu/m(3); and A. tamarii: 0.5-11.8 cfu/m(3) of air. Aerial Aspergillus allergen(s) concentration varied from species to species: A. flavus: 26.8-680.8 ng; A. fumigatus: 18.0-380.4 ng; A. niger: 28.2-1879.0 ng; and A. tamarii: 9.2-238.3 ng/m(3) of air. Seasonal distribution of airborne colony counts of the four species didn't correlate with their respective allergen content.
CONCLUSION: Aspergillus allergens were present in the air of Delhi area throughout the year with seasonal variations. The authors feel that by using the immunochemical technique it will be possible to measure actual exposure of patients to various airborne Aspergillus allergens.

PMID: 20716013 [PubMed - indexed for MEDLINE]

551. Mol Cell Biol. 2010 Oct;30(20):4840-50. Epub 2010 Aug 16.

Srs2 plays a critical role in reversible G2 arrest upon chronic and low doses of UV irradiation via two distinct homologous recombination-dependent mechanisms in postreplication repair-deficient cells.

Hishida T, Hirade Y, Haruta N, Kubota Y, Iwasaki H.

Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan. hishida@biken.osaka-u.ac.jp

Differential posttranslational modification of proliferating cell nuclear antigen (PCNA) by ubiquitin or SUMO plays an important role in coordinating the processes of DNA replication and DNA damage tolerance. Previously it was shown that the loss of RAD6-dependent error-free postreplication repair (PRR) results in DNA damage checkpoint-mediated G(2) arrest in cells exposed to chronic low-dose UV radiation (CLUV), whereas wild-type and nucleotide excision repair-deficient cells are largely unaffected. In this study, we report that suppression of homologous recombination (HR) in PRR-deficient cells by Srs2 and PCNA sumoylation is required for checkpoint activation and checkpoint maintenance during CLUV irradiation. Cyclin-dependent kinase (CDK1)-dependent phosphorylation of Srs2 did not influence checkpoint-mediated G(2) arrest or maintenance in PRR-deficient cells but was critical for HR-dependent checkpoint recovery following release from CLUV exposure. These results indicate that Srs2 plays an important role in checkpoint-mediated reversible G(2) arrest in PRR-deficient cells via two separate HR-dependent mechanisms. The first (required to suppress HR during PRR) is regulated by PCNA sumoylation, whereas the second (required for HR-dependent recovery following CLUV exposure) is regulated by CDK1-dependent phosphorylation.

PMCID: PMC2950541 PMID: 20713444 [PubMed - indexed for MEDLINE]

552. PLoS One. 2010 Aug 11;5(8):e12081.

Synergy in efficacy of fungal entomopathogens and permethrin against West African insecticide-resistant Anopheles gambiae mosquitoes.

Farenhorst M, Knols BG, Thomas MB, Howard AF, Takken W, Rowland M, N'Guessan R.

Laboratory of Entomology, Wageningen University and Research Center, Wageningen, The Netherlands. marit.farenhorst@wur.nl

BACKGROUND: Increasing incidences of insecticide resistance in malaria vectors are threatening the sustainable use of contemporary chemical vector control measures. Fungal entomopathogens provide a possible additional tool for the control of insecticide-resistant malaria mosquitoes. This study investigated the compatibility of the pyrethroid insecticide permethrin and two mosquito-pathogenic fungi, Beauveria bassiana and Metarhizium anisopliae, against a laboratory colony and field population of West African insecticide-resistant Anopheles gambiae s.s. mosquitoes. METHODOLOGY/FINDINGS: A range of fungus-insecticide combinations was used to test effects of timing and sequence of exposure. Both the laboratory-reared and field-collected mosquitoes were highly resistant to permethrin but susceptible to B. bassiana and M. anisopliae infection, inducing 100% mortality within nine days. Combinations of insecticide and fungus showed synergistic effects on mosquito survival. Fungal infection increased permethrin-induced mortality rates in wild An. gambiae s.s. mosquitoes and reciprocally, exposure to permethrin increased subsequent fungal-induced mortality rates in both colonies. Simultaneous co-exposure induced the highest mortality; up to 70.3+/-2% for a combined Beauveria and permethrin exposure within a time range of one gonotrophic cycle (4 days). CONCLUSIONS/SIGNIFICANCE: Combining fungi and permethrin induced a higher impact on mosquito survival than the use of these control agents alone. The observed synergism in efficacy shows the potential for integrated fungus-insecticide control measures to dramatically reduce malaria transmission and enable control at more moderate levels of coverage even in areas where insecticide resistance has rendered pyrethroids essentially ineffective.

PMCID: PMC2920335 PMID: 20711409 [PubMed - indexed for MEDLINE]

553. Med Oral Patol Oral Cir Bucal. 2011 Jan 1;16(1):e23-8.

Antifungal and post-antifungal effects of chlorhexidine, fluconazole, chitosan and its combinations on Candida albicans.

Calamari SE, Bojanich MA, Barembaum SR, Berdicevski N, Azcurra AI.

Oral Biology Department, Faculty of Dentistry, National University of Córdoba, Córdoba, Argentina.

OBJECTIVE: The aim of this work was to assess the antifungal and post-antifungal effects of chlorhexidine, fluconazole, chitosan and its combinations on virulence factors of Candida albicans. STUDY DESIGN: Ten isolated strains of Candida albicans obtained from 10 patients with oral candidiasis and a collection strain of C. albicans were treated with antifungal agents in different concentrations or combinations of them. Virulence factors analyzed were the cell surface hydrophobicity, the germinative tube development, the phospholipase activity and the post-antifungal effect of that exposure.
RESULTS: Virulence factors of the isolated strains obtained from patients together with the collection strain showed significant decreases with the different antifungal treatments, except for hydrophobicity and phospholipase activity. The development of germinative tube was the most sensitive factor to all the antifungal agents used. Untreated strains as well as the ones treated with antifungal agents showed a positive correlation among the virulence factors analyzed. No synergic effects arose from the combinations of the used drugs.
CONCLUSIONS: C. albicans isolated strains from patients showed high phospholipase activity and germinative tube production, which corroborates their capacity to infect the oral mucosa and the high prevalence of species. As a whole, our results imply that short exposures to sub-inhibitory concentrations of the antifungal agents under analysis, isolated or combined, can modulate the way virulence factors get manifested, thus decreasing their pathogenicity.

PMID: 20711160 [PubMed - indexed for MEDLINE]

554. Ecotoxicol Environ Saf. 2010 Oct;73(7):1785-8. Epub 2010 Aug 14.

Time- and dose-dependency of the effects of nitrogen pollution on lichens.

Munzi S, Pisani T, Paoli L, Loppi S.

Department of Environmental Science, University of Siena, via Mattioli 4, 53100 Siena, Italy. munzi@unisi.it

The present work aims at testing if exposure time and dose play a role in the response of lichen species to nitrogen (N) pollution. To this purpose, samples of the N-sensitive Evernia prunastri and the N-tolerant Xanthoria parietina were treated for 5 weeks either with solutions of NH(4)NO(3) 0.05 and 1 M, or (NH(4))(2)SO(4) 0.025 and 0.5 M. Photosynthetic efficiency was measured as an indicator of sample vitality. The results showed that the lowest concentrations were ineffective at the beginning, but after several supplies both compounds inhibited photosynthetic activity of E. prunastri. The highest concentrations had a deleterious effect, but with a temporal trend. For X. parietina no effect was found for the lowest concentrations, while the same trend shown by E. prunastri was instead observed following treatments with the highest concentrations. It was concluded that the response of lichens to N supply is not only species-specific, but also time- and dose-dependent. The results give a clue on field studies on the relationships between lichens and N pollution.

PMID: 20709396 [PubMed - indexed for MEDLINE]

555. J Toxicol Environ Health A. 2010;73(17-18):1194-201.

Microbiological hazards resulting from application of dairy sewage sludge: effects on occurrence of pathogenic microorganisms in soil.

Jezierska-Tys S, Frac M, Tys J.

Department of Agricultural Microbiology, University of Life Sciences, Lublin, Poland.

The aims of this study were to (1) examine the extent of bacterial contamination of soils subjected to exposure to dairy sewage sludge applied to soils as measured by determination of number of bacteria from the Escherichia coli family and (2) determine the effects of dairy sewage sludge and straw on populations of other microbial species present in gray-brown podzolic soil. The gray-brown podzolic soil was formed from heavy loamy sand, which is characterized by the following granulometric composition: a sand fraction, 65%; a silt fraction, 19%; and a silt and clay fraction; 16%. The brown soil was formed from silt-loam and characterized by the following granulometric composition of silty-clay deposit: sand fraction, 8%; silt fraction, 48%; and clay and silt fraction, 46%. In dairy sewage sludge the total bacteria number as defined by Alef and Nannipieri (1995) was 51 x 10(4) colony-forming units (cfu)/ kg dry matter (dm), fungi total number 10 x 10(3) cfu/ kg dm, and E. coli bacteria 9.5 x 10(3) most probable number (MPN)/kg dm. In dairy sewage sludge mixed with straw, total number of bacteria and total number of fungi decreased to 10(3) and 10(2), respectively. Competition for nitrogen, glucose, and lactose and organic acids such as acetic and succinic with soil microorganisms, as well as soil conditions such as lack of oxygen, lower soil pH, and temperature, may account for the reduction in the number of E. coli bacteria in soils to which dairy sewage sludge was applied. Dairy sewage sludge may provide a beneficial impact on soil environment and adversely affect microorganisms such that dairy sewage sludge may be used as a safe organic fertilizer.

PMID: 20706944 [PubMed - indexed for MEDLINE]

556. Radiat Environ Biophys. 2010 Nov;49(4):625-34. Epub 2010 Aug 13.

Transfer of radionuclides to ants, mosses and lichens in semi-natural ecosystems.

Dragović S, Janković Mandić Lj.

Institute for the Application of Nuclear Energy, University of Belgrade, Belgrade, Serbia. sdragovic@inep.co.rs

There is a scarcity of data on transfer of both natural and anthropogenic radionuclides to detritivorous invertebrates for use in the assessment of radiation exposure. Although mosses and lichens have been extensively used in biomonitoring programs, the data on transfer of radionuclides to these species are limited, particularly for natural radionuclides. To enhance the available data, activity concentrations of (137)Cs, (226)Ra and (228)Ra were measured in ants, mosses and lichens and corresponding undisturbed soil collected from semi-natural ecosystems in Serbia and Montenegro and biota/soil concentration ratios (CR) calculated. Since the majority of internal dose to biota is expected to come from (40)K, the activity concentrations of this radionuclide were also determined. The mean CR values for (137)Cs, (226)Ra and (228)Ra in ants analyzed in this study were found to be 0.02, 0.06 and 0.02, respectively. The mean CR values of radionuclides in mosses were found to be 2.84 for (137)Cs, 0.19 for (226)Ra and 0.16 for (228)Ra, while those in lichens were found to be 1.08 for (137)Cs, 0.15 for (226)Ra and 0.13 for (228)Ra. The CR values obtained in this study were compared with default CR values used in the ERICA Tool database and also with those reported in other studies.

PMID: 20706729 [PubMed - indexed for MEDLINE]

557. Mutat Res. 2010 Oct 13;692(1-2):34-41. Epub 2010 Aug 7.

Photosensitization induced by the antibacterial fluoroquinolone Rufloxacin leads to mutagenesis in yeast.

Serrentino ME, Catalfo A, Angelin AR, de Guidi G, Sage E.

Institut Curie, Centre de Recherche, Centre Universitaire, F-91405 Orsay, France.

Rufloxacin (RFX) is an antibacterial fluoroquinolone that exhibits UVA photosensitization properties. Photosensitization reactions lead to the formation of oxidative damage, mainly via singlet oxygen. Here we explore the phototoxic and photomutagenic potency of RFX using a panel of yeast (Saccharomyces cerevisiae) mutants affected in different DNA repair pathways. Yeast mutants provide a sensitive tool to identify the photodamage and the DNA repair pathways that cope with it. Cell viability test at increasing dose of UVA shows that both the DNA repair deficient and wild type cells are equally sensitive to RFX-induced photosensitization, demonstrating that phototoxic effect is not due to DNA injury. Photomutagenicity of RFX is evaluated by measuring the frequency of forward Can(R) mutations. The mutation induction is low in wild type cells. A high increase in mutation frequency is observed in strains affected in Ogg1 gene, compared to wild type and other base excision repair deficient strains. The mutation spectrum photomediated by RFX in wild type cells reveals a bias in favour of GC>TA transversions, whereas transition and frameshift mutations are less represented. Altogether data demonstrates that 8-oxo-7,8-dihydroguanine (8-oxoGua) is by far the major DNA damage produced by RFX photosensitization, leading to mutagenesis. We also explore the role played by DNA mismatch repair, translesion synthesis and post-replication repair in the prevention of mutagenic effects due to RFX exposure. In addition, we show that most of RFX photodegradation products are not mutagenic. This study defines the phototoxic and photomutagenic properties of antibacterial RFX and point out possible unwanted side effects in skin under sunlight.

PMID: 20696178 [PubMed - indexed for MEDLINE]

558. OMICS. 2010 Dec;14(6):651-63. Epub 2010 Aug 9.

Functional genomics of drug-induced ion homeostasis identifies a novel regulatory crosstalk of iron and zinc regulons in yeast.

Landstetter N, Glaser W, Gregori C, Seipelt J, Kuchler K.

Medical University Vienna, Max F. Perutz Laboratories, Campus Vienna Biocenter, A-1030 Vienna, Austria.

Pyrrolidine dithiocarbamate (PDTC), a known inhibitor of NFκB activation, has antioxidative as well as antiviral activities. PDTC is effective against several virus families, indicating that its antiviral mechanism targets host rather than viral functions. To investigate its mode of action, we used baker's yeast as a simple eukaryotic model system and two types of genome-wide analysis. First, expression profiling using whole-genome DNA microarrays identifies more than 200 genes differentially regulated upon PDTC exposure. Interestingly, the Aft1-dependent iron regulon is a main target of PDTC, indicating a lack of iron availability. Moreover, the PDTC-caused zinc influx triggers a strong regulatory effect on zinc transporters due to the cytoplasmic zinc excess. Second, phenotypic screening the EUROSCARF collection for PDTC hypersensitivity identifies numerous mutants implicated in vacuolar maintenance, acidification as well as in transport, mitochondrial organization, and translation. Notably, the screening data indicate significant overlaps of PDTC-sensitive genes and those mediating zinc tolerance. Hence, we show that PDTC induces cytoplasmic zinc excess, eliciting vacuolar detoxification, which in turn, disturbs iron homeostasis and activates the iron-dependent regulator Aft1. Our work reveals a complex crosstalk in yeast ion homeostasis and the underlying regulatory networks.

PMID: 20695822 [PubMed - indexed for MEDLINE]

559. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2010 Nov;27(11):1566-73.

Lifetime, low-dose ochratoxin A dietary study on renal carcinogenesis in male Fischer rats.

Mantle P, Kulinskaya E.

Centre for Environmental Policy, Imperial College London, London SW7 2AZ, UK. p.mantle@imperial.ac.uk

Carcinoma arising from male rat renal parenchyma is an aspect of the nephrotoxicity of ochratoxin A (OTA) and is a factor in considering application of animal data to human health risk assessment. We present experimental data to complement already published and to complete dose-response findings for dietary OTA. From 34 rats, only four unilateral renal carcinomas (12%) developed during a 2-year exposure to dietary OTA, contaminated to give the same weekly overall dosage as in the 50 µg kg(-1) gavage-dosing regimen of an NTP study (30%). Statistical analysis included adjustment for premature leukaemia deaths, resulting in the carcinoma incidence of 35% (10-81%), and showed no significant difference from NTP (incidence of 43% (23-49%)) due to the smaller number of animals. However, absence of microscopic neoplastic renal lesions in premature decedents argues for minimal effect of the 47% leukaemia on carcinoma expression in the present experiment. This would fit with previously published findings showing significantly less carcinoma expression from a regimen administering an OTA dose in feed than was achieved by a lower dose by gavage as in the NTP study. It is concluded that chronic gavage administration of OTA to male rats may optimise carcinoma incidence for toxicological purposes, but that the dietary mode gives data more applicable to assessing putative health risk for humans.

PMID: 20694869 [PubMed - indexed for MEDLINE]

560. Food Chem Toxicol. 2010 Nov;48(11):3080-4. Epub 2010 Aug 6.

Safety assessment of Cordyceps guangdongensis.

Yan WJ, Li TH, Lin QY, Song B, Jiang ZD.

South China Agricultural University, Guangzhou, China.

Cordyceps guangdongensis as a kind of fungus, has been discovered and cultivated successfully in recent years. However, its safety assessments have not been studied. In this report, a serial of tests for toxicological safety assessments were depicted in details. These tests included bacterial reverse mutation (Ames) study, bone marrow cell micronucleus test in mice, sperm aberration test in mice, teratogenicaction test in rats, acute toxicity test and 13-week oral toxicity study in rats. After a profound analysis of these tests, it clearly demonstrated that C. guangdongensis did not have any mutagenic, clastogenic nor genotoxic effects; the oral LD50 of the biomass in rats was greater than 15 g/kg body weight; the no-observed adverse-effect-levels (NOAEL) was 5.33 g/kg body weight according to the 13-week oral toxicity analysis. Therefore, a conclusion can be drawn that C. guangdongensis is considered safe for long term consumption.

PMID: 20692314 [PubMed - indexed for MEDLINE]

561. MLO Med Lab Obs. 2010 Jul;42(7):10, 12-3; quiz 20-1.

Blood safety win, lose, or draw lose, or draw. Survey sheds new light on blood-splash exposures.

Ballance LO.

Center for Phlebotomy Education, Corydon, IN, USA.

PMID: 20690449 [PubMed - indexed for MEDLINE]

562. Microbiology. 2010 Nov;156(Pt 11):3432-44. Epub 2010 Aug 5.

Deletion of the Candida albicans histidine kinase gene CHK1 improves recognition by phagocytes through an increased exposure of cell wall beta-1,3-glucans.

Klippel N, Cui S, Groebe L, Bilitewski U.

Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124 Braunschweig, Germany.

The pathogenic fungus Candida albicans is able to cover its most potent proinflammatory cell wall molecules, the β-glucans, underneath a dense mannan layer, so that the pathogen becomes partly invisible for immune cells such as phagocytes. As the C. albicans histidine kinases Chk1p, Cos1p and CaSln1p had been reported to be involved in virulence and cell wall biosynthesis, we investigated whether deletion of the respective genes influences the activity of phagocytes against C. albicans. We found that among all histidine kinase genes, CHK1 plays a prominent role in phagocyte activation. Uptake of the deletion mutant Δchk1 as well as the acidification of Δchk1-carrying phagosomes was significantly increased compared with the parental strain. These improved activities could be correlated with an enhanced accessibility of the mutant β-1,3-glucans for immunolabelling. In addition, any inhibition of β-1,3-glucan-mediated phagocytosis resulted in a reduced uptake of Δchk1, while ingestion of the parental strain was hardly affected. Moreover, deletion of CHK1 caused an enhanced release of interleukins 6 and 10, indicating a stronger activation of the β-1,3-glucan receptor dectin-1. In conclusion, the Chk1p protein is likely to be involved in masking β-1,3-glucans from immune recognition. As there are no homologues of fungal histidine kinases in mammals, Chk1p has to be considered as a promising target for new antifungal agents.

PMID: 20688824 [PubMed - indexed for MEDLINE]

563. Microbiology. 2010 Oct;156(Pt 10):2887-900. Epub 2010 Aug 5.

Reproduction without sex: conidiation in the filamentous fungus Trichoderma.

Steyaert JM, Weld RJ, Mendoza-Mendoza A, Stewart A.

Bio-Protection Research Centre, PO Box 84, Lincoln University, Lincoln 7647, New Zealand. johanna.steyaert@lincoln.ac.nz

Trichoderma spp. have served as models for asexual reproduction in filamentous fungi for over 50 years. Physical stimuli, such as light exposure and mechanical injury to the mycelium, trigger conidiation; however, conidiogenesis itself is a holistic response determined by the cell's metabolic state, as influenced by the environment and endogenous biological rhythms. Key environmental parameters are the carbon and nitrogen status and the C : N ratio, the ambient pH and the level of calcium ions. Recent advances in our understanding of the molecular biology of this fungus have revealed a conserved mechanism of environmental perception through the White Collar orthologues BLR-1 and BLR-2. Also implicated in the molecular regulation are the PacC pathways and the conidial regulator VELVET. Signal transduction cascades which link environmental signals to physiological outputs have also been revealed.

PMID: 20688823 [PubMed - indexed for MEDLINE]

564. PLoS One. 2010 Jul 29;5(7):e11889.

Rad51 inhibits translocation formation by non-conservative homologous recombination in Saccharomyces cerevisiae.

Manthey GM, Bailis AM.

Department of Molecular and Cellular Biology, Beckman Research Institute, City of Hope National Medical Center, Duarte, California, United States of America.

Chromosomal translocations are a primary biological response to ionizing radiation (IR) exposure, and are likely to result from the inappropriate repair of the DNA double-strand breaks (DSBs) that are created. An abundance of repetitive sequences in eukaryotic genomes provides ample opportunity for such breaks to be repaired by homologous recombination (HR) between non-allelic repeats. Interestingly, in the budding yeast, Saccharomyces cerevisiae the central strand exchange protein, Rad51 that is required for DSB repair by gene conversion between unlinked repeats that conserves genomic structure also suppresses translocation formation by several HR mechanisms. In particular, Rad51 suppresses translocation formation by single-strand annealing (SSA), perhaps the most efficient mechanism for translocation formation by HR in both yeast and mammalian cells. Further, the enhanced translocation formation that emerges in the absence of Rad51 displays a distinct pattern of genetic control, suggesting that this occurs by a separate mechanism. Since hypomorphic mutations in RAD51 in mammalian cells also reduce DSB repair by conservative gene conversion and stimulate non-conservative repair by SSA, this mechanism may also operate in humans and, perhaps contribute to the genome instability that propels the development of cancer.

PMCID: PMC2912366 PMID: 20686691 [PubMed - indexed for MEDLINE]

565. J Invertebr Pathol. 2010 Oct;105(2):139-44. Epub 2010 May 26.

Effects of fluctuating moisture and temperature regimes on the persistence of quiescent conidia of Isaria fumosorosea.

Bouamama N, Vidal C, Fargues J.

INRA, UMR 1062, Centre de Biologie et de Gestion des Populations, F-34000 Montpellier, France.

Conidia of Isaria fumosorosea were submitted to three regimes of temperature and moisture to simulate microclimatic conditions which prevail in temperate (43% RH and 28 degrees C to 98% RH and 15 degrees C), subtropical (75% RH and 35 degrees C to 98% RH and 25 degrees C), and arid areas (13% RH and 40 degrees C to 33% RH and 15 degrees C) with daily fluctuating cycles. Germination, conidial viability, and virulence to Spodoptera frugiperda larvae were less affected after 20 days exposure under temperate cycling conditions than under arid and subtropical conditions. Exposure of conidia for 20 days to constant nocturnal simulated conditions of any tested regime weakly affected conidial persistence, whereas diurnal conditions exerted the most detrimental effects of high temperatures. However, when tested at both 45 degrees C and 50 degrees C at 33% RH for 160 h, the persistence of I. fumosorosea conidia was relatively higher than expected. These results emphasize that climatic conditions prevailing in environments and ecological fitness of fungal isolates have to be taken into account for assessing microbial control strategies.

PMID: 20685211 [PubMed - indexed for MEDLINE]

566. Ann Agric Environ Med. 2010 Jun;17(1):101-6.

Contents of microscopic fungi in dusts coming from cereal analysis laboratories.

Szwajkowska-Michalek L, Stuper K, Lakomy P, Matysiak A, Perkowski J.

Department of Chemistry, Poznan University of Life Science, Wojska Polskiego 75, Poznan, Poland.

Microscopic fungi - components of bioaerosol found in the workplace environment of individuals employed in the agricultural sector - constitute a considerable hazard for their health. This study includes quantitative and qualitative analyses of mycobionta contained in 20 samples of dusts collected from laboratories conducting analyses of cereals. A total of 27 species of viable microscopic fungi were isolated. The most frequently isolated genera Penicillium and Aspergillus, accounting for 27 percent and 26 percent of analyzed isolates. The content of fungal biomass was determined quantitatively using a fungal marker, ergosterol (ERG). Concentrations of this metabolite for all samples ranged from 0.48 mg/kg-212.36 mg/kg. Based on the analyses, it may be stated that the concentration of microfungi in settled dust from laboratories conducting analyses of cereals was varied, and in several cases markedly exceeded admissible concentration levels.

PMID: 20684486 [PubMed - indexed for MEDLINE]

567. Ann Agric Environ Med. 2010 Jun;17(1):9-13.

Organic dust induced pulmonary disease - the role of mould derived beta-glucan.

Rylander R.

BioFact Environmental Research Center, Bjorkasv 21, Lerum, Sweden. envhealth@biofact.se

The objective of the study was to evaluate the role of the mould cell wall agent beta-glucan in environmentally related pulmonary disease. All published articles where beta-glucan was administered by the airways, either as intratracheal injection or as inhalation were utilised as data sources. Data reporting consisted of analysis of data reports concerning the effects of beta-glucan on the immune system on the cellular level, particularly on the aggregation of inflammatory cells or production of inflammatory cytokines. High doses of soluble and particulate beta-glucan cause an inflammatory response characterized by cytokine activation and neutrophil invasion in the lung tissue. At lower doses, closer to environmental exposure levels, the predominant effect is an influence on the response to antigens, the reactivity of eosinophils and other Th2 driven immune responses. It is concluded that, beta-glucan can induce Th1 as well asTh2 driven immune responses. The pathology of atopy/allergy, hypersensitivity pneumonitis, and toxic penumonitis might be induced by exposure to beta-glucan. Measurements of beta-glucan in different environments are useful for risk control and prevention.

PMID: 20684476 [PubMed - indexed for MEDLINE]

568. Occup Med (Lond). 2010 Oct;60(7):540-5. Epub 2010 Aug 3.

Management of blood and body fluid exposures in police service staff.

Dunleavy K, Taylor A, Gow J, Cullen B, Roy K.

Institute for Applied Social and Health Research, University of the West of Scotland, Paisley PA1 2BE, UK. karen.dunleavy@uws.ac.uk

BACKGROUND: Police service staff are at risk of occupational exposure to blood and body fluids with the consequent risk of blood-borne virus (BBV) infection. AIMS: To examine the types of occupational exposure incidents experienced by Scottish police service staff and to evaluate the post-incident management provided by their occupational health (OH) services.
METHODS: Data were collected on the circumstances and the post-incident management of each incident reported to OH over 12 months. An expert panel reviewed the post-incident management provided by OH.
RESULTS: The panel considered that the majority of cases of occupational exposure incurred little or no risk of BBV transmission. In general, the expert panel assessed the post-incident management provided by OH units serving the police as adequate and appropriate. However, some concerns were raised in relation to a small number of incorrect risk assessments and an inconsistent approach to hepatitis C virus (HCV) follow-up blood testing.
CONCLUSIONS: The study findings suggest that most Scottish police OH departments were providing adequate post-incident management. There is, however, a need for more clarity around BBV risk assessment terminology and development of a standardized HCV testing protocol.

PMID: 20682741 [PubMed - indexed for MEDLINE]

569. Radiat Res. 2010 Aug;174(2):238-50.

Yields of clustered DNA damage induced by charged-particle radiations of similar kinetic energy per nucleon: LET dependence in different DNA microenvironments.

Keszenman DJ, Sutherland BM.

Biology Department, Brookhaven National Laboratory, Upton, New York 11973, USA. keszenman@bnl.gov

To determine the linear energy transfer (LET) dependence of the biological effects of densely ionizing radiation in relation to changes in the ionization density along the track, we measured the yields and spectrum of clustered DNA damages induced by charged particles of different atomic number but similar kinetic energy per nucleon in different DNA microenvironments. Yeast DNA embedded in agarose in solutions of different free radical scavenging capacity was irradiated with 1 GeV protons, 1 GeV/nucleon oxygen ions, 980 MeV/nucleon titanium ions or 968 MeV/nucleon iron ions. The frequencies of double-strand breaks (DSBs), abasic sites and oxypurine clusters were quantified. The total DNA damage yields per absorbed dose induced in non-radioquenching solution decreased with LET, with minor variations in radioquenching conditions being detected. However, the total damage yields per particle fluence increased with LET in both conditions, indicating a higher efficiency per particle to induce clustered DNA damages. The yields of DSBs and non-DSB clusters as well as the damage spectra varied with LET and DNA milieu, suggesting the involvement of more than one mechanism in the formation of the different types of clustered damages.

PMID: 20681790 [PubMed - indexed for MEDLINE]

570. Crit Care Med. 2010 Aug;38(8 Suppl):S306-14.

Lessons learned: protection of healthcare workers from infectious disease risks.

Weber DJ, Rutala WA, Schaffner W.

Department of Medicine, University of North Carolina at Chapel Hill, NC, USA.

OBJECTIVE: To summarize current concepts on preventing occupationally acquired infections in healthcare workers. DESIGN: Review of the pertinent medical literature. SETTINGS: Focus on healthcare workers practicing in acute care hospitals, especially intensive care units. SUBJECTS: Healthcare workers. MEASUREMENTS AND MAIN RESULTS: Key components of an effective infection control program include the following: 1) pre-exposure immunization with vaccines to prevent mumps, measles, rubella, varicella, pertussis, hepatitis B, and viral influenza; 2) adherence to standard precautions when providing patient care, especially the performance of hand hygiene before and after patient care; 3) rapid evaluation and initiation of appropriate isolation precautions for patients with potentially communicable diseases; 4) proper use of personal protective equipment such as masks, N95 respirators, eye protection, and gowns when caring for patients with potentially communicable diseases; and 5) evaluation of personnel with exposure to communicable diseases for receipt of postexposure prophylaxis.
CONCLUSIONS: Risks of acquisition of infectious diseases by healthcare workers can be minimized by adherence to current infection control guidelines.

PMID: 20647788 [PubMed - indexed for MEDLINE]

571. Parasitol Res. 2010 Oct;107(5):1271-4. Epub 2010 Aug 3.

Pathogenicity of some hypocrealean fungi to adult Aedes aegypti (Diptera: Culicidae).

Leles RN, Sousa NA, Rocha LF, Santos AH, Silva HH, Luz C.

Instituto de Patologia Tropical e Saúde Pública, UFG, Caixa Postal 131, 74001-970 Goiânia, GO, Brazil.

The pathogenicity of 19 hypocrealean entomopathogenic fungi from seven different genera in adult Aedes aegypti was tested. All fungi proved to be pathogenic, and Isaria fumosorosea, Lecanicillium muscarium, Lecanicillium psalliotae, Metarhizium anisopliae, Metarhizium lepidiotae, Metarhizium majus, Metarhizium frigidum, Paecilomyces carneus, and Paecilomyces lilacinus caused total mortality within 15 days of exposure of mosquitoes to the fungal culture. All fungi developed on dead individuals. The high susceptibility of adults to most tested strains underlines the interest of entomopathogenic fungi-especially those of the genera Metarhizium, Isaria, Paecilomyces and Lecanicillium--for biological control of A. aegypti.

PMID: 20680340 [PubMed - indexed for MEDLINE]

572. Med Pr. 2010;61(3):257-69.

[Exposure to bioaerosols among CAFO workers (swine feeding)].

[Article in Polish]

Szadkowska-Stańczyk I, Bródka K, Buczyńska A, Cyprowski M, Kozajda A, Sowiak M.

Zakład Srodowiskowych Zagrozeń Zdrowia, Instytut Medycyny Pracy im. prof. J. Nofera, Łódź. irenasta@imp.lodz.pl

BACKGROUND: In this paper the exposure assessment to airborne biohazards (organic dust, microorganisms, endotoxins and ((1 --> 3)-beta-D-glucans) as well as to ammonia and hydrogen sulfide among CAFO (swine farms) workers is presented. MATERIALS AND METHODS: Occupational exposure assessment was carried out on 30 swine farms. Personal dosimetry was carried out among 90 swine farm workers to assess the exposure to organic dust, endotoxins and glucans. Concentrations of ammonia and hydrogen sulfide were measured using Draeger pipes. Endotoxins were assayed with the LAL test in a kinetic, chromogenic version and ((1 --> 3)-beta-D-glucans with the Glucatell test in a kinetic version.
RESULTS: Concentrations of inhalable dust ranged from 0.16 to 37.2 mg/m3, with AM = 3.65 mg/m3, whereas AM for respirable fraction was 0.39 mg/m3 with the range from zero to 4.28 mg/m3. Mean concentration of culturable bacteria was 4.79 x 10 (5) jtk/m3, and fungi concentration was ten times lower - 1.55 x 10(4) jtk/m3. Exposure to endotoxins with high degree of differentiation ranged from 95 to 147 885 EU/m3 in inhalable and from 5.5 to 18 708 EU/m3 in respirable fractions. Glucan concentrations ranged from 6 to > 5200 ng/m3 in unhalable and from 1 to 800 ng/m3 in respirable fraction. Ammonia concentrations in the workplace air ranged from 1.78 mg/m3 (2.50 ppm) to 30.1 mg/m3 (42.4 ppm). Hydrogen sulfide did not exceed the level of 4.1 mg/m3.
CONCLUSION: Work conditions found in CAFOs may induce adverse effects on workers' respiratory system and should be considered as an important harmful agent. The protection of workers respiratory airways should be recommended.

PMID: 20677425 [PubMed - indexed for MEDLINE]

573. DNA Repair (Amst). 2010 Sep 4;9(9):976-84. Epub 2010 Jul 31.

Proficient repair in chromatin remodeling defective ino80 mutants of Saccharomyces cerevisiae highlights replication defects as the main contributor to DNA damage sensitivity.

Czaja W, Bespalov VA, Hinz JM, Smerdon MJ.

Biochemistry and Biophysics, School of Molecular Biosciences, Washington State University, Pullman, WA 99164-4660, United States.

Ino80 is an evolutionarily conserved member of the SWI2/SNF2-family of ATPases in Saccharomyces cerevisiae. It resides in a multiprotein helicase/chromatin remodeling complex, and has been shown to play a key role in the stability of replication forks during replication stress. Though yeast with defects in ino80 show sensitivity to killing by a variety of DNA-damaging agents, a role for the INO80 protein complex in the repair of DNA has only been assessed for double-strand breaks, and the results are contradictory and inconclusive. We report that ino80Delta cells are hypersensitive to DNA base lesions induced by ultraviolet (UV) radiation and methyl methanesulfonate (MMS), but show little (or no) increased sensitivity to the DNA double-strand break (DSB)-inducing agents ionizing radiation and camptothecin. Importantly, ino80Delta cells display efficient removal of UV-induced cyclobutane pyrimidine dimers, and show a normal rate of removal of DNA methylation damage after MMS exposure. In addition, ino80Delta cells have an overall normal rate of repair of DSBs induced by ionizing radiation. Altogether, our data support a model of INO80 as an important suppressor of genome instability in yeast involved in DNA damage tolerance through a role in stability and recovery of broken replication forks, but not in the repair of lesions leading to such events. This conclusion is in contrast to strong evidence for the DNA repair-promoting role of the corresponding INO80 complexes in higher eukaryotes. Thus, our results provide insight into the specialized roles of the INO80 subunits and the differential needs of different species for chromatin remodeling complexes in genome maintenance.

PMCID: PMC2929300 PMID: 20674516 [PubMed - indexed for MEDLINE]

574. Sci Total Environ. 2010 Sep 15;408(20):4826-32. Epub 2010 Aug 1.

The use of modelling to predict levels of estrogens in a river catchment: how does modelled data compare with chemical analysis and in vitro yeast assay results?

Balaam JL, Grover D, Johnson AC, Jürgens M, Readman J, Smith AJ, White S, Williams R, Zhou JL.

Centre for Environment, Fisheries and Aquaculture Science, Pakefield Road, Lowestoft, NR33 0HT, UK. jan.balaam@cefas.co.uk

Effluent discharges at Rodbourne sewage treatment works (STWs) were assessed using chemical and in vitro biological analysis as well as modelling predictions. Results showed that Rodbourne STW discharged less estrone (E1) than expected, but similar 17beta-estradiol (E2) and 17alpha-ethinyl estradiol (EE2) to those predicted by a widely cited effluent prediction model. The Exposure Analysis Modelling System (EXAMS) model was set up using measured effluent concentrations as its starting point to predict estrogen concentrations along a 10 km length of the receiving water of the River Ray. The model adequately simulated estrogen concentrations along the river when compared to July 2007 measured data. The model predicted combined estrogen equivalents in reasonable agreement with estrogenicity as measured by passive sampler (POCIS) extracts using the yeast estrogen screen. Using gauged mean flow values for 2007 the model indicated that the most important determinand for estrogen exposure in the Ray was not season, but proximity to the Rodbourne effluent. Thus, fish in the first 3 km downstream of Rodbourne were typically exposed to two or even three times more estrogens than those living 7-10 km further downstream. The modelling indicated that, assuming the effluent estrogen concentrations measured in February 2008 were typical, throughout the year the whole length of the Ray downstream of Rodbourne would be estrogenic, i.e. exceeding the 1 ng/L E2 equivalent threshold for endocrine disruption.

PMID: 20673965 [PubMed - indexed for MEDLINE]

575. Environ Microbiol. 2010 Aug;12(8):2133-41. doi: 10.1111/j.1462-2920.2009.02082.x. Epub 2009 Oct 14.

Zn pollution counteracts Cd toxicity in metal-tolerant ectomycorrhizal fungi and their host plant, Pinus sylvestris.

Krznaric E, Wevers JH, Cloquet C, Vangronsveld J, Vanhaecke F, Colpaert JV.

Hasselt University, Centre for Environmental Sciences, Environmental Biology Group, Agoralaan, Gebouw D, 3590 Diepenbeek, Belgium.

Adaptive Zn and Cd tolerance have evolved in populations of the ectomycorrhizal fungus Suillus luteus. When exposed to high concentrations of both metals in vitro, a one-sided antagonism was apparent in the Zn- and Cd-tolerant isolates. Addition of high Zn concentrations restored growth of Cd-stressed isolates, but not vice versa. The antagonistic effect was not detected in a S. luteus isolate from non-contaminated land and in Paxillus involutus. The fungi were inoculated on pine seedlings and subsequently exposed to ecologically relevant Zn and Cd concentrations in single and mixed treatments. The applied doses severely reduced nutrient acquisition of non-mycorrhizal pines and pines inoculated with metal-sensitive S. luteus. Highest translocation of Zn and Cd to shoots occurred in the same plants. Seedlings inoculated with fungi collected from the polluted site reduced metal transfer to their host and maintained nutrient acquisition under high metal exposure. The isolate showing highest tolerance in vitro also offered best protection in symbiosis. The antagonistic effect of high Zn on Cd toxicity was confirmed in the plant experiment. The results indicate that a Zn- and Cd-polluted soil has selected ectomycorrhizal fungi that are able to survive and protect their phytobiont from nutrient starvation and excessive metal uptake.

PMID: 21966908 [PubMed - indexed for MEDLINE]

576. Photochem Photobiol. 2010 Sep-Oct;86(5):1109-17. doi: 10.1111/j.1751-1097.2010.00774.x. Epub 2010 Jul 28.

Inactivation of food-borne spoilage and pathogenic micro-organisms on the surface of a photoactive polymer.

Zerdin K, Scully AD.

CSIRO Food and Nutritional Sciences, North Ryde, NSW, Australia.

The photodynamic action of a novel photoactive polymer comprising covalently bound anthraquinone (AQ) moieties was evaluated after developing a methodology to reliably immobilize viable micro-organisms onto polymer film surfaces. The survival of Escherichia coli, Bacillus cereus (vegetative cells and spores), Fusarium oxysporum and Saccharomyces cerevisiae microbes inoculated on the surface of inert polymeric substrates was assessed to determine the effect of inoculum composition, drying rate and exposure to ultraviolet (UV-A) radiation. Their survival was highly dependent on microbial genus, with E. coli consistently displaying markedly shorter survival times than the other microbes, and B. cereus spores being the most resistant. Inoculation of the microbes onto the surface of the photoactive polymer films, followed by exposure to UV-A radiation, dramatically accelerated the inactivation of all microbial types studied compared with their survival on the surface of inert polymer substrates. Simultaneous exposure to both oxygen and UV-A radiation is required to affect cell survival, which is consistent with this effect most likely originating from the photoinduced production of singlet oxygen by the photoactive polymer. These results provide further compelling evidence that singlet oxygen produced exogenously by this photoactive polymeric substrate can successfully inactivate a broad spectrum of microbes on the substrate's surface.

PMID: 20670362 [PubMed - indexed for MEDLINE]

577. Obstet Gynecol. 2010 Aug;116(2 Pt 1):387-92.

Chorioamnionitis and cerebral palsy: a meta-analysis.

Shatrov JG, Birch SC, Lam LT, Quinlivan JA, McIntyre S, Mendz GL.

School of Medicine, Sydney, The University of Notre Dame Australia and Cerebral Palsy Institute, Darlinghurst, New South Wales, Australia.

Comment in Obstet Gynecol. 2010 Dec;116(6):1454; author reply 1454.

OBJECTIVE: To examine the relationships between clinical or histological chorioamnionitis and cerebral palsy using a meta-analysis approach. DATA SOURCES: A systematic review of the literature appeared in PubMed between 2000 and 2009 was conducted using the search terms "cerebral palsy" and "infection," with broad-scope variations in terminology of "white matter damage," "periventricular leukomalacia," "cystic periventricular leukomalacia," "chorioamnionitis," "intrauterine infection," "intraventricular hemorrhage," "funisitis," "fetal inflammatory response," "early neonatal sepsis," "neurological impairment," "virus," "bacteria," "fungi," and "protozoa," with variations of suffixes (eg, "viral," "bacterial," "fungal," "protozoan," etc), and "urinary tract infection," "bacterial vaginosis," "bacteriuria," and "cytokines." The related key words "gestational age," "small for gestational age," "preterm," and "low birth weight" also were added to the search terms. Only studies published in English were included.
METHODS: Three hundred eight articles were retrieved and systematically reviewed independently by two authors. Application of four inclusion criteria led to 15 studies being considered for data abstraction. An exposure was considered relevant if it met the established criteria for clinical or histological chorioamnionitis. The outcome was a diagnosis of cerebral palsy in accordance with established criteria.
RESULTS: The data were abstracted onto standard forms, correlated according to eight characteristics, and tabulated. Twelve of the 15 studies contained information on the association between clinical chorioamnionitis and cerebral palsy, and eight studies included information on the association between histological chorioamnionitis and cerebral palsy. The results indicated that there were significant associations between clinical chorioamnionitis or histological chorioamnionitis and cerebral palsy, for clinical chorioamnionitis (chi1=13.91; P<.001) with a pooled odds ratio of 2.42 (95% confidence interval 1.52-3.84), and for histological chorioamnionitis (chi1=6.86; P=.009) with a pooled odds ratio of 1.83 (95% confidence interval, 1.17-2.89). The data suggested increased risks of 140% and 80% for neonates exposed to clinical chorioamnionitis or histological chorioamnionitis, respectively.
CONCLUSION: The significant association of clinical or histological chorioamnionitis with cerebral palsy suggested that clinical strategies to prevent or reduce chorioamnionitis would lead to a reduction in cerebral palsy. The culture techniques currently used to diagnose the presence of pathogenic microorganisms during pregnancy need to improve, both in their methodology and in the length of time they require.

PMID: 20664400 [PubMed - indexed for MEDLINE]

578. Vet Parasitol. 2010 Oct 29;173(3-4):262-70. Epub 2010 Jun 30.

The biological control of Ancylostoma spp. dog infective larvae by Duddingtonia flagrans in a soil microcosm.

Maciel AS, Freitas LG, Campos AK, Lopes EA, Araújo JV.

Laboratório de Parasitologia, Departamento de Veterinária, Universidade Federal de Viçosa, Minas Gerais, 36570-000, Brazil. ale_spalenza@yahoo.com.br

Experiments to evaluate the potential ability of the nematode-trapping fungus Duddingtonia flagrans (Isolate CG768) to prey on the Ancylostoma spp. dog infective larvae (L(3)) in pasteurized soil were performed through several laboratory assays. A microcosm approach was used with increasing fungal concentrations in an inoculum of a chlamydospore water suspension. The highest fungal concentrations provide a more consistent larval reduction than the lowest concentrations, but no difference was observed from 10,000 to 25,000 chlamydospores per grain of soil. When using D. flagrans in a water suspension, in white rice and in milled maize, there were reductions in the larval population of 72.0%, 78.4% and 79.4%, respectively, but there was no difference between white rice and milled maize (p<0.05). To evaluate the nematode control by D. flagrans inoculated in milled maize at 10,000 chlamydospores per grain of soil under greenhouse conditions, observations were performed at 10, 15, 20, 25 and 30 days after inoculation and the percent reduction in the larval population was 61.4%, 73.2%, 70.8%, 64.5% and 57%, respectively (p<0.05). There was an inverse relationship between the number of L(3) recovered from the soil and the total days of exposure to the fungus (p<0.05). These results showed that D. flagrans could present some potential to be used as a non-chemotherapeutic alternative for regulation of Ancylostoma spp. populations in the environment.

PMID: 20663612 [PubMed - indexed for MEDLINE]

579. Med Mycol. 2011 Apr;49 Suppl 1:S150-7. Epub 2010 Jul 22.

Severe asthma and fungi: current evidence.

Agarwal R, Gupta D.

Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India. riteshpgi@gmail.com

Bronchial asthma is an inflammatory disease of the airways which may be worsened due to numerous extrinsic factors. The most common trigger is continuous exposure to allergens of which fungal agents are important factors. There is overwhelming evidence for the presence of fungal sensitization in patients with asthma. The diagnosis of fungal sensitization can be made either with skin testing with antigens derived from fungi or measuring specific IgE levels. There is also a strong association between fungal sensitization and severity of asthma. Whether this relationship is causal or just casual remains to be investigated. A variety of fungi are known to cause sensitization in asthmatics, but the most important fungal agent(s) causing severe asthma with fungal sensitization (SAFS) are currently unknown. Aspergillus species seem to be the strongest candidates as only with Aspergillus spp. does one encounter two extreme immunologic phenomena, i.e., the Aspergillus-sensitive asthma and allergic bronchopulmonary aspergillosis. The initial clinical management of SAFS should be the same as asthmatics without fungal sensitization. There is some evidence of the role of itraconazole in the management of SAFS but its routine use in SAFS requires further evaluation. This review summarizes the current evidence on the link between fungi and severe asthma.

PMID: 20662637 [PubMed - in process]

580. Appl Microbiol Biotechnol. 2010 Sep;88(1):231-9. Epub 2010 Jul 27.

Transcriptional changes associated with ethanol tolerance in Saccharomyces cerevisiae.

Stanley D, Chambers PJ, Stanley GA, Borneman A, Fraser S.

School of Engineering and Science, Victoria University, PO Box 14428, Melbourne, Australia. Dana.Stanley@csiro.au

Saccharomyces spp. are widely used for ethanol production; however, fermentation productivity is negatively affected by the impact of ethanol accumulation on yeast metabolic rate and viability. This study used microarray and statistical two-way ANOVA analysis to compare and evaluate gene expression profiles of two previously generated ethanol-tolerant mutants, CM1 and SM1, with their parent, Saccharomyces cerevisiae W303-1A, in the presence and absence of ethanol stress. Although sharing the same parentage, the mutants were created differently: SM1 by adaptive evolution involving long-term exposure to ethanol stress and CM1 using chemical mutagenesis followed by adaptive evolution-based screening. Compared to the parent, differences in the expression levels of genes associated with a number of gene ontology categories in the mutants suggest that their improved ethanol stress response is a consequence of increased mitochondrial and NADH oxidation activities, stimulating glycolysis and other energy-yielding pathways. This leads to increased activity of energy-demanding processes associated with the production of proteins and plasma membrane components, which are necessary for acclimation to ethanol stress. It is suggested that a key function of the ethanol stress response is restoration of the NAD(+)/NADH redox balance, which increases glyceraldehyde-3-phosphate dehydrogenase activity, and higher glycolytic flux in the ethanol-stressed cell. Both mutants achieved this by a constitutive increase in carbon flux in the glycerol pathway as a means of increasing NADH oxidation.

PMID: 20661734 [PubMed - indexed for MEDLINE]

581. Eukaryot Cell. 2010 Sep;9(9):1403-15. Epub 2010 Jul 23.

The Aspergillus fumigatus cspA gene encoding a repeat-rich cell wall protein is important for normal conidial cell wall architecture and interaction with host cells.

Levdansky E, Kashi O, Sharon H, Shadkchan Y, Osherov N.

Department of Human Microbiology, Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Tel Aviv, Israel.

cspA (for cell surface protein A) encodes a repeat-rich glycophosphatidylinositol (GPI)-anchored cell wall protein (CWP) in the pathogenic fungus Aspergillus fumigatus. The number of repeats in cspA varies among isolates, and this trait is used for typing closely related strains of A. fumigatus. We have previously shown that deletion of cspA is associated with rapid conidial germination and reduced adhesion of dormant conidia. Here we show that cspA can be extracted with hydrofluoric acid (HF) from the cell wall, suggesting that it is a GPI-anchored CWP. The cspA-encoded CWP is unmasked during conidial germination and is surface expressed during hyphal growth. Deletion of cspA results in weakening of the conidial cell wall, whereas its overexpression increases conidial resistance to cell wall-degrading enzymes and inhibits conidial germination. Double mutant analysis indicates that cspA functionally interacts with the cell wall protein-encoding genes ECM33 and GEL2. Deletion of cspA together with ECM33 or GEL2 results in strongly reduced conidial adhesion, increased disorganization of the conidial cell wall, and exposure of the underlying layers of chitin and beta-glucan. This is correlated with increasing susceptibility of the DeltacspA, DeltaECM33, and DeltacspA DeltaECM33 mutants to conidial phagocytosis and killing by human macrophages and hyphal damage induced by neutrophils. However, these strains did not exhibit altered virulence in mice with infected lungs. Collectively, these results suggest a role for cspA in maintaining the strength and integrity of the cell wall.

PMCID: PMC2937338 PMID: 20656913 [PubMed - indexed for MEDLINE]

582. Sci Total Environ. 2010 Sep 15;408(20):4285-95. Epub 2010 Jul 23.

Can we use indoor fungi as bioindicators of indoor air quality? Historical perspectives and open questions.

Cabral JP.

Faculdade de Ciências & Centro Interdisciplinar de Investigação Marinha e Ambiental, Universidade do Porto, Rua do Campo Alegre, Edifício FC4, 4169-007 Porto, Portugal. jpcabral@fc.up.pt

Microbiological analysis of atmospheres witnessed substantial technical improvements in the 1940s to 1960s. May's cascade impactor and Hirst's spore trap allowed the counting of total cells but had limited capacity for identification of the spores. Bourdillon's sampler enabled the counting of cultivable fungi and their identification. A great step forward was given with the Andersen's six-stage impactor, which allowed discrimination of particles by size, counting of cultivable cells, and species identification. This period also witnessed the development of impingers, namely, the AGI-30 described by Malligo and Idoine, and the three-stage model designed by K. R. May. The 1990s to 2000s witnessed innovative discoveries on the biology of indoor fungi. Work carried out in several laboratories showed that indoor fungi can release groups of spores, individual spores and fungal fragments, and produce volatile organic compounds and mycotoxins. Integrating all findings a holistic interpretation emerged for the sick building syndrome. Healthy houses and buildings, with low indoor humidity, display no appreciable indoor fungal growth, and outdoor Cladosporium dominates. On the contrary, in sick houses and buildings, high indoor humidity allows fungal growth (mainly of Penicillium and Aspergillus), with concomitant release of conidia and fragments into the atmosphere. The intoxication probably results from a chronic exposure to volatile organic compounds and mycotoxins produced by Penicillium, Aspergillus, and Stachybotrys. Very clean atmospheres are difficult to study by conventional methods. However, some of these atmospheres, namely, those of hospital rooms, should be monitored. Sedimentary sampling, chemical methods applied to impinger's collection liquid, and selected molecular methods can be useful in this context. It was concluded that fungi can be useful indicators of indoor air quality and that it is important to deepen the studies of indoor atmospheres in order to promote air quality, the health and well-being of all, and a better understanding of the biology of indoor fungi.

PMID: 20655574 [PubMed - indexed for MEDLINE]

583. Genome Biol. 2010;11(7):R77. Epub 2010 Jul 23.

Evolutionary divergence in the fungal response to fluconazole revealed by soft clustering.

Kuo D, Tan K, Zinman G, Ravasi T, Bar-Joseph Z, Ideker T.

Department of Bioengineering, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.

BACKGROUND: Fungal infections are an emerging health risk, especially those involving yeast that are resistant to antifungal agents. To understand the range of mechanisms by which yeasts can respond to anti-fungals, we compared gene expression patterns across three evolutionarily distant species - Saccharomyces cerevisiae, Candida glabrata and Kluyveromyces lactis - over time following fluconazole exposure.
RESULTS: Conserved and diverged expression patterns were identified using a novel soft clustering algorithm that concurrently clusters data from all species while incorporating sequence orthology. The analysis suggests complementary strategies for coping with ergosterol depletion by azoles - Saccharomyces imports exogenous ergosterol, Candida exports fluconazole, while Kluyveromyces does neither, leading to extreme sensitivity. In support of this hypothesis we find that only Saccharomyces becomes more azole resistant in ergosterol-supplemented media; that this depends on sterol importers Aus1 and Pdr11; and that transgenic expression of sterol importers in Kluyveromyces alleviates its drug sensitivity.
CONCLUSIONS: We have compared the dynamic transcriptional responses of three diverse yeast species to fluconazole treatment using a novel clustering algorithm. This approach revealed significant divergence among regulatory programs associated with fluconazole sensitivity. In future, such approaches might be used to survey a wider range of species, drug concentrations and stimuli to reveal conserved and divergent molecular response pathways.

PMCID: PMC2926788 PMID: 20653936 [PubMed - indexed for MEDLINE]

584. Mol Plant Microbe Interact. 2010 Dec;23(12):1635-42.

Stem rust spores elicit rapid RPG1 phosphorylation.

Nirmala J, Drader T, Chen X, Steffenson B, Kleinhofs A.

Department of Crop and Soil Sciences, Washington State University, Pullman 99164, USA.

Stem rust threatens cereal production worldwide. Understanding the mechanism by which durable resistance genes, such as Rpg1, function is critical. We show that the RPG1 protein is phosphorylated within 5 min by exposure to spores from avirulent but not virulent races of stem rust. Transgenic mutants encoding an RPG1 protein with an in vitro inactive kinase domain fail to phosphorylate RPG1 in vivo and are susceptible to stem rust, demonstrating that phosphorylation is a prerequisite for disease resistance. Protein kinase inhibitors prevent RPG1 phosphorylation and result in susceptibility to stem rust, providing further evidence for the importance of phosphorylation in disease resistance. We conclude that phosphorylation of the RPG1 protein by the kinase activity of the pK2 domain induced by the interaction with an unknown pathogen spore product is required for resistance to the avirulent stem rust races. The pseudokinase pK1 domain is required for disease resistance but not phosphorylation. The very rapid phosphorylation of RPG1 suggests that an effector is already present in or on the stem rust urediniospores when they are placed on the leaf surface. However, spores must be alive, as determined by their ability to germinate, in order to elicit RPG1 phosphorylation.

PMID: 20653415 [PubMed - indexed for MEDLINE]

585. Glycoconj J. 2010 Jul;27(5):533-48. Epub 2010 Jul 23.

Cloning and characterization of a sialidase from the filamentous fungus, Aspergillus fumigatus.

Warwas ML, Yeung JH, Indurugalla D, Mooers AO, Bennet AJ, Moore MM.

Department of Biological Sciences, Simon Fraser University, 8888 University Drive, Burnaby, British Columbia, V5A 1S6, Canada.

A gene encoding a putative sialidase was identified in the genome of the opportunistic fungal pathogen, Aspergillus fumigatus. Computational analysis showed that this protein has Asp box and FRIP domains, it was predicted to have an extracellular localization, and a mass of 42 kDa, all of which are characteristics of sialidases. Structural modeling predicted a canonical 6-bladed beta-propeller structure with the model's highly conserved catalytic residues aligning well with those of an experimentally determined sialidase structure. The gene encoding the putative Af sialidase was cloned and expressed in Escherichia coli. Enzymatic characterization found that the enzyme was able to cleave the synthetic sialic acid substrate, 4-methylumbelliferyl alpha-D-N-acetylneuraminic acid (MUN), and had a pH optimum of 3.5. Further kinetic characterization using 4-methylumbelliferyl alpha-D-N-acetylneuraminylgalactopyranoside revealed that Af sialidase preferred alpha2-3-linked sialic acids over the alpha2-6 isomers. No trans-sialidase activity was detected. qPCR studies showed that exposure to MEM plus human serum induced expression. Purified Af sialidase released sialic acid from diverse substrates such as mucin, fetuin, epithelial cell glycans and colominic acid, though A. fumigatus was unable to use either sialic acid or colominic acid as a sole source of carbon. Phylogenetic analysis revealed that the fungal sialidases were more closely related to those of bacteria than to sialidases from other eukaryotes.

PMID: 20652740 [PubMed - indexed for MEDLINE]

586. Phytopathology. 2010 Nov;100(11):1240-9.

Effects of acute low-temperature events on development of Erysiphe necator and susceptibility of Vitis vinifera.

Moyer MM, Gadoury DM, Cadle-Davidson L, Dry IB, Magarey PA, Wilcox WF, Seem RC.

Department of Plant Pathology and Plant-Microbe Biology, Cornell University, Geneva, NY, USA. mmm78@cornell.edu

Growth and development of Erysiphe necator (syn. Uncinula necator) has been extensively studied under controlled conditions, primarily with a focus on development of grapevine powdery mildew within the optimal temperature range and the lethal effects of high temperatures. However, little is known of the effect of cold temperatures (above freezing but <8 degrees C) on pathogen development or host resistance. Pretreatment of susceptible Vitis vinifera leaf tissue by exposure to cold temperatures (2 to 8 degrees C for 2 to 8 h) reduced infection efficiency and colony expansion when tissues were subsequently inoculated. Furthermore, nascent colonies exposed to similar cold events exhibited hyphal mortality, reduced expansion, and increased latent periods. Historical weather data and an analysis of the radiational cooling of leaf tissues in the field indicated that early-season cold events capable of inducing the foregoing responses occur commonly and frequently across many if not most viticultural regions worldwide. These phenomena may partially explain (i) the unexpectedly slow development of powdery mildew during the first month after budbreak in some regions and (ii) the sudden increase in epidemic development once seasonal temperatures increase above the threshold for acute cold events.

PMID: 20649419 [PubMed - indexed for MEDLINE]

587. Am J Epidemiol. 2010 Aug 15;172(4):451-9. Epub 2010 Jul 16.

Home dampness and molds as determinants of allergic rhinitis in childhood: a 6-year, population-based cohort study.

Jaakkola JJ, Hwang BF, Jaakkola MS.

Jaakkola, Institute of Health Sciences, Aapistie 1, P.O. Box 5000, 90014 Oulu, Finland. jouni.jaakkola@oulu.fi

The authors assessed the relation between exposure to dampness and molds in dwellings and the development of allergic rhinitis in childhood in a 6-year, population-based prospective cohort study of 1,863 children aged 1-7 years at baseline in 1991 (follow-up rate, 77%) from Espoo, Finland. The studied exposures were history of water damage, presence of moisture and visible mold, and perceived mold odor in the home, based on parent-administered questionnaire. A total of 246 (13.2%) children developed physician-diagnosed allergic rhinitis during the study period, resulting in an incidence rate of 440 cases per 10,000 person-years (95% confidence interval (CI): 387, 499). In logistic regression adjusting for confounding, any mold or dampness exposure indicator at baseline (adjusted odds ratio = 1.55, 95% CI: 1.10, 2.18), at follow-up (adjusted odds ratio = 1.62, 95% CI: 1.21, 2.18), or both (adjusted odds ratio = 1.96, 95% CI: 1.29, 2.98) was an important independent determinant of the risk of allergic rhinitis. Of the individual indicators, water damage and moisture on the surfaces were consistent determinants of allergic rhinitis. The results of this cohort study, which assessed exposure before the onset of allergic rhinitis, strengthen considerably the evidence of the role of indoor dampness problems as determinants of allergic rhinitis in children.

PMID: 20639287 [PubMed - indexed for MEDLINE]

588. J Travel Med. 2010 Jul-Aug;17(4):264-8.

Human immunodeficiency virus postexposure prophylaxis for medical trainees on international rotations.

Mohan S, Sarfaty S, Hamer DH.

Department of Otolaryngology, Head and Neck Surgery, St Louis University Hospital, St Louis, MO, USA.

PMID: 20636600 [PubMed - indexed for MEDLINE]

589. Leuk Lymphoma. 2010 Sep;51(9):1623-31.

Approaches to the early treatment of invasive fungal infection.

Ito JI, Kriengkauykiat J, Dadwal SS, Arfons LM, Lazarus HM.

Division of Infectious Diseases, City of Hope, Duarte, CA 91706, USA. jito@coh.org

Invasive fungal infections account for significant morbidity and mortality in the seriously immunocompromised host, especially those suffering from hematologic malignancies and the recipients of hematopoietic cell transplant. One of the reasons for the continuing high mortality rates due to invasive fungal infection is the delay in administering appropriate therapy. As preemptive antifungal therapy is not feasible for lack of a predictive test, early empiric therapy is currently the only approach likely to result in improvement in survival. Here, we present our approach to both invasive candidiasis and invasive mold infection. Therapy should be initiated at the first signs and symptoms of disease, utilizing knowledge of local fungal epidemiology, the patient's recent antifungal agent exposure, and the diagnostic tests immediately available, to select an appropriate antifungal agent most likely to be effective against the suspected fungal species.

PMID: 20629521 [PubMed - indexed for MEDLINE]

590. J Biosci Bioeng. 2010 Nov;110(5):511-22. Epub 2010 Jul 10.

Toxicogenomics using yeast DNA microarrays.

Yasokawa D, Iwahashi H.

Hokkaido Food Processing Research Center, Department of Food Development, 589-4 Bunkyodai Midorimachi, Ebetsu, Hokkaido 0690836, Japan. yasokawa-daisuke@hro.or.jp

Development of genomics and bioinformatics enable us to analyze the global gene expression profiles of cells by DNA microarray. Changes in gene expression patterns indicate changes in its physiological conditions. Following the exposure of an organism or cell to toxic chemicals or other environmental stresses, the global genetic responses can be expeditiously and easily analyzed. Baker's yeast, Saccharomyces cerevisiae, is one of the most studied and useful model eukaryotes. The biggest advantage of yeast genomics is the available functional information for each gene and a considerable number of data are accumulating in the field of toxicity assessment using yeast DNA microarray. In this review, we discuss the toxicogenomics of metal ions, alcohols and aldehydes, and other chemicals.

PMID: 20624688 [PubMed - indexed for MEDLINE]

591. Appl Environ Microbiol. 2010 Sep;76(17):5874-81. Epub 2010 Jul 9.

Exposure to bioaerosols during the growth season of tomatoes in an organic greenhouse using Supresivit (Trichoderma harzianum) and Mycostop (Streptomyces griseoviridis).

Hansen VM, Winding A, Madsen AM.

The National Research Centre for the Working Environment, Lersø Parkalle 105, DK-2100 Copenhagen Ø, Denmark.

In working environments, especially in confined spaces like greenhouses, elevated concentrations of airborne microorganisms may become a problem for workers' health. Additionally, the use of microbial pest control agents (MPCAs) may increase exposure to microorganisms. The aim of this study was to investigate tomato growers' exposure to naturally occurring bioaerosol components [dust, bacteria, fungi, actinomycetes, (1-->3)-beta-D-glucans, and endotoxin] and MPCAs applied by drip irrigation. Airborne dust was collected with filter samplers and analyzed for microorganisms by plate counts and total counts using a microscope. Analysis of (1-->3)-beta-D-glucan and endotoxin content was performed by kinetic, chromatic Limulus amoebocyte lysate tests. The fungal strain (Trichoderma harzianum) from the biocontrol product Supresivit was identified by PCR analysis. Measurements were performed on the day of drip irrigation and 1 week, 1 month, and 3 months after the irrigation. T. harzianum from Supresivit could be detected only on the day of treatment. Streptomyces griseoviridis, an applied MPCA, was not detected in the air during this investigation. We found that bioaerosol exposure increases during the growth season and that exposure to fungi, bacteria, and endotoxin can reach levels during the harvest period that may cause respiratory symptoms in growers. The collected data indicate that MPCAs applied by drip irrigation do not become airborne later in the season.

PMCID: PMC2935076 PMID: 20622135 [PubMed - indexed for MEDLINE]

592. Appl Environ Microbiol. 2010 Sep;76(17):5736-44. Epub 2010 Jul 9.

Exploring the role of microorganisms in the disease-like syndrome affecting the sponge Ianthella basta.

Luter HM, Whalan S, Webster NS.

School of Marine and Tropical Biology, James Cook University, Townsville, Queensland 4811, Australia.

A disease-like syndrome is currently affecting a large percentage of the Ianthella basta populations from the Great Barrier Reef and central Torres Strait. Symptoms of the syndrome include discolored, necrotic spots leading to tissue degradation, exposure of the skeletal fibers, and disruption of the choanocyte chambers. To ascertain the role of microbes in the disease process, a comprehensive comparison of bacteria, viruses, fungi, and other eukaryotes was performed in healthy and diseased sponges using multiple techniques. A low diversity of microbes was observed in both healthy and diseased sponge communities, with all sponges dominated by an Alphaproteobacteria, a Gammaproteobacteria, and a group I crenarchaeota. Bacterial cultivation, community analysis by denaturing gradient gel electrophoresis (Bacteria and Eukarya), sequencing of 16S rRNA clone libraries (Bacteria and Archaea), and direct visual assessment by electron microscopy failed to reveal any putative pathogens. In addition, infection assays could not establish the syndrome in healthy sponges even after direct physical contact with affected tissue. These results suggest that microbes are not responsible for the formation of brown spot lesions and necrosis in I. basta.

PMCID: PMC2935071 PMID: 20622129 [PubMed - indexed for MEDLINE]

593. Br J Oral Maxillofac Surg. 2011 Jul;49(5):400-3. Epub 2010 Jul 10.

Blood-borne viruses: are we taking them seriously? A survey of UK oral and maxillofacial surgeons.

Lazenby MG, Anderud J, Whitley SP.

Restorative Dentistry Department, Barts and The London Dental Hospital, New Road, London, E1 1BB, United Kingdom. martin.lazenby@bartsandthelondon.nhs.uk

The nature of the work done by oral and maxillofacial surgeons (OMFSs) potentially places them at risk of transmission of blood-borne viruses from patients. We investigated the incidence of exposure to infected blood among OMF surgeons, and whether enough protection is being used. An anonymous postal questionnaire was sent to all OMFS consultants working in the UK in 2008 (n=344) to investigate three areas relating to blood-borne viruses: incidence of surgeons experiencing and reporting exposure to potentially infected blood, their opinions about which patients pose a particular risk, and treatment plans and equipment selected when given two set clinical situations. A total of 148 consultants (43%) responded. Of the 80 respondents (61%) who had been exposed to blood within the last five years, more than two-thirds (n=55) did not always report such incidents. Eighty-five (60%) stated that they considered that all patients posed a risk to the surgeon, and 104 (73%) altered their practice depending on the perceived risk from the individual patient.

PMID: 20621400 [PubMed - indexed for MEDLINE]

594. Toxicology. 2010 Sep 30;276(1):49-57. Epub 2010 Jul 16.

The Fusarium mycotoxins enniatins and beauvericin cause mitochondrial dysfunction by affecting the mitochondrial volume regulation, oxidative phosphorylation and ion homeostasis.

Tonshin AA, Teplova VV, Andersson MA, Salkinoja-Salonen MS.

Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow RU-119899, Russia.

The mechanisms of cell toxicity of mycotoxins of the enniatin family produced by Fusarium sp. enniatin B, a mixture of enniatin homologues (3% A, 20% A(1), 19% B, 54% B1) and beauvericin, were investigated. In isolated rat liver mitochondria, exposure to submicromolar concentrations of the enniatin mycotoxins depleted the mitochondrial transmembrane potential, uncoupled oxidative phosphorylation, induced mitochondrial swelling and decreased calcium retention capacity of the mitochondria. The mitochondrial effects were strongly connected with the potassium (K(+)) ionophoric activity of the enniatins. The observed enniatins induced K(+) uptake by mitochondria. This shows that the enniatins acted as ionophores highly selective for potassium ions. The effects were observed in potassium containing media whereas less or no effect remained to be observed when K(+) was partially or totally replaced by isomolar concentrations of Na(+). The rank order of enniatin induced mitochondrial impairment was beauvericin>enniatin mixture>enniatin B. Exposure to the enniatins depleted the mitochondrial membrane potential also in intact human neural (Paju), murine insulinoma (Min-6) cells as well as boar spermatozoa. Exposure to enniatin B in media with physiological (4mM) or low (<1mM) but not in high (60mM) external concentration of K(+) induced hyperpolarization of the spermatozoal plasma membrane indicating enniatin that catalysed efflux of the cytosolic K(+) ions. These results indicate that the cellular toxicity targets of the enniatin mycotoxins are the mitochondrion and the homeostasis of potassium ions.

PMID: 20621153 [PubMed - indexed for MEDLINE]

595. FEMS Microbiol Lett. 2010 Sep 1;310(1):32-8. Epub 2010 Jun 16.

Isolation and partial characterization of antibiotics produced by Paenibacillus elgii B69.

Wu XC, Shen XB, Ding R, Qian CD, Fang HH, Li O.

Institute of Microbiology, College of Life Sciences, Zhejiang University, Hangzhou, China. mblab@163.com

A newly isolated strain B69 with broad antimicrobial activity was identified as Paenibacillus elgii by 16S rRNA gene sequence analysis, along with physiological and biochemical characterization. Two antimicrobial compounds, named as Pelgipeptins A and B, were isolated from the culture medium using MCI GEL CHP20P column chromatography and HPLC methods. The molecular masses of Pelgipeptins A and B were 1072 and 1100 Da, respectively. The ESI-CID-MS and amino acid analysis suggested that both of them belonged to the polypeptin family, and Pelgipeptin A was unequivocally characterized as a new antibiotic. These two antibiotics were active against all the tested bacterial strains and displayed strong antifungal activity against several soil-borne fungal pathogens, with minimal inhibitory concentration values of 6.25-50 mug mL(-1). Furthermore, stability analysis indicated that the inhibitory activity of Pelgipeptins in the cell-free supernatant was unaffected during exposure to 60 degrees C for 2 h or a pH ranging from 1.0 to 8.0. Based on the strong antifungal activity and attractive biochemical properties, Pelgipeptins might provide an alternative resource of chemical pesticides for the biocontrol of plant diseases.

PMID: 20618851 [PubMed - indexed for MEDLINE]

596. Mycopathologia. 2011 Jan;171(1):11-21. Epub 2010 Jul 9.

Molecular mechanisms of resistance to 5-fluorocytosine in laboratory mutants of Candida glabrata.

Vandeputte P, Pineau L, Larcher G, Noel T, Brèthes D, Chabasse D, Bouchara JP.

Groupe d'Etude des Interactions Hôte-Pathogène, UPRES-EA 3142, Université d'Angers, Bâtiment Montéclair, Centre Hospitalier Universitaire, 4 rue Larrey, 49933, Angers Cedex 9, France. patrick.vandeputte@etud.univ-angers.fr

Resistance to 5-fluorocytosine (5-FC) has been poorly investigated in the yeast Candida glabrata. This study was conducted on laboratory mutants obtained by exposure of a wild-type isolate to 5-FC. Based on their susceptibility to 5-fluorouracil (5-FU), two of these mutants were selected for further analysis of the molecular mechanisms of 5-FC resistance. One mutant, resistant to both compounds, exhibited a missense mutation in the gene coding the cytosine deaminase and a decrease in the expression level of the gene coding the uridine monophosphate pyrophosphorylase. The other mutant that showed a reduced susceptibility to 5-FC and 5-FU exhibited an overexpression of the genes coding the thymidylate synthase and a cytosine permease, associated with a missense mutation in the last gene. Thus, beside mutations in the FUR1 gene which represent the most common cause of resistance to 5-FC, other mechanisms may also occur in C. glabrata.

PMID: 20617462 [PubMed - indexed for MEDLINE]

597. Appl Microbiol Biotechnol. 2010 Sep;88(1):219-29. Epub 2010 Jul 9.

Allicin-induced global gene expression profile of Saccharomyces cerevisiae.

Yu L, Guo N, Meng R, Liu B, Tang X, Jin J, Cui Y, Deng X.

Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Animal Science and Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun, 130062, People's Republic of China.

To understand the response mechanisms of fungus cells upon exposure to the natural fungicide allicin, we performed commercial oligonucleotide microarrays to determine the overall transcriptional response of allicin-treated Saccharomyces cerevisiae strain L1190. Compared with the transcriptional profiles of untreated cultures, 147 genes were significantly upregulated, and 145 genes were significantly downregulated in the allicin-treated cells. We interpreted the microarray data with the hierarchical clustering tool, T-profiler. Major transcriptional responses were induced by allicin and included the following: first, Rpn4p-mediated responses involved in proteasome gene expression; second, the Rsc1p-mediated response involved in iron ion transporter activity; third, the Gcn4p-mediated response, also known as general amino acid control; finally, the Yap1p-, Msn2/4p-, Crz1p-, and Cin5p-mediated multiple stress response. Interestingly, allicin treatment, similar to mycotoxin patulin and artificial fungicide thiuram treatment, was found to induce genes involved in sulfur amino acid metabolism and the defense system for oxidative stress, especially DNA repair, which suggests a potential mutagenicity for allicin. Quantitative real-time reverse transcription-polymerase chain reaction was performed for selected genes to verify the microarray results. To our knowledge, this is the first report of the global transcriptional profiling of allicin-treated S. cerevisiae by microarray.

PMID: 20617313 [PubMed - indexed for MEDLINE]

598. PLoS One. 2010 Jun 30;5(6):e11389.

Asc1 supports cell-wall integrity near bud sites by a Pkc1 independent mechanism.

Melamed D, Bar-Ziv L, Truzman Y, Arava Y.

Department of Biology, Technion-Israel Institute of Technology, Haifa, Israel.

BACKGROUND: The yeast ribosomal protein Asc1 is a WD-protein family member. Its mammalian ortholog, RACK1 was initially discovered as a receptor for activated protein C kinase (PKC) that functions to maintain the active conformation of PKC and to support its movement to target sites. In the budding yeast though, a connection between Asc1p and the PKC signaling pathway has never been reported. METHODOLOGY/PRINCIPAL FINDINGS: In the present study we found that asc1-deletion mutant (asc1Delta) presents some of the hallmarks of PKC signaling mutants. These include an increased sensitivity to staurosporine, a specific Pkc1p inhibitor, and susceptibility to cell-wall perturbing treatments such as hypotonic- and heat shock conditions and zymolase treatment. Microscopic analysis of asc1Delta cells revealed cell-wall invaginations near bud sites after exposure to hypotonic conditions, and the dynamic of cells' survival after this stress further supports the involvement of Asc1p in maintaining the cell-wall integrity during the mid-to late stages of bud formation. Genetic interactions between asc1 and pkc1 reveal synergistic sensitivities of a double-knock out mutant (asc1Delta/pkc1Delta) to cell-wall stress conditions, and high basal level of PKC signaling in asc1Delta. Furthermore, Asc1p has no effect on the cellular distribution or redistribution of Pkc1p at optimal or at cell-wall stress conditions. CONCLUSIONS/SIGNIFICANCE: Taken together, our data support the idea that unlike its mammalian orthologs, Asc1p acts remotely from Pkc1p, to regulate the integrity of the cell-wall. We speculate that its role is exerted through translation regulation of bud-site related mRNAs during cells' growth.

PMCID: PMC2894943 PMID: 20613984 [PubMed - indexed for MEDLINE]

599. FEMS Yeast Res. 2010 Sep;10(6):747-56. Epub 2010 Jun 7.

Adaptive tolerance to oxidative stress and the induction of antioxidant enzymatic activities in Candida albicans are independent of the Hog1 and Cap1-mediated pathways.

Gónzalez-Párraga P, Alonso-Monge R, Plá J, Argüelles JC.

Area de Microbiología, Universidad de Murcia,Murcia, Spain.

In the pathogenic yeast Candida albicans, the MAP-kinase Hog1 mediates an essential protective role against oxidative stress, a feature shared with the transcription factor Cap1. We analysed the adaptive oxidative response of strains with both elements altered. Pretreatment with gentle doses of oxidants or thermal upshifts (28-->37 and 37-->42 degrees C) improved survival in the face of high concentrations of oxidants (50 mM H(2)O(2) or 40 mM menadione), pointing to a functional cross-protective mechanism in the mutants. The oxidative challenge promoted a marked intracellular synthesis of trehalose, although hog1 (but not cap1) cells always displayed high basal trehalose levels. Hydrogen peroxide (H(2)O(2)) induced mRNA expression of the trehalose biosynthetic genes (TPS1 and TPS2) in the tested strains. Furthermore, oxidative stress also triggered a differential activation of various antioxidant activities, whose intensity was greater after HOG1 and CAP1 deletion. The pattern of activity was dependent on the oxidant dosage applied: low concentrations of H(2)O(2) (0.5-5 mM) clearly induced catalase and glutathione reductase (GR), whereas drastic H(2)O(2) exposure (50 mM) increased Mn-superoxide dismutase (SOD) isozyme-mediated SOD activity. These results firmly support the existence in C. albicans of both Hog1- and Cap1-independent mechanisms against oxidative stress.

PMID: 20608985 [PubMed - indexed for MEDLINE]

600. Allergy. 2011 Jan;66(1):110-9. doi: 10.1111/j.1398-9995.2010.02437.x.

Mast cells generated from patients with atopic eczema have enhanced levels of granule mediators and an impaired Dectin-1 expression.

Ribbing C, Engblom C, Lappalainen J, Lindstedt K, Kovanen PT, Karlsson MA, Lundeberg L, Johansson C, Nilsson G, Lunderius-Andersson C, Scheynius A.

Department of Medicine Solna Clinical Allergy Research Unit, Karolinska Institutet and University Hospital Solna, Stockholm, Sweden.

BACKGROUND: The disrupted skin barrier of patients with atopic eczema (AE) might facilitate contact between mast cells (MCs) in the skin and environmental triggers of the disease. One such trigger is the skin-colonizing yeast Malassezia sympodialis (M. sympodialis). In this study, we investigated the interaction of MC with M. sympodialis.
METHODS: Mast cells were generated from peripheral blood CD34(+) progenitor cells of healthy controls (HC) and M. sympodialis-sensitized AE patients. Biopsy specimens were taken from HC and lesional AE skin for immunohistological stainings.
RESULTS: The progenitor-derived MCs expressed the macrophage-inducible C-type lectin receptor Mincle, and exposure of these cells to M. sympodialis induced up-regulation of the mRNA expression of Mincle. Furthermore, we demonstrate that, when compared to HC, the progenitor-derived MCs from AE patients (i) contain more intrinsic granule mediators such as histamine, (ii) exhibit enhanced IL-6 release in response to M. sympodialis exposure, and (iii) have an impaired up-regulation of the fungal recognition receptor Dectin-1. In addition, analysis of skin sections from HC and AE patients revealed MCs as the predominant Dectin-1-expressing cell type in the skin.
CONCLUSION: Our data indicate that progenitor-derived MCs from AE patients differ from those from HC. Further investigations with skin-derived MCs are necessary to confirm the observed differences which could provide new insights into the pathogenic mechanisms underlying AE.

PMID: 20608913 [PubMed - indexed for MEDLINE]

601. Med Mycol. 2010 Dec;48(8):1049-55. Epub 2010 Jul 7.

Primary in vitro culture of porcine tracheal epithelial cells in an air-liquid interface as a model to study airway epithelium and Aspergillus fumigatus interactions.

Khoufache K, Cabaret O, Farrugia C, Rivollet D, Alliot A, Allaire E, Cordonnier C, Bretagne S, Botterel F.

UPEC, UMR BIPAR, ENVA, AFSSA, Créteil, France.

Since the airway epithelium is the first tissue encountered by airborne fungal spores, specific models are needed to study this interaction. We developed such a model using primary porcine tracheal epithelial cells (PTEC) as a possible alternative to the use of primary human cells. PTEC were obtained from pigs and were cultivated in an air-liquid interface. Fluorescent brightener was employed to quantify the internalization of Aspergillus fumigatus conidia. Potential differences (Vt) and transepithelial resistances (Rt) after challenge with the mycotoxin, verruculogen, were studied. Primers for porcine inflammatory mediator genes IL-8, TNF-alpha, and GM-CSF were designed for a quantitative real-time PCR procedure to study cellular responses to challenges with A. fumigatus conidia. TEM showed the differentiation of ciliated cells and the PTEC ability to internalize conidia. The internalization rate was 21.9 ± 1.4% after 8 h of incubation. Verruculogen (10(-6) M) significantly increased Vt without having an effect on the Rt. Exposure of PTEC to live A. fumigatus conidia for 24 h induced a 10- to 40-fold increase in the mRNA levels of inflammatory mediator genes. PTEC behave similarly to human cells and are therefore a suitable alternative to human cells for studying interaction between airway epithelium and A. fumigatus.

PMID: 20608777 [PubMed - indexed for MEDLINE]

602. Infect Immun. 2010 Sep;78(9):4040-50. Epub 2010 Jul 6.

Paracoccidioides brasiliensis enolase is a surface protein that binds plasminogen and mediates interaction of yeast forms with host cells.

Nogueira SV, Fonseca FL, Rodrigues ML, Mundodi V, Abi-Chacra EA, Winters MS, Alderete JF, de Almeida Soares CM.

Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, ICBII, Campus II, Universidade Federal de Goiás, 74001-970, Goiânia, Goiás, Brazil.

Paracoccidioidomycosis (PCM), caused by the dimorphic fungus Paracoccidioides brasiliensis, is a disseminated, systemic disorder that involves the lungs and other organs. The ability of the pathogen to interact with host components, including extracellular matrix (ECM) proteins, is essential to further colonization, invasion, and growth. Previously, enolase (EC 4.2.1.11) was characterized as a fibronectin binding protein in P. brasiliensis. Interaction of surface-bound enolase with plasminogen has been incriminated in tissue invasion for pathogenesis in several pathogens. In this paper, enolase was expressed in Escherichia coli as a recombinant glutathione S-transferase (GST) fusion protein (recombinant P. brasiliensis enolase [rPbEno]). The P. brasiliensis native enolase (PbEno) was detected at the fungus surface and cytoplasm by immunofluorescence with an anti-rPbEno antibody. Immobilized purified rPbEno bound plasminogen in a specific, concentration-dependent fashion. Both native enolase and rPbEno activated conversion of plasminogen to plasmin through tissue plasminogen activator. The association between PbEno and plasminogen was lysine dependent. In competition experiments, purified rPbEno, in its soluble form, inhibited plasminogen binding to fixed P. brasiliensis, suggesting that this interaction required surface-localized PbEno. Plasminogen-coated P. brasiliensis yeast cells were capable of degrading purified fibronectin, providing in vitro evidence for the generation of active plasmin on the fungus surface. Exposure of epithelial cells and phagocytes to enolase was associated with an increased expression of surface sites of adhesion. In fact, the association of P. brasiliensis with epithelial cells and phagocytes was increased in the presence of rPbEno. The expression of PbEno was upregulated in yeast cells derived from mouse-infected tissues. These data indicate that surface-associated PbEno may contribute to the pathogenesis of P. brasiliensis.

PMCID: PMC2937444 PMID: 20605975 [PubMed - indexed for MEDLINE]

603. Environ Health. 2010 Jul 6;9:34.

Participatory testing and reporting in an environmental-justice community of Worcester, Massachusetts: a pilot project.

Downs TJ, Ross L, Mucciarone D, Calvache MC, Taylor O, Goble R.

Environmental Science and Policy Program, Clark University, 950 Main Street, Worcester, Massachusetts 01610, USA. tdowns@clarku.edu

BACKGROUND: Despite indoor home environments being where people spend most time, involving residents in testing those environments has been very limited, especially in marginalized communities. We piloted participatory testing and reporting that combined relatively simple tests with actionable reporting to empower residents in Main South/Piedmont neighborhoods of Worcester, Massachusetts. We answered: 1) How do we design and implement the approach for neighborhood and household environments using participatory methods? 2) What do pilot tests reveal? 3) How does our experience inform testing practice?
METHODS: The approach was designed and implemented with community partners using community-based participatory research. Residents and researchers tested fourteen homes for: lead in dust indoors, soil outdoors, paint indoors and drinking water; radon in basement air; PM2.5 in indoor air; mold spores in indoor/outdoor air; and drinking water quality. Monitoring of neighborhood particulates by residents and researchers used real-time data to stimulate dialogue.
RESULTS: Given the newness of our partnership and unforeseen conflicts, we achieved moderate-high success overall based on process and outcome criteria: methods, test results, reporting, lessons learned. The conflict burden we experienced may be attributable less to generic university-community differences in interests/culture, and more to territoriality and interpersonal issues. Lead-in-paint touch-swab results were poor proxies for lead-in-dust. Of eight units tested in summer, three had very high lead-in-dust (>1000 microg/ft2), six exceeded at least one USEPA standard for lead-in-dust and/or soil. Tap water tests showed no significant exposures. Monitoring of neighborhood particulates raised awareness of environmental health risks, especially asthma.
CONCLUSIONS: Timely reporting back home-toxics' results to residents is ethical but it must be empowering. Future work should fund the active participation of a few motivated residents as representatives of the target population. Although difficult and demanding in time and effort, the approach can educate residents and inform exposure assessment. It should be considered as a core ingredient of comprehensive household toxics' testing, and has potential to improve participant retention and the overall positive impact of long-term environmental health research efforts.

PMCID: PMC2914716 PMID: 20604953 [PubMed - indexed for MEDLINE]

604. Clin Infect Dis. 2010 Aug 15;51(4):e28-33.

Interhuman transmission as a potential key parameter for geographical variation in the prevalence of Pneumocystis jirovecii dihydropteroate synthase mutations.

Hauser PM, Nahimana A, Taffe P, Weber R, Francioli P, Bille J, Rabodonirina M.

Institute of Microbiology, Swiss HIV Cohort Study, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.

BACKGROUND: Pneumocystis jirovecii dihydropteroate synthase (DHPS) mutations are associated with failure of prophylaxis with sulfa drugs. This retrospective study sought to better understand the geographical variation in the prevalence of these mutations.
METHODS: DHPS polymorphisms in 394 clinical specimens from immunosuppressed patients who received a diagnosis of P. jirovecii pneumonia and who were hospitalized in 3 European cities were examined using polymerase chain reaction (PCR) single-strand conformation polymorphism. Demographic and clinical characteristics were obtained from patients' medical charts.
RESULTS: Of the 394 patients, 79 (20%) were infected with a P. jirovecii strain harboring one or both of the previously reported DHPS mutations. The prevalence of DHPS mutations was significantly higher in Lyon than in Switzerland (33.0% vs 7.5%; P < .001). The proportion of patients with no evidence of sulfa exposure who harbored a mutant P. jirovecii DHPS genotype was significantly higher in Lyon than in Switzerland (29.7% vs 3.0%; P < .001). During the study period in Lyon, in contrast to the Swiss hospitals, measures to prevent dissemination of P. jirovecii from patients with P. jirovecii pneumonia were generally not implemented, and most patients received suboptimal prophylaxis, the failure of which was strictly associated with mutated P. jirovecii. Thus, nosocomial interhuman transmission of mutated strains directly or indirectly from other individuals in whom selection of mutants occurred may explain the high proportion of mutations without sulfa exposure in Lyon.
CONCLUSIONS: Interhuman transmission of P. jirovecii, rather than selection pressure by sulfa prophylaxis, may play a predominant role in the geographical variation in the prevalence in the P. jirovecii DHPS mutations.

PMID: 20604718 [PubMed - indexed for MEDLINE]

605. Int J Biol Macromol. 2010 Nov 1;47(4):454-7. Epub 2010 Jul 13.

Anticandidal action of fungal chitosan against Candida albicans.

Tayel AA, Moussa S, el-Tras WF, Knittel D, Opwis K, Schollmeyer E.

Genetic Engineering and Biotechnology Research Institute, Minufiya University, El-Sadat City, Egypt. tayel ahmad@yahoo.com

The anticandidal activity of four fungal chitosan types, produced from Mucor rouxii DSM-1191, against three Candida albicans strains was determined. The most bioactive chitosan type, to inhibit C. albicans growth, had the lowest molecular weight (32 kDa) and the highest deacetylation degree (94%). Water soluble types had stronger anticandidal activity than soluble types in 1% acetic acid solution. Scanning electron micrographs of treated C. albicans with fungal chitosan proved that chitosan principally interact with yeast cell wall, causing severe swelling and asymmetric rough shapes, and subsequent cell wall lyses with the prolonging of exposure time. Fungal chitosan could be recommended for C. albicans control as a powerful and safe alternative to synthetic and chemical fungicides.

PMID: 20603144 [PubMed - indexed for MEDLINE]

606. Eur J Pharmacol. 2010 Sep 15;643(1):42-7. Epub 2010 Jul 2.

Viability of Saccharomyces cerevisiae cells following exposure to H2O2 and protective effect of minocycline depend on the presence of VDAC.

Gałgańska H, Karachitos A, Baranek M, Budzińska M, Jordán J, Kmita H.

Laboratory of Bioenergetics, Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz University, Poznan, Poland.

Proteins involved in apoptosis are still a matter of debate. Therefore, we decided to check the effect of the presence of VDAC (voltage dependent anion selective channel) on viability of Saccharomyces cerevisiae cells following their exposure to H(2)O(2) that is known to induce apoptosis both in S. cerevisiae and in mammalian cells. Mitochondria of S. cerevisiae contain only one channel-forming VDAC isoform (VDAC1), which simplifies studies on the channel. Using S. cerevisiae mutant depleted of VDAC1 (termed here VDAC) and the isogenic wild type, we have shown that VDAC is important for protection of S. cerevisiae cells against H(2)O(2) treatment, particularly in exponential growth phase that is known to be more affected by H(2)O(2). The increased viability of H(2)O(2) pretreated exponentially growing cells containing VDAC was accompanied by clear changes of the cytosol redox state and was potentiated by minocycline, an antibiotic of the tetracycline family that displays cytoprotective potency. The protective effect of minocycline also coincided with distinct changes of cytosol redox state. Thus, we conclude that the ability to change the cytosol redox state following exposure to H(2)O(2) or/and minocycline appears to be an intrinsic feature of exponentially growing cells (young cells) containing VDAC. Moreover, the ability seems to be crucial for both cell viability and protective effect of minocycline.

PMID: 20599912 [PubMed - indexed for MEDLINE]

607. Indoor Air. 2010 Oct;20(5):380-91. doi: 10.1111/j.1600-0668.2010.00660.x.

A comparison of the allergic responses induced by Penicillium chrysogenum and house dust mite extracts in a mouse model.

Ward MD, Chung YJ, Copeland LB, Doerfler DL.

National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA. ward.marsha@epa.gov

A report by the Institute of Medicine suggested that more research is needed to better understand mold effects on allergic disease, particularly asthma development. We compared the ability of the fungal Penicillium chrysogenum (PCE) and house dust mite (HDM) extracts to induce allergic responses in BALB/c mice. The extracts were administered by intratracheal aspiration (IA) at several doses (0, 2.5, 5, 10, 20, 40, and 80 μg) four times over a 4-week period. Three days after the last IA exposure, serum and bronchoalveolar lavage fluid (BALF) were collected. The relative allergenicity of the extracts was evaluated based on the lowest dose able to induce a significant response compared to control (0 μg) and the robustness of the response. PCE induced the most robust response at the lowest dose for most endpoints examined: BALF total, macrophage, neutrophil, and eosinophil cell counts, and antigen-specific IgE. Taken together, our data suggest that PCE may induce a more robust allergic and inflammatory response at lower doses than HDM. PRACTICAL IMPLICATIONS: Our data suggest that Penicillium chrysogenum is a robust allergen and may be a more potent allergen source than house dust mite (HDM) in this mouse model. Two critical factors in the development of human allergic disease, exposure levels and sensitization thresholds, are unknown for most allergens including molds/fungi. Human exposure levels are not within the scope of this article. However, the data presented suggest a threshold dose for the induction of allergic responsiveness to P. chrysogenum. Additionally, P. chrysogenum as well as other molds may play an important role in asthma development in our society.

PMID: 20590919 [PubMed - indexed for MEDLINE]

608. Indoor Air. 2010 Oct;20(5):392-8. doi: 10.1111/j.1600-0668.2010.00663.x.

A dose-dependent relationship between the severity of visible mold growth and IgE levels of pre-school-aged resident children in Taiwan.

Hsu NY, Wang JY, Su HJ.

Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

To demonstrate a dose-dependent relationship between severity of indoor visible mold growth and serum total IgE levels of resident children. A total of 97 children (4-7 years old) identified from previously established birth-cohort, with information pertaining to indoor environmental conditions after child's birth, were successfully recruited while sera were concurrently collected for total IgE and specific IgE analysis during clinical visits. Severity of visible mold growth at homes was scaled into three levels accordingly. A statistically significant dose-dependent relationship was found between severity of indoor visible mold growth and total serum IgE levels. The trend sustains after the model was adjusted for resident child's age, gender, pet-keeping history, number of siblings, atopic history of parents, presence of incense burning, and environmental tobacco smoking (ETS) at home. Further analysis of specific IgE to commonly examined fungal allergens did not substantiate the correlation. Rather, resident child's specific IgE to mite allergens, although without statistical significance, seemed to better associate with the ranked severity of indoor mold growth in this study. An adjuvant role of fungal exposure to enhance sensitization in indoor environment is therefore suggested in Taiwanese population with high prevalence of building dampness. PRACTICAL IMPLICATIONS: The presence of indoor visible mold growth, potentially resulting in fungal exposure, was not associated directly with changing biomarker levels of allergic response in resident children, rather playing an adjuvant role to enhance sensitization. On the other hand, other allergens, such as mite allergen examined in this study, appeared to support a more plausible etiology for directly triggering the ultimate allergic symptoms and diseases of interest. Evidence as such may derive different priority-setting when designing preventive measures for managing indoor air quality.

PMID: 20590918 [PubMed - indexed for MEDLINE]

609. Arh Hig Rada Toksikol. 2010 Jun 1;61(2):167-73.

Determination of Aspergillus fumigatus allergen 1 in poultry farms using the enzyme immunoassay.

Prester L, Macan J, Matković K, Vucemilo M.

Institute for Medical Research and Occupational Health, Zagreb, Croatia. prester@imi.hr

Poultry farms contain high levels of allergenic fungi, and Aspergillus spp. is the most common genus of moulds. Aspergillus fumigatus antigens are responsible for the development of several respiratory diseases including asthma. The aim of this study was to measure the mass fraction of Asp f 1, a major allergen of Asperillus fumigatus in 37 indoor dust samples collected from four poultry farms in a rural area of the Zagreb County (Croatia) using the enzyme-linked immunosorbent assay. More than 62 % of dust samples had detectable Asp f 1 levels (limit of detection 3.6 ng g(-1)). The overall mean Asp f 1 level was 17.9 ng g(-1) [range (3.8 to 72.4) ng g(-1)]. Satisfactory results were obtained for analytical within-run imprecision (6.7 %), between-run imprecision (10.5 %), and accuracy (91 % to 115 %). Microclimate parameters (air temperature, relative humidity, and velocity) were within the recommended ranges in all poultry farms. This study has shown that Asp f 1 settles on dust at poultry farms and that occupational exposure to this allergen deserves monitoring in livestock buildings.

PMID: 20587390 [PubMed - indexed for MEDLINE]

610. Curr Allergy Asthma Rep. 2010 Sep;10(5):308-9.

Exposure to indoor fungi: a new paradigm.

Bush RK.

University of Wisconsin-Madison, 600 Highland Avenue, Madison, WI, 53792, USA. rkb@medicine.wisc.edu

Comment on Mucosal Immunol. 2009 Nov;2(6):504-17.

PMID: 20585904 [PubMed]

611. Infect Immun. 2010 Sep;78(9):3981-92. Epub 2010 Jun 28.

Immune defenses against Batrachochytrium dendrobatidis, a fungus linked to global amphibian declines, in the South African clawed frog, Xenopus laevis.

Ramsey JP, Reinert LK, Harper LK, Woodhams DC, Rollins-Smith LA.

Department of Microbiology and Immunology, A-5301 Medical Center North, Vanderbilt University, Nashville, TN 37232, USA.

Batrachochytrium dendrobatidis is a chytrid fungus that causes the lethal skin disease chytridiomycosis in amphibians. It is regarded as an emerging infectious disease affecting diverse amphibian populations in many parts of the world. Because there are few model amphibian species for immunological studies, little is known about immune defenses against B. dendrobatidis. We show here that the South African clawed frog, Xenopus laevis, is a suitable model for investigating immunity to this pathogen. After an experimental exposure, a mild infection developed over 20 to 30 days and declined by 45 days postexposure. Either purified antimicrobial peptides or mixtures of peptides in the skin mucus inhibited B. dendrobatidis growth in vitro. Skin peptide secretion was maximally induced by injection of norepinephrine, and this treatment resulted in sustained skin peptide depletion and increased susceptibility to infection. Sublethal X-irradiation of frogs decreased leukocyte numbers in the spleen and resulted in greater susceptibility to infection. Immunization against B. dendrobatidis induced elevated pathogen-specific IgM and IgY serum antibodies. Mucus secretions from X. laevis previously exposed to B. dendrobatidis contained significant amounts of IgM, IgY, and IgX antibodies that bind to B. dendrobatidis. These data strongly suggest that both innate and adaptive immune defenses are involved in the resistance of X. laevis to lethal B. dendrobatidis infections.

PMCID: PMC2937463 PMID: 20584973 [PubMed - indexed for MEDLINE]

612. Vet Rec. 2010 Jun 26;166(26):832; author reply 832.

Exposure to Encephalitozoon cuniculi in rabbits with dental disease.

Cooper P.

Comment on Vet Rec. 2010 Jun 5;166(23):730.

PMID: 20581368 [PubMed - indexed for MEDLINE]

613. N Biotechnol. 2010 Sep 30;27(4):397-402. Epub 2010 May 24.

Activity and characterization of secondary metabolites produced by a new microorganism for control of plant diseases.

Ko WH, Tsou YJ, Lin MJ, Chern LL.

Department of Plant Pathology, National Chung Hsing University, Taichung, Taiwan. kowh@dragon.nchu.edu.tw

Microorganisms capable of utilizing vegetable tissues for growth in soils were isolated and their vegetable broth cultures were individually sprayed directly on leaves to test their ability to control Phytophthora blight of bell pepper caused by Phytophthora capsici. Liquid culture of Streptomyces strain TKA-5, a previously undescribed species obtained in this study, displayed several desirable disease control characteristics in nature, including high potency, long lasting and ability to control also black leaf spot of spoon cabbage caused by Alternaria brassicicolca. The extract was fungicidal to P. capsici but fungistatic to A. brassicicola. It was stable at high temperature and high pH. However, after exposure to pH 2 for 24h, the extract was no longer inhibitory to P. capsici although it was still strongly inhibitory to A. brassicicola. After treatment with cation or anion exchange resins, the extract lost its inhibitory effect against P. capsici but not A. brassicicola. The results suggest that the extract contained two different kinds of inhibitory metabolites, one against P. capsici with both positive and negative charges on its molecule and another against A. brassicicola with no charges on its molecule. The inhibitory metabolites were soluble in ethanol or methanol but not in water, ether or chloroform. They were dialyzable in the membrane tubing with molecular weight cut-off of 10,000, 1000 or 500 but not 100, indicating that the inhibitors have a molecular weight between 500 and 100. Results also showed that both inhibitors are not proteins.

PMID: 20580869 [PubMed - indexed for MEDLINE]

614. Peptides. 2010 Aug;31(8):1449-58. Epub 2010 May 24.

Evaluation of the epinecidin-1 peptide as an active ingredient in cleaning solutions against pathogens.

Pan CY, Rajanbabu V, Chen JY, Her GM, Nan FH.

Marine Research Station, Institute of Cellular and Organismic Biology, Academia Sinica, 23-10 Dahuen Rd., Jiaushi, Ilan 262, Taiwan.

We tested the activity of epinecidin-1, a novel antimicrobial peptide structurally related to pleurocidin, in commercial cleaning solutions stored at 4 and 25 degrees C for 7 and 14 days. The peptide's activities against Enterococcus faecalis, Escherichia coli, Klebsiella oxytoca, Pseudomonas aeruginosa, Staphylococcus aureus, Propionibacterium acnes, and Candida albicans were measured in a minimum inhibitory concentration (MIC) determination, minimal bactericidal concentration (MBC) determination, disk diffusion test, and a count of the bacterial numbers. Exposure to epinecidn-1 in a cleaning solution following MIC value comparisons in the disk diffusion test and counts of bacterial numbers after 16, 24, 48, and 72 h suggested that bacterial numbers were much lower than those treated with only commercial cleaning solutions for all bacteria. The efficacy of the antimicrobial activities of inhibiting bacterial numbers by epinecidin-1 in cleaning solutions at a low pH and a low temperature was not affected. Given its simple structure and antimicrobial activity, epinecidin-1 may be a useful component of microbicides designed to prevent pathogen infections and/or remediate abnormal vaginal or skin flora.

PMID: 20580756 [PubMed - indexed for MEDLINE]

615. J Forensic Sci. 2010 Sep;55(5):1359-61.

Trichophyton mentagrophytes perforates hair of adult corpses in the gaseous period.

Filho RE, Sidrim JJ, Cordeiro Rde A, Caetano EP, Rocha MF, Brilhante RS.

Specialized Medical Mycology Center, Federal University of Ceará, Fortaleza, CE, Brazil.

Despite the substantial literature on mycology, there are still limited reports of the interaction between fungi and human hosts in the postmortem period. Thus, the main goal of this study was to investigate the in vitro perforation test using Trichophyton mentagrophytes on hair from adult corpses in the postmortem period (gaseous period). The protocol was carried out with positive (prepubescent children's hair) and negative controls (healthy adult hair) as well. One strain of Trichophyton rubrum was also used as a negative perforation control. Perforations were found in all the hair samples from corpses and prepubescent children after 12–14 days exposure to T. mentagrophytes and were absent in the hair samples of healthy adults. Furthermore, hair perforation was not observed with T. rubrum. Our preliminary findings suggest the use of T. mentagrophytes as a potential marker of the death interval in forensic science.

PMID: 20579231 [PubMed - indexed for MEDLINE]

616. Nature. 2010 Jun 24;465(7301):1039-43.

Structural basis for the suppression of skin cancers by DNA polymerase eta.

Silverstein TD, Johnson RE, Jain R, Prakash L, Prakash S, Aggarwal AK.

Department of Structural and Chemical Biology, Mount Sinai School of Medicine, Box 1677, 1425 Madison Avenue, New York, New York 10029, USA.

Comment in Nature. 2010 Jun 24;465(7301):1023-4.

DNA polymerase eta (Poleta) is unique among eukaryotic polymerases in its proficient ability for error-free replication through ultraviolet-induced cyclobutane pyrimidine dimers, and inactivation of Poleta (also known as POLH) in humans causes the variant form of xeroderma pigmentosum (XPV). We present the crystal structures of Saccharomyces cerevisiae Poleta (also known as RAD30) in ternary complex with a cis-syn thymine-thymine (T-T) dimer and with undamaged DNA. The structures reveal that the ability of Poleta to replicate efficiently through the ultraviolet-induced lesion derives from a simple and yet elegant mechanism, wherein the two Ts of the T-T dimer are accommodated in an active site cleft that is much more open than in other polymerases. We also show by structural, biochemical and genetic analysis that the two Ts are maintained in a stable configuration in the active site via interactions with Gln 55, Arg 73 and Met 74. Together, these features define the basis for Poleta's action on ultraviolet-damaged DNA that is crucial in suppressing the mutagenic and carcinogenic consequences of sun exposure, thereby reducing the incidence of skin cancers in humans.

PMCID: PMC3030469 PMID: 20577207 [PubMed - indexed for MEDLINE]

617. Int J Food Microbiol. 2010 Aug 15;142(1-2):14-8. Epub 2010 May 10.

Ethanol, vinegar and Origanum vulgare oil vapour suppress the development of anthracnose rot in tomato fruit.

Tzortzakis NG.

Department of Hydroponics and Aromatic Plants, National Agricultural Research Foundation (NAGREF), Agrokipion, Chania, Greece. ntzortzakis@staff.teicrete.gr

Anthracnose rot (Colletotrichum coccodes) development in vitro or in tomato (Lycopersicon esculentum L.) fruit was evaluated after treatment with absolute ethyl alcohol (AEA), vinegar (VIN), chlorine (CHL) or origanum oil (ORI) and storage at 12 degrees C and 95% relative humidity during or following exposure to the volatiles. Fruit treated with vapours reduced fungal spore germination/production, but in the case of AEA- and VIN-treated fruits, fungal mycelium development was accelerated. Fruit lesion development was suppressed after fruit exposure to pure (100% v/v) AEA or ORI vapours which were accompanied by increased fruit cracking. Exposure to pure VIN-, CHL- and ORI vapours reduced (up to 92%) spore germination in vitro, but no differences were observed in the AEA treatment. The benefits associated with volatiles-enrichment were maintained in fruit pre-exposed to vapours, resulting in suppression in spore germination and spore production. However, studies performed on fungi grown on Potato Dextrose Agar revealed fewer direct effects of volatiles on fungal colony development and spore germination per se, implying that suppression of pathogen development was due in a large part to the impact of volatiles on fruit-pathogen interactions and/or 'memory' effects on fruit tissue. Work is currently focussing on the mechanisms underlying the impacts of volatiles on fruit quality related attributes. The results of this study indicate that volatiles may be considered as an alternative to the traditional postharvest sanitizing techniques. Each commodity needs to be individually assessed, and the volatile concentration and sanitising technique optimised, before the volatile treatment is used commercially.

PMID: 20576303 [PubMed - indexed for MEDLINE]

618. J Toxicol Environ Health A. 2010;73(16):1075-89.

Estrogenic pyrethroid pesticides regulate expression of estrogen receptor transcripts in mouse Sertoli cells differently from 17beta-estradiol.

Taylor JS, Thomson BM, Lang CN, Sin FY, Podivinsky E.

University of Canterbury, Christchurch.

Studies suggested that exposure to agricultural pesticides may affect male fertility. Pyrethroids are widely used pesticides due to their insecticidal potency and low mammalian toxicity. A recombinant yeast assay system incorporating the human alpha-estrogen receptor was used to analyze the estrogenicity of a range of readily available pyrethroid pesticides. The commercial product Ripcord Plus showed estrogenic activity by this assay. To determine whether pyrethroid compounds might exert an effect on male fertility, mouse Sertoli cells were exposed in vitro to the endogenous estrogen, 17beta-estradiol, and selected estrogenic pyrethroids. Following exposure, transcript levels of the alpha- and beta-estrogen receptors were assessed. Exposure of Sertoli cells to the pyrethroid compounds, both at high and at low published serum concentrations, affected the expression of the two estrogen receptors; however, the influence on estrogen receptor gene expression was different from the effect from exposure to 17beta-estradiol. These results from our model systems suggest that (1) estrogenic pyrethroid pesticides affect the estrogen receptors, and therefore potentially the endocrine system, in a different manner from that of endogenous estrogen, and (2) should cells in the male testes be exposed to pyrethroid pesticides, male fertility may be affected through molecular mechanisms involving estrogen receptors.

PMID: 20574910 [PubMed - indexed for MEDLINE]

619. Mycopathologia. 2011 Jan;171(1):67-75. Epub 2010 Jun 23.

Persistence of Isaria fumosorosea (Hypocreales: Cordycipitaceae) SFP-198 conidia in corn oil-based suspension.

Kim JS, Je YH, Woo EO, Park JS.

Entomology Research Laboratory, Department of Plant and Soil Science, University of Vermont, 661 Spear Street, Burlington, VT 05405-0105, USA, jae-su.kim@uvm.edu

Long-term persistence of entomopathogenic fungi as biopesticides is a major requirement for successful industrialization. Corn oil carrier was superior in maintaining germination rates of Isaria fumosorosea SFP-198 conidia during exposure to 50°C for 2 h, when compared with other oils, such as soybean oil, cottonseed oil, paraffin oil, and methyl oleate. The corn oil-based conidial suspension (91.6% germination) was also better in this regard than conidial powder (28.4% germination) after 50°C for 8 h. Long-term storage stabilities of corn oil-based conidial suspension and conidial powder at 4 and 25°C for 24 months were investigated, based on the correlation of germination rate with insecticidal activity against greenhouse whiteflies, Trialeurodes vaporariorum. Viability of conidia in corn oil was more than 98.4% for up to 9 months of storage at 25°C, and followed by 23% at 21 months. However, conidial powder had only 34% viability after 3 months of storage at 25°C, after which its viability rapidly decreased. The two conidial preparations stored at 4°C had better viabilities than those at 25°C, showing the same pattern as above. These results indicate that corn oil-based conidial suspension can be used to improve conidial persistence in long-term storage and be further applied to the formulation of other thermo-susceptible biological control agents.

PMID: 20571913 [PubMed - indexed for MEDLINE]

620. Photochem Photobiol Sci. 2010 Aug;9(8):1145-51. Epub 2010 Jun 23.

Photoprotection by carotenoid pigments in the yeast Rhodotorula mucilaginosa: the role of torularhodin.

Moliné M, Flores MR, Libkind D, Diéguez Mdel C, Farías ME, van Broock M.

Laboratorio de Microbiología Aplicada y Biotecnología, Instituto de Investigaciones en Biodiversidad y Medio Ambiente, INIBIOMA (CONICET-UNComahue), Quintral 1250, 8400, San Carlos de Bariloche, Río Negro, Argentina.

In this paper we report the relationship between carotenoids and ergosterol and cell UV-B resistance in different strains of the yeast Rhodotorula mucilaginosa. Cell survival was studied using a set of 13 strains; additionally, two mutants (a hyper-producing one and a colourless one) in combination with diphenylamine (DPA), a carotenogenesis inhibitor, were used. A positive correlation between total carotenoids and survival to UV-B radiation was found. However, when individual carotenoid concentrations were tested, only torularhodin was found to be significantly related to UV-B survival. On the contrary, ergosterol did not affect survival. The hyper-pigmented strain showed an enhanced survival (up to 250%) compared to the parental strain, while the survival of the albino mutant was similar to that experienced by the parental strain; however, observed changes in survival were dose dependent. The cyclobutane pyrimidine dimers (CPDs), one of the major forms of DNA damage caused by UV exposure, appears as unrelated to the accumulation of carotenoids and cell survival. These results indicate that bearing higher torularhodin concentrations enhances UV-B survival in yeasts and, thus, the accumulation of this pigment constitutes an important mechanism that improves the resistance of yeasts to UV-B.

PMID: 20571712 [PubMed - indexed for MEDLINE]

621. J Biol Chem. 2010 Aug 27;285(35):26832-41. Epub 2010 Jun 22.

Oleate inhibits steryl ester synthesis and causes liposensitivity in yeast.

Connerth M, Czabany T, Wagner A, Zellnig G, Leitner E, Steyrer E, Daum G.

Institute of Biochemistry, Graz University of Technology, Petersgasse 12/2, Graz, Austria.

In the yeast Saccharomyces cerevisiae, neutral lipids can be synthesized by four acyltransferases, namely Dga1p and Lro1p producing triacylglycerols (TAG) and Are1p and Are2p forming steryl esters (SE). TAG and SE are stored in an organelle called lipid particles/droplet. Growth of yeast cells on oleate-supplemented media strongly induced proliferation of lipid particles and specifically the synthesis of TAG, which serve as the major pool for the excess of fatty acids. Surprisingly, SE synthesis was strongly inhibited under these conditions. Here, we show that this effect was not due to decreased expression of ARE2 encoding the major yeast SE synthase at the transcriptional level but to competitive enzymatic inhibition of Are2p by free oleate. Consequently, a triple mutant dga1Deltalro1Deltaare1DeltaARE2(+) grown on oleate did not form substantial amounts of SE and exhibited a growth phenotype similar to the dga1Deltalro1Deltaare1Deltaare2Delta quadruple mutant, including lack of lipid particles. Growth of these mutants on oleate was strongly delayed, and cell viability was decreased but rescued by adaptation. In these strains, oleate stress caused morphological changes of intracellular membranes, altered phospholipid composition and formation of an additional lipid class, ethyl esters of fatty acids. In summary, our data showed that exposure to oleate led to disturbed lipid and membrane homeostasis along with liposensitivity of the yeast.

PMCID: PMC2930682 PMID: 20571028 [PubMed - indexed for MEDLINE]

622. Environ Health Perspect. 2010 Oct;118(10):1497-502. Epub 2010 Jun 22.

Short-term effects of air pollution on wheeze in asthmatic children in Fresno, California.

Mann JK, Balmes JR, Bruckner TA, Mortimer KM, Margolis HG, Pratt B, Hammond SK, Lurmann FW, Tager IB.

Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, California, USA.

BACKGROUND: Although studies have demonstrated that air pollution is associated with exacerbation of asthma symptoms in children with asthma, little is known about the susceptibility of subgroups, particularly those with atopy.
OBJECTIVE: This study was designed to evaluate our a priori hypothesis that identifiable subgroups of asthmatic children are more likely to wheeze with exposure to ambient air pollution.
METHODS: A cohort of 315 children with asthma, 6-11 years of age, was recruited for longitudinal follow-up in Fresno, California (USA). During the baseline visit, children were administered a respiratory symptom questionnaire and allergen skin-prick test. Three times a year, participants completed 14-day panels during which they answered symptom questions twice daily. Ambient air quality data from a central monitoring station were used to assign exposures to the following pollutants: particulate matter ≤ 2.5 μm in aerodynamic diameter, particulate matter between 2.5 and 10 μm in aerodynamic diameter (PM10-2.5), elemental carbon, nitrogen dioxide (NO2), nitrate, and O3.
RESULTS: For the group as a whole, wheeze was significantly associated with short-term exposures to NO2 [odds ratio (OR) = 1.10 for 8.7-ppb increase; 95% confidence interval (CI), 1.02-1.20] and PM10-2.5 (OR = 1.11 for 14.7-μg/m3 increase; 95% CI, 1.01-1.22). The association with wheeze was stronger for these two pollutants in children who were skin-test positive to cat or common fungi and in boys with mild intermittent asthma.
CONCLUSION: A pollutant associated with traffic emissions, NO2, and a pollutant with bioactive constituents, PM10-2.5, were associated with increased risk of wheeze in asthmatic children living in Fresno, California. Children with atopy to cat or common fungi and boys with mild intermittent asthma were the subgroups for which we observed the largest associations.

PMCID: PMC2957935 PMID: 20570778 [PubMed - indexed for MEDLINE]

623. Adolesc Med State Art Rev. 2010 Apr;21(1):57-71, viii-ix.

The role of allergen exposure and avoidance in asthma.

Baxi SN, Phipatanakul W.

Division of Immunology, Children's Hospital, Boston/Harvard Medical School, 300 Longwood Avenue, Fegan 6, Boston, MA 02445, USA.

Allergy testing and avoidance of allergens plays an important role in asthma control. Increased allergen exposure, in genetically susceptible individuals, can lead to allergic sensitization. Continued allergen exposure can increase the risk of asthma and other allergic diseases. In a patient with persistent asthma, identification of indoor and outdoor allergens and subsequent avoidance can improve symptoms. Often times, a patient will have multiple allergies and the avoidance plan should target all positive allergens. Several studies have shown that successful allergen remediation includes a comprehensive approach including education, cleaning, physical barriers, and maintaining these practices.

PMCID: PMC2975603 PMID: 20568555 [PubMed - indexed for MEDLINE]

624. Am J Ind Med. 2010 Nov;53(11):1119-27.

The Snowman: A model of injuries and near-misses for the prevention of sharps injuries.

Kim H, Kriebel D, Quinn MM, Davis L.

Department of Work Environment, University of Massachusetts Lowell, USA. hyun.kim@mssm.edu

BACKGROUND: Sharps injuries (SI) and other blood/body fluid exposures (BBFE) present bloodborne pathogen risks for home healthcare (HHC) workers. While SI and BBFE are sufficiently frequent in HHC to be serious public health concerns, even moderately large surveys can still have insufficient power to identify risk factors. In this study, a new conceptual model for using near-misses for SI and BBFE was developed and its utility in statistical analyses of SI and BBFE risk factors was evaluated.
METHODS: A survey of HHC nurses (n = 787) and aides (n = 282) gathered data on the numbers of SI, BBFE, and near-misses in the past year. Questions focused on the circumstances leading up to the SI, BBFE, and near-misses. After evaluating the hypothesis that near-misses and events lie along the same causal pathway, we combined these outcomes to estimate their association with an important risk factor: employment status.
RESULTS: There were similar frequencies of risk factors for the events SI, BBFE, and their near-misses, suggesting that they may share common causal pathways. Combined data on events and near-misses confirmed our hypothesis that part-time and temporary HHC aides were at higher risk than full-timers.
CONCLUSIONS: Analyses combining injuries and near-misses may be useful in risk factor investigations.

PMID: 20568269 [PubMed - indexed for MEDLINE]

625. BMC Biotechnol. 2010 Jun 18;10:45.

Real-time detection of viable microorganisms by intracellular phototautomerism.

Kort R, Nocker A, de Kat Angelino-Bart A, van Veen S, Verheij H, Schuren F, Montijn R.

Business Unit Food and Biotechnology Innovations, Microbial Genomics Group, TNO Quality of Life, Zeist, The Netherlands. remco.kort@tno.nl

BACKGROUND: To date, the detection of live microorganisms present in the environment or involved in infections is carried out by enumeration of colony forming units on agar plates, which is time consuming, laborious and limited to readily cultivable microorganisms. Although cultivation-independent methods are available, they involve multiple incubation steps and do mostly not discriminate between dead or live microorganisms. We present a novel generic method that is able to specifically monitor living microorganisms in a real-time manner.
RESULTS: The developed method includes exposure of cells to a weak acid probe at low pH. The neutral probe rapidly permeates the membrane and enters the cytosol. In dead cells no signal is obtained, as the cytosolic pH reflects that of the acidic extracellular environment. In live cells with a neutral internal pH, the probe dissociates into a fluorescent phototautomeric anion. After reaching peak fluorescence, the population of live cells decays. This decay can be followed real-time as cell death coincides with intracellular acidification and return of the probe to its uncharged non-fluorescent state. The rise and decay of the fluorescence signal depends on the probe structure and appears discriminative for bacteria, fungi, and spores. We identified 13 unique probes, which can be applied in the real-time viability method described here. Under the experimental conditions used in a microplate reader, the reported method shows a detection limit of 10(6) bacteria ml(-1), while the frequently used LIVE/DEAD BacLight Syto9 and propidium iodide stains show detection down to 10(6) and 10(7) bacteria ml(-1), respectively.
CONCLUSIONS: We present a novel fluorescence-based method for viability assessment, which is applicable to all bacteria and eukaryotic cell types tested so far. The RTV method will have a significant impact in many areas of applied microbiology including research on biocidal activity, improvement of preservation strategies and membrane permeation and stability. The assay allows for high-throughput applications and has great potential for rapid monitoring of microbial content in air, liquids or on surfaces.

PMCID: PMC2906424 PMID: 20565844 [PubMed - indexed for MEDLINE]

626. Am J Phys Anthropol. 2010 Sep;143(1):151-4.

Brief communication: Mass spectroscopic characterization of tetracycline in the skeletal remains of an ancient population from Sudanese Nubia 350-550 CE.

Nelson ML, Dinardo A, Hochberg J, Armelagos GJ.

Paratek Pharmaceuticals, Inc., Boston, MA 02111, USA. mnelson@paratekpharm.com

Histological evidence of tetracycline use has been reported in an ancient X-Group population (350-550 CE) from Sudanese Nubia (Bassett et al., 1980). When bone samples were examined by fluorescent microscopy under UV light at 490 A yellow-green fluorophore deposition bands, similar to those produced by tetracycline, were observed, suggesting significant exposure of the population to the antibiotic. These reports were met skeptically with claims that the fluorescence was the result of postmortem taphonomic infiltration of bacteria and fungi. Herein, we report the acid extraction and mass spectroscopic characterization of the antibiotic tetracycline from these samples. The bone samples were demineralized in anhydrous hydrogen fluoride which dissolved the bone-complexed tetracycline, followed by isolation by solid phase extraction on reverse-phase media. Chemical characterization by high pressure liquid chromatography mass-spectroscopic procedures showed that the retention times and mass spectra of the bone extract were identical to tetracycline when treated similarly. These results indicate that a natural product tetracycline was detectable within the sampled bone and was converted to the acid-stable form, anhydrotetracycline, with a mass + H of 427.1 amu. Our findings show that the bone sampled is labeled by the antibiotic tetracycline, and that the NAX population ingested and were exposed to tetracycline-containing materials in their dietary regime.

PMID: 20564518 [PubMed - indexed for MEDLINE]

627. Saudi Med J. 2010 Jun;31(6):640-3.

Effectiveness of a 20% Miswak extract against a mixture of Candida albicans and Enterococcus faecalis.

Al-Obaida MI, Al-Essa MA, Asiri AA, Al-Rahla AA.

Department of Restorative Dental Sciences, College of Dentistry, King Saud University, PO Box 60169, Riyadh 11545, Kingdom of Saudi Arabia. malobaida@ksu.edu.sa

OBJECTIVE: To examine the in vitro antimicrobial effect of a 20% Miswak extract against a mixture of Candida albicans (C. albicans) and Enterococcus faecalis (E. faecalis) using the dilution tube susceptibility test, which allows direct contact between the tested material and the microorganisms.
METHODS: The study samples were collected and processed between August 2009 and January 2010 in the College of Dentistry, King Saud University, Riyadh, Saudi Arabia. Each microorganism was obtained in a suspension and exposed to a 20% Miswak extract in plastic tissue culture clusters containing 24 wells. Six wells were used per group. The Miswak extract was incubated with the microorganisms for one, 6, and 24 hours.
RESULTS: This in vitro study showed that Miswak extract was an effective antifungal and antibacterial agent at all tested experimental time periods, except one hour exposure of a 20% Miswak extract to E. faecalis and a mixture of E. faecalis and C. albicans, which was ineffective in inhibiting their growth.
CONCLUSION: Twenty percent Miswak extract is an effective antifungal and antibacterial agent against C. albicans and E. faecalis.

PMID: 20563361 [PubMed - indexed for MEDLINE]

628. Allergy. 2010 Sep;65(9):1073-81. Epub 2010 Jun 17.

Projections of the effects of climate change on allergic asthma: the contribution of aerobiology.

Cecchi L, D'Amato G, Ayres JG, Galan C, Forastiere F, Forsberg B, Gerritsen J, Nunes C, Behrendt H, Akdis C, Dahl R, Annesi-Maesano I.

Interdepartmental Centre of Bioclimatology, University of Florence, Florence, Italy. lorenzo.cecchi@unifi.it

Climate change is unequivocal and represents a possible threat for patients affected by allergic conditions. It has already had an impact on living organisms, including plants and fungi with current scenarios projecting further effects by the end of the century. Over the last three decades, studies have shown changes in production, dispersion and allergen content of pollen and spores, which may be region- and species-specific. In addition, these changes may have been influenced by urban air pollutants interacting directly with pollen. Data suggest an increasing effect of aeroallergens on allergic patients over this period, which may also imply a greater likelihood of the development of an allergic respiratory disease in sensitized subjects and exacerbation of symptomatic patients. There are a number of limitations that make predictions uncertain, and further and specifically designed studies are needed to clarify current effects and future scenarios. We recommend: More stress on pollen/spore exposure in the diagnosis and treatment guidelines of respiratory and allergic diseases; collection of aerobiological data in a structured way at the European level; creation, promotion and support of multidisciplinary research teams in this area; lobbying the European Union and other funders to finance this research.

PMID: 20560904 [PubMed - indexed for MEDLINE]

629. J Asthma. 2010 Jun;47(5):513-20.

Home environmental factors associated with poor asthma control in Montreal children: a population-based study.

Değer L, Plante C, Goudreau S, Smargiassi A, Perron S, Thivierge RL, Jacques L.

Département de santé environnementale et santé au travail, Université de Montréal, Montréal, Canada.

BACKGROUND: Home environmental exposures may aggravate asthma. Few population-based studies have investigated the relationship between asthma control in children and home environmental exposures. Objective: Identify home environmental exposures associated with poor control of asthma among asthmatic children less than 12 years of age in Montreal (Quebec, Canada).
METHODS: This cross-sectional population-based study used data from a respiratory health survey of Montreal children aged 6 months to 12 years conducted in 2006 (n = 7980). Asthma control was assessed (n = 980) using an adaptation of the Canadian asthma consensus report clinical parameters. Using log-binomial regression models, prevalence ratios (PRs) with 95% confidence intervals (95% CIs) were estimated to explore the relationship between inadequate control of asthma and environmental home exposures, including allergens, irritants, mold, and dampness indicators. Subjects with acceptable asthma control were compared with those with inadequate disease control.
RESULTS: Of 980 children with active asthma in the year prior to the survey, 36% met at least one of the five criteria as to poor control of their disease. The population's characteristics found to be related with a lack of asthma control were younger age, history of parental atopy, low maternal education level, foreign-born mothers, and tenant occupancy. After adjustments, children living along high-traffic density streets (PR, 1.35; 95% CI, 1.00-1.81) and those with their bedroom or residence at the basement level (PR, 1.30; 95% CI, 1.01-1.66) were found to be at increased risk of poor asthma control.
CONCLUSIONS: Suboptimal asthma control appears to be mostly associated with traffic, along with mold and moisture conditions, the latter being a more frequent exposure and therefore having a greater public health impact.

PMID: 20560826 [PubMed - indexed for MEDLINE]

630. Nature. 2010 Jun 17;465(7300):956-60.

TFIIA and the transactivator Rap1 cooperate to commit TFIID for transcription initiation.

Papai G, Tripathi MK, Ruhlmann C, Layer JH, Weil PA, Schultz P.

Department of Structural Biology and Genomics, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), 1 rue Laurent Fries, BP10142, 67404 Illkirch, France.

Transcription of eukaryotic messenger RNA (mRNA) encoding genes by RNA polymerase II (Pol II) is triggered by the binding of transactivating proteins to enhancer DNA, which stimulates the recruitment of general transcription factors (TFIIA, B, D, E, F, H) and Pol II on the cis-linked promoter, leading to pre-initiation complex formation and transcription. In TFIID-dependent activation pathways, this general transcription factor containing TATA-box-binding protein is first recruited on the promoter through interaction with activators and cooperates with TFIIA to form a committed pre-initiation complex. However, neither the mechanisms by which activation signals are communicated between these factors nor the structural organization of the activated pre-initiation complex are known. Here we used cryo-electron microscopy to determine the architecture of nucleoprotein complexes composed of TFIID, TFIIA, the transcriptional activator Rap1 and yeast enhancer-promoter DNA. These structures revealed the mode of binding of Rap1 and TFIIA to TFIID, as well as a reorganization of TFIIA induced by its interaction with Rap1. We propose that this change in position increases the exposure of TATA-box-binding protein within TFIID, consequently enhancing its ability to interact with the promoter. A large Rap1-dependent DNA loop forms between the activator-binding site and the proximal promoter region. This loop is topologically locked by a TFIIA-Rap1 protein bridge that folds over the DNA. These results highlight the role of TFIIA in transcriptional activation, define a molecular mechanism for enhancer-promoter communication and provide structural insights into the pathways of intramolecular communication that convey transcription activation signals through the TFIID complex.

PMCID: PMC2900199 PMID: 20559389 [PubMed - indexed for MEDLINE]

631. Mycoses. 2011 Sep;54(5):e330-5. doi: 10.1111/j.1439-0507.2010.01915.x. Epub 2010 Jun 14.

The effect of brief exposure to sub-therapeutic concentrations of chlorhexidine gluconate on germ tube formation of oral Candida dubliniensis.

Ellepola AN.

Department of Bioclinical Sciences, Faculty of Dentistry, Health Sciences Center, Kuwait University, Safat, Kuwait. arjuna@hsc.edu.kw

Adherence of Candida has been implicated as the first step in the pathogenesis of oral candidosis, and germ tube formation, a contributory attribute. While chlorhexidine gluconate is by far the most common antiseptic mouthwash prescribed in dentistry, its intraoral concentration fluctuates considerably because of the dynamics of the oral cavity. Hence, the main objective of this study was to investigate the effect of brief exposure to three different sub-therapeutic concentrations of chlorhexidine gluconate on germ tube formation of Candida dubliniensis. Twelve oral isolates of C. dubliniensis were exposed to three different sub-therapeutic concentrations of 0.005%, 0.0025% and 0.00125% chlorhexidine gluconate for 30 min. The antiseptic was removed, and following subsequent incubation in a germ tube inducing medium, the germ tube formation of these isolates was quantified microscopically. When compared with the controls, brief exposure to 0.005%, 0.0025% and 0.00125% chlorhexidine gluconate suppressed the ability to form germ tubes by 76.53% (P < 0.01), 49.17% (P < 0.01) and 3.45% (P > 0.05) respectively. These findings imply that brief exposure to sub-therapeutic levels of chlorhexidine gluconate may modulate germ tube formation of C. dubliniensis, thereby suppressing its pathogenicity in vivo.

PMID: 20557460 [PubMed - indexed for MEDLINE]

632. Indoor Air. 2010 Aug;20(4):329-40. Epub 2010 Apr 16.

Culturable mold in indoor air and its association with moisture-related problems and asthma and allergy among Swedish children.

Holme J, Hägerhed-Engman L, Mattsson J, Sundell J, Bornehag CG.

Department of Materials and Structures, SINTEF Building and Infrastructure, Norwegian University of Science, and Technology, Trondheim, Norway. jonas.holme@sintef.no

Comment in Indoor Air. 2011 Jun;21(3):264.

In a nested case-control study with 198 children with asthmatic and allergic symptoms (cases) and 202 healthy controls in Värmland, Sweden, we have investigated the relationship between mold spore exposure (mean colony-forming unit) indoor and (i) different indexes of moldy odor indoor (observed by professional inspectors and reported by parents), (ii) visible signs of dampness in the homes of the children (observed and reported), and (iii) doctor-diagnosed asthma/allergy in children. No association was found between the spore concentration indoor and moldy odor and signs of visible dampness in the homes. When a semi-quantitative method in distinguishing between moldy houses or non-moldy houses was used, there were no significant differences between the observed indexes of moldy odor or visible signs of dampness (both observed and reported). No association could be found between the spore concentration in indoor air and asthma/allergy in the children. PRACTICAL IMPLICATIONS: Mold spore exposure indoor have been suggested as a possible explanation for airway problems such as asthma and allergy among people living in buildings with moisture-related problems. However, this investigation could not find any associations between the spore concentrations in indoor air and signs of dampness and moldy odor reported by parents or observed by professional inspectors. Neither was there any association between the indoor spore concentration and asthma/allergy among children. With these results, there is no reason for one-time air sampling of mold colony-forming unit (CFU) in indoor air of homes to identify risk factors for asthma/allergy in children living in Scandinavian countries.

PMID: 20557376 [PubMed - indexed for MEDLINE]

633. J Appl Microbiol. 2010 Oct;109(4):1441-9. doi: 10.1111/j.1365-2672.2010.04775.x. Epub 2010 Jun 10.

Cellular damage induced by a sequential oxidative treatment on Penicillium digitatum.

Cerioni L, Volentini SI, Prado FE, Rapisarda VA, Rodríguez-Montelongo L.

Instituto de Química Biológica Dr Bernabé Bloj, Facultad de Bioquímica, Química y Farmacia and Departamento Bioquímica de la Nutrición, Instituto Superior de Investigaciones Biológicas (CONICET), UNT, Tucumán, Argentina.

AIM: To investigate the cellular damage on Penicillium digitatum produced by a sequential oxidative treatment (SOT), previously standardized in our laboratory, to prevent the conidia growth. Lethal SOT consists of 2-min preincubation with 10 ppm NaClO followed by 2-min incubation with 6 mmol l(-1) CuSO(4) and 100 mmol l(-1) H(2)O(2) at 25°C. METHODS AND RESULTS: After the application of lethal SOT or sublethal SOT (decreasing only the H(2)O(2) concentration), we analysed several conidia features such as germination, oxygen consumption, ultrastructure and integrity of the cellular wall and membrane. Also, we measured the production of reactive oxygen species (ROS) and the content of thiobarbituric acid-reactive species (TBARS). With the increase of H(2)O(2) concentration in the SOT, germination and oxygen consumption of conidia became inhibited, while the membrane permeability, ROS production and TBARS content of conidia increased. Several studies revealed ultrastructural disorganization in P. digitatum conidia after lethal SOT, showing severe cellular damage without apparent damage to the cell wall. In addition, mycelium of P. digitatum was more sensitive than conidia to the oxidative treatment, because growth ceased and permeability of the membranes increased after exposure of the mycelium to a SOT with only 50 mmol l(-1) H(2)O(2) compared to a SOT of 100 mmol l(-1) for these effects to occur on conidia.
CONCLUSION: Our insights into cellular changes produced by the lethal SOT are consistent with the mode of action of the oxidant compounds, by producing both alteration of membrane integrity and intracellular damage. SIGNIFICANCE AND IMPACT OF THE STUDY: Our results allow the understanding of SOT effects on P. digitatum, which will be useful to develop a reliable treatment to control postharvest diseases in view of its future application in packing houses.

PMID: 20553342 [PubMed - indexed for MEDLINE]

634. PLoS Pathog. 2010 Jun 10;6(6):e1000952.

Self-protection against gliotoxin--a component of the gliotoxin biosynthetic cluster, GliT, completely protects Aspergillus fumigatus against exogenous gliotoxin.

Schrettl M, Carberry S, Kavanagh K, Haas H, Jones GW, O'Brien J, Nolan A, Stephens J, Fenelon O, Doyle S.

Department of Biology and National Institute for Cellular Biotechnology, National University of Ireland Maynooth, Maynooth, Co. Kildare, Ireland.

Gliotoxin, and other related molecules, are encoded by multi-gene clusters and biosynthesized by fungi using non-ribosomal biosynthetic mechanisms. Almost universally described in terms of its toxicity towards mammalian cells, gliotoxin has come to be considered as a component of the virulence arsenal of Aspergillus fumigatus. Here we show that deletion of a single gene, gliT, in the gliotoxin biosynthetic cluster of two A. fumigatus strains, rendered the organism highly sensitive to exogenous gliotoxin and completely disrupted gliotoxin secretion. Addition of glutathione to both A. fumigatus Delta gliT strains relieved gliotoxin inhibition. Moreover, expression of gliT appears to be independently regulated compared to all other cluster components and is up-regulated by exogenous gliotoxin presence, at both the transcript and protein level. Upon gliotoxin exposure, gliT is also expressed in A. fumigatus Delta gliZ, which cannot express any other genes in the gliotoxin biosynthetic cluster, indicating that gliT is primarily responsible for protecting this strain against exogenous gliotoxin. GliT exhibits a gliotoxin reductase activity up to 9 microM gliotoxin and appears to prevent irreversible depletion of intracellular glutathione stores by reduction of the oxidized form of gliotoxin. Cross-species resistance to exogenous gliotoxin is acquired by A. nidulans and Saccharomyces cerevisiae, respectively, when transformed with gliT. We hypothesise that the primary role of gliotoxin may be as an antioxidant and that in addition to GliT functionality, gliotoxin secretion may be a component of an auto-protective mechanism, deployed by A. fumigatus to protect itself against this potent biomolecule.

PMCID: PMC2883607 PMID: 20548963 [PubMed - indexed for MEDLINE]

635. Infect Immun. 2010 Sep;78(9):3861-70. Epub 2010 Jun 14.

Immunomodulatory effects of serotype B glucuronoxylomannan from Cryptococcus gattii correlate with polysaccharide diameter.

Fonseca FL, Nohara LL, Cordero RJ, Frases S, Casadevall A, Almeida IC, Nimrichter L, Rodrigues ML.

Instituto de Microbiologia, UFRJ, Rio de Janeiro, RJ, Brazil, 21941-902.

Glucuronoxylomannan (GXM), the major capsular component in the Cryptococcus complex, interacts with the immune system in multiple ways, which include the activation of Toll-like receptors (TLRs) and the modulation of nitric oxide (NO) production by phagocytes. In this study, we analyzed several structural parameters of GXM samples from Cryptococcus neoformans (serotypes A and D) and Cryptococcus gattii (serotypes B and C) and correlated them with the production of NO by phagocytes and the activation of TLRs. GXM fractions were differentially recognized by TLR2/TLR1 (TLR2/1) and TLR2/6 heterodimers expressed on TLR-transfected HEK293A cells. Higher NF-kappaB luciferase reporter activity induced by GXM was observed in cells expressing TLR2/1 than in cells transfected with TLR2/6 constructs. A serotype B GXM from C. gattii was the most effective polysaccharide fraction activating the TLR-mediated response. This serotype B polysaccharide, which was also highly efficient at eliciting the production of NO by macrophages, was similar to the other GXM samples in monosaccharide composition, zeta potential, and electrophoretic mobility. However, immunofluorescence with four different monoclonal antibodies and dynamic light-scattering analysis revealed that the serotype B GXM showed particularities in serological reactivity and had the smallest effective diameter among the GXM samples analyzed in this study. Fractionation of additional serotype B GXMs, followed by exposure of these fractions to macrophages, revealed a correlation between NO production and reduced effective diameters. Our results demonstrate a great functional diversity in GXM samples from different isolates and establish their abilities to differentially activate cellular responses. We propose that serological properties as well as physical chemical parameters, such as the diameter of polysaccharide molecules, may potentially influence the inflammatory response against Cryptococcus spp. and may contribute to the differences in granulomatous inflammation between cryptococcal species.

PMCID: PMC2937472 PMID: 20547742 [PubMed - indexed for MEDLINE]

636. Water Res. 2010 Jul;44(14):4137-42. Epub 2010 Jun 1.

Poor elimination rates in waste water treatment plants lead to continuous emission of deoxynivalenol into the aquatic environment.

Wettstein FE, Bucheli TD.

Agroscope Reckenholz-Tänikon, Research Station ART, Reckenholzstrasse 191, 8046 Zürich, Switzerland.

Deoxynivalenol (DON) is one of the most prominent mycotoxins generated by fungi of the generus Fusarium on crops. Its presence in surface waters was recently demonstrated. Here, we elucidate the occurrence and behaviour of DON in three Swiss waste water treatment plants (WWTP) as a result of human consumption and excretion. DON was shown to be omnipresent in the primary effluent samples of these WWTP in concentrations from 32 to 118 ng/L. Corresponding loads were a factor of 1.3-2.3 higher than predicted based on human excretion data from the literature. DON elimination rates in WWTP ranged from 33 to 57%. These rather low percentages were confirmed with a further, more detailled study conducted at WWTP Kloten/Opfikon (average elimination rate 32%). The relative importance of WWTP as a source of DON in surface waters was compared with agricultural emissions due to runoff from Fusarium infected crops. Both sources seem to contribute equally to the total DON exposure of surface waters of a few ng/L, however, their input dynamics vary considerably in space and time.

PMID: 20547404 [PubMed - indexed for MEDLINE]

637. Int J Radiat Biol. 2010 Jul;86(7):602-11.

Effect of 2.45 mT sinusoidal 50 Hz magnetic field on Saccharomyces cerevisiae strains deficient in DNA strand breaks repair.

Ruiz-Gómez MJ, Sendra-Portero F, Martínez-Morillo M.

Laboratory of Radiobiology, Department of Radiology and Physical Medicine, Faculty of Medicine, University of Malaga, Malaga, Spain. mjrg@uma.es

PURPOSE: To investigate whether extremely-low frequency magnetic field (MF) exposure produce alterations in the growth, cell cycle, survival and DNA damage of wild type (wt) and mutant yeast strains. MATERIALS AND METHODS: wt and high affinity DNA binding factor 1 (hdf1), radiation sensitive 52 (rad52), rad52 hdf1 mutant Saccharomyces cerevisiae strains were exposed to 2.45 mT, sinusoidal 50 Hz MF for 96 h. MF was generated by a pair of Helmholtz coils. During this time the growth was monitored by measuring the optical density at 600 nm and cell cycle evolution were analysed by microscopic morphological analysis. Then, yeast survival was assayed by the drop test and DNA was extracted and electrophoresed.
RESULTS: A significant increase in the growth was observed for rad52 strain (P = 0.005, Analysis of Variance [ANOVA]) and close to significance for rad52 hdf1 strain (P = 0.069, ANOVA). In addition, the surviving fraction values obtained for MF-exposed samples were in all cases less than for the controls, being the P value obtained for the whole set of MF-treated strains close to significance (P = 0.066, Student's t-test). In contrast, the cell cycle evolution and the DNA pattern obtained for wt and the mutant strains were not altered after exposure to MF.
CONCLUSIONS: The data presented in the current report show that the applied MF (2.45 mT, sinusoidal 50 Hz, 96 h) induces alterations in the growth and survival of S. cerevisiae strains deficient in DNA strand breaks repair. In contrast, the MF treatment does not induce alterations in the cell cycle and does not cause DNA damage.

PMID: 20545572 [PubMed - indexed for MEDLINE]

638. J Hosp Infect. 2010 Sep;76(1):56-9. Epub 2010 Jun 9.

Point-of-use filtration method for the prevention of fungal contamination of hospital water.

Warris A, Onken A, Gaustad P, Janssen W, van der Lee H, Verweij PE, Abrahamsen TG.

Department of Pediatrics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. a.warris@cukz.umcn.nl

Published data implicate hospital water as a potential source of opportunistic fungi that may cause life-threatening infections in immunocompromised patients. Point-of-care filters are known to retain bacteria, but little is known about their efficacy in reducing exposure to moulds. We investigated the effect of point-of-use filters (Pall-Aquasafe) on the level of contamination of Aspergillus fumigatus and other filamentous fungi. The point-of-use filters were applied to several outlets (taps and showers) on the paediatric bone marrow transplantation (BMT) unit of the National Hospital in Oslo, Norway. In addition the efficacy was investigated using a test rig. The laboratory experiments showed that the filters were highly effective in reducing the number of colony-forming units for a period of at least 15 days. In the BMT unit the filters eliminated the fungi from the water on day 1 but due to particles present in the water the filters occluded, which prevented further evaluations. Our results show that point-of-use filtration might be an effective preventive measure to eliminate filamentous fungi at individual points of water use, thereby reducing patients' exposure.

PMID: 20542590 [PubMed - indexed for MEDLINE]

639. Am J Respir Crit Care Med. 2010 Oct 1;182(7):884-9. Epub 2010 Jun 10.

Fungal exposure modulates the effect of polymorphisms of chitinases on emergency department visits and hospitalizations.

Wu AC, Lasky-Su J, Rogers CA, Klanderman BJ, Litonjua AA.

Department of Population Medicine, Harvard Pilgrim Health Care Institute and Harvard Medical School, Boston, Massachusetts, USA. ann.wu@childrens.harvard.edu

RATIONALE: Chitinases are enzymes that cleave chitin, which is present in fungal cells. Two types of human chitinases, chitotriosidase and acidic mammalian chitinase, and the chitinase-like protein, YKL-40, seem to play an important role in asthma. We hypothesized that exposure to environmental fungi may modulate the effect of chitinases in individuals with asthma. OBJECTIVES: To explore whether interactions between high fungal exposure and common genetic variants in the two chitinases in humans, CHIT1 and CHIA, and the chitinase 3-like 1 gene, CHI3L1, are associated with severe asthma exacerbations and other asthma-related outcomes.
METHODS: Forty-eight single nucleotide polymorphisms (SNPs) in CHIT1, CHIA, and CHI3L1 and one CHIT1 duplication were genotyped in 395 subjects and their parents as part of the Childhood Asthma Management Program. Household levels of mold (an index of fungal exposure) were determined on house dust samples. We conducted family-based association tests with gene-environment interactions. Our outcome was severe exacerbation, defined as emergency department visits and hospitalizations from asthma over a 4-year period, and our secondary outcomes included indices of lung function and allergy-related phenotypes. MEASUREMENTS AND MAIN RESULTS: Of the 395 subjects who had mold levels at randomization, 24% (95 subjects) had levels that were greater than 25,000 units per gram of house dust (high mold exposure). High mold exposure significantly modified the relation between three SNPs in CHIT1 (rs2486953, rs4950936, and rs1417149) and severe exacerbations (P for interaction 0.0010 for rs2486953, 0.0008 for rs4950936, and 0.0005 for rs1417149). High mold exposure did not significantly modify the relationship between any of the other variants and outcomes.
CONCLUSIONS: Environmental exposure to fungi, modifies the effect of CHIT1 SNPs on severe asthma exacerbations.

PMCID: PMC2970860 PMID: 20538957 [PubMed - indexed for MEDLINE]

640. Mol Oral Microbiol. 2010 Jun;25(3):215-25.

Candida albicans induces early apoptosis followed by secondary necrosis in oral epithelial cells.

Villar CC, Zhao XR.

Department of Periodontics, The University of Texas, Health Science Center at San Antonio, San Antonio, TX 78229-3900, USA. villar@uthscsa.edu

The capacity of Candida albicans to invade and damage oral epithelial cells is critical for its ability to establish and maintain symptomatic oropharyngeal infection. Although oral epithelial cells are reported dead after 18 h of candidal infection, activation of specific epithelial cell-death pathways in response to C. albicans infection has not yet been demonstrated. Considering the key role of oral epithelial cell damage in the pathogenesis of oropharyngeal candidiasis, the aim of this study was to characterize this event during infection. Using an oral epithelial-C. albicans co-culture system, we examined the ability of C. albicans to induce classic necrotic, pyroptotic and apoptotic cellular alterations in oral epithelial cells such as osmotic lysis, exposure of phosphatidylserine on the epithelial cell plasma membrane and internucleosomal DNA fragmentation. It was found that the ability of C. albicans to kill oral epithelial cells depends on its capacity to physically interact with and invade these cells. Caspase-dependent apoptotic pathways were activated early during C. albicans infection and contributed to C. albicans-induced oral epithelial cell death. Earlier apoptotic events were followed by necrotic death of infected oral epithelial cells. Hence, C. albicans stimulates oral epithelial signaling pathways that promote early apoptotic cell death through the activation of cellular caspases, followed by late necrosis.

PMID: 20536749 [PubMed - indexed for MEDLINE]

641. J Biomater Sci Polym Ed. 2010;21(10):1359-70. Epub 2010 Jun 8.

Antimicrobial/Antimold polymer-grafted starches for recycled cellulose fibers.

Ziaee Z, Qian L, Guan Y, Fatehi P, Xiao H.

Department of Chemical Engineering, University of New Brunswick, Fredericton, NB, Canada.

In this work, an antimicrobial guanidine polymer (PHGH) was grafted onto starch as a carrier to form branched or grafted chains along the starch backbone. This grafting improved the antimicrobial properties and the adsorption of the starch on recycled cellulose fibers. Similar work was also conducted on bleached sulfite fibers for comparison. The results showed that the starch, grafted with 12 wt% PHGH, adsorbed more on recycled fibers than on sulfite fibers. By applying the antimicrobial-modified starch to recycled or sulfite pulps up to 20 mg/g, both antimicrobial and antimold performances of the papers were improved substantially. Additionally, the PHGH-modified starch increased the tensile index of papers, but decreased the tear index slightly. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) were employed to investigate the morphologic changes of Escherichia coli bacteria and Chaetomium globosum fungi upon exposure to the PHGH-modified starch, thus demonstrating that the antimicrobial mechanism is based on the damage of bacterial membrane.

PMID: 20534190 [PubMed - indexed for MEDLINE]

642. Annu Rev Microbiol. 2010;64:585-610.

Fungi, hidden in soil or up in the air: light makes a difference.

Rodriguez-Romero J, Hedtke M, Kastner C, Müller S, Fischer R.

Karlsruhe Institute of Technology, Institute for Applied Biosciences, Department of Microbiology, D-76187 Karlsruhe, Germany.

Light is one of the most important environmental factors for orientation of almost all organisms on Earth. Whereas light sensing is of crucial importance in plants to optimize light-dependent energy conservation, in nonphotosynthetic organisms, the synchronization of biological clocks to the length of a day is an important function. Filamentous fungi may use the light signal as an indicator for the exposure of hyphae to air and adapt their physiology to this situation or induce morphogenetic pathways. Although a yes/no decision appears to be sufficient for the light-sensing function in fungi, most species apply a number of different, wavelength-specific receptors. The core of all receptor types is a chromophore, a low-molecular-weight organic molecule, such as flavin, retinal, or linear tetrapyrrols for blue-, green-, or red-light sensing, respectively. Whereas the blue-light response in fungi is one of the best-studied light responses, all other light-sensing mechanisms are less well studied or largely unknown. The discovery of phytochrome in bacteria and fungi in recent years not only advanced the scientific field significantly, but also had great impact on our view of the evolution of phytochrome-like photoreceptors.

PMID: 20533875 [PubMed - indexed for MEDLINE]

643. Surg Infect (Larchmt). 2010 Jun;11(3):325-31.

Current risks of occupational blood-borne viral infection.

Mohebati A, Davis JM, Fry DE.

Department of Surgery, University of Medicine and Dentistry of New Jersey, Newark, New Jersey, USA.

BACKGROUND: Human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and other viruses remain occupational risks for both surgeons and patients in the operating room environment. In the past, this concern attracted great attention, but recently, this subject has been given much less attention.
METHODS: Review of the literature over the past 50 years on occupational risks of viral infection in the operating room.
RESULTS: Transmission of HIV still looms as a potential pathogen in the operating room, but no case has been documented in the United States. Infection with HBV can be prevented by a safe and effective vaccine. Chronic HCV infection is present in more than three million U.S. residents and remains a risk that can be managed only by adhering to strict infection control practices and avoiding blood exposure.
CONCLUSIONS: The risks of viral infection in the operating room remain the same as a decade ago even though attention to this issue has waned. The avoidance of blood exposure to prevent transmission of both known and unknown blood-borne pathogens continues to be a goal for all surgeons.

PMID: 20528133 [PubMed - indexed for MEDLINE]

644. Asian Pac J Allergy Immunol. 2010 Mar;28(1):53-7.

The stability and sterility of epinephrine prefilled syringe.

Kerddonfak S, Manuyakorn W, Kamchaisatian W, Sasisakulporn C, Teawsomboonkit W, Benjaponpitak S.

Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

The commercially available auto-injector epinephrine is considerable expensive. Epinephrine prefilled syringe is an alternative treatment for anaphylaxis patients. The objective of the present study was to evaluate the stability and sterility of epinephrine prefilled syringe. Epinephrine prefilled syringe was kept in the pencil box to prevent from light exposure. The active ingredients, integrity and level of potency were measured by high-performance liquid chromatography (HPLC). The sterility was accessed by aerobic bacteria and fungi culture. The epinephrine concentration at 1, 2 and 3 months after the preparation was 101.36, 99.31 and 101.09%, respectively (acceptable range 90 - 110%). The pH was 3.17 - 3.23 (acceptable range 2.8 - 3.6). Nor-epinephrine was undetected. The cultures for bacteria and fungus were both negative. Consequently, epinephrine prefilled syringe was stable and sterile at least three month after preparation. Epinephrine prefilled syrine is an alternative low cost treatment for anaphylaxis patient.

PMID: 20527517 [PubMed - indexed for MEDLINE]

645. Vet Rec. 2010 Jun 5;166(23):730.

Exposure to Encephalitozoon cuniculi in rabbits with dental disease.

Lewis W.

Comment in Vet Rec. 2010 Jun 26;166(26):832; author reply 832.

Comment on Vet Rec. 2004 Oct 9;155(15):443.

PMID: 20525957 [PubMed - indexed for MEDLINE]

646. Mycologia. 2010 May-Jun;102(3):552-9.

Anticryptococcal cytotoxicity of murine nonadherent cells is perforin and nonperforin mediated.

Petković L, Arsenijević VA, Skvarc M, Kopitar A, Kotnik V, Simicic S, Wraber B, Matos T, Ihan A.

Institute of Microbiology and Immunology, Faculty of Medicine, University of Belgrade, Dr Subotića 1, 11 000 Belgrade, Serbia. pljub@yahoo.com

The encapsulated fungal pathogen Cryptococcus neoformans is a significant agent of life-threatening infections, particularly in people with suppressed cell-mediated immunity. The cellular cytotoxicity against C. neoformans infection is mainly mediated by NK and T cells, but effector mechanisms are not well understood. The objective of this study was (i) to determine whether prior exposure to the cryptococcal antigens enhances anticryptococcal activity of cytotoxic cells in mice and (ii) the contribution of perforin- and nonperforin-mediated cytotoxicity of NK and T cells in growth inhibition of C. neoformans. Our data showed that in vitro exposure of nonadherent (NA) spleen mononuclear cells from nonimmunized mice to heat-killed C. neoformans strain Cap67 unencapsulated mutant of B3501 (Ag1) or its supernatant (Ag2) demonstrated higher anticryptococcal activity. This effector mechanism can be enhanced further after immunization with either Ag1 or Ag2. There is a synergistic effect of immunization and in vitro incubation of the NA cells with the same antigens. Concanamycin A (CMA) and strontium chloride (SrCl2) inhibition assays were performed to clarify the contribution of perforin- and nonperforin-mediated anticryptococcal cytotoxicity of NA cells in these events. Treatment with these inhibitors demonstrated that anticryptococcal cytotoxicity of nonprimed NA cells was primarily perforin mediated. Anticryptococcal activity of the NA cells obtained from immunized mice after in vitro incubation with cryptococcal antigens was both perforin and nonperforin mediated. Taken together these data demonstrate that in mice a nonperforin-mediated pathway of anticryptococcal cytotoxicity can be induced by immunization. Further research is needed to examine their potential role for human vaccines strategies and/or therapies.

PMID: 20524588 [PubMed - indexed for MEDLINE]

647. PLoS One. 2010 May 26;5(5):e10846.

A chemical genetic screen for modulators of asymmetrical 2,2'-dimeric naphthoquinones cytotoxicity in yeast.

Emadi A, Ross AE, Cowan KM, Fortenberry YM, Vuica-Ross M.

Department of Internal Medicine and Oncology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.

BACKGROUND: Dimeric naphthoquinones (BiQ) were originally synthesized as a new class of HIV integrase inhibitors but have shown integrase-independent cytotoxicity in acute lymphoblastic leukemia cell lines suggesting their use as potential anti-neoplastic agents. The mechanism of this cytotoxicity is unknown. In order to gain insight into the mode of action of binaphthoquinones we performed a systematic high-throughput screen in a yeast isogenic deletion mutant array for enhanced or suppressed growth in the presence of binaphthoquinones. METHODOLOGY/PRINCIPAL FINDINGS: Exposure of wild type yeast strains to various BiQs demonstrated inhibition of yeast growth with IC(50)s in the microM range. Drug sensitivity and resistance screens were performed by exposing arrays of a haploid yeast deletion mutant library to BiQs at concentrations near their IC(50). Sensitivity screens identified yeast with deletions affecting mitochondrial function and cellular respiration as having increased sensitivity to BiQs. Corresponding to this, wild type yeast grown in the absence of a fermentable carbon source were particularly sensitive to BiQs, and treatment with BiQs was shown to disrupt the mitochondrial membrane potential and lead to the generation of reactive oxygen species (ROS). Furthermore, baseline ROS production in BiQ sensitive mutant strains was increased compared to wild type and could be further augmented by the presence of BiQ. Screens for resistance to BiQ action identified the mitochondrial external NAD(P)H dehydrogenase, NDE1, as critical to BiQ toxicity and over-expression of this gene resulted in increased ROS production and increased sensitivity of wild type yeast to BiQ. CONCLUSIONS/SIGNIFICANCE: In yeast, binaphthoquinone cytotoxicity is likely mediated through NAD(P)H:quonine oxidoreductases leading to ROS production and dysfunctional mitochondria. Further studies are required to validate this mechanism in mammalian cells.

PMCID: PMC2877097 PMID: 20520766 [PubMed - indexed for MEDLINE]

648. J Microbiol Biotechnol. 2010 May;20(5):946-9.

Specific expression patterns of xyl1, xyl2 and xyl3 in response to different sugars in Pichia stipitis.

Han JH, Park JY, Kang HW, Choi GW, Chung BW, Min J.

Department of Bioprocess Engineering, Chonbuk National University, Jeonju, Korea.

The effects of two different sugars (glucose and xylose) on the expression levels and patterns of xylose reductase (xyl1), xylitol dehydrogenase (xyl2) and xylulokinase (xyl3) genes were analyzed using Pichia stipitis. A significant increase in mRNA levels of xyl1 was observed after 6 hours growth in culture conditions using xylose as a sole carbon source, but expressions of the three genes were not influenced by normal culture media with glucose. In addition expression levels of xyl2 and xyl3 were not observed during the entire culture period during which xylose was added. It also was found that the expression level of xyl1 increased as a function of the xylose concentration (40, 60, 80 g/l) used in this study, indicating that xyl1 expression sensitively responded to xylose presence in the culture media. Although the induced level of xyl2 increased slightly after 48 hours in the xylose-supplemented culture conditions, the expression level of xyl2 was not observed in the xylitol-supplemented culture conditions. Finally, considering the expression of each gene in response to glucose or xylose, the absolute expression levels of the three genes indicate that xyl1 is induced primarily by exposure to xylose.

PMID: 20519920 [PubMed - indexed for MEDLINE]

649. Mol Biol Cell. 2010 Aug 1;21(15):2624-38. Epub 2010 Jun 2.

Defects in the secretory pathway and high Ca2+ induce multiple P-bodies.

Kilchert C, Weidner J, Prescianotto-Baschong C, Spang A.

Biozentrum, Growth and Development, University of Basel, CH-4056 Basel, Switzerland.

mRNA is sequestered and turned over in cytoplasmic processing bodies (PBs), which are induced by various cellular stresses. Unexpectedly, in Saccharomyces cerevisiae, mutants of the small GTPase Arf1 and various secretory pathway mutants induced a significant increase in PB number, compared with PB induction by starvation or oxidative stress. Exposure of wild-type cells to osmotic stress or high extracellular Ca(2+) mimicked this increase in PB number. Conversely, intracellular Ca(2+)-depletion strongly reduced PB formation in the secretory mutants. In contrast to PB induction through starvation or osmotic stress, PB formation in secretory mutants and by Ca(2+) required the PB components Pat1 and Scd6, and calmodulin, indicating that different stressors act through distinct pathways. Consistent with this hypothesis, when stresses were combined, PB number did not correlate with the strength of the translational block, but rather with the type of stress encountered. Interestingly, independent of the stressor, PBs appear as spheres of approximately 40-100 nm connected to the endoplasmic reticulum (ER), consistent with the idea that translation and silencing/degradation occur in a spatially coordinated manner at the ER. We propose that PB assembly in response to stress occurs at the ER and depends on intracellular signals that regulate PB number.

PMCID: PMC2912349 PMID: 20519435 [PubMed - indexed for MEDLINE]

650. Am J Vet Res. 2010 Jun;71(6):682-9.

Experimental induction of recurrent airway obstruction with inhaled fungal spores, lipopolysaccharide, and silica microspheres in horses.

Beeler-Marfisi J, Clark ME, Wen X, Sears W, Huber L, Ackerley C, Viel L, Bienzle D.

Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada.

OBJECTIVE: To evaluate experimental induction of recurrent airway obstruction (RAO) with inhaled fungal spores, lipopolysaccharide, and silica microspheres in horses. ANIMALS: 7 horses with and 3 horses without a history of RAO. PROCEDURES: RAO-susceptible horses ranged in age from 17 to approximately 30 years, and control horses ranged in age from 7 to approximately 15 years. Pure mold cultures were derived from repeated culture of hay and identified via gene amplification and sequencing. Pulmonary function testing and bronchoalveolar lavage were performed before and after nebulization with a suspension of spores derived from 3 fungi, lipopolysaccharide, and 1-microm silica microspheres in all horses. This was followed by a 4-month washout period and a further pulmonary function test followed by saline (0.9% NaCl) solution challenge and bronchoalveolar lavage.
RESULTS: Lichtheimia corymbifera, Aspergillus fumigatus, and Eurotium amstelodami were consistently identified in cultures of moldy hay. Nebulization with fungal spores, lipopolysaccharide, and microspheres induced significant increases in pleural pressure in RAO-susceptible but not control horses. Airway neutrophilia developed in both groups of horses with exposure to challenge material but more severely in RAO-susceptible horses. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that inhalation of fungal spores in combination with lipopolysaccharide and silica microspheres can induce disease exacerbation in susceptible horses and may thus be a useful model for future standardized studies of RAO in horses.

PMID: 20513185 [PubMed - indexed for MEDLINE]

651. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2010 Aug;27(8):1153-60.

Modification of aflatoxin B1 and ochratoxin A toxicokinetics in rats administered a yeast cell wall preparation.

Firmin S, Gandia P, Morgavi DP, Houin G, Jouany JP, Bertin G, Boudra H.

INRA, UR1213 Herbivores, Site de Theix, F-63122 Saint Genès-Champanelle, France.

The cell wall of Saccharomyces cerevisiae can bind mycotoxins in vitro, but there is scarce information on whether this property decreases the absorption of mycotoxins in vivo. The effect of a yeast cell wall preparation (YCW) on toxicokinetics and balance excretion (urine and faeces) of aflatoxin B(1) (AFB1) and ochratoxin A (OTA) was tested in rats after oral administration of each toxin. The (3)H-labelled mycotoxins were used at low doses. Co-administration of YCW with AFB1 decreased the extent, but not the rate, of absorption. Concurrently, radioactivity excreted in faeces increased by up to 55% when compared with controls, whilst the excretion in urine decreased (p < 0.05). The effect of YCW on OTA was less marked, although it increased radioactivity excretion in faeces (up to 16%; p < 0.05) it did not result in changes in urine and toxicokinetic parameters. The in vivo effect is in agreement with the reported in vitro binding ability for these toxins (AFB1 > OTA). In conclusion, these results indicate that YCW could be used to protect monogastric animals against exposure to low dietary levels of selected mycotoxins.

PMID: 20512710 [PubMed - indexed for MEDLINE]

652. Infect Control Hosp Epidemiol. 2010 Jul;31(7):748-54.

Population risk of syringe reuse: estimating the probability of transmitting bloodborne disease.

Sikora C, Chandran AU, Joffe AM, Johnson D, Johnson M.

Community Medicine Residency Program, School of Public Health, University of Alberta, Edmonton, Canada. csikora@ualberta.ca

BACKGROUND: In 2008, the Medical Officer of Health at Alberta Health Services (Edmonton, Canada) was notified that, in some practice settings, a syringe was used to administer medication through the side port of an intravenous circuit and then the syringe, with residual drug, was used to administer medication to other patients in the same manner. This practice has been implicated in several outbreaks of bloodborne infection in hospital and clinic settings.
METHODS: A risk assessment model was developed to predict the risk of a patient contracting a bloodborne viral infection from the practice. The risk of transmission was defined as the product of 5 factors: (1) the population prevalence of a specific bloodborne pathogen, (2) the probability of finding a viral bloodborne pathogen in an intravenous circuit, (3) the rate of syringe reuse, (4) the probability of causing disease given a bloodborne pathogen exposure, and (5) the susceptibility of the exposed person.
RESULTS: The risk was modeled first with consistent use of the proximal port of the intravenous circuit. The risk of transmission of hepatitis B virus was approximately 12-53 transmission events per 1,000,000 exposure events for a range of practice probabilities (ie, frequency of the risk practice) from 20% to 80%, respectively. The risk of transmission of hepatitis C virus was approximately 1.0-4.3 transmission events per 1,000,000 exposure events for the same practice probability range, and the risk of transmission of human immunodeficiency virus was approximately 0.03-0.15 transmission events per 1,000,000 exposure events for the same practice probability range. The use of the distal port was associated with a 10-fold decrease in the risk.
CONCLUSIONS: Practitioners must practice safe, aseptic injection techniques. The model presented here can be used to estimate the risk of disease transmission in situations where reuse has occurred and can serve as a framework for informing public health action.

PMID: 20509761 [PubMed - indexed for MEDLINE]

653. Med Pr. 2010;61(2):133-41.

[Fungal allergy among art conservators: prevalence, risk factors and clinical symptoms].

[Article in Polish]

Wiszniewska M, Swierczyńska-Machura D, Cezary P, Walusiak-Skorupa J.

Instytut Medycyny Pracy im. prof. J. Nofera, Klinika Chorób Zawodowych i Toksykologi, Łódź. martaz@imp.lodz.pl

BACKGROUND: The aim of the study was to evaluate the prevalence of hypersensitivity to fungi among art conservators and museum workers. MATERIAL AND METHODS: 200 art conservators and museum workers were examined using a questionnaire, skin prick tests to common mite and fungal allergens. Moreover, the level of serum specific IgE to fungi were evaluated, and rest spirometry was performed in all subjects.
RESULTS: The most frequent symptoms reported by the examined subjects were: rhinitis (N=132, 66%), conjunctivitis (N=137, 68.5%), skin symptoms (N=108, 54%), chronic cough (N=52, 26%) and dyspnoea (N=56, 28%). 69 subjects (34.5%) developed symptoms during work with objects contaminated by biological agents. 90 art conservators and museum workers (46.2%) were sensitized to at least one of common allergens, and 47 (23.5%) to fungal allergens. Specific IgE to fungi were found in 14 (7%) cases, most frequently to Candida albicans and Penicillium notatum, Cladosporium herbarum, Aspergillus fumigatus, Alternaria alternata.
CONCLUSIONS: 85% of art conservators and museum workers reported allergic symptoms. Cladosporium, Alternaria and Yeats were the species that played the most important role in the development of fungal hypersensitivity among art conservators and museum workers. Duration of occupational exposure of more than 5 years, presence of domestic animals especially a cat at home, elevated total IgE level, allergic rhinitis and skin hyperreactivity to common allergens (grass pollens and mites) are significant risk factors for the development of hypersensitivity to fungi among art conservators and museum workers.

PMID: 20509551 [PubMed - indexed for MEDLINE]

654. Hum Exp Toxicol. 2011 Apr;30(4):307-17. Epub 2010 May 27.

Mushroom lectin protects arsenic induced apoptosis in hepatocytes of rodents.

Rana T, Bera AK, Das S, Bhattacharya D, Pan D, Bandyopadhyay S, De S, Das SK.

Indian Veterinary Research Institute, Eastern Regional Station, 37, Belgachia Road, Kolkata, India.

Acute and chronic arsenic exposure result in toxicity both in human and animal beings and cause many hepatic and renal manifestations. The present study stated that mushroom lectin prevents arsenic-induced apoptosis. Apoptosis was measured by morphological alterations, cell proliferation index (CPI), phagocytic activity (nitro blue tetrazolium index; NBT), nitric oxide (NO) production, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, DNA fragmentation and caspase-3 activity. Arsenic exposure at 5 μM in the form of sodium arsenite resulted in significant elevation of deformed cells, NO production, TUNEL stained nuclei of hepatocytes, DNA fragmentation and caspase-3 activity. But the CPI and NBT index were significantly declined in arsenic-treated hepatocytes. The beneficial effect of mushroom lectin at 10 μg/mL, 20 μg/mL and 50 μg/mL) showed increased CPI and phagocytic activity. Mushroom lectin at those concentrations reduced deformed cells, NO production, DNA fragmentation and caspase-3 activity of hepatocytes. But significant better protection was observed in 50 μg/mL mushroom lectin-treated hepatocytes. This finding may be of therapeutic benefit in people suffering from chronic arsenic exposure.

PMID: 20507870 [PubMed - indexed for MEDLINE]

655. Diagn Mol Pathol. 2010 Jun;19(2):99-104.

In situ hybridization for Coccidioides immitis 5.8S ribosomal RNA sequences in formalin-fixed, paraffin-embedded pulmonary specimens using a locked nucleic acid probe: a rapid means for identification in tissue sections.

Montone KT, Litzky LA, Feldman MD, Peterman H, Mathis B, Baliff J, Kaiser LR, Kucharczuk J, Nachamkin I.

Department of Pathology and Laboratory Medicine, Division of Thoracic Surgery, University of Pennsylvania, Philadelphia, PA 19104, USA. kmontone@mail.med.upenn.edu

Coccidioides immitis/Coccidioides posadasii are common causes of pulmonary infection in certain geographic areas, and are highly infectious when working with culture isolates in the laboratory. Rapid techniques to accurately identify this pathogen in tissues may be of benefit for diagnosis and in limiting the exposure of laboratory personnel to this agent. Locked nucleic acids (LNA) are modified nucleotides in which a ribonucleoside is linked between the 2'-oxygen and the 4'-carbon atoms with a methylene unit. LNA oligonucleotides exhibit increased thermal stability and make excellent probes for in situ hybridization (ISH). In this study, ISH utilizing a biotin-labeled LNA probe targeting Coccidioides sp. ribosomal RNA sequences in 6 formalin-fixed, paraffin-embedded pulmonary tissue specimens from 6 patients with culture positive or histologic findings suggestive of Coccidioides sp. infection is described. The cultures of the pulmonary specimens confirmed C. immitis in 3 of 6 patients. The ISH procedure with the LNA probe was positive in all 6 cases, although the number of organisms that were highlighted varied from rare to numerous. ISH with a biotin-labeled DNA probe of the same sequence was positive in 4 of the 6 cases and the signal intensity and number of organisms was much less than that observed with the LNA probe. Negative control tissues containing a variety of different fungal pathogens including Aspergillus sp., Fusarium sp., Blastomyces dermatitidis, Candida sp, Histoplasma capsulatum, and Zygomyces did not hybridize with the LNA and DNA probes. ISH with an LNA oligonucleotide probe targeting Coccidioides sp. ribosomal RNA is useful for rapid ISH. ISH could be rapidly performed when fungal pathogens are observed in tissue but cultures are negative or have not been performed.

PMID: 20502187 [PubMed - indexed for MEDLINE]

656. Parasitol Res. 2010 Aug;107(3):651-5. Epub 2010 May 25.

Pathogenicity of Fusarium oxysporum against the larvae of Culex quinquefasciatus (Say) and Anopheles stephensi (Liston) in laboratory.

Prakash S, Singh G, Soni N, Sharma S.

Department of Zoology, Environmental and Advanced Parasitology and Vector Control Biotechnology Laboratories, Dayalbagh Educational Institute, Dayalbagh, Agra, India. soamprakash@indiatimes.com

The entomopathogenic fungi Fusarium oxysporum are the next generation mosquito controlling agent. F. oxysporum basically contains unique toxin and can be a selectively good agent in tropical countries. We are reporting here the efficacy of the metabolites of F. oxysporum against the larvae of Anopheles stephensi and Culex quinquefasciatus in the laboratory. F. oxysporum was grown on Czapek Dox broth. The bioassays were run at five different concentrations (1.30, 1.60, 1.77, 1.90, and 2.00 ppm). The LC(50), LC(90), and LC(99) values with 95% fiducial limits and probit equations were calculated by probit analysis. The mortality was observed after 24, 48, and 72 h against all instars. The LC(90) values in the case of C. quinquefasciatus after 48 h when calculated were 1.85, 1.92, 1.87, and 1.87 ppm, respectively, while LC(99) values calculated were 2.24, 2.25, 2.18, and 2.19 ppm. Moreover, after 48 h in the case of A. stephensi, the LC(50) values for the first, second, third, and fourth instars were recorded as 1.48, 1.51, 1.71, and 1.50 ppm, respectively. The LC(90) values recorded were 1.88, 1.91, 1.93, and 1.89 ppm and LC(99) values observed were 2.36, 2.23, 2.26, and 2.21 ppm. The results obtained 24, 48, and 72 h have been compared and it was observed significantly that 48 h after exposure the metabolite has more pathogenicity. The results of the metabolites of F. oxysporum may be considered as a new bio-control agent for vector mosquitoes if the field trial succeeds.

PMID: 20499096 [PubMed - indexed for MEDLINE]

657. Antimicrob Agents Chemother. 2010 Aug;54(8):3149-54. Epub 2010 May 24.

Risk factors for fluconazole-resistant candidemia.

Garnacho-Montero J, Díaz-Martín A, García-Cabrera E, Ruiz Pérez de Pipaón M, Hernández-Caballero C, Aznar-Martín J, Cisneros JM, Ortiz-Leyba C.

Critical Care and Emergency Department, Intensive Care Unit, Virgen del Rocío University Hospital, Avenida Manuel Siurot s/n, Seville 41013, Spain. jose.garnacho.sspa@juntadeandalucia.es

Previous studies have sought to determine the risk factors associated with candidemia caused by non-albicans Candida spp. or with potentially fluconazole-resistant Candida spp. (C. glabrata and C. krusei). Non-albicans Candida strains are a heterogeneous group that includes species with different levels of virulence, and only a limited number of C. glabrata isolates are resistant to fluconazole. We set out to identify the risk factors associated with microbiologically proven fluconazole-resistant candidemia. A prospective study including adult patients with candidemia was performed. Data were collected on patient demographics; underlying diseases; exposure to corticosteroids, antibiotics, or fluconazole; and invasive procedures. Risk factors associated either with non-albicans Candida spp. or potentially fluconazole-resistant Candida spp. (C. glabrata or C. krusei) or with Candida spp. with microbiologically confirmed fluconazole resistance were assessed using logistic regressions. We included 226 candidemia episodes. Non-albicans Candida isolates accounted for 53.1% of the fungal isolates, but only 18.2% of the cases were caused by potentially fluconazole-resistant organisms. Thirty isolates exhibited microbiologically confirmed fluconazole resistance. The multivariate analysis revealed that independent predictors associated with fluconazole-resistant Candida spp. were neutropenia (odds ratio [OR]=4.94; 95% confidence interval [CI]=1.50 to 16.20; P=0.008), chronic renal disease (OR=4.82; 95% CI=1.47 to 15.88; P=0.01), and previous fluconazole exposure (OR=5.09; 95% CI=1.66 to 15.6; P=0.004). Independently significant variables associated with non-albicans Candida bloodstream infection or with potentially fluconazole-resistant Candida spp. did not include previous fluconazole exposure. We concluded that prior fluconazole treatment is an independent risk factor only for candidemia caused by microbiologically confirmed fluconazole resistant species. Our findings may be of value for selecting empirical antifungal therapy.

PMCID: PMC2916332 PMID: 20498325 [PubMed - indexed for MEDLINE]

658. J Infect Dis. 2010 Jul 1;202(1):171-5.

Genetic basis of Candida biofilm resistance due to drug-sequestering matrix glucan.

Nett JE, Sanchez H, Cain MT, Andes DR.

Department of Medicine, University of Wisconsin, Madison, WI 53792, USA.

Medical devices provide an ecological niche for microbes to flourish as a biofilm community, protected from antimicrobials and host defenses. Biofilms formed by Candida albicans, the most common fungal pathogen, survive exposure to extraordinarily high drug concentrations. Here, we show that beta-glucan synthase Fks1p produces glucan, which is deposited in the biofilm matrix. The extracellular glucan is required for biofilm resistance and acts by sequestering antifungals, rendering cells resistant to their action. These findings provide the genetic basis for how biofilm matrix production governs drug resistance by impeding drug diffusion and also identify a useful biofilm drug target.

PMCID: PMC2880631 PMID: 20497051 [PubMed - indexed for MEDLINE]

659. Mol Cells. 2010 Jun;29(6):567-74. Epub 2010 May 22.

A cyclophilin A CPR1 overexpression enhances stress acquisition in Saccharomyces cerevisiae.

Kim IS, Kim HY, Shin SY, Kim YS, Lee DH, Park KM, Yoon HS.

Department of Biology, Kyungpook National University, Daegu, 702-701, Korea.

Cyclophilins are conserved cis-trans peptidyl-prolyl isomerase that are implicated in protein folding and function as molecular chaperones. We found the expression of cyclophilin A, Cpr1, changes in response to exposure to yeast Saccharomyces cerevisiae to abiotic stress conditions. The effect of Cpr1 overexpression in stress responses was therefore examined. The CPR1 gene was cloned to the yeast expression vector pVTU260 under regulation of an endogenous alcohol dehydrogenase (ADH) promoter. The overexpression of Cpr1 drastically increased cell viability of yeast in the presence of stress inducers, such as cadmium, cobalt, copper, hydrogen peroxide, tert-butyl hydroperoxide (t-BOOH), and sodium dodecyl sulfate (SDS). The Cpr1 expression also enhanced the cell rescue program resulting in a variety of antioxidant enzymes including thioredoxin system (particularly, thioredoxin peroxidase), metabolic enzymes (glucose-6-phosphate dehydrogenase and glyceraldehyde-3-phosphate dehydrogenase), and molecular chaperones (Hsp104, Hsp90, Hsp60 and Hsp42). Thus, our study illustrates the importance of Cpr1 as a molecular chaperone that improves cellular stress responses through collaborative relationships with other proteins when yeast cells are exposed to adverse conditions, and it also premises the improvement of yeast strains.

PMID: 20496120 [PubMed - indexed for MEDLINE]

660. Eukaryot Cell. 2010 Jul;9(7):991-1008. Epub 2010 May 21.

Genomic plasticity of the human fungal pathogen Candida albicans.

Selmecki A, Forche A, Berman J.

Department of Genetics, Cell Biology, and Development, 6-160 Jackson Hall, University of Minnesota, Minneapolis, MN 55455, USA.

The genomic plasticity of Candida albicans, a commensal and common opportunistic fungal pathogen, continues to reveal unexpected surprises. Once thought to be asexual, we now know that the organism can generate genetic diversity through several mechanisms, including mating between cells of the opposite or of the same mating type and by a parasexual reduction in chromosome number that can be accompanied by recombination events (2, 12, 14, 53, 77, 115). In addition, dramatic genome changes can appear quite rapidly in mitotic cells propagated in vitro as well as in vivo. The detection of aneuploidy in other fungal pathogens isolated directly from patients (145) and from environmental samples (71) suggests that variations in chromosome organization and copy number are a common mechanism used by pathogenic fungi to rapidly generate diversity in response to stressful growth conditions, including, but not limited to, antifungal drug exposure. Since cancer cells often become polyploid and/or aneuploid, some of the lessons learned from studies of genome plasticity in C. albicans may provide important insights into how these processes occur in higher-eukaryotic cells exposed to stresses such as anticancer drugs.

PMCID: PMC2901674 PMID: 20495058 [PubMed - indexed for MEDLINE]

661. Int J Antimicrob Agents. 2010 Aug;36(2):99-105. Epub 2010 May 21.

Non-pyogenic infections of the spine.

Skaf GS, Kanafani ZA, Araj GF, Kanj SS.

Division of Neurosurgery, Department of Surgery, American University of Beirut Medical Center, Beirut, Lebanon.

Subacute and chronic spondylodiscitis can be caused by a wide spectrum of infectious aetiologies including Mycobacterium tuberculosis, Brucella spp. and a variety of fungi including Aspergillus spp., Candida spp. and Cryptococcus neoformans. Knowledge of the local epidemiology and prior exposure might suggest the aetiology. Non-invasive diagnostic approaches, such as blood culture or antibody titres in the case of Brucella or antigen detection in the case of fungal infections, can be helpful in reaching the diagnosis. However, direct aspiration or tissue biopsy is usually necessary to identify the causative organism. Specimens are usually sent for pathology, special stains, cultures and, when indicated, molecular analysis. To minimise morbidity and mortality, antibiotic treatment should be initiated promptly directed against the suspected organism, and later adjusted according to the confirmed aetiology. Surgical treatment is reserved for recurrent infection, unstable spinal segment or marked kyphosis in the face of any neurological deficits and uncontrollable pain. Surgical approaches are dictated by the anatomic location of the offending lesion. Once medical treatment fails and surgery becomes warranted, we advocate the use of a two-stage surgical treatment for non-fixed kyphosis and a three-stage operation for fixed kyphosis.

PMID: 20494559 [PubMed - indexed for MEDLINE]

662. FEMS Yeast Res. 2010 Aug 1;10(5):579-86. Epub 2010 May 29.

Antimicrobial peptide MUC7 12-mer activates the calcium/calcineurin pathway in Candida albicans.

Lis M, Liu TT, Barker KS, Rogers PD, Bobek LA.

Department of Oral Biology, University at Buffalo, The State University of New York, Buffalo, New York 14214, USA.

MUC7 12-mer is a cationic antimicrobial peptide derived from the N-terminal region of human low-molecular-weight salivary mucin. In order to gain new insights into the modes of action of the 12-mer against opportunistic fungal pathogen Candida albicans, we examined changes in the gene expression profile of C. albicans upon exposure to this peptide. Cells at an early logarithmic phase were exposed to 6 muM peptide and grown until an OD(600 nm) of approximately 0.4 was reached. Changes in gene expression were determined by microarray analysis and showed that 19 out of the total of 531 genes, whose expression was elevated in response to the peptide, are regulated by the calcium/calcineurin signalling pathway. Inactivation of this pathway by deletions, or by FK506, caused hypersensitivity to the peptide, demonstrating the importance of this pathway to the defense of C. albicans against the MUC7 peptide. Other differentially expressed genes that were detected include those encoding subunits of proteasome, and genes involved in cell stress, iron metabolism, cell wall maintenance and small-molecule transport. The presented results suggest that the calcium/calcineurin signalling pathway plays a role in the adaptation of C. albicans to the MUC7 antimicrobial peptide.

PMCID: PMC2911779 PMID: 20491945 [PubMed - indexed for MEDLINE]

663. Br J Oral Maxillofac Surg. 2011 Apr;49(3):221-4. Epub 2010 May 21.

Incidence and patterns of needlestick injuries during intermaxillary fixation.

Bali R, Sharma P, Garg A.

Department of OMFS, D.A.V Dental College and M.M General Hospital, Yamunanagar, Haryana, India. rshbali@hotmail.co.uk

Intermaxillary fixation (IMF) carries an appreciable risk of occupational exposure to bloodborne viruses. Our aim was to establish the incidence and patterns of needlestick injuries during IMF at DAV Dental College. We surveyed 12 residents working in the Department of Maxillofacial Surgery for 1 year (December 2008 to December 2009) to find out how many injuries occurred during IMF. A total of 40 needlestick injuries were recorded during 172 IMF procedures (23%). Most injuries occurred in the maxillary left quadrant (n=16, 40%). Procedures done during the night had a much higher incidence (13/29, 45%) compared with 27/153 (18%) done during the day. Of the 40 injuries, 31 (78%) were recorded as superficial, the rest being deep. All injuries affected the non-working hand, and 39 (98%) were caused by a wire. Surgeons are at high risk of occupational exposure to bloodborne viruses from needlestick injuries during IMF. Detailed attention to the pattern of these injuries could help to develop improved strategies to minimise the incidence.

PMID: 20488595 [PubMed - indexed for MEDLINE]

664. Ann Allergy Asthma Immunol. 2010 May;104(5):434-9.

Rhinovirus-infected nasal polyp epithelial cells: effect on the activation and migration of eosinophils by airborne fungi.

Jang YJ, Lee YH, Shin SH.

Department of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

BACKGROUND: Rhinovirus and fungi are common environmental factors able to induce airway inflammation. They are associated with the production of chemical mediators by direct activation of epithelial cells.
OBJECTIVE: To evaluate the effect of fungal stimulation of rhinovirus-infected nasal polyp epithelial cells (NPECs) on the activation and migration of eosinophils.
METHODS: Rhinovirus-infected NPECs were stimulated with Alternaria and Aspergillus for 48 hours. Then, epithelial cells were co-cultured with freshly isolated eosinophils. An eosinophil migration study was performed with epithelial cell-conditioned media. Interleukin 6, interleukin 8, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor levels were measured to determine the activation of cells.
RESULTS: Airborne fungi enhanced the production of cytokines from rhinovirus 16-infected NPECs compared with fungi stimulation or rhinovirus 16 infection alone. Rhinovirus 16-infected NPECs were co-cultured with eosinophils, and cytokine production was not significantly increased except tumor necrosis factor-alpha production by Aspergillus. Epithelial cell-conditioned media, which were stimulated with fungi, enhanced the migration of eosinophils.
CONCLUSIONS: There was some synergism between rhinovirus 16 infection and airborne fungal exposure, enhancing the inflammatory response of airway epithelial cells.

PMID: 20486335 [PubMed - indexed for MEDLINE]

665. J Craniofac Surg. 2010 May;21(3):910-2.

Resolution of posttraumatic recurrent nasal fistula using temporoparietal fascia.

Chang SC, Wu CI, Jung SM.

Department of Plastic Surgery, China Medical University Hospital, Taichung, Taiwan. scnchang@gmail.com

Temporoparietal fascial grafts have been used for both nasal and facial contouring, for vascularized tissue coverage, and to augment the nose and lip. The temporoparietal fascial graft provides thin, broad, pliable, easily neovascularized, adequate coverage, contour, and bulk on the cartilage dorsum of the nose, as well as an inconspicuous donor site. A 23-year-old female motorcyclist had an accident with 1 angular laceration wound on the dorsum of the nose in 2006. There was intermittent discharge in the dorsal nose 2 weeks after primary repair. Six months later, the open-tip rhinoplasty was applied to the recurrent fistula of the nose dorsum. There were 2 fistulous orifices and 1 fibrotic cavity with hair ingrowth. After replacement of the rolled temporoparietal fascia, external nasal splinting was applied to mold the shape for 1 week. There was neither graft exposure nor recurrent infection. The procedure is a useful method to eliminate inflammatory squeals. The smooth nasal dorsum skin was regained with adequate nasal projection.

PMID: 20485079 [PubMed - indexed for MEDLINE]

666. Med Mycol. 2010 Dec;48(8):1056-65. Epub 2010 May 20.

An inhalation model of airway allergic response to inhalation of environmental Aspergillus fumigatus conidia in sensitized BALB/c mice.

Hoselton SA, Samarasinghe AE, Seydel JM, Schuh JM.

Department of Veterinary and Microbiological Sciences, North Dakota State University, Fargo, North Dakota, USA.

Fungal exposure may elicit a number of pulmonary diseases in man, including allergic asthma. Fungal sensitization is linked to asthma severity, although the basis for this increased pathology remains ambiguous. To create conditions simulating environmental fungal allergen exposure in a human, nose-only inhalation delivery of Aspergillus fumigatus conidia was employed in mice previously sensitized to Aspergillus antigen extract. BALB/c mice were immunized with subcutaneous and intraperitoneal injections of soluble A. fumigatus extract in alum, which was followed by three intranasal inoculations of the same fungal antigens dissolved in saline to elicit global sensitization in a manner similar to other published models. The animals were then challenged with a 10-min inhaled dose of live conidia blown directly from the surface of a mature A. fumigatus culture. After a single challenge with inhaled A. fumigatus conidia, allergic pulmonary inflammation and airway hyperresponsiveness were significantly increased above that of either naïve animals or animals that had been sensitized to A. fumigatus antigens but not challenged with conidia. The architecture of the lung was changed by inhalation of conidia when compared to controls in that there were significant increases in epithelial thickness, goblet cell metaplasia, and peribronchial collagen deposition. Additionally, α-smooth muscle actin staining of histological sections showed visual evidence of increased peribronchial smooth muscle mass after fungal challenge. In summary, the delivery of live A. fumigatus conidia to the sensitized airways of BALB/c mice advances the study of the pulmonary response to fungi by providing a more natural route of exposure and, for the first time, demonstrates the consistent development of fibrosis and smooth muscle changes accompanying exposure to inhaled fungal conidia in a mouse model.

PMCID: PMC3113699 PMID: 20482452 [PubMed - indexed for MEDLINE]

667. J Drugs Dermatol. 2010 May;9(5):562-4.

X-linked chronic granulomatous disease with voriconazole-induced photosensitivity/ photoaging reaction.

Frisch S, Askari SK, Beaty SR, Burkemper CN.

Department of Dermatology, Saint Louis University School of Medicine, Saint Louis, MO 63104, USA.

Due to the mutations in the nicotinamide dinucleotide phosphate (NADPH) oxidase complex in X-linked chronic granulomatous disease (CGD), the phagocytic activity in these patients is curtailed by a dysfunctional respiratory burst. This can lead to life-threatening bacterial and fungal infections. The prognosis for patients with CGD has dramatically improved with the advent of effective prophylactic drugs targeting catalase-positive bacteria, opportunistic Gram-negative bacteria and fungi. Voriconazole, a second-generation triazole, is a commonly used agent for prophylaxis in this population. The authors report a case of photoaging and photosensitivity reaction associated with voriconazole exposure in a 10-year-old boy with X-linked CGD. With broad-spectrum sunscreen, topical steroids, and discontinuation of voriconazole, the patient showed significant improvement.

PMID: 20480802 [PubMed - indexed for MEDLINE]

668. Drug Metab Rev. 2010 Nov;42(4):612-20.

Ozone applications to prevent and degrade mycotoxins: a review.

Freitas-Silva O, Venâncio A.

Institute for Biotechnology and Bioengineering (IBB), Centre of Biological Engineering, Universidade do Minho, Braga, Portugal. ofreitas@deb.uminho.pt

Ozone, a powerful oxidant, may be used for the inactivation of various microorganisms and the degradation of chemical contaminants. Although there are not many reports on the use of ozone against filamentous fungi or their mycotoxins, promising results have been reported. With a short half-time, at neutral pH and ambient temperature, ozone is able to inactivate microorganisms and decompose their toxic metabolites, leaving no traces of ozone in the treated commodity. This fact makes the use of ozone safe in food applications. There has been relatively limited research in this topic, especially with the use of aqueous ozone. The best management strategy still remains to be developed, but initial studies have indicated that an application of ozone for a short period of exposure is capable of controlling the proliferation of filamentous fungi and of degrading many mycotoxins.

PMID: 20477724 [PubMed - indexed for MEDLINE]

669. Curr Genet. 2010 Aug;56(4):349-60. Epub 2010 May 16.

Identification and function of a polyketide synthase gene responsible for 1,8-dihydroxynaphthalene-melanin pigment biosynthesis in Ascochyta rabiei.

Akamatsu HO, Chilvers MI, Stewart JE, Peever TL.

Department of Plant Pathology, Washington State University, Pullman, WA 99164-6430, USA. akamatho@affrc.go.jp

Ascochyta rabiei produces and accumulates one of the well-known fungal polyketides, 1,8-dihydroxynaphthalene-melanin pigment (DHN-melanin), in asexual and sexual fruiting bodies. Degenerate PCR primers were used to isolate an ArPKS1 of A. rabiei encoding a polypeptide with high similarity to polyketide synthase (PKS) involved in biosynthesis of DHN-melanin in other ascomycetous fungi. Site-directed mutagenesis of ArPKS1 in A. rabiei generated melanin-deficient pycnidial mutants but caused no significant reduction of pathogenicity to chickpea. Pycnidiospores in ArPKS1-mutant pycnidia showed higher sensitivity to UV light exposure compared to pycnidiospores in melanized pycnidia of the wild-type progenitor isolate. Integration of an orthologous PKS1 gene from Bipolaris oryzae into the genome of the mutants complemented the dysfunctional ArPKS1 gene. This study demonstrated that A. rabiei uses a DHN-melanin pathway for pigmentation of pycnidia and this molecule may protect pycnidiospores from UV irradiation.

PMID: 20473673 [PubMed - indexed for MEDLINE]

670. Parasitol Res. 2010 Jul;107(2):381-8. Epub 2010 May 14.

Effect of bacterial metabolites on microsporidian Nosema ceranae and on its host Apis mellifera.

Porrini MP, Audisio MC, Sabaté DC, Ibarguren C, Medici SK, Sarlo EG, Garrido PM, Eguaras MJ.

Arthropods Laboratory FCEyN, UNMdP, Mar del Plata, Argentina. mporrini@mdp.edu.ar

Nosemosis, a disease caused by a microsporidian infection, is one of the most frequently observed parasitic pathologies affecting adult honeybees. Presently, Nosema ceranae seems to be the main microsporidian infection in Apis mellifera. The antibiotic fumagillin is the only compound available to treat Nosema diseases; however, it is no longer licensed in most EU member states; therefore, the need to identify new molecules/substances prevails. The intent of this paper is to test bacterial metabolites by Bacillus and Enterococcus strains, isolated from bee midgut and honey. The toxicity on bees and the antiparasitic activity on N. ceranae were assessed under laboratory conditions. Results did not yield toxicity for the administered surfactin or bacteriocin concentrations. Spores exposed to direct contact with a particular surfactin revealed a significant infectivity reduction when inoculated on bees. This surfactin, administered ad libitum from the individuals' emergence, led to a significant reduction in parasitosis development when bees were infected with untreated spores 7 days postemergence. Based on the results obtained, one of the surfactins is herein postulated as a molecule capable of reducing N. ceranae development, acting either by direct exposure to purified spores or incorporated into the digestive tract of the bee.

PMID: 20467753 [PubMed - indexed for MEDLINE]

671. Plant Cell Rep. 2010 Aug;29(8):813-28. Epub 2010 May 14.

Molecular characterization and differential expression of beta-1,3-glucanase during ripening in banana fruit in response to ethylene, auxin, ABA, wounding, cold and light-dark cycles.

Roy Choudhury S, Roy S, Singh SK, Sengupta DN.

Division of Plant Biology, Bose Institute, 93/1, Acharya Prafulla Chandra Road, Kolkata, West Bengal, 700 009, India. src.bose@gmail.com

beta-1,3-Glucanases (E.C. 3.2.1.39) are widely distributed enzyme among bacteria, fungi, and higher plants. Analyses of accumulation levels of beta-1,3-glucanase protein in various tissues in banana have clearly indicated abundance of beta-1,3-glucanase protein accumulation in ripe pulp tissue. After cloning of beta-1,3-glucanase from banana pulp (cultivar Cavendish), we have carried out an in silico analysis to investigate the sequential, structural, and phylogenetic characteristics of the putative banana beta-1,3-glucanase protein. As like other ripening specific genes, beta-1,3-glucanase is regulated in response to a wide variety of factors. Therefore, we have analyzed the transcript accumulation pattern and protein levels of beta-1,3-glucanase in response to ethylene, auxin, ABA, wounding and, low temperature in preclimacteric banana fruit. Expression profile analyses have indicated that whereas exogenous application of ethylene strongly stimulated beta-1,3-glucanase transcript accumulation, ABA partially induced the expression of the gene. On the other hand, wound treatment did not induce beta-1,3-glucanase expression. Conversely, auxin and cold treatment negatively regulated beta-1,3-glucanase gene expression and thus inhibited glucanase activity. In addition, beta-1,3-glucanase transcript level was markedly decreased by constant exposure to white light. Protein level and enzymatic activity of beta-1,3-glucanase were substantially increased with considerable decrease in fruit firmness by ethylene treatment and reduced exposure to white light conditions as compared with other treatments. Together, the overall study of beta-1,3-glucanase expression pattern, glucanase activity, and changes in fruit firmness during ripening in various conditions suggest the possible physiological function of beta-1,3-glucanase in fruit pulp softening.

PMID: 20467747 [PubMed - indexed for MEDLINE]

672. Toxicol Sci. 2010 Aug;116(2):433-40. Epub 2010 May 13.

Kinetics of satratoxin g tissue distribution and excretion following intranasal exposure in the mouse.

Amuzie CJ, Islam Z, Kim JK, Seo JH, Pestka JJ.

Center for Integrative Toxicology, Michigan State University, East Lansing, Michigan 48824, USA.

Intranasal exposure of mice to satratoxin G (SG), a macrocyclic trichothecene produced by the indoor air mold Stachybotrys chartarum, selectively induces apoptosis in olfactory sensory neurons (OSNs) of the nose and brain. The purpose of this study was to measure the kinetics of distribution and clearance of SG in the mouse. Following intranasal instillation of female C57B16 mice with SG (500 microg/kg bw), the toxin was detectable from 5 to 60 min in blood and plasma, with the highest concentrations, 30 and 19 ng/ml, respectively, being observed at 5 min. SG clearance from plasma was rapid and followed single-compartment kinetics (t(1/2) = 20 min) and differed markedly from that of other tissues. SG concentrations were maximal at 15-30 min in nasal turbinates (480 ng/g), kidney (280 ng/g), lung (250 ng/g), spleen (200 ng/g), liver (140 ng/g), thymus (90 ng/g), heart (70 ng/g), olfactory bulb (14 ng/g), and brain (3 ng/g). The half-lives of SG in the nasal turbinate and thymus were 7.6 and 10.1 h, respectively, whereas in other organs, these ranged from 2.3 to 4.4 h. SG was detectable in feces and urine, but cumulative excretion over 5 days via these routes accounted for less than 0.3% of the total dose administered. Taken together, SG was rapidly taken up from the nose, distributed to tissues involved in respiratory, immune, and neuronal function, and subsequently cleared. However, a significant amount of the toxin was retained in the nasal turbinate, which might contribute to SG's capacity to evoke OSN death.

PMCID: PMC2909734 PMID: 20466779 [PubMed - indexed for MEDLINE]

673. Proc Am Thorac Soc. 2010 May;7(3):245-52.

Allergic fungal rhinitis and rhinosinusitis.

Hamilos DL.

Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, 55 Fruit Street, Bulfinch-422, Boston, MA 02114, USA. dhamilos@partners.org

The intent of this article is to review the published literature addressing the role of fungi as causative agents in allergic rhinitis and rhinosinusitis. Ambient mold spores are widely distributed in nature, and an estimated 3 to 10% of the world's population is allergic to molds. There are compelling epidemiologic links between mold (fungal) allergy and illnesses such as asthma and "asthma with allergic rhinitis." Fungal allergy is more prevalent in areas of high ambient mold spore concentrations. However, epidemiologic studies have failed to demonstrate a direct relationship between fungal allergy and allergic rhinitis either via outdoor or indoor exposure. Fungal allergy is clearly linked to a subset of chronic rhinosinusitis (CRS) known as allergic fungal rhinosinusitis (AFRS). This condition represents an intense allergic response against colonizing fungi giving rise to formation of allergic (eosinophilic) mucin, mucostasis, and sinus opacification. A broader role for colonizing fungi has been postulated in CRS owing to the demonstration of fungi in mucus in the vast majority of cases of CRS, and in vitro studies demonstrating that certain fungi, particularly Alternaria, elicit a "modified" allergic response in patients with CRS that is independent of IgE.

PMID: 20463255 [PubMed - indexed for MEDLINE]

674. Mol Biol Cell. 2010 Jul 1;21(13):2161-71. Epub 2010 May 12.

Suspended animation extends survival limits of Caenorhabditis elegans and Saccharomyces cerevisiae at low temperature.

Chan K, Goldmark JP, Roth MB.

Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.

The orderly progression through the cell division cycle is of paramount importance to all organisms, as improper progression through the cycle could result in defects with grave consequences. Previously, our lab has shown that model eukaryotes such as Saccharomyces cerevisiae, Caenorhabditis elegans, and Danio rerio all retain high viability after prolonged arrest in a state of anoxia-induced suspended animation, implying that in such a state, progression through the cell division cycle is reversibly arrested in an orderly manner. Here, we show that S. cerevisiae (both wild-type and several cold-sensitive strains) and C. elegans embryos exhibit a dramatic decrease in viability that is associated with dysregulation of the cell cycle when exposed to low temperatures. Further, we find that when the yeast or worms are first transitioned into a state of anoxia-induced suspended animation before cold exposure, the associated cold-induced viability defects are largely abrogated. We present evidence that by imposing an anoxia-induced reversible arrest of the cell cycle, the cells are prevented from engaging in aberrant cell cycle events in the cold, thus allowing the organisms to avoid the lethality that would have occurred in a cold, oxygenated environment.

PMCID: PMC2893981 PMID: 20462960 [PubMed - indexed for MEDLINE]

675. G Ital Dermatol Venereol. 2010 Jun;145(3):415-24.

Update on antifungal therapy with terbinafine.

Gianni C.

Department of Dermatology, S. Raffaele Scientific Institute, Milan, Italy.

Terbinafine, a synthetic antifungal of allylamine class, has fungicidal activity against dermatophytes, moulds and certain dimorphic fungi and fungistatic activity against Candida albicans. Following oral administration the terbinafine is absorbed rapidly (>70%) and reaches within 2 hours the peak plasma concentration. The drug is highly lipophilic and keratophilic and is highly bound to plasma protein (>90%) with a bioavailability of 70% to 80%. The drug is rapidly delivered and it is present in the stratum corneum, sebum, nails and hair for months after stopping the medication. The drug has been proven to be the choice treatment in the therapy of onychomycosis as it is very effective, well tolerated and has a relatively low potential for drug interactions. The pharmacologic and pharmacokinetic properties of terbinafine give strong support to the possibility that the pulse therapy may be equally effective in onychomycoses, possibly reducing medication costs and drug exposure. Several therapeutic patterns have been proposed: weekly intermittent terbinafine (500 mg/d for 1 week each month for 4 months), or single-dose terbinafine (1000 mg per month for 4 months). Use of topical terbinafine 1% may be practical where the tinea involvement is not extensive or chronic. Recently, the terbinafine is available in a novel topical solution (film-forming solution--FFS) effective in the treatment of tinea pedis (athlete's foot).

PMID: 20461049 [PubMed - indexed for MEDLINE]

676. Yakugaku Zasshi. 2010 May;130(5):747-54.

[Investigation of in vitro and in vivo efficacy of a novel alcohol based hand rub, MR06B7].

[Article in Japanese]

Okunishi J, Okamoto K, Nishihara Y, Tsujitani K, Miura T, Matsuse H, Yagi T, Wada Y, Goto J, Seto M, Ikeda M.

Maruishi Pharmaceutical Co., Ltd., Osaka, Japan. junji_okunishi@maruishi-pharm.co.jp

Alcohol based hand rubs have been used for hand hygiene in health-care settings. Compared with hand scrubbing, using suitable alcohol based hand rub provides several advantages like usability in a ward with no tap, requiring less time and mildly-irritating. Alcohol provides immediate activity, but poor virucidal activity against certain viruses including norovirus. It is important to develop further improved alcohol based hand rubs which have characteristics of sufficient effectiveness, skin-safe and extended spectrum to non-enveloped viruses for infection control. In the study, in vitro microbicidal evaluations and in vivo efficacy evaluation study were investigated to clarify the characteristics of a novel hand antiseptic MR06B7 composed of additives with synergetic activities. MR06B7 showed bactericidal activity of more than 5 Log(10) reduction within 15 sec against 20 challenged strains. MR06B7 also demonstrated potent fungicidal activities at exposure time of 30 sec (more than 4 Log(10) reduction). Against all test viruses including non-enveloped viruses (adenovirus, feline calicivirus, murine norovirus and poliovirus), MR06B7 had excellent virucidal activity to reduce the titer of viability to the limit of detection within 30 sec exposure (more than 4 Log(10) reduction), whereas 83%(v/v) ethanol indicated the inadequate effectiveness. On the clinical study conducted in accordance with standard method for Healthcare Personnel Handwash of American Society for Testing and Materials, MR06B7 showed excellent immediate antimicrobial activity. The result surpassed the critical indices set forth in the FDA's Tentative Final Monograph. These findings suggest MR06B7 which satisfies most requirements of efficacy qualifications including potent virucidal activity against non-enveloped viruses may contribute to accomplish advanced infection control in clinical practice.

PMID: 20460874 [PubMed - indexed for MEDLINE]

677. Biol Blood Marrow Transplant. 2011 Apr;17(4):507-15. Epub 2010 May 9.

Efficacy, safety, and breakthrough infections associated with standard long-term posaconazole antifungal prophylaxis in allogeneic stem cell transplantation recipients.

Winston DJ, Bartoni K, Territo MC, Schiller GJ.

Division of Hematology-Oncology, Department of Medicine, UCLA Medical Center, University of California-Los Angeles, CA 90095, USA. dwinston@mednet.ucla.edu

Based on favorable results from randomized clinical trials, oral posaconazole has been approved for prophylaxis in neutropenic patients and stem cell transplantation (SCT) recipients. However, routine use of a prophylactic drug may yield different results than those from clinical trials. We collected data on the efficacy, safety, breakthrough infections, and antimicrobial resistance associated with standard long-term posaconazole prophylaxis in adult allogeneic SCT recipients at the UCLA Medical Center. Oral posaconazole (200 mg 3 times daily) was started on day 1 after SCT and continued until day 100. After day 100, posaconazole was continued in patients who still required corticosteroids for prevention or treatment of graft-versus-host disease. From January 2007 through December 2008, 106 consecutive patients received prophylactic posaconazole. Breakthrough invasive fungal infections on posaconazole occurred in 8 patients (7.5%) within 6 months after SCT; 3 additional patients developed invasive fungal infection after discontinuation of prophylactic posaconazole. The infective organisms were Candida (8 cases), Aspergillus (2 cases), and Aspergillus plus Coccidioides immitis (1 case). There were no Zygomycetes infections. Only 2 (both Candida glabrata) of 9 infecting isolates tested were resistant to posaconazole (minimal inhibitory concentration >1 μg/mL). Mortality from invasive fungal infection occurred in 4 patients (3.7%). Except for nausea in 9 patients, no clinical adverse event or laboratory abnormality could be attributed to posaconazole. Mean peak and trough plasma posaconazole concentrations were relatively low (<400 ng/mL) in neutropenic patients with oral mucositis and other factors possibly affecting optimal absorption of posaconazole. These results demonstrate that standard long-term oral posaconazole prophylaxis after allogeneic SCT is safe and associated with few invasive mold infections. However, breakthrough infections caused by posaconazole-susceptible organisms (frequently Candida) may occur at currently recommended prophylactic doses. Thus, strategies to improve posaconazole exposure, including the use of higher doses, administration with an acidic beverage, and restriction of proton pump inhibitors, need to be considered when using prophylactic posaconazole.

PMID: 20460163 [PubMed - indexed for MEDLINE]

678. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2010 May;27(5):658-76.

Evaluating the technical feasibility of aflatoxin risk reduction strategies in Africa.

Wu F, Khlangwiset P.

Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA 15219, USA. few8@pitt.edu

Public health interventions must be readily accepted by their target populations to have any meaningful impact and must have financial and infrastructural support to be feasible in the parts of the world where they are most needed. At the same time, these interventions must be assessed for potential unintended consequences, either to the environment or to human health. In this paper, we evaluate the technical feasibility of interventions to control aflatoxin risk, to be potentially deployed in parts of Africa where aflatoxin exposure poses a significant public health concern. We have applied a conceptual framework for feasibility to four interventions, one associated with each of four different stages of aflatoxin risk: biocontrol (pre-harvest), a post-harvest intervention package (post-harvest), NovaSil clay (dietary), and hepatitis B vaccination (clinical). For each intervention, we have assessed the following four components of technical feasibility: (1) characteristics of the basic intervention, (2) characteristics of delivery, (3) requirements on government capacity, and (4) usage characteristics. We propose ways in which feasibility of each intervention is currently high or low from the perspective of adoption in Africa, how public education is crucial for each of these interventions to succeed, and how to align economic incentives to make the interventions more suitable for less developed countries.

PMCID: PMC2882709 PMID: 20455160 [PubMed - indexed for MEDLINE]

679. Aging (Albany NY). 2010 Apr;2(4):231-7.

Living on the edge: stress and activation of stress responses promote lifespan extension.

Zuin A, Castellano-Esteve D, Ayté J, Hidalgo E.

Oxidative Stress and Cell Cycle Group, Universitat Pompeu Fabra, 08003 Barcelona, Spain.

Oxidative stress constitutes the basis of physio-pathological situations such as neurodegenerative diseases and aging. However, sublethal exposure to toxic molecules such as reactive oxygen species can induce cellular responses that result in stress fitness. Studies in Schizosaccharomyces pombe have recently showed that the Sty1 MAP kinase, known to be activated by hydrogen peroxide and other cellular stressors, plays a pivotal role in promoting fitness and longevity when it becomes activated by calorie restriction, a situation which induces oxidative metabolism and reactive oxygen species production. Activation of the MAP kinase by calorie restriction during logarithmic growth induces a transcriptional anti-stress response including genes essential to promote lifespan extension. Importantly enough, the lifespan promotion exerted by deletion of the pka1 or sck2 genes, inactivating the two main nutrient-responsive pathways, is dependent on the presence of a functional Sty1 stress pathway, since double mutants also lacking Sty1 or its main substrate Atf1 do not display extended viability. In this Research Perspective, we review these findings in relation to previous reports and extend important aspects of the original study. We propose that moderate stress levels that are not harmful for cells can make them stronger.

PMCID: PMC2881511 PMID: 20453258 [PubMed - indexed for MEDLINE]

680. OMICS. 2010 Jun;14(3):249-59.

Dynamic transcriptional and metabolic responses in yeast adapting to temperature stress.

Strassburg K, Walther D, Takahashi H, Kanaya S, Kopka J.

Max Planck Institute of Molecular Plant Physiology, Potsdam-Golm, Germany.

Understanding the response processes in cellular systems to external perturbations is a central goal of large-scale molecular profiling experiments. We investigated the molecular response of yeast to increased and lowered temperatures relative to optimal reference conditions across two levels of molecular organization: the transcriptome using a whole yeast genome microarray and the metabolome applying the gas chromatography/mass spectrometry (GC/MS) technology with in vivo stable-isotope labeling for accurate relative quantification of a total of 50 different metabolites. The molecular adaptation of yeast to increased or lowered temperatures relative control conditions at both the metabolic and transcriptional level is dominated by temperature-inverted differential regulation patterns of transcriptional and metabolite responses and the temporal response observed to be biphasic. The set of previously described general environmental stress response (ESR) genes showed particularly strong temperature-inverted response patterns. Among the metabolites measured, trehalose was detected to respond strongest to the temperature stress and with temperature-inverted up- and downregulation relative to control, midtemperature conditions. Although associated with the same principal environmental parameter, the two different temperature regimes caused very distinct molecular response patterns at both the metabolite and the transcript level. While pairwise correlations between different transcripts and between different metabolites were found generally preserved under the various conditions, substantial differences were also observed indicative of changed underlying network architectures or modified regulatory relationships. Gene and associated gene functions were identified that are differentially regulated specifically under the gradual stress induction applied here compared to abrupt stress exposure investigated in previous studies, including genes of as of yet unidentified function and genes involved in protein synthesis and energy metabolism.

PMCID: PMC3128302 PMID: 20450442 [PubMed - indexed for MEDLINE]

681. Occup Med (Lond). 2010 Jun;60(4):270-6. Epub 2010 May 6.

Impact of new guidelines for blood exposure incidents in The Netherlands.

van Wijk PT, Boland GJ, Voss A, Schneeberger PM.

Department of Medical Microbiology and Infection Control, Jeroen Bosch Hospital, 5200 ME 's-Hertogenbosch, The Netherlands. p.v.wijk@jbz.nl

BACKGROUND: In 2007, a new set of guidelines for blood exposure incidents was introduced in The Netherlands to standardize management and reduce use of hepatitis B immunoglobulin (HBIg). Accidents now have to be assigned into risk categories with the corresponding medical intervention. AIMS: To study the consequences of the guidelines on overall risk assessment and costs of hepatitis B virus (HBV) prevention.
METHODS: Incidents (n = 461) from both hospital as well as non-hospital health care workers and others registered by a call centre from the year 2005 were reassessed and reclassified as 'no-risk', 'high-risk' or 'low-risk' according to the corresponding risk categories of the new guidelines. The differences in classification, use of HBV immunoglobulin, source testing and the costs of the HBV prevention strategy were evaluated.
RESULTS: Of all incidents, 86% could be reassigned directly into the new risk categories. However, there was a significant shift from 'low-' to 'high-risk' incidents. Overall, administration of HBV vaccination increased and administration of HBIg decreased significantly, although within the group of high-risk incidents, administration of HBIg increased. There was no effect on the frequency of reference serum taken after an incident. While fewer incidents needed intervention, the total costs of HBV prevention still increased by 50%. Total costs increased by 13%, due to a shift in classification.
CONCLUSIONS: The use of the new protocol facilitated standardized risk assessment for blood exposure accidents. HBIg administration and source testing decreased. An increased proportion of high-risk classifications resulted in an increase in the associated costs.

PMID: 20448058 [PubMed - indexed for MEDLINE]

682. Med Mycol. 2010 Nov;48(7):922-31.

The effect of Leptospermum petersonii essential oil on Candida albicans and Aspergillus fumigatus.

Hood JR, Burton DM, Wilkinson JM, Cavanagh HM.

Surveillance Branch, Office of Health Protection, Department of Health and Ageing, Canberra, Australia.

A variety of assays were utilized to determine the effects of Leptospermum petersonii essential oil on both Candida albicans and Aspergillus fumigatus. Hyphal morphology, susceptibility of spheroplasts and uptake of propidium iodide following exposure to the oil suggest that the mode of action of L. petersonii essential oil is through direct disturbance of the fungal cell membrane. Data also confirms that the volatile component of the oil is highly antifungal, independent of direct contact between the liquid oil and the fungal membrane. The degree of inhibition was greater when fungi were directly exposed to oil volatiles compared to pre-inoculation exposure of oil volatiles into the agar. It is likely that the essential oil volatiles are acting both directly and indirectly on the fungi to produce growth inhibition.

PMID: 20446888 [PubMed - indexed for MEDLINE]

683. Acta Crystallogr D Biol Crystallogr. 2010 May;66(Pt 5):539-48. Epub 2010 Apr 21.

Polymorphism of microcrystalline urate oxidase from Aspergillus flavus.

Collings I, Watier Y, Giffard M, Dagogo S, Kahn R, Bonneté F, Wright JP, Fitch AN, Margiolaki I.

European Synchrotron Radiation Facility, BP-220, F-38043 Grenoble CEDEX 9, France.

Different polymorphs of rasburicase, a recombinant urate oxidase enzyme (Uox) from Aspergillus flavus, were obtained as a series of polycrystalline precipitates. Different crystallization protocols were followed in which the salt type, pH and polyethylene glycol 8000 (PEG 8000) concentration were varied. The related crystalline phases were characterized by means of high-resolution synchrotron X-ray powder diffraction. In all cases, Uox complexed with the inhibitor 8-azaxanthine (AZA) was not altered from its robust orthorhombic I222 phase by variation of any of the factors listed above. However, in the absence of AZA during crystallization ligand-free Uox was significantly affected by the type of salt, resulting in different crystal forms for the four salts tested: sodium chloride, potassium chloride, ammonium chloride and ammonium sulfate. Remarkable alterations of some of these phases were observed upon gradual increase of the exposure time of the sample to the synchrotron beam in addition to variation of the PEG 8000 concentration. When Uox was crystallized in Tris buffer or pure water in the absence of salt, a distinct polymorph of orthorhombic symmetry (P2(1)2(1)2) was obtained that was associated with significantly altered lattice dimensions in comparison to a previously reported isosymmetrical structure. The latter form of Uox exhibits enhanced stability to variation of pH and PEG 8000 concentration accompanied by minor modifications of the unit-cell dimensions in the ranges under study. Accurate lattice parameters were extracted for all crystalline phases. This study reveals the rich phase diagram of Uox, a protein of high pharmaceutical importance, which is associated with an enhanced degree of polymorphism. The outcome of our analysis verifies previously reported results as well as demonstrating polymorphs that have altered unit-cell dimensions with respect to known structural models.

PMID: 20445229 [PubMed - indexed for MEDLINE]

684. Proc Biol Sci. 2010 Sep 22;277(1695):2821-8. Epub 2010 May 5.

Rapid anti-pathogen response in ant societies relies on high genetic diversity.

Ugelvig LV, Kronauer DJ, Schrempf A, Heinze J, Cremer S.

Evolution, Behaviour and Genetics, Biology I, University of Regensburg, Universitätsstrasse 31, , 93040 Regensburg, Germany.

Social organisms are constantly exposed to infectious agents via physical contact with conspecifics. While previous work has shown that disease susceptibility at the individual and group level is influenced by genetic diversity within and between group members, it remains poorly understood how group-level resistance to pathogens relates directly to individual physiology, defence behaviour and social interactions. We investigated the effects of high versus low genetic diversity on both the individual and collective disease defences in the ant Cardiocondyla obscurior. We compared the antiseptic behaviours (grooming and hygienic behaviour) of workers from genetically homogeneous and diverse colonies after exposure of their brood to the entomopathogenic fungus Metarhizium anisopliae. While workers from diverse colonies performed intensive allogrooming and quickly removed larvae covered with live fungal spores from the nest, workers from homogeneous colonies only removed sick larvae late after infection. This difference was not caused by a reduced repertoire of antiseptic behaviours or a generally decreased brood care activity in ants from homogeneous colonies. Our data instead suggest that reduced genetic diversity compromises the ability of Cardiocondyla colonies to quickly detect or react to the presence of pathogenic fungal spores before an infection is established, thereby affecting the dynamics of social immunity in the colony.

PMCID: PMC2981995 PMID: 20444720 [PubMed - indexed for MEDLINE]

685. Pediatr Allergy Immunol. 2010 Mar;21(2 Pt 1):268-76.

Effects of pet exposure in the first year of life on respiratory and allergic symptoms in 7-yr-old children. The SIDRIA-2 study.

Lombardi E, Simoni M, La Grutta S, Viegi G, Bisanti L, Chellini E, Dell'Orco V, Migliore E, Petronio MG, Pistelli R, Rusconi F, Sestini P, Forastiere F, Galassi C; SIDRIA-2 Collaborative Group.

Section of Respiratory Medicine, Department of Paediatrics, University of Florence, Anna Meyer Children's University Hospital, Florence, Italy. e.lombardi@meyer.it

The effects of pet exposure on the development of respiratory symptoms have recently been the matter of vivid discussion. Our objective was to determine the effects of exposure to cat or dog in the first year of life on subsequent respiratory/allergic symptoms in children in a large Italian multicentre study. As part of the SIDRIA-2 Study (Studi Italiani sui Disturbi Respiratori dell'Infanzia e l'Ambiente 2002), the parents of 20016 children (median age 7 yr) provided information on indoor exposures at different times in life and respiratory/allergic symptoms through questionnaires. Logistic regression analyses were performed taking into account cat or dog exposure at different times in life and adjusting for the presence of the other pet, mould exposure, gender, age, parental education, maternal smoking during the first year of life, current passive smoking, family history of asthma/rhinitis/eczema and other potential confounders. Neither significant effects of dog exposure in the first year of life nor in other periods were found on respiratory/allergic symptoms after adjusting for the other covariates. Cat exposure in the first year of life was significantly and independently associated with current wheezing [OR (95% CI) 1.88 (1.33-2.68), p < 0.001] and current asthma [1.74 (1.10-2.78), p < 0.05] and border-line associated with current rhinoconjunctivitis [1.43 (0.97-2.11), p = 0.07]. No other effects of cat exposure were found on respiratory/allergic symptoms. Cat, but not dog, exposure in the first year of life is an independent risk factor for current wheezing, current asthma and current rhinoconjunctivitis at the age of 7.

PMID: 20444167 [PubMed - indexed for MEDLINE]

686. Genetics. 2010 Jul;185(3):871-82. Epub 2010 May 3.

Autophosphorylation within the Atg1 activation loop is required for both kinase activity and the induction of autophagy in Saccharomyces cerevisiae.

Yeh YY, Wrasman K, Herman PK.

Department of Molecular Genetics, The Ohio State University, Columbus Ohio 43210, USA.

Autophagy is an evolutionarily conserved degradative pathway that has been implicated in a number of physiological events important for human health. This process was originally identified as a response to nutrient deprivation and is thought to serve in a recycling capacity during periods of nutritional stress. Autophagy activity appears to be highly regulated and multiple signaling pathways are known to target a complex of proteins that contains the Atg1 protein kinase. The data here extend these observations and identify a particular phosphorylation event on Atg1 as a potential control point within the autophagy pathway in Saccharomyces cerevisiae. This phosphorylation occurs at a threonine residue, T226, within the Atg1 activation loop that is conserved in all Atg1 orthologs. Replacing this threonine with a nonphosphorylatable residue resulted in a loss of Atg1 protein kinase activity and a failure to induce autophagy. This phosphorylation required the presence of a functional Atg1 kinase domain and two known regulators of Atg1 activity, Atg13 and Atg17. Interestingly, the levels of this modification were found to increase dramatically upon exposure to conditions that induce autophagy. In addition, T226 phosphorylation was associated with an autophosphorylated form of Atg1 that was found specifically in cells undergoing the autophagy process. In all, these data suggest that autophosphorylation within the Atg1 activation loop may represent a point of regulatory control for this degradative process.

PMCID: PMC2907206 PMID: 20439775 [PubMed - indexed for MEDLINE]

687. Environ Health Perspect. 2010 May;118(5):653-8.

Ecological niche modeling of Cryptococcus gattii in British Columbia, Canada.

Mak S, Klinkenberg B, Bartlett K, Fyfe M.

Epidemiology Services, British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada. sunny.mak@bccdc.ca

BACKGROUND: Cryptococcus gattii emerged on Vancouver Island, British Columbia (BC), Canada, in 1999, causing human and animal illness. Environmental sampling for C.gattii in southwestern BC has isolated the fungal organism from native vegetation, soil, air, and water. OBJECTIVES: Our aim was to help public health officials in BC delineate where C.gattii is currently established and forecast areas that could support C.gattii in the future. We also examined the utility of ecological niche modeling (ENM) based on human and animal C.gattii disease surveillance data.
METHODS: We performed ENM using the Genetic Algorithm for Rule-set Prediction (GARP) to predict the optimal and potential ecological niche areas of C.gattii in BC. Human and animal surveillance and environmental sampling data were used to build and test the models based on 15 predictor environmental data layers.
RESULTS: ENM provided very accurate predictions (> 98% accuracy, p-value < 0.001) for C.gattii in BC. The models identified optimal C.gattii ecological niche areas along the central and south eastern coast of Vancouver Island and within the Vancouver Lower Mainland. Elevation, biogeoclimatic zone, and January temperature were good predictors for identifying the ecological niche of C.gattii in BC.
CONCLUSIONS: The use of human and animal case data for ENM proved useful and effective in identifying the ecological niche of C.gattii in BC. These results are shared with public health to increase public and physician awareness of cryptococcal disease in regions at risk of environmental colonization of C.gattii.

PMCID: PMC2866681 PMID: 20439176 [PubMed - indexed for MEDLINE]

688. Appl Environ Microbiol. 2010 Jun;76(12):3806-17. Epub 2010 Apr 30.

Iron-dependent remodeling of fungal metabolic pathways associated with ferrichrome biosynthesis.

Mercier A, Labbé S.

Département de Biochimie, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, 3001, 12e Avenue Nord, Sherbrooke, QC, Canada J1H 5N4.

The fission yeast Schizosaccharomyces pombe excretes and accumulates the hydroxamate-type siderophore ferrichrome. The sib1(+) and sib2(+) genes encode, respectively, a siderophore synthetase and an l-ornithine N(5)-oxygenase that participate in ferrichrome biosynthesis. In the present report, we demonstrate that sib1(+) and sib2(+) are repressed by the GATA-type transcriptional repressor Fep1 in response to high levels of iron. We further found that the loss of Fep1 results in increased ferrichrome production. We showed that a sib1Delta sib2Delta mutant strain exhibits a severe growth defect on iron-poor media. We determined that two metabolic pathways are involved in biosynthesis of ornithine, an obligatory precursor of ferrichrome. Ornithine is produced by hydrolysis of arginine by the Car1 and Car3 proteins. Although car3(+) was constitutively expressed, car1(+) transcription levels were repressed upon exposure to iron, with a concomitant decrease of Car1 arginase activity. Ornithine is also generated by transformation of glutamate, which itself is produced by two separate biosynthetic pathways which are transcriptionally regulated by iron in an opposite fashion. In one pathway, the glutamate dehydrogenase Gdh1, which produces glutamate from 2-ketoglutarate, was repressed under iron-replete conditions in a Fep1-dependent manner. The other pathway involves two coupled enzymes, glutamine synthetase Gln1 and Fe-S cluster-containing glutamate synthase Glt1, which were both repressed under iron-limiting conditions but were expressed under iron-replete conditions. Collectively, these results indicate that under conditions of iron deprivation, yeast remodels metabolic pathways linked to ferrichrome synthesis in order to limit iron utilization without compromising siderophore production and its ability to sequester iron from the environment.

PMCID: PMC2893484 PMID: 20435771 [PubMed - indexed for MEDLINE]

689. J Invertebr Pathol. 2010 Sep;105(1):1-10. Epub 2010 May 8.

Host specificity of microsporidia pathogenic to the gypsy moth, Lymantria dispar (L.): field studies in Slovakia.

Solter LF, Pilarska DK, McManus ML, Zúbrik M, Patocka J, Huang WF, Novotný J.

Illinois Natural History Survey, Champaign, IL 61820, USA. lsolter@illinois.edu

Several species of microsporidia are important chronic pathogens of Lymantria dispar in Europe but have never been recovered from North American gypsy moth populations. The major issue for their introduction into North American L. dispar populations is concern about their safety to native non-target insects. In this study, we evaluated the susceptibility of sympatric non-target Lepidoptera to two species of microsporidia, Nosema lymantriae and Vairimorpha disparis, isolated from European populations of L. dispar and applied in field plots in Slovakia. Application of ultra low volume sprays of the microsporidia maximized coverage of infective spores in a complex natural environment and, thus, exposure of non-target species to the pathogens. Of 653 non-target larvae collected from plots treated with V. disparis in 2002, 18 individual larvae representing nine species in four families were infected. These plots were monitored for two subsequent seasons and V. disparis was not recovered from non-target species. Of 2571 non-target larvae collected in N. lymantriae-treated sites, one larva was found to be infected. Both species of microsporidia, particularly N. lymantriae, appear to have a very narrow host range in the field, even when an inundative technique is used for their introduction. V. disparis infections in L. dispar exceeded 40% of recovered larvae in the treated study sites; infection rates were lower in sites sprayed with N. lymantriae. Several naturally-occurring pathogens were recorded from the non-target species. The most common pathogen, isolated from 21 species in eight families, was a microsporidium in the genus Cystosporogenes.

PMID: 20435042 [PubMed - indexed for MEDLINE]

690. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2010 Jul;27(7):917-25.

Gynaecomastia linked to the intake of a herbal supplement fortified with diethylstilbestrol.

Toorians AW, Bovee TF, De Rooy J, Stolker LA, Hoogenboom RL.

St. Anna Zorggroep, PO Box 90, NL-5660 AB Geldrop, the Netherlands.

This study reports the findings of a supplement marketed on the Internet for prostate problems. The supplement was orally taken by a 60-year-old man with divergent hormonal levels and who was surgically treated for gynaecomastia: development of abnormally large mammary glands in males. The supplement showed a strong effect in a yeast oestrogen bioassay, expressing a yeast-enhanced green fluorescent protein (yEGFP) upon exposure to oestrogens. Using both nuclear magnetic resonance (NMR) and a gradient liquid chromatographic time-of-flight mass spectrometric (LC/TOF-MS) method, the response was shown to be caused by very high levels of diethylstilbestrol, known for causing gynaecomastia. The gynaecomastia was most probably caused by this orally taken 'natural' herbal supplement, as the patient's hormonal levels also returned to normal again when stopping the use of it. This case demonstrates that physicians need to be aware of the use of supplements with illegal components that may be responsible for unwanted side-effects.

PMID: 20432093 [PubMed - indexed for MEDLINE]

691. Parasitol Res. 2010 Jun;107(1):163-6. Epub 2010 Apr 30.

Efficacy of Chrysosporium tropicum metabolite against mixed population of adult mosquito (Culex quinquefasciatus, Anopheles stephensii, and Aedes aegypti) after purification with flash chromatography.

Verma P, Prakash S.

Advanced Parasitology and Vector Control Biotechnology Laboratory, Department of Zoology, Faculty of Science, Dayalbagh Educational Institute, Dayalbagh, Agra 282005, India. verma.preeti07@gamil.com

Chrysosporium tropicum is a keratinophilic fungus and an effective mosquito control agent. This fungus was grown in Richards broth at 27 +/- 2 degrees C and a relative humidity of 75% +/- 5% for 15 +/- 2 days. Filtration was done with Whatman number 1 filter paper, column chromatography, and flash chromatography. Adulticidal efficacy was performed against a mixed population of mosquitoes including Culex quinquefasciatus, Anophelese stephensii, Aedes aegypti at five different concentrations 5:5, 6:4, 7:3, 8:2, 9:1 by adding fungal filtrate of flash chromatography to methanol in different ratio (metabolite/methanol). The experiment was conducted in the cage with an area of 2 x 2 x 3 ft. The mortality in mosquito population was recorded after 8 hours of exposure, and adulticidal activity was tested by probit analysis. The LC(50) was determined to be 4.9921 ml. Results of present study confirm that metabolites of C. tropicum can be utilized as alternative biological control agents for adult mosquitoes.

PMID: 20431895 [PubMed - indexed for MEDLINE]

692. J Biol Chem. 2010 Jun 25;285(26):20088-96. Epub 2010 Apr 29.

The activity of yeast Hog1 MAPK is required during endoplasmic reticulum stress induced by tunicamycin exposure.

Torres-Quiroz F, García-Marqués S, Coria R, Randez-Gil F, Prieto JA.

Department of Biotechnology, Instituto de Agroquímica y Tecnología de los Alimentos, Consejo Superior de Investigaciones Científicas, E-46100 Burjassot, Valencia, Spain.

Accumulation of unfolded proteins in the endoplasmic reticulum (ER) triggers the so-called unfolded protein response (UPR), a conserved signaling pathway that drives the transcription of genes such as chaperones and folding enzymes. Nevertheless, the activity of the UPR accounts only for a part of the gene expression program activated upon ER stress. Moreover, the mechanism(s) for how cells adapt and survive to this stress are largely unknown. Here, we show that the yeast high osmolarity glycerol (HOG) pathway plays a role in ER stress resistance. Strains lacking the MAPK Hog1p displayed sensitivity to tunicamycin or beta-mercaptoethanol, whereas hyperactivation of the pathway enhanced their resistance. However, these effects were not due to Hog1p-mediated regulation of the UPR. Northern blot analysis demonstrated that Hog1p controls the tunicamycin-induced transcriptional change of GPD1 and that wild-type cells exposed to the drug accumulated glycerol in a Hog1p-dependent manner. Consistent with this, deletion of genes involved in glycerol synthesis caused increased sensitivity to tunicamycin, whereas overexpression of GPD1 provided higher tolerance to both wild-type and hog1Delta mutant cells. Quite remarkably, these effects were mediated by the basal activity of the MAPK because tunicamycin exposure does not trigger the phosphorylation of Hog1p or its nuclear import. Hence, our results describe new aspects of the yeast response to ER stress and identify additional functions of glycerol and the Hog1p MAPK to provide stress resistance.

PMCID: PMC2888421 PMID: 20430884 [PubMed - indexed for MEDLINE]

693. J Antimicrob Chemother. 2010 Jul;65(7):1460-5. Epub 2010 Apr 29.

Candidaemia associated with decreased in vitro fluconazole susceptibility: is Candida speciation predictive of the susceptibility pattern?

Oxman DA, Chow JK, Frendl G, Hadley S, Hershkovitz S, Ireland P, McDermott LA, Tsai K, Marty FM, Kontoyiannis DP, Golan Y.

Tufts Medical Center, 800 Washington Street, Boston, MA 02111, USA. doxman@partners.org

BACKGROUND: Candidaemia is often treated with fluconazole in the absence of susceptibility testing. We examined factors associated with candidaemia caused by Candida isolates with reduced susceptibility to fluconazole.
METHODS: We identified consecutive episodes of candidaemia at two hospitals from 2001 to 2007. Species identification followed CLSI methodology and fluconazole susceptibility was determined by Etest or broth microdilution. Susceptibility to fluconazole was defined as: full susceptibility (MIC < or = 8 mg/L); and reduced susceptibility (MIC > or = 32 mg/L). Complete resistance was defined as an MIC > 32 mg/L.
RESULTS: Of 243 episodes of candidaemia, 190 (78%) were fully susceptible to fluconazole and 45 (19%) had reduced susceptibility (of which 27 were fully resistant). Of Candida krusei and Candida glabrata isolates, 100% and 51%, respectively, had reduced susceptibility. Despite the small proportion of Candida albicans (8%), Candida tropicalis (4%) and Candida parapsilosis (4%) with reduced fluconazole susceptibility, these species composed 36% of the reduced-susceptibility group and 48% of the fully resistant group. In multivariate analysis, independent factors associated with reduced fluconazole susceptibility included male sex [odds ratio (OR) 3.2, P < 0.01], chronic lung disease (OR 2.7, P = 0.01), the presence of a central vascular catheter (OR 4.0, P < 0.01) and prior exposure to antifungal agents (OR 2.2, P = 0.04).
CONCLUSIONS: A significant proportion of candidaemia with reduced fluconazole susceptibility may be caused by C. albicans, C. tropicalis and C. parapsilosis, species usually considered fully susceptible to fluconazole. Thus, identification of these species may not be predictive of fluconazole susceptibility. Other factors that are associated with reduced fluconazole susceptibility may help clinicians choose adequate empirical anti-Candida therapy.

PMID: 20430790 [PubMed - indexed for MEDLINE]

694. Drug Chem Toxicol. 2010 Jul;33(3):269-78.

Effects of metals on growth and sporulation of aquatic fungi.

Azevedo MM, Cássio F.

Department of Sciences, School D. Maria II, V. N. Famalicao, Portugal. mariamanuel12001@megamail.pt

Aquatic hyphomycetes are a relevant group of fungi that play a crucial role as intermediaries between plant detritus and invertebrates in clean or metal-polluted streams. In this study, we investigated the effects of Zn, Cu, Ni, and Cd on the growth and sporulation of several aquatic hyphomycete species. Effects of these metals on growth were assessed in solid and liquid media with different compositions [1% malt extract (ME) and a mineral medium supplemented with vitamins and 2% glucose (MK)], and fungal sensitivity to metals was compared. The exposure to Zn or Cd inhibited the sporulation of Heliscus submersus and Tricladium chaetocladium, with these effects being stronger in the latter species. In solid medium, mydelial growth was linear, and, in most cases, metals negatively affected fungal growth. The sensitivity of aquatic hyphomycetes to metals, assessed as the metal concentration inhibiting biomass production in 50% (EC(50)), showed that Ypsilina graminea and Varicosporium elodeae were the most resistant species to Zn, while Alatospora acuminata, H. submersus, and Flagellospora curta appeared to be the most resistant fungus to Cu. Generally, lower toxicity of Zn or Cu than Ni or Cd was found. However, EC(50) values were about 20 times higher in solid than in liquid medium. Changes in nutrient supplies to fungi affected metal toxicity, as shown by higher EC(50) values in MK than ME. Complementarily, fungal tolerance to metals varied with fungal species as well as metal type.

PMID: 20429804 [PubMed - indexed for MEDLINE]

695. Braz J Infect Dis. 2010 Jan-Feb;14(1):30-4.

Isolation of pathogenic yeasts in the air from hospital environments in the city of Fortaleza, northeast Brazil.

Cordeiro RA, Brilhante RS, Pantoja LD, Moreira Filho RE, Vieira PR, Rocha MF, Monteiro AJ, Sidrim JJ.

Specialized Medical Mycology Center, Universidade Federal do Ceará, Fortaleza, Ceará, Brazil.

This paper reports the results of environmental surveillance of yeasts in specific areas of two tertiary local hospitals. From March 2007 to February 2008, samples from the air of two public hospitals were collected on a monthly basis. The samples were collected through passive sedimentation method (day and night exposure) of Petri dishes. A total of 240 air samples from 10 hospital environments were analyzed. These environments presented similar contamination levels, from which 80 fungi isolates were isolated: Candida parapsilosis (n = 34), Rhodotorula spp. (19), Trichosporon asahii (11), C. tropicalis (8), C. albicans (4), C. glabrata (1), C. guilliermondii (1), C. krusei (1) and Saccharomyces spp. (1). Regarding the presence of yeasts and climatic conditions, there were 40 strains (50%) in semi-critical areas (natural ventilation) and critical areas (air conditioned). Considering the presence of microorganisms with pathogenic potential, environmental monitoring is necessary to prevent possible hospital infections.

PMID: 20428651 [PubMed - indexed for MEDLINE]

696. Ann Saudi Med. 2010 May-Jun;30(3):239-42.

Delayed presentation of severe combined immunodeficiency due to prolonged maternal T cell engraftment.

Al-Muhsen SZ.

Department of Pediatrics, King Khaled University Hospital, King Saud University, Riyadh, Saudi Arabia. almuhsen@ksu.edu.sa

Comment in Ann Saudi Med. 2011 Mar-Apr;31(2):202; author reply 202.

Severe combined immunodeficiency (SCID) is a primary immunodeficiency disorder with heterogenous genetic etiologies. We describe a typical case in a 9-year-old boy that was masked by a clinically functional maternal T cell engraftment leading to late presentation with Pneumocystis jiroveci pneumonia and cytomegalovirus infection, probably following exhaustion of maternally engrafted cells. Based on immunological findings, he had a T- B+SCID phenotype.This report suggests that in rare cases, engrafted maternal T cell might persist for long time leading to partial constitution of immune function and delayed clinical presentation of SCID.

PMCID: PMC2886877 PMID: 20427943 [PubMed - indexed for MEDLINE]

697. Curr Allergy Asthma Rep. 2010 Jan;10(1):49-55.

Does exposure to indoor allergens contribute to the development of asthma and allergy?

Arshad SH.

Infection, Inflammation, and Immunity Research Division, School of Medicine, University of Southampton, Southampton General Hospital, 810 Level F, South Block, Southampton, United Kingdom. sha@soton.ac.uk

Common indoor allergens include house dust mite, cockroach, animal dander, and certain molds. In genetically susceptible children, exposure to these indoor allergens during the critical postnatal period may lead to sensitization in early childhood. Consistent evidence indicates that children sensitized to common indoor allergens are at several-fold higher risk of asthma and allergy. Due to conflicting evidence from prospective studies, some doubt remains regarding a direct and dose-response relationship between exposure and development of asthma. However, in recent years, evidence has accumulated that exposure to indoor allergen causes asthma and allergy, but this effect may depend on dose and type of allergen as well as the underlying genetic susceptibility of the child.

PMID: 20425514 [PubMed - indexed for MEDLINE]

698. Ind Health. 2010;48(2):236-43.

Distribution characteristics of airborne bacteria and fungi in the general hospitals of Korea.

Kim KY, Kim YS, Kim D.

Institute of Industrial and Environmental Medicine, Hanyang University, Seoul, Republic of Korea. kkysnu5@empal.com

The objective of this study is to provide fundamental data related to size-based characteristics of bioaerosol distributed in the general hospital. Measurement sites are main lobby, ICU, surgical ward and biomedical laboratory and total five times were sampled with six-stage cascade impactor. Mean concentrations of airborne bacteria and fungi were the highest in main lobby as followed by an order of surgical ward, ICU and biomedical laboratory. The predominant genera of airborne bacteria identified in the general hospital were Staphylococcus spp. (50%), Micrococcus spp. (15-20%), Corynebacterium spp. (5-20%), and Bacillus spp. (5-15%). On the other hand, the predominant genera of airborne fungi identified in the general hospital were Cladosporium spp. (30%), Penicillium spp. (20-25%), Aspergillus spp. (15-20%), and Alternaria spp. (10-20%). The detection rate was generally highest on stage 5 (1.1-2.1 microm) for airborne bacteria and on stage 1 (>7.0 microm) for airborne fungi.

PMID: 20424357 [PubMed - indexed for MEDLINE]

699. J Biol Chem. 2010 Jun 25;285(26):19884-90. Epub 2010 Apr 27.

Forward genetic analysis reveals multiple gating mechanisms of TRPV4.

Loukin S, Su Z, Zhou X, Kung C.

Laboratory of Molecular Biology, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA. shloukin@wisc.edu

TRPV4 is a polymodal cation channel gain-of-function (GOF) allele which causes skeletal dysplasia in humans. To better understand its gating, we screened for additional GOF alleles based on their ability to block yeast proliferation. Repeatedly, only a limited number of such growth-blocking mutations were isolated. Expressed in oocytes, wild-type channels can be strongly activated by either hypotonicity or exposure to the potent agonist 4alphaPDD, although the GOF channels behaved as if they were fully prestimulated as well as lacking a previously uncharacterized voltage-dependent inactivation. Five of six mutations occurred at or near the inner ends of the predicted core helices, giving further direct evidence that this region indeed forms the main intracellular gate in TRP channels. Surprisingly, both wild-type channels as well as these GOF channels maintain strong steady-state outward rectification that is not due to a Ca(2+) block, as has been proposed elsewhere. We conclude that TRPV4 contains an additional voltage-dependent gating mechanism in series with the main intracellular gate.

PMCID: PMC2888399 PMID: 20424166 [PubMed - indexed for MEDLINE]

700. Appl Microbiol Biotechnol. 2010 Jul;87(3):1089-99. Epub 2010 Apr 27.

New insights into the effect of medium-chain-length lactones on yeast membranes. Importance of the culture medium.

Ta TM, Cao-Hoang L, Phan-Thi H, Tran HD, Souffou N, Gresti J, Marechal PA, Cavin JF, Waché Y.

Laboratoire GPMA, IFR92, AgroSup Dijon & Université de Bourgogne, 1, esplanade Erasme, 21000, Dijon, France.

In hydrophobic compounds biotechnology, medium-chain-length metabolites often perturb cell activity. Their effect is usually studied in model conditions of growth in glucose media. Here, we study whether culture on lipids has an impact on the resistance of Yarrowia lipolytica to such compounds: Cells were cultured on glucose or oleate and submitted to gamma-dodecalactone. After a 60-min exposure to 3 g L(-1), about 80% of the glucose-grown cells (yeast extract peptone dextrose (YPD) cells) had lost their cultivability, 38% their membrane integrity, and 31% their reducing capacity as shown with propidium iodide and methylene blue, respectively. For oleate-grown cells, treatment at 6 g L(-1) did not alter cultivability despite some transient loss of membrane integrity from 3 g L(-1). It was shown with diphenylhexatriene and 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene that oleate-grown cells had membranes more fluid and less sensitive to the lactone-induced fluidization. Analyses revealed also higher contents of ergosterol but, for YPD- and minimum-oleate-grown cells (YNBO cells), the addition of lactone provoked a decrease in the concentration of ergosterol in a way similar to the depletion by methyl-beta-cyclodextrin and an important membrane fluidization. Ergosterol depletion or incorporation increased or decreased, respectively, cell sensitivity to lactone. This study shows that the embedment of oleate moieties into membranes as well as higher concentrations of sterol play a role in the higher resistance to lactone of oleate-grown cells (YPO cells). Similar oleate-induced increase in resistance was also observed for Rhodotorula and Candida strains able to grow on oleate as the sole carbon source whereas Saccharomyces and Sporidiobolus cells were more sensitive after induction.

PMID: 20422183 [PubMed - indexed for MEDLINE]

701. J Clin Microbiol. 2010 Jul;48(7):2373-80. Epub 2010 Apr 26.

Breakthrough invasive candidiasis in patients on micafungin.

Pfeiffer CD, Garcia-Effron G, Zaas AK, Perfect JR, Perlin DS, Alexander BD.

Division of Infectious Diseases, Duke University Medical Center, Durham, NC 27710, USA. christopher.pfeiffer@duke.edu

For Candida species, a bimodal wild-type MIC distribution for echinocandins exists, but resistance to echinocandins is rare. We characterized isolates from patients with invasive candidiasis (IC) breaking through >or=3 doses of micafungin therapy during the first 28 months of its use at our center: MICs were determined and hot-spot regions within FKS genes were sequenced. Eleven of 12 breakthrough IC cases identified were in transplant recipients. The median duration of micafungin exposure prior to breakthrough was 33 days (range, 5 to 165). Seventeen breakthrough isolates were recovered: FKS hot-spot mutations were found in 5 C. glabrata and 2 C. tropicalis isolates; of these, 5 (including all C. glabrata isolates) had micafungin MICs of >2 microg/ml, but all demonstrated caspofungin MICs of >2 microg/ml. Five C. parapsilosis isolates had wild-type FKS sequences and caspofungin MICs of 0.5 to 1 microg/ml, but 4/5 had micafungin MICs of >2 microg/ml. The remaining isolates retained echinocandin MICs of 2 microg/ml and clinical breakthrough or an alternative mechanism contributes to the nonsusceptible echinocandin MICs in C. parapsilosis requires further study.

PMCID: PMC2897493 PMID: 20421445 [PubMed - indexed for MEDLINE]

702. Indian J Med Res. 2010 Mar;131:405-10.

Needle stick injuries among health care workers in a tertiary care hospital of India.

Muralidhar S, Singh PK, Jain RK, Malhotra M, Bala M.

Regional STD Teaching Training & Research Centre, Safdarjang Hospital, New Delhi, India. sumu3579@yahoo.com

Comment in Indian J Med Res. 2010 Mar;131:384-6.

BACKGROUND & OBJECTIVES: Percutaneous injuries caused by needlesticks, pose a significant risk of occupational transmission of bloodborne pathogens. Their incidence is considerably higher than current estimates, and hence a low injury rate should not be interpreted as a non existent problem. The present study was carried out to determine the occurrence of NSI among various categories of health care workers (HCWs), and the causal factors, the circumstances under which these occur and to, explore the possibilities of measures to prevent these through improvements in knowledge, attitude and practice.
METHODS: The study group consisted of 428 HCWs of various categories of a tertiary care hospital in New Delhi, and was carried out with the help of an anonymous, self-reporting questionnaire structured specifically to identify predictive factors associated with NSIs.
RESULTS: The commonest clinical activity to cause the NSI was blood withdrawal (55%), followed by suturing (20.3%) and vaccination (11.7%). The practice of recapping needles after use was still prevalent among HCWs (66.3%). Some HCWs also revealed that they bent the needles before discarding (11.4%). It was alarming to note that only 40 per cent of the HCWs knew about the availability of PEP services in the hospital and 75 per cent of exposed nursing students did not seek PEP. INTERPRETATION & CONCLUSIONS: The present study showed a high occurrence of NSI in HCWs with a high rate of ignorance and apathy. These issues need to be addressed, through appropriate education and other interventional strategies by the hospital infection control committee.

PMID: 20418554 [PubMed - indexed for MEDLINE]

703. J Antibiot (Tokyo). 2010 Jun;63(6):309-14. Epub 2010 Apr 23.

Inhibitory activity of blasticidin A, a strong aflatoxin production inhibitor, on protein synthesis of yeast: selective inhibition of aflatoxin production by protein synthesis inhibitors.

Yoshinari T, Noda Y, Yoda K, Sezaki H, Nagasawa H, Sakuda S.

Department of Applied Biological Chemistry, University of Tokyo, Bunkyo-ku, Tokyo, Japan.

Blasticidin A (BcA), an antibiotic produced by Streptomyces, inhibits aflatoxin production without strong growth inhibition toward aflatoxin-producing fungi. During the course of our study on the mode of action of BcA by two-dimensional differential gel electrophoresis (2D-DIGE), we found a decrease in the abundances of ribosomal proteins in Saccharomyces cerevisiae after exposure to BcA. This phenomenon was also observed by treatment with blasticidin S (BcS) or cycloheximide. BcA inhibited protein synthesis in a galactose-induced expression system in S. cerevisiae similar to BcS and cycloheximide. BcS, but not cycloheximide, inhibited aflatoxin production in Aspergillus parasiticus without inhibition of fungal growth, similar to BcA. A decrease in the abundances of aflatoxin biosynthetic enzymes was observed in 2D-DIGE experiments with Aspergillus flavus after exposure to BcA or BcS. These results suggested that protein synthesis inhibitors are useful to control aflatoxin production.

PMID: 20414321 [PubMed - indexed for MEDLINE]

704. Clin Exp Allergy. 2010 Oct;40(10):1507-15. doi: 10.1111/j.1365-2222.2010.03520.x.

Aspergillus fumigatus regulates mite allergen-pulsed dendritic cells in the development of asthma.

Fukahori S, Matsuse H, Tsuchida T, Kawano T, Tomari S, Fukushima C, Kohno S.

Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.

BACKGROUND: The role in allergic asthma development of the immune response against fungi with concomitant exposure to other common aeroallergens has yet to be determined. In particular, there is little understanding of how inhaled fungi affect the host response to mite allergens.
OBJECTIVE: To characterize the in vitro and in vivo effects of concurrent exposure of Aspergillus fumigatus (Af) and Dermatophagoides farinae (Derf) on dendritic cells (DCs) in the development of allergic asthma.
METHODS: Murine bone marrow-derived DCs were pulsed with Derf and/or live or heat-inactivated Af. Cytokine production and the expression of pathogen recognition receptors (PRRs) were determined in vitro. Subsequently, these DCs were inoculated into the airway of naïve mice to assess the development of allergic airway inflammation in vivo. The effect of antibodies against PRRs was also evaluated.
RESULTS: Live Af significantly enhanced IL-10 production and the expression of Toll-like receptor (TLR) 2 and Dectin-1 in Derf-pulsed DCs. Live Af infection significantly attenuated Derf-pulsed DC-induced allergic airway inflammation in vivo. Antibodies against either TLR2 or Dectin-1 significantly reversed the inhibitory effects of live Af in the development of Derf-pulsed DC-induced allergic airway inflammation.
CONCLUSION: Concurrent exposure of DCs to fungal antigens has profound influences on the subsequent mite allergen-induced allergic airway inflammation. Live Af could regulate the functions of airway DCs in the development of mite allergen-induced allergic airway inflammation via regulation of their PRRs. Our results suggest that concurrent exposure to pathogens such as fungi and mite allergens has profound influences on the subsequent allergen-induced allergic airway inflammation. Furthermore, modulating PRR signalling could provide a therapeutic regimen for the development of asthma.

PMID: 20412133 [PubMed - indexed for MEDLINE]

705. Genes Genet Syst. 2010 Feb;85(1):1-8.

Effects of Saccharomyces cerevisiae mec1, tel1, and mre11 mutations on spontaneous and methylmethane sulfonate-induced genome instability.

Suetomi K, Mochizuki M, Suzuki S, Yamamoto H, Yamamoto K.

Graduate School of Life Sciences, Tohoku University, Sendai 980-8577, Japan.

In eukaryotes, together with the Mre11/Rad50/Xrs2 (or Nbs1) complex, a family of related protein kinases (the ATM family) is involved in checkpoint activation in response to DNA double-strand breaks. In Saccharomyces cerevisiae, two members of this family, MEC1 and TEL1, have functionally redundant roles in DNA damage repair. Strains with mutations in their mec1 as well as mre11 genes are very sensitive to DNA damaging agents, show defective induction of damage-induced cell-cycle checkpoints, and defective damage-induced homologous recombination. However, the fact that both the mec1Delta and mre11Delta strains exhibit the spontaneous hyper-recombination phenotype is paradoxical in light of the homologous recombination defects in these strains. In this study, we constructed yeast mec1, tel1, and mre11 null mutations and characterized their genome stability properties. Spontaneous and methylmethane sulfonate (MMS)-induced point mutations, base-substitutions, and frameshifts occurred to an almost equal extent in the wild-type, mec1Delta, tel1Delta, and mre11Delta strains. Thus, Mec1, Tel1, and Mre11 do not play roles in the point mutation response. We then found that the mec1Delta, mre11Delta, and mec1Delta tel1Delta strains demonstrated increased rates of spontaneous loss of heterozygosity (LOH), which includes crossover, gene conversion, and chromosome loss, compared with the wild-type strain. In the tel1Delta strain, the rate of spontaneous LOH was as low as that in the wild-type strain. Finally, no induction of LOH by MMS was observed in the mec1Delta, mre11Delta, or mec1Delta tel1Delta strain; however, it was detected in the wild-type and tel1Delta strains upon exposure to MMS. The elevated level of spontaneous LOH but not MMS-induced LOH in the mec1Delta, mre11Delta, and mec1Delta tel1Delta strains suggests the presence of high levels of spontaneous recombinogenic DNA damage, which differs from the damage induced by MMS treatment, in these strains.

PMID: 20410660 [PubMed - indexed for MEDLINE]

706. Proc Natl Acad Sci U S A. 2010 May 4;107(18):8219-24. Epub 2010 Apr 19.

Postreplication gaps at UV lesions are signals for checkpoint activation.

Callegari AJ, Clark E, Pneuman A, Kelly TJ.

Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.

Exposure of eukaryotic cells to UV light induces a checkpoint response that delays cell-cycle progression after cells enter S phase. It has been hypothesized that this checkpoint response provides time for repair by signaling the presence of structures generated when the replication fork encounters UV-induced DNA damage. To gain insight into the nature of the signaling structures, we used time-lapse microscopy to determine the effects of deficiencies in translesion DNA polymerases on the checkpoint response of the fission yeast Schizosaccharomyces pombe. We found that disruption of the genes encoding translesion DNA polymerases Polkappa and Poleta significantly prolonged the checkpoint response, indicating that the substrates of these enzymes are signals for checkpoint activation. Surprisingly, we found no evidence that the translesion polymerases Rev1 and Polzeta repair structures that are recognized by the checkpoint despite their role in maintaining viability after UV irradiation. Quantitative flow cytometry revealed that cells lacking translesion polymerases replicate UV-damaged DNA at the same rate at WT cells, indicating that the enhanced checkpoint response of cells lacking Polkappa and Poleta is not the result of stalled replication forks. These observations support a model in which postreplication DNA gaps with unrepaired UV lesions in the template strand act both as substrates for translesion polymerases and as signals for checkpoint activation.

PMCID: PMC2889594 PMID: 20404181 [PubMed - indexed for MEDLINE]

707. Astrobiology. 2010 Mar;10(2):215-27.

Survival potential and photosynthetic activity of lichens under Mars-like conditions: a laboratory study.

de Vera JP, Möhlmann D, Butina F, Lorek A, Wernecke R, Ott S.

DLR Institute of Planetary Research, Rutherfordstrasse 2, Berlin, Germany. jean-pierre.devera@dlr.de

Lichens were repetitively exposed over 22 days to thermophysical Mars-like conditions at low-and mid-latitudes. The simulated parameters and the experimental setup are described. Natural samples of the lichen Xanthoria elegans were used to investigate their ability to survive the applied Mars-like conditions. The effects of atmospheric pressure, CO(2) concentration, low temperature, water availability, and light on Mars were also studied. The results of these experiments indicate that no significant decrease in the vitality of the lichen occurred after exposure to simulated martian conditions, which was demonstrated by confocal laser scanning microscopy analysis, and a 95% CO(2) atmosphere with 100% humidity, low pressure (partial pressure of CO(2) was 600 Pa), and low temperature has a balancing effect on photosynthetic activity as a function of temperature. This means a starting low photosynthetic activity at high CO(2) concentrations with Earth-like pressure has a reduction of 60%. But, if the simulated atmospheric pressure is reduced to Mars-like conditions with the maintenance of the same Mars-like 95% CO(2) concentration, the photosynthetic activity increases and again reaches similar values as those exhibited under terrestrial atmospheric pressure and concentration. Based on these results, we presume that, in any region on Mars where liquid water might be available, even for short periods of time, a eukaryotic symbiotic organism would have the ability to survive, at least over weeks, and to temporarily photosynthesize.

PMID: 20402583 [PubMed - indexed for MEDLINE]

708. Toxicol In Vitro. 2010 Jun;24(4):1273-8. Epub 2010 Apr 14.

Biological activities of respirable dust from Eastern Canadian peat moss factories.

Létourneau V, Mériaux A, Goyer N, Chakir J, Cormier Y, Duchaine C.

Institut universitaire de cardiologie et de pneumologie de Québec (Hôpital Laval), 2725 chemin Sainte-Foy, Québec, Canada G1V 4G5. valerie.letourneau@criucpq.ulaval.ca

Bacteria, moulds, endotoxin and quartz from respirable dust of agricultural and industrial buildings are typically incriminated for the respiratory health decline of exposed workers despite that dust being an undefined mixture and quantification methods of aerosolized bacteria, moulds or endotoxin not being standardized yet. We developed an in vitro alveolar epithelial cell system in which biological activities of peat moss factories' dust might be correlated to bacteria, mould, endotoxin and quartz concentrations of the analyzed samples. Following exposure, interleukin-8 protein secretion, necrosis and apoptosis of the exposed A549 cells were monitored respectively with ELISA on cell supernatants, trypan blue exclusion and DNA fragmentation detection by flow cytometry. Respirable dust was collected with liquid impingers and respirable quartz with 10mm Dorr-Oliver cyclones. We quantified mesophilic bacteria, mesophilic moulds and endotoxins from liquid impinger samples. No correlation was observed between biological activities of dust and bacteria, mould, endotoxin or quartz concentrations under our experimental conditions. Our speculation is that simple measurements, such as dust concentrations, may not be adequate indicators of the human respiratory health hazard for a given environment.

PMID: 20398748 [PubMed - indexed for MEDLINE]

709. Med Mycol. 2010 Jun;48(4):598-605.

Proteomic analysis of proteins released from growth-arrested Candida albicans following exposure to caspofungin.

Kelly J, Kavanagh K.

Medical Mycology Unit, Department of Biology, National Institute for Cellular Biotechnology, National University of Ireland Maynooth, Co. Kildare, Ireland.

The echinocandins (e.g., caspofungin) are a relatively new class of antifungal drugs that function by inhibiting the synthesis of beta-1,3-glucan in the cell wall and thus lead to lysis of the cell. In this work the effect of caspofungin on the release of peptides from non-growing cells of the yeast Candida albicans that had been exposed to the drug was monitored. Exposure to 0.19 mug/ml caspofungin resulted in the release of amino acids from cells and of both small and large molecular weight proteins as demonstrated by 1- and 2-dimensional gel electrophoresis. Matrix-assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-ToF) mass spectrometry was employed to identify a number of escaped peptides that were found to have increased in intensity upon exposure to the drug. A number of wall-associated proteins (e.g., phosphoglycerate kinase) and a number of glycolytic enzymes (phosphoglycerate mutase 1, fructose-bisphosphate aldolase) were identified. Importantly, several released proteins (e.g., pyruvate kinase, enolase 1, phosphoglycerate mutase, glyceraldehydes 3-phosphate dehydrogenase, fructose bisphosphate aldolase and alcohol dehydrogenase 1) are highly immunogenic in nature. The results presented here demonstrate that non-growing C. albicans cells are susceptible to the effect of caspofungin and that the caspofungin-mediated release of proteins from such cells could lead to a stronger immune response in vivo. This report illustrates that, in addition to hampering cell wall synthesis, caspofungin may also interfere with the permeability of the fungal cell wall.

PMID: 20392151 [PubMed - indexed for MEDLINE]

710. J Toxicol Environ Health A. 2010;73(10):684-700.

Muramic acid, endotoxin, 3-hydroxy fatty acids, and ergosterol content explain monocyte and epithelial cell inflammatory responses to agricultural dusts.

Poole JA, Dooley GP, Saito R, Burrell AM, Bailey KL, Romberger DJ, Mehaffy J, Reynolds SJ.

Omaha Veterans Administration Medical Center, Omaha, Nebraska, USA. japoole@unmc.edu

In agricultural and other environments, inhalation of airborne microorganisms is linked to respiratory disease development. Bacterial endotoxins, peptidoglycans, and fungi are potential causative agents, but relative microbial characterization and inflammatory comparisons amongst agricultural dusts are not well described. The aim of this study was to determine the distribution of microbial endotoxin, 3-hydroxy fatty acids (3-OHFA), muramic acid, and ergosterol and evaluate inflammatory responses in human monocytes and bronchial epithelial cells with various dust samples. Settled surface dust was obtained from five environments: swine facility, dairy barn, grain elevator, domestic home (no pets), and domestic home with dog. Endotoxin concentration was determined by recombinant factor C (rFC). 3-OHFA, muramic acid, and ergosterol were measured using gas chromatography-mass spectrometry. Dust-induced inflammatory cytokine secretion in human monocytes and bronchial epithelial cells was evaluated. Endotoxin-independent dust-induced inflammatory responses were evaluated. Endotoxin and 3-OHFA levels were highest in agricultural dusts. Muramic acid, endotoxin, 3-OHFA, and ergosterol were detected in dusts samples. Muramic acid was highest in animal farming dusts. Ergosterol was most significant in grain elevator dust. Agricultural dusts induced monocyte tumor necrosis factor (TNF) alpha, interleukin (IL)-6, IL-8, and epithelial cell IL-6 and IL-8 secretion. Monocyte and epithelial IL-6 and IL-8 secretion was not dependent on endotoxin. House dust(s) induced monocyte TNFalpha, IL-6, and IL-8 secretion. Swine facility dust generally produced elevated responses compared to other dusts. Agricultural dusts are complex with significant microbial component contribution. Large animal farming dust(s)-induced inflammation is not entirely dependent on endotoxin. Addition of muramic acid to endotoxin in large animal farming environment monitoring is warranted.

PMCID: PMC2856089 PMID: 20391112 [PubMed - indexed for MEDLINE]

711. J Environ Sci Health B. 2010 Apr;45(3):222-8.

Effects of methamidophos on the community structure, antagonism towards Rhizoctonia solani, and phlD diversity of soil Pseudomonas.

Wu M, Li X, Zhang H, Cai Y, Zhang C.

Chinese Academy of Science, Institute of Applied Ecology, Shenyang, China.

A microcosm incubation study using an aquic brown soil from northeast China (a Cambisol in the UN Food and Agriculture Organization FAO Soil Taxonomy) was conducted to examine the effects of different concentrations (0, 50, 150, and 250 mg kg(-1)) of methamidophos (O,S-dimethyl phosphoramidothioato) on Pseudomonas, one of the most important gram-negative bacteria in soil. Amplified ribosomal DNA restriction analysis (ARDRA) was performed to study the Pseudomonas community structure, an in vitro assay was made to test the antagonistic activity of isolated Pseudomonas strains against soil-borne Rhizoctonia solani, a major member of the pathogens highly related to soil-borne plant diseases, and special primer amplification and sequencing were performed to investigate the diversity of phlD, an essential gene in the biosynthesis of 2, 4-diacetylphloroglucinol (2, 4-DAPG), which has biocontrol activity in phlD(+)isolates. With exposure to increasing methamidophos concentrations, the total number of soil Pseudomonas ARDRA patterns decreased significantly, but with less change in the same treatments over 1, 3, and 5 weeks of incubation. The number of isolated Pseudomonas strains with antagonistic activity against R. solani as well as the diversity and appearance frequency of the strains' phlD gene also decreased with increasing concentrations of methamidophos, especially at high methamidophos concentrations. Applying methamidophos could increase the risk of soil-borne plant diseases by decreasing the diversity of the soil Pseudomonas community and the amount of R. solani antagonists, particularly those with the phlD gene.

PMID: 20390954 [PubMed - indexed for MEDLINE]

712. J Environ Sci Health B. 2010 Apr;45(3):190-7.

Influence of tetracycline exposure on the growth of wheat seedlings and the rhizosphere microbial community structure in hydroponic culture.

Yang Q, Zhang J, Zhang W, Wang Z, Xie Y, Zhang H.

College of Life Sciences, Henan Normal University, Xinxiang, China.

In this study, the effects of tetracycline exposure on wheat growth and the microbial community structure in the rhizosphere were investigated under hydroponic culture conditions. Exposure to various concentrations of tetracycline resulted in significant suppression of the growth of wheat roots and shoots, with minimum doses of 0.8 mg L(-1) and 4 mg L(-1) resulting in inhibition rates of 32% and 15.4%, respectively. Complete inhibition of the growth of these two parts of wheat plants was observed in response to treatment with tetracycline at 20 mg L(-1) and 100 mg L(-1), respectively. However, the germination of wheat seeds was not sensitive to exposure to tetracycline. The effects of tetracycline exposure on the microbial community in the wheat rhizosphere were evaluated through traditional cultivation and molecular biological analyses. The cultivation results indicated that bacteria were the dominant population, being present in concentrations of 1x 10(8)-2.45x 10(9)CFUs mL(-1), although 39% to 87% inhibition occurred in response to tetracycline. The concentration of fungi increased in all tetracycline treated samples to 2.5 to 15.8 times that of the control. The highest concentration of fungi (4.27x 10(8) CFU mL(-1)) was observed in response to 60 mg L(-1) tetracycline after 15 days of cultivation. In this stage, a large amount of fungal colonies was observed on the surface of the culture solution, the wheat roots became rotted and the plants became atrophic or even died. Molecular biological analysis indicated that the bacterial community structure was significantly different in samples that were exposed to high levels of tetracycline (over 20 mg L(-1)) than in samples that were exposed to lower concentrations. As the concentration of tetracycline increased, the diversity of the bacteria decreased. Additionally, several dominant sensitive species such as Sphingobacterium multivorum were suppressed by tetracycline, while some resistant species such as Acinetobacter sp. appeared or were conserved. The bacteria population tended to stabilize when the drug concentration exceeded 40 mg L(-1).

PMID: 20390950 [PubMed - indexed for MEDLINE]

713. Environ Entomol. 2010 Apr;39(2):468-75.

Pathogenicity of entomopathogenic fungi Metarhizium anisopliae and Beauveria bassiana (Hypocreales: Clavicipitaceae) isolates to the adult pea leafminer (Diptera: Agromyzidae) and prospects of an autoinoculation device for infection in the field.

Migiro LN, Maniania NK, Chabi-Olaye A, Vandenberg J.

International Centre of Insect Physiology and Ecology, PO Box 30772-00100, Nairobi, Kenya, South Africa. nmaniania@icipe.org.

Seventeen isolates of Metarhizium anisopliae (Metschnikoff) Sorokin and three isolates of Beauveria bassiana (Balsamo) Vuillemin (Hypocreales: Clavicipitaceae) were evaluated for their pathogenicity to the adult pea leafminer, Liriomyza huidobrensis (Blanchard) (Diptera: Agromyzidae), in the laboratory. Flies were contaminated with dry conidia through a velvet material wrapped around the inner side of a cylindrical plastic tube. All the isolates were pathogenic to the pea leafminer, causing mortality between 40 and 100% at 5 d after exposure. The lethal time for 50% mortality (LT(50)) ranged from 2.6 to 5.4 d, whereas the LT(90) values varied between 3.2 and 9.1 d depending on the isolate. An autoinoculation device was evaluated in cage field experiments using only one of the virulent isolates, M. anisopliae ICIPE 20. The device was loaded with 2-3 g of dry conidia. Mortality of up to 100% was observed in flies captured from fungus-treated cages held under laboratory conditions. The average number of spores picked up by a single fly visiting the device increased with days after inoculation. One day after the inoculation, adults picked up an average of 4.1 +/- 0.7 x 10(5) conidia and 39.6 +/- 4.0 x 10(5) conidia 5 d after inoculation. Depending on the sampling date, the LT(50) varied between 1.8 and 3.4 d. Results indicate that some isolates of B. bassiana and M. anisopliae are highly pathogenic to L. huidobrensis, suggesting a potential for their use in the control of this pest. They also suggest the possibility of L. huidobrensis suppression with fungi using an autoinoculation device.

PMID: 20388276 [PubMed - indexed for MEDLINE]

714. Antimicrob Agents Chemother. 2010 Jun;54(6):2497-506. Epub 2010 Apr 12.

In vivo comparison of the pharmacodynamic targets for echinocandin drugs against Candida species.

Andes D, Diekema DJ, Pfaller MA, Bohrmuller J, Marchillo K, Lepak A.

Department of Medicine and Department of Medical Microbiology and Immunology, University of Wisconsin, Madison, WI 53792, USA. dra@medicine.wisc.edu

Previous pharmacodynamic studies using in vivo candidiasis models have demonstrated that the 24-h area under the concentration-time curve (AUC)/MIC is a good descriptor of the echinocandin exposure-response relationship. Further studies investigating the 24-h AUC/MIC target for a stasis endpoint identified free-drug 24-h AUC/MIC against Candida albicans and were similar for two echinocandins, anidulafungin and micafungin. The current studies expand investigation of a third echinocandin (caspofungin) and compare the pharmacodynamic target among C. albicans, Candida glabrata, and Candida parapsilosis. Treatment studies were conducted with six C. albicans, nine C. glabrata, and 15 C. parapsilosis strains with various MICs (anidulafungin, 0.015 to 4.0 microg/ml; caspofungin, 0.03 to 4.0 microg/ml; and micafungin, 0.008 to 1.0 microg/ml). Efficacy was closely tied to MIC and the 24-h AUC/MIC. Therapy against C. parapsilosis required more of each echinocandin on a mg/kg basis. Caspofungin required less drug on a mg/kg basis for efficacy against all of the organisms than did the other two drugs. However, the 24-h AUC/MIC targets were similar among the echinocandins when free drug concentrations were considered, suggesting the relevance of protein binding. The targets for C. parapsilosis (mean, 7) and C. glabrata (mean, 7) were significantly lower than those for C. albicans (mean, 20) for each echinocandin. The results suggest that current susceptibility breakpoints and the consideration of organism species in these determinations should be reexplored.

PMCID: PMC2876357 PMID: 20385855 [PubMed - indexed for MEDLINE]

715. Clin Rheumatol. 2010 Sep;29(9):1061-5. Epub 2010 Apr 12.

Fungal arthritis of the knee caused by Mycoleptodiscus indicus.

Dewar CL, Sigler L.

Division of Rheumatology, Department of Medicine, Lions Gate Hospital, 406A-125 East 13th Street, North Vancouver, British Columbia, Canada, V7L 2L3. c.dewar@telus.net

Mycoleptodiscus indicus is a recognized plant pathogen which has very rarely been reported as a cause of human infection. It is a tropical or subtropical fungus which is difficult to culture and identify from clinical specimens. This is the first report of septic arthritis with this fungus in a healthy Canadian male. The fungal infection was contracted on a vacation in Costa Rica, probably through direct inoculation through injured skin. The fungus was isolated from synovial fluid and identification was confirmed by DNA sequencing. There has only been one previous case of septic arthritis of the knee and one skin infection reported with this fungus; both cases involved immunocompromised hosts. Both septic arthritis patients required joint surgery and lavage to eradicate the fungus, however, only the immunocompromised patient required antifungal medications. In the future, it is very likely that the number of patients identified with M. indicus infection will rise due to increasing awareness of this pathogen as well as increasing exposure. Many immunocompromised patients on anti-retroviral or biologic therapy are healthy enough to travel, thereby exposing themselves to exotic and infected plants which increase the risk of unusual fungal infections.

PMID: 20383730 [PubMed - indexed for MEDLINE]

716. Acta Pharmacol Sin. 2010 May;31(5):616-28. Epub 2010 Apr 12.

Transcriptional response of Candida albicans biofilms following exposure to 2-amino-nonyl-6-methoxyl-tetralin muriate.

Liang RM, Cao YB, Zhou YJ, Xu Y, Gao PH, Dai BD, Yang F, Tang H, Jiang YY.

Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.

AIM: To identify changes in the gene expression profile of Candida albicans (C albicans) biofilms following exposed to 2-amino-nonyl-6-methoxyl-tetralin muriate(10b) and clarify the mechanism of 10b against C albicans biofilms.
METHODS: Anti-biofilm activity of 10b was assessed by tetrazolium (XTT) reduction assay and the action mechanism against biofilms was investigated by cDNA microarray analysis and real-time RT-PCR assay.
RESULTS: Ten differentially expressed genes were directly linked to biofilm formation and filamentous or hyphal growth (eg, NRG1, ECE1 and CSA1). Decreased gene expression was involved in glycolysis (eg, HXK2 and PFK1) and antioxidant defense (eg, SOD5), while increased gene expression was associated with enzymes that specifically hydrolyzed beta-1,3 glucan (XOG1), and with lipid, fatty acid and sterol metabolism (eg, SLD1, ERG6 and ERG2). Functional analysis indicated that addition of anti-oxidant ascorbic acid reduced inhibitory efficiency of 10b on mature biofilm.
CONCLUSION: Inhibition of 10b on biofilm formation possibly depends on impairing the ability of C albicans to change its morphology via altering the expression of biofilm formation genes. Mitochondrial aerobic respiration shift and endogenous ROS augmentation might be a major contribution to reduce mature biofilm metabolic activity. The data may be useful for the development of new strategies to reduce the incidence of device-associated infections.

PMID: 20383169 [PubMed - indexed for MEDLINE]

717. Eukaryot Cell. 2010 Jun;9(6):835-46. Epub 2010 Apr 9.

Cryptococcal interactions with the host immune system.

Voelz K, May RC.

School of Biosciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom.

Opportunistic pathogens have become of increasing medical importance over the last decade due to the AIDS pandemic. Not only is cryptococcosis the fourth-most-common fatal infectious disease in sub-Saharan Africa, but also Cryptococcus is an emerging pathogen of immunocompetent individuals. The interaction between Cryptococcus and the host's immune system is a major determinant for the outcome of disease. Despite initial infection in early childhood with Cryptococcus neoformans and frequent exposure to C. neoformans within the environment, immunocompetent individuals are generally able to contain the fungus or maintain the yeast in a latent state. However, immune deficiencies lead to disseminating infections that are uniformly fatal without rapid clinical intervention. This review will discuss the innate and adaptive immune responses to Cryptococcus and cryptococcal strategies to evade the host's defense mechanisms. It will also address the importance of these strategies in pathogenesis and the potential of immunotherapy in cryptococcosis treatment.

PMCID: PMC2901644 PMID: 20382758 [PubMed - indexed for MEDLINE]

718. Arch Oral Biol. 2010 Jun;55(6):397-400. Epub 2010 Apr 9.

Antimicrobial activity of super-oxidised water against oral microorganisms.

Yamada K, Yama M, Takaku Y, Kakizawa T, Kimizuka R, Okuda K, Kato T.

Department of Clinical Oral Health Science, Tokyo Dental College, Tokyo, Japan.

OBJECTIVE: The radical anion of oxygen (O(-)) is extremely oxidative and shows high reactivity. In this study, the antibacterial activity of water super-oxidised water containing high concentration of O(-) (O(-)-water) was tested against cultured planktonic cells of cariogenic bacteria, periodontopathic bacteria and Candida albicans.
METHODS: O(-)-water was prepared using the AOE-750 (Oxy Japan Corporation, Japan) and its antibacterial activity against pure culture of Streptococcus sobrinus, Porphyromonas gingivalis, Prevotella intermedia, Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum and C. albicans evaluated. Each oral microorganism (10(4) to 10(8)CFU/ml) was exposed to three concentrations of O(-)-water at room temperature or 37 degrees C for 15s to 24h.
RESULTS: Exposure to O(-)-water resulted in a bactericidal effect against all cariogenic and periodontopathic bacteria tested. No significant fungicidal effect was observed on C. albicans, however.
CONCLUSION: The results demonstrate that O(-)-water exerts an antibacterial effect on cariogenic and periodontopathic bacteria.

PMID: 20381790 [PubMed - indexed for MEDLINE]

719. Ecology. 2010 Jan;91(1):22-7.

Food quality and the risk of light exposure affect patch-choice decisions in the slime mold Physarum polycephalum.

Latty T, Beekman M.

Behaviour and Genetics of Social Insects Lab, School of Biological Sciences A12, Science Road, University of Sydney, Sydney, New South Wales 2006, Australia. tlatty@mail.usyd.edu.au

How individuals deal with multiple conflicting demands is an important aspect of foraging ecology, yet work on foraging behavior has typically neglected neurologically simple organisms. Here we examine the impact of an abiotic risk (light) and energetic status on the foraging decisions of a protist, the slime mold Physarum polycephalum. We examined patch choice in a "non-risky" environment by presenting starved and non-starved P. polycephalum amoebas with a choice between two shaded food patches (one high quality, one low quality). We next examined patch choice in the presence of a conflict between foraging risk (light exposure) and food quality by presenting amoebas with a choice between a shaded, low-quality patch, and a light-exposed, high-quality patch. When both patches were shaded, 100% of amoebas selected the higher quality food patch, irrespective of food-quality differences or the individual's energetic status. When light exposure and food quality conflicted, amoebas selected the patch with the higher food quality when the quality difference between the patches was high. When the quality difference between patches was small, amoebas selected the shaded, lower quality patch.

PMID: 20380191 [PubMed - indexed for MEDLINE]

720. Hum Exp Toxicol. 2011 Jan;30(1):38-43. Epub 2010 Apr 8.

Influence of commonly used clinical antidotes on antioxidant systems in human hepatocyte culture intoxicated with alpha-amanitin.

Magdalan J, Piotrowska A, Gomułkiewicz A, Sozański T, Szeląg A, Dziegięl P.

Department of Pharmacology, Wrocław Medical University, Mikulicza-Radeckiego 2, Wrocław, Poland.

α-Amanitin (α-AMA) is the main toxin of Amanita phalloides and its subspecies (A. virosa and A. verna). The primary mechanism of α-AMA toxicity is associated with protein synthesis blocking in hepatocytes. Additionally, α-AMA exhibits prooxidant properties that may contribute to its severe hepatotoxicity. The aim of the present study was to assess the effect of α-AMA on lipid peroxidation and the activities of superoxide dismutase (SOD) and catalase (CAT) in human hepatocyte culture. The effects of benzylpenicillin (BPCN), N-acetyl-L-cysteine (ACC), and silibinin (SIL) on SOD and CAT activities and on lipid peroxidation in human hepatocyte culture intoxicated with α-AMA were also examined. In human hepatocyte culture, 48-hour exposure to α-AMA at a 2-μM concentration caused an increase in SOD activity, a reduction of CAT activity, and a significant increase in lipid peroxidation. Changes in SOD and CAT activity caused by α-AMA could probably enhance lipid peroxidation by increased generation of hydrogen peroxide combined with reduced detoxification of that oxygen radical. The addition of antidotes (ACC or SIL) to the culture medium provided more effective protection against lipid peroxidation in human hepatocytes intoxicated with α-AMA than the addition of BPCN, possessing no antioxidant properties.

PMID: 20378659 [PubMed - indexed for MEDLINE]

721. Clin Microbiol Rev. 2010 Apr;23(2):367-81.

Clinical and laboratory update on blastomycosis.

Saccente M, Woods GL.

Department of Internal Medicine, University of Arkansas for Medical Sciences, 4301 West Markham Street, Slot #639, Little Rock, AR 72205, USA. saccentemichael@uams.edu

Blastomycosis is endemic in regions of North America that border the Great Lakes and the St. Lawrence River, as well as in the Mississippi River and Ohio River basins. Men are affected more often than women and children because men are more likely to participate in activities that put them at risk for exposure to Blastomyces dermatitidis. Human infection occurs when soil containing microfoci of mycelia is disturbed and airborne conidia are inhaled. If natural defenses in the alveoli fail to contain the infection, lymphohematogenous dissemination ensues. Normal host responses generate a characteristic pyogranulomatous reaction. The most common sites of clinical disease are the lung and skin; osseous, genitourinary, and central nervous system manifestations follow in decreasing order of frequency. Blastomycosis is one of the great mimickers in medicine; verrucous cutaneous blastomycosis resembles malignancy, and mass-like lung opacities due to B. dermatitidis often are confused with cancer. Blastomycosis may be clinically indistinguishable from tuberculosis. Diagnosis is based on culture and direct visualization of round, multinucleated yeast forms that produce daughter cells from a single broad-based bud. Although a long course of amphotericin B is usually curative, itraconazole is also highly effective and is the mainstay of therapy for most patients with blastomycosis.

PMCID: PMC2863359 PMID: 20375357 [PubMed - indexed for MEDLINE]

722. ACS Nano. 2010 Apr 27;4(4):1790-8.

Nitrogen-doped graphene and its application in electrochemical biosensing.

Wang Y, Shao Y, Matson DW, Li J, Lin Y.

Department of Chemistry, Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua University, Beijing 100084, People's Republic of China.

Chemical doping with foreign atoms is an effective method to intrinsically modify the properties of host materials. Among them, nitrogen doping plays a critical role in regulating the electronic properties of carbon materials. Recently, graphene, as a true two-dimensional carbon material, has shown fascinating applications in bioelectronics and biosensors. In this paper, we report a facile strategy to prepare N-doped graphene by using nitrogen plasma treatment of graphene synthesized via a chemical method. Meanwhile, a possible schematic diagram has been proposed to detail the structure of N-doped graphene. By controlling the exposure time, the N percentage in host graphene can be regulated, ranging from 0.11 to 1.35%. Moreover, the as-prepared N-doped graphene has displayed high electrocatalytic activity for reduction of hydrogen peroxide and fast direct electron transfer kinetics for glucose oxidase. The N-doped graphene has further been used for glucose biosensing with concentrations as low as 0.01 mM in the presence of interferences.

PMID: 20373745 [PubMed - indexed for MEDLINE]

723. Tenn Med. 2010 Mar;103(3):35.

TOSHA updates: hazard control.

Bachman A.

Compliance Department at DoctorsManagement. abachman@drsmgmt.com

PMID: 20373641 [PubMed - indexed for MEDLINE]

724. J Biol Chem. 2010 Jun 4;285(23):17359-70. Epub 2010 Apr 6.

Identification and functional characterization of a novel mitochondrial carrier for citrate and oxoglutarate in Saccharomyces cerevisiae.

Castegna A, Scarcia P, Agrimi G, Palmieri L, Rottensteiner H, Spera I, Germinario L, Palmieri F.

Department of Pharmaco-Biology, Laboratory of Biochemistry and Molecular Biology, University of Bari, 70125 Bari, Italy.

Mitochondrial carriers are a family of transport proteins that shuttle metabolites, nucleotides, and coenzymes across the mitochondrial membrane. The function of only a few of the 35 Saccharomyces cerevisiae mitochondrial carriers still remains to be uncovered. In this study, we have functionally defined and characterized the S. cerevisiae mitochondrial carrier Yhm2p. The YHM2 gene was overexpressed in S. cerevisiae, and its product was purified and reconstituted into liposomes. Its transport properties, kinetic parameters, and targeting to mitochondria show that Yhm2p is a mitochondrial transporter for citrate and oxoglutarate. Reconstituted Yhm2p also transported oxaloacetate, succinate, and fumarate to a lesser extent, but virtually not malate and isocitrate. Yhm2p catalyzed only a counter-exchange transport that was saturable and inhibited by sulfhydryl-blocking reagents but not by 1,2,3-benzenetricarboxylate (a powerful inhibitor of the citrate/malate carrier). The physiological role of Yhm2p is to increase the NADPH reducing power in the cytosol (required for biosynthetic and antioxidant reactions) and probably to act as a key component of the citrate-oxoglutarate NADPH redox shuttle between mitochondria and cytosol. This protein function is based on observations documenting a decrease in the NADPH/NADP(+) and GSH/GSSG ratios in the cytosol of DeltaYHM2 cells as well as an increase in the NADPH/NADP(+) ratio in their mitochondria compared with wild-type cells. Our proposal is also supported by the growth defect displayed by the DeltaYHM2 strain and more so by the DeltaYHM2DeltaZWF1 strain upon H(2)O(2) exposure, implying that Yhm2p has an antioxidant function.

PMCID: PMC2878499 PMID: 20371607 [PubMed - indexed for MEDLINE]

725. Am J Infect Control. 2010 Aug;38(6):456-60. Epub 2010 Apr 3.

Risk factors for fluconazole resistance in patients with Candida glabrata bloodstream infection: potential impact of control group selection on characterizing the association between previous fluconazole use and fluconazole resistance.

Lee I, Zaoutis TE, Fishman NO, Morales KH, Nachamkin I, Lautenbach E.

Division of Infectious Diseases, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. ingi.lee@uphs.upenn.edu

BACKGROUND: Although Candida glabrata is an emerging infection, risk factors for fluconazole resistance in patients with C glabrata bloodstram infection (BSI) have not been well elucidated.
METHODS: A case-control study was conducted to evaluate the primary risk factor of interest, previous fluconazole use, adjusting for demographics, comorbidities, time at risk, and antimicrobial exposure and assessing for effect modification. Secondary analyses were performed limiting the case group to C glabrata BSIs with a minimum inhibitory concentration (MIC) > or =64 microg/mL.
RESULTS: Previous fluconazole use was not a significant risk factor for fluconazole-resistant C glabrata BSI in primary analysis (adjusted odds ratio [aOR], 1.5; 95% confidence interval [CI], 0.7-3.2) but was borderline significant in secondary analysis (aOR, 3.2; 95% CI, 0.9-11.3). Increased time at risk was an independent risk factor in primary (aOR, 1.02; 95% CI, 1.002-1.04) and secondary analyses (aOR, 1.03; 95% CI, 1.004-1.06).
CONCLUSION: Increased time at risk was the only significant risk factor for fluconazole resistance. Future studies are needed to further evaluate the relationship between previous fluconazole use and fluconazole-resistant C glabrata BSI isolates with MIC > or =64 microg/mL.

PMID: 20371135 [PubMed - indexed for MEDLINE]

726. Med Mycol. 2010 May;48(3):498-505.

Analysis of the response of Candida albicans cells to Silver(I).

Rowan R, McCann M, Kavanagh K.

Medical Mycology Unit, Department of Biology, National University of Ireland-Maynooth, Co. Kildare, Ireland.

The response of the pathogenic yeast Candida albicans to the silver(I) perchlorate salt (AgClO(4)) was assessed. By employing an anti-phospho-p38 MAPK antibody, dual phosphorylation of a high osmolarity protein (Hog1p) in C. albicans in the presence of AgClO(4) was demonstrated. Phosphorylation of C. albicans Hog1p in response to hydrogen peroxide or AgClO(4) resulted in the translocation of this mitogen-activated protein (MAP) kinase to the nucleus. Nuclear translocation of C. albicans activating protein-1 (Cap1p) was demonstrated by Western blot analysis and detected using polyclonal anti-Cap1p antibody. Upon AgClO(4)-induced translocation of Cap1p there was a concomitant activation of genes coding for glutathione reductase-1 and Mn-superoxide dismutase but no increase in the expression of flavin oxidoreductase or mitochondrial processing protease was recorded. In addition, exposure to AgClO(4) increased the activity of superoxide dismutase, glutathione reductase and catalase. The activation of C. albicans oxidative stress response genes and enzymes following exposure to AgClO(4) is evidence of the generation of oxidative stress within this medically important yeast.

PMID: 20370363 [PubMed - indexed for MEDLINE]

727. Scand J Infect Dis. 2010 Jul;42(6-7):506-9.

Prior antimicrobial exposure and the risk for bloodstream infection with fluconazole-non-susceptible Candida strains.

Hebert C, Villaran R, Tolentino J, Best L, Boonlayangoor S, Pitrak D, Lin M, Weber SG.

Section of Infectious Diseases, University of Chicago Medical Center, Chicago, IL 60637, USA. Courtney.hebert@uchospitals.edu

Candida species are a common cause of bloodstream infection among hospitalized patients. Increasingly these infections are caused by strains resistant to commonly used antifungal agents. The aim of this study was to assess the association between exposure to specific antimicrobial agents and subsequent bloodstream infection with fluconazole-non-susceptible and fluconazole-susceptible Candida strains. A retrospective case-case-control study was performed. From 2002 to 2006, 50 consecutive patients with hospital-acquired bloodstream infection caused by Candida strains not fully susceptible to fluconazole were identified (case group 1). For comparison, 54 patients with fluconazole-susceptible candidaemia (case group 2) and a control group of 104 patients without candidaemia were studied. Models were adjusted for demographic and clinical risk factors. The risk for candidaemia associated with exposure to specific antimicrobial agents was assessed. Piperacillin/tazobactam (odds ratio (OR) 6.8, 95% confidence interval (CI) 1.4-32.2) and ciprofloxacin (OR 8.0, 95% CI 1.5-42.5), but not fluconazole, were significant risk factors for bloodstream infection with fluconazole-non-susceptible Candida. Only ciprofloxacin (OR 7.8, 95% CI 1.2-50.7) was associated with bloodstream infection with fluconazole-susceptible Candida. Despite adjustment for prior exposure to fluconazole, exposure to specific antibacterial agents was associated with hospital-acquired bloodstream infection with fluconazole-non-susceptible Candida.

PMID: 20370357 [PubMed - indexed for MEDLINE]

728. PLoS Pathog. 2010 Apr 1;6(4):e1000848.

Cryptococcus neoformans overcomes stress of azole drugs by formation of disomy in specific multiple chromosomes.

Sionov E, Lee H, Chang YC, Kwon-Chung KJ.

Molecular Microbiology Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, United States of America.

Cryptococcus neoformans is a haploid environmental organism and the major cause of fungal meningoencephalitis in AIDS patients. Fluconazole (FLC), a triazole, is widely used for the maintenance therapy of cryptococcosis. Heteroresistance to FLC, an adaptive mode of azole resistance, was associated with FLC therapy failure cases but the mechanism underlying the resistance was unknown. We used comparative genome hybridization and quantitative real-time PCR in order to show that C. neoformans adapts to high concentrations of FLC by duplication of multiple chromosomes. Formation of disomic chromosomes in response to FLC stress was observed in both serotype A and D strains. Strains that adapted to FLC concentrations higher than their minimal inhibitory concentration (MIC) contained disomies of chromosome 1 and stepwise exposure to even higher drug concentrations induced additional duplications of several other specific chromosomes. The number of disomic chromosomes in each resistant strain directly correlated with the concentration of FLC tolerated by each strain. Upon removal of the drug pressure, strains that had adapted to high concentrations of FLC returned to their original level of susceptibility by initially losing the extra copy of chromosome 1 followed by loss of the extra copies of the remaining disomic chromosomes. The duplication of chromosome 1 was closely associated with two of its resident genes: ERG11, the target of FLC and AFR1, the major transporter of azoles in C. neoformans. This adaptive mechanism in C. neoformans may play an important role in FLC therapy failure of cryptococcosis leading to relapse during azole maintenance therapy.

PMCID: PMC2848560 PMID: 20368972 [PubMed - indexed for MEDLINE]

729. Leuk Lymphoma. 2010 May;51(5):797-801.

High incidence of Pneumocystis jirovecii pneumonia in patients receiving biweekly rituximab and cyclophosphamide, adriamycin, vincristine, and prednisone.

Kamel S, O'Connor S, Lee N, Filshie R, Nandurkar H, Tam CS.

Hematology Department, St Vincent's Hospital, Melbourne, Victoria, Australia.

Comment in Leuk Lymphoma. 2010 May;51(5):737-8.

The risk of infection with Pneumocystis jirovecii pneumonia (PCP) in patients undergoing chemotherapy is closely related to the intensity of corticosteroid exposure. PCP is uncommon with classical (3-weekly) R-CHOP, but the risk may be higher with biweekly R-CHOP (R-CHOP-14) due to the increased frequency of prednisolone pulses. Among 47 consecutive patients treated with R-CHOP-14 at our institution, five (11%) developed microbiologically proven PCP, with a further two (4%) having classical clinical and radiological features of PCP, but without microbiological confirmation. None of these patients were HIV-positive or had additional risk factors for PCP. Our experience suggests that PCP prophylaxis should be considered in institutions using R-CHOP-14 for the treatment of patients with aggressive lymphomas.

PMID: 20367135 [PubMed - indexed for MEDLINE]

730. PLoS Negl Trop Dis. 2010 Mar 30;4(3):e643.

First description of a cluster of acute/subacute paracoccidioidomycosis cases and its association with a climatic anomaly.

Barrozo LV, Benard G, Silva ME, Bagagli E, Marques SA, Mendes RP.

Department of Geography, School of Phylosophy, Literature and Human Sciences, University of São Paulo, São Paulo, São Paulo State, Brazil. lija@usp.br

BACKGROUND: Identifying clusters of acute paracoccidioidomycosis cases could potentially help in identifying the environmental factors that influence the incidence of this mycosis. However, unlike other endemic mycoses, there are no published reports of clusters of paracoccidioidomycosis. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective cluster detection test was applied to verify if an excess of acute form (AF) paracoccidioidomycosis cases in time and/or space occurred in Botucatu, an endemic area in São Paulo State. The scan-test SaTScan v7.0.3 was set to find clusters for the maximum temporal period of 1 year. The temporal test indicated a significant cluster in 1985 (P<0.005). This cluster comprised 10 cases, although 2.19 were expected for this year in this area. Age and clinical presentation of these cases were typical of AF paracccidioidomycosis. The space-time test confirmed the temporal cluster in 1985 and showed the localities where the risk was higher in that year. The cluster suggests that some particularities took place in the antecedent years in those localities. Analysis of climate variables showed that soil water storage was atypically high in 1982/83 ( approximately 2.11/2.5 SD above mean), and the absolute air humidity in 1984, the year preceding the cluster, was much higher than normal ( approximately 1.6 SD above mean), conditions that may have favored, respectively, antecedent fungal growth in the soil and conidia liberation in 1984, the probable year of exposure. These climatic anomalies in this area was due to the 1982/83 El Niño event, the strongest in the last 50 years. CONCLUSIONS/SIGNIFICANCE: We describe the first cluster of AF paracoccidioidomycosis, which was potentially linked to a climatic anomaly caused by the 1982/83 El Niño Southern Oscillation. This finding is important because it may help to clarify the conditions that favor Paracoccidioides brasiliensis survival and growth in the environment and that enhance human exposure, thus allowing the development of preventive measures.

PMCID: PMC2846938 PMID: 20361032 [PubMed - indexed for MEDLINE]

731. New Solut. 2010;20(1):145-58.

"Serving two masters"--an interview with school teacher and union organizer Debra Askwith.

Scammell MK, Rodrigues E.

Boston University School of Public Health, Department of Environmental Health, Boston, MA 02118, USA. mls@bu.edu

Debra Askwith is a teacher, union member, and environmental health and safety activist in the public schools of Springfield, Massachusetts. In the following interview, she talks about her experiences organizing around the right to public information as a teacher and a union member. Working with the assistance of lawyers, she has learned to maneuver in the hierarchy of city and school administrators as well as the city's department of education, finding allies and meeting resistance in a variety of places. She has worked on asbestos, mold, indoor air quality, infectious disease, and civil rights to protect all students and workers.

PMID: 20359998 [PubMed - indexed for MEDLINE]

732. J Int Assoc Physicians AIDS Care (Chic). 2010 May-Jun;9(3):187-90. Epub 2010 Mar 31.

Human immunodeficiency virus postexposure prophylaxis at IBadan, Nigeria.

Olowookere SA, Fatiregun AA.

Department of Medicine, State Hospital, Oshogbo, Nigeria.

HIV infection from occupational and nonoccupational exposures can be prevented through risk assessment and management with antiretroviral drug therapy (ART). This study sought to examine the pattern of presentation and outcome of clients who were given postexposure prophylaxis (PEP) at the University College Hospital, Ibadan, Nigeria. A retrospective review of case notes of clients presenting for HIV PEP from January 2005 to December 2006 was carried out. A total of 48 clients with a mean age of 27.9 +/- 12.3 years underwent PEP during the period under review. Rape constituted 50% of reasons for PEP, while needle pricks and blood splash into mucous membranes constituted 25% each. Among those who received therapy, 10 (23.8%) could not complete drug therapy because of side effects. Although no client was HIV positive after the recommended 6 months of follow-up, 8 (16.7%) clients did not complete attendance to the clinic during the period.

PMID: 20357035 [PubMed - indexed for MEDLINE]

733. Med Mycol. 2010 Nov;48(7):981-7.

New evidence of the involvement of Lichtheimia corymbifera in farmer's lung disease.

Bellanger AP, Reboux G, Botterel F, Candido C, Roussel S, Rognon B, Dalphin JC, Bretagne S, Millon L.

CNRS-University of Franche Comté/UMR 6249 Chrono-environnement, Parasitology-Mycology Department, University Hospital Jean Minjoz, Besançon, France.

Farmer's lung disease (FLD) is a form of hypersensitivity pneumonitis resulting from recurrent exposure to moldy plant materials. We investigated and compared the initial response of respiratory epithelium after exposure to extracts of Sacharopolyspora rectivirgula, Lichtheimia corymbifera (formerly Absidia corymbifera), Eurotium amstelodami and Wallemia sebi. The two criteria for selection of these species were their high prevalence in the hay handled by FLD patients and the presence of high levels of specific precipitins to these molds in FLD patients’ sera. Hydrosoluble extracts were prepared from spores and hyphae grown in culture under optimal conditions for each of the four species. Confluent A549 cells were inoculated with one of the four calibrated soluble extracts. Two mediators, one inflammatory (Interleukin (IL)-8) and one allergic (IL-13), were quantified using real-time PCR and ELISA assay, after four exposure periods (30 min, 2 h, 4 h and 8 h). S. rectivirgula and L. corymbifera extracts were the only ones which induced a marked upregulation of IL-8, as shown by both real-time PCR and ELISA assay 8 h after the initial contact. This study adds to the growing body of evidence that L. corymbifera should be recognized as an etiologic agent of FLD along with S. rectivirgula.

PMID: 20353311 [PubMed - indexed for MEDLINE]

734. Toxins (Basel). 2010 Apr;2(4):738-57. Epub 2010 Apr 19.

Antigenotoxic studies of different substances to reduce the DNA damage induced by aflatoxin b(1) and ochratoxin a.

Madrigal-Santillán E, Morales-González JA, Vargas-Mendoza N, Reyes-Ramírez P, Cruz-Jaime S, Sumaya-Martínez T, Pérez-Pastén R, Madrigal-Bujaidar E.

Instituto de Ciencias de la Salud, Universidad Autónoma del Estado de Hidalgo., Ex-Hacienda de la Concepción. Tilcuautla. Pachuca de Soto, Hidalgo. CP 42080, México; Email: jmorales101@yahoo.com.mx (J.A.M.); nvargas_mendoza@hotmail.com (N.V.); pattyreyes_1@hotmail.com (P.R.); crzjms@msn.com (S.C.); teresumaya@hotmail.com (T.S.).

Mycotoxins are produced mainly by the mycelial structure of filamentous fungi, or more specifically, molds. These secondary metabolites are synthesized during the end of the exponential growth phase and appear to have no biochemical significance in fungal growth and development. The contamination of foods and feeds with mycotoxins is a significant problem for the adverse effects on humans, animals, and crops that result in illnesses and economic losses. The toxic effect of the ingestion of mycotoxins in humans and animals depends on a number of factors including intake levels, duration of exposure, toxin species, mechanisms of action, metabolism, and defense mechanisms. In general, the consumption of contaminated food and feed with mycotoxin induces to neurotoxic, immunosuppressive, teratogenic, mutagenic, and carcinogenic effect in humans and/or animals. The most significant mycotoxins in terms of public health and agronomic perspective include the aflatoxins, ochratoxin A (OTA), trichothecenes, fumonisins, patulin, and the ergot alkaloids. Due to the detrimental effects of these mycotoxins, several strategies have been developed in order to reduce the risk of exposure. These include the degradation, destruction, inactivation or removal of mycotoxins through chemical, physical and biological methods. However, the results obtained with these methods have not been optimal, because they may change the organoleptic characteristics and nutritional values of food. Another alternative strategy to prevent or reduce the toxic effects of mycotoxins is by applying antimutagenic agents. These substances act according to several extra- or intracellular mechanisms, their main goal being to avoid the interaction of mycotoxins with DNA; as a consequence of their action, these agents would inhibit mutagenesis and carcinogenesis. This article reviews the main strategies used to control AFB(1) and ochratoxin A and contains an analysis of some antigenotoxic substances that reduce the DNA damage caused by these mycotoxins.

PMCID: PMC3153197 PMID: 22069607 [PubMed]

735. Toxins (Basel). 2010 Apr;2(4):613-31. Epub 2010 Apr 5.

Biosynthesis and toxicological effects of patulin.

Puel O, Galtier P, Oswald IP.

INRA, UR66 Pharmacologie-Toxicologie, F-31027 Toulouse, France; Email: pgaltier@toulouse.inra.fr (P.G.); ioswald@toulouse.inra.fr (I.P.O.).

Patulin is a toxic chemical contaminant produced by several species of mold, especially within Aspergillus, Penicillium and Byssochlamys. It is the most common mycotoxin found in apples and apple-derived products such as juice, cider, compotes and other food intended for young children. Exposure to this mycotoxin is associated with immunological, neurological and gastrointestinal outcomes. Assessment of the health risks due to patulin consumption by humans has led many countries to regulate the quantity in food. A full understanding of the molecular genetics of patulin biosynthesis is incomplete, unlike other regulated mycotoxins (aflatoxins, trichothecenes and fumonisins), although the chemical structures of patulin precursors are now known. The biosynthetic pathway consists of approximately 10 steps, as suggested by biochemical studies. Recently, a cluster of 15 genes involved in patulin biosynthesis was reported, containing characterized enzymes, a regulation factor and transporter genes. This review includes information on the current understanding of the mechanisms of patulin toxinogenesis and summarizes its toxicological effects.

PMCID: PMC3153204 PMID: 22069602 [PubMed]

736. J Clin Microbiol. 2010 Jun;48(6):2016-21. Epub 2010 Mar 29.

High prevalence of dihydropteroate synthase mutations in Pneumocystis jirovecii isolated from patients with Pneumocystis pneumonia in South Africa.

Dini L, du Plessis M, Frean J, Fernandez V.

Department of Parasitology, Mycology, and Environmental Microbiology, Swedish Institute for Infectious Disease Control, Solna, Sweden. leigh.dini@smi.se

Pneumocystis jirovecii pneumonia (PCP) is an important cause of morbidity and mortality in immunocompromised patients. Sulfa-containing drugs are used for the treatment and prophylaxis of PCP. Mutations in the P. jirovecii fas gene, which encodes dihydropteroate synthase (DHPS), are associated with prior exposure to sulfa drugs, and their appearance suggests the emergence of variants with reduced sulfa susceptibility. The present study examined the prevalence of DHPS mutations in P. jirovecii strains isolated from South African patients with PCP. P. jirovecii infection was investigated by immunofluorescence microscopy and quantitative real-time PCR with respiratory specimens from 712 patients (93% of whom were >15 years of age) with suspected PCP consecutively received for the detection of P. jirovecii over 1 year. PCR amplification and sequencing of the DHPS fas gene was attempted with DNA from the P. jirovecii-positive samples. P. jirovecii infection was confirmed by immunofluorescence microscopy in 168/712 (24%) of the patients. Carriage of the fungus was revealed by real-time PCR in 17% of the patients with negative microscopy results. The P. jirovecii fas gene was successfully amplified from specimens from 151 patients and sequenced. Mutations resulting in the Thr55Ala and/or Pro57Ser amino acid substitution were detected in P. jirovecii strains from 85/151 (56%) patients. The high frequency of PCP episodes with P. jirovecii harboring DHPS mutations in South Africa indicates that populations of this fungus are evolving under the considerable selective pressure exerted by sulfa-containing antibiotics. These results, similar to previous observations of sulfa drug resistance in bacterial populations, underscore the importance of the rational use of sulfa medications either prophylactically against PCP or for the treatment of other infections.

PMCID: PMC2884465 PMID: 20351205 [PubMed - indexed for MEDLINE]

737. Clin Dermatol. 2010 Mar 4;28(2):185-9.

Pathogenesis of dermatophytosis and tinea versicolor.

Mendez-Tovar LJ.

Laboratory of Dermatology and Medical Mycology Research, Specialties Hospital, National Medical Center, IMSS, Apdo postal A-032, Coahuila No 5 Col Roma, 06703, México, DF, México. ljmt@servidor.unam.mx

Dermatophytoses are infections caused by keratinophilic fungi known as dermatophytes. Several steps are required for infection to take place: contact, adherence, and invasion of keratin layers. The severity of the infection depends on the type of agent, environmental factors, and the host immunologic status. Tinea versicolor is caused by the Malassezia spp yeasts, which are microorganisms that belong to normal biota in seborrheic areas, but some contributing factors, such as the application of oily preparations, creams, an increase in ambient humidity, corticosteroid abuse, or genetic predisposition can induce its overgrowth in both filamentous and yeast structures. Exposure to sunlight stimulates the production of azelaic acid, which causes the appearance of hypopigmented spots. Currently, there is no scientific explanation for hyperpigmented lesions.

PMID: 20347661 [PubMed - indexed for MEDLINE]

738. Rev Iberoam Micol. 2010 Jun 30;27(2):62-5. Epub 2010 Mar 24.

A zoonotic ringworm outbreak caused by a dysgonic strain of Microsporum canis from stray cats.

Hermoso de Mendoza M, Hermoso de Mendoza J, Alonso JM, Rey JM, Sanchez S, Martin R, Bermejo F, Cortes M, Benitez JM, Garcia WL, Garcia-Sanchez A.

Cátedra de Patología Infecciosa, Facultad de Veterinaria, Universidad de Extremadura, Cáceres, España. mhermoso@unex.es

BACKGROUND: Cats are frequent carriers of Microsporum canis and veterinary students are at high risk of exposure and acquisition of the organism a la infección. OBJECTIVES: An outbreak of zoonotic ringworm carried by a litter of stray cats is described. Four veterinary students, four dogs, and six cats living in five separate locations were affected. All had direct or indirect contact with the infected kitten litter. We tried to identify the causal dermatophyte.
METHODS: Conventional and mycological culture methods were used.
RESULTS: Microscopic features of scrapings and hairs treated with 20% KOH strongly suggested a M. canis etiology, and a diagnosis of ringworm was empirically supported by successful treatment of humans and animals. Nevertheless, cultures failed to show the expected morphology.
CONCLUSIONS: Culture features of our strain are compared with those described by other authors for dysgonic M. canis strains. Epidemiological features are also discussed.

PMID: 20346301 [PubMed - indexed for MEDLINE]

739. J Hosp Infect. 2010 May;75(1):47-51. Epub 2010 Mar 25.

Educational intervention for preventing bloodborne infection among medical students in China.

Zhang Z, Yamamoto T, Wu XN, Moji K, Cai GX, Kuroiwa C.

Department of International Health, Institute of Tropical Medicine (NEKKEN), Global Center of Excellence, Nagasaki University, Nagasaki, Japan. zzhuozhang@gmail.com

Although medical students are known to be at risk for bloodborne infections, there have been no systematic studies, effective intervention programmes, or guidelines for them in China. We developed prevention guidelines, implemented an intervention, and evaluated the effectiveness of knowledge among medical students. This study was designed as a cluster randomised controlled trial. All those who completed a consent form were randomly assigned either to an intervention or to a control group. The intervention group underwent an educational intervention programme consisting of a series of lectures and videos following a baseline survey. The control group completed the same intervention programme after the study was completed. A questionnaire of 25 items was sent to participants three months and nine months after the initial intervention programme. Outcomes measured before and after intervention included knowledge of transmission route, first-aid care, and post-exposure prophylaxis. Pearson's chi(2)-test was used, and the efficacy of students was analysed to control for bias. Intervention in the form of a one-time bloodborne pathogen educational prevention programme for Chinese medical students had little effect on knowledge.

PMID: 20338670 [PubMed - indexed for MEDLINE]

740. Lett Appl Microbiol. 2010 Jun 1;50(6):571-7. Epub 2010 Mar 17.

Pyrogenic activity of air to characterize bioaerosol exposure in public buildings: a pilot study.

Bernasconi C, Rodolfi M, Picco AM, Grisoli P, Dacarro C, Rembges D.

European Commission, Joint Research Centre, Institute for Health and Consumer Protection, Ispra, Italy. camilla.bernasconi@jrc.ec.europa.eu

AIMS: The aim of our study was to investigate indoor air quality (IAQ) by comparing pyrogen concentration and microbiological contamination in offices in public buildings. METHODS AND RESULTS: Air samples were collected during cold and warm seasons in 39 offices in four European cities. Pyrogens were measured by the in vitro pyrogen test (IPT), moulds and bacteria by classical microbiology. In 92% of the investigated offices, pyrogen and microbial contaminations were below 150 EEU m(-3) and 10(3) CFU m(-3), respectively, whilst in 75%, moulds did not exceed 10(2) CFU m(-3).
CONCLUSIONS: The IPT is a rapid, reliable tool for measuring pyrogens that could be used as an 'early warning' indicator of IAQ. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study on pyrogenic compound detection in offices using IPT, which could serve for developing future indoor air guidelines.

PMID: 20337928 [PubMed - indexed for MEDLINE]

741. Invest Ophthalmol Vis Sci. 2010 Aug;51(8):3950-3. Epub 2010 Mar 24.

In vitro efficacy of antifungal treatment using riboflavin/UV-A (365 nm) combination and amphotericin B.

Sauer A, Letscher-Bru V, Speeg-Schatz C, Touboul D, Colin J, Candolfi E, Bourcier T.

Service d'Ophtalmologie, Hopitaux Universitaires de Strasbourg, Nouvel Hopital Civil, Strasbourg, France. arnaud.sauer@chru-strasbourg.fr

PURPOSE: To demonstrate the antimicrobial properties of riboflavin/UV-A (365 nm) against fungal pathogens.
METHODS: The antimicrobial properties of riboflavin/UV-A (365 nm), with or without previous treatment with amphotericin B, were tested on three groups of fungi selected from severe cases of keratomycosis: Candida albicans, Fusarium sp, and Aspergillus fumigatus. They were tested by using Kirby-Bauer discs with empty disc (control), riboflavin 0.1% alone (R), UV-A alone (UV-A), riboflavin 0.1% and additional UV-A exposure (R+UV-A), amphotericin B alone (A), amphotericin B and riboflavin 0.1% (A+R), amphotericin B and UV-A (A+UV-A), amphotericin B and riboflavin 0.1%, and additional UV-A exposure (A+R+UV-A). The mean growth inhibition zone (GIZ) was measured around the discs.
RESULTS: C. albicans, Fusarium sp, and A. fumigatus did not show any increased GIZ after treatment without previous amphotericin B medication. However, GIZ was significantly greater after pretreatment with amphotericin B and riboflavin/UV-A (A+R+UV-A) for C. albicans (P = 0.0005), Fusarium sp (P = 0.0023) and A. fumigatus (P = 0.0008) compared with A, A+R, and A+UV-A.
CONCLUSIONS: Amphotericin B is believed to interact with fungi membrane sterols to produce aggregates that form transmembrane channels. Given that collagen is one of the principal components of the cornea, it is also probable that amphotericin B may diffuse easily after cross-linking. Previous treatment with amphotericin B allowed riboflavin/UV-A effectiveness against C. albicans, Fusarium sp, and A. fumigatus. This schema might be used in the future for the treatment of keratomycosis.

PMID: 20335618 [PubMed - indexed for MEDLINE]

742. J Antimicrob Chemother. 2010 Jun;65(6):1207-14. Epub 2010 Mar 23.

Acidified nitrite enhances hydrogen peroxide disinfection of Acanthamoeba, bacteria and fungi.

Heaselgrave W, Andrew PW, Kilvington S.

Department of Infection, Immunity & Inflammation, University of Leicester, Medical Sciences Building, PO Box 138, University Road, Leicester LE1 9HN, UK. wh12@leicester.ac.uk

OBJECTIVES: In the human innate immune system, stimulated phagocytes release reactive nitrogen intermediates that can react with superoxide to form the powerful oxidant peroxynitrite and other less abundant species. In this study, the efficacy of hydrogen peroxide (H2O2) and acidified nitrite (NaNO2) alone and in combination was compared against a variety of bacteria, fungi and protozoa.
METHODS: Challenge test assays based on the international standard (ISO 14729) were used to determine the antimicrobial activity of H2O2 and acidified NaNO2 at pH 5 alone and in combination against Pseudomonas aeruginosa, Serratia marcescens, Staphylococcus aureus, Mycobacterium aurum, Bacillus subtilis spores, Candida albicans, Fusarium solani conidia and Acanthamoeba polyphaga trophozoites and cysts.
RESULTS: When tested alone, both H2O2 (0.4% v/v) and NaNO2 (2 mg/mL, pH 5) produced a >or=4 log reduction in viability after 4 h of exposure for all bacteria and A. polyphaga trophozoites, but not B. subtilis spores, F. solani and A. polyphaga cysts, which gave a or=4 log kill of all test organisms within 1 h. Addition of NaNO2 also enhanced the antimicrobial efficacy of a H2O2-based contact lens disinfection system.
CONCLUSIONS: The findings of this study demonstrate that acidified NaNO2 can significantly enhance the antimicrobial activity of H2O2 probably through the generation of peroxynitrite. The addition of acidified nitrite to 3% (v/v) H2O2 solution may represent an improved one-step method for the disinfection of contact lenses, especially against highly resistant cysts of Acanthamoeba spp.

PMID: 20335189 [PubMed - indexed for MEDLINE]

743. Sci Total Environ. 2010 May 15;408(12):2543-8. Epub 2010 Mar 23.

Accumulation of potassium, rubidium and caesium (133Cs and 137Cs in various fractions of soil and fungi in a Swedish forest.

Vinichuk M, Taylor AF, Rosén K, Johanson KJ.

Department of Soil and Environment, Swedish University of Agricultural Sciences, P.O. Box 7014, SE-750 07, Uppsala, Sweden. Mykhailo.Vinichuk@mark.slu.se

Radiocaesium ((137)Cs) was widely deposited over large areas of forest in Sweden as a result of the Chernobyl accident in 1986 and many people in Sweden eat wild fungi and game obtained from these contaminated forests. In terms of radioisotope accumulation in the food chain, it is well known that fungal sporocarps efficiently accumulate radiocaesium ((137)Cs), as well as the alkali metals potassium (K), rubidium (Rb) and caesium (Cs). The fungi then enhance uptake of these elements into host plants. This study compared the accumulation of these three alkali metals in bulk soil, rhizosphere, soil-root interface, fungal mycelium and sporocarps of mycorrhizal fungi in a Swedish forest. The soil-root interface was found to be distinctly enriched in K and Rb compared with the bulk soil. Potassium concentrations increased in the order: bulk soil

PMID: 20334900 [PubMed - indexed for MEDLINE]

744. Infect Control Hosp Epidemiol. 2010 May;31(5):498-502.

Comparison of 4 different types of surgical gloves used for preventing blood contact.

Wittmann A, Kralj N, Köver J, Gasthaus K, Lerch H, Hofmann F.

Department of Safety Engineering, University of Wuppertal, D-42119 Wuppertal, Germany. andwitt@uni-wuppertal.de

BACKGROUND: Needlestick injuries are always associated with a risk of infection, because these types of punctures may expose healthcare workers to a patient's blood and/or body fluids.
OBJECTIVE: To compare the efficacy of 4 different types of surgical gloves for preventing exposure to blood as a result of needlestick injury.
METHODS: For simulation of needlestick injury, a circular sample of pork skin was tightened onto a bracket, and a single finger from a medical glove was stretched over the sample. First, a powder-free surgical glove with a gel coating was used to test blood contact. Second, a glove with a patented puncture indication system was used to test blood contact with a double-gloved hand. Third, 2 powder-free latex medical gloves of the same size and hand were combined for double gloving, again to test blood contact. Finally, we tested a glove with an integrated disinfectant on the inside. The punctures were carried out using diverse sharp surgical devices that were contaminated with (99)Tc-marked blood. The amount of blood contact was determined from the transmitted radioactivity.
RESULTS: For the powder-free surgical glove with a gel coating, a mean volume of 0.048 microL of blood (standard error of the mean [SEM], 0.077 microL) was transferred in punctures with an automated lancet at a depth of 2.4 mm through 1 layer of latex. For the glove with an integrated disinfectant on the inside, the mean volume of blood transferred was 0.030 microL (SEM, 0.0056 microL) with a single glove and was 0.024 microL (SEM, 0.003 microL) with 2 gloves. For the glove with the patented puncture indication system, a mean volume of 0.024 microL (SEM, 0.003 microL) of blood was transferred.
CONCLUSIONS: Double gloving or the use of a glove with disinfectant can result in a decrease in the volume of blood transferred. Therefore, the use of either of these gloving systems could help to minimize the risk of bloodborne infections for medical staff.

PMID: 20334549 [PubMed - indexed for MEDLINE]

745. Proc Natl Acad Sci U S A. 2010 Apr 6;107(14):6394-9. Epub 2010 Mar 22.

Ribosome-associated peroxiredoxins suppress oxidative stress-induced de novo formation of the [PSI+] prion in yeast.

Sideri TC, Stojanovski K, Tuite MF, Grant CM.

Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, United Kingdom.

Peroxiredoxins (Prxs) are ubiquitous antioxidants that protect cells against oxidative stress. We show that the yeast Tsa1/Tsa2 Prxs colocalize to ribosomes and function to protect the Sup35 translation termination factor against oxidative stress-induced formation of its heritable [PSI(+)] prion conformation. In a tsa1 tsa2 [psi(-)] [PIN(+)] strain, the frequency of [PSI(+)] de novo formation is significantly elevated. The Tsa1/Tsa2 Prxs, like other 2-Cys Prxs, have dual activities as peroxidases and chaperones, and we show that the peroxidase activity is required to suppress spontaneous de novo [PSI(+)] prion formation. Molecular oxygen is required for [PSI(+)] prion formation as growth under anaerobic conditions prevents prion formation in the tsa1 tsa2 mutant. Conversely, oxidative stress conditions induced by exposure to hydrogen peroxide elevates the rate of de novo [PSI(+)] prion formation leading to increased suppression of all three termination codons in the tsa1 tsa2 mutant. Altered translational fidelity in [PSI(+)] strains may provide a mechanism that promotes genetic variation and phenotypic diversity (True HL, Lindquist SL (2000) Nature 407:477-483). In agreement, we find that prion formation provides yeast cells with an adaptive advantage under oxidative stress conditions, as elimination of the [PSI(+)] prion from tsa1 tsa2 mutants renders the resulting [psi(-)] [pin(-)] cells hypersensitive to hydrogen peroxide. These data support a model in which Prxs function to protect the ribosomal machinery against oxidative damage, but when these systems become overwhelmed, [PSI(+)] prion formation provides a mechanism for uncovering genetic traits that aid survival during oxidative stress conditions.

PMCID: PMC2851942 PMID: 20308573 [PubMed - indexed for MEDLINE]

746. J Occup Health. 2010;52(3):186-93. Epub 2010 Mar 19.

Distribution and identification of airborne fungi in railway stations in Tokyo, Japan.

Kawasaki T, Kyotani T, Ushiogi T, Izumi Y, Lee H, Hayakawa T.

Environmental Biotechnology Laboratory, Railway Technical Research Institute, 2-3-38 Hikari-cho, Kokobunji-shi, Tokyo, Japan. tamami@rtri.or.jp

OBJECTIVES: The current study was performed to (1) understand the distribution of airborne fungi culturable on dichloran-glycerol agar (DG18) media over a one-year monitoring period, (2) identify the types of airborne fungi collected, and (3) compare and contrast under- and above-ground spaces, in two railway stations in Tokyo, Japan.
METHODS: Measurements of airborne fungi were taken at stations A and B located in Tokyo. Station A had under- and above-ground concourses and platforms whereas station B had spaces only above-ground. Airborne fungi at each measurement position were collected with an air sampler on DG18 media. After cultivation of the sample plates, the number of fungi colonies was counted on each agar plate.
RESULTS: In station A, the underground platform was characterized as (1) having the highest humidity and (2) a high concentration of airborne fungi, with (3) a high proportion of non-sporulating fungi (NSF) and Aspergillus versicolor. There was a strong positive correlation between the concentrations of airborne particles and fungi in station A. Common aspects of the two stations were (1) that fungi were mostly detected in autumn, and (2) there was no correlation between the humidity and concentration of fungi throughout the year.
CONCLUSIONS: The results of this study indicate that the distribution and composition of fungi differ depending on the structure of the station.

PMID: 20299760 [PubMed - indexed for MEDLINE]

747. Methods Mol Biol. 2010;638:225-33.

A method to visualize the actin and microtubule cytoskeleton by indirect immunofluorescence.

Banuett F.

Department of Biological Sciences, California State University, Long Beach, CA, USA.

The cytoskeleton provides the basic architectural organization and shape of the eukaryotic cell, and plays a key role in segregation of the genetic material. A method to visualize the actin and microtubule cytoskeleton in the fungus Ustilago maydis by indirect immunofluorescence is described here. The method entails growth of cells to early logarithmic phase, fixation with a cross-linking agent or organic solvent, partial digestion of the cell wall and permeabilization of cells with a detergent to allow entry of antibodies, exposure to primary antibody, followed by treatment with secondary antibody conjugated to a fluorophore to allow visualization with fluorescence microscopy.

PMID: 20238273 [PubMed - indexed for MEDLINE]

748. Virol J. 2010 Mar 17;7:62.

Human herpesvirus-8 in northwestern China: epidemiology and characterization among blood donors.

Wang X, He B, Zhang Z, Liu T, Wang H, Li X, Zhang Q, Lan K, Lu X, Wen H.

First Teaching Hospital of Xinjiang Medical University, Urumqi, Xinjiang, PR China. wangxing7610@yahoo.com.cn

BACKGROUND: Human herpes virus 8 (HHV-8) is the etiologic agent associated with development of classical, AIDS-related, iatrogenic, and endemic Kaposi's sarcoma (KS). Several studies provide strong evidence that HHV-8 can be transmitted by blood transfusion. We evaluated the seroprevalence and potential risk factors of HHV-8 infection in blood donors in one region. We surveyed HHV-8 infection among 4461 blood donors in Xinjiang, China, a unique endemic area for HHV-8 and KS.
RESULTS: The HHV-8 seroprevalence was higher in local minority groups which comprise most KS cases in China, than in Han people. HHV-8 prevalence was 18.6% in the Han ethnic group, 25.9% in Uygur subjects, 29.2% in Kazak subjects, 36.8% in Mongolian subjects, and 21.9% in other ethnic groups. In several subgroups, the time of donation of whole blood seemed to be a risk factor. In HHV-8-seropositive subjects, a larger fraction of local minorities (23.9%) had high HHV-8 titers than that of Han subjects (9.2%). HHV-8 infection was associated with ethnicity and residence.
CONCLUSION: HHV-8 seroprevalence was significantly high among blood donors in Xinjiang, where the prevalence of KS correlates with HHV-8 prevalence and titers in Uygur and Kazak ethnic groups. Blood exposure represented by the frequency of blood donation indicated a possible blood-borne transmission route of HHV-8 in Xinjiang. Detecting anti-HHV-8 antibodies before donation in this region is therefore important.

PMCID: PMC2852390 PMID: 20236530 [PubMed - indexed for MEDLINE]

749. Mycoses. 2011 Jul;54(4):e175-7. doi: 10.1111/j.1439-0507.2010.01867.x. Epub 2010 Mar 4.

Repeated exposure of Candida spp. to miconazole demonstrates no development of resistance.

Ghannoum MA, Herbert J, Isham N.

Center for Medical Mycology, Case Western Reserve University, Cleveland, OH 44106, USA. mahmoud.ghannoum@case.edu

Oropharyngeal candidiasis (OPC) is a common infection among the immuno-compromised population. Treatments include both systemic azoles, most commonly fluconazole (FLU), and topical agents such as miconazole (MICON). However, resistance to FLU has been reported with a greater frequency. The aim of this study was to determine the potential for development of resistance following repeated exposure of Candida spp. to MICON. Two clinical isolates each of Candida albicans, C. glabrata, and C. tropicalis were tested. Fifteen passages of each strain were performed in concentrations of MICON at 0.5 minimum inhibitory concentration (MIC), 1 MIC, 2 MIC and 4 MIC, with MIC determinations performed on growth obtained following each passage. There was no increase in the MIC of four of the six strains following fifteen passages in MICON. One C. albicans strain demonstrated a four-five dilution increase in MICON MIC at all concentrations and one C. glabrata strain showed a fivefold MICON MIC increase when exposed to 4 MIC. Although an increase in MIC was noted in these two isolates, the MICON MIC was still very low (0.5 μg ml(-1)). In general, there was no increase in MIC demonstrated by repeated exposure to MICON in this study.

PMCID: PMC2955168 [Available on 2012/7/1] PMID: 20236241 [PubMed - indexed for MEDLINE]

750. Inhal Toxicol. 2010 May;22(6):460-8.

The relative allergenicity of Stachybotrys chartarum compared to house dust mite extracts in a mouse model.

Chung YJ, Copeland LB, Doerfler DL, Ward MD.

US Environmental Protection Agency, Cardiopulmonary and Immunotoxicology Branch, Research Triangle Park, North Carolina, USA.

A report by the Institute of Medicine suggested that more research is needed to better understand mold effects on allergic disease, particularly asthma development. The authors compared the ability of the fungus Stachybotrys chartarum (SCE) and house dust mite (HDM) extracts to induce allergic responses in BALB/c mice. The extracts were administered by intratracheal aspiration (IA) at several doses (0, 2.5, 5, 10, 20, 40, and 80 microg) 4 times over a 4-week period. Three days after the last IA exposure, serum and bronchoalveolar lavage fluid (BALF) were collected. The relative allergenicity of the extracts was evaluated based on the lowest dose that induced a significant response compared to control (0 microg) and the linear regression slope analysis across the dose range. SCE induced a more robust response than HDM for BALF some inflammatory cells (macrophage and neutrophils), whereas HDM induced more robust BALF lymphocyte and eosinophil responses. Although SCE induced a more robust serum total immunoglobulin E (IgE) response than did HDM, the induction of a similar response in a functional, antigen-specific IgE assay required approximately twice as much SCE as HDM. Even though SCE demonstrates the ability to induce allergic responses in the mouse model, considering the importance and relevance of eosinophil, lymphocyte, and antigen-specific IgE in allergic airway disease, it is concluded that HDM is more potent than SCE in the induction of allergic responses. These data suggest a threshold dose for SCE allergy induction. Furthermore, in damp water-damaged environments, exposure to S. chartarum might easily exceed the sensitization threshold for a susceptible population.

PMID: 20235799 [PubMed - indexed for MEDLINE]

751. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2010 Apr;27(4):510-20.

Decontamination and detoxification strategies for the Fusarium mycotoxin deoxynivalenol in animal feed and the effectiveness of microbial biodegradation.

Awad WA, Ghareeb K, Bohm J, Zentek J.

Institute of Nutrition, Department of Veterinary Public Health and Food Science, University of Veterinary Medicine, A-1210 Vienna, Austria.

Trichothecenes are a group of mycotoxins mainly produced by fungi of the Fusarium genus. Deoxynivalenol (DON) is one of the most abundant and important trichothecenes in food and feed, and is a significant contaminants due to its frequent occurrence in toxicologically relevant concentrations worldwide. Since toxin production depends strongly on environmental conditions, such as temperature and humidity, Fusarium toxin contamination can not be avoided completely. Therefore, exposure to this toxin is a permanent health risk for both humans and farm animals. As cereal crops are commonly contaminated with DON and animal diets consist mainly of cereals, it can be assumed that animals are frequently exposed to DON-contaminated feeds. Many strategies can be undertaken to reduce the toxic effect of DON. In addition to the general necessity for minimizing all risk factors that might influence the contamination of cereals with DON, such as the so-called field toxins before harvest, several post-harvest strategies can be applied to counteract possible deleterious effects of this mycotoxin in farm animals. Another approach for decontamination in feedstuffs is the use of adsorbent materials. Adsorbent materials may bind mycotoxins in the gastrointestinal tract and reduce absorption and systemic toxicity. It has been shown that some adsorbents are suitable to alleviate the toxic effects of specific mycotoxins, but its efficacy against trichothecenes is practically zero. Therefore, alternative strategies to reduce animal and human health risk are needed. The use of microbial additives is a method which uses microorganisms having the capability to detoxify mycotoxins by metabolism or degradation prior to their resorption in the gastrointestinal tract. DON has been reported to be completely transformed to de-epoxy-DON by ruminal and intestinal microflora. Eubacterium BBSH 797 was capable of DON degradation and counteracted the toxic effects of DON in animals. This review focuses on the efficacy of microbial feed additives in ameliorating the toxic effects of DON. According to the results of experiments to date, it appears that microorganisms are the main living organisms suitable for this mycotoxin biodegradation. However, the use of this approach depends on its effectiveness from both a practical and economic perspective.

PMID: 20234966 [PubMed - indexed for MEDLINE]

752. J Antimicrob Chemother. 2010 May;65(5):842-52. Epub 2010 Mar 16.

Clinically significant micafungin resistance in Candida albicans involves modification of a glucan synthase catalytic subunit GSC1 (FKS1) allele followed by loss of heterozygosity.

Niimi K, Monk BC, Hirai A, Hatakenaka K, Umeyama T, Lamping E, Maki K, Tanabe K, Kamimura T, Ikeda F, Uehara Y, Kano R, Hasegawa A, Cannon RD, Niimi M.

Department of Oral Sciences, University of Otago, 310 Great King St, Dunedin 9054, New Zealand. kyoko.niimi@otago.ac.nz

OBJECTIVES: To determine the mechanism of intermediate- and high-level echinocandin resistance, resulting from heterozygous and homozygous mutations in GSC1 (FKS1), in both laboratory-generated and clinical isolates of Candida albicans.
METHODS: The DNA sequences of the entire open reading frames of GSC1, GSL1 (FKS3) and RHO1, which may contribute to the beta-1,3-glucan synthase of a micafungin-susceptible strain and a resistant clinical isolate, were compared. A spontaneous heterozygous mutant isolated by selection for micafungin resistance, and a panel of laboratory-generated homozygous and heterozygous mutants that possessed combinations of the echinocandin-susceptible and -resistant alleles, or mutants with individual GSC1 alleles deleted, were used to compare levels of echinocandin resistance and inhibition of glucan synthase activity.
RESULTS: DNA sequence analysis identified a mutation, S645P, in both alleles of GSC1 from the clinical isolate. GSL1 had two homozygous amino acid changes and five non-synonymous nucleotide polymorphisms due to allelic variation. The predicted amino acid sequence of Rho1p was conserved between strains. Reconstruction of the heterozygous (S645/S645F) and homozygous (S645F/S645F) mutation showed that the homozygous mutation conferred a higher level of micafungin resistance (4 mg/L) than the heterozygous mutation (1 mg/L). Exposure of the heterozygous mutant to micafungin resulted in a loss of heterozygosity. Kinetic analysis of beta-1,3-glucan synthase activity showed that the homozygous and heterozygous mutations gave echinocandin susceptibility profiles that correlated with their MIC values.
CONCLUSIONS: A homozygous hot-spot mutation in GSC1, caused by mutation in one allele and then loss of heterozygosity, is required for high-level echinocandin resistance in C. albicans. Both alleles of GSC1 contribute equally and independently to beta-1,3-glucan synthase activity.

PMID: 20233776 [PubMed - indexed for MEDLINE]

753. Parasit Vectors. 2010 Mar 16;3(1):18.

An extra-domiciliary method of delivering entomopathogenic fungus, Metharizium anisopliae IP 46 for controlling adult populations of the malaria vector, Anopheles arabiensis.

Lwetoijera DW, Sumaye RD, Madumla EP, Kavishe DR, Mnyone LL, Russell TL, Okumu FO.

Biomedical and Environmental Thematic Group, Ifakara Health Institute, PO Box 53, Ifakara, Tanzania. dwilson@ihi.or.tz.

ABSTRACT: Fungal biopesticides have the potential to significantly reduce densities of malaria vectors as well as associated malaria transmission. In previous field trials, entomopathogenic fungus was delivered from within human dwellings, where its efficacy was limited by low infection rates of target mosquitoes, high costs of spraying fungus inside houses, and potential public health concerns associated with introducing fungal conidia inside houses. Here we have demonstrated that Metarhizium anisopliae IP 46, delivered within an extra-domiciliary odor-baited station (OBS), can infect and slowly-kill a high proportion of the wild adult malaria vector, Anopheles arabiensis which entered and exited the OBS. This study, carried out in rural Tanzania, showed that by using a concentration of 3.9 x 1010 conidia/m2, more than 95% of mosquitoes that flew in and out of the OBS died within 14 days post-exposure. At least 86% infection of mosquito cadavers was recorded with a significant reduction in the probability of daily survival of exposed An. arabiensis in both treatments tested: low quantity of conidia (eave baffles plus one cotton panel; HR = 2.65, P < 0.0001) and high quantity of conidia (eave baffles plus two cotton panels; HR = 2.32, P < 0.0001). We conclude that high infection rates of entomopathogenic fungi on wild malaria vectors and possibly significant disruption of malaria transmission can be achieved if the fungus is delivered using optimally located outdoor odor-baited stations.

PMCID: PMC2848008 PMID: 20233423 [PubMed - in process]

754. Bioresour Technol. 2010 Jul;101(14):5186-93. Epub 2010 Mar 15.

Identification and characterization of bioemulsifier-producing yeasts isolated from effluents of a dairy industry.

Monteiro AS, Bonfim MR, Domingues VS, Corrêa A Jr, Siqueira EP, Zani CL, Santos VL.

Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, CP 486, 31270-901 Belo Horizonte, MG, Brazil. andreasmont@gmail.com

New bioemulsifier-producing yeasts were isolated from the biological wastewater treatment plant of a dairy industry. Of the 31 bioemulsifier-producing strains, 12 showed emulsifying activity after 2months of incubation, with E(24) values ranging from 7% to 78%. However, only Trichosporon loubieri CLV20, Geotrichum sp. CLOA40, and T. montevideense CLOA70 exhibited high emulsion-stabilizing capacity, with E(24) values of 78%, 67%, and 66%, respectively. These isolates were shown to induce a strong emulsion stabilizing activity rather than the reduction of the interfacial tension. These strains exhibited similar growth rates in the exponential growth phase, with a clear acceleration after 24h and stabilization of the activity after 144h. Emulsification and stability properties of the bioemulsifiers were compared to those of commercial surfactants after the addition of NaCl and exposure to temperature of 100 degrees C. The compounds produced by the isolates appeared to be lipid-polysaccharide complexes. Gas chromatograph analysis of the lipidic fraction of the bioemulsifiers from CLV20, CLOA40, and CLOA70 shows the prevalence of (9Z,12Z)-octadeca-9,12-dienoic acid, in concentrations of 42.8%, 25.9%, and 49.8%, respectively. The carbohydrate composition, as determined by GC-MS of their alditol acetate derivatives, showed a predominance of mannose, galactose, xylose and arabinose.

PMID: 20231088 [PubMed - indexed for MEDLINE]

755. J Chem Ecol. 2010 Apr;36(4):351-60. Epub 2010 Mar 13.

Arbuscular mycorrhizal fungi protect a native plant from allelopathic effects of an invader.

Barto K, Friese C, Cipollini D.

Department of Biological Sciences, Wright State University, Dayton, OH 45435, USA. barto@zedat.fu-berlin.de

The allelopathic potential of the Eurasian invasive plant Alliaria petiolata has been well documented, with the bulk of the effects believed to be mediated by arbuscular mycorrhizal fungi (AMF). We exposed the herbaceous annual Impatiens pallida, which is native to North America, to fractionated A. petiolata extracts at four developmental stages (germination, presymbiosis growth, symbiosis formation, and symbiosis growth) by using exposure levels expected to be similar to field levels. Surprisingly, we found strong direct effects on I. pallida germination and growth, but no indirect effects on I. pallida growth mediated by AMF. We also observed strong synergistic effects with a complete A. petiolata extract that inhibited I. pallida germination and presymbiosis root growth more than either a glucosinolate or flavonoid enriched fraction alone. In fact, the flavonoid enriched fraction tended to stimulate germination and presymbiosis root growth. In contrast to these strong direct effects, I. pallida plant growth during both the symbiosis formation and symbiosis growth phases was unaffected by A. petiolata extracts. We also found no inhibition of AMF colonization of roots or soils by A. petiolata extracts. We show that AMF can actually ameliorate allelopathic effects of an invasive plant, and suggest that previously observed allelopathic effects of A. petiolata may be due to direct inhibition of plant and fungal growth before symbiosis formation.

PMID: 20229215 [PubMed - indexed for MEDLINE]

756. Appl Environ Microbiol. 2010 May;76(9):3032-8. Epub 2010 Mar 12.

Five-year cohort study of Nosema spp. in Germany: does climate shape virulence and assertiveness of Nosema ceranae?

Gisder S, Hedtke K, Möckel N, Frielitz MC, Linde A, Genersch E.

Institute for Bee Research, Friedrich-Engels-Str. 32, Hohen Neuendorf, Germany.

Nosema ceranae and Nosema apis are two fungal pathogens belonging to the phylum Microsporidia and infecting the European honeybee, Apis mellifera. Recent studies have suggested that N. ceranae is more virulent than N. apis both at the individual insect level and at the colony level. Severe colony losses could be attributed to N. ceranae infections, and an unusual form of nosemosis is caused by this pathogen. In the present study, data from a 5-year cohort study of the prevalence of Nosema spp. in Germany, involving about 220 honeybee colonies and a total of 1,997 samples collected from these colonies each spring and autumn and analyzed via species-specific PCR-restriction fragment length polymorphism (RFLP), are described. Statistical analysis of the data revealed no relation between colony mortality and detectable levels of infection with N. ceranae or N. apis. In addition, N. apis is still more prevalent than N. ceranae in the cohort of the German bee population that was analyzed. A possible explanation for these findings could be the marked decrease in spore germination that was observed after even a short exposure to low temperatures (+4 degrees C) for N. ceranae only. Reduced or inhibited N. ceranae spore germination at low temperatures should hamper the infectivity and spread of this pathogen in climatic regions characterized by a rather cold winter season.

PMCID: PMC2863439 PMID: 20228103 [PubMed - indexed for MEDLINE]

757. J Hazard Mater. 2010 Jun 15;178(1-3):1085-93. Epub 2010 Feb 20.

Study of the mechanisms of Cu2+ biosorption by ethanol/caustic-pretreated baker's yeast biomass.

Zhang Y, Liu W, Xu M, Zheng F, Zhao M.

College of Life and Science, Sichuan Agricultural University, Yaan 625014, PR China.

Baker's yeast biomass was pretreated by ethanol and caustic soda, and then the pristine baker's yeast, ethanol pretreated baker's yeast (ethanol-baker's yeast) and caustic soda pretreated baker's yeast (caustic-baker's yeast) were utilized as biosorbents to adsorb Cu(2+) in aqueous solution. The influence of different parameters on Cu(2+) uptake by the three biomasses, such as initial Cu(2+) concentration, initial pH of solution, contact time and temperature, was studied. The mechanism of Cu(2+) binding by biomass was investigated by a number of techniques. Evidence from potentiometric titration revealed that the concentration of carboxyl and amino groups is higher on the caustic and ethanol-baker's yeast compared to the pristine baker's yeast and FTIR spectra confirmed carboxyl, and amino groups on the surface of baker's yeast could be available for characteristic coordination bonding with Cu(2+). In addition, SEM and Zeta potential of the three samples show that caustic and ethanol-pretreatment resulted in the change of baker's yeast surface structure and charge which is relative to adsorption. These results demonstrate that the increase of biosorption capacity for Cu(2+) by ethanol and caustic-baker's yeast was attributed to the increase and exposure of carboxyl and amino groups on the surface of biomass sample.

PMID: 20226588 [PubMed - indexed for MEDLINE]

758. Chem Biol Interact. 2010 Sep 6;187(1-3):34-43. Epub 2010 Mar 10.

Cholinesterases (ChEs) and the cholinergic system in ontogenesis and phylogenesis, and non-classical roles of cholinesterases - a review.

Karczmar AG.

Research Service, Edward Hines, Jr., VA Hospital, Hines, IL 60153, USA. karczmar@sbcglobal.net

The enigma of the cholinergic function concerns the role of ChEs and other components of the cholinergic system in non-transmittive, non-synaptic phenomena. The notion that such unorthodox, non-classical phenomena must exist is clearly supported by several lines of evidence, such as the presence of ChEs and other cholinergic components early before neurogenesis, and indeed in unfertilized and fertilized eggs and in the sperm of many species, and their presence throughout phylogenesis, including non-motile, monocellular organisms, fungi and plants and many anervous and ephemeral tissues. The "flexibility" of ChEs, expressed in their polymorphism and their changeability during ontogenesis also speaks for the notion of non-classical functions of ChEs. Today, there is direct evidence that such functions do indeed exist, as for example, the evidence as to the role of ChEs and other cholinergic components in processes of cell proliferation and differentiation of synaptic and myoneural structures. Also, ChEs participate in cell communications as examplified by immunity processes, as well as pathological states, including Alzheimer's disease and states induced by "insults" such as stress and exposure to agents such as antiChEs. Finally, consistent with the non-classical roles of ChEs and cholinergic components are the morphogenetic and teratologic effects of antiChEs, including OP compounds and cholinergic agonists and antagonists. The structural homology between ChEs on the one hand, and adhesion molecules and protohormones on the other may explain some of this phenomenology. It is proposed that the phylogenetic ubiquity of ChEs and their basic capacities that are important for evolutionary phylogenesis, such as the capacity to promote cell adhesion and cell communication speaks for ChEs as "Ur" proteins.

PMID: 20226178 [PubMed - indexed for MEDLINE]

759. Dis Aquat Organ. 2010 Jan 25;88(2):177-81.

Efficacy of SYBR 14/propidium iodide viability stain for the amphibian chytrid fungus Batrachochytrium dendrobatidis.

Stockwell MP, Clulow J, Mahony MJ.

School of Environmental and Life Sciences, University of Newcastle, Callaghan Drive, Callaghan, New South Wales 2308, Australia. michelle.stockwell@newcastle.edu.au

The amphibian chytrid fungus Batrachochytrium dendrobatidis is a recently described pathogen that has been implicated as a causal agent in the global decline in amphibians. Research into its biology and epidemiology has frequently involved in vitro experimentation. However, this research is currently limited by the inability to differentiate between viable and inviable zoospores. Stains are frequently used to determine cell viability, and this study tested a 2-colour fluorescence assay for the detection and quantification of viable B. dendrobatidis zoospores. The results show that the nucleic acid stains SYBR 14 and propidium iodide are effective in distinguishing live from dead zoospores, and a protocol has been optimized for their use. This viability assay provides an efficient and reliable tool that will have applications in B. dendrobatidis challenge and amphibian exposure experiments.

PMID: 20225679 [PubMed - indexed for MEDLINE]

760. Fungal Genet Biol. 2010 May;47(5):484-96. Epub 2010 Mar 15.

The flavohemoglobin BCFHG1 is the main NO detoxification system and confers protection against nitrosative conditions but is not a virulence factor in the fungal necrotroph Botrytis cinerea.

Turrion-Gomez JL, Eslava AP, Benito EP.

Centro Hispano-Luso de Investigaciones Agrarias (CIALE), Departamento de Microbiología y Genética, Universidad de Salamanca. C. Río Duero, No. 12., Campus de Villamayor, Parque Científico, 37185 Villamayor, Salamanca, Spain.

Flavohemoglobins constitute a group of proteins involved in the metabolism of nitric oxide (NO). Botrytis cinerea was shown to have a single flavohemoglobin coding gene, Bcfhg1. Its expression was developmentally regulated, with maximum expression levels during germination of conidia, and was enhanced very quickly upon exposure to NO of germinating conidia, but not of mycelium growing and branching actively. Expression in planta paralleled the expression pattern during saprophytic growth with maximal expression occurring during the very early stages of the infection process. Bcfhg1 complemented the Saccharomyces cerevisiae yhb1 mutation, indicating that the encoded enzyme has NO dioxygenase activity. Biochemical and functional characterization of DeltaBcfhg1 mutants in comparison with the wild type strain demonstrated that, although BCFHG1 showed a high affinity for its substrate, appeared to represent the main inducible NO detoxification system and conferred protection against nitrosative stress in B. cinerea, the ability of the DeltaBcfhg1 mutant strains to infect different hosts was not affected.

PMID: 20223291 [PubMed - indexed for MEDLINE]

761. J Virol. 2010 May;84(10):5124-30. Epub 2010 Mar 10.

Early spatial and temporal events of human T-lymphotropic virus type 1 spread following blood-borne transmission in a rabbit model of infection.

Haynes RA 2nd, Zimmerman B, Millward L, Ware E, Premanandan C, Yu L, Phipps AJ, Lairmore MD.

Department of Veterinary Biosciences, The Ohio State University, 1925 Coffey Road, Columbus, OH 43210, USA.

Human T-lymphotropic virus type 1 (HTLV-1) infection causes adult T-cell leukemia/lymphoma (ATL) and is associated with a variety of lymphocyte-mediated disorders. HTLV-1 transmission occurs by transmission of infected cells via breast-feeding by infected mothers, sexual intercourse, and contaminated blood products. The route of exposure and early virus replication events are believed to be key determinants of virus-associated spread, antiviral immune responses, and ultimately disease outcomes. The lack of knowledge of early events of HTLV-1 spread following blood-borne transmission of the virus in vivo hinders a more complete understanding of the immunopathogenesis of HTLV-1 infections. Herein, we have used an established animal model of HTLV-1 infection to study early spatial and temporal events of the viral infection. Twelve-week-old rabbits were injected intravenously with cell-associated HTLV-1 (ACH-transformed R49). Blood and tissues were collected at defined intervals throughout the study to test the early spread of the infection. Antibody and hematologic responses were monitored throughout the infection. HTLV-1 intracellular Tax and soluble p19 matrix were tested from ex vivo cultured lymphocytes. Proviral copy numbers were measured by real-time PCR from blood and tissue mononuclear leukocytes. Our data indicate that intravenous infection with cell-associated HTLV-1 targets lymphocytes located in both primary lymphoid and gut-associated lymphoid compartments. A transient lymphocytosis that correlated with peak virus detection parameters was observed by 1 week postinfection before returning to baseline levels. Our data support emerging evidence that HTLV-1 promotes lymphocyte proliferation preceding early viral spread in lymphoid compartments to establish and maintain persistent infection.

PMCID: PMC2863820 PMID: 20219918 [PubMed - indexed for MEDLINE]

762. Clin Microbiol Infect. 2010 Nov;16(11):1676-82. doi: 10.1111/j.1469-0691.2010.03208.x.

Predictors of candidaemia caused by non-albicans Candida species: results of a population-based surveillance in Barcelona, Spain.

Rodríguez D, Almirante B, Cuenca-Estrella M, Rodríguez-Tudela JL, Mensa J, Ayats J, Sanchez F, Pahissa A; Barcelona Candidemia Project Study Group.

Collaborators: Fridkin S, Hajjeh R, Park B, Morgan J, Warnock DW, Planes AM, Almela M, Reverter FM, Soler CM, Salvadó M, Saballs P, Gener A, Fontanals D, Xercavins M, Falgueras L, Torroella MT, de Ramon M, Alonso C, de Otero J, Sierra M, Martinez-Montauti J, Morera MA, Giménez M.

Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain. dolorodriguez@vhebron.net

Although Candida albicans (CA) is the most common cause of Candida bloodstream infections (BSIs), recent studies have observed an increasing percentage of candidaemias caused by non-albicans Candida species (NAC). In the present study, we attempted to identify the predictors of candidaemia due to NAC compared to CA. We analyzed data from an active population-based surveillance in Barcelona (Spain) from January 2002 to December 2003. Factors associated with NAC fungaemia were determined by multivariate analysis. A total of 339 episodes of Candida BSI, in 336 patients (median age 63 years, interquartile range: 41-72 years), were included. CA was the most commonly isolated (52%), followed by Candida parapsilosis (23%), Candida tropicalis (10%), Candida glabrata (8.6%), Candida krusei (3.4%) and other NAC spp. (3%).Overall, 48% of cases were due to NAC spp. Multivariate logistic regression analysis identified factors associated with a risk of BSI due to NAC spp.: having received a haematologic transplant (OR 10.8; 95% CI 1.31-90.01; p 0.027), previous fluconazole exposure (OR 4.47; 95% CI 2.12-9.43; p <0.001) and neonatal age (OR 4.42; 95% CI 1.63-12.04; p 0.004). Conversely, previous CA colonization (OR 0.33; 95% CI 0.19-0.57; p 0.001) and previous antibiotic use (OR 0.42; 95% CI 0.21-0.85; p 0.017) were associated with CA fungaemia compared to NAC. In conclusion, NAC candidaemia comprised 48% of cases in our series. Predictors of NAC include having received a haematologic transplant, neonatal age and previous fluconazole use.

PMID: 20219079 [PubMed - indexed for MEDLINE]

763. Aquat Toxicol. 2010 Jun 1;98(1):99-106. Epub 2010 Feb 4.

Perfluorooctane sulfonate accumulation and parasite infestation in a field population of the amphipod Monoporeia affinis after microcosm exposure.

Jacobson T, Holmström K, Yang G, Ford AT, Berger U, Sundelin B.

Department of Applied Environmental Science, Stockholm University, SE-106 91 Stockholm, Sweden.

Perfluorooctane sulfonate (PFOS) is the focus of intense toxicity research due to its persistence and widespread occurrence in biota. Studies on benthic invertebrates have shown them to be subjects of high PFOS exposure. However, effects on benthic invertebrates exposed to PFOS in the field are still far from elucidated. To fill a knowledge gap on concentrations and effects in benthic invertebrates, a microcosm study on the benthic amphipod Monoporeia affinis was performed. Field collected M. affinis were analysed for PFOS and showed average background concentrations 39 and 58 ng/g (wet weight) in two different samplings. The field collected animals were exposed to three concentrations of PFOS (50, 200 and 5000 microg PFOS/L water) for 3 weeks during gonad development. Body burdens of PFOS were determined after experiment termination. Results showed negative effects on survival and reproduction effects such as decreased sexual maturation and decreased oocyte viability caused by PFOS exposure. Additionally, a follow-up experiment demonstrated a significant increase in the infection incidence by a microsporidian muscle parasite in animals exposed to PFOS at tissue concentrations in the range of concentrations found in field collected benthic amphipods. This is the first study to demonstrate increased microsporidian infection with pollutant exposure and it suggests that ecologically relevant PFOS concentrations could be sufficient to elicit these effects.

PMID: 20211497 [PubMed - indexed for MEDLINE]

764. Respirology. 2010 Apr;15(3):573-6. Epub 2010 Feb 24.

Sauna lung: hypersensitivity pneumonitis due to Exophiala jeanselmei.

Huang WC, Lu YH, Lin ZG, Su WL.

Department of Internal Medicine, Tri-Service General Hospital, Taipei, Taiwan.

A 55-year-old man developed progressive cough and dyspnoea after regular attendance at a public steam bath. Hypoxaemia, diffuse pulmonary infiltrates and a predominance of lymphocytes with an increased percentage of CD8+ T cells in his bronchoalveolar lavage fluid suggested hypersensitivity pneumonitis. Microbial cultures from the steam bath room and tank identified Exophiala jeanselmei. Immunoblotting assays from the patient's serum confirmed the major antigenic stimulus. The patient recovered fully after systemic corticosteroid treatment and cessation of further exposure.

PMID: 20210895 [PubMed - indexed for MEDLINE]

765. Rev Mal Respir. 2010 Feb;27(2):180-7. Epub 2010 Feb 12.

[Non allergic disorders associated with domestic moulds].

[Article in French]

Palot A, Charpin-Kadouch C, Dumon H, Charpin D.

Service de pneumologie-allergologie, hôpital Nord, chemin des Bourrelly, 13015 Marseille, France.

INTRODUCTION: Mouldy surfaces are encountered in up to 20 % of dwellings. Because this indoor air contamination is so widespread, respiratory physicians should be aware of its effects on health and especially of its impact on respiratory diseases.
BACKGROUND: The air contaminants within mouldy dwellings are very diverse. Therefore, a given heath effect cannot be attributed specifically to an individual contaminant. In the field of respiratory diseases, excluding asthma and allergy, long-term exposure to indoor moulds has been recognized as a risk factor for both ENT and bronchial symptoms. Hydrophilic moulds seem to have a larger health impact than other mould species. Among respiratory diseases, inhalation fever and, to a lesser extent, childhood respiratory infections are linked to exposure to moulds. In contrast, the relationship between exposure to indoor moulds and diseases such as sinusitis, mucous irritation syndrome, recurrent respiratory infections in adults, COPD and pulmonary haemorrhage has not been clearly established. VIEWPOINT: There are still many scientific uncertainties in this field. However, the authorities are becoming more active in dealing with unhealthy buildings and encouraging research.
CONCLUSION: The health impact of mouldy dwellings represents a major public health issue. It needs incentives from institutions and financial support as well as the involvement of many specialists.

PMID: 20206066 [PubMed - indexed for MEDLINE]

766. Rev Mal Respir. 2010 Feb;27(2):169-79. Epub 2010 Jan 25.

[Moulds in dwellings: health risks and involved species].

[Article in French]

Reboux G, Bellanger AP, Roussel S, Grenouillet F, Millon L.

Laboratoire de parasitologie-mycologie, CHU Jean-Minjoz, 2, boulevard Fleming, 25030 Besançon, France. gabriel.reboux@univ-fcomte.fr

INTRODUCTION: In industrialized countries the population spends 90% of its time in enclosed spaces. Since 1973, energy consumption for heating decreased on average by 36% per dwelling. Low-quality insulation, a fall in temperature and inadequate ventilation translated into high humidity in dwellings, which led to proliferation of moulds.
BACKGROUND: The allergenic, toxic and infectious effects of moulds on human health are documented. However, the potential dose/effect relationship between measured concentrations of indoor moulds and respiratory disorders often remains difficult to assess accurately. In several cases, fungi were demonstrated only as a promoter of health disorders. In a few cases (hypersensitivity pneumonitis, invasive fungal infections), the pathogenesis is without doubt due to environmental fungal exposure in a limited number of patients. On the other hand, the role of fungi was suspected but not proven for some well-defined pathologies, and some ill-defined health disorders, affecting large numbers of patients, such as the Sick Building Syndrome, rhinitis, sinusitis and conjunctivitis, as well as asthma and exacerbations of bronchitis. Eighteen fungal species, suspected of playing a role in public health, have been listed by the French Superior Council of Public Health. For each species, the proliferation conditions, type of substrates contaminated and heath effects reported in the literature are described. VIEWPOINT: The lack of standardization of measurements of concentrations of fungal species, the interactions with chemical compounds (formaldehydes), organic compounds (mycotoxins, endotoxins) and between species, makes the analysis of indoor fungal contamination complicated. The time has come to establish clearly a relationship between exposure to fungi and health disorders, rather than continuing to investigate factors related to the level of indoor fungal contamination.

PMID: 20206065 [PubMed - indexed for MEDLINE]

767. J Med Microbiol. 2010 Jun;59(Pt 6):625-33. Epub 2010 Mar 4.

Inhibition of neutrophil function following exposure to the Aspergillus fumigatus toxin fumagillin.

Fallon JP, Reeves EP, Kavanagh K.

Medical Mycology Unit, Department of Biology, National Institute for Cellular Biotechnology, National University of Ireland Maynooth, Co. Kildare, Ireland.

The filamentous fungus Aspergillus fumigatus produces a variety of enzymes and toxins that may facilitate fungal colonization of tissue and evasion of the host immune response. One such toxin, fumagillin, was investigated for its ability to inhibit the action of neutrophils, which are a central component of the innate immune response to microbial infection. Neutrophils exposed to 2 microg fumagillin ml(-1) for 25 min showed a significantly reduced ability to kill yeast cells (P<0.02), to phagocytose conidia of A. fumigatus (P<0.023) and to consume oxygen (P<0.032). The ability of neutrophils to generate superoxide is dependent upon the action of a functional NADPH oxidase complex which is composed of cytosolic (p40phox, p47phox, p67phox, Rac2) and membrane (gp91phox) proteins. Exposure of neutrophils to fumagillin inhibited the formation of the NADPH oxidase complex by blocking the translocation of p47phox from the cytosolic to the membrane fraction (P=0.02). In addition to the production of superoxide, neutrophils also undergo degranulation, which leads to the release of proteolytic enzymes that contribute to the microbicidal activity of the cell. Fumagillin-treated neutrophils showed reduced degranulation as evidenced by lower myeloperoxidase activity (P<0.019). Fumagillin-treated cells demonstrated reduced levels of F-actin, thus indicating that retarding the formation of F-actin may contribute to the inhibition of the structural rearrangements required in the activated neutrophil. This work indicates that fumagillin may contribute to reducing the local immune response by altering the activity of neutrophils and thus facilitate the continued persistence and growth of A. fumigatus in the host.

PMID: 20203215 [PubMed - indexed for MEDLINE]

768. J Antimicrob Chemother. 2010 May;65(5):1042-51. Epub 2010 Mar 4.

Candidaemia in adult cancer patients: risks for fluconazole-resistant isolates and death.

Slavin MA, Sorrell TC, Marriott D, Thursky KA, Nguyen Q, Ellis DH, Morrissey CO, Chen SC; Australian Candidemia Study, Australasian Society for Infectious Diseases.

Peter MacCallum Cancer Centre and the Centre for Research Excellence in Infectious Diseases, Royal Melbourne Hospital, Parkville, VIC 3050, Australia. monica.slavin@petermac.org

BACKGROUND: Candidaemia in cancer patients is associated with increasing fluconazole resistance. Models for predicting such isolates and their clinical impact are required.
METHODS: Clinical, treatment and outcome data from a population-based candidaemia survey (2001-2004) were collected at 5 and 30 days after diagnosis. Speciation and antifungal susceptibility testing was performed.
RESULTS: There were 138 candidaemia episodes (33% Candida albicans) in adults with haematological malignancies and 150 (51% C. albicans) in adults with solid organ malignancies. Thirty-nine isolates had fluconazole MICs of >or=64 mg/L and 40 had MICs of 16-32 mg/L (predominantly Candida glabrata and Candida krusei). By multivariate analysis, triazole therapy, gastrointestinal tract (GIT) surgery in the 30 days before candidaemia and age >65 years were predictive of fluconazole-resistant candidaemia. Thirty day crude mortality was 40% in haematology patients and 45% in oncology patients. Fluconazole-resistant isolates were associated with increased risk of mortality by univariate (P = 0.04) and Kaplan-Meier survival analyses. By Cox proportional hazards modelling, the strongest predictors of mortality at onset of candidaemia were invasive ventilation, elevated creatinine, intensive care unit (ICU) admission and receipt of systemic triazoles or corticosteroids in the previous 30 days. Removal of a central venous access device (CVAD) at or within 5 days of onset was associated with decreased mortality.
CONCLUSIONS: Risk factors for fluconazole-resistant candidaemia in adults with cancer include fluconazole/triazole exposure and GIT surgery. ICU admission, invasive ventilation, renal impairment, age >65 years and prior exposure to corticosteroids and triazoles are risk factors for death. CVAD removal reduced mortality. These findings should be integrated into surveillance and treatment algorithms.

PMID: 20202987 [PubMed - indexed for MEDLINE]

769. Ann Occup Hyg. 2010 Apr;54(3):309-18. Epub 2010 Mar 3.

Exposure to flour dust in South African supermarket bakeries: modeling of baseline measurements of an intervention study.

Baatjies R, Meijster T, Lopata A, Sander I, Raulf-Heimsoth M, Heederik D, Jeebhay M.

Department of Environmental and Occupational Studies, Faculty of Applied Sciences, Cape Peninsula University of Technology, Cape Town 8001, South Africa.

INTRODUCTION: Exposure to flour dust has been reported as an important risk factor for allergic respiratory disease among bakery workers. A high prevalence of allergic sensitization and asthma was recently reported in South African supermarket bakeries. The aim of this study was to conduct a detailed exposure assessment of these bakeries so as to provide the baseline for a broader intervention study.
METHODS: A total of 211 full-shift personal samples were collected on randomly selected individuals within five different job categories in 18 bakeries. The samples were analyzed for particulate mass and specific flour dust allergens (wheat, rye, and fungal alpha-amylase). Exposure models were developed using job, bakery size, tasks, and specific ingredients used. Bakery and worker were regarded as random effect components.
RESULTS: Bread bakers had the highest average (geometric mean) exposures (1.33 mg m(-3) flour dust particulate, 13.66 microg m(-3) wheat allergens, and 5.14 microg m(-3) rye allergens). For alpha-amylase allergens, most samples were below the limit of detection for several occupational titles. In the mixed effect models, the significant predictors of elevated exposure to inhalable dust particulate as well as wheat and rye allergen concentrations were large bakery size, bread baking, and use of cereal flours, while tasks such as confectionery work were negatively correlated with these exposure metrics. Weighing tasks and use of premix products were associated with increased exposure to fungal alpha-amylase. A high correlation between particulate dust and wheat (r = 0.84) as well as rye (r = 0.86) was observed, with a much lower correlation between particulate dust and fungal alpha-amylase (r = 0.33). Overall, a low proportion (39%) of bakery stores implemented various control measures to reduce dust exposures in the bakeries.
CONCLUSIONS: This study confirms that current exposure control strategies in supermarket bakery stores are inadequate in reducing dust exposures to protect the health of bakery workers.

PMID: 20200089 [PubMed - indexed for MEDLINE]

770. J Allergy Clin Immunol. 2010 Feb;125(2 Suppl 2):S150-60.

Environmental and occupational allergies.

Peden D, Reed CE.

Department of Pediatrics, University of North Carolina, Chapel Hill, USA.

Airborne allergens are the major cause of allergic rhinitis and asthma. Daily exposure comes from indoor sources, chiefly at home but occasionally at schools or offices. Seasonal exposure to outdoor allergens, pollens, and molds is another important source. Exposure to unusual substances at work causes occupational asthma, accounting for about 5% of asthma in adults. Indoor and outdoor air pollutants trigger airway inflammation and increase the severity of asthma. Diesel exhaust particles increase the production of IgE antibodies. Identification and reduction of exposure to allergens is a very important part of the management of respiratory allergic diseases. The first section of this chapter discusses domestic allergens, arthropods (mites and cockroaches), molds, and mammals (pets and mice). Indoor humidity and water damage are important factors in the production of mite and mold allergens, and discarded human food items are important sources of proliferation of cockroaches and mice. Means of identifying and reducing exposure are presented. The second section discusses outdoor allergens: pollens and molds. The particular plants or molds and the amount of exposure to these allergens is determined by the local climate, and local pollen and mold counts are available to determine the time and amount of exposure. Climate change is already having an important effect on the distribution and amount of outdoor allergens. The third section discusses indoor and outdoor air pollution and methods that individuals can take to reduce indoor pollution in addition to eliminating cigarette smoking. The fourth section discusses the diagnosis and management of occupational asthma.

PMID: 20176257 [PubMed - indexed for MEDLINE]

771. Acta Biochim Pol. 2010;57(1):43-8. Epub 2010 Mar 2.

Purification and characterization of an antibacterial protein from dried fruiting bodies of the wild mushroom Clitocybe sinopica.

Zheng S, Liu Q, Zhang G, Wang H, Ng TB.

State Key Laboratory for Agrobiotechnology and Department of Microbiology, China Agricultural University, Beijing, China.

A novel antibacterial protein with a molecular mass of 44 kDa has been isolated from dried fruiting bodies of the wild mushroom Clitocybe sinopica. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis showed that the protein was composed of two subunits each with a molecular mass of 22 kDa. Its N-terminal amino-acid sequence, SVQATVNGDKML, has not been reported for other antimicrobial proteins. The purification protocol included ion exchange chromatography on DEAE-cellulose, CM-cellulose and Q-Sepharose, and gel filtration by fast protein liquid chromatography on Superdex 75. The antibacterial protein was adsorbed on all three ion exchangers. The antimicrobial activity profile of the protein against tested bacterial and fungal strains disclosed that it possessed potent antibacterial activity against Agrobacterium rhizogenes, A. tumefaciens, A. vitis, Xanthomonas oryzae and X. malvacearum with a minimum inhibitory concentration mostly below 0.6 microM. However, it had no antibacterial activity against Pseudomonas batatae, Erwinia herbicola, Escherichia coli, and Staphylococcus aureus, and no antifungal activity against Setosphaeria turcica, Fusarium oxysporum, Verticillium dahliae, Bipolaris maydis, and B. sativum. The antibacterial antivity against A. tumefaciens was stable after exposure to 20-60 degrees C for 30 min and to pH 4-9 for 1 h.

PMID: 20198215 [PubMed - indexed for MEDLINE]

772. Microbiol Mol Biol Rev. 2010 Mar;74(1):95-120.

Alkali metal cation transport and homeostasis in yeasts.

Ariño J, Ramos J, Sychrová H.

Departament de Bioquímica i Biologia Molecular, Ed. V, Universitat Autònoma de Barcelona, Bellaterra 08193, Barcelona, Spain. Joaquin.Arino@uab.es

The maintenance of appropriate intracellular concentrations of alkali metal cations, principally K(+) and Na(+), is of utmost importance for living cells, since they determine cell volume, intracellular pH, and potential across the plasma membrane, among other important cellular parameters. Yeasts have developed a number of strategies to adapt to large variations in the concentrations of these cations in the environment, basically by controlling transport processes. Plasma membrane high-affinity K(+) transporters allow intracellular accumulation of this cation even when it is scarce in the environment. Exposure to high concentrations of Na(+) can be tolerated due to the existence of an Na(+), K(+)-ATPase and an Na(+), K(+)/H(+)-antiporter, which contribute to the potassium balance as well. Cations can also be sequestered through various antiporters into intracellular organelles, such as the vacuole. Although some uncertainties still persist, the nature of the major structural components responsible for alkali metal cation fluxes across yeast membranes has been defined within the last 20 years. In contrast, the regulatory components and their interactions are, in many cases, still unclear. Conserved signaling pathways (e.g., calcineurin and HOG) are known to participate in the regulation of influx and efflux processes at the plasma membrane level, even though the molecular details are obscure. Similarly, very little is known about the regulation of organellar transport and homeostasis of alkali metal cations. The aim of this review is to provide a comprehensive and up-to-date vision of the mechanisms responsible for alkali metal cation transport and their regulation in the model yeast Saccharomyces cerevisiae and to establish, when possible, comparisons with other yeasts and higher plants.

PMCID: PMC2832347 PMID: 20197501 [PubMed - indexed for MEDLINE]

773. Antimicrob Agents Chemother. 2010 May;54(5):2096-111. Epub 2010 Mar 1.

Interaction of Candida albicans biofilms with antifungals: transcriptional response and binding of antifungals to beta-glucans.

Vediyappan G, Rossignol T, d'Enfert C.

Unité Biologie et Pathogénicité Fongiques, Institut Pasteur, Paris, France.

Candida albicans can form biofilms that exhibit elevated intrinsic resistance to various antifungal agents, in particular azoles and polyenes. The molecular mechanisms involved in the antifungal resistance of biofilms remain poorly understood. We have used transcript profiling to explore the early transcriptional responses of mature C. albicans biofilms exposed to various antifungal agents. Mature C. albicans biofilms grown under continuous flow were exposed for as long as 2 h to concentrations of fluconazole (FLU), amphotericin B (AMB), and caspofungin (CAS) that, while lethal for planktonic cells, were not lethal for biofilms. Interestingly, FLU-exposed biofilms showed no significant changes in gene expression over the course of the experiment. In AMB-exposed biofilms, 2.7% of the genes showed altered expression, while in CAS-exposed biofilms, 13.0% of the genes had their expression modified. In particular, exposure to CAS resulted in the upregulation of hypha-specific genes known to play a role in biofilm formation, such as ALS3 and HWP1. There was little overlap between AMB- or CAS-responsive genes in biofilms and those that have been identified as AMB, FLU, or CAS responsive in C. albicans planktonic cultures. These results suggested that the resistance of C. albicans biofilms to azoles or polyenes was due not to the activation of specific mechanisms in response to exposure to these antifungals but rather to the intrinsic properties of the mature biofilms. In this regard, our study led us to observe that AMB physically bound C. albicans biofilms and beta-glucans, which have been proposed to be major constituents of the biofilm extracellular matrix and to prevent azoles from reaching biofilm cells. Thus, enhanced extracellular matrix or beta-glucan synthesis during biofilm growth might prevent antifungals, such as azoles and polyenes, from reaching biofilm cells, thus limiting their toxicity to these cells and the associated transcriptional responses.

PMCID: PMC2863626 PMID: 20194705 [PubMed - indexed for MEDLINE]

774. Antimicrob Agents Chemother. 2010 May;54(5):1753-61. Epub 2010 Mar 1.

Mechanism of the synergistic effect of amiodarone and fluconazole in Candida albicans.

Gamarra S, Rocha EM, Zhang YQ, Park S, Rao R, Perlin DS.

Public Health Research Institute, New Jersey Medical School-UMDNJ, Newark, NJ 07103-3535, USA.

The antiarrhythmic drug amiodarone has been found to have fungicidal activity. In Saccharomyces cerevisiae, its antifungal activity is mediated by calcium overload stress, which leads to a rapid nuclear accumulation of the calcineurin-regulated transcription factor CRZ1. In addition, low doses of amiodarone have been reported to be synergistic with fluconazole in fluconazole-resistant Candida albicans. To establish its mechanism of toxicity in C. albicans, we used expression profiling of key pathway genes to examine cellular responses to amiodarone alone and in combination with fluconazole. Gene expression profiling of 59 genes was done in five C. albicans strains (three fluconazole-susceptible strains and two fluconazole-resistant strains) after amiodarone and/or fluconazole exposure. Of the 59 genes, 27 analyzed showed a significant change (>2-fold) in expression levels after amiodarone exposure. The up- or downregulated genes included genes involved in Ca(2+) homeostasis, cell wall synthesis, vacuolar/lysosomal transport, diverse pathway regulation, stress response, and pseudohyphal morphogenesis. As expected, fluconazole induces an increase in ergosterol pathway genes expression levels. The combination treatment significantly dampened the transcriptional response to either drug, suggesting that synergism was due to an inhibition of compensatory response pathways. This dampening resulted in a decrease in total ergosterol levels and decreased pseudohyphal formation, a finding consistent with decreased virulence in a murine candidiasis model.

PMCID: PMC2863688 PMID: 20194694 [PubMed - indexed for MEDLINE]

775. Expert Rev Anti Infect Ther. 2010 Mar;8(3):317-24.

Use of antibiotics in severe acute pancreatitis.

De Waele JJ.

Department of Critical Care Medicine, Intensive Care Unit 1K12-C, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium. jan.dewaele@ugent.be

Infectious complications in severe acute pancreatitis are an important problem and determine outcome in patients who survived the first inflammatory hit of the disease. Timely diagnosis of infected pancreatic necrosis is often challenging, but should not delay adequate treatment, which consists of source control and antibiotic treatment. Prophylactic antibiotics are not effective in reducing the incidence of (peri)pancreatic infection in patients with severe acute pancreatitis (or necrotizing pancreatitis). The only rational indication for antibiotics at this moment is documented infection. The spectrum of empiric antibiotics should cover both Gram-negative, Gram-positive and anaerobic microorganisms (also keeping in mind exposure to nosocomial microorganisms), and local ecology should be taken into account. Fungal infections are often present, and antifungal coverage should be considered, especially if multiple risk factors for invasive candidiasis are present. Currently, no tools are available to guide antimicrobial treatment.

PMID: 20192685 [PubMed - indexed for MEDLINE]

776. Sci Total Environ. 2010 Apr 15;408(10):2199-207. Epub 2010 Feb 26.

A risk factor study of coccidioidomycosis by controlling differential misclassifications of exposure and susceptibility using a landscape ecology approach.

Tabor JA, O'Rourke MK.

Office of Arid Lands Studies, College of Agriculture and Life Sciences, The University of Arizona, Tucson, Arizona, 85721, USA. jatabor@u.arizona.edu

State-reported coccidioidomycosis cases in Arizona have dramatically increased since 1997, raising concerns about a possible epidemic, its cause, and associated risk factors, including spatio-temporal differences in susceptibility and exposure. This stratified, two-stage, cross-sectional study evaluates inherent, socio-economic, and environmental risk factors of coccidioidomycosis from information collected during an address-based telephone survey of 5460 households containing 14,105 individuals in greater Tucson, Arizona. Three geomorphic and two demographic strata controlled for differences in group-level exposures and susceptibility, and assured recruitment of a minority population. Logistic regression of self-reported cases indicates that location of residence by geomorphic and demographic strata was a risk factor that confounded the associations of coccidioidomycosis with age, race-ethnicity, and educational attainment. The risk due to age is more evenly distributed across the population than bivariate results when individual- and group-level exposure and susceptibility factors are controlled. Similarly the association for being Hispanic decreased from strong bivariate 0.28 odds ratio to a weak multivariate 0.75. Location of residence confounded the risk due to race-ethnicity and was an effect modifier of risk due to age. Differential misclassification of exposure to Coccidioides spores and susceptibility to coccidioidomycosis was reduced through landscape stratification by demographics and geomorphic types. Landscape epidemiological studies of diseases with strong environmental and demographic determinants can reduce residual confounding and account for spatial and temporal differences between neighborhoods and at broader scales.

PMID: 20188397 [PubMed - indexed for MEDLINE]

777. Appl Microbiol Biotechnol. 2010 Mar;86(1):327-34.

Oxygen-induced expression of Delta(6)-, Delta(9)- and Delta(12)-desaturase genes modulates fatty acid composition in Mucor rouxii.

Ruenwai R, Cheevadhanarak S, Rachdawong S, Tanticharoen M, Laoteng K.

School of Bioresources and Technology, King Mongkut's University of Technology Thonburi, Bangkhuntien, Bangkok 10150, Thailand.

The effect of oxygen availability on the molecular mechanisms of fatty acid biosynthesis was investigated in Mucor rouxii, a Mucorale fungus capable of producing gamma-linolenic acid through perturbation of the gaseous environment. Shifting of the M. rouxii culture from anaerobic to aerobic conditions resulted in an increase of the biomass and total fatty acid content of the M. rouxii culture. In addition, the levels of unsaturated fatty acids were enhanced accompanied by a decrease in the levels of medium- and long-chain saturated fatty acids. These results correspond to the levels of expressions of the Delta(9)-, Delta(12)- and Delta(6)-desaturases genes, all of which were coordinately up-regulated after the shift. The transcriptional response observed was rapid and transient, with the maximal mRNA levels detected between 0.5 h and 1.0 h after the shift. Together, our findings indicate that the anaerobic M. rouxii culture acclimatised to oxygen exposure by modulating fatty acid composition that was transcriptionally co-regulated by Delta(9)-, Delta(12)- and Delta(6)-desaturase genes.

PMID: 20187298 [PubMed - indexed for MEDLINE]

778. Dis Aquat Organ. 2009 Dec 22;88(1):69-84.

Pseudoloma neurophilia infections in zebrafish Danio rerio: effects of stress on survival, growth, and reproduction.

Ramsay JM, Watral V, Schreck CB, Kent ML.

Department of Fisheries and Wildlife, U.S. Geological Survey, USA.

Pseudoloma neurophilia (Microsporidia) is a common disease of zebrafish Danio rerio, including those used as research models. We conducted a study comprised of 4 separate experiments to determine the effects of husbandry stress on preexisting and experimental P. neurophilia infections and the subsequent effects on survival, infection onset and intensity, fish growth, and reproduction. In fish (AB strain) with preexisting infections, stress or feeding cortisol significantly increased mortality over 7 wk compared to no stress or cortisol treatment. In contrast, no mortality was observed in fish (TL strain) experimentally exposed to P. neurophilia over 10 wk. A third experiment involved experimental exposure of AB fish to P. neurophilia and exposure to crowding and handling stressors. No mortality was associated with P. neurophilia regardless of stress treatment over a period of 20 wk. However, the onset of infection occurred sooner in stress-treated fish. Stress significantly increased the mean intensity of infection (described as xenoma area/spinal cord area in histological sections) at Week 20 post-exposure (PE). In fish with preexisting infections, myositis was significantly greater in stressed and cortisol-treated fish than those not stressed. With experimental exposure of AB fish, stressed and infected groups weighed significantly less than the control group at Week 20 PE. Regarding fecundity, the number of larvae hatched at 5 d post fertilization was negatively associated with mean infection intensity among P. neurophilia-infected and stressed AB fish. These experiments are the first to show empirically that P. neurophilia can be associated with reduced weight and fecundity, and that stress can exacerbate the severity of the infection.

PMID: 20183967 [PubMed - indexed for MEDLINE]

779. Small. 2010 Mar 22;6(6):768-75.

Fabrication of hierarchical pillar arrays from thermoplastic and photosensitive SU-8.

Zhang Y, Lin CT, Yang S.

Department of Materials Science and Engineering, University of Pennsylvania, 3231 Walnut Street, Philadelphia, PA 19104, USA.

By exploiting the thermoplastic and photosensitive nature of SU-8 photoresists, different types of hierarchical pillar arrays with variable aspect ratios are fabricated through capillary force lithography (CFL), followed by photopatterning. The thermoplastic nature of SU-8 enables the imprinting of micropillar arrays with variable aspect ratios by CFL using a single poly(dimethylsiloxane) mold, simply by tuning the initial film thickness of SU-8 on a substrate. The pillar array is subsequently photopatterned through a photomask, followed by post-exposure baking above the glass transition temperature (T(g)) of SU-8. The pillars in the exposed region become highly crosslinked and, therefore, neither soluble nor able to reflow above T(g), whereas the pillars in the unexposed regions can reflow and flatten out. Two developing strategies are investigated after UV exposure of the SU-8 pillar arrays including i) solvent development and drying and ii) thermal reflow to create bilevel hierarchical structures with short pillars and single-level, dual-scaled, high-aspect-ratio (up to 7.7) pillars in a microdot array, respectively.

PMID: 20183811 [PubMed - indexed for MEDLINE]

780. Hum Exp Toxicol. 2010 Oct;29(10):823-32. Epub 2010 Feb 23.

Is MARS system enough for A. phalloides-induced liver failure treatment?

Sorodoc L, Lionte C, Sorodoc V, Petris O, Jaba I.

Emergency Clinic Hospital, Department of Internal Medicine, University of Medicine and Pharmacy, Iasi, Romania. laurentiusorodoc@yahoo.com

Patients with Amanita phalloides-induced liver failure (LF) have a high mortality, despite significant advances in intensive care management. Our study evaluated the effect of Molecular Absorbents Recirculating System (MARS) comparative with optimal intensive care (OIC) in adults with this condition, in the absence of liver transplantation (LT). Six consecutive patients (women, range 16-61 years) affected by A. phalloides-induced LF were treated with OIC (3 patients) and MARS (3 patients). Laboratory parameters and hepeatic encephalopaty were evaluated 15 min before and 24 hours following each MARS treatment. Three 6-hour sessions per patient were performed in MARS group, with a statistically significant decrease in ammonia (p value 0.011), alaninaminotransferase (ALT) and prothrombin time (PT) (p value 0.004). Two patients had a significant rebound in bilirubin (+116%; p value 0. 04) 24 hours following MARS. Mortality in MARS group was 66.7%. Survival rate in OIC was 0%. Negative prognostic markers: lack of PT and hepatic encephalopaty improvement, rebound in bilirubin, and delay of MARS therapy initiation. No significant adverse reactions occurred during MARS. MARS is an effective depurative therapy in adults with A. phalloides-induced LF, but alone is not enough. Survival is predicted by the results of the initial MARS, amount of mushroom consumed, and time from toxin exposure.

PMID: 20179021 [PubMed - indexed for MEDLINE]

781. Environ Health Perspect. 2010 Jun;118(6):818-24. Epub 2010 Feb 19.

Global burden of aflatoxin-induced hepatocellular carcinoma: a risk assessment.

Liu Y, Wu F.

Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15219 , USA.

Comment in Environ Health Perspect. 2010 Jun;118(6):A258.

BACKGROUND: Hepatocellular carcinoma (HCC), or liver cancer, is the third leading cause of cancer deaths worldwide, with prevalence 16-32 times higher in developing countries than in developed countries. Aflatoxin, a contaminant produced by the fungi Aspergillus flavus and Aspergillus parasiticus in maize and nuts, is a known human liver carcinogen. OBJECTIVES: We sought to determine the global burden of HCC attributable to aflatoxin exposure.
METHODS: We conducted a quantitative cancer risk assessment, for which we collected global data on food-borne aflatoxin levels, consumption of aflatoxin-contaminated foods, and hepatitis B virus (HBV) prevalence. We calculated the cancer potency of aflatoxin for HBV-postive and HBV-negative individuals, as well as the uncertainty in all variables, to estimate the global burden of aflatoxin-related HCC.
RESULTS: Of the 550,000-600,000 new HCC cases worldwide each year, about 25,200-155,000 may be attributable to aflatoxin exposure. Most cases occur in sub-Saharan Africa, Southeast Asia, and China where populations suffer from both high HBV prevalence and largely uncontrolled aflatoxin exposure in food.
CONCLUSIONS: Aflatoxin may play a causative role in 4.6-28.2% of all global HCC cases.

PMCID: PMC2898859 PMID: 20172840 [PubMed - indexed for MEDLINE]

782. Res Microbiol. 2010 May;161(4):284-92. Epub 2010 Feb 17.

Transcriptional response to fluconazole and amphotericin B in Candida albicans biofilms.

Nailis H, Vandenbosch D, Deforce D, Nelis HJ, Coenye T.

Laboratory of Pharmaceutical Microbiology, Ghent University, Harelbekestraat 72, B-9000, Ghent, Belgium. heleen.nailis@ugent.be

Biofilm formation is often associated with persistent Candida albicans infections. Treatment of these infections is difficult, since sessile C. albicans cells show increased resistance towards antifungal agents. The molecular mechanisms behind biofilm resistance in C. albicans are not yet understood. In the present study, we investigated the transcriptional response in young and mature in vitro-grown biofilms after a short and longer exposure time to high doses of fluconazole or amphotericin B. Treatment of biofilms with high doses of antifungal agents resulted in a drug-specific transcriptional response. Exposure of biofilms to fluconazole induced upregulation of genes encoding enzymes involved in ergosterol biosynthesis (ERG1, ERG3, ERG11 and ERG25). Treatment of biofilms with amphotericin B resulted in an overexpression of KRE1 and SKN1, two genes encoding proteins involved in beta-1,6-glucan biosynthesis. Our data indicate that sessile C. albicans cells show controlled regulation of gene expression, as they quickly mount a drug-specific transcriptional response in the presence of high doses of antifungal agents. These transcriptional changes suggest upregulation of ergosterol biosynthesis (fluconazole) and upregulation of beta-1,6-glucan biosynthesis (amphotericin B) in sessile C. albicans cells that might contribute to a resistant biofilm phenotype.

PMID: 20170727 [PubMed - indexed for MEDLINE]

783. J Biol Chem. 2010 Apr 23;285(17):13066-78. Epub 2010 Feb 17.

Structural determination and tryptophan fluorescence of heterokaryon incompatibility C2 protein (HET-C2), a fungal glycolipid transfer protein (GLTP), provide novel insights into glycolipid specificity and membrane interaction by the GLTP fold.

Kenoth R, Simanshu DK, Kamlekar RK, Pike HM, Molotkovsky JG, Benson LM, Bergen HR 3rd, Prendergast FG, Malinina L, Venyaminov SY, Patel DJ, Brown RE.

Hormel Institute, University of Minnesota, Austin, Minnesota 55912, USA.

HET-C2 is a fungal protein that transfers glycosphingolipids between membranes and has limited sequence homology with human glycolipid transfer protein (GLTP). The human GLTP fold is unique among lipid binding/transfer proteins, defining the GLTP superfamily. Herein, GLTP fold formation by HET-C2, its glycolipid transfer specificity, and the functional role(s) of its two Trp residues have been investigated. X-ray diffraction (1.9 A) revealed a GLTP fold with all key sugar headgroup recognition residues (Asp(66), Asn(70), Lys(73), Trp(109), and His(147)) conserved and properly oriented for glycolipid binding. Far-UV CD showed secondary structure dominated by alpha-helices and a cooperative thermal unfolding transition of 49 degrees C, features consistent with a GLTP fold. Environmentally induced optical activity of Trp/Tyr/Phe (2:4:12) detected by near-UV CD was unaffected by membranes containing glycolipid but was slightly altered by membranes lacking glycolipid. Trp fluorescence was maximal at approximately 355 nm and accessible to aqueous quenchers, indicating free exposure to the aqueous milieu and consistent with surface localization of the two Trps. Interaction with membranes lacking glycolipid triggered significant decreases in Trp emission intensity but lesser than decreases induced by membranes containing glycolipid. Binding of glycolipid (confirmed by electrospray injection mass spectrometry) resulted in a blue-shifted emission wavelength maximum (approximately 6 nm) permitting determination of binding affinities. The unique positioning of Trp(208) at the HET-C2 C terminus revealed membrane-induced conformational changes that precede glycolipid uptake, whereas key differences in residues of the sugar headgroup recognition center accounted for altered glycolipid specificity and suggested evolutionary adaptation for the simpler glycosphingolipid compositions of filamentous fungi.

PMCID: PMC2857133 PMID: 20164530 [PubMed - indexed for MEDLINE]

784. J Biol Chem. 2010 Apr 16;285(16):12087-95. Epub 2010 Feb 17.

A multifunctional mannosyltransferase family in Candida albicans determines cell wall mannan structure and host-fungus interactions.

Mora-Montes HM, Bates S, Netea MG, Castillo L, Brand A, Buurman ET, Díaz-Jiménez DF, Jan Kullberg B, Brown AJ, Odds FC, Gow NA.

School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, Scotland, UK.

The cell wall proteins of fungi are modified by N- and O-linked mannosylation and phosphomannosylation, resulting in changes to the physical and immunological properties of the cell. Glycosylation of cell wall proteins involves the activities of families of endoplasmic reticulum and Golgi-located glycosyl transferases whose activities are difficult to infer through bioinformatics. The Candida albicans MNT1/KRE2 mannosyl transferase family is represented by five members. We showed previously that Mnt1 and Mnt2 are involved in O-linked mannosylation and are required for virulence. Here, the role of C. albicans MNT3, MNT4, and MNT5 was determined by generating single and multiple MnTDelta null mutants and by functional complementation experiments in Saccharomyces cerevisiae. CaMnt3, CaMnt4, and CaMnt5 did not participate in O-linked mannosylation, but CaMnt3 and CaMnt5 had redundant activities in phosphomannosylation and were responsible for attachment of approximately half of the phosphomannan attached to N-linked mannans. CaMnt4 and CaMnt5 participated in N-mannan branching. Deletion of CaMNT3, CaMNT4, and CaMNT5 affected the growth rate and virulence of C. albicans, affected the recognition of the yeast by human monocytes and cytokine stimulation, and led to increased cell wall chitin content and exposure of beta-glucan at the cell wall surface. Therefore, the MNT1/KRE2 gene family participates in three types of protein mannosylation in C. albicans, and these modifications play vital roles in fungal cell wall structure and cell surface recognition by the innate immune system.

PMCID: PMC2852947 PMID: 20164191 [PubMed - indexed for MEDLINE]

785. Tex Dent J. 2010 Jan;127(1):15-25.

Is your office prepared for an accidental needlestick or other unexpected exposure incident?

Alexander RE, Limes S.

Department of Oral & Maxillofacial Surgery, Texas A&M University Health Science Center, Baylor College of Dentistry, Dallas, TX, USA. ralexander@bcd.tamhsc.edu

Recommendations and mandatory guidelines for preventing and managing needlestick incidents and other accidental exposures to bloodborne pathogens in healthcare facilities have been published by the Occupational Safety and Health Administration (OSHA) and the Centers for Disease Control and Prevention (CDC) for more than 2 decades. Over the years, the incidence of official enforcement actions has declined and a complacency about the standards may have evolved in some dental offices. Some practitioners may not have written an occupational exposure incident protocol or made appropriate arrangements for medical laboratory testing and postexposure medical evaluation following an unexpected needlestick or other exposure incident in the office. When an unexpected event occurs, practitioners may become confused regarding the steps to be taken, and may turn to their local dental society or fellow practitioners for guidance. The provided information may or may not be complete, accurate and/or current. Implementation of periodic personnel training to prevent exposure incidents is extremely important and could ultimately save a dental practice thousands of dollars in expenses related to the occurrence of even one exposure incident, as well as save the life and/or career of a dental healthcare provider. This article does not comprehensively detail all infection control and bloodborne pathogen transmission prevention requirements for dental offices. Rather, the article provides suggestions for dental practitioners regarding the step by step management of exposure incidents, and provides resource information for additional steps that can be taken towards prevention, improved office compliance, and improved litigation protection.

PMID: 20162939 [PubMed - indexed for MEDLINE]

786. Arch Environ Contam Toxicol. 2010 Aug;59(2):312-21. Epub 2010 Feb 17.

Intraspecific and interspecific tolerance to copper sulphate in five Iberian amphibian species at two developmental stages.

García-Muñoz E, Guerrero F, Parra G.

Departamento de Biología Animal, Biología Vegetal y Ecología, Universidad de Jaén, Campus de las Lagunillas s/n, 23071, Jaén, Spain. egmunoz@ujaen.es

Intraspecific and interspecific variations have been observed across many taxa with respect to resistance to natural environmental stressors. It has already been well documented that amphibians are sensitive to habitat degradation and are regarded as bioindicators of aquatic and agricultural ecosystems. In southern Spain, different toxic substances, including copper sulphate, which is used to control Cycloconium oleaginum (Fungi, Ascomycota, Venturiaceae) during spring and autumn, are used in intensive olive tree agriculture. In this context, many wetlands are affected by a diffuse pollution process. Thus, toxicological studies using different species living in wetlands surrounded by agricultural activity are needed to understand the alterations suffered by these ecosystems. To achieve this understanding, individuals of five amphibian species (Bufo bufo, Epidalea calamita, Discoglossus jeanneae, Pelobates cultripes, and Pelophylax perezi) at Gosner developmental stages 19 and 25 were exposed to different copper sulphate concentrations in 96 h acute toxicity tests. Exposure to copper sulphate had a negative effect on total larval length reached at the end of the experimental period and generated approximately 30% of growth reduction respect to control treatments. P. perezi was the most tolerant species studied and showed no mortality at the maximum concentration tested (0.20 mg Cu L(-1)), whereas the most sensitive species (B. bufo, E. calamita, and D. jeanneae) showed approximately 90% mortality at the same concentration. These results indicates that the sole presence in wetlands of P. perezi, the most abundant species in southeast of Iberian Peninsula, might be correlated with its high tolerance to agrochemicals.

PMID: 20162266 [PubMed - indexed for MEDLINE]

787. J Ind Microbiol Biotechnol. 2010 Apr;37(4):419-23. Epub 2010 Feb 16.

Production of thermotolerant entomopathogenic Isaria fumosorosea SFP-198 conidia in corn-corn oil mixture.

Kim JS, Je YH, Roh JY.

Entomology Research Laboratory, Department of Plant and Soil Science, University of Vermont, 661 Spear Street, Burlington, VT 05405-0105, USA. jae-su.kim@uvm.edu

Low thermotolerance of entomopathogenic fungi is a major impediment to long-term storage and effective application of these biopesticides under seasonal high temperatures. The effects of high temperatures on the viability of an entomopathogenic fungus, Isaria fumosorosea SFP-198 (KCTC 0499BP), produced on different substrates amended with various additives were explored. Ground corn was found to be superior in producing the most thermotolerant conidia compared to yellow soybean, red kidney bean, and rice in a polyethylene bag production system. Using ground corn mixed with corn oil as a substrate resulted in only 7% reduction in germination compared to ground corn alone (67% reduction) after exposure of conidia to 50 degrees C for 2 h. Corn oil as an additive for ground corn was followed by inorganic salts (KCl and NaCl), carbohydrates (sucrose and dextrin), a sugar alcohol (sorbitol), and plant oils (soybean oil and cotton seed oil) in ability to improve conidial thermotolerance. Unsaturated fatty acids, such as linoleic acid and oleic acid, the main components of corn oil, served as effective additives for conidial thermotolerance in a dosage-dependent manner, possibly explaining the improvement by corn oil. This finding suggests that the corn-corn oil mixture can be used to produce highly thermotolerant SFP-198 conidia and provides the relation of unsaturated fatty acids as substrates with conidial thermotolerance.

PMID: 20157761 [PubMed - indexed for MEDLINE]

788. J Adhes Dent. 2010 Aug;12(4):311-7. doi: 10.3290/j.jad.a17710.

Mechanical testing of indirect composite materials directly applied on implant abutments.

Andriani W Jr, Suzuki M, Bonfante EA, Carvalho RM, Silva NR, Coelho PG.

Department of Prosthodontics, Universidade Federal de Santa Catarina, Florianopolis, Brazil.

PURPOSE: To test the strength to failure and fracture mode of three indirect composite materials directly applied onto Ti-6Al-4V implant abutments vs cemented standard porcelain-fused-to-metal (PFM) crowns. MATERIALS AND METHODS: Sixty-four locking taper abutments were randomly allocated to four groups and were cleaned in ethanol in an ultrasonic bath for 5 min. After drying under ambient conditions, the abutments were grit blasted and a custom 4-cusp molar crown mold was utilized to produce identical crowns (n = 16 per group) of Tescera (Bisco), Ceramage (Shofu), and Diamond Crown (DRM) according to the manufacturer's instructions. The porcelain-fused-to-metal crowns were fabricated by conventional means involving the construction and a wax pattern and casting of a metallic coping followed by sintering of increasing layers of porcelain. All crowns were loaded to failure by an indenter placed at one of the cusp tips at a 1 mm/min rate. Subsequently, fracture analysis was performed by means of stereomicroscopy and scanning electron microscopy. One-way ANOVA at 95% level of significance was utilized for statistical analysis.
RESULTS: The single load to failure (± SD) results were: Tescera (1130 ± 239 N), Ceramage (1099 ± 257 N), Diamond Crown (1155 ± 284 N), and PFM (1081 ± 243 N). Stereomicroscopy analysis showed two distinct failure modes, where the loaded cusp failed either with or without abutment/metallic coping exposure. SEM analysis of the fractures showed multiple crack propagation towards the cervical region of the crown below a region of plastic deformation at the indenter contact region.
CONCLUSION: The three indirect composites and PFM systems fractured at loads higher than those typically associated with normal occlusal function. Although each material had a different composition and handling technique, no significant differences were found concerning their single load to fracture resistance among composite systems and PFM.

PMID: 20157657 [PubMed - indexed for MEDLINE]

789. Curr Microbiol. 2010 Oct;61(4):261-6. Epub 2010 Feb 13.

Bioaccumulation and biovolatilisation of pentavalent arsenic by Penicillin janthinellum, Fusarium oxysporum and Trichoderma asperellum under laboratory conditions.

Su S, Zeng X, Bai L, Jiang X, Li L.

Key Laboratory of Agro-Environment & Climate Change, The Ministry of Agriculture of China, Institute of Environment and Sustainable Development in Agriculture, Chinese Academy of Agricultural Sciences, 100081 Beijing, People's Republic of China. sushiming002@163.com

Some fungi are able to control and remediate arsenic (As)-contaminated soil, sediment, or water. Here, we investigate potential accumulation and volatilisation of As by three fungi strains. Results indicated that the highest level of As was accumulated by Penicillin janthinellum with 39.54 μg after 10 days in the culture system amended with 2,500 μg As(V), which represents 50 mg/l As. Fusarium oxysporum showed the highest amount of volatilised As with 304.06 μg after 15 days. The As content in the treated system (filter paper + As + fungi) was significantly higher than that in the control (filter paper + As; filter paper + fungi; filter paper). Trichoderma asperellum and F. oxysporum showed superior abilities for the absorption of extracellular As and accumulation of intracellular As, which accounted for 82.2 and 63.4% of the total accumulated As, respectively. However, P. janthinellum presented an equal distribution of intracellular and extracellular As. Scanning electron microscope (SEM) analysis suggested that little impact on mycelium growth of the three fungal strains was seen after exposure to 50 mg/l As(V) for 5 days, while the growth of fungi in the control was inhibited. The present results demonstrate that P. janthinellum, F. oxysporum, and T. asperellum would be expected to tackle As-contaminated environments.

PMID: 20155358 [PubMed - indexed for MEDLINE]

790. Toxicol Sci. 2010 May;115(1):140-55. Epub 2010 Feb 11.

DNA damage and DNA damage responses in THP-1 monocytes after exposure to spores of either Stachybotrys chartarum or Aspergillus versicolor or to T-2 toxin.

Rakkestad KE, Skaar I, Ansteinsson VE, Solhaug A, Holme JA, Pestka JJ, Samuelsen JT, Dahlman HJ, Hongslo JK, Becher R.

Department of Air Pollution and Noise, Division of Environmental Medicine, Norwegian Institute of Public Health, Oslo, Norway.

We have characterized cell death in THP-1 cells after exposure to heat-treated spores from satratoxin G-producing Stachybotrys chartarum isolate IBT 9631, atranone-producing S. chartarum isolate IBT 9634, and sterigmatocystin-producing Aspergillus versicolor isolate IBT 3781, as well as the trichothecenes T-2 and satratoxin G. Spores induced cell death within 3-6 h, with Stachybotrys appearing most potent. IBT 9631 induced both apoptosis and necrosis, while IBT 9634 and IBT 3781 induced mostly necrosis. T-2 toxin and satratoxin G caused mainly apoptosis. Comet assay +/- formamidopyrimidine DNA glycosylase showed that only the spore exposures induced early (3h) oxidative DNA damage. Likewise, only the spores increased the formation of reactive oxygen species (ROS), suggesting that spores as particles may induce ROS formation and oxidative DNA damage. Increased Ataxia Telangiectasia Mutated (ATM) phosphorylation, indicating DNA damage, was observed after all exposures. The DNA damage response induced by IBT 9631 as well as satratoxin G was characterized by rapid (15 min) activation of p38 and H2AX. The p38 inhibitor SB 202190 reduced IBT 9631-induced H2AX activation. Both IBT 9631 and T-2 induced activation of Chk2 and H2AX after 3 h. The ATM inhibitor KU 55933, as well as transfection of cells with ATM siRNA, reduced this activation, suggesting a partial role for ATM as upstream activator for Chk2 and H2AX. In conclusion, activation of Chk2 and H2AX correlated with spore- and toxin-induced apoptosis. For IBT 9631 and satratoxin G, additional factors may be involved in triggering apoptosis, most notably p38 activation.

PMCID: PMC2902923 PMID: 20150440 [PubMed - indexed for MEDLINE]

791. J Med Microbiol. 2010 Jun;59(Pt 6):718-23. Epub 2010 Feb 11.

Characterization of the gastrointestinal yeast microbiota of cockatiels (Nymphicus hollandicus): a potential hazard to human health.

Brilhante RS, Castelo-Branco DS, Soares GD, Astete-Medrano DJ, Monteiro AJ, Cordeiro RA, Sidrim JJ, Rocha MF.

School of Veterinary Medicine, Postgraduate Program in Veterinary Science, State University of Ceará, Avenida Paranjana 1700, CEP 60.740-903, Fortaleza, Ceará, Brazil. brilhante@ufc.br

Cockatiels are the world's second most popular psittacine pet bird, but no data characterizing their gastrointestinal microbiota have been found. Thus, the aim of this work was to characterize the yeast gastrointestinal microbiota of cockatiels and to evaluate the relevance of cockatiels as carriers of potentially pathogenic yeasts. A total of 60 cockatiels, from 15 different premises, were assessed. A thorough clinical examination was performed with each bird, and samples were collected from oral cavity, crop and cloaca. The stools were collected from cages where the birds were kept. The isolates were identified according to morphological and biochemical characteristics. Yeasts were isolated from at least one anatomical site of 65% of the birds and 64.3% of the stool samples. The oral cavity (53.3%) and the crop (58.3%) were the anatomical sites with the highest prevalence and the highest number of yeast isolates. Overall, 120 yeast isolates, belonging to 13 species, were obtained. The most frequently isolated species were Candida albicans, with 39 (32.5%) isolates, followed by Candida tropicalis (20%), Trichosporon asteroides (12.5%), Candida famata (10%) and others. Mixed yeast colonies were isolated from 23.3% of the birds and C. albicans was seldom found in association with other species (P<0.05). The results of this work demonstrated that cockatiels harbour potentially pathogenic yeasts throughout their gastrointestinal tract and in stools, and are prone to disseminating them in the environment.

PMID: 20150318 [PubMed - indexed for MEDLINE]

792. Parasitol Res. 2010 Apr;106(5):1103-8. Epub 2010 Feb 10.

Relationships among bather density, levels of human waterborne pathogens, and fecal coliform counts in marine recreational beach water.

Graczyk TK, Sunderland D, Awantang GN, Mashinski Y, Lucy FE, Graczyk Z, Chomicz L, Breysse PN.

Department of Environmental Health Sciences, Division of Environmental Health Engineering, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD, 21205, USA. tgraczyk@jhsph.edu

During summer months, samples of marine beach water were tested weekly for human waterborne pathogens in association with high and low bather numbers during weekends and weekdays, respectively. The numbers of bathers on weekends were significantly higher than on weekdays (P < 0.001), and this was associated with a significant (P < 0.04) increase in water turbidity. The proportion of water samples containing Cryptosporidium parvum, Giardia duodenalis, and Enterocytozoon bieneusi was significantly higher (P < 0.03) on weekends than on weekdays, and significantly (P < 0.01) correlated with enterococci counts. The concentration of all three waterborne pathogens was significantly correlated with bather density (P < 0.01). The study demonstrated that: (a) human pathogens were present in beach water on days deemed acceptable for bathing according to fecal bacterial standards; (b) enterococci count was a good indicator for the presence of Cryptosporidium, Giardia, and microsporidian spores in recreational marine beach water; (c) water should be tested for enterococci during times when bather numbers are high; (d) re-suspension of bottom sediments by bathers caused elevated levels of enterococci and waterborne parasites, thus bathers themselves can create a non-point source for water contamination; and (e) exposure to recreational bathing waters can play a role in epidemiology of microsporidiosis. In order to protect public health, it is recommended to: (a) prevent diapered children from entering beach water; (b) introduce bather number limits to recreational areas; (c) advise people with gastroenteritis to avoid bathing; and (d) use showers prior to and after bathing.

PMID: 20145953 [PubMed - indexed for MEDLINE]

793. Antimicrob Agents Chemother. 2010 May;54(5):1655-64. Epub 2010 Feb 9.

Changes in the proteome of Candida albicans in response to azole, polyene, and echinocandin antifungal agents.

Hoehamer CF, Cummings ED, Hilliard GM, Rogers PD.

Department of Clinical Pharmacy, Colleges of Pharmacy and Medicine, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA.

The yeast Candida albicans is an opportunistic human fungal pathogen and the cause of superficial and systemic infections in immunocompromised patients. The classes of antifungal agents most commonly used to treat Candida infections are the azoles, polyenes, and echinocandins. In the present study, we identified changes in C. albicans protein abundance using two-dimensional polyacrylamide gel electrophoresis and matrix-assisted laser desorption ionization-time of flight mass spectroscopy following exposure to representatives of the azole (ketoconazole), polyene (amphotericin B), and echinocandin (caspofungin) antifungals in an effort to elucidate the adaptive responses to these classes of antifungal agents. We identified 39 proteins whose abundance changed in response to ketoconazole exposure. Some of these proteins are involved in ergosterol biosynthesis and are associated with azole resistance. Exposure to amphotericin B altered the abundance of 43 proteins, including those associated with oxidative stress and osmotic tolerance. We identified 50 proteins whose abundance changed after exposure to caspofungin, including enzymes involved in cell wall biosynthesis and integrity, as well as the regulator of beta-1,3-glucan synthase activity, Rho1p. Exposure to caspofungin also increased the abundance of the proteins involved in oxidative and osmotic stress. The common adaptive responses shared by all three antifungal agents included proteins involved in carbohydrate metabolism. Some of these antifungal-responsive proteins may represent potential targets for the development of novel therapeutics that could enhance the antifungal activities of these drugs.

PMCID: PMC2863685 PMID: 20145080 [PubMed - indexed for MEDLINE]

794. Fungal Genet Biol. 2010 May;47(5):468-76. Epub 2010 Feb 6.

Crucial factors of the light perception machinery and their impact on growth and cellulase gene transcription in Trichoderma reesei.

Castellanos F, Schmoll M, Martínez P, Tisch D, Kubicek CP, Herrera-Estrella A, Esquivel-Naranjo EU.

Laboratorio Nacional de Genómica para Biodiversidad, and Departamento de Ingeniería Genética de Plantas, CINVESTAV Irapuato, Apartado Postal 629, Irapuato 36821, Mexico.

In Trichoderma reesei light stimulates transcription of cellulase genes and this regulation has been found to occur, at least in part, through the protein ENVOY. Here we analyzed the role of the BLR photoreceptor complex (BLR1/BLR2) in photoconidiation and the regulation of gene expression. Both responses were dependent on both BLR proteins. Analyses of Deltablr1, Deltablr2 and Deltaenv1 mutants showed that the BLR proteins regulate growth under illumination. Analysis of env1 mutant strains indicated that ENVOY allows the fungus to tolerate continuous exposure to light, damped the capacity of Trichoderma to perceive changes in light intensity, and suggested that it participates in a negative regulatory feedback. Its activity as repressor establishes a period of insensitivity to a second light treatment. Interestingly, the stimulation of cellulase gene expression by light was also modulated by both blr1 and blr2, indicating a key role of the BLR proteins in this pathway.

PMID: 20144726 [PubMed - indexed for MEDLINE]

795. Fungal Genet Biol. 2010 May;47(5):458-67. Epub 2010 Feb 6.

Characterization of a novel 2,4,6-trichlorophenol-inducible gene encoding chlorophenol O-methyltransferase from Trichoderma longibrachiatum responsible for the formation of chloroanisoles and detoxification of chlorophenols.

Feltrer R, Alvarez-Rodríguez ML, Barreiro C, Godio RP, Coque JJ.

Instituto de Biotecnología INBIOTEC, Parque Científico de León, Avenida Real, 24006 León, Spain.

De novo sequencing of eight internal peptides of purified chlorophenol O-methyltransferase, or CMT1 (before named as CPOMT), from Trichoderma longibrachiatum was performed by MALDI-TOF/TOF and ESI-IT. A novel gene (cmt1) encoding CMT1 was cloned by using a PCR approach based on the amino acid sequence of two internal peptides. The gene (1637 bp) encoded a protein of 468 amino acids with a deduced molecular mass of 52.4 kDa, and a theoretical isoelectric point of 5.93. This gene contains four introns, whose location was confirmed by comparison of cDNA and chromosomal sequences. The expression of cmt1 gene was induced at transcriptional level by exposure of fungal mycelia to 2,4,6-trichlorophenol (2,4,6-TCP). Putative homologous genes were detected in many different fungal strains, including other Trichoderma species. Partial silencing of cmt1 gene resulted in a 48.9% (+/-5.2) decrease of CMT1 activity levels in a T. longibrachiatum At37 transformant strain by comparison with the wild type, whereas a decrease of up to 53.0% was observed in the levels of 2,4,6-TCA produced in liquid cultures. Efficient expression of cmt1 gene in Escherichia coli unequivocally confirmed that it encodes a CMT1 enzyme.

PMID: 20144725 [PubMed - indexed for MEDLINE]

796. Environ Sci Technol. 2010 Mar 1;44(5):1742-6.

Design and application of an inertial impactor in combination with an ATP bioluminescence detector for in situ rapid estimation of the efficacies of air controlling devices on removal of bioaerosols.

Yoon KY, Park CW, Byeon JH, Hwang J.

School of Mechanical Engineering, Yonsei University, Seoul 120-749, Republic of Korea, and LCD Division, Samsung Electronics Co., Ltd., Yongin 446-711, Republic of Korea.

We proposed a rapid method to estimate the efficacies of air controlling devices in situ using ATP bioluminescence in combination with an inertial impactor. The inertial impactor was designed to have 1 mum of cutoff diameter, and its performance was estimated analytically, numerically, and experimentally. The proposed method was characterized using Staphylococcus epidermidis, which was aerosolized with a nebulizer. The bioaerosol concentrations were estimated within 25 min using the proposed method without a culturing process, which requires several days for colony formation. A linear relationship was obtained between the results of the proposed ATP method (RLU/m(3)) and the conventional culture-based method (CFU/m(3)), with R(2) 0.9283. The proposed method was applied to estimate the concentration of indoor bioaerosols, which were identified as a mixture of various microbial species including bacteria, fungi, and actinomycetes, in an occupational indoor environment, controlled by mechanical ventilation and an air cleaner. Consequently, the proposed method showed a linearity with the culture-based method for indoor bioaerosols with R(2) 0.8189, even though various kinds of microorganisms existed in the indoor air. The proposed method may be effective in monitoring the changes of relative concentration of indoor bioaerosols and estimating the effectiveness of air control devices in indoor environments.

PMID: 20143821 [PubMed - indexed for MEDLINE]

797. Planta Med. 2010 Jul;76(10):969-74. Epub 2010 Feb 8.

Cellular mechanisms of the anticancer effects of the lichen compound usnic acid.

Einarsdóttir E, Groeneweg J, Björnsdóttir GG, Harethardottir G, Omarsdóttir S, Ingólfsdóttir K, Ogmundsdóttir HM.

Faculty of Pharmaceutical Sciences, University of Iceland, Reykjavik, Iceland.

The lichen compound usnic acid is used for its antimicrobial activities in cosmetic products and is also a component of slimming agents. Its effect against cancer cells was first noted over 30 years ago. In this study possible mechanisms of this effect were investigated using two human cell lines, the breast cancer cell line T-47D and the pancreatic cancer cell line Capan-2. Pure (+)-usnic acid from CLADONIA ARBUSCULA and (-)-usnic acid from ALECTORIA OCHROLEUCA were shown to be equally effective inhibitors of DNA synthesis, with IC (50) 4.2 microg/mL and 4.0 microg/mL for (+) and (-)-usnic acid against T-47D, and 5.3 microg/mL and 5.0 microg/mL against Capan-2, respectively. Flow cytometric analysis confirmed the inhibited entry into the S-phase and showed reduction in cell size. Classical apoptosis, as assessed by TUNEL staining, was not observed. Necrosis, measured by LDH release, was seen only in Capan-2 after exposure for 48 hours. Staining with the mitochondrial dye JC-1 demonstrated dose-dependent loss of mitochondrial membrane potential following treatment with usnic acid in both cell lines. In conclusion, usnic acid had a marked inhibitory effect on growth and proliferation of two different human cancer cell lines and led to loss of mitochondrial membrane potential. Cell survival was little affected; late necrosis was seen in one of the cell lines. No difference was noted between the two enantiomers.

Georg Thieme Verlag KG Stuttgart.New York.

PMID: 20143294 [PubMed - indexed for MEDLINE]

798. Arch Microbiol. 2010 Apr;192(4):247-57. Epub 2010 Feb 9.

Relationship between endoplasmic reticulum- and Golgi-associated calcium homeostasis and 4-NQO-induced DNA repair in Saccharomyces cerevisiae.

Poletto NP, Henriques JA, Bonatto D.

Instituto de Biotecnologia, Centro de Ciências Biológicas e da Saúde, Universidade de Caxias do Sul, Rio Grande do Sul, Brazil.

Calcium (Ca(2+)) is an important ion that is necessary for the activation of different DNA repair mechanisms. However, the mechanism by which DNA repair and Ca(2+) homeostasis cooperate remains unclear. We undertook a systems biology approach to verify the relationship between proteins associated with Ca(2+) homeostasis and DNA repair for Saccharomyces cerevisiae. Our data indicate that Pmr1p, a Ca(2+) transporter of Golgi complex, interacts with Cod1p, which regulates Ca(2+) levels in the endoplasmic reticulum (ER), and with Rad4p, which is a nucleotide excision repair (NER) protein. This information was used to construct single and double mutants defective for Pmr1p, Cod1p, and Rad4p followed by cytotoxic, cytostatic, and cell cycle arrest analyses after cell exposure to different concentrations of 4-nitroquinoline 1-oxide (4-NQO). The results indicated that cod1Delta, cod1Deltarad4Delta, and cod1Deltapmr1Delta strains have an elevated sensitivity to 4-NQO when compared to its wild-type (WT) strain. Moreover, both cod1Deltapmr1Delta and cod1Deltarad4Delta strains have a strong arrest at G(2)/M phases of cell cycle after 4-NQO treatment, while pmr1Deltarad4Delta have a similar sensitivity and cell cycle arrest profile when compared to rad4Delta after 4-NQO exposure. Taken together, our results indicate that deletion in Golgi- and ER-associated Ca(2+) transporters affect the repair of 4-NQO-induced DNA damage.

PMID: 20143049 [PubMed - indexed for MEDLINE]

799. Food Microbiol. 2010 Apr;27(2):187-98. Epub 2009 Dec 2.

A review on ochratoxin A occurrence and effects of processing of cereal and cereal derived food products.

Duarte SC, Pena A, Lino CM.

Group of Health Surveillance, Center of Pharmaceutical Studies, University of Coimbra, Pólo III, 3000-548, Coimbra, Portugal. sofiacanceladuarte@gmail.com

Ochratoxin A (OTA) continues to grab global attention and concern for the hazard and impact that embody for both human and animals, based on its toxicity and occurrence. Despite OTA has been described in a myriad of foodstuffs, cereal and its derivatives remain the major contributors to OTA exposure. For that reason, a critical review on OTA occurrence reported by recent studies worldwide focusing on unprocessed and processed cereal foodstuffs is made in this work. Special attention is drawn to the major cereal derived products, namely flour, bread, breakfast cereals, baby/infant foods and the inherently involved technological food processing methods and its influence on the redistribution and chemical modification of OTA. The paper further examines the factors that influence the OTA content of cereal and its derived products, explicitly the different ecological niches of the ochratoxigenic mycobiota -Aspergillus spp. and Penicillium verrucosum, the agricultural practice involved, harvest procedures and storage conditions, the type of grain, and the nature and extent of technological processing as well as the ultimate stages of analytical quality level of the sampling and analysis of the suspected ingredients or foods.

PMID: 20141935 [PubMed - indexed for MEDLINE]

800. Folia Microbiol (Praha). 2009 Nov;54(6):505-8. Epub 2010 Feb 7.

Modulation of enzyme activities of a lead-adapted strain of Rhizopus arrhizus during bioaccumulation of lead.

Bhattacharyya S, Pal TK, Basumajumdar A.

Department of Chemical Technology, University of Calcutta, Kolkata, India. sauryya@hotmail.com

Activity of some enzymes of a Pb-adapted strain of Rhizopus arrhizus augmented significantly during bioaccumulation of Pb from a chemically defined medium. The mycelium of a Pb-adapted strain exposed to 1 microg/mL Pb in a defined medium for 10 d at 28 +/- 2 degrees C exhibited, relative to a wild-type strain, increased activities of antioxidant enzymes, i.e. SOD, CAT and GPX and of enzymes like AP and PPO involved in defense against pathogens. Another response is a significant increase in the cellular thiol content after 4 d. The responses to Pb exposure thus include an increase in the antioxidant and anti-pathogen defense, and an increased metal-chelating ability.

PMID: 20140717 [PubMed - indexed for MEDLINE]

801. Rev Chilena Infectol. 2010 Feb;27(1):34-9. Epub 2010 Feb 3.

[Biological risk accidents among undergraduate healthcare students: five years experience].

[Article in Spanish]

Fica C A, Jemenao P MI, Ruiz R G, Larrondo L M, Hurtado H C, Muñoz G G, Sepulveda C C.

Comité de Infecciones Intrahospitalarias, Hospital Clínico Universidad de Chile, Santiago, Chile. albertofica@gmail.com

Erratum in Rev Chilena Infectol. 2010 Apr;27(2):178.

Undergraduate healthcare students are exposed to bloodborne pathogens, and data from developing countries is scarce. We report the experience of a comprehensive program dedicated to the management of this risk. The program includes financial coverage, a 24-hour attention system, HIV, HBV, HCV testing, and free provision of post-exposure antiretroviral drugs. During 2003-2007, incidence rates of these exposures reached 0.9 per 100 student-years. Events were only observed among medicine, nursing, and midwifery students, with rates highest among nursing students (RR 3.5 IC95 1.93 - 6.51). Cuts and needle stick injuries predominated (74.7% of accidents). Three students were exposed to HIV patients (1.9%), all of them received prophylactic drugs, infection was discarded after follow up, and also discarded after exposures to HBV or HCV (0.6% of all accidents). Cost per 1000 student-year was less than 2000 USD. Healthcare students are exposed to biological risks during their studies and a comprehensive program is feasible in a developing country.

PMID: 20140312 [PubMed - indexed for MEDLINE]

802. Int J Antimicrob Agents. 2010 Apr;35(4):396-9. Epub 2010 Feb 9.

Susceptibility to five antifungals of Aspergillus fumigatus strains isolated from chronically colonised cystic fibrosis patients receiving azole therapy.

Amorim A, Guedes-Vaz L, Araujo R.

Department of Pneumology, Faculty of Medicine, University of Porto, Alameda Prof. Hernani Monteiro, 4200-319 Porto, Portugal.

Exposure of Aspergillus fumigatus to stressful antifungal therapies may result in decreased susceptibility. The aim of the present work was to evaluate the susceptibility to azole and non-azole antifungals of 159 isolates of A. fumigatus collected from cystic fibrosis (CF) patients receiving azole antifungal therapy. The genetic diversity of the fungal isolates was assessed using microsatellite genotyping, and some strains were found in patient's sputum samples more than 4 years apart. No resistant isolates [minimal inhibitory concentration (MIC)/minimal effective concentration (MEC)>or=4 microg/mL] were identified to the antifungals amphotericin B, caspofungin, itraconazole and voriconazole. A single A. fumigatus isolate was identified outside of the epidemiological cut-off of 0.25 microg/mL for posaconazole. Susceptibility of the recurrent isolates was in agreement with the susceptibility of the first isolate identified (100% essential agreement). Even after azole exposure, several recurrent A. fumigatus strains were detected in the subsequent sputum samples. Development of resistance in A. fumigatus to antifungals appears to be rare amongst CF patients. However, it remains crucial to evaluate the importance of antifungal agents for allergic fungal diseases.

PMID: 20138740 [PubMed - indexed for MEDLINE]

803. J Allergy Clin Immunol. 2010 Mar;125(3):593-9. Epub 2010 Feb 4.

Differential effects of outdoor versus indoor fungal spores on asthma morbidity in inner-city children.

Pongracic JA, O'Connor GT, Muilenberg ML, Vaughn B, Gold DR, Kattan M, Morgan WJ, Gruchalla RS, Smartt E, Mitchell HE.

Children's Memorial Hospital, Northwestern University Feinberg School of Medicine, Chicago, Ill, USA. j-pongracic@northwestern.edu

BACKGROUND: Although sensitization to fungal allergens is prevalent in inner-city children with asthma, the relationship between fungal exposure and morbidity is poorly understood.
OBJECTIVE: We examined relationships between fungal sensitization, exposure, and asthma morbidity in inner-city children.
METHODS: Participants were 5 to 11 years old and enrolled in the Inner-City Asthma Study. This report includes the subset of children with at least 1 positive skin test (PST) response to a fungal allergen extract; for these children, indoor and outdoor airborne culturable fungi levels were measured at baseline and throughout the 2-year study. Asthma morbidity measures were collected prospectively. The primary outcome was symptom days per 2 weeks.
RESULTS: At baseline, children with a PST response to a fungal allergen extract had significantly more symptom days compared with those without a PST response to any fungal allergen extract (6.3 vs 5.7 days per 2 weeks, P = .04). During the study, increases in total fungal exposure and indoor Penicillium species exposure were associated with increases in symptom days and asthma-related unscheduled visits. Indoor exposures to total fungi and to Penicillium species were associated with significant increases in unscheduled visits, even after controlling for outdoor fungal levels. Adverse effects associated with exposure to a specific fungus were stronger among children with PST responses to that fungal allergen extract compared with those seen in children with negative skin test responses.
CONCLUSION: Outdoor fungal exposure is primarily associated with increased asthma symptoms and increased risk of exacerbations in this population.

PMID: 20132971 [PubMed - indexed for MEDLINE]

804. Int Arch Occup Environ Health. 2010 Dec;83(8):855-65. Epub 2010 Feb 3.

New-onset adult asthma in relation to damp and moldy workplaces.

Karvala K, Toskala E, Luukkonen R, Lappalainen S, Uitti J, Nordman H.

Occupational Medicine Team, Finnish Institute of Occupational Health (FIOH), Topeliuksenkatu 41 a A, 00250, Helsinki, Finland. kirsi.karvala@ttl.fi

OBJECTIVE: Damp and moldy indoor environments aggravate pre-existing asthma. Recent meta-analyses suggest that exposure to such environments may also induce new-onset asthma. We assessed the probability of molds being the cause of asthma in a patient series examined because of respiratory symptoms in relation to workplace dampness and molds.
METHODS: Altogether 694 such patients had been clinically assessed between 1995 and 2004. According to their histories, they had all been exposed to molds at work and had suffered from work-related lower respiratory symptoms. The investigations had included specific inhalation challenge (SIC) tests with mold extracts and serial peak expiratory flow (PEF) recordings. Using internationally recommended diagnostic criteria for occupational asthma (OA), we categorized the patients into three groups: probable, possible, and unlikely OA (156, 45, and 475 patients, respectively). The clinical details of 258 patients were analyzed, and their levels of microbial exposure were evaluated.
RESULTS: The agreement between the serial PEF recordings and SIC tests (both being either positive or negative) was 56%. In the group of probable OA, mold sensitization was found in 20%. The level of exposure and sensitization to molds was associated with probable OA. At 6 months, the follow-up examinations of 136 patients with probable OA showed that the symptoms were persistent, and no improvement in spirometry was noted despite adequate treatment. Only 58% of the patients had returned to work.
CONCLUSIONS: Exposure to damp and moldy workplaces can induce new-onset adult asthma. IgE mediation is a rare mechanism, whereas other mechanisms are unknown.

PMID: 20127354 [PubMed - indexed for MEDLINE]

805. J Environ Biol. 2009 Jul;30(4):567-75.

Determination of fungal diseases, site and stand characteristics in mixed stands in Ilgaz-Yenice forest district, Cankiri, Turkey.

Oner N, Dogan HH, Ozturk C, Gurer M.

Faculty of Forestry, Cankiri Karatekin University, 18200, Cankiri, Turkey.

Fungal diseases, site and stand characteristics were investigated in Yenice forest sub-district headquarters belonging to Ilgaz forest enterprise. Diseases and wood decaying fungi on fallen and cut tree stumps were determined on scots pine (Pinus sylvestris), crimean pine (P. nigra subsp. nigra varcaramanica), and uludag fir (Abies nordmanniana subsp. bommulleriana). Altitude (m), exposure, slope (%), relief, rate of mixture (%) and anthropogenic effects were noted for 56 sample plots which have various stand compositions. Age, breast height diameter (cm), top height (m), crown and bole quality regeneration quality and development of representative tree species were also recorded into vegetation forms. Yellow witches' broom (Melampsorella caryophyllacearum), which caused drying of uludag fir trees, was determined. Besides, 53 macrofungi species belonging to 3 divisions, 10 orders, 25 families and 36 genera were determined. Some of them cause white and brown decay on living and core wood. The most common parasitic and saprobe fungi are Galerina Ganoderma, Gloeophyllum, Gymnopilus, Hypholoma, Lentinus, Phellinus, Pleurotus, Polyporus and Stereum species in the research area. Trichaptum abietinum is also typical wood decay fungi for living or cut fir trees and it is very common in the research area.

PMID: 20120498 [PubMed - indexed for MEDLINE]

806. J Toxicol Sci. 2010 Feb;35(1):125-9.

DNA microarray analysis of genomic responses of yeast Saccharomyces cerevisiae to nickel chloride.

Takumi S, Kimura H, Matsusaki H, Kawazoe S, Tominaga N, Arizono K.

Faculty of Environmental and Symbiotic Sciences, Prefectural University of Kumamoto.

In order to investigate nickel toxicity against the yeast Saccharomyces cerevisiae, genomic responses to nickel chloride were examined using yeast DNA microarrays. Microarray analysis revealed that exposure to 25 mM nickel chloride for 2 hr induced changes in gene expression in S. cerevisiae. Nickel chloride increased expression levels in 601 genes and decreased expression levels in 696 genes in S. cerevisiae.

PMID: 20118633 [PubMed - indexed for MEDLINE]

807. Am J Respir Cell Mol Biol. 2011 Jan;44(1):11-23. Epub 2010 Jan 29.

Airway epithelial indoleamine 2,3-dioxygenase inhibits CD4+ T cells during Aspergillus fumigatus antigen exposure.

Paveglio SA, Allard J, Foster Hodgkins SR, Ather JL, Bevelander M, Campbell JM, Whittaker LeClair LA, McCarthy SM, van der Vliet A, Suratt BT, Boyson JE, Uematsu S, Akira S, Poynter ME.

Vermont Lung Center, and Division of Pulmonary Disease and Critical Care, Department of Medicine, University of Vermont, 149 Beaumont Ave., Burlington, VT 05405, USA.

Indoleamine 2,3-dioxygenase (IDO) suppresses the functions of CD4(+) T cells through its ability to metabolize the essential amino acid tryptophan. Although the activity of IDO is required for the immunosuppression of allergic airway disease by the Toll-Like-Receptor 9 (TLR9) agonist, oligonucleotides comprised of cytosine and guanine nucleotides linked by phosphodiester bonds (CpG) DNA, it is unclear whether IDO expression by resident lung epithelial cells is sufficient to elicit these effects. Therefore, we created a transgenic mouse inducibly overexpressing IDO within nonciliated airway epithelial cells. Upon inhalation of formalin-fixed Aspergillus fumigatus hyphal antigens, the overexpression of IDO from airway epithelial cells of these mice reduced the number of CD4(+) T cells within the inflamed lung and impaired the capacity of antigen-specific splenic CD4(+) effector T cells to secrete the cytokines IL-4, IL-5, IL-13, and IFN-γ. Despite these effects, allergic airway disease pathology was largely unaffected in mice expressing IDO in airway epithelium. In support of the concept that dendritic cells are the major cell type contributing to the IDO-inducing effects of CpG DNA, mice expressing TLR9 only in the airway epithelium did not augment IDO expression subsequent to the administration of CpG DNA. Furthermore, the systemic depletion of CD11c(+) cells rendered mice incapable of CpG DNA-induced IDO expression. Our results demonstrate that an overexpression of IDO within the airway epithelium represents a novel mechanism by which the number of CD4(+) T cells recruited to the lung and their capacity to produce cytokines can be diminished in a model of allergic airway disease, and these results also highlight the critical role of dendritic cells in the antiasthmatic effects of IDO induction by CpG DNA.

PMCID: PMC3028254 PMID: 20118221 [PubMed - indexed for MEDLINE]

808. Curr Biol. 2010 Feb 9;20(3):249-52. Epub 2010 Jan 28.

Moribund ants leave their nests to die in social isolation.

Heinze J, Walter B.

Biologie I, Universität Regensburg, 93040 Regensburg, Germany. juergen.heinze@biologie.uni-regensburg.de

Comment in Curr Biol. 2010 Feb 9;20(3):R104-5.

Animal societies provide perfect conditions for the spread of infections and are therefore expected to employ mechanisms that reduce the probability of transmitting pathogens to group members [1-4]. Death in nature rarely results from old age but commonly results from diseases. Leaving one's group to die in seclusion might be an efficient way of minimizing the risk of infecting kin. Anecdotal observations of moribund individuals deserting from their groups exist for several species, including humans (e.g., [5]), but have rarely been substantiated by quantitative analysis. Furthermore, to confirm that dying in solitude has evolved because of its altruistic benefits requires refuting the alternative explanation of pathogen manipulation of host behavior. Here we show that workers of the ant Temnothorax unifasciatus dying from fungal infection, uninfected workers whose life expectancy was reduced by exposure to 95% CO(2)[6, 7], and workers dying spontaneously in observation colonies exhibited the same suite of behavior of isolating themselves from their nestmates days or hours before death. Actively leaving the nest and breaking off all social interactions thus occurred regardless of whether individuals were infected or not. Social withdrawal might be a commonly overlooked altruistic trait serving the inclusive fitness interests of dying individuals in social animals.

PMID: 20116243 [PubMed - indexed for MEDLINE]

809. Emerg Infect Dis. 2010 Feb;16(2):335-7.

Seropositivity for Enterocytozoon bieneusi, Czech Republic.

Sak B, Kucerova Z, Kvac M, Kvetonova D, Rost M, Secor EW.

Biology Centre of the Academy of Sciences of the Czech Republic, Ceske Budejovice, Czech Republic.

To determine seropositivity for Enterocytozoon bieneusi in the Czech Republic, we tested 115 serum samples from various groups. We found that 20% from HIV-positive persons, 33% from persons with occupational exposure to animals, and 10% from healthy persons were positive by indirect immunofluorescence assay. Proteins of 32 kDa were detected in serum samples from seropositive persons.

PMID: 20113575 [PubMed - indexed for MEDLINE]

810. Photochem Photobiol. 2010 May-Jun;86(3):653-61. Epub 2010 Jan 22.

Photodynamic inactivation of conidia of the fungi Metarhizium anisopliae and Aspergillus nidulans with methylene blue and toluidine blue.

Gonzales FP, da Silva SH, Roberts DW, Braga GU.

Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.

Antimicrobial photodynamic treatment (PDT) is a promising method that can be used to control localized mycoses or kill fungi in the environment. A major objective of the current study was to compare the conidial photosensitization of two fungal species (Metarhizium anisopliae and Aspergillus nidulans) with methylene blue (MB) and toluidine blue (TBO) under different incubation and light conditions. Parameters examined were media, photosensitizer (PS) concentration and light source. PDT with MB and TBO resulted in an incomplete inactivation of the conidia of both fungal species. Conidial inactivation reached up to 99.7%, but none of the treatments was sufficient to achieve a 100% fungicidal effect using either MB or TBO. PDT delayed the germination of the surviving conidia. Washing the conidia to remove unbound PS before light exposure drastically reduced the photosensitization of A. nidulans. The reduction was much smaller in M. anisopliae conidia, indicating that the conidia of the two species interact differently with MB and TBO. Conidia of green and yellow M. anisopliae mutants were less affected by PDT than mutants with white and violet conidia. In contrast to what occurred in PBS, photosensitization of M. anisopliae and A. nidulans conidia was not observed when PDT was performed in potato dextrose media.

PMID: 20113427 [PubMed - indexed for MEDLINE]

811. Mycoses. 2011 Jul;54(4):e62-8. doi: 10.1111/j.1439-0507.2009.01834.x. Epub 2010 Jan 27.

Fungicidal activity and morphological alterations of Candida albicans induced by echinocandins: study of strains with reduced caspofungin susceptibility.

Dunyach C, Drakulovski P, Bertout S, Jouvert S, Reynes J, Mallié M.

Laboratoire de Parasitologie et Mycologie Médicale, UMR 145 IRD/Université Montpellier I VIH/SIDA et Maladies Associées, Faculté de Pharmacie, Montpellier, France.

Caspofungin is a member of the echinocandin class of antifungal compounds that inhibit 1,3-β-d-Glucan synthase. As patient exposure to caspofungin (CAS) broadens, the number of infecting strains with reduced susceptibility to this drug is expected to rise. In the present study, the in vitro effects of varying concentrations of CAS against Candida albicans isolates presenting reduced susceptibility to CAS were studied in comparison with a reference strain. Two C. albicans isolates presenting high minimal inhibitory concentrations (MIC = 8 μg ml(-1) ) were selected: one isolate obtained in the laboratory under continuous antifungal selection pressure (CaIn-R) and one clinical isolate (CaClin-R) from a patient with a therapeutic failure. Results showed that after 24 h of CAS exposure, CaIn-R and CaClin-R presented a partial growth inhibition in comparison with the reference strain. Moreover, scanning electron microscopy and transmission electron microscopy studies showed that the cell walls of CaIn-R and CaClin-R were less altered than that of the reference strain. These observations suggested that although CaIn-R and CaClin-R cells were misshapen after CAS exposure, cell lysis was limited after 24 h of treatment indicating higher survival ability for CaIn-R and CaClin-R in the presence of CAS.

PMID: 20113400 [PubMed - indexed for MEDLINE]

812. J Environ Sci (China). 2009;21(5):700-6.

Non-UV germicidal activity of fresh TiO2 and Ag/TiO2.

Liu L, Barford J, Yeung KL.

Key Laboratory of Industrial Ecology and Environmental Engineering, Ministry of Education of China, School of Environmental and Biological Science & Technology, Dalian University of Technology, Dalian 116024, China. kelifen@hotmail.com

Fresh TiO2 was found to possess a strong germicidal activity even without UV irradiation. Live Yeast (Saccharomyces cerevisiae) cells in contact with fresh TiO2 were found deformed and dead after 15 min contact. The cause of germicidal activity was discussed from the observed cell deformation, lysis and increased absorption at 1680 cm(-1) in FT-IR spectra of the affected cells, which proved the oxidizing effect of fresh TiO2 to cells. The deformation caused by the stretching of cell wall and pressure built-up inside the cell, led to cell burst and release of intracellular materials. The degree of cell deformation was found positively related with the wetting property of TiO2. Cells are negatively charged, for Gram-negative cell (thinner cell wall), a higher germicidal effect was observed than Gram-positive cells. The germicidal effect of TiO2 gradually decreased after exposure to air at room temperature, as the wetting property decreased. This kind of germicidal activity was more effective compared to other germicidal process such as UVA/TiO2 or Ag+. This shed light on designing new germicidal material either maintained by visible light irradiation, or by oxidation effect generated by reactive oxygen species.

PMID: 20108675 [PubMed - indexed for MEDLINE]

813. Mt Sinai J Med. 2010 Jan-Feb;77(1):114-23.

Translating knowledge about environmental health to practitioners: are we doing enough?

Trasande L, Newman N, Long L, Howe G, Kerwin BJ, Martin RJ, Gahagan SA, Weil WB.

Department of Preventive Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA. leo.trasande@mssm.edu

BACKGROUND: Practitioners see a large number of children affected by environmental exposures each year. A national network of pediatric environmental health specialty units has been established to strengthen prevention capacity, yet the effectiveness of that translational resource has not been assessed.
METHODS: We supplemented a qualitative systematic review of previous assessments of healthcare provider capacity with a self-administered survey sent to the membership of the Michigan chapter of the American Academy of Pediatrics. We mailed surveys twice between October 2007 and January 2008 and obtained a 39.4% response rate.
RESULTS: Our systematic review identified 8 relevant studies, all of which relied on self-report questionnaires and surveys. Recognizing this methodological weakness, we found that national and state samples consistently identified significant gaps in self-efficacy and knowledge about environmental hazards across a broad range of child care providers. In the Michigan survey, respondents voiced high self-efficacy in dealing with lead and second-hand smoke, but confidence in managing pesticide, mercury, mold, polychlorinated biphenyl, and air pollution exposures was much lower (P < 0.0001). Pediatricians routinely referred affected patients to lead/toxicology clinics and allergist/immunologists but not to the regional pediatric environmental health specialty unit.
CONCLUSIONS: Gaps persist in practitioner knowledge about environmental health nationwide and across disciplines. Despite methodological weaknesses, educational opportunities and other efforts should be studied to determine best practices for enhancing the evaluation of environmental health concerns in children.

PMID: 20101722 [PubMed - indexed for MEDLINE]

814. Infect Immun. 2010 Apr;78(4):1426-36. Epub 2010 Jan 25.

Candida albicans beta-glucan exposure is controlled by the fungal CEK1-mediated mitogen-activated protein kinase pathway that modulates immune responses triggered through dectin-1.

Galán-Díez M, Arana DM, Serrano-Gómez D, Kremer L, Casasnovas JM, Ortega M, Cuesta-Domínguez A, Corbí AL, Pla J, Fernández-Ruiz E.

Unidad de Biología Molecular, Hospital Universitario de la Princesa, 28006 Madrid, Spain.

Innate immunity to Candida albicans depends upon the recognition of molecular patterns on the fungal cell wall. However, the masking of major components such as beta-glucan seems to be a mechanism that fungi have evolved to avoid immune cell recognition through the dectin-1 receptor. Although the role of C. albicans mitogen-activated protein kinase (MAPK) pathways as virulence determinants has been established previously with animal models, the mechanism involved in this behavior is largely unknown. In this study we demonstrate that a disruption of the C. albicans extracellular signal-regulated kinase (ERK)-like 1 (CEK1)-mediated MAPK pathway causes enhanced cell wall beta-glucan exposure, triggering immune responses more efficiently than the wild type, as measured by dectin-1-mediated specific binding and human dendritic cell (hDC)- and macrophage-mediated phagocytosis, killing, and activation of intracellular signaling pathways. At the molecular level, the disruption of CEK1 resulted in altered spleen tyrosine kinase (Syk), Raf-1, and ERK1/2 activations together with IkappaB degradation on hDCs and increased dectin-1-dependent activator protein 1 (AP-1) activation on transfected cells. In addition, concurring with these altered pathways, we detected increased reactive oxygen species production and cytokine secretion. In conclusion, the CEK1-mediated MAPK pathway is involved in beta-glucan exposure in a fungal pathogen, hence influencing dectin-1-dependent immune cell recognition, thus establishing this fungal intracellular signaling route as a promising novel therapeutic target.

PMCID: PMC2849429 PMID: 20100861 [PubMed - indexed for MEDLINE]

815. J Asthma. 2010 Feb;47(1):2-6.

Severe asthma with fungal sensitization: a case report and review of literature.

Madani Y, Barlow A, Taher F.

Department of Respiratory Medicine, Watford General Hospital, Watford, Hertfordshire, WD18 0HB, United Kingdom. yasser.madani@doctors.org.uk

There is a substantial body of evidence supporting an association between asthma severity and fungal exposure and sensitization. Fungal allergens are a recognized risk factor for severe asthma. We describe the case of a 44-year-old asthmatic whose asthma control deteriorated after moving to a new flat with walls covered in mould. Allergic bronchopulmonary aspergillosis was excluded. Although sensitization to Candida was demonstrated by a positive Candida-specific radioallergosorbent test, the patient did not entirely satisfy the criteria for a diagnosis of allergic bronchopulmonary candidiasis. The patient's asthma control improved after engaging in a monthly washing regimen of the walls. This case further demonstrates the association between fungal sensitization and asthma severity. The term severe asthma with fungal sensitization has been recently coined to describe this phenomenon.

PMID: 20100013 [PubMed - indexed for MEDLINE]

816. Pharmazie. 2009 Nov;64(11):760-4.

Poria cocos water extract (PCW) protects PC12 neuronal cells from beta-amyloid-induced cell death through antioxidant and antiapoptotic functions.

Park YH, Son IH, Kim B, Lyu YS, Moon HI, Kang HW.

INAM Neuroscience Research Center, Sanbon Medical Center, Wonkwang University, South Korea.

Beta-amyloid (Abeta)-induced neurotoxicity is considered to be mediated through the formation of reactive oxygen species (ROS). In this study, the protective effects of Poria cocos water extract (PCW) against Abeta1-42-induced cell death were investigated using rat pheochromocytoma (PC12) cells. Exposure of PC12 cells to the Abeta1-42 (20 microM) for 48h resulted in neuronal cell death, whereas pretreatment with PCW at the concentration range of 5-125 microg/ml reduced Abeta1-42-induced cell death. In addition, PC12 cells treated with Abeta1-42 exhibited increased accumulation of intracellular oxidative damages and underwent apoptotic death as determined by characteristic morphological alterations and positive in situ terminal end-labeling (TUNEL staining). However, PCW attenuated Abeta1-42-induced cytotoxicity, apoptotic features, and accumulation of intracellular oxidative damage. Moreover, PCW (5 to 125 microg/ml) decreased expression of apoptotic protein Bax and activity of caspase-3, but enhanced expression of anti-apoptotic protein Bcl-2. These results suggest that PCW may protect cells through suppressing the oxidative stress and the apoptosis induced by Abeta1-42, implying that PCW may be potential natural agents for Alzheimer's diseases.

PMID: 20099523 [PubMed - indexed for MEDLINE]

817. Eukaryot Cell. 2010 Mar;9(3):438-48. Epub 2010 Jan 22.

The transposon impala is activated by low temperatures: use of a controlled transposition system to identify genes critical for viability of Aspergillus fumigatus.

Carr PD, Tuckwell D, Hey PM, Simon L, d'Enfert C, Birch M, Oliver JD, Bromley MJ.

F2G Limited, Lankro Way, Eccles, Manchester, United Kingdom.

Genes that are essential for viability represent potential targets for the development of anti-infective agents. However, relatively few have been determined in the filamentous fungal pathogen Aspergillus fumigatus. A novel solution employing parasexual genetics coupled with transposon mutagenesis using the Fusarium oxysporum transposon impala had previously enabled the identification of 20 essential genes from A. fumigatus; however, further use of this system required a better understanding of the mode of action of the transposon itself. Examination of a range of conditions indicated that impala is activated by prolonged exposure to low temperatures. This newly identified property was then harnessed to identify 96 loci that are critical for viability in A. fumigatus, including genes required for RNA metabolism, organelle organization, protein transport, ribosome biogenesis, and transcription, as well as a number of noncoding RNAs. A number of these genes represent potential targets for much-needed novel antifungal drugs.

PMCID: PMC2837977 PMID: 20097738 [PubMed - indexed for MEDLINE]

818. Int J Food Microbiol. 2010 Mar 31;138(1-2):181-5. Epub 2010 Jan 11.

Antioxidant N-acetyltransferase Mpr1/2 of industrial baker's yeast enhances fermentation ability after air-drying stress in bread dough.

Sasano Y, Takahashi S, Shima J, Takagi H.

Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara, Japan.

During bread-making processes, yeast cells are exposed to multiple stresses. Air-drying stress is one of the most harmful stresses by generation of reactive oxygen species (ROS). Previously, we discovered that the novel N-acetyltransferase Mpr1/2 confers oxidative stress tolerance by reducing intracellular ROS level in Saccharomyces cerevisiae Sigma1278b strain. In this study, we revealed that Japanese industrial baker's yeast possesses one MPR gene. The nucleotide sequence of the MPR gene in industrial baker's yeast was identical to the MPR2 gene in Sigma1278b strain. Gene disruption analysis showed that the MPR2 gene in industrial baker's yeast is involved in air-drying stress tolerance by reducing the intracellular oxidation levels. We also found that expression of the Lys63Arg and Phe65Leu variants with enhanced enzymatic activity and stability, respectively, increased the fermentation ability of bread dough after exposure to air-drying stress compared with the wild-type Mpr1. In addition, our recent study showed that industrial baker's yeast cells accumulating proline exhibited enhanced freeze tolerance in bread dough. Proline accumulation also enhanced the fermentation ability after air-drying stress treatment in industrial baker's yeast. Hence, the antioxidant enzyme Mpr1/2 could be promising for breeding novel yeast strains that are tolerant to air-drying stress.

PMID: 20096471 [PubMed - indexed for MEDLINE]

819. Curr Opin Allergy Clin Immunol. 2010 Apr;10(2):99-103.

Hypersensitivity pneumonitis.

Girard M, Cormier Y.

Centre de recherche de l'Institut universitaire de Cardiologie et de Pneumologie de Québec, Quebec City, Quebec, Canada.

PURPOSE OF REVIEW: To bring readers up to date on recent reports, both clinical and basic understanding, on hypersensitivity pneumonitis.
RECENT FINDINGS: Although many antigens and environmental settings have already been described as sources of this hyperimmune pulmonary disease, the literature continues to bring forth other conditions that can cause hypersensitivity pneumonitis. We also highlight new findings in the diagnosis of hypersensitivity pneumonitis, its histopathology, insight into its potential outcomes, and understanding of its immune mechanisms that could lead to new treatments. SUMMARY: The review will help clinicians in their diagnostic approach to hypersensitivity pneumonitis and lead them to look for other potential sources of the disease. The findings described will help guide further research on the pathophysiology and seek new treatments for this worldwide orphan disease.

PMID: 20093932 [PubMed - indexed for MEDLINE]

820. Med Mycol. 2010 Aug;48(5):725-34.

The post-antifungal effect (PAFE) of amphotericin B, nystatin, ketoconazole and 5-fluorocytosine and its impact on the colonization traits of Candida glabrata.

Samaranayake YH, Yau JY, Thein ZM, Jayatilake JA, Yeung KW, Samaranayake LP.

Oral Bio-sciences, Faculty of Dentistry, University of Hong Kong, Hong Kong. lakshman@hkucc.hku.hk

The post-antifungal effect (PAFE) has been shown to affect Candida pathogenicity, but there is little information on either PAFE or its association with the colonization traits of Candida glabrata. The objective of this study was to determine, in vitro, the PAFE on 14 C. glabrata isolates following exposure to amphotericin B (AMB), nystatin (NYS), ketoconazole (KETO) and 5-fluorocytosine (5FC). In addition, we evaluated the impact of PAFE on yeast adherence to buccal epithelial cells (BEC), cell-surface-hydrophobicity (CSH) and biofilm growth (BG) on denture acrylic surfaces. PAFE was induced following a 1-h exposure of yeasts to (x1-x4MIC) of AMB, NYS, KETO and 5FC in RPMI medium and, measured using automated turbidometry. The BEC adhesion, CSH and BG assays were performed by the methods of Kimura & Pearsall, Sweet et al., and Jin et al., respectively. Significant differences in PAFE (P < 0.001) were observed after exposure to AMB and NYS, but not KETO and 5FC. Following exposure to AMB, NYS, KETO and 5FC, significant inter-strain differences (P < 0.001) were observed in percentage terms in adhesion (39.0%, 43.48%, 38.28%, 35.07%) and biofilm growth (42.86%, 39.86%, 42.81%, 36.38%), respectively. Short exposure of C. glabrata to sub-cidal concentrations of antifungals modulates yeast growth and also affects some of their colonization traits.

PMID: 20092419 [PubMed - indexed for MEDLINE]

821. Carcinogenesis. 2010 May;31(5):785-93. Epub 2010 Jan 20.

Polo-like kinase 1 enhances survival and mutagenesis after genotoxic stress in normal cells through cell cycle checkpoint bypass.

Chun G, Bae D, Nickens K, O'Brien TJ, Patierno SR, Ceryak S.

Department of Pharmacology and Physiology, The George Washington University Medical Center, Washington, DC 20037, USA.

Polo-like kinase 1 (Plk1) is a key regulator of mitosis. Aberrant Plk1 activity is found in tumors, but little is known regarding its role in the DNA damage response of normal cells and its potential contribution to the early stages of carcinogenesis. Inappropriate survival signaling after DNA damage may facilitate clonal expansion of genetically compromised cells, and it is known that protein tyrosine phosphatase (PTP) inhibitors activate key survival pathways. In this study, we employed hexavalent chromium [Cr(VI)], a well-documented genotoxicant, to investigate the mechanism by which survival pathway activation could lead to loss of checkpoint control via a mechanism involving Plk1. We recently reported that PTP inhibition enhances clonogenic survival and mutagenesis after Cr(VI) exposure by overriding Cr-induced growth arrest. Here, we report that checkpoint bypass, facilitated by PTP inhibition, was associated with decreased Cdk1 Tyr15 phosphorylation, as well as increased Plk1 activity and nuclear localization. Plk1 was necessary for increased survival after PTP inhibition and Cr(VI) exposure in normal human fibroblasts via enhanced mitotic progression. In addition, pharmacological inhibition of Plk1 abolished the PTP inhibitor-induced bypass of the G(2)/M checkpoint. Notably, Plk1 overexpression increased survival and mutagenesis after Cr(VI) exposure in wild-type Saccharomyces cerevisiae. Taken together, our data indicate that Plk1 activation and nuclear localization are necessary for PTP-regulated mitotic progression after DNA damage. Our studies highlight a role for Plk1 in the loss of checkpoint control, increased survival and mutagenesis after genotoxic exposure in normal cells, which in turn may lead to genomic instability and carcinogenesis.

PMCID: PMC2864408 PMID: 20089605 [PubMed - indexed for MEDLINE]

822. Malar J. 2010 Jan 19;9:22.

Factors affecting fungus-induced larval mortality in Anopheles gambiae and Anopheles stephensi.

Bukhari T, Middelman A, Koenraadt CJ, Takken W, Knols BG.

Laboratory of Entomology, Wageningen University, Wageningen, the Netherlands.

BACKGROUND: Entomopathogenic fungi have shown great potential for the control of adult malaria vectors. However, their ability to control aquatic stages of anopheline vectors remains largely unexplored. Therefore, how larval characteristics (Anopheles species, age and larval density), fungus (species and concentration) and environmental effects (exposure duration and food availability) influence larval mortality caused by fungus, was studied.
METHODS: Laboratory bioassays were performed on the larval stages of Anopheles gambiae and Anopheles stephensi with spores of two fungus species, Metarhizium anisopliae and Beauveria bassiana. For various larval and fungal characteristics and environmental effects the time to death was determined and survival curves established. These curves were compared by Kaplan Meier and Cox regression analyses.
RESULTS: Beauveria bassiana and Metarhizium anisopliae caused high mortality of An. gambiae and An. stephensi larvae. However, Beauveria bassiana was less effective (Hazard ratio (HR) <1) compared to Metarhizium anisopliae. Anopheles stephensi and An. gambiae were equally susceptible to each fungus. Older larvae were less likely to die than young larvae (HR < 1). The effect of increase in fungus concentration on larval mortality was influenced by spore clumping. One day exposure to fungal spores was found to be equally effective as seven days exposure. In different exposure time treatments 0 - 4.9% of the total larvae, exposed to fungus, showed infection at either the pupal or adult stage. Mortality rate increased with increasing larval density and amount of available food.
CONCLUSIONS: This study shows that both fungus species have potential to kill mosquitoes in the larval stage, and that mortality rate depends on fungus species itself, larval stage targeted, larval density and amount of nutrients available to the larvae. Increasing the concentration of fungal spores or reducing the exposure time to spores did not show a proportional increase and decrease in mortality rate, respectively, because the spores clumped together. As a result spores did not provide uniform coverage over space and time. It is, therefore, necessary to develop a formulation that allows the spores to spread over the water surface. Apart from formulation appropriate delivery methods are also necessary to avoid exposing non-target organisms to fungus.

PMCID: PMC2817704 PMID: 20085659 [PubMed - indexed for MEDLINE]

823. Genet Mol Res. 2010 Jan 12;9(1):48-57.

DNA repair mutant pso2 of Saccharomyces cerevisiae is sensitive to intracellular acetaldehyde accumulated by disulfiram-mediated inhibition of acetaldehyde dehydrogenase.

Brendel M, Marisco G, Ganda I, Wolter R, Pungartnik C.

Pós-Graduação em Genética e Biologia Molecular, Universidade Estadual de Santa Cruz, Ilhéus, BA, Brasil.

Blocking aldehyde dehydrogenase with the drug disulfiram leads to an accumulation of intracellular acetaldehyde, which negatively affects the viability of the yeast Saccharomyces cerevisiae. Mutants of the yeast gene PSO2, which encodes a protein specific for repair of DNA interstrand cross-links, showed higher sensitivity to disulfiram compared to the wild type. This leads us to suggest that accumulated acetaldehyde induces DNA lesions, including highly deleterious interstrand cross-links. Acetaldehyde induced the expression of a PSO2-lacZ reporter construct that is specifically inducible by bi- or poly-functional mutagens, e.g., nitrogen mustard and photo-activated psoralens. Chronic exposure of yeast cells to disulfiram and acute exposure to acetaldehyde induced forward mutagenesis in the yeast CAN1 gene. Disulfiram-induced mutability of a pso2Delta mutant was significantly increased over that of the isogenic wild type; however, this was not found for acetaldehyde-induced mutagenesis. Spontaneous mutability at the CAN1 locus was elevated in pso2Delta, suggesting that growth of glucose-repressed yeast produces DNA lesions that, in the absence of Pso2p-mediated crosslink repair, are partially removed by an error-prone DNA repair mechanism. The use of disulfiram in the control of human alcohol abuse increases cellular acetaldehyde pools, which, based on our observations, enhances the risk of mutagenesis and of other genetic damage.

PMID: 20082270 [PubMed - indexed for MEDLINE]

824. Proc Natl Acad Sci U S A. 2010 Jan 12;107(2):616-21. Epub 2009 Dec 22.

Engineering the cell wall by reducing de-methyl-esterified homogalacturonan improves saccharification of plant tissues for bioconversion.

Lionetti V, Francocci F, Ferrari S, Volpi C, Bellincampi D, Galletti R, D'Ovidio R, De Lorenzo G, Cervone F.

Dipartimento di Biologia Vegetale, Istituto Pasteur Fondazione Cenci Bolognetti, Sapienza Università di Roma, Piazzale Aldo Moro 5, 00185 Rome, Italy.

Plant cell walls represent an abundant, renewable source of biofuel and other useful products. The major bottleneck for the industrial scale-up of their conversion to simple sugars (saccharification), to be subsequently converted by microorganisms into ethanol or other products, is their recalcitrance to enzymatic saccharification. We investigated whether the structure of pectin that embeds the cellulose-hemicellulose network affects the exposure of cellulose to enzymes and consequently the process of saccharification. Reduction of de-methyl-esterified homogalacturonan (HGA) in Arabidopsis plants through the expression of a fungal polygalacturonase (PG) or an inhibitor of pectin methylesterase (PMEI) increased the efficiency of enzymatic saccharification. The improved enzymatic saccharification efficiency observed in transformed plants could also reduce the need for acid pretreatment. Similar results were obtained in PG-expressing tobacco plants and in PMEI-expressing wheat plants, indicating that reduction of de-methyl-esterified HGA may be used in crop species to facilitate the process of biomass saccharification.

PMCID: PMC2818903 PMID: 20080727 [PubMed - indexed for MEDLINE]

825. BMC Microbiol. 2010 Jan 15;10:12.

Identification of possible targets of the Aspergillus fumigatus CRZ1 homologue, CrzA.

Soriani FM, Malavazi I, Savoldi M, Espeso E, Dinamarco TM, Bernardes LA, Ferreira ME, Goldman MH, Goldman GH.

Centro de Ciência e Tecnologia do Bioetanol and Faculdade de Ciências Farmacêuticas de Ribeirão Preto Universidade de São Paulo, São Paulo, Ribeirão Preto 14040-903, Brazil.

BACKGROUND: Calcineurin, a serine/threonine-specific protein phosphatase, plays an important role in the control of cell morphology and virulence in fungi. Calcineurin regulates localization and activity of a transcription factor called CRZ1. Recently, we characterize Aspergillus fumigatus CRZ1 homologue, AfCrzA. Here, we investigate which pathways are influenced by A. fumigatus AfCrzA during a short pulse of calcium by comparatively determining the transcriptional profile of A. fumigatus wild type and DeltaAfcrzA mutant strains.
RESULTS: We were able to observe 3,622 genes modulated in at least one timepoint in the mutant when compared to the wild type strain (3,211 and 411 at 10 and 30 minutes, respectively). Decreased mRNA abundance in the DeltacrzA was seen for genes encoding calcium transporters, transcription factors and genes that could be directly or indirectly involved in calcium metabolism. Increased mRNA accumulation was observed for some genes encoding proteins involved in stress response. AfCrzA overexpression in A. fumigatus increases the expression of several of these genes. The deleted strain of one of these genes, AfRcnA, belonging to a class of endogenous calcineurin regulators, calcipressins, had more calcineurin activity after exposure to calcium and was less sensitive to menadione 30 microM, hydrogen peroxide 2.5 mM, EGTA 25 mM, and MnCl2 25 mM. We constructed deletion, overexpression, and GFP fusion protein for the closely related A. nidulans AnRcnA. GFP::RcnA was mostly detected along the germling, did not accumulate in the nuclei and its location is not affected by the cellular response to calcium chloride.
CONCLUSION: We have performed a transcriptional profiling analysis of the A. fumigatus DeltaAfcrzA mutant strain exposed to calcium stress. This provided an excellent opportunity to identify genes and pathways that are under the influence of AfCrzA. AfRcnA, one of these selected genes, encodes a modulator of calcineurin activity. Concomitantly with A. fumigatus AfrcnA molecular analysis, we decided to exploit the conserved features of A. nidulans calcineurin system and investigated the A. nidulans AnRcnA homologue. A. nidulans AnRcnA mutation is suppressing CnaA mutation and it is responsible for modulating the calcineurin activity and mRNA accumulation of genes encoding calcium transporters.

PMCID: PMC2818617 PMID: 20078882 [PubMed - indexed for MEDLINE]

826. Masui. 2010 Jan;59(1):31-5.

[Management of needlestick injuries for healthcare workers in hospitals].

[Article in Japanese]

Koh A.

Japanese Nursing Association, Tokyo.

The needlestick injury (NSI) has been one of the major issues in the protection of the healthcare workers from the occupationally related blood borne pathogen infection, and vigorous preventive action has been practiced worldwide. In the United Sates, its preventive practices have been proposed nationwide by Centers for Disease Control and Prevention (CDC) providing the guidelines since mid-1980s when HBV and especially HIV infections were reported amomg healthcare workers. The hospitals were required to prepare the hard system to discard the blood contaminated sharp instruments and needles and to keep the official records of related injuries. It has been well recognized in Japan that we are facing a large numbers of NSIs, and the occupational infection from bloodborne pathogens is one of the serious problems in medical care.

PMID: 20077768 [PubMed - indexed for MEDLINE]

827. J Toxicol Environ Health A. 2009;72(21-22):1475-83.

Inhibitory effect of proanthocyanidin on ultraviolet B irradiation-induced melanogenesis.

Cho HS, Kwak DH, Choi IS, Park HK, Kang SJ, Yoo HS, Lee MS, Oh KW, Hong JT.

College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, Republic of Korea.

Repetitive exposure of the skin to ultraviolet (UV) radiation induces various adverse effects, including skin thickening, wrinkle formation, inflammation, and pigmentation. Various natural and synthetic compounds were studied to determine whether they might prevent UV induction of these adverse effects. In particular, naturally occurring antioxidants were used for regulating skin damage induced by UV radiation since several antioxidants were found to inhibit photoaging through prevention of collagen synthesis via inhibition of matrix metalloproteinases (MMP) and/or decrease of melanin synthesis. The L values in pigmented skin were lower at 4 wk (52.97 +/- 2.09) than at the start of this study (0 wk, 62.89 +/- 0.56) in the control. In the proanthocyanidin mixture group, the L value was increased (56.83 +/- 1.71) similar to the control (52.97 +/- 2.09). Proanthocyanidin also suppressed the expression levels of tyrosinase by 20-40%, and blocked the expression of MITF, TRP-1, and TRP-2, which are factors implicated in the control of melanogenesis. Taken together, these data indicate that proanthocyanidin may be useful to attenuate UVB-induced melanogenesis.

PMID: 20077221 [PubMed - indexed for MEDLINE]

828. J Toxicol Environ Health A. 2009;72(20):1242-51.

Purification and comparative neurotoxicity of the trichothecenes satratoxin G and roridin L2 from Stachybotrys chartarum.

Islam Z, Shinozuka J, Harkema JR, Pestka JJ.

Department of Food Science and Human Nutrition, Michigan State University, East Lansing, Michigan 48824-1224, USA.

Satratoxin G (SG), a macrocyclic trichothecene produced by Stachybotrys chartarum, induces apoptosis in cultured neuronal cells as well as nasal olfactory sensory neurons (OSN) in the nose and brain of mice exposed intranasally to this toxin. The purposes of this study were to (1) develop a facile method for production and purification of both SG and its putative biosynthetic precursor, roridin L2 (RL2), from S. chartarum cultures and (2) compare their relative neurotoxicity in vitro and in vivo. Stachybotrys chartarum 29-58-17 was cultured in Fernbach flasks on rice (5 x 10(5) spores/250 g rice) for 4 to 6 wk. Following extraction with acetonitrile, the extract was dried, dissolved in dichloromethane, and subjected to Michel-Miller silica-gel chromatography using a stepwise acetonitrile-dichloromethane gradient with SG and RL2 eluting in the 30 and 40% acetonitrile fractions, respectively. Purification of the two compounds was completed by C18 semipreparative reverse-phase liquid chromatography using an acetonitrile-water gradient, and purity was confirmed by electrospray ionization/collision-induced dissociation (ESI-CID) tandem mass spectroscopy. Although viability significantly decreased in PC-12 neuronal cells treated with 10 to 25 ng/ml of SG, RL2 at concentrations up to 1000 ng/ml was not toxic. Flow cytometry and agarose DNA fragmentation assays revealed that SG at 10 to 25 ng/ml induced apoptotic death in the PC-12 cells, while RL2 at concentrations up to 1000 ng/ml was without effect. In a similar fashion, intranasal exposure of mice (female B6C3F1) to SG at 100 microg/kg body weight (bw) induced marked OSN apoptosis and atrophy of the olfactory epithelium, whereas RL2 at the equivalent dose did not exhibit toxicity. Taken together, an optimized protocol for production and isolation of trichothecenes from S. chartarum cultures is described and further demonstrates that while the macrocyclic SG was neurotoxic in vitro and in vivo, its biosynthetic precursor, RL2, was nontoxic.

PMCID: PMC2808125 PMID: 20077192 [PubMed - indexed for MEDLINE]

829. J Appl Microbiol. 2010 Aug;109(2):408-14. Epub 2010 Jan 11.

Use of the Weibull model to describe inactivation of dry-harvested conidia of different Penicillium species by ethanol vapours.

Dao T, Dejardin J, Bensoussan M, Dantigny P.

Laboratoire de Génie des Procédés Microbiologiques et Alimentaires, Université de Bourgogne, ENS.BANA, Dijon, France.

AIMS: This study aimed at modelling the effect of ethanol vapours, in the range 0.7-7.5 kPa, on the inactivation of dry-harvested conidia of Penicillium chrysogenum, Penicillium digitatum and Penicillium italicum. METHODS AND RESULTS: Survival curves were modelled by a Weibull model: log (N/N(0)) = -1/2.303 (t/alpha)(beta). The shape parameter beta was different from one in all cases, indicating that the classical first-order kinetics approach is the exception rather than the rule. Survival curves exhibited upward concavity (beta < 1) with the notable exception of P. chrysogenum at ethanol vapour pressures 0.7 and 1.5 kPa. The scale parameter alpha (h) varied greatly depending on the ethanol vapour pressure and on the species.
CONCLUSIONS: For safety reasons, it is recommended not to exceed an ethanol vapour pressure of 3.3 kPa. At 2.8 kPa, more than 4 log(10) reductions in viable conidia were achieved for all the species after 24-h exposure. SIGNIFICANCE AND IMPACT OF THE STUDY: Ethanol has GRAS status in the USA and represents an interesting alternative to fungicides. The effectiveness of ethanol vapours to inactivate dry-harvested conidia of some Penicillium was demonstrated in this study.

PMID: 20070448 [PubMed - indexed for MEDLINE]

830. Annu Rev Public Health. 2010 Apr 21;31:165-78 1 p following 178.

Mold exposure and health effects following hurricanes Katrina and Rita.

Barbeau DN, Grimsley LF, White LE, El-Dahr JM, Lichtveld M.

Department of Environmental Health Sciences, Tulane University School of Public Health, New Orleans, Louisiana 70112, USA.

The extensive flooding in the aftermath of Hurricanes Katrina and Rita created conditions ideal for indoor mold growth, raising concerns about the possible adverse health effects associated with indoor mold exposure. Studies evaluating the levels of indoor and outdoor molds in the months following the hurricanes found high levels of mold growth. Homes with greater flood damage, especially those with >3 feet of indoor flooding, demonstrated higher levels of mold growth compared with homes with little or no flooding. Water intrusion due to roof damage was also associated with mold growth. However, no increase in the occurrence of adverse health outcomes has been observed in published reports to date. This article considers reasons why studies of mold exposure after the hurricane do not show a greater health impact.

PMID: 20070193 [PubMed - indexed for MEDLINE]

831. J Econ Entomol. 2009 Dec;102(6):2041-7.

Pupal mortality and adult emergence of western cherry fruit fly (Diptera: Tephritidae) exposed to the fungus Muscodor albus (Xylariales: Xylariaceae).

Yee WL, Lacey LA, Bishop BJ.

USDA-ARS, Yakima Agricultural Research Laboratory, Wapato, WA 98951, USA. wee.yee@ars.usda.gov

Western cherry fruit fly, Rhagoletis indifferens Curran (Diptera: Tephritidae), is a major pest of sweet cherry, Prunus avium (L.) L. (Rosales: Rosaceae), that is conventionally controlled using insecticides. One alternative to the use of insecticides alone for fly control could be fumigation of the fly's overwintering habitat using the fungus Muscodor albus Worapong, Strobel & Hess (Xylariales: Xylariaceae) in conjunction with reduced insecticide use. The fungus produces a mixture of volatile organic compounds (VOCs) that are biocidal for a variety of organisms. In this study, the main objectives were to determine the effects of M. albus VOCs on mortality of R. indifferens pupae and on adult emergence under laboratory conditions. In fumigation chamber experiments, a 14-d exposure of pupae in soil to VOCs resulted in 61.9% control, and exposure to VOCs for 7, 10, and 14 d reduced fly emergence by 44.2, 70.0, and 86.3%, respectively, relative to controls. In an experiment using plastic covers to retain VOCs in treated soil, a concentration of 1% M. albus formulation (fungus + rye grain) did not affect pupal mortality and fly emergence, but a concentration of 5% M. albus formulation resulted in 27.4% control and reduced fly emergence by 30.1% relative to the control. Larvae of R. indifferens that were dropped onto soil with 1% M. albus formulation were not affected by the fungus. Results indicate that prolonged exposure and high concentrations of M. albus VOCs can cause significant mortality of R. indifferens pupae in soil and delay adult emergence.

PMID: 20069829 [PubMed - indexed for MEDLINE]

832. Cien Saude Colet. 2009 Nov-Dec;14(6):2135-41.

[Bio-security with emphasis in biological polluting agents in health workers].

[Article in Spanish]

Ardila AM, Muñoz AI.

Departamento de Salud de Colectivos, Facultad de Enfermería, Universidad Nacional de Colombia. anamaria_ardila13@hotmail.com

Health workers of the emergency service are frequently exposed to different dangers, among them the contact with biological polluting agents. This is a study of descriptive character, with the objective to characterize workers on social demographic aspects, and also to verify the level of application of the bio-security norms at the emergency services of a health institution in the city of Bogota, Colombia. 68,3% of the workers are with a contract in the modality of benefit of services, the 31,7%, are in the modality of indefinite term. 44,6% of the personnel have not received the qualification on bio-security, and 42,4% do not apply the suitable technique of washing hands. In relation to the aspect of the return to use needles, 31% was doing this practice. All workers have the complete kit of Hepatitis B vaccine, but the same percentage does not have measurement of Hepatitis B antibodies. It is fundamental the provision of elements of personal protection and set of elements and containers that contribute to the bio-security. Pedagogical activities can be used to sensitize and create critical awareness to all personnel who work at emergency, about dangers and consequences that are exposed in their workplace. Measurements of titles of Hepatitis B are necessary to verify the immunological state of the workers.

PMID: 20069181 [PubMed - indexed for MEDLINE]

833. Cryobiology. 2010 Jun;60(3):245-61. Epub 2010 Jan 11.

Comparative analysis of transcriptional responses to the cryoprotectants, dimethyl sulfoxide and trehalose, which confer tolerance to freeze-thaw stress in Saccharomyces cerevisiae.

Momose Y, Matsumoto R, Maruyama A, Yamaoka M.

International Patent Organism Depositary, National Institute of Advanced Industrial Science and Technology, Ibaraki 305-8566, Japan. y.momose@aist.go.jp

We have used microarray analysis to monitor the gene expression profile of Saccharomyces cerevisiae BY4743 in the presence of the cryoprotectants, dimethyl sulfoxide (Me(2)SO) and trehalose. Analysis of these profiles suggests that both cryoprotectants increased the expression of genes involved in protein synthesis, ribosomal biogenesis, fatty acid biosynthesis, ergosterol biosynthesis, cell wall biosynthesis, and cellular accumulation of low molecular compounds such as glycerol, arginine and proline. Cryoprotectant treatment reduced the expression of genes involved in the beta-oxidation of fatty acids. In addition, Me(2)SO increased the expression of genes involved in protein refolding and trehalose increased the expression of genes involved in spore formation. This study supported that exposure to cryoprotectants prior to freezing not only reduce the freeze-thaw damage but also provide various process to the recovery from freeze-thaw damage.

PMID: 20067782 [PubMed - indexed for MEDLINE]

834. PLoS Genet. 2010 Jan;6(1):e1000807. Epub 2010 Jan 8.

Activation of mutant enzyme function in vivo by proteasome inhibitors and treatments that induce Hsp70.

Singh LR, Gupta S, Honig NH, Kraus JP, Kruger WD.

Cancer Genetics and Signaling Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania, United States of America.

Missense mutant proteins, such as those produced in individuals with genetic diseases, are often misfolded and subject to processing by intracellular quality control systems. Previously, we have shown using a yeast system that enzymatic function could be restored to I278T cystathionine beta-synthase (CBS), a cause of homocystinuria, by treatments that affect the intracellular chaperone environment. Here, we extend these studies and show that it is possible to restore significant levels of enzyme activity to 17 of 18 (94%) disease causing missense mutations in human cystathionine beta-synthase (CBS) expressed in Saccharomyces cerevisiae by exposure to ethanol, proteasome inhibitors, or deletion of the Hsp26 small heat shock protein. All three of these treatments induce Hsp70, which is necessary but not sufficient for rescue. In addition to CBS, these same treatments can rescue disease-causing mutations in human p53 and the methylene tetrahydrofolate reductase gene. These findings do not appear restricted to S. cerevisiae, as proteasome inhibitors can restore significant CBS enzymatic activity to CBS alleles expressed in fibroblasts derived from homocystinuric patients and in a mouse model for homocystinuria that expresses human I278T CBS. These findings suggest that proteasome inhibitors and other Hsp70 inducing agents may be useful in the treatment of a variety of genetic diseases caused by missense mutations.

PMCID: PMC2795852 PMID: 20066033 [PubMed - indexed for MEDLINE]

835. Biochim Biophys Acta. 2010 Apr;1800(4):439-47. Epub 2010 Jan 11.

Plagiochin E, an antifungal active macrocyclic bis(bibenzyl), induced apoptosis in Candida albicans through a metacaspase-dependent apoptotic pathway.

Wu XZ, Chang WQ, Cheng AX, Sun LM, Lou HX.

Department of Natural Products Chemistry, School of Pharmaceutical Sciences, Shandong University, No. 44 West Wenhua Road, Jinan 250012, PR China.

BACKGROUND: Plagiochin E (PLE) is an antifungal active macrocyclic bis(bibenzyl) isolated from liverwort Marchantia polymorpha L. To elucidate the mechanism of action, previous studies revealed that the antifungal effect of PLE was associated with the accumulation of ROS, an important regulator of apoptosis in Candida albicans. The present study was designed to find whether PLE caused apoptosis in C. albicans.
METHODS: We assayed the cell cycle by flow cytometry using PI staining, observed the ultrastructure by transmission electron microscopy, studied the nuclear fragmentation by DAPI staining, and investigated the exposure of phosphatidylserine at the outer layer of the cytoplasmic membrane by the FITC-annexin V staining. The effect of PLE on expression of CDC28, CLB2, and CLB4 was determined by RT-PCR. Besides, the activity of metacaspase was detected by FITC-VAD-FMK staining, and the release of cytochrome c from mitochondria was also determined. Furthermore, the effect of antioxidant L-cysteine on PLE-induced apoptosis in C. albicans was also investigated.
RESULTS: Cells treated with PLE showed typical markers of apoptosis: G(2)/M cell cycle arrest, chromatin condensation, nuclear fragmentation, and phosphatidylserine exposure. The expression of CDC28, CLB2, and CLB4 was down-regulated by PLE, which may contribute to PLE-induced G(2)/M cell cycle arrest. Besides, PLE promoted the cytochrome c release and activated the metacaspase, which resulted in the yeast apoptosis. The addition of L-cysteine prevented PLE-induced nuclear fragmentation, phosphatidylserine exposure, and metacaspase activation, indicating the ROS was an important mediator of PLE-induced apoptosis.
CONCLUSIONS: PLE induced apoptosis in C. albicans through a metacaspase-dependent apoptotic pathway.
GENERAL SIGNIFICANCE: In this study, we reported for the first time that PLE induced apoptosis in C. albicans through activating the metacaspase. These results would conduce to elucidate its underlying antifungal mechanism.

PMID: 20064588 [PubMed - indexed for MEDLINE]

836. Med Mycol. 2010 Mar;48(2):217-28.

Murine models of airway fungal exposure and allergic sensitization.

Templeton SP, Buskirk AD, Green BJ, Beezhold DH, Schmechel D.

Inhalation of common indoor filamentous fungi has been associated with the induction or exacerbation of allergic respiratory disease. The understanding of fungal inhalation and allergic sensitization has significantly advanced with the use of small animal models, especially mouse models. Numerous studies have employed different animal exposure and sensitization techniques, each with inherent advantages and disadvantages that are addressed in this review. In addition, most studies involve exposure of animals to fungal spores or spore extracts while neglecting the influence of hyphal or subcellular fragment exposures. Recent literature examining the potential for hyphae and fungal fragments to induce or exacerbate allergy is discussed. Innate immune recognition of fungal elements and their contribution to lung allergic inflammation in animal models are also reviewed. Though physical properties of fungi play an important role following exposure, host immune development is also critical in airway inflammation and allergy. We discuss the importance of environmental factors that influence early immune development and subsequent susceptibility to allergy. Murine studies that examine the role of intestinal microflora and prenatal or early life environmental factors that promote allergic sensitization are also evaluated. Future studies will require animal models that accurately reflect natural fungal exposures and identify environmental factors that influence immune development and thus promote respiratory fungal allergy and disease.

PMID: 20055736 [PubMed - indexed for MEDLINE]

837. Phytopathology. 2010 Feb;100(2):150-9.

Variation in competitive ability among isolates of Aspergillus flavus from different vegetative compatibility groups during maize infection.

Mehl HL, Cotty PJ.

ABSTRACT Aspergillus flavus, the primary causal agent of aflatoxin contamination, includes many genetically diverse vegetative compatibility groups (VCGs). Competitive ability during infection of living maize kernels was quantified for isolates from 38 VCGs. Kernels were inoculated with both a common VCG, CG136, and another VCG; after 7 days (31 degrees C), conidia were washed from kernels, and aflatoxins and DNA were extracted from kernels and conidia separately. CG136-specific single-nucleotide polymorphisms were quantified by pyrosequencing; VCGs co-inoculated with CG136 produced 46 to 85 and 51 to 84% of A. flavus DNA from kernels and conidia, respectively. Co-inoculation with atoxigenic isolates reduced aflatoxin up to 90% and, in some cases, more than predicted by competitive exclusion alone. Conidia contained up to 42 ppm aflatoxin B(1), indicating airborne conidia as potentially important sources of environmental exposure. Aflatoxin-producing potential and sporulation were negatively correlated. For some VCGs, sporulation during co-infection was greater than that predicted by kernel infection, suggesting that some VCGs increase dispersal while sacrificing competitive ability during host tissue colonization. The results indicate both life strategy and adaptive differences among A. flavus isolates and provide a basis for selection of biocontrol strains with improved competitive ability, sporulation, and aflatoxin reduction on target hosts.

PMID: 20055649 [PubMed - indexed for MEDLINE]

838. J Mol Biol. 2010 Mar 12;396(5):1197-210. Epub 2010 Jan 4.

Glycine-rich loop of mitochondrial processing peptidase alpha-subunit is responsible for substrate recognition by a mechanism analogous to mitochondrial receptor Tom20.

Dvoráková-Holá K, Matusková A, Kubala M, Otyepka M, Kucera T, Vecer J, Herman P, Parkhomenko N, Kutejova E, Janata J.

Institute of Microbiology, Academy of Sciences of the Czech Republic, Vídenská 1083, 142 20 Prague 4, Czech Republic.

Tryptophan fluorescence measurements were used to characterize the local dynamics of the highly conserved glycine-rich loop (GRL) of the mitochondrial processing peptidase (MPP) alpha-subunit in the presence of the substrate precursor. Reporter tryptophan residue was introduced into the GRL of the yeast alpha-MPP (Y299W) or at a proximal site (Y303W). Time-resolved and steady-state fluorescence spectroscopy demonstrated that for Trp299, the primary contact with the yeast malate dehydrogenase precursor evokes a change of the local GRL mobility. Moreover, time-resolved measurements showed that a functionless alpha-MPP with a single-residue deletion in the loop (Y303W/DeltaG292) is defective particularly in the primary contact with substrate. Thus, the GRL was proved to be part of a contact site of the enzyme specifically recognizing the substrate. Regarding the surface exposure and presence of the hydrophobic patches within the GRL, we proposed a functional analogy between the presequence recognition by the hydrophobic binding groove of the Tom20 mitochondrial import receptor and the GRL of the alpha-MPP. A molecular dynamics (MD) simulation of the MPP-substrate peptide complex model was employed to test this hypothesis. The initial positioning and conformation of the substrate peptide in the model fitting were chosen based on the analogy of its interaction with the Tom20 binding groove. MD simulation confirmed the stability of the proposed interaction and showed also a decrease in GRL flexibility in the presence of substrate, in agreement with fluorescence measurements. Moreover, conserved substrate hydrophobic residues in positions +1 and -4 to the cleavage site remain in close contact with the side chains of the GRL during the entire production part of MD simulation as stabilizing points of the hydrophobic interaction. We conclude that the GRL of the MPP alpha-subunit is the crucial evolutional outcome of the presequence recognition by MPP and represents a functional parallel with Tom20 import receptor.

PMID: 20053354 [PubMed - indexed for MEDLINE]

839. Opt Express. 2009 Dec 7;17(25):22735-46. doi: 10.1364/OE.17.022735.

In vivo real-time recording of UV-induced changes in the autofluorescence of a melanin-containing fungus using a micro-spectrofluorimeter and a low-cost webcam.

Raimondi V, Agati G, Cecchi G, Gomoiu I, Lognoli D, Palombi L.

Nello Carrara Applied Physics Institute - National Research Council, Via Madonna del Piano 10, I- 50019 Sesto Fiorentino, Firenze, Italy. v.raimondi@ifac.cnr.it

An optical epifluorescence microscope, coupled to a CCD camera, a standard webcam and a microspectrofluorimeter, are used to record in vivo real-time changes in the autofluorescence of spores and hyphae in Aspergillus niger, a fungus containing melanin, while exposed to UV irradiation. The results point out major changes in both signal intensity and the spectral shape of the autofluorescence signal after only few minutes of exposure, and can contribute to the interpretation of data obtained with other fluorescence techniques, including those, such as GPF labeling, in which endogenous fluorophores constitute a major disturbance.

PMID: 20052199 [PubMed - indexed for MEDLINE]

840. Ned Tijdschr Geneeskd. 2009;153:A765.

[Azole-resistant invasive aspergillosis].

[Article in Dutch]

van der Linden JW, Warris A, van der Meer JW, Bresters D, Melchers WJ, Verweij PE.

Universitair Medisch Centrum St. Radboud, Afd. Medische Microbiologie, Nijmegen, The Netherlands. j.vanderlinden@mmb.umcn.nl

Invasive aspergillosis caused by medical triazole-resistant Aspergillus fumigatus is described in two patients. A 31-year-old male with chronic granulomatous disease developed pulmonary aspergillosis despite itraconazole prophylaxis. A. fumigatus was cultured from the lung and was found to be azole-resistant. The patient was successfully treated with caspofungin. The second patient was a 13-year-old boy with acute lymphoid leukaemia. He developed pulmonary aspergillosis that failed to respond to voriconazole therapy. The infection spread to the brain and an azole-resistant isolate was cultured from a lung biopsy. Despite a switch to liposomal amphotericin B in combination with caspofungin, the infection progressed and the patient died. Azole-resistance has emerged in A. fumigatus and may develop through the treatment of patients. However, there is evidence that in the Netherlands, resistance might be emerging through fungal exposure to azole fungicides. Azole resistance further complicates the management of invasive aspergillosis and should be considered as cause for treatment failure.

PMID: 20051169 [PubMed - indexed for MEDLINE]

841. Ann Agric Environ Med. 2009 Dec;16(2):183-96.

Exposure to the airborne mould Botrytis and its health effects.

Jurgensen CW, Madsen A.

The National Research Centre for the Working Environment, Lerso Parkalle 105, DK-2100 Copenhagen O, Denmark.

Most investigations into the correlation between exposure to fungi and detrimental health effects focus on the 2-4 most prevalent genera in ambient air, both outdoors and indoors. Yet over 80 genera of fungi have been shown to have allergenic potential. Also, there is no agreement about threshold values for exposure to fungi. One of the fungal genera expected to be less prevalent in ambient air and known to cause allergy is Botrytis. In this review, we investigate the airborne exposure level and health effect of Botrytis, both at general exposure and in occupational settings. The surveyed papers show that Botrytis is found globally with different spore seasons depending on the region investigated. The levels of Botrytis in the percentage of all fungi have a calculated median of around 1.1% in the different environments, confirming that it is among the less prevalent fungi. Furthermore, a substantial proportion of patients and workers are allergic to Botrytis cinerea, and when B. cinerea was included in extended test panels additional allergic patients were found. Thus, B. cinerea is as important as the more prevalent mould genera Cladosporium and Alternaria and we suggest that it should be included in standard allergic tests panels.

PMID: 20047250 [PubMed - indexed for MEDLINE]

842. Toxicol Appl Pharmacol. 2010 Apr 15;244(2):144-55. Epub 2010 Jan 4.

Biomarkers of acute respiratory allergen exposure: screening for sensitization potential.

Pucheu-Haston CM, Copeland LB, Vallanat B, Boykin E, Ward MD.

Curriculum in Toxicology, University of North Carolina-Chapel Hill, CB# 7270, Chapel Hill, NC 27599-7270, USA. Pucheu-Haston.Cherie@epa.gov

Effective hazard screening will require the development of high-throughput or in vitro assays for the identification of potential sensitizers. The goal of this preliminary study was to identify potential biomarkers that differentiate the response to allergens vs non-allergens following an acute exposure in naïve individuals. Female BALB/c mice received a single intratracheal aspiration exposure to Metarhizium anisopliae crude antigen (MACA) or bovine serum albumin (BSA) in Hank's Balanced Salt Solution (HBSS) or HBSS alone. Mice were terminated after 1, 3, 6, 12, 18 and 24 h. Bronchoalveolar lavage fluid (BALF) was evaluated to determine total and differential cellularity, total protein concentration and LDH activity. RNA was isolated from lung tissue for microarray analysis and qRT-PCR. MACA administration induced a rapid increase in BALF neutrophils, lymphocytes, eosinophils and total protein compared to BSA or HBSS. Microarray analysis demonstrated differential expression of genes involved in cytokine production, signaling, inflammatory cell recruitment, adhesion and activation in 3 and 12 h MACA-treated samples compared to BSA or HBSS. Further analyses allowed identification of approximately 100 candidate biomarker genes. Eleven genes were selected for further assessment by qRT-PCR. Of these, 6 demonstrated persistently increased expression (Ccl17, Ccl22, Ccl7, Cxcl10, Cxcl2, Saa1), while C3ar1 increased from 6-24 h. In conclusion, a single respiratory exposure of mice to an allergenic mold extract induces an inflammatory response which is distinct in phenotype and gene transcription from the response to a control protein. Further validation of these biomarkers with additional allergens and irritants is needed. These biomarkers may facilitate improvements in screening methods.

PMID: 20045013 [PubMed - indexed for MEDLINE]

843. Pan Afr Med J. 2010;7:14. Epub 2010 Nov 19.

Natural occurrence of aflatoxin residues in fresh and sun-dried meat in Nigeria.

Olufunmilayo GO, Oyefolu AB.

Department of Biology, The Polytechnic, Ibadan, Nigeria.

INTRODUCTION: In recent times, food safety and security have generally remained basic human needs, therefore because of the largely unregulated nature of the Nigerian markets, coupled with the poor housing and feeding conditions to which animals are subjected in the abattoirs, a survey for assessing potential mycotoxin exposure through meat consumption was undertaken.
METHODS: Eighty Samples of meat bought randomly from 5 major markets distributed in 5 local government areas of Oyo state , Nigeria were analysed for contaminating mycoflora using the plate count and micromorphological methods, while aflatoxin detection and quantification was by Thin Layer Chromatography (TLC).
RESULTS: Mycological analysis of samples revealed a higher contamination level in the sun-dried samples. Eighteen fungi species belonging to 8 genera, namely, Aspergillus, Penicilliu, Alternaria, Cladosporium, Fusarium, Neurospora, Rhizopus and yeast were identified. The predominant genus Aspergillus yielded 7 species while the potential toxicogenic fungi represented 38% of the isolated mycoflora. The genera requiring higher water activity for growth ( Alternaria, Fusarium and yeast) were not obtained from the dried meat. Aflatoxins B1, B2, G1 and G2 were detected in all the samples analysed. The fresh samples with the exception of the total aflatoxin G (AFG) in kidney gave the highest mean concentrations for all aflatoxins, also an exceptionally high aflatoxin content was found in all the kidney samples.
CONCLUSION: Aflatoxin detection in meat should be addressed urgently to avert the possible adverse health effects like aflatoxicosis, exacerbated malnutrition, suppression of growth and immune functions on consumers. Also the animal health inspectors should pay more attention to the feeding conditions of the animals on farm and the abattoirs.

PMCID: PMC3172626 PMID: 21918701 [PubMed - in process]

844. Int J Antimicrob Agents. 2010 Mar;35(3):211-8. Epub 2009 Dec 29.

Characterisation of breakthrough invasive mycoses in echinocandin recipients: an evidence-based review.

Sun HY, Singh N.

VA Pittsburgh Healthcare System, Pittsburgh, PA 15240, USA.

The echinocandins have emerged as important antifungal agents in the current era. Despite their potent antifungal activity, breakthrough invasive mycoses occur in echinocandin recipients, however their precise incidence and causative pathogens are not well delineated. This review shows that breakthrough mycoses occur in 2.4% of patients receiving echinocandins as prophylaxis and are predominantly due to non-albicans Candida spp. and less frequently to invasive aspergillosis. Candida isolates demonstrating reduced susceptibility occurred following prolonged exposure to the echinocandins, primarily in severely immunocompromised patients, and manifested as recurrent episodes of candidaemia or invasive candidiasis.

Published by Elsevier B.V.

PMID: 20036518 [PubMed - indexed for MEDLINE]

845. Malar J. 2009 Dec 23;8:309.

Infection of the malaria mosquito, Anopheles gambiae, with two species of entomopathogenic fungi: effects of concentration, co-formulation, exposure time and persistence.

Mnyone LL, Kirby MJ, Lwetoijera DW, Mpingwa MW, Knols BG, Takken W, Russell TL.

Biomedical and Environmental Group, Ifakara Health Institute, PO Box 53, Off Mlabani Passage, Ifakara, Tanzania. llaurent@ihi.or.tz

BACKGROUND: Entomopathogenic fungi Metarhizium anisopliae and Beauveria bassiana isolates have been shown to infect and reduce the survival of mosquito vectors.
METHODS: Here four different bioassays were conducted to study the effect of conidia concentration, co-formulation, exposure time and persistence of the isolates M. anisopliae ICIPE-30 and B. bassiana I93-925 on infection and survival rates of female Anopheles gambiae sensu stricto. Test concentrations and exposure times ranged between 1 x 10(7) - 4 x 10(10) conidia m(-2) and 15 min - 6 h. In co-formulations, 2 x 10(10) conidia m(-2) of both fungus isolates were mixed at ratios of 4:1, 2:1, 1:1,1:0, 0:1, 1:2 and 1:4. To determine persistence, mosquitoes were exposed to surfaces treated 1, 14 or 28 d previously, with conidia concentrations of 2 x 10(9), 2 x 10(10) or 4 x 10(10).
RESULTS: Mosquito survival varied with conidia concentration; 2 x 10(10) conidia m(-2) was the concentration above which no further reductions in survival were detectable for both isolates of fungus. The survival of mosquitoes exposed to single and co-formulated treatments was similar and no synergistic or additive effects were observed. Mosquitoes were infected within 30 min and longer exposure times did not result in a more rapid killing effect. Fifteen min exposure still achieved considerable mortality rates (100% mortality by 14 d) of mosquitoes, but at lower speed than with 30 min exposure (100% mortality by 9 d). Conidia remained infective up to 28 d post-application but higher concentrations did not increase persistence.
CONCLUSION: Both fungus isolates are effective and persistent at low concentrations and short exposure times.

PMCID: PMC2808315 PMID: 20030834 [PubMed - indexed for MEDLINE]

846. BMC Genomics. 2009 Dec 22;10:624.

Potential impact of stress activated retrotransposons on genome evolution in a marine diatom.

Maumus F, Allen AE, Mhiri C, Hu H, Jabbari K, Vardi A, Grandbastien MA, Bowler C.

CNRS UMR8186, Biologie Moléculaire des Organismes Photosynthétiques, Ecole Normale Supérieure, 75230 Paris cedex05, France. maumus@biologie.ens.fr

BACKGROUND: Transposable elements (TEs) are mobile DNA sequences present in the genomes of most organisms. They have been extensively studied in animals, fungi, and plants, and have been shown to have important functions in genome dynamics and species evolution. Recent genomic data can now enlarge the identification and study of TEs to other branches of the eukaryotic tree of life. Diatoms, which belong to the heterokont group, are unicellular eukaryotic algae responsible for around 40% of marine primary productivity. The genomes of a centric diatom, Thalassiosira pseudonana, and a pennate diatom, Phaeodactylum tricornutum, that likely diverged around 90 Mya, have recently become available.
RESULTS: In the present work, we establish that LTR retrotransposons (LTR-RTs) are the most abundant TEs inhabiting these genomes, with a much higher presence in the P. tricornutum genome. We show that the LTR-RTs found in diatoms form two new phylogenetic lineages that appear to be diatom specific and are also found in environmental samples taken from different oceans. Comparative expression analysis in P. tricornutum cells cultured under 16 different conditions demonstrate high levels of transcriptional activity of LTR retrotransposons in response to nitrate limitation and upon exposure to diatom-derived reactive aldehydes, which are known to induce stress responses and cell death. Regulatory aspects of P. tricornutum retrotransposon transcription also include the occurrence of nitrate limitation sensitive cis-regulatory components within LTR elements and cytosine methylation dynamics. Differential insertion patterns in different P. tricornutum accessions isolated from around the world infer the role of LTR-RTs in generating intraspecific genetic variability.
CONCLUSION: Based on these findings we propose that LTR-RTs may have been important for promoting genome rearrangements in diatoms.

PMCID: PMC2806351 PMID: 20028555 [PubMed - indexed for MEDLINE]

847. Genetics. 2010 Mar;184(3):651-8. Epub 2009 Dec 21.

Regulation by blue light of the fluffy gene encoding a major regulator of conidiation in Neurospora crassa.

Olmedo M, Ruger-Herreros C, Corrochano LM.

Departamento de Genética, Facultad de Biología, Universidad de Sevilla, 41012 Sevilla, Spain.

The development of asexual spores, that is, the process of conidiation, in the fungus Neurospora crassa is increased by light. The fluffy (fl) gene, encoding a major regulator of conidiation, is activated by light. We describe here a detailed characterization of the regulation by blue light of fl in vegetative hyphae. This induction requires the white collar complex (WCC) while the FLD protein acts as a dark repressor of fl transcription. We show that the WCC directly regulates fl transcription in response to blue light after transiently binding the promoter. We propose that fl is repressed by FLD in vegetative mycelia and that the repression is lost after light exposure and WCC activation. The increase in fl mRNA in vegetative mycelia after light exposure, and the corresponding increase in the amount of the regulatory FL protein, should promote the activation of the conidiation pathway. The activation by light of fl provides a simple mechanism for the activation of conidiation by blue light in Neurospora that may be at work in other fungi.

PMCID: PMC2845335 PMID: 20026679 [PubMed - indexed for MEDLINE]

848. J Biol Chem. 2010 Feb 26;285(9):6739-49. Epub 2009 Dec 21.

Dynamic changes in the subcellular distribution of Gpd1p in response to cell stress.

Jung S, Marelli M, Rachubinski RA, Goodlett DR, Aitchison JD.

Institute for Systems Biology, Seattle, Washington 98103, USA.

Gpd1p is a cytosolic NAD(+)-dependent glycerol 3-phosphate dehydrogenase that also localizes to peroxisomes and plays an essential role in the cellular response to osmotic stress and a role in redox balance. Here, we show that Gpd1p is directed to peroxisomes by virtue of an N-terminal type 2 peroxisomal targeting signal (PTS2) in a Pex7p-dependent manner. Significantly, localization of Gpd1p to peroxisomes is dependent on the metabolic status of cells and the phosphorylation of aminoacyl residues adjacent to the targeting signal. Exposure of cells to osmotic stress induces changes in the subcellular distribution of Gpd1p to the cytosol and nucleus. This behavior is similar to Pnc1p, which is coordinately expressed with Gpd1p, and under conditions of cell stress changes its subcellular distribution from peroxisomes to the nucleus where it mediates chromatin silencing. Although peroxisomes are necessary for the beta-oxidation of fatty acids in yeast, the localization of Gpd1p to peroxisomes is not. Rather, shifts in the distribution of Gpd1p to different cellular compartments in response to changing cellular status suggests a role for Gpd1p in the spatial regulation of redox potential, a process critical to cell survival, especially under the complex stress conditions expected to occur in the wild.

PMCID: PMC2825468 PMID: 20026609 [PubMed - indexed for MEDLINE]

849. Appl Environ Microbiol. 2010 Feb;76(3):851-9. Epub 2009 Dec 18.

Metabolic impact of increased NADH availability in Saccharomyces cerevisiae.

Hou J, Scalcinati G, Oldiges M, Vemuri GN.

State Key Laboratory of Microbial Technology, Shandong University, Jinan 250100, People's Republic of China.

Engineering the level of metabolic cofactors to manipulate metabolic flux is emerging as an attractive strategy for bioprocess applications. We present the metabolic consequences of increasing NADH in the cytosol and the mitochondria of Saccharomyces cerevisiae. In a strain that was disabled in formate metabolism, we either overexpressed the native NAD(+)-dependent formate dehydrogenase in the cytosol or directed it into the mitochondria by fusing it with the mitochondrial signal sequence encoded by the CYB2 gene. Upon exposure to formate, the mutant strains readily consumed formate and induced fermentative metabolism even under conditions of glucose derepression. Cytosolic overexpression of formate dehydrogenase resulted in the production of glycerol, while when this enzyme was directed into the mitochondria, we observed glycerol and ethanol production. Clearly, these results point toward different patterns of compartmental regulation of redox homeostasis. When pulsed with formate, S. cerevisiae cells growing in a steady state on glucose immediately consumed formate. However, formate consumption ceased after 20 min. Our analysis revealed that metabolites at key branch points of metabolic pathways were affected the most by the genetic perturbations and that the intracellular concentrations of sugar phosphates were specifically affected by time. In conclusion, the results have implications for the design of metabolic networks in yeast for industrial applications.

PMCID: PMC2813004 PMID: 20023106 [PubMed - indexed for MEDLINE]

850. Biosens Bioelectron. 2010 Mar 15;25(7):1816-9. Epub 2009 Nov 24.

Rapid and direct magnetization of GFP-reporter yeast for micro-screening systems.

García-Alonso J, Fakhrullin RF, Paunov VN.

Department of Biological Sciences, University of Hull, Hull HU6 7RX, UK. j.garcia-alonso@nhm.ac.uk

Saccharomyces cerevisiae containing fluorescent markers are ideal candidates for applications in microfluidic screening systems as fluorescence signal is emitted without the need of additional reagents. Here we develop a method for magnetic functionalization of such cells which allows their handling and immobilization in micro-screening devices. After exposure of the magnetized GFP-reporter yeast (GreenScreen) to a genotoxic compound, the fluorescence emission was detected using fluorescent spectrometer and an Epi-fluorescent microscope. Results demonstrate that GFP production and fluorescence emission is not altered by their magnetic functionalization, indicating its potential employment on biosensors, bioreactors and micro-screening studies.

PMID: 20022481 [PubMed - indexed for MEDLINE]

851. Sci Total Environ. 2010 Feb 1;408(5):1195-8. Epub 2009 Dec 16.

Monitoring of ochratoxin A exposure of the Portuguese population through a nationwide urine survey--Winter 2007.

Duarte S, Bento J, Pena A, Lino CM, Delerue-Matos C, Oliva-Teles T, Morais S, Correia M, Oliveira MB, Alves MR, Pereira JA.

Group of Health Surveillance, Center of Pharmaceutical Studies, University of Coimbra, Health Sciences Campus, Azinhaga de Santa Comba, 3000-548, Coimbra, Portugal.

Ochratoxin A (OTA) is a mycotoxin produced by a variety of fungi, such as Penicillium verrucosum and Aspergillium spp., which has been found to have a wide number of potentially deadly toxic effects, and can enter the human organism through a variety of means. It then finds its way into the bloodstream and, after a lengthy process, is eventually excreted through the urine. It can thus be detected in its original form not only in blood samples but also in this biological medium. As such, and in an attempt to evaluate the exposure of the Portuguese population to this mycotoxin, morning urine samples were collected during the Winter of 2007, from each of five geographically distinct Portuguese locations--Bragança, Porto, Coimbra, Alentejo, and Algarve--and subjected to extraction by immunoaffinity columns and to OTA quantification through liquid chromatography coupled with fluorescence detection. Prevalent incidence was higher than 95% with Coimbra being the exception (incidence of 73.3%). In nearly all locations, the OTA content of most samples was found to be above the limit of quantification (LOQ) of 0.008 ng/ml. Indeed, excluding Coimbra, with an OTA content level of 0.014 ng/ml, all regions featured content values over 0.021 ng/ml.

PMID: 20018347 [PubMed - indexed for MEDLINE]

852. Bioresour Technol. 2010 Apr;101(7):2230-5. Epub 2009 Dec 16.

Dye decolorization and detoxification by laccase immobilized on porous glass beads.

Champagne PP, Ramsay JA.

Chemical Engineering, Queen's University, Kingston, Ontario, Canada K7L 3N6.

The decolorization and detoxification of textile dyes by fungal laccase immobilized on porous glass beads were evaluated. Anthraquinone (Reactive blue 19 and Dispersed blue 3) and indigoid (Acid blue 74) dyes were degraded more rapidly than the azo dyes (Acid red 27 and Reactive black 5). There was no dye sorption to the enzyme bed when decolorization rates were high (>12 microM dye/U-h) but at moderate rates (8 to>0.06 microM/U-h), there was a transient color which disappeared upon prolonged exposure. With Reactive black 5, permanent adsorption occurred most likely because laccase had been totally inactivated. Although laccase treatment was more efficient at decolorizing the anthraquinone dyes, their toxicity (as determined by the Microtox assay) increased while the less efficiently decolorized solutions of azo and indigoid dyes became less toxic. These results demonstrate the potential and limitations of using immobilized laccase to enzymatically decolorize a range of different dye classes and reduce dye toxicity in a single step.

PMID: 20015643 [PubMed - indexed for MEDLINE]

853. BMC Cell Biol. 2009 Dec 16;10:87.

Global transcriptional response after exposure of fission yeast cells to ultraviolet light.

Skjølberg HC, Fensgård O, Nilsen H, Grallert B, Boye E.

Department of Cell Biology, Institute for Cancer Research, Oslo University Hospital, Radiumhospitalet, Montebello, 0310 Oslo, Norway. henriette.c.skjolberg@rr-research.no

BACKGROUND: In many cell types, including the fission yeast Schizosaccharomyces pombe, a set of checkpoints are induced by perturbations of the cell cycle or by DNA damage. Many of the checkpoint responses include a substantial change of the transcriptional pattern. As part of characterising a novel G1/S checkpoint in fission yeast we have investigated whether a transcriptional response is induced after irradiation with ultraviolet light.
RESULTS: Microarray analyses were used to measure the global transcription levels of all open reading frames of fission yeast after 254 nm ultraviolet irradiation, which is known to induce a G1/S checkpoint. We discovered a surprisingly weak transcriptional response, which is quite unlike the marked changes detected after some other types of treatment and in several other checkpoints. Interestingly, the alterations in gene expression after ultraviolet irradiation were not similar to those observed after ionising radiation or oxidative stress. Pathway analysis suggests that there is little systematic transcriptional response to the irradiation by ultraviolet light, but a marked, coordinated transcriptional response was noted on progression of the cells from G1 to S phase.
CONCLUSION: There is little response in fission yeast to ultraviolet light at the transcriptional level. Amongst the genes induced or repressed after ultraviolet irradiation we found none that are likely to be involved in the G1/S checkpoint mechanism, suggesting that the checkpoint is not dependent upon transcriptional regulation.

PMCID: PMC2806298 PMID: 20015352 [PubMed - indexed for MEDLINE]

854. Anal Bioanal Chem. 2010 Feb;396(4):1441-50. Epub 2009 Dec 12.

Synchrotron FTIR microspectroscopy of the yeast Saccharomyces cerevisiae after exposure to plasma-deposited nanosilver-containing coating.

Saulou C, Jamme F, Maranges C, Fourquaux I, Despax B, Raynaud P, Dumas P, Mercier-Bonin M.

Synchrotron SOLEIL, Gif-sur-Yvette, France.

The present work was focused on elucidating changes in the model yeast Saccharomyces cerevisiae (cell composition, ultrastructure) after exposure to antimicrobial plasma-mediated nanocomposite films. In order to achieve this, a nanosilver-containing coating was deposited onto stainless steel using radiofrequency HMDSO plasma deposition, combined with simultaneous silver sputtering. X-ray photoelectron spectroscopy (XPS) confirmed the presence of silver nanoparticles embedded in an organosilicon matrix. In addition, scanning electron microscopy (SEM) demonstrated the nanoparticle-based morphology of the deposited layer. The antifungal properties towards S. cerevisiae were established, since a 1.4 log reduction in viable counts was observed after a 24-h adhesion compared to control conditions with the matrix alone. Differences in cell composition after exposure to the nanosilver was assessed for the protein region using, for the first time, synchrotron Fourier-transform infrared (FTIR) microspectroscopy of single S. cerevisiae cells, through in situ mapping with sub-cellular spatial resolution. IR spectrum of yeast cells recovered after a 24-h adhesion to the nanosilver-containing coating revealed a significant downshift (20 cm(-1)) of the amide I peak at 1655 cm(-1), compared to freshly harvested cells. This lower band position, corresponding to a loss in alpha-helix structures, is indicative of the disordered secondary structures of proteins, due to the transition between active and inactive conformations under nanosilver-induced stress conditions. No significant effect on the nucleic acid region was detected. The inhibitory action of silver was targeted against both cell wall and intracellular proteins such as enzymes. Transmission electron microscopy (TEM) observations of the yeast ultrastructure confirmed serious morphological and structural damages. A homogeneous protein-binding distribution of nanosilver all over the cell was assumed, since the presence of electron-dense silver clusters was detected not only on the cell surface but also within the cell. For control experiments with the organosilicon matrix alone, no antimicrobial effect was observed, which was consistent with synchrotron FTIR results and TEM observations.

PMID: 20012742 [PubMed - indexed for MEDLINE]

855. Curr Genet. 2010 Feb;56(1):87-100. Epub 2009 Dec 11.

RAD59 and RAD1 cooperate in translocation formation by single-strand annealing in Saccharomyces cerevisiae.

Pannunzio NR, Manthey GM, Bailis AM.

Department of Molecular and Cellular Biology, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA. npannunzio@coh.org

Studies in the budding yeast, Saccharomyces cerevisiae, have demonstrated that a substantial fraction of double-strand break repair following acute radiation exposure involves homologous recombination between repetitive genomic elements. We have previously described an assay in S. cerevisiae that allows us to model how repair of multiple breaks leads to the formation of chromosomal translocations by single-strand annealing (SSA) and found that Rad59, a paralog of the single-stranded DNA annealing protein Rad52, is critically important in this process. We have constructed several rad59 missense alleles to study its function more closely. Characterization of these mutants revealed proportional defects in both translocation formation and spontaneous direct-repeat recombination, which is also thought to occur by SSA. Combining the rad59 missense alleles with a null allele of RAD1, which encodes a subunit of a nuclease required for the removal of non-homologous tails from annealed intermediates, substantially suppressed the low frequency of translocations observed in rad1-null single mutants. These data suggest that at least one role of Rad59 in translocation formation by SSA is supporting the machinery required for cleavage of non-homologous tails.

PMCID: PMC2808509 PMID: 20012294 [PubMed - indexed for MEDLINE]

856. Eukaryot Cell. 2010 Feb;9(2):315-24. Epub 2009 Dec 11.

Defects in DNA lesion bypass lead to spontaneous chromosomal rearrangements and increased cell death.

Schmidt KH, Viebranz EB, Harris LB, Mirzaei-Souderjani H, Syed S, Medicus R.

Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, FL 33620, USA. kschmidt@cas.usf.edu

Rev3 polymerase and Mph1 DNA helicase participate in error-prone and error-free pathways, respectively, for the bypassing of template lesions during DNA replication. Here we have investigated the role of these pathways and their genetic interaction with recombination factors, other nonreplicative DNA helicases, and DNA damage checkpoint components in the maintenance of genome stability, viability, and sensitivity to the DNA-damaging agent methyl methanesulfonate (MMS). We find that cells lacking Rev3 and Mph1 exhibit a synergistic, Srs2-dependent increase in the rate of accumulating spontaneous, gross chromosomal rearrangements, suggesting that the suppression of point mutations by deletion of REV3 may lead to chromosomal rearrangements. While mph1Delta is epistatic to homologous recombination (HR) genes, both Rad51 and Rad52, but not Rad59, are required for normal growth of the rev3Delta mutant and are essential for survival of rev3Delta cells during exposure to MMS, indicating that Mph1 acts in a Rad51-dependent, Rad59-independent subpathway of HR-mediated lesion bypass. Deletion of MPH1 helicase leads to synergistic DNA damage sensitivity increases in cells with chl1Delta or rrm3Delta helicase mutations, whereas mph1Delta is hypostatic to sgs1Delta. Previously reported slow growth of mph1Delta srs2Delta cells is accompanied by G(2)/M arrest and fully suppressed by disruption of the Mec3-dependent DNA damage checkpoint. We propose a model for replication fork rescue mediated by translesion DNA synthesis and homologous recombination that integrates the role of Mph1 in unwinding D loops and its genetic interaction with Rev3 and Srs2-regulated pathways in the suppression of spontaneous genome rearrangements and in mutation avoidance.

PMCID: PMC2823012 PMID: 20008080 [PubMed - indexed for MEDLINE]

857. Chem Biol Interact. 2010 Sep 6;187(1-3):253-8. Epub 2009 Dec 11.

Next generation OP-bioscavengers: a circulatory long-lived 4-PEG hypolysine mutant of F338A-HuAChE with optimal pharmacokinetics and pseudo-catalytic characteristics.

Kronman C, Cohen O, Mazor O, Ordentlich A, Raveh L, Velan B, Shafferman A.

Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, 24 Rueven St., P.O. Box 19, Ness-Ziona 74100, Israel.

We have shown previously that conjugation of polyethylene glycol (PEG) chains to recombinant human acetylcholinesterase (rHuAChE) results in the extension of its residence time in the circulation of mice and monkeys [1,2]. By profiling the pharmacokinetic behavior of an array of well-defined hypolysine human mutant AChE molecules following PEGylation, we now determine that the duration of these enzyme forms in the circulation of rhesus macaques correlates with their number of appended PEG moieties, and is influenced by the actual location of the PEG chains at the molecule surface, as well. These findings, which concur with those we have previously established in mice, indicate that a common set of rules dictates the circulatory fate of PEGylated HuAChEs in rodents and non-human primates. In addition to its effect on circulatory residence, PEGylation reduces the ability of the rHuAChE bioscavenger to elicit an immune response in the heterologous mouse animal system. Thus, an inverse relationship between anti-AChE antibody production and PEG loading was observed following repeated administration of the different PEGylated hypolysine human AChEs to mice. We note however, that in rhesus macaques, the essentially homologous (human) AChE does not induce specific anti-AChE antibodies after repeated administration of high doses of the enzyme in its PEGylated form, and even in its non-PEGylated form. Taken together, these findings indicate that PEG acts by veiling enzyme-related epitopes, which would otherwise interact with host circulatory elimination pathways and immune system. The barring of such interactions by obstructive PEGs, confers the enzyme molecule with both extended circulatory residence and mitigated immunogenic properties. Further modulation by incorporation of the F338A mutation into the PEGylated hypolysine rHuAChE enzyme mold, resulted in the generation of an OP-bioscavenger that displayed reduced aging rates and could effectively protect mice against repeated exposure to CW agents. This selected 4-PEG F338A-AChE can serve as a paradigm for new generation OP-bioscavengers, specifically tailored for prophylactic treatment against toxic OP-agents.

PMID: 20005217 [PubMed - indexed for MEDLINE]

858. J Appl Microbiol. 2010 Jul;109(1):137-45. doi: 10.1111/j.1365-2672.2009.04637.x. Epub 2009 Nov 28.

Soya bean tempe extracts show antibacterial activity against Bacillus cereus cells and spores.

Roubos-van den Hil PJ, Dalmas E, Nout MJ, Abee T.

Laboratory of Food Microbiology, Wageningen University, Wageningen, the Netherlands. Petra.Roubos@wur.nl

AIMS: Tempe, a Rhizopus ssp.-fermented soya bean food product, was investigated for bacteriostatic and/or bactericidal effects against cells and spores of the food-borne pathogen Bacillus cereus. METHODS AND RESULTS: Tempe extract showed a high antibacterial activity against B. cereus ATCC 14579 based on optical density and viable count measurements. This growth inhibition was manifested by a 4 log CFU ml(-1) reduction, within the first 15 min of exposure. Tempe extracts also rapidly inactivated B. cereus spores upon germination. Viability and membrane permeability assessments using fluorescence probes showed rapid inactivation and permeabilization of the cytoplasmic membrane confirming the bactericidal mode of action. Cooked beans and Rhizopus grown on different media did not show antibacterial activity, indicating the unique association of the antibacterial activity with tempe. Subsequent characterization of the antibacterial activity revealed that heat treatment and protease addition nullified the bactericidal effect, indicating the proteinaceous nature of the bioactive compound.
CONCLUSIONS: During fermentation of soya beans with Rhizopus, compounds are released with extensive antibacterial activity against B. cereus cells and spores. SIGNIFICANCE AND IMPACT OF STUDY: The results show the potential of producing natural antibacterial compounds that could be used as ingredients in food preservation and pathogen control.

PMID: 20002864 [PubMed - indexed for MEDLINE]

859. J Asthma. 2009 Dec;46(10):995-1000.

Modifiable risk factors for asthma morbidity in Bronx versus other inner-city children.

Warman K, Silver EJ, Wood PR.

Department of Pediatrics, Division of General Pediatrics, Albert Einstein College of Medicine/Children's Hospital at Montefiore, Bronx, New York 10461, USA. KWarman@montefiore.org

BACKGROUND: Bronx children have higher asthma prevalence and asthma morbidity than other US children.
OBJECTIVE: To compare risk factors for asthma morbidity present in Bronx children with those of children from other US inner-city areas.
METHODS: Cross-sectional, multi-state study of 1772 children ages 5-11 yrs. old with persistent asthma. Parental responses to the Child Asthma Risk Assessment Tool for 265 Bronx children are compared with those of 1507 children from 7 other sites (1 Northeast, 2 South, 2 Midwest, 2 West).
RESULTS: Bronx children were significantly more likely to be sensitized to reported aeroallergens in their homes than were children from the other sites (86% vs. 58%; p < .001). More Bronx parents reported household cockroaches (65% v 20%; p < .001), mice (42% v 11%; p < .001), and rats (7% v 3%; p < .001); using a gas stove to heat the home (20% v 9%; p < .001); and visible mold (48% v 25%; p < .001). Bronx parents were more likely to report pessimistic beliefs about controlling asthma (63% v 26%; p < .001) and high parental stress (48% v 37%; p < .01).
CONCLUSIONS: Compared with other inner-city children with asthma, Bronx children are more likely to be exposed to household aeroallergens to which they are sensitized and have poor housing conditions. Their parents are more likely to report low expectations for asthma control and high levels of psychological stress. Interventions that address these identified needs may help to reduce the disproportionate burden of asthma morbidity experienced by Bronx children.

PMCID: PMC2892895 PMID: 19995136 [PubMed - indexed for MEDLINE]

860. J Agric Food Chem. 2010 Jan 13;58(1):66-71.

Occurrence of mycotoxins in feed as analyzed by a multi-mycotoxin LC-MS/MS method.

Monbaliu S, Van Poucke C, Detavernier C, Dumoulin F, Van De Velde M, Schoeters E, Van Dyck S, Averkieva O, Van Peteghem C, De Saeger S.

Laboratory of Food Analysis, Ghent University, Harelbekestraat 72, 9000 Ghent, Belgium. Sofie.Monbaliu@UGent.be

Crops used for animal feed can be easily contaminated by fungi during growth, harvest, or storage, resulting in the occurrence of mycotoxins. Because animal feed plays an important role in the food safety chain, the European Commission has set maximum levels for aflatoxin B1 and recommended maximum levels for deoxynivalenol, zearalenone, ochratoxin A, and the sum of fumonisin B1 and B2. A multimycotoxin LC-MS/MS method was developed, validated according to Commission Decision 2002/657/EC and EN ISO 17025 accredited for the simultaneous detection of 23 mycotoxins (aflatoxin-B1, aflatoxin-B2, aflatoxin-G1, aflatoxin-G2, ochratoxin A, deoxynivalenol, zearalenone, fumonisin B1, fumonisin B2, fumonisin B3, T2-toxin, HT2-toxin, nivalenol, 3-acetyldeoxynivalenol, 15-acetyldeoxynivalenol, diacetoxyscirpenol, fusarenon-X, neosolaniol, altenuene, alternariol, alternariol methyl ether, roquefortine-C, and sterigmatocystin) in feed. The decision limits of the multimycotoxin method varied from 0.7 to 60.6 microg/kg. The apparent recovery and the results of the precision study fulfilled the performance criteria as set in Commission Decision 2002/657/EC. The analysis of three different feed matrices (sow feed, wheat, and maize) provided a good basis for the evaluation of the toxin exposure in animal production. In total, 67 samples out of 82 (82%) were contaminated; type B-trichothecenes and fumonisins occurred most often. The majority of the infected feed samples (75%) were contaminated with more than one type of mycotoxin.

PMID: 19994896 [PubMed - indexed for MEDLINE]

861. J Ind Microbiol Biotechnol. 2010 Mar;37(3):297-306. Epub 2009 Dec 5.

Enhanced production of gibberellin A4 (GA4) by a mutant of Gibberella fujikuroi in wheat gluten medium.

Lale G, Gadre R.

Chemical Engineering and Process Development Division, National Chemical Laboratory, Pune, 411008, India.

Mutants of Gibberella fujikuroi with different colony characteristics, morphology and pigmentation were generated by exposure to UV radiation. A mutant, Mor-189, was selected based on its short filament length, relatively high gibberellin A(4) (GA(4)) and gibberellin A(3) (GA(3)) production, as well as its lack of pigmentation. Production of GA(4) by Mor-189 was studied using different inorganic and organic nitrogen sources, carbon sources and by maintaining the pH of the fermentation medium using calcium carbonate. Analysis of GA(4) and GA(3) was done by reversed-phase high-performance liquid chromatography and LC-MS. The mutants of G. fujikuroi produced more GA(4) when the pH of the medium was maintained above 5. During shake flask studies, the mutant Mor-189 produced 210 mg l(-1) GA(4) in media containing wheat gluten as the nitrogen source and glucose as the carbon source. Fed-batch fermentation in a 14 l agitated fermenter was performed to evaluate the applicability of the mutant Mor-189 for the production of GA(4). In 7-day fed-batch fermentation, 600 mg l(-1) GA(4) were obtained in the culture filtrate. The concentration of GA(4) and GA(3) combined was 713 mg l(-1), of which GA(4) accounted for 84% of the total gibberellin. These values are substantially higher than those published previously. The present study indicated that, along with maintenance of pH and controlled glucose feeding, the use of wheat gluten as the sole nitrogen source considerably enhances GA(4) production by the mutant Mor-189.

PMID: 19967447 [PubMed - indexed for MEDLINE]

862. Proc Natl Acad Sci U S A. 2010 Jan 5;107(1):34-9. Epub 2009 Dec 4.

A protein kinase network regulates the function of aminophospholipid flippases.

Roelants FM, Baltz AG, Trott AE, Fereres S, Thorner J.

Division of Biochemistry and Molecular Biology, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3202, USA.

Limited exposure of aminophospholipids on the outer leaflet of the plasma membrane is a fundamental feature of eukaryotic cells and is maintained by the action of inward-directed P-type ATPases ("flippases"). Yeast S. cerevisiae has five flippases (Dnf1, Dnf2, Dnf3, Drs2, and Neo1), but their regulation is poorly understood. Two paralogous plasma membrane-associated protein kinases, Pkh1 and Pkh2 (orthologs of mammalian PDK1), are required for viability of S. cerevisiae cells because they activate several essential downstream protein kinases by phosphorylating a critical Thr in their activation loops. Two such targets are related protein kinases Ypk1 and Ypk2 (orthologs of mammalian SGK1), which have been implicated in multiple processes, including endocytosis and coupling of membrane expansion to cell wall remodeling, but the downstream effector(s) of these kinases have been elusive. Here we show that a physiologically relevant substrate of Ypk1 is another protein kinase, Fpk1, a known flippase activator. We show that Ypk1 phosphorylates and thereby down-regulates Fpk1, and further that a complex sphingolipid counteracts the down-regulation of Fpk1 by Ypk1. Our findings delineate a unique regulatory mechanism for imposing a balance between sphingolipid content and aminophospholipid asymmetry in eukaryotic plasma membranes.

PMCID: PMC2806694 PMID: 19966303 [PubMed - indexed for MEDLINE]

863. AORN J. 2009 Dec;90(6):867-72.

Reducing scalpel injuries in the operating room.

Vose JG, McAdara-Berkowitz J.

PEAK Surgical, Inc, Palo Alto, CA, USA.

Scalpel injuries can expose surgeons, nurses, and other OR personnel to bloodborne pathogens. Direct and indirect costs of managing exposure include time spent reporting, treating, and following up on the injuries; salaries and benefits for injured staff members; laboratory testing of exposure sources and exposed personnel; and postexposure prophylaxis. Standard precautions, training and awareness for those at risk, the use of neutral passing zones, and safety-engineered devices have helped decrease the incidence of injury for specific categories of sharps. One new safety device is a hand piece that uses electrosurgical plasma induced with pulsed radio-frequency energy to cut tissue.

PMID: 19961972 [PubMed - indexed for MEDLINE]

864. J Proteome Res. 2010 Feb 5;9(2):730-6.

Oxidative stress studies in yeast with a frataxin mutant: a proteomics perspective.

Kim JH, Sedlak M, Gao Q, Riley CP, Regnier FE, Adamec J.

Department of Chemistry, Purdue University, West Lafayette, Idiana 47907, USA.

Cellular response of wild-type Saccharomyces cerevisiae and the Delta yfh1 mutant to oxidative stress (OS) was examined by stressing cells through the addition of H(2)O(2) to the growth medium. The Delta yfh1 mutant is unusual in that it accumulates iron in it is mitochondria. Wild-type growth was immediately arrested and recovered in 2 h following H(2)O(2) treatment. No change in viability was observed. Growth of the mutant, on the other hand, was similar to wild-type yeast for 4 h but then rapidly declined, eventually reaching zero. Levels of carbonyl groups and reactive oxygen species (ROS) reached their maximum at 3 h following exposure. The impact of OS on protein function was also evaluated by proteomic techniques targeting protein carbonylation. Oxidized proteins were selected by affinity chromatography, and following trypsin digestion, peptide fragments were identified by RPLC-MS/MS. A total of 53 proteins were identified in both wild-type and mutant cells, respectively.

PMID: 19957947 [PubMed - indexed for MEDLINE]

865. Appl Microbiol Biotechnol. 2010 Mar;86(2):721-9. Epub 2009 Dec 2.

Inhibitory effect of hydroxycinnamic acids on Dekkera spp.

Harris V, Jiranek V, Ford CM, Grbin PR.

School of Agriculture, Food and Wine, The University of Adelaide, PMB1, Glen Osmond 5064, Adelaide, South Australia, Australia. victoria.harris@adelaide.edu.au

Simple phenolic components of wine, hydroxycinnamic acids (HCAs) are known to have antimicrobial properties. This study sought to determine the potential of ferulic acid as an antifungal agent for the control of Dekkera. Growth was inhibited by all HCAs examined in this study, with ferulic acid being the most potent at all concentrations. In the presence of ethanol, the inhibitory effects of ferulic acid were amplified. Scanning electron microscopy images reveal cellular damage upon exposure to ferulic acid. Thus, manipulation of ferulic acid concentrations could be of industrial significance for control of Dekkera and may be the basis for differences in susceptibility of wines to Dekkera spoilage.

PMID: 19957080 [PubMed - indexed for MEDLINE]

866. Mutagenesis. 2010 Mar;25(2):155-62. Epub 2009 Dec 2.

Investigations on the role of base excision repair and non-homologous end-joining pathways in sodium selenite-induced toxicity and mutagenicity in Saccharomyces cerevisiae.

Mániková D, Vlasáková D, Loduhová J, Letavayová L, Vigasová D, Krascsenitsová E, Vlcková V, Brozmanová J, Chovanec M.

Laboratory of Molecular Genetics, Cancer Research Institute, Vlárska 7, 833 91 Bratislava, Slovak Republic.

Selenium (Se) belongs to nutrients that are essential for human health. Biological activity of this compound, however, mainly depends on its dose, with a potential of Se to induce detrimental effects at high doses. Although mechanisms lying behind detrimental effects of Se are poorly understood yet, they involve DNA damage induction. Consequently, DNA damage response and repair pathways may play a crucial role in cellular response to Se. Using Saccharomyces cerevisiae we showed that sodium selenite (SeL), an inorganic form of Se, can be toxic and mutagenic in this organism due to its ability to induce DNA double-strand breaks (DSBs). Moreover, we reported that a spectrum of mutations induced by this compound in the stationary phase of growth is mainly represented by 1-4 bp deletions. Consequently, we proposed that SeL acts as an oxidizing agent in yeast producing oxidative damage to DNA. As short deletions could be anticipated to arise as a result of action of non-homologous end-joining (NHEJ) and oxidative damage to DNA is primarily coped with base excision repair (BER), a contribution of these two pathways towards survival, DSB induction, mutation frequency and types of mutations following SeL exposure was examined in present study. First, we show that while NHEJ plays no role in repairing toxic DNA lesions induced by SeL, cells with impairment in BER are sensitized towards this compound. Of BER activities examined, those responsible for processing of 3'-blocking DNA termini seem to be the most crucial for manifestation of the toxic effects of SeL in yeast. Second, an impact of NHEJ and BER on DSB induction after SeL exposure turned to be inappreciable, as no increase in DNA double-strand breakage in NHEJ and BER single or NHEJ BER double mutant upon SeL exposure was observed. Finally, we demonstrate that impairment in both these pathways does not importantly change mutation frequency after SeL exposure and that NHEJ is not responsible for generation of short deletions after SeL treatment, as these were comparably induced in the wild-type and NHEJ-defective cells.

PMID: 19955329 [PubMed - indexed for MEDLINE]

867. J Intensive Care Med. 2010 Mar-Apr;25(2):78-92. Epub 2009 Dec 1.

Invasive fungal infections in the ICU.

Shoham S, Marwaha S.

Section of Infectious Diseases, Washington Hospital Center, Washington, D.C., MedStar Research Institute, Washington, DC 20010, USA. Shmuel.Shoham@medstar.net

Invasive fungal infections are major causes of morbidity and mortality in critically ill patients. Foremost among these is invasive candidiasis. In recent years, invasive aspergillosis (IA) and zygomycosis have emerged as major problems in susceptible, critically ill patients. Risk factors for invasive fungal infections, including disrupted anatomic barriers, suppressed antifungal host responses, and exposure to potentially opportunistic fungi are common in critically ill patients. The expanded antifungal armamentarium and advent of rapid diagnostic techniques are altering the approach to invasive fungal infections in the intensive care unit (ICU). Herein, we review recent developments in the field of antifungal host defenses, the changing epidemiology of fungal infections in the ICU, the pharmacology of antifungal agents of importance to critically ill patients, and the evolving approaches to therapy in this setting.

PMID: 19955115 [PubMed - indexed for MEDLINE]

868. Ethiop Med J. 2009 Jul;47(3):213-9.

Occupational exposure of health workers to blood and body fluids in six hospitals of Tigray region (August 1-30, 2006): magnitude and management.

Gessessew A, Kahsu A.

Department of Gynecology, Mekele Hospital, Tigray.

BACKGROUND: Health care workers are at risk of acquiring blood born infections in their workplace. Needle stick injuries, blood and body fluids contact to non-intact skin and accidental splash to the mucus membrane are known to transmit infections. There is paucity of reports of such type of exposure in Ethiopia.
OBJECTIVE: To assess the incidence of exposure of health care workers to blood and body fluids and their practice to prevent infection after exposure.
METHODS: A cross sectional study by interviewing all health care workers in six hospitals of Tigray from August 1, 2006 to August 30, 2006.
RESULTS: A total of 618 health care workers were interviewed about exposure in the past three months prior this interview. Needle stick injury was reported in 106 health care workers (17.2%), 348 (56.3%) had contact of blood and body fluid to their skin and 154 (24.9%) reported exposure to their mucus membrane. Working in the delivery room (80.4%) and gynecological wards (75%) had higher risk of exposure to the skin. Regarding their knowledge to preventive measures, only 254 (41.1%) of all health care workers said they wash their skin immediately and 318 (51.5%) flash their eyes with clean water or saline if their skin and mucous membrane are exposed Incorrect method of processing instruments were practiced by high number of health care workers, namely, decontamination by 47.5%, disinfection by 46.5% and sterilization by 41.5% of them.
CONCLUSION: Health care workers are at a very high risk of exposure to blood and body fluids. Poor efforts are made to prevent infection after exposure. Wrong practice of processing instrument is shown to be high. It is recommended that health care workers should follow and practice all the standard measure to prevent transmission of infection in a clinical setting.

PMID: 19954124 [PubMed - indexed for MEDLINE]

869. J Occup Environ Hyg. 2010 Feb;7(2):94-102.

Impact of production systems on swine confinement buildings bioaerosols.

Létourneau V, Nehmé B, Mériaux A, Massé D, Duchaine C.

Departement de biochimie et de microbiologie, Faculte des sciences et de genie, Universite Laval, Quebec, Canada.

Hog production has been substantially intensified in Eastern Canada. Hogs are now fattened in swine confinement buildings with controlled ventilation systems and high animal densities. Newly designed buildings are equipped with conventional manure handling and management systems, shallow or deep litter systems, or source separation systems to manage the large volumes of waste. However, the impacts of those alternative production systems on bioaerosol concentrations within the barns have never been evaluated. Bioaerosols were characterized in 18 modern swine confinement buildings, and the differences in bioaerosol composition in the three different production systems were evaluated. Total dust, endotoxins, culturable actinomycetes, fungi, and bacteria were collected with various apparatuses. The total DNA of the air samples was extracted, and quantitative polymerase chain reaction (PCR) was used to assess the total number of bacterial genomes, as a total (culturable and nonculturable) bacterial assessment. The measured total dust and endotoxin concentrations were not statistically different in the three studied production systems. In buildings with sawdust beds, actinomycetes and molds were found in higher concentrations than in the conventional barns. Aspergillus, Cladosporium, Penicillium, and Scopulariopsis species were identified in all the studied swine confinement buildings. A. flavus, A. terreus, and A. versicolor were abundantly present in the facilities with sawdust beds. Thermotolerant A. fumigatus and Mucor were usually found in all the buildings. The culturable bacteria concentrations were higher in the barns with litters than in the conventional buildings, while real-time PCR revealed nonstatistically different concentrations of total bacteria in all the studied swine confinement buildings. In terms of workers' respiratory health, barns equipped with a solid/liquid separation system may offer better air quality than conventional buildings or barns with sawdust beds. The impact of ventilation rates, air distribution, or building design still has to be explored.

PMID: 19953413 [PubMed - indexed for MEDLINE]

870. J Antimicrob Chemother. 2010 Feb;65(2):285-8. Epub 2009 Dec 1.

Antifungal activity of Leptospermum petersonii oil volatiles against Aspergillus spp. in vitro and in vivo.

Hood JR, Burton D, Wilkinson JM, Cavanagh HM.

School of Biomedical Sciences, Charles Sturt University, Boorooma Street, Wagga Wagga NSW 2650, Australia.

OBJECTIVES: This study investigates the volatile (vapour) component of an essential oil derived from the Australian native Leptospermum petersonii as a potential treatment for aspergillosis.
METHODS: The in vitro antifungal effects of the volatiles were assayed by a variety of methods. In vitro mammalian cell toxicity of the oil and the oil volatiles was also determined prior to animal testing. Efficacy of the volatiles in vivo was assessed using a murine model.
RESULTS: L. petersonii oil volatiles were found to be potent inhibitors of fungal growth in vitro, with fungicidal activity displayed following short exposure times (< or =1 h). No significant mammalian cell toxicity was found to be associated with the volatiles. In the absence of treatment, Aspergillus fumigatus infection of animals resulted in an increase in inflammatory cell counts and high fungal burden within the lung tissue. Chitin levels in treated animals were significantly reduced compared with control animals. No viable fungi could be recovered from animals that had completed the treatment regimen.
CONCLUSIONS: The significant reduction in fungal burden in the lungs of infected animals by the volatiles of L. petersonii oil was larger than that reported for conventional antifungal drugs of choice.

PMID: 19952013 [PubMed - indexed for MEDLINE]

871. Clin Infect Dis. 2010 Jan 1;50(1):85-92.

Recognition, diagnosis, and treatment of histoplasmosis complicating tumor necrosis factor blocker therapy.

Hage CA, Bowyer S, Tarvin SE, Helper D, Kleiman MB, Joseph Wheat L.

Pulmonary-Critical Care and Infectious Diseases, Roudebush Veterans Affairs Medical Center, Indianapolis, Indiana 46202, USA. chage@iupui.edu

Life-threatening histoplasmosis is one of the most common opportunistic infections in patients receiving tumor necrosis factor (TNF) blockers. Delays in considering the diagnosis may lead to increased morbidity and mortality. Most affected patients present with pneumonitis, usually accompanied by additional signs of progressive dissemination, or with signs of progressive dissemination alone. The diagnosis often can be promptly established using antigen detection or direct examination of bronchoalveolar lavage specimens. If histoplasmosis is diagnosed promptly, antifungal therapy is highly effective. After a favorable clinical response, the safety of both discontinuation of antifungal therapy and the resumption of TNF blocker remains undetermined. The management of the immune reconstitution inflammatory syndrome that may follow discontinuation of TNF blockers also requires investigation. Prescribers should become aware of the recognition, diagnosis, and treatment of histoplasmosis and educate recipients about decreasing their risk of exposure and both recognizing and reporting signs of early infection.

PMID: 19951231 [PubMed - indexed for MEDLINE]

872. Immunopharmacol Immunotoxicol. 2009;31(1):140-5.

Soluble cell wall beta-glucan of Candida induces/enhances apoptosis and oxidative stress in murine lung.

Inoue K, Takano H, Oda T, Yanagisawa R, Tamura H, Adachi Y, Ishibashi K, Ohno N.

Environmental Health Sciences Division, National Institute for Environmental Studies, Tsukuba, Ibaraki, Japan. inoue.kenichirou@nies.go.jp

The bioactivity of cell wall component(s) of fungi has not been fully investigated, especially in vivo. We have successfully extracted a soluble cell wall beta-glucan from C. albicans (CSBG), and shown that pulmonary exposure to CSBG induces lung inflammation in mice. CSBG-induced lung inflammation was concomitant with the nuclear translocation of signal transducer and activator of transcription (STAT)6 and enhanced lung expression of various cytokines and chemokines. However, the effects of CSBG on the murine respiratory system and their mechanisms have not been fully investigated. In this study, we further explored the effects of pulmonary exposure to CSBG on lung pathophysiology in terms of the induction of apoptosis and enhancement of oxidative stress. ICR mice were intratracheally instilled with vehicle, CSBG, or structurally degraded products of CSBG by formic acid (DEG-CSBG), and 24 h later, the lungs were isolated and evaluated for apoptosis by the TUNEL assay and oxidative stress by immunohistochemistry of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a proper marker of the oxidative DNA damage. In another experiment, the mice were sacrificed and lungs were isolated 4 h after the instillation with vehicle or CSBG for evaluation of transcriptional level of heme oxygenase (HO)-1, a stress responsive protein. Pulmonary exposure to CSBG significantly induced apoptosis and enhanced the formation of 8-OHdG in the lung parenchyma as compared to vehicle or DEG-CSBG exposure. CSBG significantly induced HO-1 in the lung. Taken together, CSBG induces/enhances apoptosis and oxidative stress in the lung in association with lung inflammation/injury.

PMID: 19951074 [PubMed - indexed for MEDLINE]

873. J Mol Biol. 2010 Feb 19;396(2):361-74. Epub 2009 Nov 26.

Redox-dependent domain rearrangement of protein disulfide isomerase coupled with exposure of its substrate-binding hydrophobic surface.

Serve O, Kamiya Y, Maeno A, Nakano M, Murakami C, Sasakawa H, Yamaguchi Y, Harada T, Kurimoto E, Yagi-Utsumi M, Iguchi T, Inaba K, Kikuchi J, Asami O, Kajino T, Oka T, Nakasako M, Kato K.

Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, Okazaki, Aichi, Japan.

Protein disulfide isomerase (PDI) is a major protein in the endoplasmic reticulum, operating as an essential folding catalyst and molecular chaperone for disulfide-containing proteins by catalyzing the formation, rearrangement, and breakage of their disulfide bridges. This enzyme has a modular structure with four thioredoxin-like domains, a, b, b', and a', along with a C-terminal extension. The homologous a and a' domains contain one cysteine pair in their active site directly involved in thiol-disulfide exchange reactions, while the b' domain putatively provides a primary binding site for unstructured regions of the substrate polypeptides. Here, we report a redox-dependent intramolecular rearrangement of the b' and a' domains of PDI from Humicola insolens, a thermophilic fungus, elucidated by combined use of nuclear magnetic resonance (NMR) and small-angle X-ray scattering (SAXS) methods. Our NMR data showed that the substrates bound to a hydrophobic surface spanning these two domains, which became more exposed to the solvent upon oxidation of the active site of the a' domain. The hydrogen-deuterium exchange and relaxation data indicated that the redox state of the a' domain influences the dynamic properties of the b' domain. Moreover, the SAXS profiles revealed that oxidation of the a' active site causes segregation of the two domains. On the basis of these data, we propose a mechanistic model of PDI action; the a' domain transfers its own disulfide bond into the unfolded protein accommodated on the hydrophobic surface of the substrate-binding region, which consequently changes into a "closed" form releasing the oxidized substrate.

PMID: 19944705 [PubMed - indexed for MEDLINE]

874. FEBS Lett. 2010 Jan 4;584(1):55-60.

Overexpression of Sna3 stabilizes tryptophan permease Tat2, potentially competing for the WW domain of Rsp5 ubiquitin ligase with its binding protein Bul1.

Hiraki T, Abe F.

Molecular Evolution and Adaptation Research, Institute of Biogeosciences, Japan Agency for Marine-Earth Science and Technology (JAMSTEC), Yokosuka, Japan.

Tryptophan permease Tat2 in Saccharomyces cerevisiae undergoes Rsp5-dependent degradation upon exposure to high hydrostatic pressure and it limits the growth of tryptophan auxotrophs. Overexpression of SNA3 encoding an endosomal/vacuolar protein possessing the PPAY motif allowed growth at 25 MPa, which was potentiated by marked stabilization of Tat2. This appeared to depend on the PPAY motif, which interacted with the WW domain of Rsp5. Subcellular localization of Rsp5 was unchanged by overexpression of either SNA3 or SNA3-AAAY. While the loss of Bul1, a binding protein of Rsp5, or the rsp5-ww3 mutation allowed high-pressure growth, overexpression of BUL1 abolished the Sna3-mediated growth at 25 MPa. These results suggest that Sna3 and Bul1 compete for the WW domain of Rsp5 upon Tat2 ubiquitination.

PMID: 19944104 [PubMed - indexed for MEDLINE]

875. EMBO J. 2010 Jan 6;29(1):4-13. Epub 2009 Nov 26.

Multilayered control of gene expression by stress-activated protein kinases.

de Nadal E, Posas F.

Cell Signaling Unit, Departament de Ciències Experimentals i de Salut, Universitat Pompeu Fabra, Barcelona, Spain. eulalia.nadal@upf.edu

Stress-activated protein kinases (SAPKs) are key elements for intracellular signalling networks that serve to respond and adapt to extracellular changes. Exposure of yeast to high osmolarity results in the activation of p38-related SAPK, Hog1, which is essential for reprogramming the gene expression capacity of the cell by regulation of several steps of the transcription process. At initiation, active Hog1 not only directly phosphorylates several transcription factors to alter their activities, but also associates at stress-responsive promoters through such transcription factors. Once at the promoters, Hog1 serves as a platform to recruit general transcription factors, chromatin-modifying activities and RNA Pol II. In addition, the SAPK pathway has a role in elongation. At the stress-responsive ORFs, Hog1 recruits the RSC chromatin-remodelling complex to modify nucleosome organization. Several SAPKs from yeast to mammals have maintained some of the regulatory abilities of Hog1. Thus, elucidating the control of gene expression by the Hog1 SAPK should help to understand how eukaryotic cells implement a massive and rapid change on their transcriptional capacity in response to adverse conditions.

PMCID: PMC2808381 PMID: 19942851 [PubMed - indexed for MEDLINE]

876. Nihon Ishinkin Gakkai Zasshi. 2009;50(4):225-8.

[Clinical pathogenesis of candidemia caused by non-albicans Candida species].

[Article in Japanese]

Myoken Y.

Department of Oral Surgery, Hiroshima Red Cross and Atomic Bomb Survivors Hospital.

A proportional increase in candidemia due to non-albicans Candida species has been reported worldwide. In our hospital, 36 of 58 candidemia cases were caused by non-albicans Candida species between 1996 and 2007. Candidemia due to non-albicans Candida species is associated with fluconazole(FLCZ)exposure. In our cases, 36 of 36 non-albicans candidemia cases received FLCZ while 18 of 22 albicans candidemia cases received this drug. In general, non-albicans Candida species including C. tropicalis, C. parapsilosis, and C. guilliermondii are susceptible to FLCZ. On the other hand, C. glabrata and C. krusei exhibit decreased susceptibility to FLCZ. Our in vitro susceptibility test revealed the same results as above although C. guilliermondii showed an elevated MIC to FLCZ(4-8 microg/ml). In addition, both C. parapsilosis and C. guilliermondii showed elevated MICs to micafungin (1 microg/ml and 0.5-2 microg/ml, respectively) which is generally useful for non-albicans Candida species.

PMID: 19942793 [PubMed - indexed for MEDLINE]

877. J Nurs Scholarsh. 2009;41(4):337-43.

Percutaneous and mucocutaneous exposures in nursing students: an Italian observational study.

Petrucci C, Alvaro R, Cicolini G, Cerone MP, Lancia L.

University of L'Aquila, Department of Internal Medicine and Public Health, Via Vetoio, 1 67010 Coppito, L'Aquila, Italy.

PURPOSE: To investigate occupational exposures to biological material potentially infected by blood-borne viruses in nursing student population during the course years. DESIGN AND METHODS: An observational retrospective study was designed. Data were collected in May 2007. Two-thousand-two-hundred-fifteen nursing students from the 3 years of degree course were enrolled in the four Italian universities. A structured questionnaire was constructed and was given out unannounced to nursing students in four universities on a randomly chosen day. The likelihood of association between nursing student exposure and certain assumed risk factors was measured. FINDINGS: The exposure risk is associated with each study year of nursing students. Specifically, the probability of accidental exposure is reduced significantly with the increase of clinical skills during the training period. The risk for exposure in the 1st year students appears significantly higher than in those of the next years (odds ratio [OR] 1.465; 95% confidence interval [CI] 1.105-1.943). Data highlighted a gradual increase of bio-safety knowledge in nursing students from the 1st to the 3rd years of study. However, a statistically significant association exists only between awareness of a correct use of gloves and exposure risk (OR 0.435; 95%CI 0.227-0.834). Mucocutaneous exposures are more frequent than percutaneous exposures (62.2%), and the hollow-bore needle is the device most often involved. In 42.5% of cases, accidental exposures occurred when nursing students are working alone in a medical ward or surgery area.
CONCLUSIONS: During their clinical training, nursing students can encounter a real risk for percutaneous and mucocutaneous exposures to blood potentially infected with blood-borne viruses. However, this risk is reduced with an increase in clinical skills. CLINICAL RELEVANCE: Results show that some new strategies are necessary for exposure risk reduction such as development of simulation laboratories for nursing practice and the adequate presence of tutors in clinical training education.

PMID: 19941578 [PubMed - indexed for MEDLINE]

878. Plant Physiol. 2010 Feb;152(2):948-67. Epub 2009 Nov 25.

The pepper 9-lipoxygenase gene CaLOX1 functions in defense and cell death responses to microbial pathogens.

Hwang IS, Hwang BK.

Laboratory of Molecular Plant Pathology, School of Life Sciences and Biotechnology, Korea University, Seoul 136-713, Republic of Korea.

Lipoxygenases (LOXs) are crucial for lipid peroxidation processes during plant defense responses to pathogen infection. A pepper (Capsicum annuum) 9-LOX gene, CaLOX1, which encodes a 9-specific lipoxygenase, was isolated from pepper leaves. Recombinant CaLOX1 protein expressed in Escherichia coli catalyzed the hydroperoxidation of linoleic acid, with a K(m) value of 113. 9 mum. Expression of CaLOX1 was differentially induced in pepper leaves not only during Xanthomonas campestris pv vesicatoria (Xcv) infection but also after exposure to abiotic elicitors. Transient expression of CaLOX1 in pepper leaves induced the cell death phenotype and defense responses. CaLOX1-silenced pepper plants were more susceptible to Xcv and Colletotrichum coccodes infection, which was accompanied by reduced expression of defense-related genes, lowered lipid peroxidation, as well as decreased reactive oxygen species and lowered salicylic acid accumulation. Infection with Xcv, especially in an incompatible interaction, rapidly stimulated LOX activity in unsilenced, but not CaLOX1-silenced, pepper leaves. Furthermore, overexpression of CaLOX1 in Arabidopsis (Arabidopsis thaliana) conferred enhanced resistance to Pseudomonas syringae pv tomato, Hyaloperonospora arabidopsidis, and Alternaria brassicicola. In contrast, mutation of the Arabidopsis CaLOX1 ortholog AtLOX1 significantly increased susceptibility to these three pathogens. Together, these results suggest that CaLOX1 and AtLOX1 positively regulate defense and cell death responses to microbial pathogens.

PMCID: PMC2815858 PMID: 19939946 [PubMed - indexed for MEDLINE]

879. Mycopathologia. 2010 Apr;169(4):279-85. Epub 2009 Nov 24.

The effect of gentian violet on virulent properties of Candida albicans.

Ying S, Qing S, Chunyang L.

Department of Dermatology and Ethology, Qilu Hospital Affiliated to Shandong University, Jinan, China. sywjzwxl@yahoo.com.cn

The aim of this study was to evaluate the effect of gentian violet (GV) on phospholipase activity, proteinase activity and germ tube formation rate of Candida albicans. Both 12 phospholipase-positive and 12 proteinase-positive C. albicans isolates with Pz values

PMID: 19937129 [PubMed - indexed for MEDLINE]

880. Biometals. 2010 Apr;23(2):207-19.

Arsenic accumulation and thiol status in lichens exposed to As(V) in controlled conditions.

Mrak T, Jeran Z, Batic F, di Toppi LS.

Department of Evironmental Sciences, Jozef Stefan Institute, Ljubljana, Slovenia.

Thalli of epiphytic lichen Hypogymnia physodes (L.) Nyl. and terricolous Cladonia furcata (Huds.) Schrad., collected from an area with background arsenic concentrations, were exposed to 0, 0.1, 1 and 10 microg mL(-1) arsenate (As(V)) solutions for 24 h. After exposure they were kept in the metabolically active state for 0, 24 and 48 h in a growth chamber. In the freeze dried samples glutathione (GSH), glutathione disulphide (GSSG), cysteine (Cys) and cystine were analysed and induction of phytochelatin (PC) synthesis measured by reversed-phase high-performance liquid chromatography in combination with fluorescence detection or UV spectrometry. Total arsenic content in thalli was measured by instrumental neutron activation analysis (INAA). In H. physodes, which contained higher amounts of arsenic compared to C. furcata, total glutathione content significantly decreased in samples exposed to 10 microg mL(-1) As(V), whereas in C. furcata a significant increase was observed. In both species PC synthesis was induced in thalli exposed to 10 microg mL(-1).

PMID: 19936941 [PubMed - indexed for MEDLINE]

881. Antimicrob Agents Chemother. 2010 Feb;54(2):811-6. Epub 2009 Nov 23.

Antimicrobial peptide hLF1-11 directs granulocyte-macrophage colony-stimulating factor-driven monocyte differentiation toward macrophages with enhanced recognition and clearance of pathogens.

van der Does AM, Bogaards SJ, Ravensbergen B, Beekhuizen H, van Dissel JT, Nibbering PH.

Department of Infectious Diseases, Leiden University Medical Center (LUMC), C5-P, P.O. Box 9600, 2300 RC Leiden, The Netherlands.

The human lactoferrin-derived peptide hLF1-11 displays antimicrobial activities in vitro and is effective against infections with antibiotic-resistant bacteria and fluconazole-resistant Candida albicans in animals. However, the mechanisms underlying these activities remain largely unclear. Since hLF1-11 is ineffective in vitro at physiological salt concentrations, we suggested modulation of the immune system as an additional mechanism of action of the peptide. We investigated whether hLF1-11 affects human monocyte-macrophage differentiation and determined the antimicrobial activities of the resulting macrophages. Monocytes were cultured for 7 days with GM-CSF in the presence of hLF1-11, control peptide, or saline for various intervals. At day 6, the cells were stimulated with lipopolysaccharide (LPS), lipoteichoic acid (LTA), or heat-killed C. albicans for 24 h. Thereafter, the levels of cytokines in the culture supernatants, the expression of pathogen recognition receptors, and the antimicrobial activities of these macrophages were determined. The results showed that a short exposure of monocytes to hLF1-11 during GM-CSF-driven differentiation is sufficient to direct differentiation of monocytes toward a macrophage subset characterized by both pro- and anti-inflammatory cytokine production and increased responsiveness to microbial structures. Moreover, these macrophages are highly effective against C. albicans and Staphylococcus aureus. In conclusion, hLF1-11 directs GM-CSF-driven differentiation of monocytes toward macrophages with enhanced effector functions.

PMCID: PMC2812139 PMID: 19933796 [PubMed - indexed for MEDLINE]

882. Genes Dev. 2009 Nov 15;23(22):2578-91.

Evolutionary conservation and adaptation in the mechanism that regulates SREBP action: what a long, strange tRIP it's been.

Osborne TF, Espenshade PJ.

Department of Molecular Biology and Biochemistry, University of California at Irvine, Irvine, California 92697, USA. tfosborn@uci.edu

Sterol regulatory element-binding proteins (SREBPs) are a subfamily of basic helix-loop-helix leucine zipper (bHLH-LZ) transcription factors that are conserved from fungi to humans and are defined by two key features: a signature tyrosine residue in the DNA-binding domain, and a membrane-tethering domain that is a target for regulated proteolysis. Recent studies including genome-wide and model organism approaches indicate SREBPs coordinate cellular lipid metabolism with other cellular physiologic processes. These functions are broadly related as cellular adaptation to environmental changes ranging from nutrient fluctuations to toxin exposure. This review integrates classic features of the SREBP pathway with newer information regarding the regulation and sensing mechanisms that serve to assimilate different cellular physiologic processes for optimal function and growth.

PMCID: PMC2779761 PMID: 19933148 [PubMed - indexed for MEDLINE]

883. Lancet Infect Dis. 2009 Dec;9(12):789-95.

Azole resistance in Aspergillus fumigatus: a side-effect of environmental fungicide use?

Verweij PE, Snelders E, Kema GH, Mellado E, Melchers WJ.

Department of Medical Microbiology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands. p.verweij@mmb.umcn.nl

Invasive aspergillosis due to multi-azole-resistant Aspergillus fumigatus has emerged in the Netherlands since 1999, with 6.0-12.8% of patients harbouring resistant isolates. The presence of a single resistance mechanism (denoted by TR/L98H), which consists of a substitution at codon 98 of cyp51A and a 34-bp tandem repeat in the gene-promoter region, was found in over 90% of clinical A fumigatus isolates. This is consistent with a route of resistance development through exposure to azole compounds in the environment. Indeed, TR/L98H A fumigatus isolates were cultured from soil and compost, were shown to be cross-resistant to azole fungicides, and genetically related to clinical resistant isolates. Azoles are abundantly used in the environment and the presence of A fumigatus resistant to medical triazoles is a major challenge because of the possibility of worldwide spread of resistant isolates. Reports of TR/L98H in other European countries indicate that resistance might already be spreading.

PMID: 19926038 [PubMed - indexed for MEDLINE]

884. PLoS One. 2009 Nov 18;4(11):e7792.

SMF-1, SMF-2 and SMF-3 DMT1 orthologues regulate and are regulated differentially by manganese levels in C. elegans.

Au C, Benedetto A, Anderson J, Labrousse A, Erikson K, Ewbank JJ, Aschner M.

Department of Pediatrics, Vanderbilt University, Nashville, Tennessee, USA.

Manganese (Mn) is an essential metal that can exert toxic effects at high concentrations, eventually leading to Parkinsonism. A major transporter of Mn in mammals is the divalent-metal transporter (DMT1). We characterize here DMT1-like proteins in the nematode C. elegans, which regulate and are regulated by Mn and iron (Fe) content. We identified three new DMT1-like genes in C. elegans: smf-1, smf-2 and smf-3. All three can functionally substitute for loss of their yeast orthologues in S. cerevisiae. In the worm, deletion of smf-1 or smf-3 led to an increased Mn tolerance, while loss of smf-2 led to increased Mn sensitivity. smf mRNA levels measured by QRT-PCR were up-regulated upon low Mn and down-regulated upon high Mn exposures. Translational GFP-fusions revealed that SMF-1 and SMF-3 strongly localize to partially overlapping apical regions of the gut epithelium, suggesting a differential role for SMF-1 and SMF-3 in Mn nutritional intake. Conversely, SMF-2 was detected in the marginal pharyngeal epithelium, possibly involved in metal-sensing. Analysis of metal content upon Mn exposure in smf mutants revealed that SMF-3 is required for normal Mn uptake, while smf-1 was dispensable. Higher smf-2 mRNA levels correlated with higher Fe content, supporting a role for SMF-2 in Fe uptake. In smf-1 and smf-3 but not in smf-2 mutants, increased Mn exposure led to decreased Fe levels, suggesting that both metals compete for transport by SMF-2. Finally, SMF-3 was post-translationally and reversibly down-regulated following Mn-exposure. In sum, we unraveled a complex interplay of transcriptional and post-translational regulations of 3 DMT1-like transporters in two adjacent tissues, which regulate metal-content in C. elegans.

PMCID: PMC2773845 PMID: 19924247 [PubMed - indexed for MEDLINE]

885. Environ Sci Technol. 2009 Oct 15;43(20):7762-9.

Spatial modeling of PAHs in lichens for fingerprinting of multisource atmospheric pollution.

Augusto S, Máguas C, Matos J, Pereira MJ, Soares A, Branquinho C.

Faculty of Sciences, Centre for Environmental Biology (CBA), University of Lisbon, FCUL, Lisboa, Portugal.

PAHs are toxic compounds emitted by several anthropogenic sources, which have a great impact on human health. We show, for the first time, how spatial models based on PAHs intercepted by lichens can be used for fingerprinting multisource atmospheric pollution in a regional area. Urban-industrial areas showed the highest atmospheric deposition of PAHs followed by urban > industrial > agricultural > forest Multivariate analysis of lichen data showed, for the first time, a clear distinction between various sources of PAHs in the same area: urban are dominated by 4-ring PAHs, forest by 3-ring PAHs, and industrial by 5- and 6-ring PAHs or by 2-ring PAHs (petrogenic or pyrogenic, respectively). Heavy metals were also used for supporting the fingerprinting of PAH sources, reinforcing the industrial origin of 5- and 6-ring PAHs and revealing their particular nature. The spatial structure of the models for different PAHs seems to be dependent on the following factors: size and hydrophilic character of different PAHs, type of emission sources (point or nonpoint), and dispersion associated with particulates of different sizes. Based on the long-term integration of PAHs in lichens, these spatial models will significantly improve our knowledge on the impact of PAH chronic-exposure to humans and ecosystems.

PMID: 19921891 [PubMed - indexed for MEDLINE]

886. Int Arch Occup Environ Health. 2010 Jan;83(1):9-19. Epub 2009 Nov 17.

Exposure to poultry dust and health effects in poultry workers: impact of mould and mite allergens.

Rimac D, Macan J, Varnai VM, Vucemilo M, Matković K, Prester L, Orct T, Trosić I, Pavicić I.

Institute for Medical Research and Occupational Health, Ksaverska cesta 2, 10000, Zagreb, Croatia.

PURPOSE: The aim of the study was to evaluate exposure to moulds and house dust mite Dermatophagoides pteronyssinus in poultry farms, and related health effects in poultry workers (PW).
METHODS: The study involved 41 PW and 45 control office workers. Working environment was evaluated for D. pteronyssinus allergen (Der p 1), moulds and endotoxin. In workers, eye, skin and respiratory symptoms, ventilatory lung function, atopy markers (skin prick test to inhalatory allergens, total IgE) and specific IgG to moulds were assessed.
RESULTS: Der p 1 levels ranged <0.1-3.3 microg/g, exposure to fungi was 4.9 x 10(3)-6.8 x 10(4) cfu/m(3), with prevailing Aspergillus, Penicillium and Mucor species, and endotoxin levels ranged 230-284 EU/m(3). In comparison to control subjects, significantly higher prevalence of work-related nose, asthma, eye and skin symptoms, and slight decline in ventilatory lung function was found in PW. PW had significantly higher prevalence of IgG antibodies to moulds comparing to controls (63 vs. 36%, respectively, P = 0.01), especially to Alternaria and Aspergillus species. The prevalence of atopy markers in PW was lower than in population-based studies.
CONCLUSIONS: Hazardous levels of Der p 1, endotoxin and moulds were determined in poultry houses. High prevalence of work-related symptoms and IgG antibodies to moulds was found in PW. Healthy worker effect is proposed as an explanation of low atopy markers prevalence among PW.

PMID: 19921239 [PubMed - indexed for MEDLINE]

887. J Immunotoxicol. 2010 Mar;7(1):57-67.

Maternal respiratory sensitization and gestational allergen exposure does not affect subsequent pup responses to homologous or heterologous allergen.

Pucheu-Haston CM, Copeland LB, Haykal-Coates N, Ward MD.

Curriculum in Toxicology, University of North Carolina-Chapel Hill, Chapel Hill, NC 27711, USA.

Evidence suggests that the predisposition towards atopy begins early in life. Maternal allergy has been associated with an increased risk of the development of allergic disease in offspring. Some studies suggest that the development of childhood atopy may also be influenced by prenatal allergen exposure. In this study, a respiratory allergen exposure model was used to determine the impact of maternal sensitization (with or without additional exposures during pregnancy) on subsequent pup responses to homologous or heterologous allergen. Female BALB/c mice received two intratracheal aspiration (IA) exposures to Metarhizium anisopliae crude antigen (MACA) or Hank's buffered salt solution (HBSS) prior to breeding. Some mice also received three additional exposures during pregnancy. Control mothers did not receive treatment. Young adult offspring received three IA exposures to MACA, house dust mite extract (HDM) or HBSS. Offspring sensitized as young adults to either HDM or MACA developed an airway inflammatory response, including increased bronchoalveolar lavage fluid lactate dehydrogenase activity, total protein and total and differential cell counts compared to offspring exposed to HBSS. Increased airway responsiveness to methacholine was observed in pups treated with HDM but not with MACA. Maternal sensitization status (with or without gestational allergen exposure) had no effect on offspring response to either MACA or HDM. In conclusion, this study demonstrates that IA administration of MACA or HDM extract to young adult BALB/c mice induces the development of an inflammatory airway response. In contrast to previous reports, neither maternal sensitization nor gestational allergen exposure could be demonstrated to have a clear effect on offspring sensitization. This discrepancy may be a function of the respiratory sensitization and exposure protocol used in this study, which mimics natural sensitization more closely than do parenteral routes of exposure.

PMID: 19916739 [PubMed - indexed for MEDLINE]

888. Am J Infect Control. 2010 Mar;38(2):130-8. Epub 2009 Nov 12.

Bloodborne pathogen risk reduction activities in the body piercing and tattooing industry.

Lehman EJ, Huy J, Levy E, Viet SM, Mobley A, McCleery TZ.

National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Cincinnati, OH 45226, USA. Elehman@cdc.gov

BACKGROUND: This study examines how well regulations for bloodborne pathogens (BBPs), established primarily to reduce exposure risk for health care workers, are being followed by workers and employers in the tattooing and body piercing industry. METHOD: Twelve shops performing tattooing and/or body piercing (body art) in Pennsylvania and Texas were assessed for compliance with 5 administrative and 10 infection control standards for reducing exposure to BBPs.
RESULTS: All shops demonstrated compliance with infection control standards, but not with administrative standards, such as maintaining an exposure control plan, offering hepatitis B vaccine, and training staff. Shops staffed with members of professional body art organizations demonstrated higher compliance with the administrative standards. Shops in locations where the body art industry was regulated and shops in nonregulated locations demonstrated similar compliance, as did contractor- and employee-staffed shops.
CONCLUSIONS: Regulations to control occupational exposure to BBPs have been in place since 1991. This study corroborates noncompliance with some standards within the body art industry reported by previous studies. Without notable enforcement, regulation at national, state, or local levels does not affect compliance. In this study, the factor most closely associated with compliance with administrative regulations was the artist's membership in a professional body art association.

Published by Mosby, Inc.

PMID: 19913330 [PubMed - indexed for MEDLINE]

889. DNA Repair (Amst). 2010 Jan 2;9(1):96-100. Epub 2009 Nov 11.

A mutation-promotive role of nucleotide excision repair in cell cycle-arrested cell populations following UV irradiation.

Heidenreich E, Eisler H, Lengheimer T, Dorninger P, Steinboeck F.

Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Borschkegasse 8a, Vienna, Austria. erich.heidenreich@meduniwien.ac.at

Growing attention is paid to the concept that mutations arising in stationary, non-proliferating cell populations considerably contribute to evolution, aging, and pathogenesis. If such mutations are beneficial to the affected cell, in the sense of allowing a restart of proliferation, they are called adaptive mutations. In order to identify cellular processes responsible for adaptive mutagenesis in eukaryotes, we study frameshift mutations occurring during auxotrophy-caused cell cycle arrest in the model organism Saccharomyces cerevisiae. Previous work has shown that an exposure of cells to UV irradiation during prolonged cell cycle arrest resulted in an increased incidence of mutations. In the present work, we determined the influence of defects in the nucleotide excision repair (NER) pathway on the incidence of UV-induced adaptive mutations in stationary cells. The mutation frequency was decreased in Rad16-deficient cells and further decreased in Rad16/Rad26 double-deficient cells. A knockout of the RAD14 gene, the ortholog of the human XPA gene, even resulted in a nearly complete abolishment of UV-induced mutagenesis in cell cycle-arrested cells. Thus, the NER pathway, responsible for a normally accurate repair of UV-induced DNA damage, paradoxically is required for the generation and/or fixation of UV-induced frameshift mutations specifically in non-replicating cells.

PMID: 19910266 [PubMed - indexed for MEDLINE]

890. J Nanosci Nanotechnol. 2009 Oct;9(10):5738-44.

Biosynthesis of size-controlled gold nanoparticles using fungus, Penicillium sp.

Zhang X, He X, Wang K, Wang Y, Li H, Tan W.

State Key Laboratory of Chemo/Biosensing and Chemometrics, Biomedical Engineering Center, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, China.

The unique optoelectronic and physicochemical properties of gold nanoparticles are significantly dependent on the particle size, shape and structure. In this paper, biosynthesis of size-controlled gold nanoparticles using fungus Penicillium sp. is reported. Fungus Penicillium sp. could successfully bioreduce and nucleate AuCl4(-) ions, and lead to the assembly and formation of intracellular Au nanoparticles with spherical morphology and good monodispersity after exposure to HAuCl4 solution. Reaction temperature, as an important physiological parameter for fungus Penicillium sp. growth, could significantly control the size of the biosynthesized Au nanoparticles. The biological compositions and FTIR spectra analysis of fungus Penicillium sp. exposed to HAuCl4 solution indicated the intracellular reducing sugar played an important role in the occurrence of intracellular reduction of AuCl4(-) ions and the growth of gold nanoparticles. Furthermore, the intracellular gold nanoparticles could be easily separated from the fungal cell lysate by ultrasonication and centrifugation.

PMID: 19908446 [PubMed - indexed for MEDLINE]

891. World J Gastroenterol. 2009 Nov 14;15(42):5249-59.

Potential role of chitinase 3-like-1 in inflammation-associated carcinogenic changes of epithelial cells.

Eurich K, Segawa M, Toei-Shimizu S, Mizoguchi E.

The family of mammalian chitinases includes members both with and without glycohydrolase enzymatic activity against chitin, a polymer of N-acetylglucosamine. Chitin is the structural component of fungi, crustaceans, insects and parasitic nematodes, but is completely absent in mammals. Exposure to antigens containing chitin- or chitin-like structures sometimes induces strong T helper type-I responses in mammals, which may be associated with the induction of mammalian chitinases. Chitinase 3-like-1 (CHI3L1), a member of the mammalian chitinase family, is induced specifically during the course of inflammation in such disorders as inflammatory bowel disease, hepatitis and asthma. In addition, CHI3L1 is expressed and secreted by several types of solid tumors including glioblastoma, colon cancer, breast cancer and malignant melanoma. Although the exact function of CHI3L1 in inflammation and cancer is still largely unknown, CHI3L1 plays a pivotal role in exacerbating the inflammatory processes and in promoting angiogenesis and remodeling of the extracellular matrix. CHI3L1 may be highly involved in the chronic engagement of inflammation which potentiates development of epithelial tumorigenesis presumably by activating the mitogen-activated protein kinase and the protein kinase B signaling pathways. Anti-CHI3L1 antibodies or pan-chitinase inhibitors may have the potential to suppress CHI3L1-mediated chronic inflammation and the subsequent carcinogenic change in epithelial cells.

PMCID: PMC2776850 PMID: 19908331 [PubMed - indexed for MEDLINE]

892. Nutr Rev. 2009 Nov;67 Suppl 2:S152-63.

Role of nutrients in the development of neonatal immune response.

Cunningham-Rundles S, Lin H, Ho-Lin D, Dnistrian A, Cassileth BR, Perlman JM.

Division of Hematology/Oncology, Host Defenses Program, Department of Pediatrics, Weill Medical College of Cornell University, New York, New York, USA. scrundle@mail.med.cornell.edu

Nutrients exert unique regulatory effects in the perinatal period that mold the developing immune system. The interactions of micronutrients and microbial and environmental antigens condition the post-birth maturation of the immune system, influencing reactions to allergens, fostering tolerance towards the emerging gastrointestinal flora and ingested antigens, and defining patterns of host defense against potential pathogens. The shared molecular structures that are present on microbes or certain plants, but not expressed by human cells, are recognized by neonatal innate immune receptors. Exposure to these activators in the environment through dietary intake in early life can modify the immune response to allergens and prime the adaptive immune response towards pathogens that express the corresponding molecular structures.

PMID: 19906219 [PubMed - indexed for MEDLINE]

893. Environ Monit Assess. 2010 Nov;170(1-4):331-43. Epub 2009 Nov 11.

Exposure assessment in Beijing, China: biological agents, ultrafine particles, and lead.

Dong S, Yao M.

State Key Joint Laboratory of Environmental Simulation and Pollution Control, College of Environmental Sciences and Engineering, Peking University, Beijing, 100871, China.

In this study, air samples were taken using a BioSampler and gelatin filters from six sites in Beijing: office, hospital, student dormitory, train station, subway, and a commercial street. Dust samples were also collected using a surface sampler from the same environments. Limulus amoebocyte lysate (LAL) and Glucatell assays were used to quantify sample endotoxin and (1,3)-β-d-glucan concentration levels, respectively. Enzyme-linked immunosorbent assay (ELISA) was used to measure the dust mite allergens (Der p 1 and Der f 1). Ultrafine particle and lead concentrations in these sampling sites were also measured using P-Trak and atomic absorption spectrometer, respectively. Analysis of variance (ANOVA) and linear regression analysis were used to analyze the concentration data. Higher culturable bacteria (12,639 CFU/m3) and fungi (1,806 CFU/m3) concentrations were observed for the train station and the subway system, respectively. For the rest of sampling sites, their concentrations were comparable to those found in western countries, ranging from 990 to 2,276 CFU/m3 for bacteria, and from 119 to 269 CFU/m3 for fungi. ANOVA analysis indicated that there were statistically significant differences between the culturable bacterial and fungal concentration levels obtained for different sites (p value=0.0001 and 0.0047). As for dust allergens, endotoxin, and (1,3)-β-D-glucan, their concentrations also seemed to be comparable to those found in the developed countries. Airborne allergen concentrations ranged from 16 to 68 ng/m3. The dust-borne allergen concentration was observed to range from 0.063 to 0.327 ng/mg. As for endotoxin, the highest airborne concentration of 25.24 ng/m3 was observed for the commercial street, and others ranged from 0.0427 to 0.1259 ng/m3. And dust-borne endotoxin concentration ranged from 58.83 to 6,427.4 ng/mg. For (1,3)-β-D-glucan, the airborne concentration ranged from 0.02 to 1.2 ng/m3. Linear regression analyses showed that there existed poor correlations between those in airborne and dust-borne states (R2=0.002~0.43). In our study, the lowest ultrafine particle concentration about 5,203 pt/cm3 was observed in office and the highest was observed at the train station, up to 32,783 pt/cm3. Lead concentration was shown to range from 80 to 170 ng/mg with the highest also observed at the train station. The information provided in this work can be used to learn the general situation of relevant health risks in Beijing. And the results here suggested that when characterizing exposure both airborne and dust-borne as well as the environments should be considered.

PMID: 19904623 [PubMed - indexed for MEDLINE]

894. Int J Food Microbiol. 2010 Jan 1;136(3):304-9. Epub 2009 Oct 17.

Activity of natural compounds on Fusarium verticillioides and fumonisin production in stored maize kernels.

Menniti AM, Gregori R, Neri F.

Department of Protection and Improvement of Agricultural Food Products, Alma Mater Studiorum, University of Bologna, Viale Fanin 46, Bologna 40127, Italy. annamaria.menniti@unibo.it

The ability of trans-2-hexenal, carvacrol and eugenol to control F. verticillioides was explored in vitro and in artificially infected kernels. The effect of the trans-2-hexenal fumigation on F. verticillioides control, fumonisin production and kernel germination was also investigated in naturally infected kernels. Trans-2-hexenal, carvacrol and eugenol vapour showed fungicidal activity against F. verticillioides, in in vitro trials. Trans-2-hexenal was the best pathogen inhibitor, followed by carvacrol and eugenol. In maize kernels, fumigations with trans-2-hexenal provided a high inhibitory effect on F. verticillioides growth and its efficacy depended on concentration and time of incubation. The most effective dose of trans-2-hexenal was 369 microL/L, but this concentration induced off-odour in maize. The exposure to 246 microL/L trans-2-hexenal provided the best control of F. verticillioides and no phytotoxic symptoms or off-odour in kernels was observed. In contrast trans-2-hexenal fumigations were ineffective in the reduction of fumonisin concentration and high concentration (369 microL/L) stimulated fumonisin levels. Reduction or delay in the germinability of the kernel was observed after trans-2-hexenal exposure. The results showed that trans-2-hexenal postharvest fumigation is effective in F. verticillioides control also in asymptomatic maize kernels, but cannot reduce fumonisin production.

PMID: 19892426 [PubMed - indexed for MEDLINE]

895. Am J Public Health. 2009 Nov;99 Suppl 3:S710-7.

Sharps injuries and other blood and body fluid exposures among home health care nurses and aides.

Quinn MM, Markkanen PK, Galligan CJ, Kriebel D, Chalupka SM, Kim H, Gore RJ, Sama SR, Laramie AK, Davis L.

Department of Work Environment, University of Massachusetts Lowell, 1 University Ave, Lowell, MA 01854, USA. margaret_quinn@uml.edu

OBJECTIVES: We quantified risks of sharp medical device (sharps) injuries and other blood and body fluid exposures among home health care nurses and aides, identified risk factors, assessed the use of sharps with safety features, and evaluated underreporting in workplace-based surveillance.
METHODS: We conducted a questionnaire survey and workplace-based surveillance, collaborating with 9 home health care agencies and 2 labor unions from 2006 to 2007.
RESULTS: Approximately 35% of nurses and 6.4% of aides had experienced at least 1 sharps injury during their home health care career; corresponding figures for other blood and body fluid exposures were 15.1% and 6.7%, respectively. Annual sharps injuries incidence rates were 5.1 per 100 full-time equivalent (FTE) nurses and 1.0 per 100 FTE aides. Medical procedures contributing to sharps injuries were injecting medications, administering fingersticks and heelsticks, and drawing blood. Other contributing factors were sharps disposal, contact with waste, and patient handling. Sharps with safety features frequently were not used. Underreporting of sharps injuries to the workplace-based surveillance system was estimated to be about 50%.
CONCLUSIONS: Sharps injuries and other blood and body fluid exposures are serious hazards for home health care nurses and aides. Improvements in hazard intervention are needed.

PMCID: PMC2774204 PMID: 19890177 [PubMed - indexed for MEDLINE]

896. Int J Antimicrob Agents. 2010 Jan;35(1):80-4. Epub 2009 Nov 4.

Characterising the post-antifungal effects of micafungin against Candida albicans, Candida glabrata, Candida parapsilosis and Candida krusei isolates.

Nguyen KT, Ta P, Hoang BT, Cheng S, Hao B, Nguyen MH, Clancy CJ.

Department of Medicine, University of Florida College of Medicine, Gainesville, FL, USA.

In this study, we measured time-kills and post-antifungal effects (PAFEs) for micafungin against Candida albicans (n=4), Candida glabrata (n=3), Candida parapsilosis (n=3) and Candida krusei (n=2) isolates and further characterised the PAFEs. Minimum inhibitory concentrations (MICs) were 0.5-1.0 mg/L against C. parapsilosis and 0.008-0.125 mg/L against the other species. Micafungin caused kills >1 log at 1 x MIC, 4 x MIC (range 1.19-3.10 log) and 16 x MIC (2.27-3.68 log), achieving fungicidal levels (> or = 3 log) against nine isolates. One-hour drug exposure during PAFE experiments resulted in kills of 0.73-2.88 log and 1.72-3.55 log at 4 x and 16 x MIC, respectively, achieving fungicidal levels against five isolates. Isolates of each species collected 8 h after a 1-h exposure to micafungin (4 x and 16 x MIC) were hypersusceptible to sodium dodecyl sulphate (SDS) and Calcofluor White. Cells tested during the PAFE period demonstrated cell wall disturbances as evident on electron micrographs as well as significant reductions in adherence to epithelial cells. Phagocytosis by J774 macrophages was significantly enhanced for three PAFE isolates tested. Micafungin is fungicidal and exerts PAFEs that kill diverse Candida spp., disturb cell walls of viable organisms, reduce adherence and enhance susceptibility to phagocytosis.

PMID: 19889519 [PubMed - indexed for MEDLINE]

897. Mol Microbiol. 2010 Jan;75(2):294-307. Epub 2009 Nov 2.

The antifungal protein PAF interferes with PKC/MPK and cAMP/PKA signalling of Aspergillus nidulans.

Binder U, Oberparleiter C, Meyer V, Marx F.

Biocenter, Division of Molecular Biology, Innsbruck Medical University, Innsbruck, Austria.

The Penicillium chrysogenum antifungal protein PAF inhibits polar growth and induces apoptosis in Aspergillus nidulans. We report here that two signalling cascades are implicated in its antifungal activity. PAF activates the cAMP/protein kinase A (Pka) signalling cascade. A pkaA deletion mutant exhibited reduced sensitivity towards PAF. This was substantiated by the use of pharmacological modulators: PAF aggravated the effect of the activator 8-Br-cAMP and partially relieved the repressive activity of caffeine. Furthermore, the Pkc/mitogen-activated protein kinase (Mpk) signalling cascade mediated basal resistance to PAF, which was independent of the small GTPase RhoA. Non-functional mutations of both genes resulted in hypersensitivity towards PAF. PAF did not increase MpkA phosphorylation or induce enzymes involved in the remodelling of the cell wall, which normally occurs in response to activators of the cell wall integrity pathway. Notably, PAF exposure resulted in actin gene repression and a deregulation of the chitin deposition at hyphal tips of A. nidulans, which offers an explanation for the morphological effects evoked by PAF and which could be attributed to the interconnection of the two signalling pathways. Thus, PAF represents an excellent tool to study signalling pathways in this model organism and to define potential fungal targets to develop new antifungals.

PMCID: PMC2814085 PMID: 19889092 [PubMed - indexed for MEDLINE]

898. Med Mycol. 2009 Nov;47(7):697-706.

Exposure to caspofungin activates Cap and Hog pathways in Candida albicans.

Kelly J, Rowan R, McCann M, Kavanagh K.

Medical Mycology Unit, Department of Biology, National Instiute for Cellular Biotechnology, NUI Maynooth, Co. Kildare, Ireland.

Caspofungin is a member of the echinocandin group of antifungals and inhibits the activity of beta-glucan synthase thus disrupting cell wall formation and function. While the potent antifungal activity of this agent is well established, this paper analyzed the response of Candida albicans to caspofungin. Exposure of yeast cells to 0.19 microg/ml caspofungin for 1 to 4 h induced nuclear translocation of Cap1p which was confirmed by Western blotting and confocal microscopy. Caspofungin-treated cells demonstrated increased expression of a number of genes associated with the oxidative stress response, including glutathione reductase (GLR1), mitochondrial processing protease (MAS1) and manganese-superoxide dismutase (SOD2) as well as elevated activity of glutathione reductase and superoxide dismutase. Caspofungin treatment also leads to the nuclear localization of Hog1p as visualized by Western blot using anti-phospho-p38 MAPK (Thr180/Tyr182) antibody. This translocation event lead to increased mRNA levels of catalase (CAT1) but not alkyl hydroperoxide reductase (AHP1). The activity of catalase was increased and reached a maximum at 2 h. In addition, pre-exposure of C. albicans to hydrogen peroxide (0.5 mM, 60 min) conferred an increased tolerance to caspofungin. The data presented here highlight the potent antifungal activity of caspofungin and demonstrate that upon exposure to this agent, C. albicans activates the Cap and Hog pathways in an attempt to limit the oxidative and osmotic stresses associated with this drug.

PMID: 19888802 [PubMed - indexed for MEDLINE]

899. J Appl Microbiol. 2010 Jun;108(6):1966-73. Epub 2009 Oct 20.

Antimicrobial efficiency of titanium dioxide-coated surfaces.

Muranyi P, Schraml C, Wunderlich J.

Fraunhofer Institute for Process Engineering and Packaging IVV, Freising, Germany. peter.muranyi@ivv.fraunhofer.de

AIMS: Development and evaluation of an antimicrobially active titanium dioxide coating. METHODS AND RESULTS: For this purpose, titanium dioxide coatings were applied to glass slides by using a sol-gel method and then exposed to a light source. The antimicrobial efficiency was determined by a count reduction test for selected test strains (Aspergillus niger, Bacillus atrophaeus, Kocuria rhizophila), which were homogenously sprayed onto surface. The bacterial count of K. rhizophila was reduced by up to 3.3 log(10) on titanium dioxide samples within 4 h of UV-A light exposure. Experiments with spore formers did not lead to any significant log reduction. A further aspect of this work was to evaluate the effect of selected parameters (relative humidity, inoculation density, radiation intensity) on the antimicrobial efficiency to gain knowledge for further optimization procedures. At a high relative humidity (85% r.h.), increased inactivation was observed for K. rhizophila (up to 5.2 log(10)). Furthermore, a dependency of the antimicrobial effect on the radiation intensity and the inoculation density was identified.
CONCLUSIONS: Antimicrobial surfaces and coatings based on titanium dioxide have the potential to effectively inactivate vegetative micro-organisms. SIGNIFICANCE AND IMPACT OF THE STUDY: Knowledge about the antimicrobial efficiency of titanium dioxide was gained. This is a prerequisite for industrial applications to improve hygiene, food quality and safety.

PMID: 19886892 [PubMed - indexed for MEDLINE]

900. J Econ Entomol. 2009 Oct;102(5):1759-66.

Evaluation of soyscreen in an oil-based formulation for UV protection of Beauveria bassiana conidia.

Behle RW, Compton DL, Laszlo JA, Shapiro-Ilan DI.

Crop Bioprotection Research Unit, USDA-ARS-NCAUR 1815 N. University Ave., Peoria, IL 61604, USA. robert.behle@ars.usda.gov

Soyscreen oil was studied as a formulation ingredient to protect Beauveria bassiana (Balsamo) Vuillemin conidia from UV degradation. Feruloylated soy glycerides, referred to as Soyscreen oil, are biobased UV-absorbing molecules made by combining molecules of soybean oil with ferulic acid. Conidia stored in Soyscreen oil for 28 wk at 25, 30, and 35 degrees C retained viability as well as conidia stored in sunflower oil, demonstrating that Soyscreen did not adversely affect viability with prolonged storage. For samples applied to glass and exposed to simulated sunlight (xenon light), conidia in sunflower oil with or without sunscreens (Soyscreen or oxyl methoxycinnimate) had similar conidia viability after exposure. These oil formulations retained conidia viability better than conidia applied as an aqueous treatment. However, the 10% Soyscreen oil formulation applied to field grown cabbage (Brassica oleracea L.) and bean (Phaseolus vulgaris L.) plants, did not improve residual insecticidal activity compared with aqueous applications of unformulated conidia or two commercial formulations when assayed against Trichoplusia ni (Hübner) larvae. Our results suggest that the oil applications lose UV protection because the oil was absorbed by the leaf. This conclusion was supported in subsequent laboratory exposures of conidia in oil-based formulations with UV screens applied to cabbage leaves or balsa wood, which lost protection as measured by decreased viability of conidia when exposed to simulated sunlight. As a result, additional formulation techniques such as encapsulation to prevent separation of the protective oil from the conidia may be required to extend protection when oil formulations are applied in the field.

PMID: 19886439 [PubMed - indexed for MEDLINE]

901. J Indian Med Assoc. 2009 May;107(5):300-2, 306-7.

National guidelines on management of occupational exposure to HIV.

Rewari BB, Negi S.

National AIDS Control Organisation, Ministry of Health and Family Welfare, Government of India, New Delhi.

During patient care, the healthcare personnel are at risk of infection of blood-borne pathogens (HIV, HBV, HCV) which is referred to as occupational exposure. Exposure to blood, semen, vaginal secretions, CSF, synovial, pleural, peritoneal, pericardial fluid, amniotic fluid and other body fluids contaminated with visible blood can lead to infection. Steps which are to be followed after occupational exposure are: (1) Step I : First aid following the exposure. (2) Step 2: Establish eligibility for postexposure prophylaxis (PEP). (3) Step 3: Counselling for PEP. (4) Step 4: Prescribe PEP. (5) HIV chemoprophylaxis. (6) Step 6: Follow-up of an exposed person. In order to get timely prophylactic therapy, PEP drugs should be kept available round-the-clock in at least three locations, casualty, ICU and labour room. Every hospital should have a written protocol and SOP for handling occupational exposure. NACO is in the process of launching a national HIV PEP Registry for capturing the cases of occupational exposure to HIV more effectively.

PMID: 19886385 [PubMed - indexed for MEDLINE]

902. Indian J Dent Res. 2009 Jul-Sep;20(3):308-12.

Effect of different light curing units on Knoop hardness and temperature of resin composite.

Guiraldo RD, Consani S, Xediek Consani RL, Mendes WB, Lympius T, Coelho Sinhoreti MA.

Pythagoras College, Belo Horizonte MG, Brazil. rickdanil@fop.unicamp.br

AIM: To evaluate the influence of quartz tungsten halogen and plasma arc curing (PAC) lights on Knoop hardness and change in polymerization temperature of resin composite. MATERIALS AND METHODS: Filtek Z250 and Esthet X composites were used in the shade A3. The temperature increase was registered with Type-k thermocouple connected to a digital thermometer (Iopetherm 46). A self-cured polymerized acrylic resin base was built in order to guide the thermocouple and to support the dentin disk of 1.0 mm thickness obtained from bovine tooth. On the acrylic resin base, elastomer mold of 2.0 mm was adapted. The temperature increase was measured after composite light curing. After 24 h, the specimens were submitted to Knoop hardness test (HMV-2000, Shimadzu, Tokyo, Japan). Data were submitted to ANOVA and Tukey's test (alpha = 0.05).
RESULTS: For both composites, there were no significant differences (P > 0.05) in the top surface hardness; however, PAC promoted statistically lower (P < 0.05) Knoop hardness number values in the bottom. The mean temperature increase showed no significant statistical differences (P > 0.05).
CONCLUSION: The standardized radiant exposure showed no influence on the temperature increase of the composite, however, showed significant effect on hardness values.

PMID: 19884714 [PubMed - indexed for MEDLINE]

903. Mol Cell Biol. 2010 Jan;30(1):131-45.

Dephosphorylation of gamma H2A by Glc7/protein phosphatase 1 promotes recovery from inhibition of DNA replication.

Bazzi M, Mantiero D, Trovesi C, Lucchini G, Longhese MP.

Dipartimento di Biotecnologie e Bioscienze, Università degli Studi di Milano-Bicocca, Milan, Italy.

Replication fork stalling caused by deoxynucleotide depletion triggers Rad53 phosphorylation and subsequent checkpoint activation, which in turn play a crucial role in maintaining functional DNA replication forks. How cells regulate checkpoint deactivation after inhibition of DNA replication is poorly understood. Here, we show that the budding yeast protein phosphatase Glc7/protein phosphatase 1 (PP1) promotes disappearance of phosphorylated Rad53 and recovery from replication fork stalling caused by the deoxynucleoside triphosphate (dNTP) synthesis inhibitor hydroxyurea (HU). Glc7 is also required for recovery from a double-strand break-induced checkpoint, while it is dispensable for checkpoint inactivation during methylmethane sulfonate exposure, which instead requires the protein phosphatases Pph3, Ptc2, and Ptc3. Furthermore, Glc7 counteracts in vivo histone H2A phosphorylation on serine 129 (gamma H2A) and dephosphorylates gamma H2A in vitro. Finally, the replication recovery defects of HU-treated glc7 mutants are partially rescued by Rad53 inactivation or lack of gamma H2A formation, and the latter also counteracts hyperphosphorylated Rad53 accumulation. We therefore propose that Glc7 activity promotes recovery from replication fork stalling caused by dNTP depletion and that gamma H2A dephosphorylation is a critical Glc7 function in this process.

PMCID: PMC2798293 PMID: 19884341 [PubMed - indexed for MEDLINE]

904. Nihon Kokyuki Gakkai Zasshi. 2009 Oct;47(10):881-9.

[Hypersensitivity pneumonitis induced by Hypsizigus marumoreus].

[Article in Japanese]

Takaku Y, Takayanagi N, Minagawa S, Tsuchiya Y, Hijikata N, Hara K, Yamaji T, Tokunaga D, Saito H, Ubukata M, Kurashima K, Yanagisawa T, Sugita Y, Kawabata Y.

Department of Respiratory Medicine, Saitama Cardiovascular and Respiratory Center.

We present the case of a 53-year-old woman who was employed at a mushroom (Pleurotus eryngii and Hypsizigus marumoreus) cultivation factory for 15 years. She was admitted to our hospital because of fever and dry cough. Chest radiography and CT scanning revealed diffuse ground glass opacity and centrilobular nodules in both lung fields. Serum KL-6 was elevated. In the bronchoalveolar lavage fluid, the CD4/CD8 ratio was reduced, and the lymphocyte fraction was very high. Transbronchial lung biopsy specimens showed lymphocyte alveolitis. After admission, the patient's symptoms improved rapidly without medication. Although these findings are compatible with hypersensitivity pneumonitis, it was difficult to identify a causative antigen. Serum antibody against Trichosporon was positive. A lymphocyte stimulation test of the peripheral blood was positive against extracts of P. eryngii and H. marumoreus. Furthermore, precipitins against the extracts of H. marumoreus were detected by a double immunodiffusion test. Therefore, we decided to conduct a challenge test using H. marumoreus. As an inhalation provocation test with H. marumoreus conducted in a sickroom caused the same clinical symptoms and signs as experienced in the workplace, we diagnosed hypersensitivity pneumonitis caused by H. marumoreus. A provocation test, in which antigen exposure is limited using a closed space, such as a sickroom, was simple, safe and effective for determining the antigen causing hypersensitivity pneumonitis.

PMID: 19882910 [PubMed - indexed for MEDLINE]

905. Eukaryot Cell. 2010 Jan;9(1):194-207. Epub 2009 Oct 30.

Role of mitogen-activated protein kinase Sty1 in regulation of eukaryotic initiation factor 2alpha kinases in response to environmental stress in Schizosaccharomyces pombe.

Berlanga JJ, Rivero D, Martín R, Herrero S, Moreno S, de Haro C.

Centro de Biología Molecular Severo Ochoa, CSIC-UAM, 28049 Madrid, Spain.

The mitogen-activated protein kinase (MAPK) Sty1 is essential for the regulation of transcriptional responses that promote cell survival in response to different types of environmental stimuli in Schizosaccharomyces pombe. In fission yeast, three distinct eukaryotic initiation factor 2alpha (eIF2alpha) kinases, two mammalian HRI-related protein kinases (Hri1 and Hri2) and the Gcn2 ortholog, regulate protein synthesis in response to cellular stress conditions. In this study, we demonstrate that both Hri1 and Hri2 exhibited an autokinase activity, specifically phosphorylated eIF2alpha, and functionally replaced the endogenous Saccharomyces cerevisiae Gcn2. We further show that Gcn2, but not Hri1 or Hri2, is activated early after exposure to hydrogen peroxide and methyl methanesulfonate (MMS). Cells lacking Gcn2 exhibit a later activation of Hri2. The activated MAPK Sty1 negatively regulates Gcn2 and Hri2 activities under oxidative stress but not in response to MMS. In contrast, Hri2 is the primary activated eIF2alpha kinase in response to heat shock. In this case, the activation of Sty1 appears to be transitory and does not contribute to the modulation of the eIF2alpha kinase stress pathway. In strains lacking Hri2, a type 2A protein phosphatase is activated soon after heat shock to reduce eIF2alpha phosphorylation. Finally, the MAPK Sty1, but not the eIF2alpha kinases, is essential for survival upon oxidative stress or heat shock, but not upon MMS treatment. These findings point to a regulatory coordination between the Sty1 MAPK and eIF2alpha kinase pathways for a particular range of stress responses.

PMCID: PMC2805304 PMID: 19880757 [PubMed - indexed for MEDLINE]

906. Transfus Clin Biol. 2009 Nov-Dec;16(5-6):482-8. Epub 2009 Oct 31.

[Genetic diversity of human erythroviruses. Consequences on infectious safety of plasma derivatives].

[Article in French]

Servant-Delmas A, Mercier M, Laperche S, Lefrère JJ.

Département des agents transmissibles par le sang, Institut national de la transfusion sanguine, 6, rue Alexandre-Cabanel, 75015 Paris, France. aservant@ints.fr

The B19 Parvovirus (B19V) has for a long time been considered as the unique human virus belonging to the genus Erythrovirus. The genetic diversity of B19V isolates has been shown to be very low. The isolation of a variant (V9 strain), with a sequence markedly distinct from that of B19V which led to attributing this classification to this family of viruses. Phylogenetic analysis of sequences of V9-related isolates indicates an organization into three well-individualized genotypes. The B19V infection can be transmitted by transfusion. In immunocompetent recipients, B19V exposure by transfusion is most often inconsequential, since a large proportion is immunized. Such an infection may have serious clinical outcome in not immunized patients with shortened red cell survival, seronegative pregnant women and immunocompromised patients. In cellular products, viral DNA detection is not performed, but a preventive strategy could be discussed for at-risk recipients. Whereas in plasma derivatives, B19V screening is performed with a threshold of 10(4)IU/ml using molecular assays. With recent data of a new classification of three genotypes within human erythrovirus, nucleic acid testing assays would be validated in accordance with the genetic variability, in order to guarantee optimal safety. Recently, a new human parvovirus (PARV4) has been discovered. The consequences on blood transfusion of this blood-borne agent and its pathogenicity are still unknown.

PMID: 19880339 [PubMed - indexed for MEDLINE]

907. J Dtsch Dermatol Ges. 2010 Sep;8(9):718-24. Epub 2009 Oct 29.

Allergy prevention.

[Article in English, German]

Muche-Borowski C, Kopp M, Reese I, Sitter H, Werfel T, Schäfer T; German Society for Allergology and Clinical Immunology (DGAKI); Society of German Allergologists (ADA); German Society for Pediatric and Adolescent Medicine (DGKJ); German Society of Dermatology (DDG); German Society of Pediatric Allergology (GPA).

Collaborators: Beyer K, Friedrichs F, Hamelmann E, Hellermann M, Huss-Marp J, Lau S, Rietschel E, Schmidt S, Schnadt S, Kleinheinz A, Rudack C, Schnitzer S.

Guideline of the German Society for Allergology and Clinical Immunology (DGAKI) in cooperation with the Society of German Allergologists (ADA), the German Society for Pediatric and Adolescent Medicine (DGKJ), the German Society of Dermatology (DDG) and the German Society of Pediatric Allergology (GPA).

The further increase of allergies in industrialized countries demands evidence-based measures of primary prevention. The recommendations as published in the guideline of 2004 were updated and consented on the basis of a systematic literature search. Evidence from the period February 2003-May 2008 was searched in the electronic databases Cochrane and MEDLINE as well as in reference lists of recent reviews and by contacting experts. The retrieved citations were screened for relevance first by title and abstract and in a second step as full paper. Levels of evidence were assigned to each included study and the methodological quality of the studies was assessed as high or low. Finally the revised recommendations were formally consented (nominal group process) by representatives of relevant societies and organizations including a self-help group. Of originally 4556 hits, 217 studies (4 Cochrane Reviews, 14 meta-analyses, 19 randomized controlled trials, 135 cohort and 45 case-control studies) were included and critically appraised. Grossly unchanged remained the recommendations on avoiding environmental tobacco smoke, breast-feeding over 4 months (alternatively hypoallergenic formulas for children at risk), avoiding a mold-promoting indoor climate, vaccination according to current recommendations, and avoidance of furry pets (especially cats) in children at risk. The recommendation on reducing the house dust mite allergen exposure as a measure of primary prevention was omitted and the impact of a delayed introduction of supplementary food was reduced. New recommendations were adopted concerning fish consumption (during pregnancy / breast-feeding and as supplementary food in the first year), avoidance of overweight, and reducing the exposure to indoor and outdoor air pollutants. The revision of this guideline on a profound evidence basis led to (1) a confirmation of existing recommendations, (2) substantial revisions, and (3) new recommendations. Thereby it is possible to give evidence-based and up-to-date recommendations on primary prevention of allergies.

PMID: 19878402 [PubMed - indexed for MEDLINE]

908. Langmuir. 2009 Dec 1;25(23):13298-301.

Nanopatterning from the gas phase: high resolution soft lithographic patterning of organosilane thin films.

George A, Blank DH, ten Elshof JE.

Inorganic Materials Science Group, MESA+ Institute for Nanotechnology, University of Twente, P.O. Box 217, Enschede, The Netherlands.

A general methodology for nanopatterning organosilane thin films directly from vapor phase precursors is presented. Aminosilane line patterns with a width of approximately 200 nm in an area of 1 cm(2) were fabricated on silicon substrates by diffusion of aminosilane vapor through the open channels of PDMS stamps bonded to a substrate. The patterned thin films were characterized by atomic force microscopy (AFM) and X-ray photoelectron spectroscopy (XPS). Patterns were initially formed at the three-phase boundary lines between substrate, PDMS mold, and vapor by exploiting the fact that vapors condense preferentially in geometrically restricted areas with a concave shape compared to flat surfaces. The lateral resolution of the formed patterns is about 1 order of magnitude smaller than the feature sizes of the PDMS stamp. Prolonged exposure to the precursor vapor resulted in micrometer-sized patterns with similar features and dimensions as the stamp. This methodology provides an easy and low cost parallel fabrication route of functional organosilane nanoscale patterns of arbitrary shape and composition from micrometer-size patterned stamps.

PMID: 19877700 [PubMed]

909. Mycopathologia. 2010 Mar;169(3):183-91. Epub 2009 Oct 30.

Sodium choleate (NaCho) effects on Candida albicans: implications for its role as a gastrointestinal tract inhabitant.

Vu B, Essmann M, Larsen B.

Drake University, Des Moines, IA, USA.

Candida albicans at times resides in the intestinal tract, where it experiences exposure to bile salts suggesting a study of the effects of crude bile salts in the form of sodium choleate (NaCho) on C. albicans growth, expression of virulent phenotypes, and adaptation to physiological challenges in vitro. Growth and phenotype alteration was examined by challenging clinical isolates of C. albicans with a wide range of NaCho concentrations by using conventional microbial physiology methods. Our results showed that (1) NaCho did not inhibit growth of yeast cells, up to 40 mg/ml; (2) NaCho powerfully stimulated the hypha formation; (3) NaCho at 2.5 and 5 mg/ml significantly induced CDR1p and biofilm formation, but these effects decreased at higher NaCho concentrations; (4) loss of cell integrity with exposure to 56 degrees C for 15 min, was exacerbated by increasing levels of NaCho; (5) NaCho protected yeast from hydrogen peroxide damage in a dose-dependent manner; and (6) catalase activity was increased by NaCho exposure.

PMID: 19876762 [PubMed - indexed for MEDLINE]

910. PLoS Genet. 2009 Oct;5(10):e1000705. Epub 2009 Oct 30.

Acquisition of aneuploidy provides increased fitness during the evolution of antifungal drug resistance.

Selmecki AM, Dulmage K, Cowen LE, Anderson JB, Berman J.

Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota, USA.

The evolution of drug resistance is an important process that affects clinical outcomes. Resistance to fluconazole, the most widely used antifungal, is often associated with acquired aneuploidy. Here we provide a longitudinal study of the prevalence and dynamics of gross chromosomal rearrangements, including aneuploidy, in the presence and absence of fluconazole during a well-controlled in vitro evolution experiment using Candida albicans, the most prevalent human fungal pathogen. While no aneuploidy was detected in any of the no-drug control populations, in all fluconazole-treated populations analyzed an isochromosome 5L [i(5L)] appeared soon after drug exposure. This isochromosome was associated with increased fitness in the presence of drug and, over time, became fixed in independent populations. In two separate cases, larger supernumerary chromosomes composed of i(5L) attached to an intact chromosome or chromosome fragment formed during exposure to the drug. Other aneuploidies, particularly trisomies of the smaller chromosomes (Chr3-7), appeared throughout the evolution experiment, and the accumulation of multiple aneuploid chromosomes per cell coincided with the highest resistance to fluconazole. Unlike the case in many other organisms, some isolates carrying i(5L) exhibited improved fitness in the presence, as well as in the absence, of fluconazole. The early appearance of aneuploidy is consistent with a model in which C. albicans becomes more permissive of chromosome rearrangements and segregation defects in the presence of fluconazole.

PMCID: PMC2760147 PMID: 19876375 [PubMed - indexed for MEDLINE]

911. Curr Opin Pulm Med. 2010 Jan;16(1):36-41.

The utility of antifungal agents for asthma.

Gore RB.

The University of Manchester, Manchester Academic Health Science Centre, University Hospitals of South Manchester NHS Foundation Trust, Manchester, UK. robin.gore@manchester.ac.uk

PURPOSE OF REVIEW: Recent work demonstrates that patients with refractory asthma are likely to be sensitized to environmental fungi and that specific antifungal treatments may be of benefit to this group.
RECENT FINDINGS: The relationships among fungal sensitization, exposure and asthma severity are imperfectly understood. Exposure to environmental fungi occurs ubiquitously and there is emerging evidence that internal airways colonization could be a source of ongoing exposure. Antifungal treatments appear to improve asthma-related quality of life. Such treatments are generally well tolerated but there are potential side-effects. The mechanisms behind the clinical improvements are not yet fully established. SUMMARY: Antifungal treatments are used in some centres for patients with refractory asthma. Further research needs to explore the questions of patient selection, optimum duration of therapy and the prediction and management of azole-corticosteroid drug interactions. Advances in our understanding of the fungal molecular allergome and in our understanding of the allergic importance of small hyphal fragments may help to more precisely define the relationships among fungal sensitization, exposure and asthma severity.

PMID: 19875960 [PubMed - indexed for MEDLINE]

912. J Environ Qual. 2009 Oct 29;38(6):2267-72. Print 2009 Nov-Dec.

Nitrogen deposition effects on carbon storage and fungal:bacterial ratios in coastal sage scrub soils of southern California.

Liu K, Crowley D.

Department of Environmental Sciences, University of California, Riverside, CA 92521, USA.

The effects of nitrogen (N) across a deposition gradient on bacterial and fungal degradation pathways were studied in southern California coastal sage scrub soils to determine whether elevated N levels alter microbial community structure and organic matter accumulation. Three sites across an N deposition gradient having low, intermediate, and high levels of atmospheric N deposition were studied for 20 mo. Fungi:bacteria (F:B) biomass ratios were determined by phospholipid fatty acid analysis. Plots at each location included control plots receiving ambient N deposition and treatment plots that were fertilized with an additional 50 kg N ha(-1) yr(-1) of slow-release urea. Results showed that organic carbon (C) levels varied seasonally but that F:B ratios were relatively stable and similar across the three locations and over time. Total organic C decreased in response to N additions only at the low N deposition site. The results suggest that organic matter degradation pathways leading to C storage in soils that have been exposed to high levels of atmospheric N deposition are not responsive to additional increases in N and that N effects on organic C in semiarid soils may be significant only in areas with prior low exposure to N pollution.

PMID: 19875783 [PubMed - indexed for MEDLINE]

913. BMC Microbiol. 2009 Oct 29;9:231.

Environmental stresses inhibit splicing in the aquatic fungus Blastocladiella emersonii.

Georg RC, Stefani RM, Gomes SL.

Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, Brazil. raphaela@iq.usp.br

BACKGROUND: Exposure of cells to environmental stress conditions can lead to the interruption of several intracellular processes, in particular those performed by macromolecular complexes such as the spliceosome.
RESULTS: During nucleotide sequencing of cDNA libraries constructed using RNA isolated from B. emersonii cells submitted to heat shock and cadmium stress, a large number of ESTs with retained introns was observed. Among the 6,350 ESTs obtained through sequencing of stress cDNA libraries, 181 ESTs presented putative introns (2.9%), while sequencing of cDNA libraries from unstressed B. emersonii cells revealed only 0.2% of ESTs containing introns. These data indicate an enrichment of ESTs with introns in B. emersonii stress cDNA libraries. Among the 85 genes corresponding to the ESTs that retained introns, 19 showed more than one intron and three showed three introns, with intron length ranging from 55 to 333 nucleotides. Canonical splicing junctions were observed in most of these introns, junction sequences being very similar to those found in introns from genes previously characterized in B. emersonii, suggesting that inhibition of splicing during stress is apparently a random process. Confirming our observations, analyses of gpx3 and hsp70 mRNAs by Northern blot and S1 protection assays revealed a strong inhibition of intron splicing in cells submitted to cadmium stress.
CONCLUSION: In conclusion, data indicate that environmental stresses, particularly cadmium treatment, inhibit intron processing in B. emersonii, revealing a new adaptive response to cellular exposure to this heavy metal.

PMCID: PMC2773782 PMID: 19874600 [PubMed - indexed for MEDLINE]

914. J Immunol. 2009 Nov 15;183(10):6708-16. Epub 2009 Oct 28.

Recognition of fungal protease activities induces cellular activation and eosinophil-derived neurotoxin release in human eosinophils.

Matsuwaki Y, Wada K, White TA, Benson LM, Charlesworth MC, Checkel JL, Inoue Y, Hotta K, Ponikau JU, Lawrence CB, Kita H.

Department of Medicine and Immunology, Mayo Clinic, Rochester, MN 55905, USA.

Eosinophils are multifunctional leukocytes implicated in the pathogenesis of asthma and in immunity to certain organisms. Associations between exposure to an environmental fungus, such as Alternaria, and asthma have been recognized clinically. Protease-activated receptors (PARs) are G protein-coupled receptors that are cleaved and activated by serine proteases, but their roles in innate immunity remain unknown. We previously found that human eosinophils respond vigorously to Alternaria organisms and to the secretory product(s) of Alternaria with eosinophils releasing their proinflammatory mediators. In this study, we investigated the roles of protease(s) produced by Alternaria and of PARs expressed on eosinophils in their immune responses against fungal organisms. We found that Alternaria alternata produces aspartate protease(s) and that human peripheral blood eosinophils degranulate in response to the cell-free extract of A. alternata. Eosinophils showed an increased intracellular calcium concentration in response to Alternaria that was desensitized by peptide and protease ligands for PAR-2 and inhibited by a PAR-2 antagonistic peptide. Alternaria-derived aspartate protease(s) cleaved PAR-2 to expose neo-ligands; these neo-ligands activated eosinophil degranulation in the absence of proteases. Finally, treatment of Alternaria extract with aspartate protease inhibitors, which are conventionally used for HIV-1 and other microbes, attenuated the eosinophils' responses to Alternaria. Thus, fungal aspartate protease and eosinophil PAR-2 appear critical for the eosinophils' innate immune response to certain fungi, suggesting a novel mechanism for pathologic inflammation in asthma and for host-pathogen interaction.

PMCID: PMC2843542 PMID: 19864598 [PubMed - indexed for MEDLINE]

915. Eur J Public Health. 2010 Jun;20(3):281-7. Epub 2009 Oct 28.

Occupational blood exposure accidents in the Netherlands.

van Wijk PT, Schneeberger PM, Heimeriks K, Boland GJ, Karagiannis I, Geraedts J, Ruijs WL.

Department of Medical Microbiology and Infection Control, Jeroen Bosch Hospital, 's-Hertogenbosch, The Netherlands. p.v.wijk@jbz.nl

BACKGROUND: To make proper evaluation of prevention policies possible, data on the incidence and associated medical costs of occupational blood exposure accidents in the Netherlands are needed.
METHODS: Descriptive analysis of blood exposure accidents and risk estimates for occupational groups. Costs of handling accidents were calculated.
RESULTS: Each year, an estimated 13,000-15,000 blood exposure accidents are reported in the Netherlands, 95% in occupational settings. Hepatitis B (HBV) vaccination is offered free of charge only to people in risk groups, the seroprevalence of HBV, hepatitis C (HCV) and human immunodeficiency virus (HIV) is low and few infections are related to blood exposure accidents. High-risk accidents occur mainly in hospitals. In nursing homes and home care settings, the majority of the accidents are low-risk. Limited data are available about occurrence of accidents in other occupational groups. Associated medical costs from occupational blood exposure accidents are mainly determined by the initial risk management.
CONCLUSIONS: Accidents must be managed effectively to prevent infection and reduce anxiety in injured employees. While strategies to reduce HCV and HIV infection should be primarily aimed at reducing the occurrence of high-risk accidents, vaccination can prevent HBV infection and cut the costs of handling low-risk accidents. The implementation of vaccination strategies, safe working policies and the proper use of safe equipment should be monitored better.

PMID: 19864365 [PubMed - indexed for MEDLINE]

916. J Asthma. 2009 Oct;46(8):849-55.

Is Bjerkandera adusta Important to fungus-associated chronic cough as an allergen? Eight cases' reports.

Ogawa H, Fujimura M, Takeuchi Y, Makimura K.

Division of Pulmonary Medicine, Ishikawa-ken Saiseikai Kanazawa Hospital, Kanazawa, Japan.

BACKGROUND: Recently, we have reported a new clinical disease concept called fungus-associated chronic cough (FACC), which entailed the following manifestations: (1) chronic cough; (2) the presence of environmental fungi, particularly basidiomycetous (BM) fungi, in the sputum; and (3) good clinical response to antifungal drugs. To clarify the relationship between the exposure to environmental fungi and the development of cough attacks, we reviewed the clinical records of patients with FACC and performed a molecular biological analysis of the BM fungi.
METHODS: We successfully selected 8 patients with chronic cough, wherein a sputum culture yielded B. adusta beforehand; moreover, we conducted allergological tests such as the immediate-type skin test, a serological test, bronchoprovocation test, and lymphocyte stimulation test (LST), using the antigenic solution of B. adusta. The efficacy of individualized therapy and the clinical manifestations in the eight patients were examined.
RESULTS: All the eight patients were diagnosed with FACC. Although three patients who did not show a positive reaction to the bronchoprovocation test or LST showed excellent clinical response to anti-fungal drugs; other 5 patients who showed a positive reaction to the bronchoprovocation test and/or LST seemed to be more intractable because of taking a longer time for complete remission and more frequent recurrence of cough.
CONCLUSION: It was suggested that so-called allergic fungal cough (AFC), which is characterized by sensitization to B. adusta, may be included in a part of chronic intractable cough.

PMID: 19863292 [PubMed - indexed for MEDLINE]

917. J Environ Sci (China). 2009;21(7):954-9.

Influence of oxytetracycline on the structure and activity of microbial community in wheat rhizosphere soil.

Yang Q, Zhang J, Zhu K, Zhang H.

College of Life Sciences, Henan Normal University, Xinxiang 453007, China. yangqx66@163.com

The microbial community composition in wheat rhizosphere was analyzed by detecting colony forming units (CFUs) in agar plates. The total CFUs in rhizosphere were 1.04 x 10(9)/g soil with 9.0 x 10(8)/g bacteria, 1.37 x 10(8)/g actinomyces and 3.6 x 10(6)/g fungi. The 10 dominant bacteria were isolated from wheat rhizosphere and were grouped into genus Bacillus according to their full length 16S rRNA gene sequences. Although belonging to the same genus, the isolated strains exhibited different sensitivities to oxytetracycline. When a series of the rhizosphere soil was exposed under various concentrations of oxytetracycline, the microbial community structure was highly affected with significant decline of CFUs of bacteria and actinomyces (22.2% and 31.7% at 10 mg/kg antibiotic, respectively). This inhibition was clearly enhanced with the increase exposure dosage of antibiotic and could not be eliminated during 30 d incubation. There was no obvious influence of this treatment on fungi population. Among the four soil enzymes (alkaline phosphatase, acidic phosphatase, dehydrogenase and urease), only alkaline phosphatase was sensitive to oxytetracycline exposure with 41.3% decline of the enzyme activity at 10 mg/kg antibiotic and further decrease of 64.3%-80.8% when the dosage over 30 mg/kg.

PMID: 19862962 [PubMed - indexed for MEDLINE]

918. Arch Toxicol. 2010 Feb;84(2):99-107. Epub 2009 Oct 28.

Benzene-induced mutational pattern in the tumour suppressor gene TP53 analysed by use of a functional assay, the functional analysis of separated alleles in yeast, in human lung cells.

Billet S, Paget V, Garçon G, Heutte N, André V, Shirali P, Sichel F.

LCE EA2598, Toxicologie Industrielle et Environnementale, Université du Littoral-Côte d'Opale, Maison de la Recherche en Environnement Industriel de Dunkerque 2, 189A, Avenue Maurice Schumann, 59140 Dunkerque, France.

Recent concern has centred on the effects of continuous exposure to low concentrations of benzene, both occupationally and environmentally. Although benzene has for a long time been recognised as a carcinogen for humans, its mechanistic pathway remains unclear. Since mutations in the tumour suppressor gene TP53 are the most common genetic alterations involved in human cancer, our objective was to establish the first mutational pattern induced by benzene on the TP53 gene in human type II-like alveolar epithelial A549 cells by using the Functional Analysis of Separated Alleles in Yeast (FASAY). Seventeen mutations linked to benzene exposure were found: 3 one- or two-base deletions, and 14 single nucleotide substitutions (1 nonsense and 13 missense mutations). A>G and G>A transitions were the most prevalent (23.5% for both). Other mutations included A>C transversions and deletions (3/17, 17.6% for both), G>T transversions (2/17, 11.8%) and A>T transversions (1/17, 5.9%). Data arising from this benzene-induced mutational pattern affecting TP53, a critical target gene in human carcinogenesis, have been compared with those reported in human acute myeloid leukaemia, the aetiology of which is clearly linked to benzene exposure, and in experimental benzene-induced carcinoma. This comparison suggests that A>G transition could be a fingerprint of benzene exposure in tumours. Furthermore, our results demonstrate that FASAY is a promising tool for the study of the carcinogenic potency of benzene in the human lung.

PMID: 19862502 [PubMed - indexed for MEDLINE]

919. Ann Pharmacother. 2009 Dec;43(12):2103-7. Epub 2009 Oct 27.

Successful use of topical voriconazole 1% alone as first-line antifungal therapy against Candida albicans keratitis.

Al-Badriyeh D, Leung L, Davies GE, Stewart K, Kong D.

Department of Pharmacy Practice, Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.

OBJECTIVE: To report the successful use of topical voriconazole 1% given alone as primary therapy against a case of Candida albicans keratitis. CASE SUMMARY: A 48-year-old previously well man presented to the emergency department with pain and foreign body sensation in the left eye following exposure to dust while driving a forklift. He wore weekly disposable soft contact lenses. Anterior stromal scar and dense infiltrate were detected in the left eye. The anterior chamber remained deep, with flare and copious white cells. Intraocular pressure was 12 mm Hg and visual acuity was 20/200. The epithelial defect persisted, with progressive thinning despite topical fluorometholone and ofloxacin 0.3% therapy for 2 days. Microbiology testing revealed C. albicans as the affecting pathogen. Hourly administration of voriconazole 1% eye drops was initiated as antifungal therapy. The corneal infiltrate began to resolve and the epithelial defect decreased in size within 2 days. Visual acuity improved to 20/120. After 4 days of voriconazole use, the epithelial defect was completely healed and visual acuity was 20/30 in the affected eye. No fungi were isolated from a second eye scrape. DISCUSSION: Topical voriconazole as salvage monotherapy to manage fungal keratitis has been previously reported. It can be argued, however, that the primary therapy has facilitated the positive response to subsequent topical voriconazole. To date, there has been no solid evidence to suggest that topical voriconazole is effective when used as primary therapy. The current report provides evidence of topical voriconazole demonstrating clinical success when used as first-line therapy to treat C. albicans keratitis. The use of topical voriconazole can reduce the costs, toxicity, and drug interactions associated with common antifungal therapies.
CONCLUSIONS: Topical voriconazole 1% eye drops administered alone demonstrated success as first-line therapy against the most common fungal keratitis, C. albicans keratitis.

PMID: 19861430 [PubMed - indexed for MEDLINE]

920. Emerg Infect Dis. 2009 Oct;15(10):1590-7.

Healthcare worker occupation and immune response to Pneumocystis jirovecii.

Tipirneni R, Daly KR, Jarlsberg LG, Koch JV, Swartzman A, Roth BM, Walzer PD, Huang L.

HIV/AIDS Division, San Francisco General Hospital/University of California, San Francisco, California, USA. rtipirneni@partners.org

The reservoir and mode of transmission of Pneumocystis jirovecii remain uncertain. We conducted a cross-sectional study of 126 San Francisco General Hospital staff in clinical (n = 103) and nonclinical (n = 23) occupations to assess whether occupational exposure was associated with immune responses to P. jirovecii. We examined antibody levels by ELISA for 3 overlapping fragments that span the P. jirovecii major surface glycoprotein (Msg): MsgA, MsgB, and MsgC1. Clinical occupation participants had higher geometric mean antibody levels to MsgC1 than did nonclinical occupation participants (21.1 vs. 8.2, p = 0.004); clinical occupation was an independent predictor of higher MsgC1 antibody levels (parameter estimate = 0.89, 95% confidence interval 0.29-1.48, p = 0.003). In contrast, occupation was not significantly associated with antibody responses to either MsgA or MsgB. Healthcare workers may have occupational exposure to P. jirovecii. Humans may be a reservoir for P. jirovecii and may transmit it from person to person.

PMCID: PMC2866396 PMID: 19861050 [PubMed - indexed for MEDLINE]

921. Mycopathologia. 2009 Dec;168(6):329-37.

Infection control measures to prevent invasive mould diseases in hematopoietic stem cell transplant recipients.

Partridge-Hinckley K, Liddell GM, Almyroudis NG, Segal BH.

Division of Infection Control, Roswell Park Cancer Institute, Elm & Carlton Streets, Buffalo, NY 14263, USA. kimberly.hinckley@roswellpark.org

Invasive mould diseases, particularly aspergillosis, are important causes of morbidity and mortality in allogeneic stem cell transplant recipients. Mould spores are ubiquitous in the environment. Guidelines established by the Centers for Disease Control (CDC) and other authoritative organizations focus on approaches to reduce exposure to mould spores. These recommendations include avoidance of areas and activities expected to result in high levels of mould spores (e.g., construction, gardening) and use of specially designed units (protected environments) where additional standards (e.g., HEPA-filtered rooms) are in place to minimize mould exposure. These recommendations are based on consensus criteria and limited clinical data largely derived from single-center retrospective studies. In addition, highly immunocompromised stem cell transplant recipients are commonly managed as outpatients, where engineering standards of the inpatient protected environment are not feasible. In the absence of an outbreak with an identified environmental source (e.g., a contaminated air vent), it is not possible to reliably distinguish community-acquired from nosocomial aspergillosis. Adherence to infection control guidelines, acknowledging their limitations, combined with evidence-based targeted antifungal prophylaxis for the highest risk transplant recipients, is likely to be the most effective approach to prevent invasive mould diseases.

PMID: 19859825 [PubMed - indexed for MEDLINE]

922. J Agric Food Chem. 2009 Nov 25;57(22):10784-92.

Characterization of commercial inactive dry yeast preparations for enological use based on their ability to release soluble compounds and their behavior toward aroma compounds in model wines.

Pozo-Bayón MA, Andujar-Ortiz I, Alcaide-Hidalgo JM, Martín-Alvarez PJ, Moreno-Arribas MV.

Instituto de Fermentaciones Industriales (CSIC), C/Juan de la Cierva 3, 28006 Madrid, Spain.

The characterization of commercial enological inactive dry yeast (IDY) with different applications in wine production has been carried out. This study was based on the yeast's ability to release soluble compounds (high molecular weight nitrogen, free amino nitrogen, peptidic nitrogen, free amino acids, and polysaccharides) into model wines and on its behavior toward the volatility of seven wine aroma compounds. Important differences in soluble compounds released into the model wines supplemented with commercial IDY were found, with the free amino acids being among the most released. The volatility of most of the aroma compounds was affected by the addition of IDY preparations at a concentration usually employed during winemaking. The extent of this effect was dependent on the physicochemical characteristics of the aroma compound and on the length of time the IDY preparations remained in contact with the model wines. Whereas shorter contact times (2, 4, and 6 days) mainly promoted a "salting-out" effect, longer exposure (9 and 13 days) provoked a retention effect, with the consequent reduction of aroma compounds in the headspace. The use of different commercial preparations also promoted different effects toward the aroma compounds that may be at least in part due to differences in their ability to release soluble compounds of yeast origin into the wines.

PMID: 19856918 [PubMed - indexed for MEDLINE]

923. Biotechnol Prog. 2010 Jan-Feb;26(1):26-33.

Exploiting the intracellular compartmentalization characteristics of the S. cerevisiae host cell for enhancing primary purification of lipid-envelope virus-like particles.

Kee GS, Jin J, Balasundaram B, Bracewell DG, Pujar NS, Titchener-Hooker NJ.

Dept. of Biochemical Engineering, Advanced Centre for Biochemical Engineering, University College London, Torrington Place, London WC1E 7JE, U.K.

This article demonstrates how the intracellular compartmentalization of the S. cerevisiae host cell can be exploited to impart selectivity during the primary purification of lipid-envelope virus-like particles (VLPs). The hepatitis B surface antigen (HBsAg) was used as the VLP model in this study. Expressed HBsAg remain localized on the endoplasmic reticulum and the recovery process involves treating cell homogenate with a detergent for HBsAg liberation. In our proposed strategy, a centrifugation step is introduced immediately following cell disruption but prior to the addition of detergent to allow the elimination of bulk cytosolic contaminants in the supernatant, achieving approximately 70% reduction of contaminating yeast proteins, lipids, and nucleic acids. Recovery and subsequent treatment of the solids fraction with detergent then releases the HBsAg into a significantly enriched product stream with a yield of approximately 80%. The selectivity of this approach is further enhanced by operating under moderate homogenization pressure conditions ( approximately 400 bar). Observed improvements in the recovery of active HBsAg and reduction of contaminating host lipids were attributed to the low-shear conditions experienced by the HBsAg product and reduced cell fragmentation, which led to lower coextraction of lipids during the detergent step. As a result of the cleaner process stream, the level of product capture during the loading stage of a downstream hydrophobic interaction chromatography stage increased by two-fold leading to a concomitant increase in the chromatography step yield. The lower level of exposure to contaminants is also expected to improve column integrity and lifespan.

PMID: 19856403 [PubMed - indexed for MEDLINE]

924. Toxicol Ind Health. 2009 Oct-Nov;25(9-10):737-40.

Towards healthy homes.

Kilburn KH.

PMID: 19854824 [PubMed - indexed for MEDLINE]

925. Toxicol Ind Health. 2009 Oct-Nov;25(9-10):723-30.

Mold remediation in a hospital.

Lee TG.

University of Calgary, Faculty of Environmental Design, Calgary, Alberta, Canada. lee@ucalgary.ca

As occupants in a hospital, patients are susceptible to air contaminants that can include biological agents dispersed throughout the premise. An exposed patient can become ill and require medical intervention. A consideration for patients is that they may have become environmentally sensitive and require placement in an environment that does not compromise their health. Unfortunately, the hospital environment often contains more biological substances than can be expected in an office or home environment. When a hospital also experiences water intrusion such as flooding or water leaks, resulting mold growth can seriously compromise the health of patients and others such as nursing staff and physicians (Burge, Indoor Air and Infectious Disease. Occupational Medicine: State of the Art Reviews, 1980; Lutz et al., Clinical Infectious Diseases 37: 786-793, 2003). Micro-organism growth can propagate if the water is not addressed quickly and effectively. Immunocompromised patients are particularly at risk when subjected to fungal infection such that the US Center for Disease Control issued guideline for building mold in health care facilities (Centers for Disease and Control [CDC], Centers for Disease and Control: Questions and Answers on Stachybotrys chartarum and Other Molds, 2000). This paper is based on mold remediation of one portion of a hospital unit due to water from construction activity and inadequate maintenance, resulting in mold growth. A large proportion of the hospital staff, primarily nurses in the dialysis unit, exhibited health symptoms consistent with mold exposure. Unfortunately, the hospital administrators did not consider the mold risk to be serious and refused an independent consultant retained by the nurse's union to examine the premise (Canadian Broadcasting Corporation [CBC], Nurses file complaints over mold at Foothills. Canadian Broadcasting Corporation, 2003). The nurse's union managed to have the premise examined by submitting a court order of detention and inspection and for an interlocutory injunction to allow their consultants to undertake air quality testing. Mold remediation procedures are readily available and are not to be discussed here (Silicato, http://www.nibs.org/BETEC/M6/ 13-Silicato_Mold-Remediation.pdf, 2004). However, the difficulty of determining the qualifications of consultants, contactors and project managers are discussed. It also describes the need and importance of a buffer zone between the occupied areas and the mold abatement containment area.

PMID: 19854823 [PubMed - indexed for MEDLINE]

926. Toxicol Ind Health. 2009 Oct-Nov;25(9-10):715-22.

Molds, mycotoxins, and nutrition.

Overberg R.

Nutriwellness and the Environmental Health Center, Dallas, TX 75240-5531, USA. drron@flash.net

Many of the patients with mold and chemical exposure that come to Environmental Health Center - Dallas (EHC-D) show signs of impaired digestion. Improving their digestion improves their nutritional status and also improves their detoxification abilities. Mold and chemical exposure also affect the patient's short-term memory and executive function. This presents a challenge when it comes to teaching the patient how to improve their nutritional status and detoxification. At the EHC-D, we use several instructions methods that have resulted in the patient's grasping the concepts and then being able to implement the required changes.

PMID: 19854822 [PubMed - indexed for MEDLINE]

927. Toxicol Ind Health. 2009 Oct-Nov;25(9-10):617-35.

Molds, mycotoxins, and sick building syndrome.

Straus DC.

Department of Microbiology and Immunology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA. david.straus@ttuhsc.edu

The following is a review of some of the work we have done since 2004 regarding the importance of molds and their mycotoxins in the phenomenon of sick building syndrome (SBS). In these studies we showed that the macrocyclic trichothecene mycotoxins (MTM) of Stachybotrys chartarum (SC) are easily dissociated from the surface of the organism as it grows and could therefore be consequently spread in buildings as the fungus experiences additional water events. We then showed that SC and Penicillium chrysogenum (PC) colonies remain viable long after a water source has been removed, and the MTM produced by SC remain toxic over extended periods of time. We next showed that PC when inhaled, can release in vivo, a protease allergen that can cause a significant allergic inflammatory reaction in the lungs of mice. We then showed, in a laboratory study, that the MTM of SC can become airborne attached to spores or SC particulates smaller than spores. Following that study, we next showed that the same phenomenon actually occurred in SC infested buildings where people were complaining of health problems potentially associated with SBS. Finally, we were able to demonstrate the presence of MTM in the sera of individuals who had been exposed to SC in indoor environments. This last study was done with enough mold exposed individuals to allow for the statistical significance of SC exposure to be evaluated.

PMID: 19854820 [PubMed - indexed for MEDLINE]

928. Toxicol Ind Health. 2009 Oct-Nov;25(9-10):577-81.

Neurologic and neuropsychiatric syndrome features of mold and mycotoxin exposure.

Empting LD.

Independent Neurodiagnostic Clinic, Atlanta, GA 30327, USA. LDEmpting@synapseatlanta.com

Human exposure to molds, mycotoxins, and water-damaged buildings can cause neurologic and neuropsychiatric signs and symptoms. Many of these clinical features can partly mimic or be similar to classic neurologic disorders including pain syndromes, movement disorders, delirium, dementia, and disorders of balance and coordination. In this article, the author delineates the signs and symptoms of a syndrome precipitated by mold and mycotoxin exposure and contrasts and separates these findings neurodiagnostically from known neurologic diseases. This clinical process is designed to further the scientific exploration of the underlying neuropathophysiologic processes and to promote better understanding of effects of mold/mycotoxin/water-damaged buildings on the human nervous system and diseases of the nervous system. It is clear that mycotoxins can affect sensitive individuals, and possibly accelerate underlying neurologic/pathologic processes, but it is crucial to separate known neurologic and neuropsychiatric disorders from mycotoxin effects in order to study it properly.

PMID: 19854819 [PubMed - indexed for MEDLINE]

929. Toxicol Ind Health. 2009 Oct-Nov;25(9-10):569.

Mold and mycotoxin symposium: towards healthy homes.

Kilburn KH.

PMID: 19854818 [PubMed - indexed for MEDLINE]

930. Eur J Pharmacol. 2010 Feb 10;627(1-3):131-5. Epub 2009 Oct 22.

Induction of energy metabolism related enzymes in yeast Saccharomyces cerevisiae exposed to ibogaine is adaptation to acute decrease in ATP energy pool.

Paskulin R, Jamnik P, Obermajer N, Slavić M, Strukelj B.

OMI Institute, Trnovska 8, 1000 Ljubljana, Slovenia. roman.paskulin@siol.net

Ibogaine has been extensively studied in the last decades in relation to its anti-addictive properties that have been repeatedly reported as being addiction interruptive and craving eliminative. In our previous study we have already demonstrated induction of energy related enzymes in rat brains treated with ibogaine at a dose of 20mg/kg i.p. 24 and 72 h prior to proteomic analysis. In this study a model organism yeast Saccharomyces cerevisiae was cultivated with ibogaine in a concentration of 1mg/l. Energy metabolism cluster enzymes glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase, enolase and alcohol dehydrogenase were induced after 5h of exposure. This is a compensation of demonstrated ATP pool decrease after ibogaine. Yeast in a stationary growth phase is an accepted model for studies of housekeeping metabolism of eukaryotes, including humans. Study showed that ibogaine's influence on metabolism is neither species nor tissue specific. Effect is not mediated by binding of ibogaine to receptors, as previously described in literature since they are lacking in this model.

PMID: 19853595 [PubMed - indexed for MEDLINE]

931. Allergol Immunopathol (Madr). 2009 Sep-Oct;37(5):239-43. Epub 2009 Oct 22.

Sensitisation to aeroallergens among asthmatic and non-asthmatic adolescents living in a poor region in the Northeast of Brazil.

Sarinho EC, Mariano J, Sarinho SW, Medeiros D, Rizzo JA, Almerinda R S, Solé D.

Departamento de Saúde Materno Infantil, Brazil. emanuel.sarinho@gmail.com

OBJECTIVES: To assess the kind and frequency of sensitisation to aeroallergens (skin prick test - SPT) of asthmatic and non-asthmatic adolescents (13-14 years old) living in the city of Caruaru, Northeast of Brazil, and to analyse their exposure to some environmental factors. METHOD: A case-control study was conducted with asthmatic (50) and non-asthmatic (150) adolescents diagnosed by the International Study of Asthma and Allergies in Childhood (ISAAC) written questionnaire. All were submitted to SPT with aeroallergens (house dust mites, cat and dog epithelium, cockroaches, moulds and grass) and completed a questionnaire to evaluate their environmental exposure.
RESULTS: There were no significant differences between groups regarding gender, age, number of siblings and environmental exposure. Asthmatic subjects exhibited a higher frequency of positive SPTs than non-asthmatic subjects (54.0% vs 33.3%, p=0.009) mainly due to Periplaneta americana (34.0% vs 12.7%, p=0.0007 respectively) and Canis familiaris (20.0% vs 8.7%, p=0.029).
CONCLUSION: Although sensitisation to aeroallergens was high among non-asthmatic adolescents, asthma was associated with parental history of atopic disease and sensitisation to P. americana and Canis familiaris but not to D. pteronyssinus showing that local studies are mandatory for the tailoring of appropriate management of allergic diseases.

PMID: 19853356 [PubMed - indexed for MEDLINE]

932. Invest Ophthalmol Vis Sci. 2010 Mar;51(3):1517-23. Epub 2009 Oct 22.

A fungal pH-responsive signaling pathway regulating Aspergillus adaptation and invasion into the cornea.

Hua X, Yuan X, Wilhelmus KR.

Sid W Richardson Ocular Microbiology Laboratory, Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, Texas 77030, USA.

PURPOSE: To investigate the role of PalB and PacC, two components of a pH-responsive signal-transduction pathway of Aspergillus nidulans, during the pathogenesis of fungal infection of the cornea.
METHODS: Fungal strains included an A. nidulans wild-type isolate (A83), loss-of-function A. nidulans mutants of the palB (B7) or pacC (C6309) genes, and reconstituted genotypic strains (B7R and C6309R). Doubling times and radial growth rates were examined under neutral and acidic conditions. Corneal virulence was assessed ex vivo by topical inoculation of scarified porcine or human corneas with A. nidulans strains maintained in buffered medium until histologic examination after days 1, 3, and 5.
RESULTS: In vitro growth kinetics were similar for A. nidulans strains in liquid medium at pH 6.0 (P = 0.24) and 7.3 (P = 0.75). The pacC mutant C6309 grew more slowly (P < 0.001) on solid medium, whereas palB and pacC rescuants had growth kinetics comparable to those of the wild-type. Wild-type A. nidulans germinated on porcine corneas and produced hyphae that progressively invaded the stroma, reaching an average maximum penetration of 56% +/- 9% at 5 days after exposure. In contrast, hyphal invasion was significantly less by mutant strains B7 (P = 0.005) and C6309 (P = 0.003). Fungal penetration by C6309 was also significantly less than the wild-type (P = 0.0005) on explanted human corneas. Both fungal rescuants showed stromal invasion similar to the wild-type.
CONCLUSIONS: Corneal invasion by filamentous hyphae is attenuated by palB and pacC mutant strains of A. nidulans. The PacC pathway is involved in regulating fungal filamentation during ex vivo Aspergillus infection of the cornea.

PMCID: PMC2868430 PMID: 19850840 [PubMed - indexed for MEDLINE]

933. Scand J Public Health. 2010 May;38(3):232-8. Epub 2009 Oct 22.

Sick building syndrome in relation to domestic exposure in Sweden--a cohort study from 1991 to 2001.

Sahlberg B, Wieslander G, Norbäck D.

Department of Occupational and Environmental Medicine, Uppsala University Hospital and Uppsala University, Uppsala, Sweden. Bo.Sahlberg@medsci.uu.se

BACKGROUND: Most studies on sick building syndrome (SBS) are cross-sectional and have dealt with symptoms among office workers. There are very few longitudinal cohort studies and few studies on SBS in relation to domestic exposures. The aim of this study was to investigate changes in SBS symptoms during the follow-up period and also to investigate changes in different types of indoor exposures at home and relate them to SBS symptoms in a population sample of adults from Sweden. We also wanted to investigate if there was any seasonal or regional variation in associations between exposure and SBS.
METHODS: A random sample of 1,000 people of the general population in Sweden (1991) was sent a self administered questionnaire. A follow-up questionnaire was sent in 2001.
RESULTS: An increased risk for onset of any skin symptoms (risk ratio (RR) 2.32, 1.37-3.93), mucosal symptoms (RR 3.17, 1.69-5.95) or general symptoms (RR 2.18, 1.29-3.70) was found for those who had dampness or moulds in the dwelling during follow-up. In addition people living in damp dwellings had a lower remission of general symptoms and skin symptoms.
CONCLUSIONS: Dampness in the dwelling is a risk factor for new onset of SBS symptoms. Focus on indoor environment improvements in dwellings can be beneficial both for the inhabitants and the general population. Reducing dampness in buildings is an important factor for reducing SBS symptoms in the general population.

PMID: 19850651 [PubMed - indexed for MEDLINE]

934. Environ Sci Technol. 2009 Oct 1;43(19):7556-63.

Fungicide risk assessment for aquatic ecosystems: importance of interspecific variation, toxic mode of action, and exposure regime.

Maltby L, Brock TC, Van den Brink PJ.

Department of Animal and Plant Sciences, The University of Sheffield, Sheffield S10 2TN, UK. l.maltby@sheffield.ac.uk

The risk assessment of fungicides in Europe uses information from ecotoxicity studies performed on vertebrates, invertebrates, and primary producers, but not nontarget fungi. But which toxicity data should be used to assess risk and how important are modes of action and exposure regimes? A data set was compiled comprising acute single-species toxicity data for 42 fungicides, semifield data for 12 fungicides, and covering seven toxic modes of action and different exposure regimes. Most fungicides were general biocides and data from all taxonomic groups were used to construct species sensitivity distributions (SSDs) and assess risk. The derived lower-limit HC5 values and HCl values were always protective of adverse ecological effects in semifield studies and HC5 values were protective for at least 3 of the fungicides. Expanding the analysis to include insecticides and herbicides, the following threshold values, derived from SSDs based on the most sensitive taxonomic group, are proposed to protect against adverse ecological effects from pesticide exposure: (i) the HC5 can be used for short-term exposures; (ii) the HC5 divided by 1.5 can be used for medium-term exposures; (iii) either the HCl or the HC5 divided by 3 can be used for long-term exposures.

PMID: 19848176 [PubMed - indexed for MEDLINE]

935. Appl Microbiol Biotechnol. 2010 Jan;85(4):885-91. Epub 2009 Oct 22.

Spaceflight and modeled microgravity effects on microbial growth and virulence.

Rosenzweig JA, Abogunde O, Thomas K, Lawal A, Nguyen YU, Sodipe A, Jejelowo O.

Department of Biology Houston, Texas Southern University, Houston, TX, USA. rosenzweigja@tsu.edu

For unsuspecting bacteria, the difference between life and death depends upon efficient and specific responses to various stressors. Facing a much larger world, microbes are invariably challenged with ever-changing environments where temperature, pH, chemicals, and nutrients are in a constant state of flux. Only those that are able to rapidly reprogram themselves and express subsets of genes needed to overcome the stress will survive and outcompete neighboring microbes. Recently, low shear stress, emulating microgravity (MG) experienced in space, has been characterized in a number of microorganisms including fungi and prokaryotes ranging from harmless surrogate organisms to bona fide pathogens. Interestingly, MG appears to induce a plethora of effects ranging from enhanced pathogenicity in several Gram-negative enterics to enhanced biofilm formation. Furthermore, MG-exposed bacteria appeared better able to handle subsequent stressors including: osmolarity, pH, temperature, and antimicrobial challenge while yeast exhibited aberrant budding post-MG-exposure. This review will focus on MG-induced alterations of virulence in various microbes with the emphasis placed on bacteria.

PMCID: PMC2804794 PMID: 19847423 [PubMed - indexed for MEDLINE]

936. J Clin Microbiol. 2009 Dec;47(12):4043-8. Epub 2009 Oct 21.

Determination of Echinocandin MICs for Candida species in less than 8 hours: comparison of the rapid susceptibility assay with the Clinical and Laboratory Standards Institute's broth microdilution assay.

Hazen KC, Dirks D, Masuoka J.

Department of Pathology, University of Virginia Health System, Charlottesville, Virginia 22908-0904, USA. khazen@virginia.edu

The echinocandins prevent fungal cell wall synthesis by inhibiting beta-1,3-glucan synthesis, a significant glucose-consuming process. Previous studies suggested that echinocandin inhibitory activity is evident within 1 h of exposure. We hypothesized that a susceptibility assay based on glucose consumption may provide clinically useful MICs rapidly. The rapid susceptibility assay (RSA), which provides MICs in less than 8 h, was compared with the standard broth microdilution susceptibility assay (Clinical and Laboratory Standards Institute, document M27-A3, 2008) for 56 Candida species strains. Variables which are known to influence MICs determined by the M27-A3 method were also assessed for their effects on the RSA results. Excellent agreement (>90%) between the results of the RSA and M27-A3 methods was achieved for all three FDA-approved echinocandins (micafungin, caspofungin, and anidulafungin). Candida lusitaniae strains were responsible for most of the discordant results. Assay variables such as the test medium, the age of the inoculum culture, and the presence of human serum affected MIC results from the RSA and the M27-A3 method similarly. The RSA is equivalent to the standard M27-A3 method for determining echinocandin MICs for Candida species. The RSA provides MIC results in less than 8 h and can be applied to old and young yeast colonies. The assay could potentially provide clinically useful MICs on the same day that yeast growth from a specimen is first detected on solid medium.

PMCID: PMC2786658 PMID: 19846655 [PubMed - indexed for MEDLINE]

937. Epidemiol Infect. 2010 Apr;138(4):507-11. Epub 2009 Oct 22.

Point-source outbreak of coccidioidomycosis in construction workers.

Cummings KC, McDowell A, Wheeler C, McNary J, Das R, Vugia DJ, Mohle-Boetani JC.

Infectious Diseases Branch, Division of Communicable Disease Control, Center for Infectious Diseases, California Department of Public Health, Richmond, CA, USA. kate.cummings@cdph.ca.gov

Coccidioidomycosis results from inhaling spores of the fungus Coccidioides spp. in soil or airborne dust in endemic areas. We investigated an outbreak of coccidioidomycosis in a 12-person civilian construction crew that excavated soil during an underground pipe installation on Camp Roberts Military Base, California in October 2007. Ten (83.3%) workers developed symptoms of coccidioidomycosis; eight (66.7%) had serologically confirmed disease, seven had abnormal chest radiographs, and one developed disseminated infection; none used respiratory protection. A diagnosis of coccidioidomycosis in an eleventh worker followed his exposure to the outbreak site in 2008. Although episodic clusters of infections have occurred at Camp Roberts, the general area is not associated with the high disease rates found in California's San Joaquin Valley. Measures to minimize exposure to airborne spores during soil-disrupting activities should be taken before work begins in any coccidioides-endemic area, including regions with only historic evidence of disease activity.

PMID: 19845993 [PubMed - indexed for MEDLINE]

938. J Immunotoxicol. 2009 Dec;6(4):276-84.

The effects of pregnancy on the exacerbation and development of maternal allergic respiratory disease.

Pucheu-Haston CM, Copeland LB, Haykal-Coates N, Ward MD.

Curriculum in Toxicology, University of North Carolina-Chapel Hill, Chapel Hill, NC 27711, USA. Pucheu-Haston.Cherie@epa.gov

The T-helper 2 (T(H)2) bias associated with pregnancy may predispose the pregnant mother to the development or exacerbation of allergic disease. To determine the effects of pregnancy on pre-existing maternal sensitization, we sensitized BALB/c mice before breeding by two intratracheal aspiration (IA) exposures to the fungal allergen, Metarhizium anisopliae crude antigen (MACA). Some mice also received three IA exposures to MACA on gestational days 11, 15, and 19. After weaning, all mice were challenged IA with MACA before killing. To determine the effects of pregnancy on susceptibility to future sensitization, naïve parous and nulliparous BALB/c mice were sensitized by three IA exposures to MACA or to Hank's buffered salt solution vehicle control. Pregnancy did not have a significant effect on individual inflammatory parameters (airway responsiveness to methacholine, total serum and bronchoalveolar lavage fluid (BALF) IgE, BALF total protein, lactate dehydrogenase activity, and total and differential cell counts) following allergen challenge in sensitized mice, regardless of post-breeding allergen exposure. In conclusion there was a weak inhibition of the overall response in mice exposed to allergen during pregnancy compared to identically treated nulliparous mice. In contrast, parous mice that did not encounter allergen post-breeding tended to have exacerbated responses. Parity had no significant impact on future susceptibility to sensitization.

PMID: 19845451 [PubMed - indexed for MEDLINE]

939. Exp Lung Res. 2009 Sep;35(7):570-90.

Preexposure to repeated low doses of zymosan increases the susceptibility to pulmonary infection in rats.

Young SH, Antonini JM, Roberts JR.

Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505, USA. sby5@cdc.gov

Chronic exposure to low levels of mold has been reported to increase susceptibility to respiratory infections. In the current study, the authors investigate the lungs' ability to clear an infection after repeated low-dose zymosan exposure. Exposure was conducted at a zymosan dose of 0.6 mg/kg body weight (bw) of rat, for a total of 4 doses, via intratracheal instillation during a 2 week period. Treated animals were allowed to recover for 1 week before pulmonary inoculation with Listeria monocytogenes. Bacterial clearance was determined by measuring colony-forming units cultured from the left lungs on days 3, 5, and 7 post bacteria infection. Bronchoalveolar lavage (BAL) was performed on the right lungs to recover phagocytes and BAL fluid to measure lung injury and the inflammatory cytokines. In contrast to the authors' previously published study that showed a single high dose (2.5 mg/kg bw) of zymosan prior to infection accelerated bacteria clearance, the repeated low-dose zymosan suppressed bacteria clearance from the lungs early after infection and induced higher lung injury and inflammation compared to control. The innate immune response was down-regulated and a Th2 immune response was preferentially induced rather than a Th1 response, the latter being more effective toward the resolution of a L. monocytogenes infection.

PMID: 19842846 [PubMed - indexed for MEDLINE]

940. Southeast Asian J Trop Med Public Health. 2009 Sep;40(5):1025-33.

In vitro antimicrobial activity of Ocimum americanum L. essential oil against oral microorganisms.

Thaweboon S, Thaweboon B.

Department of Microbiology, Faculty of Dentistry, Mahidol University, Bangkok, Thailand. dtstw@mahidol.ac.th

The aim of the present study was to evaluate the efficacy of the essential oil of Ocimum americanum L. on in vitro activity against Streptococcus mutans, Lactobacillus casei and Candida albicans. An agar disk diffusion method was employed for screening antimicrobial activity. Minimum inhibitory concentration (MIC) and minimum cidal concentration (MCC) values of the oil against planktonic cells were determined using the Millipore membrane method. The antimicrobial potential of the essential oil was also investigated with a biofilm model. The results indicate that essential oil has antimicrobial activity against all tested microorganisms. The MIC values of the oil against the three organisms was 0.04% v/v whereas the MCC values for S. mutans, L. casei and C. albicans were 0.08%, 0.3% and 0.08% v/v, respectively. S. mutans and C. albicans were more sensitive to the essential oil than L. casei. With the biofilm assay, a 5-minute exposure to 3% v/v essential oil eliminated 3 logo10 of the tested microorganisms. At a lower concentration (0.3% v/v), a 2 log10 reduction in S. mutans and C. albicans was observed while the lactobacilli were more resistant. This finding indicates the possibility of using the essential oil of O. americanum L. in oral health care products for reducing these pathogenic microorganisms in the oral cavity.

PMID: 19842385 [PubMed - indexed for MEDLINE]

941. J Clin Oncol. 2010 Feb 1;28(4):667-74. Epub 2009 Oct 19.

Clinically driven diagnostic antifungal approach in neutropenic patients: a prospective feasibility study.

Girmenia C, Micozzi A, Gentile G, Santilli S, Arleo E, Cardarelli L, Capria S, Minotti C, Cartoni C, Brocchieri S, Guerrisi V, Meloni G, Foà R, Martino P.

Dipartimento di Ematologia Oncologia, Anatomia Patologica e Medicina Rigenerativa, Azienda Policlinico Umberto I, Sapienza University, Rome, Italy. girmenia@bce.uniroma1.it

Comment in Natl Med J India. 2011 Jan-Feb;24(1):28-9.

PURPOSE: Preemptive strategies in neutropenic patients based on serum galactomannan (GM) -guided triggering of diagnostic work-up may be time-consuming and expensive when applied to the entire population. We have assessed the feasibility of a clinically driven diagnostic strategy without GM screening. PATIENTS AND METHODS: Patients with neutropenic fever underwent a baseline diagnostic work-up (BDWU; three blood cultures and other examinations as indicated). An intensive diagnostic work-up (IDWU; GM for 3 days, chest computed tomography and other examinations as indicated) was reserved for patients with 4 days of persisting or relapsing fever or with other clinical findings possibly related to an invasive fungal diseaser (IFD). Antifungal therapy was administered to patients diagnosed with IFD and empirically (negative IDWU) only to those with persisting neutropenic fever and worsening clinical conditions.
RESULTS: Of 220 neutropenia episodes, fever occurred in 159 cases and recurred in 28 cases. Overall, 49 IFDs were diagnosed (two by BDWU and 47 by IDWU) during 48 episodes (21.8%). Diagnostic-driven therapy was administered to 48 patients with IFDs; one patient with zygomycosis died without treatment. Only one patient received empirical therapy. IDWU was required in 40% of neutropenia episodes, and only 1.4 mean blood samples per neutropenia episode were tested for GM. Our strategy allowed a 43% reduction in antifungal treatments compared with a standard empirical approach. At 3-month follow-up, 63% of patients with IFD survived, and no undetected IFDs were found.
CONCLUSION: A clinically driven diagnostic approach in selected neutropenia episodes offered effective antifungal control and reduced the exposure to unnecessary antifungal treatment.

PMID: 19841328 [PubMed - indexed for MEDLINE]

942. Genetics. 2010 Jan;184(1):27-42. Epub 2009 Oct 19.

Participation of DNA polymerase zeta in replication of undamaged DNA in Saccharomyces cerevisiae.

Northam MR, Robinson HA, Kochenova OV, Shcherbakova PV.

Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA.

Translesion synthesis DNA polymerases contribute to DNA damage tolerance by mediating replication of damaged templates. Due to the low fidelity of these enzymes, lesion bypass is often mutagenic. We have previously shown that, in Saccharomyces cerevisiae, the contribution of the error-prone DNA polymerase zeta (Polzeta) to replication and mutagenesis is greatly enhanced if the normal replisome is defective due to mutations in replication genes. Here we present evidence that this defective-replisome-induced mutagenesis (DRIM) results from the participation of Polzeta in the copying of undamaged DNA rather than from mutagenic lesion bypass. First, DRIM is not elevated in strains that have a high level of endogenous DNA lesions due to defects in nucleotide excision repair or base excision repair pathways. Second, DRIM remains unchanged when the level of endogenous oxidative DNA damage is decreased by using anaerobic growth conditions. Third, analysis of the spectrum of mutations occurring during DRIM reveals the characteristic error signature seen during replication of undamaged DNA by Polzeta in vitro. These results extend earlier findings in Escherichia coli indicating that Y-family DNA polymerases can contribute to the copying of undamaged DNA. We also show that exposure of wild-type yeast cells to the replication inhibitor hydroxyurea causes a Polzeta-dependent increase in mutagenesis. This suggests that DRIM represents a response to replication impediment per se rather than to specific defects in the replisome components.

PMCID: PMC2815923 PMID: 19841096 [PubMed - indexed for MEDLINE]

943. Environ Microbiol. 2009 Oct 14. [Epub ahead of print]

Zn pollution counteracts Cd toxicity in metal-tolerant ectomycorrhizal fungi and their host plant, Pinus sylvestris.

Krznaric E, Wevers JH, Cloquet C, Vangronsveld J, Vanhaecke F, Colpaert JV.

Hasselt University, Centre for Environmental Sciences, Environmental Biology Group, Agoralaan, Gebouw D, 3590 Diepenbeek, Belgium.

Summary Adaptive Zn and Cd tolerance have evolved in populations of the ectomycorrhizal fungus Suillus luteus. When exposed to high concentrations of both metals in vitro, a one-sided antagonism was apparent in the Zn- and Cd-tolerant isolates. Addition of high Zn concentrations restored growth of Cd-stressed isolates, but not vice versa. The antagonistic effect was not detected in a S. luteus isolate from non-contaminated land and in Paxillus involutus. The fungi were inoculated on pine seedlings and subsequently exposed to ecologically relevant Zn and Cd concentrations in single and mixed treatments. The applied doses severely reduced nutrient acquisition of non-mycorrhizal pines and pines inoculated with metal-sensitive S. luteus. Highest translocation of Zn and Cd to shoots occurred in the same plants. Seedlings inoculated with fungi collected from the polluted site reduced metal transfer to their host and maintained nutrient acquisition under high metal exposure. The isolate showing highest tolerance in vitro also offered best protection in symbiosis. The antagonistic effect of high Zn on Cd toxicity was confirmed in the plant experiment. The results indicate that a Zn- and Cd-polluted soil has selected ectomycorrhizal fungi that are able to survive and protect their phytobiont from nutrient starvation and excessive metal uptake.

PMID: 19840099 [PubMed - as supplied by publisher]

944. Appl Environ Microbiol. 2009 Dec;75(24):7655-62. Epub 2009 Oct 16.

Assessment of the total inflammatory potential of bioaerosols by using a granulocyte assay.

Timm M, Madsen AM, Hansen JV, Moesby L, Hansen EW.

Department of Pharmacology and Pharmacotherapy, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark. mt@farma.ku.dk

Occupational health symptoms related to bioaerosol exposure have been observed in a variety of working environments. Bioaerosols contain microorganisms and microbial components. The aim of this study was to estimate the total inflammatory potential (TIP) of bioaerosols using an in vitro assay based on granulocyte-like cells. A total of 129 bioaerosol samples were collected in the breathing zone of workers during their daily working routine at 22 biofuel plants. The samples were analyzed by traditional assays for dust, endotoxin, fungal spores, (1-->3)-beta-d-glucan, total number of bacteria, the enzyme N-acetyl-beta-d-glucosaminidase (NAGase; primarily originating from fungi), Aspergillus fumigatus, and mesophilic and thermophilic actinomycetes; the samples were also assayed for TIP. In a multilinear regression four factors were significant for the TIP values obtained: endotoxin (P < 0.0001), fungal spores (P < 0.0001), (1-->3)-beta-d-glucan (P = 0.0005), and mesophilic actinomycetes (P = 0.0063). Using this model to estimate TIP values on the basis of microbial composition, the correlation to the measured values was r = 0.91. When TIP values obtained in the granulocyte assay were related to the primary working area, we found that bioaerosol samples from personnel working in straw storage facilities showed high TIP values ( approximately 50 times the TIP of unstimulated controls). In contrast, bioaerosol samples from personnel with work functions in offices or laboratories showed low TIP values ( approximately 5 times the TIP of the unstimulated control). This indicates, as expected, that these areas were less contaminated. In conclusion, the granulocyte assay reacts to multiple contaminants in the environmental samples and can be used to obtain a measurement of TIP. Therefore, potential occupational health effects related to inflammation of the airways in a working environment can be estimated using this assay.

PMCID: PMC2794106 PMID: 19837831 [PubMed - indexed for MEDLINE]

945. Curr Biol. 2009 Dec 1;19(22):1907-11.

Stress-induced phosphorylation of S. pombe Atf1 abrogates its interaction with F box protein Fbh1.

Lawrence CL, Jones N, Wilkinson CR.

Paterson Institute for Cancer Research, University of Manchester, UK.

The Atf1 transcription factor is critical for directing stress-induced gene expression in fission yeast [1]. Upon exposure to stress, Atf1 is hyperphosphorylated by the mitogen-activated protein kinase (MAPK) Sty1 [2, 3], which results in its stabilization [4]. The resulting increase in Atf1 is vital for a robust response to certain stresses [4]. Here we investigated the mechanism by which phosphorylation stabilizes Atf1. We show that Atf1 is a target for the ubiquitin-proteasome system and that its degradation is dependent upon an SCF E3 ligase containing the F box protein Fbh1. Turnover of Atf1 requires an intact F box, but not DNA helicase activity of Fbh1. Accordingly, disruption of Fbh1 F box function suppresses phenotypes associated with loss of Atf1 phosphorylation. Atf1 and Fbh1 interact under basal conditions, but this binding is lost upon stress. In contrast, a version of Atf1 lacking all intact MAPK sites still interacts with Fbh1 upon stress, indicating that the association between the F box protein and substrate is disrupted by stress-induced phosphorylation. Most F box protein-substrate interactions described to date are mediated positively by phosphorylation [5]. Thus, our findings represent a novel means of regulating the interaction between an F box protein and its substrate. Moreover, Atf1 is the first target described in any organism for the Fbh1 F box protein.

PMID: 19836238 [PubMed - indexed for MEDLINE]

946. J Environ Sci Health A Tox Hazard Subst Environ Eng. 2009 Aug;44(10):995-1003.

Detection and hazard assessment of pathogenic microorganisms in medical wastes.

Park H, Lee K, Kim M, Lee J, Seong SY, Ko G.

Department of Environmental Health, School of Public Health, Seoul National University, Seoul, Korea.

This study was undertaken to investigate the types and concentrations of microbial agents in various medical wastes as well as to characterize their survivals in these wastes at different temperatures for microbial risk assessment. Medical wastes collected from 5 major hospitals in South Korea were classified and stored at three different temperatures (-20, 6, and 30 degrees C). Presence of various microorganisms such as pathogenic viruses and bacteria were investigated by both cultivation and by (RT)-PCR assays. A number of (opportunistic) pathogenic bacteria, including Pseudomonas spp., Lactobacillus spp., Staphylococcus spp., Micrococcus spp., Kocuria spp., Brevibacillus spp., Microbacterium oxydans, and Propionibacterium acnes, were identified from the various medical wastes. In addition, pathogenic viruses such as noroviruses and hepatitis B virus were also detected in one of the human tissue wastes. Commonly identified bacterial and viral pathogens such as Pseudomonas spp., Corynebacterium diphtheriae, Escherichia coli, Staphylococcus spp., and respiratory synctial virus (RSV) were inoculated into either gauzes or diapers, and their survivals were characterized. Viral agents such as RSV showed poor survival in most environmental conditions, and demonstrated that various pathogens could be present in medical wastes but that the associated health risk appeared to be low. However, medical waste should be carefully controlled and monitored to prevent nosocomial infection associated with the exposure to these wastes.

PMID: 19827491 [PubMed - indexed for MEDLINE]

947. Pediatr Allergy Immunol. 2010 Mar;21(2 Pt 1):253-9. Epub 2009 Oct 12.

Exposure to traffic exhaust and night cough during early childhood: the CCAAPS birth cohort.

Sucharew H, Ryan PH, Bernstein D, Succop P, Khurana Hershey GK, Lockey J, Villareal M, Reponen T, Grinshpun S, LeMasters G.

Department of Environmental Health, University of Cincinnati Medical Center, Cincinnati, OH 45267-0056, USA. sucharhj@email.uc.edu

Comment in Pediatr Allergy Immunol. 2011 Feb;22(1 Pt 1):85-6.

Though studies have investigated the association between air pollution and respiratory health outcomes in children, few have focused on night cough. The study objective was to simultaneously evaluate family factors (i.e., race, gender, maternal and paternal asthma, and breastfeeding), health (allergen sensitization and wheezing symptoms), home factors (dog, cat, mold, endotoxin, and dust mite), and other environmental exposures (traffic exhaust and second-hand tobacco smoke) for associations with recurrent dry night cough (RNC) during early childhood. A structural equation model with repeat measures was developed assessing RNC at ages one, two, and three. The prevalence of RNC was relatively large and similar at ages, one, two, and three at 21.6%, 17.3%, and 21.1%, respectively. Children exposed to the highest tertile of traffic exhaust had an estimated 45% increase in risk of RNC compared with children less exposed (adjusted OR 1.45, 95% CI: 1.09, 1.94). Also, wheezing was associated with a 76% higher risk of RNC (adjusted OR 1.76, 95% CI: 1.36, 2.26). A protective trend for breastfeeding was found with a 27% reduction in risk associated with breastfeeding (adjusted OR 0.73, 95% CI: 0.53, 1.01). No other factors were significant. These results suggest that traffic exhaust exposure may be a risk factor for night cough in young children.

PMID: 19824943 [PubMed - indexed for MEDLINE]

948. Proteomics. 2009 Oct;9(20):4686-703.

A proteomic analysis of the salt, cadmium and peroxide stress responses in Candida albicans and the role of the Hog1 stress-activated MAPK in regulating the stress-induced proteome.

Yin Z, Stead D, Walker J, Selway L, Smith DA, Brown AJ, Quinn J.

School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK.

Stress responses are important for the virulence of the major fungal pathogen of humans, Candida albicans. In this study we employed a 2-DE approach to examine the impact of exposure to peroxide (5 mM H(2)O(2)), salt (300 mM NaCl) or cadmium stress (0.5 mM Cd(2+)) upon the C. albicans proteome. Highly reproducible changes in the C. albicans proteome were observed in response to each stress condition. Significantly more proteins were up-regulated in response to cadmium (77) than to the salt (35) or peroxide stresses (35). These proteomic changes displayed minimal overlap with those observed in the transcriptome under equivalent conditions and, importantly, revealed functional categories that respond to stress at the protein level but not the transcript level. Six proteins were up-regulated by all three conditions: Adh1, Atp2, Cip1, Eft2, Ssa1 and Ssb1, which is consistent with the concept that a core stress response exists in C. albicans. This is the first time that a fungal core stress response has been defined at the proteomic level. We have also shown that the Hog1 stress-activated mitogen-activated protein kinase, which is activated in response to the stresses examined in this study, makes a major contribution to the C. albicans stress proteome.

PMID: 19824012 [PubMed - indexed for MEDLINE]

949. J Fluoresc. 2010 Jan;20(1):305-13. Epub 2009 Oct 13.

Steady state and time resolved fluorescence quenching and chemical modification studies of a lectin from endophytic fungus Fusarium solani.

Khan F, Ahmad A, Khan MI.

Division of Biochemical Sciences, National Chemical Laboratory, Pune, 411 008, India.

The solute quenching studies of a lectin from endophytic fungus Fusarium solani were carried out using different quenchers such as acrylamide, succinimide, potassium iodide and cesium chloride. The lectin showed emission maximum at 348 nm indicating relative exposure of tryptophan. The quenchable fraction of the fluorophore was 100% with acrylamide, whereas it was only 50% with succinimide. The ionic quenchers iodide and cesium showed opposite effects at different pH. In the case of cesium, raising the pH resulted in increased quenching and accessibility of typtophan residue, while the iodide showed just opposite effect. These studies showed that the single tryptophan residue of the lectin (per monomer) is relatively exposed, and might be in the vicinity of positively charged amino acid residues. Various amino acids of the F. solani lectin were modified using different reagents to obtain information about the hemagglutinating site. The chemical modification studies suggested tyrosine residues can be modified using N-acetylimidazole, which results in complete loss of hemagglutination activity of the lectin. Kinetics of chemical modification suggested involvement of only 2 tyrosine residues. Modification of arginine, cysteine, histidine, lysine, aspartate, glutamate and tryptophan did not result in loss of hemagglutinating activity of the lectin.

PMID: 19823920 [PubMed - indexed for MEDLINE]

950. Bioelectromagnetics. 2010 Apr;31(3):220-5.

Static magnetic field exposure fails to affect the viability of different bacteria strains.

László J, Kutasi J.

Section for Mathematics, Hungarian Academy of Sciences, Nádor u. 7, Budapest, Hungary. laszloj@office.mta.hu

The viability of the microbes Saccharomyces cerevisiae, Bacillus circulans, Escherichia coli, Micrococcus luteus, Pseudomonas fluorescens, Salmonella enteritidis, Serratia marcescens, and Staphylococcus aureus was tested under static magnetic field exposure up to 24 h in either a homogeneous (159.2 +/- 13.4 mT) or three types of inhomogeneous static magnetic fields: (i) peak-to-peak magnetic flux density 476.7 +/- 0.1 mT with a lateral magnetic flux density gradient of 47.7 T/m, (ii) 12.0 +/- 0.1 mT with 1.2 T/m, or (iii) 2.8 +/- 0.1 mT with 0.3 T/m. Even the longest period of exposure failed to produce any effect in the growth of bacteriae that could be correlated with static magnetic field exposure.

PMID: 19821495 [PubMed - indexed for MEDLINE]

951. Curr Genet. 2009 Dec;55(6):611-21. Epub 2009 Oct 10.

Dse1 may control cross talk between the pheromone and filamentation pathways in yeast.

Draper E, Dubrovskyi O, Bar EE, Stone DE.

Laboratory for Molecular Biology (M/C 567), Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA.

The filamentous/invasive growth pathway is activated by nutrient limitation in the haploid form of the yeast Saccharomyces cerevisiae, whereas exposure to mating-pheromone causes cells to differentiate into gametes. Although these two pathways respond to very different stimuli and generate very different responses, they utilize many of the same signaling components. This implies the need for robust mechanisms to maintain signal fidelity. Dse1 was identified in an allele-specific suppressor screen for proteins that interact with the pheromone-responsive Gbetagamma, and found to bind both to a Gbetagamma-affinity column, and to the shared MEKK, Ste11. Although overexpression of Dse1 stimulated invasive growth and transcription of both filamentation and mating-specific transcriptional reporters, deletion of DSE1 had no effect on these outputs. In contrast, pheromone hyper-induced transcription of the filamentation reporter in cells lacking Dse1 and in cells expressing a mutant form of Gbeta that exhibits diminished interaction with Dse1. Thus, the interaction of Dse1 with both Gbeta and Ste11 may be designed to control cross talk between the pheromone and filamentation pathways.

PMID: 19820940 [PubMed - indexed for MEDLINE]

952. Mem Inst Oswaldo Cruz. 2009 Aug;104(5):769-74.

Molecular characterisation of Sporothrix schenckii isolates from humans and cats involved in the sporotrichosis epidemic in Rio de Janeiro, Brazil.

Reis RS, Almeida-Paes R, Muniz Mde M, Tavares PM, Monteiro PC, Schubach TM, Gutierrez-Galhardo MC, Zancopé-Oliveira RM.

Laboratório de Micologia, Instituto de Pesquisa Clínica Evandro Chagas-Fiocruz, Rio de Janeiro, RJ, Brazil. rosani.reis@ipec.fiocruz.br

An epidemic of sporotrichosis, a subcutaneous mycosis caused by the fungus Sporothrix schenckii, is ongoing in Rio de Janeiro, Brazil, in which cases of human infection are related to exposure to cats. In an attempt to demonstrate the zoonotic character of this epidemic using molecular methodology, we characterised by DNA-based typing methods 19 human and 25 animal S. schenckii isolates from the epidemic, as well as two control strains. To analyse the isolates, the random amplified polymorphic DNA (RAPD) technique was performed using three different primers, together with DNA fingerprinting using the minisatellite derived from the wild-type phage M13 core-sequence. The analyses generated amplicons with considerable polymorphism. Although isolates exhibited high levels of genetic relatedness, they could be clustered into 5-10 genotypes. The RAPD profiles of epidemic S. schenckii isolates could be distinguished from that of the United States isolate, displaying 20% similarity to each primer and 60% when amplified with the M13 primer. DNA fingerprinting of S. schenckii isolated from the nails (42.8%) and the oral cavities (66%) of cats were identical to related human samples, suggesting that there is a common infection source for animals and humans in this epidemic. It is clear that cats act as a vehicle for dissemination of S. schenckii.

PMID: 19820840 [PubMed - indexed for MEDLINE]

953. J Bras Pneumol. 2009 Sep;35(9):920-30.

Chapter 2: coccidioidomycosis.

[Article in English, Portuguese]

Deus Filho A.

Universidade Federal do Piauí, Teresina, PI, Brasil. mdedeus@uol.com.br

Coccidioidomycosis is a systemic mycosis caused by the dimorphic fungi Coccidioides immitis and Coccidioides posadasii. Infection is acquired by inhalation of infective arthroconidia that live in the soil. In 60% of cases, the infection is benign and resolves spontaneously. In the northern hemisphere, coccidioidomycosis is endemic to arid and semi-arid regions at latitudes between 40 degrees N and 40 degrees S, particularly in the southwestern United States and in northern Mexico. In the semi-arid northeastern region of Brazil, cases of coccidioidomycosis have recently been reported in four states: Piauí (100 cases); Ceará (20 cases); Maranhão (6 cases); and Bahia (2 cases). The illness manifests in one of three clinical forms: the primary pulmonary form; the progressive pulmonary form; or the disseminated form. On average, the symptoms of respiratory infection appear 10 days after exposure. The diagnosis is made by the isolation of Coccidioides sp. in culture or by positive results from smear microscopy (10% potassium hydroxide test), periodic acid-Schiff staining or silver staining of any suspect material (sputum, cerebrospinal fluid, skin exudate, lymph node aspirate, etc.) Agar gel immunodiffusion is the diagnostic test most widely used. The most common finding on X-rays and CT scans is diffuse distribution of multiple pulmonary nodules, most of which are cavitated. The recommended treatment is fluconazole or itraconazole, the mean dose ranging from 200 to 400 mg/day, although as much as 1,200 mg/day is used in certain cases. In severe cases, amphotericin B can be the drug of choice. In cases of neurological involvement, the recommended treatment is administration of fluconazole, at a minimum dose of 400 mg/day.

PMID: 19820819 [PubMed - indexed for MEDLINE]

954. DNA Repair (Amst). 2009 Dec 3;8(12):1390-9. Epub 2009 Oct 12.

Mms1-Mms22 complex protects genome integrity in Schizosaccharomyces pombe.

Dovey CL, Aslanian A, Sofueva S, Yates JR 3rd, Russell P.

Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.

Mms1 and Mms22 are subunits of an Rtt101-based E3 ubiquitin ligase required for replication of damaged DNA templates in Saccharomyces cerevisiae. The function and evolutionary conservation of this DNA repair module are unknown. Here we report the characterization of an Mms1 ortholog in Schizosaccharomyces pombe. Fission yeast Mms1 was discovered through its physical association with S. pombe Mms22 (also known as Mus7). Loss of S. pombe Mms1 results in the accumulation of spontaneous DNA damage, mitotic delay, and hypersensitivity to genotoxins such as camptothecin that perturb replisome progression. Homologous recombination repair proteins Rhp51 and Rad22 (Rad51 and Rad52 orthologs, respectively) are critical for survival in the absence of Mms1; however, there is no such requirement for Mus81-Eme1 Holliday junction resolvase that is essential for recovery from broken replication forks. Mms1 and Mms22 mutants share similar phenotypes and are genetically epistatic under unperturbed growth conditions and following exposure to genotoxins. From these data we conclude that an evolutionary conserved Mms1-Mms22 complex is required for replication of damaged DNA in fission yeast.

PMCID: PMC2787726 PMID: 19819763 [PubMed - indexed for MEDLINE]

955. Chem Biol Interact. 2010 Jan 5;183(1):113-24.

Inflammation-associated gene transcription and expression in mouse lungs induced by low molecular weight compounds from fungi from the built environment.

Miller JD, Sun M, Gilyan A, Roy J, Rand TG.

Department of Chemistry, Carleton University, Ottawa, Ontario, Canada K1S 5B6.

Few metabolites from fungi found indoors have been tested for inflammatory mediators endpoints in primary cultures of alveolar macrophages or in vivo. In this study, mice were intratracheally instilled with a single dose comprising 4x10(-5)moletoxin/kg lung wt dose of either atranone C, brevianamide, cladosporin, mycophenolic acid, neoechinulin A & B, sterigmatocystin or TMC-120A. These toxins are from fungi common on damp building materials. The dose used was comparable to the estimated doses of possible human exposure. Hematoxylin and eosin (H&E) histology and Alcian Blue/Periodic Acid Schiff (AB/PAS) histochemistry were used to evaluate lungs for time course (4h and 12h post-exposure (PE)) inflammatory and toxic changes. Reverse-transcription (RT)-PCR based arrays were also employed to evaluate time course inflammation-associated gene transcription in lung tissues of the different toxins. Immunohistochemistry (IHC) was used to probe MIP-2 and Tnf-alpha protein expression in treatment lungs to determine whether responses correspond with gene transcription data. Both histology and histochemistry revealed that toxin exposed lungs at 12h PE showed evidence of inflammation. H&E revealed that bronchioli were lined with irregularly thickened and sometimes sloughing epithelium and bronchiolar spaces supported infiltration of leukocytes, cellular and mucus-like debris while alveolar spaces supported swollen macrophages and modest amorphous debris accumulations. All toxin-instilled lungs exhibited copious mucus production and alveolar macrophages with red stained cytoplasm on bronchiolar surfaces, especially at 12h PE. Array analysis of 83 inflammation-associated genes extracted from lung tissue demonstrated a number of patterns, compared to controls. 82 genes assayed at 4h PE and 75 genes at 12h PE were significantly altered (p< or =0.05; >or =1.5-fold or < or =-1.5-fold change) in the different treatment animal groups. Expression of transcriptionally regulated genes was confirmed using immunohistochemistry that demonstrated MIP-2 and Tnf-alpha staining in respiratory bronchiolar epithelia, alveolar macrophages and alveolar type II cells. The transcriptional regulation in these genes in the treatment groups suggests that they may serve central roles in the immunomodulation of toxin-induced pro-inflammatory lung responses. Hierarchical cluster analysis revealed significant patterns of gene transcription linking the response of the toxins at equimolar doses in three groups: (1) brevianamide, mycophenolic acid and neoechinulin B, (2) neoechinulin A and sterigmatocystin, and (3) cladosporin, atranone C and TMC-120. The results further confirm the inflammatory nature of metabolites/toxins from such fungi can contribute to the development of non-allergenic respiratory health effects.

PMID: 19818335 [PubMed - indexed for MEDLINE]

956. Arch Bronconeumol. 2010 May;46(5):275-7. Epub 2009 Oct 7.

[Hypersensitivity pneumonitis after exposure to Candida spp].

[Article in Spanish]

Serrano C, Torrego A, Loosli A, Valero A, Picado C.

Unidad de Alergia, Hospital Fundación Valle del Lili, Cali, Colombia.

Hypersensitivity pneumonitis (HP) is a lung disease caused by heavy and recurrent inhalation of antigens. We describe the case of a patient with HP caused by domestic exposure to Candida spp. The diagnosis was made by taking into consideration the, clinical presentation, exposure history, radiological findings, bronchoalveolar lavage, lung function and the immuno-allergy study. The diagnosis was definitively confirmed by performing a specific bronchial provocation test. It has been shown that there is cross-reactivity between different Candida species, and despite making the diagnosis in this case with Candida albicans, we were unable to define exactly which species was responsible for the HP.

PMID: 19815326 [PubMed - indexed for MEDLINE]

957. Ophthalmology. 2009 Dec;116(12):2348-53. Epub 2009 Oct 7.

Emerging prevalence of microsporidial keratitis in Singapore: epidemiology, clinical features, and management.

Loh RS, Chan CM, Ti SE, Lim L, Chan KS, Tan DT.

Singapore National Eye Centre, Singapore, Singapore.

OBJECTIVE: To investigate the incidence and epidemiologic factors involved in the development of microsporidial keratitis. The association of host immune status and clinical pattern, clinical features, and the role of fluoroquinolone monotherapy in treatment are also examined. DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: All cases (124 patients, 134 eyes) of microsporidial keratitis confirmed with modified trichrome stain positive of corneal scrape over a 4-year period.
METHODS: Epidemiologic factors were observed. Host immune status with human immunodeficiency virus (HIV) serology and CD4/CD8 analysis was performed when consent was obtained. Visual acuity (VA) and slit-lamp examination throughout the course of keratitis was recorded. Treatment used included topical fluoroquinolones (ciprofloxacin 0.3%, moxifloxacin 0.5%, gatifloxacin 0.5%, levofloxacin 0.5%, or norfloxacin 0.3%) as monotherapy or in combination with topical fumagillin and/or systemic albendazole. Where corneal edema developed, ultrasound corneal pachymetry was recorded. MAIN OUTCOME MEASURES: Demographic features and epidemiologic factors, including host immune status. Clinical features and disease course, including the response to different therapeutic regimes.
RESULTS: Patients ranged in age from 11 to 68 years (mean, 31.9; median, 30) with a male:female ratio of 8:1 (females n = 17 [13.7%]). We performed HIV serology and CD4/CD8 in 45.9% of cases (n = 57); all the cases tested were negative with normal T-cell indices. Epidemiologic factors included soil exposure (50%), contact lens wear (21.1%), and topical steroid treatment (17.1%). The VA on presentation ranged from 20/20 to 20/100 (median, 20/30) with no loss in lines of VA on resolution. Common features were follicular papillary conjunctivitis and coarse punctate epithelial lesions in 3 patterns--diffuse, peripheral, and paracentral--evolving into nummular keratitis before resolution. Resolution occurred in 99% of cases on topical fluoroquinolone monotherapy. Four patients had recurrent disease that resolved with repeat fluoroquinolone or fluoroquinolone/oral albendazole combination. Two new clinical features were identified--diffuse endotheliitis (19.4%) with corneal edema and limbitis.
CONCLUSIONS: This study identifies an increasing incidence of microsporidial keratitis in Singapore with a strong correlation with prior soil exposure. Diffuse endotheliitis and limbitis have not been described and resolves with topical steroid therapy. Topical fluoroquinolone monotherapy is a valid treatment option.

PMID: 19815287 [PubMed - indexed for MEDLINE]

958. Ecotoxicol Environ Saf. 2010 Jan;73(1):24-31. Epub 2009 Oct 6.

Genotoxicity of two pathogenic strains of zoosporic fungi (Achlya klebsiana and Aphanomyces laevis) on erythrocytes of Nile tilapia Oreochromis niloticus niloticus.

Osman A, Ali E, Hashem M, Mostafa M, Mekkawy I.

Zoology Department, Faculty of Science, Al-Azhar University (Assiut Branch), 71524 Assiut, Egypt. agosman2@yahoo.com

In the present work we have described the genotoxic potential of two pathogenic strains of zoosporic fungi (Achlya klebsiana and Aphanomyces laevis) on erythrocytes of Nile tilapia Oreochromis niloticus niloticus for the first time by three complementary tests: micronucleus test (MN), nuclear lesions (NL) and comet assay (CA). The groups exposed to the zoosporic fungi subjected to the MN and NL test showed statistically significant differences in MN and NL frequencies with respect to the control one. Also, a significant increase (p<0.001) in micronuclei and nuclear lesions frequencies were recorded with the increase in exposure time. A correlation was observed between the frequencies of MN and NL, suggesting the importance for recording this anomaly in order to improve the information obtained with the MN test. Therefore, our results suggest that the nuclear lesions found here should be considered indicators of genotoxicity, in addition to the typical micronuclei forms. The result of the comet assay showed a significant difference in the percentages of the damaged DNA in the comet tail (%TDNA) of the treated groups comparing to the control. A significant (p<0.001) increase in the DNA damage of the treated groups with the increase in exposure time was recorded, confirming the results of the MN and the NL tests. The results of the current study will be useful for future work involving the biomonitoring of regions where Nile tilapia survive. These data allow us to consider O. niloticus niloticus as a good bioindicator of the effects of genotoxic agents that might be present in the aquatic habitat.

PMID: 19811832 [PubMed - indexed for MEDLINE]

959. J Basic Microbiol. 2010 Feb;50(1):21-36.

Interference of chromium with biological systems in yeasts and fungi: a review.

Poljsak B, Pócsi I, Raspor P, Pesti M.

Chair of Environmental Health, Faculty of Health Studies, University of Ljubljana, Slovenia.

This paper deals with the interactions of chromium (Cr) with biological systems, focusing in particular on yeasts and fungi. These interactions are analysed with primarily regard to biochemical functions, but higher levels of organization are also considered. Thus, the morphological and cytological characteristics of selected microorganisms in response to exposure to chromium ions are evaluated. The different oxidation states of chromium and reactive oxygen species (ROS) generated in redox reactions with chromium ions are presented and characterized. The interactions of the most exposed subcellular structures, including the cell wall, plasma membrane and nuclei, have been deeply investigated in recent years, for two major reasons. The first is the toxicity of chromium ions and their strong impact on the metabolism of many species, ranging from microbes to humans. The second is the still disputed usefulness of chromium ions, and in particular trivalent chromium, in the glucose and fat metabolisms. Chromium pollution is still an important issue in many regions of the world, and various solutions have been proposed for the bioremediation of soil and water with selected microbial species. Yeasts and especially moulds have been most widely investigated from this aspect, and the biosorption and bioaccumulation of chromium for bioremediation purposes have been demonstrated. Accordingly, the mechanisms of chromium tolerance or resistance of selected microbes are of particular importance in both bioremediation and waste water treatment technologies. The mechanisms of chromium toxicity and detoxification have been studied extensively in yeasts and fungi, and some promising results have emerged in this area.

PMID: 19810050 [PubMed - indexed for MEDLINE]

960. J Basic Microbiol. 2009 Dec;49(6):553-63.

Characterization of new biosurfactant produced by Trichosporon montevideense CLOA 72 isolated from dairy industry effluents.

Monteiro AS, Coutinho JO, Júnior AC, Rosa CA, Siqueira EP, Santos VL.

Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, MG, Brazil.

The yeast strain CLOA 72 isolated from the effluent of a dairy industry in Brazil and identified as Trichosporon montevideense, was able to grow and produce a glycolipid biosurfactant when cultured on a mineral medium (MM) with sunflower oil as the carbon source. Biosurfactant production was partially growth-associated and maximal emulsification activity was observed at 144 h of cultivation (78.92%). The biosurfactant purified by precipitation with ethanol showed 78.66% emulsifying activity when used in concentrations above 4.5 mg/ml and was able to reduce the surface tension of water to values below 44.9 mN/m. The critical micellar concentration (CMC) was found to be 2.2 mg/ml. The highest emulsifying activity (E(24)) has been observed with vegetable oils, toluene, kerosene, isooctane, cyclohexane, hexane, diesel oil and hexadecane as compared to mineral oil and oleic acid. The biosurfactant also showed good stability during exposure to 100 degrees C for different periods of time (10 to 60 min), to high salinity (30% of NaCl, KCl and NaHCO(3)), and to a wide range of pH values (1-10). The biosurfactant purified by gel filtration chromatography is a glycolipid, with lipid portion containing 16.03% (9Z)-octadec-9-enoic acid, 14.92% hexadecanoic acid, and 9.63% (E) octadec-9-enoic acid and the carbohydrate portion containing mannose (35.29%), xylose (41.99%), arabinose (17.47%), and glucose (5.25%).

PMID: 19810042 [PubMed - indexed for MEDLINE]

961. Bull Environ Contam Toxicol. 2010 Jan;84(1):96-100. Epub 2009 Oct 7.

Synergistic action of exogenous salicylic acid and arbuscular mycorrhizal fungus colonization in Avena nuda seedlings in response to NO(2) exposure.

Li R, Jiang Y, Xu J, Zhou B, Ma C, Liu C, Yang C, Xiao Y, Xu Q, Hao L.

College of Life and Chemistry Sciences, Shenyang Normal University, 110034, Shenyang, People's Republic of China.

Colonization of arbuscular mycorrhizal fungi Glomus mosseae or exogenous salicylic acid (SA) treatment can increase Avena nuda plant tolerance to elevated NO(2) exposure. The combination of the two factors, namely application of SA to the mycorrhizal plants, further promoted NO(2) tolerance, as indicated by an alleviated plant biomass decrease compared to the respective treatment. The analysis of antioxidant capacity, redox status and photon energy utilization showed that the increased NO(2) tolerance in the treated plants may be associated, at least in part, with scavenging reactive oxygen species, maintaining CO(2) assimilated rate and reducing conditions in cells.

PMID: 19809772 [PubMed - indexed for MEDLINE]

962. J Environ Monit. 2009 Oct;11(10):1849-58. Epub 2009 Jul 20.

JEM Spotlight: Fungi, mycotoxins and microbial volatile organic compounds in mouldy interiors from water-damaged buildings.

Polizzi V, Delmulle B, Adams A, Moretti A, Susca A, Picco AM, Rosseel Y, Kindt R, Van Bocxlaer J, De Kimpe N, Van Peteghem C, De Saeger S.

Ghent University, Faculty of Pharmaceutical Sciences, Laboratory of Food Analysis, Harelbekestraat 72, B-9000 Ghent, Belgium.

Comment in J Environ Monit. 2009 Oct;11(10):1847-8.

Concerns have been raised about exposure to mycotoxin producing fungi and the microbial volatile organic compounds (MVOCs) they produce in indoor environments. Therefore, the presence of fungi and mycotoxins was investigated in 99 samples (air, dust, wallpaper, mycelium or silicone) collected in the mouldy interiors of seven water-damaged buildings. In addition, volatile organic compounds (VOCs) were sampled. The mycotoxins were analysed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) (20 target mycotoxins) and quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS). Morphological and molecular identifications of fungi were performed. Of the 99 samples analysed, the presence of one or more mycotoxins was shown in 62 samples by means of LC-MS/MS analysis. The mycotoxins found were mainly roquefortine C, chaetoglobosin A and sterigmatocystin but also roridin E, ochratoxin A, aflatoxin B(1) and aflatoxin B(2) were detected. Q-TOF-MS analysis elucidated the possible occurrence of another 42 different fungal metabolites. In general, the fungi identified matched well with the mycotoxins detected. The most common fungal species found were Penicillium chrysogenum, Aspergillus versicolor (group), Chaetomium spp. and Cladosporium spp. In addition, one hundred and seventeen (M)VOCs were identified, especially linear alkanes (C(9)-C(17)), aldehydes, aromatic compounds and monoterpenes.

PMID: 19809708 [PubMed - indexed for MEDLINE]

963. Toxicol Ind Health. 2009 Oct-Nov;25(9-10):669-80. Epub 2009 Oct 6.

Fungal exposure endocrinopathy in sinusitis with growth hormone deficiency: Dennis-Robertson syndrome.

Dennis D, Robertson D, Curtis L, Black J.

Northside Hospital, USA. ddennis@mindspring.com

A retrospective study was carried out on 79 patients with a history of mold exposure, fatigue, and chronic rhinosinusitis (CRS) to determine whether there is a causal relationship between fungal exposure and chronic sinusitis, fatigue, and anterior hypopituitarism, especially growth hormone deficiency (GHD). Of the patients, 94% had a history of CRS, endoscopically and/or computed tomography (CT) confirmed; 100% had chronic fatigue and 100% had either significant history of indoor mold exposure and/or positive mold plate testing as measured by settle plates, with an average colony count of 21 (0-4 normal). A total of 62 had positive mold plate testing and 17 had positive history of mold exposure. Of 75, 73 (97.3%) had positive serum immunoglobulin G (IgG)-specific antibodies to fungal antigens. Out of 8, 7 were positive for urinary trichothecenes. Resting levels of insulin-like growth factor 1 (IGF-1) averaged 123 ng/mL (range 43-285, normal 88-249 ng/mL). Despite normal resting levels of IGF-1, significant deficiency of serum human growth hormone (GH) was confirmed by insulin tolerance test (ITT) in 40 of 50 tested. In all, 51% (40/79) were GH deficient. Primary or secondary hypothyroidism in T3 and/or T4 was seen in 81% (64/79) patients; 75% (59/79) had adrenocorticotrophic hormone (ACTH) deficiency. Fungal exposure endocrinopathy likely represents the major cause of GHD, affecting approximately 4.8 million people compared to approximately known 60,000 cases from all other causes. A literature review indicates a possible mechanism of GHD in fungal exposure is that the fungal glucan receptors in the lenticulostellate cells of the anterior pituitary bind to fungal cells wall glucans and activate the innate immune system, which activates macrophages that destroy the fungus and lenticulostellate tissue. Treatment of patients included normal saline nasal irrigations, antifungal and antibiotic nasal sprays, appropriate use of oral antibiotics and antifungals, facial steamer with CitriDrops. Thymate and/or Intramax vitamin supplements, hormone replacement, and reduction of indoor mold levels. Resolution of rhinosinusitis was seen in 93% (41 of 45) of the patients who achieved a mold count by settling plates of 0-4 colonies. Thirty patients were unable to lower their mold counts below four colonies and had various degrees of mucosal disease and fatigue remaining. Fatigue was improved in all 37 patients who received GH and cortisol and/or thyroid hormone, which were deficient. Fatigue was partially relieved in 7 of the 37 who did not achieve mold counts of fewer than four colonies.

PMID: 19808744 [PubMed - indexed for MEDLINE]

964. Toxicol Ind Health. 2009 Oct-Nov;25(9-10):571-6. Epub 2009 Oct 6.

Epidemics of mold poisoning past and present.

Meggs WJ.

Division of Toxicology, Department of Emergency Medicine, Brody School of Medicine, East Carolina University, Greenville, NC 27858, USA. meggsw@ecu.edu

Molds are ubiquitous throughout the biosphere of planet earth and cause infectious, allergic, and toxic diseases. Toxic diseases arise from exposure to mycotoxins produced by molds. Throughout history, there have been a number of toxic epidemics associated with exposure to mycotoxins. Acute epidemics of ergotism are caused by consumption of grain infested by fungi of the genus Claviceps, which produce the bioactive amine ergotamine that mimics the neurotransmitters norepinephrine, serotonin, and dopamine. Acute aflatoxin outbreaks have occurred from ingestion of corn stored in damp conditions that potentiate growth of the molds of the species Aspergillus. Contemporary construction methods that use cellulose substrates such as fiber board and indoor moisture have caused an outbreak of contaminated buildings with Stachybotrys chartarum, with the extent of health effects still a subject of debate and ongoing research. This article reviews several of the more prominent epidemics and discusses the nature of the toxins. Two diseases that were leading causes of childhood mortality in England in the 1970s and vanished with changing dietary habits, putrid malignant fever, and slow nervous fever were most likely toxic mold epidemics.

PMID: 19808743 [PubMed - indexed for MEDLINE]

965. Genetics. 2009 Dec;183(4):1249-60. Epub 2009 Oct 5.

Centromere replication timing determines different forms of genomic instability in Saccharomyces cerevisiae checkpoint mutants during replication stress.

Feng W, Bachant J, Collingwood D, Raghuraman MK, Brewer BJ.

Department of Genome Sciences, University of Washington, Box 355065 Foege Bldg., Room S041, 1705 NE Pacific St., Seattle, Washington 98195, USA.

Yeast replication checkpoint mutants lose viability following transient exposure to hydroxyurea, a replication-impeding drug. In an effort to understand the basis for this lethality, we discovered that different events are responsible for inviability in checkpoint-deficient cells harboring mutations in the mec1 and rad53 genes. By monitoring genomewide replication dynamics of cells exposed to hydroxyurea, we show that cells with a checkpoint deficient allele of RAD53, rad53K227A, fail to duplicate centromeres. Following removal of the drug, however, rad53K227A cells recover substantial DNA replication, including replication through centromeres. Despite this recovery, the rad53K227A mutant fails to achieve biorientation of sister centromeres during recovery from hydroxyurea, leading to secondary activation of the spindle assembly checkpoint (SAC), aneuploidy, and lethal chromosome segregation errors. We demonstrate that cell lethality from this segregation defect could be partially remedied by reinforcing bipolar attachment. In contrast, cells with the mec1-1 sml1-1 mutations suffer from severely impaired replication resumption upon removal of hydroxyurea. mec1-1 sml1-1 cells can, however, duplicate at least some of their centromeres and achieve bipolar attachment, leading to abortive segregation and fragmentation of incompletely replicated chromosomes. Our results highlight the importance of replicating yeast centromeres early and reveal different mechanisms of cell death due to differences in replication fork progression.

PMCID: PMC2787418 PMID: 19805819 [PubMed - indexed for MEDLINE]

966. Proc Natl Acad Sci U S A. 2009 Oct 13;106(41):17443-7. Epub 2009 Sep 24.

Fungal infection counters insecticide resistance in African malaria mosquitoes.

Farenhorst M, Mouatcho JC, Kikankie CK, Brooke BD, Hunt RH, Thomas MB, Koekemoer LL, Knols BG, Coetzee M.

Laboratory of Entomology, Wageningen University and Research Centre, P.O. Box 8031, 6700 EH Wageningen, The Netherlands.

The evolution of insecticide resistance in mosquitoes is threatening the effectiveness and sustainability of malaria control programs in various parts of the world. Through their unique mode of action, entomopathogenic fungi provide promising alternatives to chemical control. However, potential interactions between fungal infection and insecticide resistance, such as cross-resistance, have not been investigated. We show that insecticide-resistant Anopheles mosquitoes remain susceptible to infection with the fungus Beauveria bassiana. Four different mosquito strains with high resistance levels against pyrethroids, organochlorines, or carbamates were equally susceptible to B. bassiana infection as their baseline counterparts, showing significantly reduced mosquito survival. Moreover, fungal infection reduced the expression of resistance to the key public health insecticides permethrin and dichlorodiphenyltrichloroethane. Mosquitoes preinfected with B. bassiana or Metarhizium anisopliae showed a significant increase in mortality after insecticide exposure compared with uninfected control mosquitoes. Our results show a high potential utility of fungal biopesticides for complementing existing vector control measures and provide products for use in resistance management strategies.

PMCID: PMC2762667 PMID: 19805146 [PubMed - indexed for MEDLINE]

967. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2010 Feb;27(2):241-8.

Production of citreoviridin by Penicillium citreonigrum strains associated with rice consumption and beriberi cases in the Maranhão State, Brazil.

Rosa CA, Keller KM, Oliveira AA, Almeida TX, Keller LA, Marassi AC, Kruger CD, Deveza MV, Monteiro BS, Nunes LM, Astoreca A, Cavaglieri LR, Direito GM, Eifert EC, Lima TA, Modernell KG, Nunes FI, Garcia AM, Luz MS, Oliveira DC.

Universidade Federal Rural do Rio de Janeiro, Instituto de Veterinária, Departamento de Microbiologia e Imunologia Veterinária, Rio de Janeiro, Brazil.

The aim of this study was to determine the levels of Penicillium citreonigrum and citreoviridin present in rice samples from Maranhão State, Brazil, where an outbreak of beriberi was reported and 32 deaths occurred (7% of the notified cases died in 2006). The ability of P. citreonigrum to produce citreoviridin was assessed, and a total of 420 samples of 21 different kinds of rice were collected. Mycobiota isolation and identification, the ability of citreoviridin strains to produce toxin, and the natural occurrence of citreoviridin were established. Rice samples were found to have high fungal counts and showed increasing levels from 2004 to 2007 harvest years. The most frequent genus was Aspergillus followed by Penicillium and Cladosporium. Ten out of eleven strains of P. citreonigrum were able to produce citreoviridin. Three rice samples had levels of citreoviridin ranging from 12 to 96.7 ng g(-1), and two bran samples had levels of 128 and 254 ng g(-1). These samples contaminated with P. citreonigrum and citreoviridin were involved in the beriberi cases from Maranhão State. Monitoring rice for mycotoxins in areas where this substrate is the basic food is crucial to prevent outbreaks like the one reported in this study, to improve management practice, and to diminish exposure risk of humans to these harmful toxins.

PMID: 19802756 [PubMed - indexed for MEDLINE]

968. Radiats Biol Radioecol. 2009 Jul-Aug;49(4):484-9.

[Radiobiological properties of progeny of yeast cells, which survive after the thermoradiate exposure].

[Article in Russian]

Zhurakovskaia GP, Dergacheva IP, Pereklad OV.

The delayed effects of the combined action of hyperthermia and ionizing radiation on yeast cells Saccharomyces cereviciae were investigated and compared with analogous effects of gamma-irradiation alone. It was shown that cells, survived after thermoradiate exposure, as well as cells, survived after gamma-irradiation form different in size colonies. The diminishing of size is accompanied by the increasing of the radiosensitivity of cells from these colonies. No significant difference between the radiosensitivity of the progeny of cells, survived the combined exposure, and the radiosensitivity of the progeny of gamma-irradiated cells was observed. A preposition can be made, that the thermal exposure of yeast cells before gamma-irradiation don't practically influence on the delayed effects. The magnitude of recovery (liquid holding recovery) on progeny of surviving cells is essentially smaller then the magnitude of recovery of irradiated parent culture without dependence on the type of initial exposure: combined action or just gamma-irradiation. This magnitude is correlated with the degree of the parental cell damage.

PMID: 19799372 [PubMed - indexed for MEDLINE]

969. J Toxicol Sci. 2009 Oct;34(5):541-5.

Tributyltin induces Yca1p-dependent cell death of yeast Saccharomyces cerevisiae.

Chahomchuen T, Akiyama K, Sekito T, Sugimoto N, Okabe M, Nishimoto S, Sugahara T, Kakinuma Y.

Tributyltin chloride (TBT), an environmental pollutant, is toxic to a variety of eukaryotic and prokaryotic organisms. Although it has been reported that TBT induces apoptotic cell death in mammalian, the action of TBT on eukaryotic microorganisms has not yet been fully investigated. In this study we examined the mechanism involved in cell death caused by TBT exposure in Saccharomyces cerevisiae. The median lethal concentration of TBT was 10 microM for the parent strain BY4741 and 3 microM for the pdr5Delta mutant defective in a major multidrug transporter, respectively. Fluorescence microscopic observations revealed nuclear condensation and chromatin fragmentation in cells treated with TBT indicating that cells underwent an apoptosis-like cell dearth. TBT-induced cell death was suppressed by deletion of the yca1 gene encoding a homologue of the mammalian caspase. In parallel, reactive oxygen species (ROS) were produced by TBT. These results suggest that TBT induces apoptosis-like cell death in yeast via an Yca1p-dependent pathway possibly downstream of the ROS production. This is the first report on TBT-induced apoptotic cell death in yeast.

PMID: 19797862 [PubMed - indexed for MEDLINE]

970. Allergy. 2009 Nov;64(11):1686-7. Epub 2009 Oct 1.

Occupational asthma IgE mediated due to Chrysonilia sitophila in coffee industry.

Monzón S, Gil J, Ledesma A, Ferrer L, San Juan S, Abós T.

susanamonzonballarin@hotmail.com

PMID: 19796225 [PubMed - indexed for MEDLINE]

971. Allergy. 2010 Feb;65(2):245-55. Epub 2009 Oct 1.

Symptoms after mould exposure including Stachybotrys chartarum, and comparison with darkroom disease.

Al-Ahmad M, Manno M, Ng V, Ribeiro M, Liss GM, Tarlo SM.

University of Toronto, Department of Medicine, ON, Canada.

BACKGROUND: Mould-attributed symptoms have included features which overlap with unexplained syndromes such as sick building syndrome. OBJECTIVES: We describe questionnaire and chart review findings in patients following exposure to moulds which include Stachybotrys and compare responses with two control groups.
METHODS: Thirty-two patients presented with symptoms attributed to mould exposures. Exposure identification for 25 patients had reported S tachybotrys chartarum as well as other mould (Aspergillus, Penicillium), 88% at work. The remaining seven had professionally visualized or self-reported/photographic exposure evidence only. A chart review was performed and a follow-up with a questionnaire, including questions on current health status, and nonspecific symptoms.
RESULTS: Cough, shortness of breath and chest tightness (at presentation) were reported in 79%, 70% and 64%, respectively, and persisted >6 weeks in 91%. Skin test(s) were positive to fungal extract(s) in 30%. Seventeen returned questionnaires were obtained 3.1 (SD 0.5) years after the initial clinic assessment. Among this subgroup, persisting asthma-like symptoms and symptoms suggestive of sick building syndrome were frequent, and similar to a group previously assessed for darkroom disease among medical radiation technologists. The mould-exposed group more commonly reported they were bothered when walking in a room with carpets, complained of a chemical or metallic taste in their mouth, and had problems in concentration when compared with a control physiotherapist group (P < 0.005).
CONCLUSIONS: Although only a minority with health concerns from indoor mould exposure had demonstrable mould-allergy, a significant proportion had asthma-like symptoms. Other symptoms were also common and persistent after the initial implicated exposure.

PMID: 19796210 [PubMed - indexed for MEDLINE]

972. Allergy. 2010 Feb;65(2):256-63. Epub 2009 Oct 1.

Risk factors for allergic rhinitis in Costa Rican children with asthma.

Bunyavanich S, Soto-Quiros ME, Avila L, Laskey D, Senter JM, Celedón JC.

Channing Laboratory, Boston, MA 02115, USA.

BACKGROUND: Risk factors for allergic rhinitis (AR) in asthmatics are likely distinct from those for AR or asthma alone. We sought to identify clinical and environmental risk factors for AR in children with asthma.
METHODS: We performed a cross-sectional study of 616 Costa Rican children aged 6-14 years with asthma. Candidate risk factors were drawn from questionnaire data, spirometry, methacholine challenge testing, skin testing, and serology. Two outcome measures, skin test reaction (STR)-positive AR and physician-diagnosed AR, were examined by logistic regression.
RESULTS: STR-positive AR had high prevalence (80%) in Costa Rican children with asthma, and its independent risk factors were nasal symptoms after exposure to dust or mold, parental history of AR, older age at asthma onset, oral steroid use in the past year, eosinophilia, and positive IgEs to dust mite and cockroach. Physician-diagnosed AR had lower prevalence (27%), and its independent risk factors were nasal symptoms after pollen exposure, STR to tree pollens, a parental history of AR, inhaled steroid and short-acting beta2 agonist use in the past year, household mold/mildew, and fewer older siblings. A physician's diagnosis was only 29.5% sensitive for STR-positive AR.
CONCLUSIONS: Risk factors for AR in children with asthma depend on the definition of AR. Indoor allergens drive risk for STR-positive AR. Outdoor allergens and home environmental conditions are risk factors for physician-diagnosed AR. We propose that children with asthma in Costa Rica and other Latin American nations undergo limited skin testing or specific IgE measurements to reduce the current under-diagnosis of AR.

PMCID: PMC2807901 PMID: 19796208 [PubMed - indexed for MEDLINE]

973. Protoplasma. 2009 Dec;238(1-4):59-66. Epub 2009 Oct 1.

Nitric oxide as a signaling molecule in the fission yeast Schizosaccharomyces pombe.

Kig C, Temizkan G.

Department of Molecular Biology and Genetics, Faculty of Science, Istanbul University, Vezneciler, 34134 Istanbul, Turkey. cenkkig@istanbul.edu.tr

Nitric oxide synthases (NOS) catalyze the synthesis of ubiquitous signaling molecule nitric oxide (NO) which controls numerous biological processes. Using a spectrofluorometric NOS assay, we have measured the rate of total NO production in the crude cell extracts of Schizosaccharomyces pombe. NO production was reduced in the absence of NOS cofactors calmodulin and tetrahydrobiopterin, and a competitive NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME) was able to cause a statistically significant inhibition on the rate of total NO production. These results, for the first time, provide evidence that an enzyme with a NOS-like activity may be present in the fission yeast. In order to assess the possible regulatory roles of NO as a signaling molecule in this yeast, using the differential display technique, we screened for NO-responsive genes whose expression decreased upon exposure to L-NAME and increased in response to an NO donor, sodium nitroprusside treatment. Differential expression patterns of byr1, pek1, sid1, and wis1 genes were confirmed by quantitative real-time PCR. The physiological experiments performed based on the functions and molecular interactions of these genes have pointed to the possibility that NO production might be required for sporulation in S. pombe. Taken together, these findings suggest that NO may function as a signaling molecule which can induce both transcriptional and physiological changes in the fission yeast. Hence, these data also imply that S. pombe can be used as a model system for investigating the mechanisms underlying NO-related complex signaling pathways.

PMID: 19795185 [PubMed - indexed for MEDLINE]

974. Toxicol Ind Health. 2009 Oct-Nov;25(9-10):681-92. Epub 2009 Sep 30.

Neurobehavioral and pulmonary impairment in 105 adults with indoor exposure to molds compared to 100 exposed to chemicals.

Kilburn KH.

University of Southern California, Keck School of Medicine, Pasadena, CA 91107, USA. khkilburn@sbcglobal.net

Patients exposed at home to molds and mycotoxins and those exposed to chemicals (CE) have many similar symptoms of eye, nose, and throat irritation and poor memory, concentration, and other neurobehavioral dysfunctions. To compare the neurobehavioral and pulmonary impairments associated with indoor exposures to mold and to chemicals. 105 consecutive adults exposed to molds (ME) indoors at home and 100 patients exposed to other chemicals were compared to 202 community referents without mold or chemical exposure. To assess brain functions, we measured 26 neurobehavioral functions. Medical and exposure histories, mood states score, and symptoms frequencies were obtained. Vital capacity and flows were measured by spirometry. Groups were compared by analysis of variance (ANOVA) after adjusting for age, educational attainment, and sex, by calculating predicted values (observed/predicted x 100 = % predicted). And p < .05 indicated statistical significance for total abnormalities, and test scores that were outside the confidence limits of the mean of the percentage predicted. People exposed to mold had a total of 6.1 abnormalities and those exposed to chemicals had 7.1 compared to 1.2 abnormalities in referents. Compared to referents, the exposed groups had balance decreased, longer reaction times, and blink reflex latentcies lengthened. Also, color discrimination errors were increased and visual field performances and grip strengths were reduced. The cognitive and memory performance measures were abnormal in both exposed groups. Culture Fair scores, digit symbol substitution, immediate and delayed verbal recall, picture completion, and information were reduced. Times for peg-placement and trail making A and B were increased. One difference was that chemically exposed patients had excess fingertip number writing errors, but the mold-exposed did not. Mood State scores and symptom frequencies were greater in both exposed groups than in referents. Vital capacities were reduced in both groups. Neurobehavioral and pulmonary impairments associated with exposures to indoor molds and mycotoxins were not different from those with various chemical exposures.

PMID: 19793776 [PubMed - indexed for MEDLINE]

975. Toxicol Ind Health. 2009 Oct-Nov;25(9-10):731-5. Epub 2009 Sep 30.

Creating healthier buildings.

Small BM.

Envirodesic Certification Program, Small & Rubin Ltd., Georgetown, ON, Canada. brucesmall@envirodesic.com

Some conventional building design, construction and maintenance practices create conditions that are capable of causing illness in healthy individuals or exacerbating illness in already sensitized individuals. Staying in faulty building environments may unnecessarily prolong environmental-related illness. Physician and patient awareness of such common building failures may help to diagnose environmental triggers of current illness. Architects would benefit from collaboration with environmental physicians to understand the importance of healthier building design to building occupants. Architectural education and practice is slowly incorporating better methods, often in the context of greening and sustainability. Architects are presently being advised that the needs of approximately 15% of the general population who are significantly sensitive cannot be ignored in building design. The author reviews a number of building failures and itemizes a set of relatively simple principles and design concepts that would help create new and renovated buildings that are healthier than current buildings.

PMID: 19793775 [PubMed - indexed for MEDLINE]

976. Toxicol Ind Health. 2009 Oct-Nov;25(9-10):583-615. Epub 2009 Sep 30.

The biocontaminants and complexity of damp indoor spaces: more than what meets the eyes.

Thrasher JD, Crawley S.

National Toxic Encephalopathy Foundation, Las Vegas, Nevada, USA. toxicologist1@msn.com

Nine types of biocontaminants in damp indoor environments from microbial growth are discussed: (1) indicator molds; (2) Gram negative and positive bacteria; (3) microbial particulates; (4) mycotoxins; (5) volatile organic compounds, both microbial (MVOCs) and non-microbial (VOCs); (6) proteins; (7) galactomannans; (8) 1-3-beta-D-glucans (glucans) and (9) lipopolysaccharides (LPS--endotoxins). When mold species exceed those outdoors contamination is deduced. Gram negative bacterial endotoxins, LPS in indoor environments, synergize with mycotoxins. The gram positive Bacillus species, Actinomycetes (Streptomyces, Nocardia and Mycobacterium), produce exotoxins. The Actinomycetes are associated with hypersensitivity pneumonitis, lung and invasive infections. Mycobacterial mycobacterium infections not from M. tuberculosis are increasing in immunocompetent individuals. In animal models, LPS enhance the toxicity of roridin A, satratoxins G and aflatoxin B1 to damage the olfactory epithelium, tract and bulbs (roridin A, satratoxin G) and liver (aflatoxin B1). Aflatoxin B1 and probably trichothecenes are transported along the olfactory tract to the temporal lobe. Co-cultured Streptomyces californicus and Stachybotrys chartarum produce a cytotoxin similar to doxorubicin and actinomycin D (chemotherapeutic agents). Trichothecenes, aflatoxins, gliotoxin and other mycotoxins are found in dust, bulk samples, air and ventilation systems of infested buildings. Macrocyclic trichothecenes are present in airborne particles <2 microm. Trichothecenes and stachylysin are present in the sera of individuals exposed to S. chartarum in contaminated indoor environments. Haemolysins are produced by S. chartarum, Memnoniella echinata and several species of Aspergillus and Penicillium. Galactomannans, glucans and LPS are upper and lower respiratory tract irritants. Gliotoxin, an immunosuppressive mycotoxin, was identified in the lung secretions and sera of cancer patients with aspergillosis produced by A. fumigatus, A. terreus, A. niger and A. flavus.

PMID: 19793773 [PubMed - indexed for MEDLINE]

977. Toxicol Ind Health. 2009 Oct-Nov;25(9-10):637-55. Epub 2009 Sep 30.

Mycotoxins in animal and human patients.

Coppock RW, Jacobsen BJ.

Toxicologist and Assoc Ltd, Vegreville, AB, Canada. r.coppock@toxicologist.ca

The majority of human food and animal feed production occurs in a highly managed agroecosystem. Management decisions include variety grown, tillage and irrigation methods and practices, fertilization, pest and disease control, harvesting methods, and storage and transportation practices. This system is generally managed for optimum returns to labor and capital investments. The spores of toxigenic fungi have ubiquitous distribution and toxigenic fungi exploit food sources when conditions of moisture and temperature are above minimums for growth. The safety margins in the agroecosystem are close and are influenced by extrinsic factors such as climatic events. Control of fungal growth is important in management of raw feedstuffs, foodstuffs, condiments-spices, botanicals, and other consumable substances as they are grown, harvested, stored, and transported. The risk factors for mycotoxin production are weather conditions during crop growth and when the crop is mature, damage to seeds before, during, and after harvest, how commodities are physically handled, the presence of weed seeds and other foreign material in grain, and how commodity moisture and temperature are managed during storage and transportation. Diversion of commodities and by-products from human consumption to animal feedstuffs can increase the risk of mycotoxicoses in animals. The toxicology of selected toxigenic fungi and the mycotoxins they produce are reviewed.

PMID: 19793772 [PubMed - indexed for MEDLINE]

978. Toxicol Ind Health. 2009 Oct-Nov;25(9-10):693-701. Epub 2009 Sep 30.

Detection of macrocyclic trichothecene mycotoxin in a caprine (goat) tracheal instillation model.

Layton RC, Purdy CW, Jumper CA, Straus DC.

Department of Microbiology and Immunology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.

This study demonstrates the detection and dynamics of macrocyclic trichothecene mycotoxin (MTM) tissue loading using a commercially available assay in a goat model. The detection of MTMs has been difficult and complex due to the uncertainty of what tissues to examine and when to sample. Twelve goats (two groups of each) were instilled with Stachybotrys chartarum conidial suspension via the trachea. The first group was challenged repeatedly with fungal conidia containing 1 mg/kg of MTM per instillation whereas the second group was exposed once, to spores with a calculated concentration of 5 microg/kg of mycotoxin. These toxin estimates were generated by the QuantiTox(TM) Kit assay; a conidium of S. chartarum possessed 8.5 pg of MTM. After repeated exposure of 3 days, MTM was detected in one of six animals. This animal and two others from the same group had mycotoxin detected in their serum 24 hours after challenge at a comparable level (1.69 ng/mL) to the six animals challenged with a single dose (2.02 ng/mL) at the same time post-instillation. Results showed that MTMs are detectable in experimental animals soon after challenge and contribute to the understanding of the role of these mycotoxins in the disease process following mold exposure.

PMID: 19793770 [PubMed - indexed for MEDLINE]

979. Przegl Lek. 2009;66(6):339-40.

Acute poisoning with Tricholoma equestre.

Anand JS, Chwaluk P, Sut M.

'Pomerania Center of Toxicology, Gdańsk, Poland. jacek.anand@gmail.com

Four cases, including three adults and one child, suffering from acute poisoning with Tricholoma equestre were described. The patients had eaten from 100 to 400 grams of the mushroom within a few consecutive meals. After consuming about 1000 grams of Tricholoma equestre for 3-4 days, the subjects developed fatigue, muscle weakness, myalgia, and in two cases acute respiratory failure with the need of respiratorotherapy. Maximal serum CK was 48136 U/L in the adults and 306 U/L in children. Maximal serum levels of AST and ALT were 802 U/L and 446 U/L in adults and 39 U/L, and 56 U/L in a child. All routine biochemical tests were within normal range. No other causes of rhabdomyolysis such as parasitic or viral infections, immune diseases, trauma or exposure to medications were found. Patient, aged 72 yrs., who developed acute respiratory failure, died in the second day of hospitalization. In other patients all the above mentioned symptoms and biochemical abnormalities disappeared from 2 to 3 weeks of hospitalization. Physicians should be aware of the possibility of appearance of rhabdo-myolysis after repeated consumption of large quantities of Tricholoma equestre.

PMID: 19788144 [PubMed - indexed for MEDLINE]

980. Biocontrol Sci. 2009 Sep;14(3):87-95.

Heat activation of Neosartorya and Talaromyces ascospores and enhancement by organic acids.

Kikoku Y, Tagashira N, Gabriel AA, Nakano H.

Graduate School of Biosphere Science, Hiroshima University, 1-4-4 Kagamiyama, Higashi-Hiroshima, Hiroshima 735-8528, Japan. yutaka_kikoku@aohata.co.jp

Neosartorya and Talaromyces are typical fungi capable of producing heat resistant ascospores responsible for the spoilage of processed fruit products. In this study, the heat activation rates of Neosartorya and Talaromyces ascospores were investigated in several suspending media at various heating temperatures. Ascospores were dispersed in pH 3.5 McIlvain buffer, organic acid/alcohol-supplemented McIlvain buffer and grape juice (pH 3.5, 5.0 degrees Brix) prior to heat treatments. In McIlvain buffer, the number of germinating ascospores increased logarithmically with longer exposure to heating at an test temperatures. Heat activation rates (k values) accelerated with increasing temperature. The calculated activation energy (Ea) values were similar among ascospores from the same genus, but the Ea of the test Neosartorya spp. were greater than that of the test Talaromyces spp. Greater k values were calculated from acetate-supplemented McIlvain buffer and grape juice. Similarly, normal- and branched-chain fatty acids were shown to enhance the heat activation rate of the ascospores in McIlvain buffer systems. These results could assist the food industry in designing adequate thermal processes for food products against the heat resistant fungi.

PMID: 19785281 [PubMed - indexed for MEDLINE]

981. J Anim Sci. 2010 Jan;88(1):408-15. Epub 2009 Sep 25.

Contractile response of fescue-naive bovine lateral saphenous veins to increasing concentrations of tall fescue alkaloids.

Klotz JL, Kirch BH, Aiken GE, Bush LP, Strickland JR.

USDA-ARS, Forage-Animal Production Research Unit, Lexington, KY 40546-0091, USA. james.klotz@ars.usda.gov

Various alkaloids found in endophyte-infected tall fescue have been shown to elicit different effects in the grazing animal. As part of an ongoing characterization of vascular response generated by different alkaloids, the objective of this study was to examine the vasoconstrictive potentials of ergonovine (a simple lysergic acid derivative) and alpha-ergocryptine, ergocristine, and ergocornine (all ergopeptine alkaloids) using bovine lateral saphenous veins (cranial branch) biopsied from fescue-naïve cattle. Segments (2 to 3 cm) of vein were surgically biopsied from healthy crossbred yearling cattle (n = 18; 274 +/- 8 kg of BW). Veins were trimmed of excess fat and connective tissue, sliced into 2 to 3 mm sections, and suspended in a myograph chamber containing 5 mL of oxygenated Krebs-Henseleit buffer (95% O(2)/5% CO(2); pH = 7.4; 37 degrees C). Tissue was allowed to equilibrate at 1 g of tension for 90 min before initiation of treatment additions. Increasing doses of each alkaloid (1 x 10(-10) to 1 x 10(-4) M) were administered every 15 min after buffer replacement. Data were normalized as a percentage of contractile response induced by a reference dose of norepinephrine (1 x 10(-4) M). Exposure of vein segments to increasing concentrations of ergocryptine, ergocristine, and ergonovine did not result in a contractile response until 1 x 10(-7) M, and ergocornine was even less potent (P < 0.05). Ergonovine had a greater maximal contractile intensity than ergocristine and ergocryptine (P < 0.05), with the 1 x 10(-4) M responses of ergonovine, ergocristine, ergocryptine, and ergocornine reaching maximums of 68.5 +/- 4.1, 45.5 +/- 4.5, 42.9 +/- 4.1%, and 57.2 +/- 9.9% of the norepinephrine maximum, respectively. The contractile response to increasing concentrations of ergonovine vs. ergocryptine, ergocristine, and ergocornine were opposite from previous evaluations of ergoline (e.g., lysergic acid) and ergopeptine (e.g., ergovaline) alkaloids using this bioassay, where the ergopeptine generated the greater contractile intensity. These data indicate that ergopeptines structurally different only at a single position of the peptide moiety do not exhibit differing contractile responses when considering contractile intensity. This difference may alter the potency when considering ergocornine was less potent than ergocryptine or ergocristine. These alkaloids may need to be considered when evaluating causative agents vasoconstriction associated with tall fescue-induced toxicosis.

PMID: 19783700 [PubMed - indexed for MEDLINE]

982. Dent Mater. 2010 Jan;26(1):76-82.

Candida albicans adherence on silicone elastomers: effect of polymerisation duration and exposure to simulated saliva and nasal secretion.

Kurtulmus H, Kumbuloglu O, Ozcan M, Ozdemir G, Vural C.

Ege University, Faculty of Dentistry, Department of Prosthodontics, Izmir, Turkey.

OBJECTIVES: The surfaces of maxillo-facial prostheses made of silicone elastomers exposed to soft tissues may interact with saliva and nasal secretion. These body fluids may lead to colonisation of microorganisms on their surfaces leading to their degradation or infection. This study investigated Candida albicans adhesion onto commercial maxillo-facial silicone elastomers based on different polymerisation processes.
METHODS: Room-temperature polymerised maxillo-facial silicone elastomers (N=48) (10 mm x 10 mm x 2 mm) processed at different durations [VerSilTal VST-30 (20 min), VST-50 (12h overnight), VST-50F (6h)] were studied. C. albicans was chosen as a model organism for this study. The specimens were randomly divided into two subgroups and incubated in either 1.5 ml simulated saliva or nasal secretion containing C. albicans (ATCC 60193, set to 0.5 OD, 540 nm in advance) for 2h. Candida assays and adherence assays were made by inoculating C. albicans into Mueller Hinton Broth, Fluka added 500 mmol sucrose overnight. After fixation, specimens were stained by using sterilised Methylene Blue stain (Merck) and evaluated under optical microscope and SEM. For each material, on each specimen 15 different areas (mm(2)) were counted. Data were analysed using one-way ANOVA, paired sample t-test and Tukey's HSD (alpha=0.05).
RESULTS: Material type (p<0.05) and exposure media (p<0.05) showed a significant influence on the C. albicans adherence. VST-30 material showed the most C. albicans adherence in both saliva and nasal secretion (mean rank: 99.84 and 53.47, respectively) (p<0.05) and VST-50 had the least colonisation in both media (10.35 and 5.57, respectively). Microscopic evaluation showed clusters of blastospore cells of C. albicans being more spread out on VST-30 whereas cells were more localised on VST-50 and VST-50F. SIGNIFICANCE: Among the tested materials, 12h room-temperature polymerised silicone elastomer resulted in less C. albicans adherence in both artificial saliva and nasal secretion.

PMID: 19782391 [PubMed - indexed for MEDLINE]

983. Environ Pollut. 2010 Feb;158(2):455-61. Epub 2009 Sep 24.

Xanthoria parietina as a monitor of ground-level ambient ammonia concentrations.

Olsen HB, Berthelsen K, Andersen HV, Søchting U.

Department of Biology, University of Copenhagen, Universitetsparken 15, 2100 Copenhagen Ø, Denmark.

Total nitrogen in transplanted and in situ lichen thalli of Xanthoria parietina were related to ambient ammonia air concentrations measured with passive ALPHA (Adapted Low-cost Passive High Absorption) diffusion samplers in Denmark. Transplants and ALPHA samplers were exposed four months in a transect on heathland close to a pig farm. Monthly mean ammonia concentrations declined exponentially approaching background levels after 300m. Nitrogen content of the lichen transplants tended to decline with distance, though only a few stations were significantly different from each other. Where ammonia concentrations were high, maximum content of nitrogen was reached after one month of exposure. Conversely, at sites with background concentrations, it took several months to reach a statistically significant uptake. The correlation between ammonia concentration in the air and in situ X. parietina was significant.

PMID: 19781828 [PubMed - indexed for MEDLINE]

984. In Vivo. 2009 Sep-Oct;23(5):761-6.

Effects of Agaricus blazei Murill extract on immune responses in normal BALB/c mice.

Tang NY, Yang JS, Lin JP, Hsia TC, Fan MJ, Lin JJ, Weng SW, Ma YS, Lu HF, Shen JJ, Lin JG, Chung JG.

School of Chinese Medicine, Taichung, Taiwan, PCR.

Agaricus blazei Murill (ABM) has shown particularly strong results in treating and preventing cancer and has also traditionally been used as a food source in Brazil. However, the exact immune responses regarding the phagocytosis of macrophage and, the activity of natural killer (NK) cells in normal mice after exposure to ABM extract was unclear. The goal of this study was to investigate whether or not ABM extract can promote immune responses in normal BALB/c mice. BALB/c mice were treated with different doses of ABM extract for different time periods. The results indicated that ABM extract significantly promoted the proliferation of splenocytes both in vitro and in vivo. ABM extract promoted the levels of interleukein-6 (IL-6) and, interferon-gamma (IFN-gamma) but reduced the levels of IL-4 in vitro and in vivo. The percentage of macrophages with phagocytosis after ABM extract treatment increased and these effects were of dose-dependent manners, both in vitro and in vivo. YAC-1 target cells were killed by NK cells from the mice after treatment with ABM extract at 3 and 6 mg/kg/day for up to 14 days at target cell ratios of 25:1 and 50:1. Taken together, these results show that ABM extract promoted immunomodulations in normal BALB/c mice in vitro and in vivo.

PMID: 19779112 [PubMed - indexed for MEDLINE]

985. New Solut. 2009;19(3):355-64.

Who's sick at school: linking poor school conditions and health disparities for Boston's children.

Graham T, Zotter J, Camacho M.

MassCOSH, Dorchester, MA 02122, USA. tolle.graham@masscosh.org

A recent review of student asthma rates and environmental audits of school buildings suggests that schools with poor indoor air quality have higher-than-average rates of asthma. Many Boston Public School (BPS) children and staff are learning and working in poor indoor environmental conditions that not only can exacerbate asthma, but also lead to other problems ranging from allergies and sinus infections to adverse academic performance [1]. The Boston Urban Asthma Coalition (BUAC) conducted a preliminary analysis of 2004-05 childhood asthma rates for BPS students and compared them to the 2004-05 environmental audits of the top 10 schools with environmental problems. This analysis suggests that schools with the highest rates of leaks, mold, and pest infestations also have higher-than-average asthma rates for children.

PMID: 19778832 [PubMed - indexed for MEDLINE]

986. J Eur Acad Dermatol Venereol. 2010 Mar;24(3):353-5. Epub 2009 Sep 18.

Carpet weaving: an occupational risk for onychomycosis?

Kaçar N, Ergin S, Ergin C, Arslan S, Erdoğan B.

Department of Dermatology, Faculty of Medicine, Pamukkale University, Denizli, Turkey. n_gelincik@yahoo.com

BACKGROUND: Some occupations carry a risk for fungal infections.
OBJECTIVE: To investigate the prevalence of onychomycosis in carpet weavers.
METHODS: Seventy-seven weavers (the mean age +/- SD = 32.97 +/- 12.38) from three factories and 77 controls (the mean age +/- SD = 38.32 +/- 12.38) were examined for onychomycosis. Samples from nails and the carpets, which were being weaved, were taken for mycological investigations.
RESULTS: Direct microscopic examination of only two controls' normal-appearing nails was positive. Fungal growth was observed in the culture of four weavers' normal-appearing nails. It was watched over that most of the weavers had polished-appearing nails and were using a glue containing cyanoacrylate to restore their broken nails due to weaving.
CONCLUSION: The fungal growth observed in weavers' nails has been accepted as colonization. There is no data about the presence of fungi on normal-appearing nails. So, we thought that the weavers with fungal colonization should be followed for the development of onychomycosis.

PMID: 19778359 [PubMed - indexed for MEDLINE]

987. Transfusion. 2010 Jan;50(1):128-38. Epub 2009 Sep 22.

A prospective study of multiple donor exposure blood recipients: surveillance value and limitations for hemovigilance.

Zou S, Wu Y, Cable R, Dorsey K, Tang Y, Hapip CA, Melmed R, Trouern-Trend J, Carrano D, Champion M, Fujii K, Fang C, Dodd R.

Jerome H. Holland Laboratory, American Red Cross Blood Services, Rockville, Maryland 20855, USA. zous@usa.redcross.org

BACKGROUND: There have been few recent systematic studies of blood recipients for direct evidence of blood safety, especially for emerging pathogens that may pose a threat to the blood supply. STUDY DESIGN AND METHODS: Recipients who would likely require transfusion from multiple donors were recruited and a blood specimen was collected before their first study transfusion and at intervals after their study transfusion(s). Blood samples associated with the units that were transfused to enrolled recipients were also collected. Part of each recipient specimen and selected donor specimens was tested for the targeted blood-borne agents, parvovirus B19 (B19) and Chlamydia pneumoniae (Cp), that were piloted in this study, and the remaining material was kept in a repository.
RESULTS: Between April 2004 and December 2006, a total of 120 recipients were recruited with 4047 subsequent donor exposures. On average, each recipient was followed up seven times. Of recipients who were adequately followed up and were initially immunoglobulin G antibody negative, one in 31 and one to two in 49 seroconverted to B19 and Cp after a total of 922 and 1413 evaluable transfusions, respectively. The detection of seroconversion was complicated by passively acquired donor antibodies for these two seroprevalent agents. Negative results for nucleic acids of the agents limited our ability to further clarify the relationship of these seroconversions to transfusion-transmitted infection.
CONCLUSION: The risk of transfusion-associated B19 infection appears to be low but no conclusion of transfusion transmission can be made for Cp. The approach piloted through this study offers added value beyond the current hemovigilance strategy in the United States.

PMID: 19778336 [PubMed - indexed for MEDLINE]

988. Toxicol Mech Methods. 2009 Feb;19(2):79-85.

Effects of Fusarium mycotoxin butenolide on myocardial mitochondria in vitro.

Wang YM, Liu JB, Peng SQ.

Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Fengtai District, Beijing, PR China.

Fusarium mycotoxin toxicosis has been implicated in the etiology of Keshan disease, an endemic mitochondrial cardiomyopathy prevailing in certain areas of China. Butenolide (4-acetamido-4-hydroxy-2-butenoic acid gamma-lactone) is one of the Fusarium mycotoxins which are frequently detected from cereal grains in endemic areas. A recent study indicates that this mycotoxin induces rat cardiotoxicity, but its effect on the myocardial mitochondria remains unclear. The present study is therefore undertaken to explore the toxic effect potential of butenolide on the myocardial mitochondria. Exposure of cultured cardiac myocytes to 50 microg/ml of butenolide provoked dissipation of mitochondrial membrane potential. Incubation of isolated rat myocardial mitochondria with butenolide of 100 microg/ml for 60 min resulted in mitochondrial swelling, indicating the occurrence of mitochondrial permeability transition. Furthermore, marked oxidative damage in myocardial mitochondria was observed after incubation of isolated myocardial mitochondria with butenolide ranging from 0 to 50 microg/ml for 60 min, as manifested by concentration-dependent increases in the production of thiobarbituric acid reactive substances, the indicator of lipid peroxidation. Contrarily, a representative antioxidant glutathione significantly alleviated this oxidative mitochondrial damage induced by butenolide. In conclusion, these observations clearly show that butenolide can induce dysfunction of myocardial mitochondria, and oxidative damage appears to play a crucial role in these deleterious effects. The present study supports the hypothesis that mycotoxin toxicosis is a probable etiological factor of Keshan disease, the mitochondrial cardiomyopathy.

PMID: 19778250 [PubMed - indexed for MEDLINE]

989. J Food Prot. 2009 Sep;72(9):2006-16.

Biological strategies to counteract the effects of mycotoxins.

Kabak B, Dobson AD.

Department of Food Engineering, Faculty of Engineering, Hitit University, Corum 19030, Turkey. bkabak@cu.edu.tr

Mycotoxins are fungal secondary metabolites that if ingested can cause a variety of adverse effects on both humans and animals, ranging from allergic responses to death. Therefore, exposure to mycotoxins should be minimized. A variety of physical, chemical, and biological methods have been developed for decontamination and/or detoxification of mycotoxins from contaminated foods and feeds. This overview details the latest developments in the biological control of both fungal infection and mycotoxin formation and describes the detoxification of many of the most important mycotoxins by microorganisms. This review also addresses the potential for use of microorganisms as mycotoxin binders in the gastrointestinal tract of both humans and animals, thereby reducing the potential deleterious effects of exposure to these toxins.

PMID: 19777908 [PubMed - indexed for MEDLINE]

990. Yeast. 2009 Dec;26(12):641-53.

Yap4 PKA- and GSK3-dependent phosphorylation affects its stability but not its nuclear localization.

Pereira J, Pimentel C, Amaral C, Menezes RA, Rodrigues-Pousada C.

Genomics and Stress Laboratory, Instituto de Tecnologia Química e Biológica, Av. da República, Apt. 127, 2781-901 Oeiras, Portugal.

Yap4 is a nuclear-resident transcription factor induced in Saccharomyces cerevisiae when exposed to several stress conditions, which include mild hyperosmotic and oxidative stress, temperature shift or metal exposure. This protein is also phosphorylated. Here we report that this modification is driven by PKA and GSK3. In order to ascertain whether Yap4 is directly or indirectly phosphorylated by PKA, we searched for stress and PKA-related kinases that could phosphorylate Yap4. We show that phosphorylation is independent of the kinases Rim15, Yak1, Sch9, Slt2, Ste20 and Ptk2. In addition, we showed that Yap4 phosphorylation is also abrogated in the triple GSK3 mutant mck1 rim11 yol128c. Furthermore, our data reveal that Yap4 nuclear localization is independent of its phosphorylation state. This protein has several putative phosphorylation sites, but only the mutation of residues T192 and S196 impairs its phosphorylation under different stress conditions. The ability of the non-phosphorylated forms of Yap4 to partially rescue the hog1 severe sensitivity phenotype is not affected, suggesting that Yap4 activity is maintained in the absence of phosphorylation. However, this modification seems to be required for stability of the protein, as the non-phosphorylated form has a shorter half-life than the phosphorylated one.

PMID: 19774548 [PubMed - indexed for MEDLINE]

991. Environ Sci Pollut Res Int. 2010 Mar;17(3):603-10. Epub 2009 Sep 23.

Bioremediation of acidic oily sludge-contaminated soil by the novel yeast strain Candida digboiensis TERI ASN6.

Sood N, Patle S, Lal B.

TERI University, India Habitat Centre, New Delhi, India.

BACKGROUND, AIM, AND SCOPE: Primitive wax refining techniques had resulted in almost 50,000 tonnes of acidic oily sludge (pH 1-3) being accumulated inside the Digboi refinery premises in Assam state, northeast India. A novel yeast species Candida digboiensis TERI ASN6 was obtained that could degrade the acidic petroleum hydrocarbons at pH 3 under laboratory conditions. The aim of this study was to evaluate the degradation potential of this strain under laboratory and field conditions. MATERIALS AND METHODS: The ability of TERI ASN6 to degrade the hydrocarbons found in the acidic oily sludge was established by gravimetry and gas chromatography-mass spectroscopy. Following this, a feasibility study was done, on site, to study various treatments for the remediation of the acidic sludge. Among the treatments, the application of C. digboiensis TERI ASN6 with nutrients showed the highest degradation of the acidic oily sludge. This treatment was then selected for the full-scale bioremediation study conducted on site, inside the refinery premises.
RESULTS: The novel yeast strain TERI ASN6 could degrade 40 mg of eicosane in 50 ml of minimal salts medium in 10 days and 72% of heneicosane in 192 h at pH 3. The degradation of alkanes yielded monocarboxylic acid intermediates while the polycyclic aromatic hydrocarbon pyrene found in the acidic oily sludge yielded the oxygenated intermediate pyrenol. In the feasibility study, the application of TERI ASN6 with nutrients showed a reduction of solvent extractable total petroleum hydrocarbon (TPH) from 160 to 28.81 g kg(-1) soil as compared to a TPH reduction from 183.85 to 151.10 g kg(-1) soil in the untreated control in 135 days. The full-scale bioremediation study in a 3,280-m(2) area in the refinery showed a reduction of TPH from 184.06 to 7.96 g kg(-1) soil in 175 days. DISCUSSION: Degradation of petroleum hydrocarbons by microbes is a well-known phenomenon, but most microbes are unable to withstand the low pH conditions found in Digboi refinery. The strain C. digboiensis could efficiently degrade the acidic oily sludge on site because of its robust nature, probably acquired by prolonged exposure to the contaminants.
CONCLUSIONS: This study establishes the potential of novel yeast strain to bioremediate hydrocarbons at low pH under field conditions. RECOMMENDATIONS AND PERSPECTIVES: Acidic oily sludge is a potential environmental hazard. The components of the oily sludge are toxic and carcinogenic, and the acidity of the sludge further increases this problem. These results establish that the novel yeast strain C. digboiensis was able to degrade hydrocarbons at low pH and can therefore be used for bioremediating soils that have been contaminated by acidic hydrocarbon wastes generated by other methods as well.

PMID: 19774407 [PubMed - indexed for MEDLINE]

992. Allergy Asthma Proc. 2009 Jul-Aug;30(4):433-42.

Clinical reactivity to ingestion challenge with mixed mold extract may be enhanced in subjects sensitized to molds.

Luccioli S, Malka-Rais J, Nsouli TM, Bellanti JA.

International Center for Interdisciplinary Studies of Immunology, National Jewish Health, Denver, Colorado, USA.

Manifestations of mold allergy are classically associated with inhalation of mold spores leading to symptoms of asthma and other respiratory illnesses. It is largely unknown, however, whether ingestion of aeroallergenic molds, mold spores, or other fungi found in food can also elicit hypersensitivity reactions in mold-sensitive individuals. The aim of this study was to evaluate the association between exposure to molds by oral challenge and elicitation of symptoms in mold- versus nonmold-sensitive individuals. Thirty-four adult atopic subjects were randomized into mold-sensitive groups based on skin test reactivity by skin percutaneous testing (SPT) and/or intradermal (ID) testing to a mixed mold (MM) extract preparation. All subjects underwent a single-blinded, placebo-controlled food challenge to the MM preparation. A modified scoring system was used to grade the clinical severity of symptoms elicited by challenge. All subjects tolerated challenges to the maximal oral mold dose concentration. However, higher symptom scores after challenge were found in mold-sensitive subjects compared with nonmold-sensitive subjects (p = 0.01). When mold-sensitive subjects were compared based on SPT and/or ID reactivity, higher symptom scores and lower symptom-eliciting concentrations of mold were associated with the SPT reactive subgroup compared with the subgroup with ID reactivity alone. In summary, based on our challenge results and scoring model, mold-sensitive subjects compared with nonmold-sensitive subjects experienced cumulatively higher symptom scores after oral challenge to an MM extract preparation. Future studies are warranted to confirm whether ingestion of aeroallergenic molds in food may be another contributor to symptoms in mold-sensitive individuals.

PMID: 19772765 [PubMed - indexed for MEDLINE]

993. Allergy Asthma Proc. 2009 Jul-Aug;30(4):377-85.

Low-cost interventions improve indoor air quality and children's health.

Johnson L, Ciaccio C, Barnes CS, Kennedy K, Forrest E, Gard LC, Pacheco F, Dowling P, Portnoy JM.

The Children's Mercy Hospital, Kansas City, Missouri 64108, USA.

Intervention in the home environment to reduce asthma triggers theoretically improves health outcomes for asthmatic children. Practical benefit from application of these interventions has proven difficult. This single-blind study tested the effectiveness of simple low-cost home interventions in improving health scores of children with asthma. Families with at least one asthmatic child were recruited. Initial health examination, health, and home assessments were conducted and targeted interventions were implemented. Interventions included dehumidification, air filtration, furnace servicing, and high-efficiency furnace filters. When present, gross fungal contamination was remediated. Asthma education was provided along with education in healthy home practices. Follow-up assessments were conducted after 6 months. Health surveys were completed at enrollment and follow-up. This study enrolled 219 children with asthma. Home inspections and interventions were conducted in 181 homes and 83 families completed all phases. Reduction in asthma and allergy-related health scores was shown in follow-up health surveys. Health improvements were significant for cough when heating, ventilation, and air conditioning (HVAC) service and dehumidification were used. Breathing problems were significantly improved for dehumidification, HVAC service, and room air cleaners. Total dust allergen load was reduced for the dehumidification group (p < 0.05). Mold spore counts were reduced one order of magnitude in 25% of the homes. Indoor spore counts adjusted for outdoor spore levels were reduced overall (p < 0.01). Simple low-cost interventions directed to producing cleaner indoor air coupled with healthy home education improve the indoor air quality and health in asthmatic children.

PMID: 19772759 [PubMed - indexed for MEDLINE]

994. Fungal Genet Biol. 2010 Feb;47(2):117-26. Epub 2009 Sep 19.

Fungal echinocandin resistance.

Walker LA, Gow NA, Munro CA.

School of Medical Sciences, University of Aberdeen, Aberdeen, AB25 2ZD, UK.

The echinocandins are the newest class of antifungal agents in the clinical armory. These secondary metabolites are non-competitive inhibitors of the synthesis of beta-(1,3)-glucan, a major structural component of the fungal cell wall. Recent work has shown that spontaneous mutations can arise in two hot spot regions of Fks1 the target protein of echinocandins that reduce the enzyme's sensitivity to the drug. However, other strains have been isolated in which the sequence of FKS1 is unaltered yet the fungus has decreased sensitivity to echinocandins. In addition it has been shown that echinocandin-treatment can induce cell wall salvage mechanisms that result in the compensatory upregulation of chitin synthesis in the cell wall. This salvage mechanism strengthens cell walls damaged by exposure to echinocandins. Therefore, fungal resistance to echinocandins can arise due to the selection of either stable mutational or reversible physiological alterations that decrease susceptibility to these antifungal agents.

PMCID: PMC2812698 PMID: 19770064 [PubMed - indexed for MEDLINE]

995. Trans Am Clin Climatol Assoc. 2009;120:33-48.

Toward a comprehensive understanding of allergic lung disease.

Corry DB, Kheradmand F.

Department of Medicine, One Baylor Plaza, BCM285, Baylor College of Medicine, Houston, TX 77030, USA. dcorry@bcm.tmc.edu

Allergic asthma is a respiratory disease induced by exposure to environmental agents that elicit allergic inflammation and transient airway obstruction and which produce the characteristic symptoms of cough and dyspnea. Prior to the advent of experimental models, asthma was believed to be caused primarily by the degranulation of mast cells and eosinophils primed by antigen-specific immunoglobulin E (IgE). More recent studies in mice have shown that T cells primarily mediate antigen-dependent airway obstruction and allergic inflammation through secretion of the cytokines interleukin 4 (IL- 4) and IL-13. Our additional studies indicate that a major environmental link to asthma may be through exposure to environmental proteinases and especially airway infection by proteinase-producing organisms such as fungi. Pending verification in humans, these findings suggest entirely new therapeutic interventions in asthma that include the restricted use of anti-inflammatory therapy and universal application of anti-fungal agents.

PMCID: PMC2744551 PMID: 19768161 [PubMed - indexed for MEDLINE]

996. Can J Microbiol. 2009 Jul;55(7):901-4.

The fate and efficacy of benomyl applied to field soils to suppress activity of arbuscular mycorrhizal fungi.

O'Connor P, Manjarrez M, Smith SE.

Soil and Land Systems, School of Earth and Environmental Sciences, Waite Campus, The University of Adelaide, Adelaide, South Australia 5005, Australia. patrick.oconnor@adelaide.edu.au

A systematic application of the fungicide benomyl was used to follow up the suppression of arbuscular mycorrhizal (AM) colonization and to determine its fungitoxic activity and persistence at different depths. Repeated applications of benomyl reduced AM colonization mainly in the upper 0-4 cm layer of the treated soils. Furthermore, AM colonization decreased with soil depth. The activity and persistence of this fungicide was reduced over small changes in depth in the first 10 cm of the soil profile beneath a semiarid herbland at Brookfield Conservation Park (South Australia). Repeated applications of the fungicide only slightly increased the levels of toxicity in the soils, probably because of biodegradation of the fungicide in soils with a recent history of exposure to the fungicide. The decline in fungicide activity at depth was correlated with a decline in the suppressive effect of the fungicide on the activity of AM fungi.

PMID: 19767864 [PubMed - indexed for MEDLINE]

997. Can J Microbiol. 2009 Jul;55(7):887-94.

Oxidative stress response of Mycosphaerella fijiensis, the causal agent of black leaf streak disease in banana plants, to hydrogen peroxide and paraquat.

Beltrán-García MJ, Manzo-Sanchez G, Guzmán-González S, Arias-Castro C, Rodríguez-Mendiola M, Avila-Miranda M, Ogura T.

Departamento de Química ICET, Universidad Autónoma de Guadalajara, Patria 1201, Lomas del Valle 44100, Guadalajara, Jalisco, México.

Mycosphaerella fijiensis causes black leaf streak disease in banana and plantain. This fungus is usually attacked by reactive oxygen species secreted by the plant or during exposure to fungicide, however, little is known about the antioxidant response of the fungus. In this study, mycelia were observed to totally decompose 30 mmol/L of hydrogen peroxide (H2O2) within 120 min, liberating oxygen bubbles, and also to survive in concentrations as high as 100 mmol/L H2O2. The oxidative stress responses to H2O2, paraquat, and hydroquinone were characterized in terms of the activities of catalase and superoxide dismutase (SOD). Two active catalase bands were seen in native PAGE induced by H2O2. Band I had monofunctional activity and band II had bifunctional catalase-peroxidase activity. Two isozymes of SOD, distinguishable by their cyanide sensitivity, were found; CuZnSOD was the main one. The combination of H2O2 and 3-aminotriazole reduced the accumulation of biomass up to 40% compared with exposure to H2O2 alone, suggesting that catalase is important for the rapid decomposition of H2O2 and has a direct bearing on cell viability. The results also suggest that the superoxide anion formed through the redox of paraquat and hydroquinone has a greater effect than H2O2 on the cellular viability of M. fijiensis.

PMID: 19767862 [PubMed - indexed for MEDLINE]

998. Semin Respir Crit Care Med. 2009 Oct;30(5):539-46. Epub 2009 Sep 16.

Atypical mycobacterial and fungal infections in cystic fibrosis.

Whittaker LA, Teneback C.

Division of Pulmonary and Critical Care Medicine, University of Vermont College of Medicine, Burlington, Vermont 05405, USA. laurie.whittaker@uvm.edu

Nontuberculous mycobacteria (NTM) and fungi are prevalent in the sputum of cystic fibrosis patients and are increasingly recognized to cause clinically significant disease. In both instances the organisms are ubiquitous within the environment making exposure common, although specific risk factors that contribute to active pulmonary infection have not been identified. A consistent and aggressive approach to screening for NTM and fungi within the cystic fibrosis airway is likely indicated, especially in the setting of clinical deterioration despite standard antipseudomonal therapies.

PMID: 19760541 [PubMed - indexed for MEDLINE]

999. Phytochemistry. 2009 Jul-Aug;70(11-12):1421-7. Epub 2009 Sep 14.

Mycorrhization alleviates benzo[a]pyrene-induced oxidative stress in an in vitro chicory root model.

Debiane D, Garçon G, Verdin A, Fontaine J, Durand R, Shirali P, Grandmougin-Ferjani A, Lounès-Hadj Sahraoui A.

Univ Lille Nord de France, F-59000 Lille, France.

Among chemicals that are widely spread both in terrestrial and aquatic ecosystems, benzo[a]pyrene is a major source of concern. However, little is known about its adverse effects on plants, as well as about the role of mycorrhization in protection of plant grown in benzo[a]pyrene-polluted conditions. Hence, to contribute to a better understanding of the adverse effects of polycyclic aromatic hydrocarbons on the partners of mycorrhizal symbiotic association, benzo[a]pyrene-induced oxidative stress was studied in transformed Cichorium intybus roots grown in vitro and colonized or not by Glomus intraradices. The arbuscular mycorrhizal fungus development (colonization, extraradical hyphae length, and spore formation) was significantly reduced in response to increasing concentrations of benzo[a]pyrene (35-280 microM). The higher length of arbuscular mycorrhizal roots, compared to non-arbuscular mycorrhizal roots following benzo[a]pyrene exposure, pointed out a lower toxicity of benzo[a]pyrene in arbuscular mycorrhizal roots, thereby suggesting protection of the roots by mycorrhization. Accordingly, in benzo[a]pyrene-exposed arbuscular mycorrhizal roots, statistically significant decreases were observed in malondialdehyde concentration and 8-hydroxy-2'-desoxyguanosine formation. The higher superoxide dismutase activity detected in mycorrhizal chicory roots could explain the benzo[a]pyrene tolerance of the colonized roots. Taken together, these results support an essential role of mycorrhizal fungi in protecting plants submitted to polycyclic aromatic hydrocarbon, notably by reducing polycyclic aromatic hydrocarbon-induced oxidative stress damage.

PMID: 19758666 [PubMed - indexed for MEDLINE]

1000. J Occup Environ Hyg. 2009 Nov;6(11):671-8.

Molds and mycotoxins in indoor environments--a survey in water-damaged buildings.

Bloom E, Nyman E, Must A, Pehrson C, Larsson L.

Lund University, Department of Laboratory Medicine, Division of Medical Microbiology, Lund, Sweden.

Mycotoxins are toxic, secondary metabolites frequently produced by molds in water-damaged indoor environments. We studied the prevalence of selected, potent mycotoxins and levels of fungal biomass in samples collected from water-damaged indoor environments in Sweden during a 1-year period. One hundred samples of building materials, 18 samples of settled dust, and 37 samples of cultured dust were analyzed for: (a) mycoflora by microscopy and culture; (b) fungal chemical marker ergosterol and hydrolysis products of macrocyclic trichothecenes and trichodermin (verrucarol and trichodermol) by gas chromatography-tandem mass spectrometry; and (c) sterigmatocystin, gliotoxin, aflatoxin B(1), and satratoxin G and H by high performance liquid chromatography-tandem mass spectrometry. Sixty-six percent of the analyzed building materials samples, 11% of the settled dust samples, and 51% of the cultured dust samples were positive for at least one of the studied mycotoxins. In addition, except in the case of gliotoxin, mycotoxin-positive building material samples contained 2-6 times more ergosterol than mycotoxin-negative samples. We show that (a) molds growing on a range of different materials indoors in water-damaged buildings generally produce mycotoxins, and (b) mycotoxin-containing particles in mold-contaminated environments may settle on surfaces above floor level. The mass spectrometry methods used in this study are valuable tools in further research to survey mycotoxin exposure and investigate potential links with health effects.

PMID: 19757292 [PubMed - indexed for MEDLINE]

1001. Neurotoxicol Teratol. 2010 Mar-Apr;32(2):226-33. Epub 2009 Sep 13.

Trolox ameliorates 3-nitropropionic acid-induced neurotoxicity in rats.

Al Mutairy A, Al Kadasah S, Elfaki I, Arshaduddin M, Malik D, Al Moutaery K, Tariq M.

Department of Biochemistry, College of Medicine, King Faisal University, Dammam, Saudi Arabia.

3-nitropropionic acid (3-NPA) is a naturally occurring neurotoxin produced by legumes of the genus Astragalus and Arthrium fungi. Acute exposure to 3-NPA results in striatal astrocytic death and variety of behavior dysfunction in rats. Oxidative stress has been reported to play an important role in 3-NPA-induced neurotoxicity. Trolox is a potent free radical chain breaking antioxidant which has been shown to restore structure and function of the nervous system following oxidative stress. This rapid and efficient antioxidant property of trolox was attributed to its enhanced water solubility as compared with alpha-tocopherol. This investigation was aimed to study the effect of trolox against 3-NPA-induced neurotoxicity in female Wistar rats. The animals received trolox (0, 40 mg, 80 mg and 160 mg/kg, orally) daily for 7 days. 3-NPA (25mg/kg, i.p.) was administered daily 30 min after trolox for the same duration. One additional group of rats served as control (vehicle only). On day 8, the animals were observed for neurobehavioral performance. Immediately after behavioral studies, the animal's brains were dissected out for histological studies. Lesions in the striatal dopaminergic neurons were assessed by immunohistochemical method using tyrosine hydroxylase immunostaining. Administration of 3-NPA alone caused significant depletion of striatal dopamine and glutathione, whereas, the levels of thiobarbituric acid reactive substance (TBARS) and nitric oxide (NO) were significantly increased suggesting an elevated level of oxidative stress. Trolox significantly and dose-dependently protected animals against 3-NPA-induced neurobehavioral, neurochemical and structural abnormalities. These results clearly suggest that protective effect of trolox against 3-NPA-induced neurotoxicity is mediated through its free radical scavenging activity.

PMID: 19755148 [PubMed - indexed for MEDLINE]

1002. Clin Microbiol Infect. 2009 Oct;15 Suppl 5:2-9.

The ecology of the Zygomycetes and its impact on environmental exposure.

Richardson M.

The University of Manchester, Manchester Academic Health Science Centre, University Hospital of South Manchester, Manchester, UK. malcolm.richardson@manchester.ac.uk

Zygomycetes are unique among filamentous fungi in their great ability to infect a broader, more heterogeneous population of human hosts than other opportunistic moulds. Various members of the Zygomycetes have been implicated in zygomycosis, although those belonging to the family Mucoraceae are isolated more frequently than those of any other family. The environmental microbiology literature provides limited insights into how common zygomycetes are in the environment, and provides a few clues about which ecological niches these fungi are found in. Mucorales are thermotolerant moulds that are supposedly ubiquitous in nature and widely found on organic substrates, including bread, decaying fruits, vegetable matter, crop debris, soil between growing seasons, compost piles, and animal excreta. The scientific and medical literature does not support this generalization. Sporangiospores released by mucorales range from 3 to 11 microm in diameter, are easily aerosolized, and are readily dispersed throughout the environment. This is the major mode of transmission. However, there are very few data concerning the levels of zygomycete sporangiospores in outdoor and indoor air, especially in geographical areas where zygomycosis is particularly prevalent. Airborne fungal spores are almost ubiquitous and can be found on all human surfaces in contact with air, especially on the upper and lower airway mucosa. Inhalation of sporangiospores must be a daily occurrence. Surprisingly, members of the Mucorales are very rarely found in nasal mucus, suggesting that spores in the mucus of airway mucosa are cleared by mucociliary transport or that there is a low level of airborne contamination. Zygomycetes are found occasionally in water-damaged buildings, as demonstrated by air-sampling, and analysis of settled dust by quantitative PCR. Moreover, inhalation of sporangiospores in dust has been linked to outbreaks of rhinocerebral or pulmonary zygomycosis due to excavation, construction, or contaminated air-conditioning filters. Whereas most zygomycete infections are community-acquired, nosocomial acquisition due to percutaneous routes of exposure is very important. Sporadic cases, and pseudo-outbreaks, have been linked to contaminated bandages and adhesive dressings, needles, and tongue depressors used to construct splints for intravenous and arterial cannulation sites in preterm infants. Insect bites or stings have been implicated in disease transmission in cases of cutaneous and subcutaneous zygomycosis, e.g. diseases caused by the Entomophthorales. Traumatic implantation of spores in dirt or in contaminated water, e.g. as occurred during the Asian tsunami, has led to infection in multiple patients.

PMID: 19754749 [PubMed - indexed for MEDLINE]

1003. Langmuir. 2009 Oct 6;25(19):11741-7.

Intracellular biogenic silver nanoparticles for the generation of carbon supported antiviral and sustained bactericidal agents.

Vijayakumar PS, Prasad BL.

Materials Chemistry Division, National Chemical Laboratory, Pune, 08, India.

Intracellular silver nanoparticles produced by exposing silver ions to the fungus Aspergillus ochraceus were heat-treated in nitrogen environment to yield silver nanoparticles embedded in carbonaceous supports. This carbonaceous matrix embedded silver nanoparticles showed antimicrobial properties against both bacteria (Gram-positive and Gram-negative) and virus (M 13 phage virus). The bactericidal effects were noticed even after washing and repeated exposure of these carbon supported silver nanoparticles to fresh bacterial cultures, revealing their sustained activity.

PMID: 19746940 [PubMed - indexed for MEDLINE]

1004. Pest Manag Sci. 2010 Feb;66(2):126-31.

Fate of vinclozolin, thiabendazole and dimethomorph during storage, handling and forcing of chicory.

Spanoghe P, Ryckaert B, Van Gheluwe C, Van Labeke MC.

Laboratory of Crop Protection Chemistry, Faculty of Bioscience Engineering, Ghent University, Ghent, Belgium.

BACKGROUND: As part of ongoing research for a sustainable production of Belgian endives, the fate of three fungicides during storage, handling and forcing of witloof chicory roots was investigated. Storage roots are protected against Sclerotinia sp. Fuckel and Phoma exigua var. exigua Desm. by means of vinclozolin and thiabendazole respectively. During hydroponic forcing, the most imminent pathogen is Phytophthora cryptogea Pethybr. & Laff., which is controlled by the use of dimethomorph.
RESULTS: Vinclozolin and thiabendazole concentrations on roots remained constant during storage at -1 degrees C. Dermal exposure of the workers in hydroponics was exceeded. Vinclozolin and thiabendazole residues were not detected 2 weeks after hydroponic forcing; dimethomorph was still detected at harvest. At harvest, the vinclozolin concentration in the chicory heads was below the maximum residue limit, but the chicory roots contained residues much above the thiabendazole and dimethomorph maximum residue level.
CONCLUSION: Vinclozolin and thiabendazole residues applied before storage are still present on the roots at the start of the forcing cycle. During the set-up of chicory roots, preventive measures are recommended, as effects of repeated human exposure to low doses of applied fungicides cannot be excluded. Dimethomorph applied at the start of the hydroponic forcing is the only pesticide detected in the drainage water at harvest. The chicory heads were safe for human consumption. However, more attention should be paid to the residues of fungicides in the roots used for cattle feeding.

PMID: 19746400 [PubMed - indexed for MEDLINE]

1005. PLoS One. 2009 Sep 10;4(9):e6946.

Synthetic morphology using alternative inputs.

Tanaka H, Yi TM.

Department of Developmental and Cell Biology, University of California Irvine, Irvine, California, USA.

Designing the shape and size of a cell is an interesting challenge for synthetic biology. Prolonged exposure to the mating pheromone alpha-factor induces an unusual morphology in yeast cells: multiple mating projections. The goal of this work was to reproduce the multiple projections phenotype in the absence of alpha-factor using a gain-of-function approach termed "Alternative Inputs (AIs)". An alternative input is defined as any genetic manipulation that can activate the signaling pathway instead of the natural input. Interestingly, none of the alternative inputs were sufficient to produce multiple projections although some produced a single projection. Then, we extended our search by creating all combinations of alternative inputs and deletions that were summarized in an AIs-Deletions matrix. We found a genetic manipulation (AI-Ste5p ste2Delta) that enhanced the formation of multiple projections. Following up this lead, we demonstrated that AI-Ste4p and AI-Ste5p were sufficient to produce multiple projections when combined. Further, we showed that overexpression of a membrane-targeted form of Ste5p alone could also induce multiple projections. Thus, we successfully re-engineered the multiple projections mating morphology using alternative inputs without alpha-factor.

PMCID: PMC2735001 PMID: 19746161 [PubMed - indexed for MEDLINE]

1006. J Colloid Interface Sci. 2009 Dec 1;340(1):74-81. Epub 2009 Aug 15.

Spontaneous dewetting-induced residue-free patterning at room temperature.

Choi SJ, Tahk D, Yoon H.

School of Chemical and Biological Engineering, Seoul National University, Seoul 151-744, South Korea. saltchoi@snu.ac.kr

A lithographic patterning method is presented that is based on dewetting induced by sequential molding under an applied pressure. Because of spontaneous dewetting taking place, the window to be opened is free from any residue and the surface exposure is instantaneously assured. This residue-free patterning can be accomplished without any heating process and surface treatment, irrespective of pattern duty ratio. The residue-free patterning is made possible with the use of a rigiflex mold and a roller that is used to bring about pressure-induced thinning leading to spontaneous dewetting. A necessary condition for the method is that the spreading coefficient of spin-coated liquid be negative. The exposed surface can be utilized as a sacrificial layer for etching of underlying layer and/or thin film deposition in a fabrication of electronic and biological devices.

PMID: 19744665 [PubMed]

1007. Infect Control Hosp Epidemiol. 2009 Oct;30(10):1000-5.

Pilot study of postexposure prophylaxis for hepatitis C virus in healthcare workers.

Corey KE, Servoss JC, Casson DR, Kim AY, Robbins GK, Franzini J, Twitchell K, Loomis SC, Abraczinskas DR, Terella AM, Dienstag JL, Chung RT.

Harvard Medical School, Boston, MA, USA.

BACKGROUND AND OBJECTIVE: Hepatitis C virus (HCV) transmission occurs in 0.2%-10% of people after accidental needlestick exposures. However, postexposure prophylaxis is not currently recommended. We sought to determine the safety, tolerability, and acceptance of postexposure prophylaxis with peginterferon alfa-2b in healthcare workers (HCWs) exposed to blood from HCV-infected patients. DESIGN: Open-label pilot trial of peginterferon alfa-2b for HCV postexposure prophylaxis. SETTING: Two academic tertiary-referral centers.
METHODS: HCWs exposed to blood from HCV-infected patients were informed of the availability of postexposure prophylaxis. Persons who elected postexposure prophylaxis were given weekly doses of peginterferon alfa-2b for 4 weeks.
RESULTS: Among 2,702 HCWs identified with potential exposures to bloodborne pathogens, 213 (7.9%) were exposed to an HCV antibody-positive source. Of 51 HCWs who enrolled in the study, 44 (86%) elected to undergo postexposure prophylaxis (treated group). Seven subjects elected not to undergo postexposure prophylaxis (untreated group). No cases of HCV transmission were observed in either the treated or untreated group, and no cases occurred in the remaining 162 HCWs who did not enroll in this study. No serious adverse events related to a peginterferon alfa-2b regimen were recorded, but minor adverse events were frequent.
CONCLUSION: In this pilot study, there was a lower than expected frequency of HCV transmission after accidental occupational exposure. Although peginterferon alfa-2b was safe, because of the lack of HCV transmission in either the treated or untreated groups there is little evidence to support routine postexposure prophylaxis against HCV in HCWs.

PMID: 19743901 [PubMed - indexed for MEDLINE]

1008. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2009 Nov;26(11):1495-500.

Fumonisin B(2) production by Aspergillus niger from grapes and natural occurrence in must.

Logrieco A, Ferracane R, Haidukowsky M, Cozzi G, Visconti A, Ritieni A.

Institute of Sciences of Food Production, CNR, Bari, Italy. antonio.logrieco@ispa.cnr.it

Aspergillus niger has been recently found to produce fumonisin B(2) (FB(2)). Thirty-one strains belonging to four Aspergillus species isolated from grape were evaluated for FB(2) production on agar plates. Four out of eight strains of A. niger produced FB(2) (29-293 microg g(-1)). None of the strains of A. uvarum (n = 7), A. tubingensis (8) and A. carbonarius (8) produced detectable amounts of toxin. The capability to produce FB(2) was also confirmed by some A. niger strains artificially inoculated on grape berries. Natural occurrence of FB(2), at levels of 0.01 and 0.4 microg ml(-1), was found in two samples of must collected in Apulian cellars in 2007. This is the first report of FB(2) contamination in must. These findings suggest that there is a potential risk of exposure to FB(2) in the grape-wine chain for consumers and that A. niger may represent the major fumonisin-producing species among black Aspergilli occurring on grapes.

PMID: 19742356 [PubMed - indexed for MEDLINE]

1009. JAMA. 2009 Sep 9;302(10):1049.

CDC links data on health and environment.

Kuehn BM.

PMID: 19738084 [PubMed - indexed for MEDLINE]

1010. J Microbiol Biotechnol. 2009 Aug;19(8):803-9.

Baicalein induces programmed cell death in Candida albicans.

Dai BD, Cao YY, Huang S, Xu YG, Gao PH, Wang Y, Jiang YY.

School of Pharmarcy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, P.R. China.

Recent evidence has revealed the occurrence of an apoptotic phenotype in Candida albicans that is inducible with environmental stresses such as acetic acid, hydrogen peroxide, and amphotericin B. In the present study, we found that the Chinese herbal medicine Baicalein (BE), which was one of the skullcapflavones, can induce apoptosis in C. albicans. The apoptotic effects of BE were detected by flow cytometry using Annexin V-FITC and DAPI, and it was confirmed by transmission electron microscopy analysis. After exposure to 4 microg/ml BE for 12 h, about 10% of C. albicans cells were apoptotic. Both the increasing intracellular levels of reactive oxygen species (ROS) and upregulation of some redox-related genes (CAP1, SOD2, TRR1) were observed. Furthermore, we compared the survivals of CAP1 deleted, wild-type, and overexpressed strains and found that Cap1p attenuated BE-initiated cell death, which was coherent with a higher mRNA level of the CAP1 gene. In addition, the mitochondrial membrane potential of C. albicans cells changed significantly ( p<0.001) upon BE treatment compared with control. Taken together, our results indicate that BE treatment induces apoptosis in C.albicans cells, and the apoptosis was associated with the breakdown of mitochondrial membrane potential.

PMID: 19734718 [PubMed - indexed for MEDLINE]

1011. Appl Environ Microbiol. 2009 Nov;75(21):6886-9. Epub 2009 Sep 4.

High-level resistance of Nosema ceranae, a parasite of the honeybee, to temperature and desiccation.

Fenoy S, Rueda C, Higes M, Martín-Hernández R, del Aguila C.

Laboratorio de Parasitología, Facultad de Farmacia, Universidad San Pablo CEU, Madrid, Spain.

Resistance of Nosema ceranae to different exposure conditions has been evaluated by using Sytox green and DAPI (4',6-diamidino-2-phenylindole) to test spore viability. High thermotolerance at 60 and 35 degrees C and resistance to desiccation were observed. However, a significant decrease in viability after freezing and a rapid degeneration of spores maintained at 4 degrees C were also detected.

PMCID: PMC2772422 PMID: 19734329 [PubMed - indexed for MEDLINE]

1012. Toxicol Appl Pharmacol. 2009 Dec 15;241(3):294-302. Epub 2009 Sep 2.

Acetylated H4K16 by MYST1 protects UROtsa cells from arsenic toxicity and is decreased following chronic arsenic exposure.

Jo WJ, Ren X, Chu F, Aleshin M, Wintz H, Burlingame A, Smith MT, Vulpe CD, Zhang L.

Department of Nutritional Sciences and Toxicology, University of California Berkeley, Berkeley, CA 94720, USA. williamjo@berkeley.edu

Arsenic, a human carcinogen that is associated with an increased risk of bladder cancer, is commonly found in drinking water. An important mechanism by which arsenic is thought to be carcinogenic is through the induction of epigenetic changes that lead to aberrant gene expression. Previously, we reported that the SAS2 gene is required for optimal growth of yeast in the presence of arsenite (As(III)). Yeast Sas2p is orthologous to human MYST1, a histone 4 lysine 16 (H4K16) acetyltransferase. Here, we show that H4K16 acetylation is necessary for the resistance of yeast to As(III) through the modulation of chromatin state. We further explored the role of MYST1 and H4K16 acetylation in arsenic toxicity and carcinogenesis in human bladder epithelial cells. The expression of MYST1 was knocked down in UROtsa cells, a model of bladder epithelium that has been used to study arsenic-induced carcinogenesis. Silencing of MYST1 reduced acetylation of H4K16 and induced sensitivity to As(III) and to its more toxic metabolite monomethylarsonous acid (MMA(III)) at doses relevant to high environmental human exposures. In addition, both As(III) and MMA(III) treatments decreased global H4K16 acetylation levels in a dose- and time-dependent manner. This indicates that acetylated H4K16 is required for resistance to arsenic and that a reduction in its levels as a consequence of arsenic exposure may contribute to toxicity in UROtsa cells. Based on these findings, we propose a novel role for the MYST1 gene in human sensitivity to arsenic.

PMCID: PMC2784148 PMID: 19732783 [PubMed - indexed for MEDLINE]

1013. Environ Sci Technol. 2009 Aug 1;43(15):6039-45.

Transcriptional profiling of Saccharomyces cerevisiae upon exposure to saxitoxin.

Cusick KD, Boyer GL, Wilhelm SW, Sayler GS.

Center for Environmental Biotechnology, The University of Tennessee 676 Dabney Hall, Knoxville, Tennessee 37966, USA.

Saxitoxin is a potent neurotoxin produced by several species of dinoflagellates and cyanobacteria. The molecular target of saxitoxin in higher eukaryotes is the voltage-gated sodium channel; however, its target in lower eukaryotic organisms remains unknown. The goal of this study was to obtain the transcriptional fingerprint of the model lower eukaryote Saccharomyces cerevisiae upon exposure to saxitoxin to identify potential genes suitable for biomarker development. Microarray analyses identified multiple genes associated with copper and iron homeostasis and sulfur metabolism as significantly differentially expressed upon exposure to saxitoxin; these results were verified with quantitative reverse-transcriptase PCR (qRT-PCR). Additionally, the qRT-PCR assays were used to generate expression profiles in a subset of the differentially regulated genes across multiple exposure times and concentrations, the results of which demonstrated that overall, genes tended to respond in a consistent manner to the toxin. In general, the genes encoding the metallothioneins CUP1 and CRS5 were induced following exposure to saxitoxin, while those encoding the ferric/ cupric reductase FRE1 and the copper uptake transporter CTR1 were repressed. The gene encoding the multicopper ferroxidase FET3, part of the high-affinity iron uptake system, was also induced in all treatments, along with the STR3 gene, which codes for the cystathionine beta-lyase found in the methionine biosynthetic pathway.

PMID: 19731715 [PubMed - indexed for MEDLINE]

1014. Nat Prod Commun. 2009 Jul;4(7):977-80.

Strain improvement and genetic characterization of indigenous Aspergillus flavus for amylolytic potential.

Shafique S, Bajwa R, Shafique S.

Institute of Mycology and Plant Pathology, University of the Punjab, Quaid-e-Azam Campus 54590-Lahore, Pakistan. sobiya_shafique@hotmail.com

Aspergillus flavus FCBP-231, a filamentous fungus, was genetically modified for its ability to reveal extra cellular alpha-amylase activity. For strain improvement, the selected strains were subjected to UV irradiation (5-40 min exposure) and EMS treatment (50-300 microg mL(-1)) for hyper activity of an alpha-amylase enzyme. The mutants were quantitatively compared with the parental strain. UV and chemical mutagenesis brought about a dramatic enhancement in enzymatic activity. The mutant strains Af-UV-5.3 and Af-Ch-5.7 exhibited 79 and 110% more enzyme activity than the native strain A. flavus FCBP-231. This improvement in enzyme activity of the mutants suggests that they are suitable strains to be used in biotechnology. RAPD-PCR analysis revealed different patterns of amplicons of native as well as mutant derivatives, which suggested that the mutation imparted changes in the genetic make up of the mutants probably involved enzyme production control.

PMID: 19731605 [PubMed - indexed for MEDLINE]

1015. Adv Appl Microbiol. 2009;69:159-82.

Chapter 6: The genomes of lager yeasts.

Bond U.

School of Genetics and Microbiology, Trinity College Dublin, Dublin 2, Ireland.

Yeasts used in the production of lagers belong to the genus Saccharomyces pastorianus. Species within this genus arose from a natural hybridization event between two yeast species that appear to be closely related to Saccharomyces cerevisiae and Saccharomyces bayanus. The resultant hybrids contain complex allopolyploid genomes and retain genetic characteristics of both parental species. Recent genome analysis using both whole genome sequencing and competitive genomic hybridization techniques has revealed the underlying composition of lager yeasts genomes. There appear to be at least 36 unique chromosomes, many of which are lager specific, resulting from recombination events between the homeologous parental chromosomes. The recombination events are limited to a defined set of genetic loci, which are highly conserved within strains of lager yeasts. In addition to the hybrid chromosomes, several non-reciprocal chromosomal translocations and inversions are also observed. Remarkably, in response to exposure to environmental stresses such as high temperatures and high osmotic pressure, the genomes appear to be highly dynamic and undergo recombination events at defined loci and alterations in the telomeric regions. The ability of environmental stress to alter the structure and composition of the genomes of lager yeasts may point to mechanisms of adaptive evolution in these species.

PMID: 19729094 [PubMed - indexed for MEDLINE]

1016. J Agric Saf Health. 2009 Jul;15(3):225-40.

Impact of in-barn manure separation on biological air quality in an experimental setup identical to that in swine buildings.

Lavoie J, Godbout S, Lemay SP, Belzile M.

Institut de Recherché Robert-Sauvé en Santé et en Sécurité du Travail (IRSST), Montreal, Québec, Canada. Lavoie.jacques@irsst.qc.ca

In-barn manure separation systems are becoming popular due to various environmental pressures on the swine industry. According to the literature, separation of feces and urine directly underneath the slats should have a positive impact on barn air quality. Removal and rapid separation of the two phases (solid/liquid) would reduce the dust and bioaerosol emissions, which would significantly improve the air quality in pig-housing facilities. From an occupational health and safety perspective, the maximum endotoxin and total bacteria concentrations to ensure workers' safety should not exceed 450 endotoxin units per cubic meter of air (EU m(-3)) and 10(4) colony-forming units per cubic meter of air (CFU m(-3)), respectively. In the current study, the effect on air quality of six in-barn manure handling systems was measured. A flat scraper system and four separation systems installed under the slats (a conveyor belt system, a conveyor net system, and a V-shaped scraper operated at two operation frequencies) were evaluated and compared to a conventional pull-plug system (control). The experiment took place in twelve independent and identical rooms housing four grower-finisher pigs each, and air samples were collected and analyzed for total dust, endotoxins, bacteria, and mold counts. The results obtained from this experimental setup show that the separation of feces and urine under the slats would concentrate at least 80% of the phosphorus in the solid phase. The total bacteria and endotoxin concentrations are lower than those found in commercial hog barns but remain higher than the recommended levels. Only the total dust concentrations are approximately 10% of their regulated value. This separation has no impact on dust and bioaerosol concentrations compared to the control.

PMID: 19728546 [PubMed - indexed for MEDLINE]

1017. SADJ. 2009 Jun;64(5):208, 210-2.

Disinfection of irreversible hydrocolloid impression material with chlorinated compounds.

Rweyendela IH, Patel M, Owen CP.

Department of Prosthodontics, School of Oral Health Sciences, University of the Witwatersrand, Johannesburg.

PROBLEM: Irreversible hydrocolloid (alginate) impressions are dimensionally unstable and difficult to disinfect.
PURPOSE: To evaluate the antimicrobial efficacy of a chlorite disinfectant (Presept) and a new formulation chlorine dioxide based disinfectant (Aseptrol) on irreversible hydrocolloid (alginate) impression material. MATERIALS AND METHODS: Alginate blocks were contaminated with Candida albicans, Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus mutans and Bacillus subtilis spores. The blocks were placed either in sterile distilled water as control, or in 48-ppm Aseptrol or Presept solution containing organic matter. Immersion times were 30 seconds, 1, 1.5, 2, 3 and 5 minutes. The blocks were then placed in sterile 0.5% sodium thiosulphate neutralizer and surviving organisms were harvested and counted using the serial dilution technique followed by culturing on appropriate media. The anti-microbial efficacy of the solution was tested for 37 days.
RESULTS: There was a consistent significant reduction (99.99%) in all tests of vegetative organisms after immersion in the Aseptrol for 30 seconds, and for spores after 1.5 minutes. It was effective against vegetative organisms for up to 27 days for a 30-second exposure. Presept significantly reduced (99.99%) C. albicans, S. aureus and S. mutans in 30 seconds, P. aeruginosa in 60 seconds, but for B. subtilis spores took at least 5 minutes. It was effective against vegetative organisms for >37 days for a 30-second exposure.
CONCLUSION: Within the limits of this study it was found that both compounds effectively disinfected the alginate in the presence of organic material, but that Aseptrol did so after an immersion time of only 1.5 minutes. This immersion time is less likely to affect the dimensional properties of the impression material. CLINICAL IMPLICATIONS: The short action time of Aseptrol may make it ideal for the disinfection of alginate impressions, and it may also find many uses for disinfection and possible sterilisation.

PMID: 19725332 [PubMed - indexed for MEDLINE]

1018. J Food Sci. 2009 Aug;74(6):M250-7.

Effects of ozone treatment on Botrytis cinerea and Sclerotinia sclerotiorum in relation to horticultural product quality.

Sharpe D, Fan L, McRae K, Walker B, MacKay R, Doucette C.

Biology Dept., Mount Saint Vincent Univ., Halifax, NS, Canada.

Botrytis cinerea and Sclerotinia sclerotiorum are fungal pathogens that cause the decay of many fruits and vegetables. Ozone may be used as an antimicrobial agent to control the decay. The effect of gaseous ozone on spore viability of B. cinerea and mycelial growth of B. cinerea and S. sclerotiorum were investigated. Spore viability of B. cinerea was reduced by over 99.5% (P < 0.01) and height of the aerial mycelium was reduced from 4.7 mm in the control to less than 1 mm after exposure to 450 or 600 ppb ozone for 48 h at 20 degrees C. Sporulation of B. cinerea was also substantially inhibited by ozone treatments. However, ozone had no significant effect on mycelial growth of S. sclerotiorum in vitro. Decay and quality parameters including color, chlorophyll fluorescence (CF), and ozone injury were further assessed for various horticultural commodities (apple, grape, highbush blueberry, and carrot) treated with 450 ppb of ozone for 48 h at 20 degrees C over a period of 12 d. Lesion size and height of the aerial mycelium were significantly reduced by the ozone treatment on carrots inoculated with mycelial agar plugs of B. cinerea or S. sclerotiorum. Lesion size was also reduced on treated apples inoculated with 5 x 10(6) spores/mL of B. cinerea, and decay incidence of treated grapes was reduced. The 450 ppb ozone for 48 h treatment had no significant effect on color of carrots and apples or on CF of apples and grapes. Ozone, an environmentally sound antimicrobial agent, inactivates microorganisms through oxidization and residual ozone spontaneously decomposes to nontoxic products. It may be applied to fruits and vegetables to reduce decay and extend shelf life.

PMID: 19723209 [PubMed - indexed for MEDLINE]

1019. J Agric Food Chem. 2009 Aug 12;57(15):7145-52.

Tolerance and stress response of Macrolepiota procera to nickel.

Baptista P, Ferreira S, Soares E, Coelho V, Bastos Mde L.

CIMO/Escola Superior Agraria, Instituto Politecnico de Braganca, Campus Santa Apolonia, Apartado 1172, 5301-855 Braganca, Portugal. pbaptista@ipb.pt

Nickel (Ni) is an essential element for many organisms; however, it is very toxic at high concentrations and also depending on the species. In macrofungi the mechanisms underlying their Ni tolerance are poorly documented. This study examines, for the first time, the participation of the antioxidative system in Macrolepiota procera exposed to different Ni2+ concentrations and their relation with Ni tolerance. The effect of the pH on Ni tolerance was also evaluated. The fungus was cultivated on solid medium with different NiCl2 concentrations (0.05, 0.2, 0.8 mM) at pH 4, 6, and 8, and fungi growth and Ni uptake were determined. The antioxidative enzymes catalase (CAT) and superoxide dismutase (SOD) and the production of hydrogen peroxide H2O2 were evaluated on fungal submerged cultures within the first hours of Ni2+ exposure. Results showed that M. procera growth decreased when Ni2+ concentrations increased, reaching a maximum growth inhibition (>80%) up to 0.2 mM of NiCl2. Ni uptake increased proportionally to Ni increase in the medium. Both Ni tolerance and Ni accumulation were affected by medium pH. Microscope observations showed differences in the size of spores produced by fungi at different Ni concentrations. Ni exposure induced oxidative stress, as indicated by the production of H2O2, the levels of which seem to be regulated by the antioxidant enzymes SOD and CAT. The time variation pattern of SOD and CAT activities indicated that the former has a greater role in alleviating the stress. The results obtained suggested that tolerance of M. procera to Ni2+ is associated with the ability of this macrofungus to initiate an efficient antioxidant defense system.

PMID: 19722588 [PubMed - indexed for MEDLINE]

1020. Genome Res. 2009 Oct;19(10):1722-31. Epub 2009 Aug 28.

Comparative genomic analyses of the human fungal pathogens Coccidioides and their relatives.

Sharpton TJ, Stajich JE, Rounsley SD, Gardner MJ, Wortman JR, Jordar VS, Maiti R, Kodira CD, Neafsey DE, Zeng Q, Hung CY, McMahan C, Muszewska A, Grynberg M, Mandel MA, Kellner EM, Barker BM, Galgiani JN, Orbach MJ, Kirkland TN, Cole GT, Henn MR, Birren BW, Taylor JW.

Department of Plant and Microbial Biology, University of California, Berkeley, 94720, USA. sharpton@berkeley.edu

While most Ascomycetes tend to associate principally with plants, the dimorphic fungi Coccidioides immitis and Coccidioides posadasii are primary pathogens of immunocompetent mammals, including humans. Infection results from environmental exposure to Coccidiodies, which is believed to grow as a soil saprophyte in arid deserts. To investigate hypotheses about the life history and evolution of Coccidioides, the genomes of several Onygenales, including C. immitis and C. posadasii; a close, nonpathogenic relative, Uncinocarpus reesii; and a more diverged pathogenic fungus, Histoplasma capsulatum, were sequenced and compared with those of 13 more distantly related Ascomycetes. This analysis identified increases and decreases in gene family size associated with a host/substrate shift from plants to animals in the Onygenales. In addition, comparison among Onygenales genomes revealed evolutionary changes in Coccidioides that may underlie its infectious phenotype, the identification of which may facilitate improved treatment and prevention of coccidioidomycosis. Overall, the results suggest that Coccidioides species are not soil saprophytes, but that they have evolved to remain associated with their dead animal hosts in soil, and that Coccidioides metabolism genes, membrane-related proteins, and putatively antigenic compounds have evolved in response to interaction with an animal host.

PMCID: PMC2765278 PMID: 19717792 [PubMed - indexed for MEDLINE]

1021. Eukaryot Cell. 2009 Nov;8(11):1616-25. Epub 2009 Aug 28.

Our paths might cross: the role of the fungal cell wall integrity pathway in stress response and cross talk with other stress response pathways.

Fuchs BB, Mylonakis E.

Harvard Medical School, Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.

Fungi occupy diverse environments and are subjected to many extreme conditions. Among the stressful conditions faced by fungi are pH changes, osmotic changes, thermal changes, oxide radicals, nutrient deprivation, and exposure to chemicals. These adversities can be found either in the environment or in animal and human hosts. The cell wall integrity (CWI) pathway provides a means to fortify and repair damages to the cell wall in order to withstand stressful environments. The CWI pathway in comprised of cell wall stress sensors that lead to activation of a mitogen-activated protein kinase (MAPK) cascade. Signaling through the MAPK cascade leads to expression of transcription factors that facilitate biosynthesis of cell wall components and actin organization. Given the relatively limited number of components of the CWI pathway and the very diverse stimuli, there must be a means of expanding the pathway. To manage the diverse stress conditions, the CWI pathway cross talks with other pathways or proteins, and these cross talk events enhance the signaling capabilities of the CWI pathway. Lateral influences that facilitate maintaining the cell wall under stress conditions are TOR signaling, calcineurin signaling, the high-osmolarity glycerol pathway, the cyclic AMP-protein kinase A pathway, and additional proteins. In this article, we highlight several of the cross talk events that have been described for Saccharomyces cerevisiae and several other fungi.

PMCID: PMC2772411 PMID: 19717745 [PubMed - indexed for MEDLINE]

1022. Appl Environ Microbiol. 2009 Nov;75(21):6635-8. Epub 2009 Aug 28.

The bacterially produced metabolite violacein is associated with survival of amphibians infected with a lethal fungus.

Becker MH, Brucker RM, Schwantes CR, Harris RN, Minbiole KP.

Department of Biological Sciences, Virginia Tech, MC 0406, Blacksburg, VA 24061, USA. mhbecker3@gmail.com

The disease chytridiomycosis, which is caused by the chytrid fungus Batrachochytrium dendrobatidis, is associated with recent declines in amphibian populations. Susceptibility to this disease varies among amphibian populations and species, and resistance appears to be attributable in part to the presence of antifungal microbial species associated with the skin of amphibians. The betaproteobacterium Janthinobacterium lividum has been isolated from the skins of several amphibian species and produces the antifungal metabolite violacein, which inhibits B. dendrobatidis. In this study, we added J. lividum to red-backed salamanders (Plethodon cinereus) to obtain an increased range of violacein concentrations on the skin. Adding J. lividum to the skin of the salamander increased the concentration of violacein on the skin, which was strongly associated with survival after experimental exposure to B. dendrobatidis. As expected from previous work, some individuals that did not receive J. lividum and were exposed to B. dendrobatidis survived. These individuals had concentrations of bacterially produced violacein on their skins that were predicted to kill B. dendrobatidis. Our study suggests that a threshold violacein concentration of about 18 microM on a salamander's skin prevents mortality and morbidity caused by B. dendrobatidis. In addition, we show that over one-half of individuals in nature support antifungal bacteria that produce violacein, which suggests that there is a mutualism between violacein-producing bacteria and P. cinereus and that adding J. lividum is effective for protecting individuals that lack violacein-producing skin bacteria.

PMCID: PMC2772424 PMID: 19717627 [PubMed - indexed for MEDLINE]

1023. Int J Food Microbiol. 2009 Oct 31;135(2):99-104. Epub 2009 Aug 11.

Mycoflora and occurrence of aflatoxin in dried vegetables in Benin, Mali and Togo, West Africa.

Hell K, Gnonlonfin BG, Kodjogbe G, Lamboni Y, Abdourhamane IK.

International Institute of Tropical Agriculture, P.O. Box 08-0932, Cotonou, Benin. k.hell@cgiar.org

Fungal infection and aflatoxin contamination was evaluated on 180 samples of dried vegetables such as okra, hot chilli, tomato, melon seeds, onion and baobab leaves from Benin, Togo and Mali collected in September to October 2006. These products are dried to preserve them for lean periods and decrease their perishability. Fungal contamination was evaluated after plating on selective media with a total of 561 fungal isolates identified, ranging from 18 in tomato and 218 in baobab leaves. Baobab leaves, followed by hot chilli and okra showed high incidence of fungal contamination compared to the other dried vegetables, while shelled melon seeds, onion leaves and dried tomato had lower levels of fungal contamination. Species of Aspergillus were dominant on all marketed dried vegetables irrespective of country. Mycotoxin assessment by Reversed-Phase High Performance Liquid Chromatography showed that only okra and hot chilli were naturally contaminated with aflatoxin B(1) and aflatoxin B(2), at concentrations of 6.0 microg/kg on okra and 3.2 microg/kg on hot pepper. This is the first time that mycotoxigenic fungi and resultant toxins were found on dried vegetable products sampled from African markets. Previous reports have mostly highlighted the risk of mycotoxin exposure from staple crops in Africa, but such risks now need to be evaluated for other products such as dried vegetables.

PMID: 19716615 [PubMed - indexed for MEDLINE]

1024. J Res Med Sci. 2009 Sep;14(5):297-300.

Microbial quality of water in dental unit waterlines.

Nikaeen M, Hatamzadeh M, Sabzevari Z, Zareh O.

Department of Environmental Health Engineering, School of Public Health, Isfahan University of Medical Sciences, Isfahan, Iran.

BACKGROUND: Dental unit waterlines (DUWLs) are ideal environment for development of microbial biofilms. Microbial contamination of water in DUWLs is thought to be the result of biofilm formation as it could serves as a haven for pathogens. The aim of this study was to assess microbial quality of water in dental unit waterlines of dental units located at the dental school of Isfahan University of Medical Sciences.
METHODS: Water samples were collected from air/water syringe and high-speed handpiece. Generally, 100-200 ml water samples were collected aseptically in sterile containers with sodium thiosulfate at the beginning of the day after a 2 minute purge. Samples were transferred to the laboratory in insulated box with cooling packs and examined for total viable heterotrophic bacteria and fungi.
RESULTS: The heterotrophic plate count levels were significantly exceeded the American Dental Association recommendations for DUWL water quality (< 200 CFU/ml), in both air/water syringe (84%, CFU/ml: 500-20000) and high-speed handpiece (96%, CFU/ml: 710-36800) samples. However, there was no significant difference between the level of contamination in the air/water syringe and high-speed handpiece. Fungi were found in 28% and 36% of air/water syringe and high-speed handpiece samples, respectively; and filamentous fungi were the most frequently isolated fungi.
CONCLUSIONS: DUWLs should be subjected to routine microbial monitoring and to a decontamination protocol in order to minimize the risk of exposure to potential pathogens from dental units.

PMCID: PMC3129099 PMID: 21772899 [PubMed]

1025. Clin Rev Allergy Immunol. 2010 Apr;38(2-3):148-55.

Mold and human health: separating the wheat from the chaff.

Pettigrew HD, Selmi CF, Teuber SS, Gershwin ME.

Division of Rheumatology, University of California at Davis School of Medicine, Genome and Biomedical Sciences Facility, 451 Health Sciences Drive, Suite 6510, Davis, CA 95616, USA.

The term "mold" is utilized to define the ubiquitous fungal species commonly found in household dust and observed as visible multicellular filaments. Several well-defined human diseases are known to be caused or exacerbated by mold or by exposure to their byproducts. Among these, a solid connection has been established with infections, allergic bronchopulmonary aspergillosis, allergic fungal rhinosinusitis, hypersensitivity pneumonitis, and asthma. In the past decades, other less-defined and generally false conditions have also been ascribed to mold. We will herein review and critically discuss the available evidence on the influence of mold on human health.

PMID: 19714500 [PubMed - indexed for MEDLINE]

1026. Planta. 2009 Oct;230(5):1057-69.

Pleiotropic changes in Arabidopsis f5h and sct mutants revealed by large-scale gene expression and metabolite analysis.

Huang J, Bhinu VS, Li X, Dallal Bashi Z, Zhou R, Hannoufa A.

Agriculture and Agri-Food Canada, Saskatoon Research Centre, Saskatoon, SK, Canada

Hydrocinnamic acid esters, lignin, flavonoids, glucosinolates, and salicylic acid protect plants against UV exposure, oxidative stress, diseases, and herbivores. Through the phenylpropanoid pathway, certain Brassicaceae family members, including Arabidopsis thaliana and Brassica napus, accumulate large amounts of the anti-nutritive sinapoylcholine (sinapine) in the seed. We successfully down-regulated activities of key enzymes in the pathway including F5H and SCT and achieved reduction of sinapine and lignin in B. napus seeds. Despite this success, it was unclear how multiple agronomic traits were affected in the transgenic plants. Here, we report altered large-scale gene expression of new alleles of f5h and sct mutants of A. thaliana and resultant accumulation of sinapoylglucose, disinapoylglucose, quercetin-3-O-rhamnoside, salicylic acid glucoside, and total indolyl glucosinolates in the two mutants. Expression of several flowering genes was altered in these mutants when grown under drought and NaCl treatments. Furthermore, both mutants were more susceptible to fungal infection than the wild type. Microarray experiments identified distinctive spatial and temporal expression patterns of gene clusters involved in silique/seed developmental processes and metabolite biosynthesis in these mutants. Taken together, these findings suggest that both f5h and sct mutants exhibit major differences in accumulation of diverse metabolites in the seed and profound changes in global large-scale gene expression, resulting in differential pleiotropic responses to environmental cues. Electronic supplementary material The online version of this article (doi:10.1007/s00425-009-1007-2) contains supplementary material, which is available to authorized users.

PMID: 19714359 [PubMed - indexed for MEDLINE]

1027. J Immunol. 2009 Sep 15;183(6):3800-9. Epub 2009 Aug 26.

Characterization of FIBCD1 as an acetyl group-binding receptor that binds chitin.

Schlosser A, Thomsen T, Moeller JB, Nielsen O, Tornøe I, Mollenhauer J, Moestrup SK, Holmskov U.

Medical Biotechnology Center, Pathology, University of Southern Denmark, Odense, Denmark. aschlosser@health.sdu.dk

Chitin is a highly acetylated compound and the second most abundant biopolymer in the world next to cellulose. Vertebrates are exposed to chitin both through food ingestion and when infected with parasites, and fungi and chitin modulate the immune response in different directions. We have identified a novel homotetrameric 55-kDa type II transmembrane protein encoded by the FIBCD1 gene and highly expressed in the gastrointestinal tract. The ectodomain of FIBCD1 is characterized by a coiled-coil region, a polycationic region and C-terminal fibrinogen-related domain that by disulfide linkage assembles the protein into tetramers. Functional analysis showed a high-affinity and calcium-dependent binding of acetylated components to the fibrinogen domain, and a function in endocytosis was demonstrated. Screening for ligands revealed that the FIBCD1 is a high-affinity receptor for chitin and chitin fragments. FIBCD1 may play an important role in controlling the exposure of intestine to chitin and chitin fragments, which is of great relevance for the immune defense against parasites and fungi and for immune response modulation.

PMID: 19710473 [PubMed - indexed for MEDLINE]

1028. Microsc Microanal. 2009 Oct;15(5):395-402. Epub 2009 Aug 27.

Three-dimensional x-ray imaging and analysis of fungi on and in wood.

Van den Bulcke J, Boone M, Van Acker J, Van Hoorebeke L.

Laboratory of Wood Technology, Faculty of Bioscience Engineering, Ghent University, Gent, Belgium. Jan.VandenBulcke@UGent.be

As wood is prone to fungal degradation, fundamental research is necessary to increase our knowledge aiming at product improvement. Several imaging modalities are capable of visualizing fungi, but the X-ray equipment presented in this article can envisage fungal mycelium in wood nondestructively in three dimensions with submicron resolution. Four types of wood subjected to the action of the white rot fungus Coriolus versicolor (Linnaeus) Quélet (CTB 863 A) were scanned using an X-ray-based approach. Comparison of wood volumes before and after fungal exposure, segmented manually or semiautomatically, showed the presence of the fungal mass on and in the wood samples and therefore demonstrated the usefulness of computed X-ray tomography for mycological and wood research. Further improvements to the experimental setup are necessary to resolve individual hyphae and enhance segmentation.

PMID: 19709462 [PubMed - indexed for MEDLINE]

1029. J Appl Microbiol. 2010 Feb;108(2):712-22. Epub 2009 Jul 13.

The global gene expression profile of the model fungus Saccharomyces cerevisiae induced by thymol.

Bi X, Guo N, Jin J, Liu J, Feng H, Shi J, Xiang H, Wu X, Dong J, Hu H, Yan S, Yu C, Wang X, Deng X, Yu L.

Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, College of Animal Science and Veterinary Medicine, Jilin University, Changchun, China.

AIM: To determine the transcriptional responses of model fungus Saccharomyces cerevisiae (S. cerevisiae) cells upon exposure to thymol (THY). METHODS AND RESULTS: Commercial oligonucleotide microarrays and quantitative real-time RT-PCR were used to study the transcriptional responses of S. cerevisiae to THY. Compared with the transcriptional profiles of untreated cultures, 305 genes were significantly upregulated, and 212 genes were significantly downregulated in THY-treated cells. We interpreted the microarray data using a hierarchical clustering tool, T-profiler. Glucose-dependent efflux of rhodamine 6G (R6G) from S. cerevisiae was performed to assay a phenotypic correlation between ATP-binding cassette transporter overexpression induced by THY and efflux of R6G. The addition of THY resulted in an increase in the concentration of released fluorescence, following the addition of glucose. Additional phenotype analysis showed that the intracellular concentration of thiamine was decreased by THY, and THY led to lesions in the membranes; these were consistent with the results of microarray.
CONCLUSION: The transcriptional response of S. cerevisiae to THY was determined, and several changes in genetic regulation were verified in physiological effects on the cell. SIGNIFICANCE AND IMPACT OF THE STUDY: Taken a whole-genome view to elucidate the mechanism of THY as a potential antifungal agent.

PMID: 19702861 [PubMed - indexed for MEDLINE]

1030. Eukaryot Cell. 2009 Oct;8(10):1554-66. Epub 2009 Aug 21.

Aneuploid chromosomes are highly unstable during DNA transformation of Candida albicans.

Bouchonville K, Forche A, Tang KE, Selmecki A, Berman J.

University of Minnesota, GCD, 6-160 Jackson Hall, 321 Church St. SE, Minneapolis, MN 55455, USA.

Candida albicans strains tolerate aneuploidy, historically detected as karyotype alterations by pulsed-field gel electrophoresis and more recently revealed by array comparative genome hybridization, which provides a comprehensive and detailed description of gene copy number. Here, we first retrospectively analyzed 411 expression array experiments to predict the frequency of aneuploidy in different strains. As expected, significant levels of aneuploidy were seen in strains exposed to stress conditions, including UV light and/or sorbose treatment, as well as in strains that are resistant to antifungal drugs. More surprisingly, strains that underwent transformation with DNA displayed the highest frequency of chromosome copy number changes, with strains that were initially aneuploid exhibiting approximately 3-fold more copy number changes than strains that were initially diploid. We then prospectively analyzed the effect of lithium acetate (LiOAc) transformation protocols on the stability of trisomic chromosomes. Consistent with the retrospective analysis, the proportion of karyotype changes was highly elevated in strains carrying aneuploid chromosomes. We then tested the hypothesis that stresses conferred by heat and/or LiOAc exposure promote chromosome number changes during DNA transformation procedures. Indeed, a short pulse of very high temperature caused frequent gains and losses of multiple chromosomes or chromosome segments. Furthermore, milder heat exposure over longer periods caused increased levels of loss of heterozygosity. Nonetheless, aneuploid chromosomes were also unstable when strains were transformed by electroporation, which does not include a heat shock step. Thus, aneuploid strains are particularly prone to undergo changes in chromosome number during the stresses of DNA transformation protocols.

PMCID: PMC2756872 PMID: 19700634 [PubMed - indexed for MEDLINE]

1031. Environ Monit Assess. 2010 Sep;168(1-4):481-7. Epub 2009 Aug 21.

A study on Aspergillus species in houses of asthmatic patients from Sari City, Iran and a brief review of the health effects of exposure to indoor Aspergillus.

Hedayati MT, Mayahi S, Denning DW.

Medical Mycology and Parasitology Department, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. hedayaty2001@yahoo.co.uk

To study the distribution of Aspergillus spp. in outdoor and indoor air of asthmatic patients' houses, as well as a review on the health effects of exposure to indoor Aspergillus. Open plates containing malt extract agar media were used to isolate fungi from the indoor (n = 360) and outdoor (n = 180) air of 90 asthmatic patients' houses living in Sari City, Iran. Plates were incubated at room temperature for 7-14 days. Cultured Aspergillus spp. were identified by standard mycological techniques. All culture plates grew fungi, a testament to the ubiquitous nature of fungal exposure. Cladosporium spp. (29.2%), Aspergillus spp. (19.0%), and Penicillium spp. (18.3%) were most common inside the houses while Cladosporium spp. (44.5%), Aspergillus spp. (12.4%), and Alternaria spp. (11.1%) were most common outside the houses. Aspergillus flavus (30.1%) and A. fumigatus (23.1%) are the most commonly isolated species in indoor air. Aspergillus flavus (44.5%) and A. fumigatus (42.6%) were the most prevalent Aspergillus spp. outside. The most colony numbers of Aspergillus were isolated from kitchens (30.4%) and the least from bedrooms (21.1%). Aspergillus flavus was the most prevalent species in all sampled rooms except in the kitchen where A. fumigatus was the most common. Aspergillus flavus is the most prevalent species among the Aspergillus spp. in the indoor and outdoor of a warm climate area. In these areas, A. flavus can be a major source of allergen in the air. Therefore, minimizing indoor fungal exposure could play an important role in reducing allergic symptoms in susceptible persons.

PMID: 19697147 [PubMed - indexed for MEDLINE]

1032. Environ Entomol. 2009 Aug;38(4):996-1004.

Variation in endophyte-plant associations influence black cutworm (Lepidoptera: Noctuidae) performance and susceptibility to the parasitic nematode Steinernema carpocapsae.

Richmond DS, Bigelow CA.

Department of Entomology, Purdue University, West Lafayette, IN 47907, USA. drichmond@purdue.edu

This study examined how variability in Neotyphodium endophyte-grass associations influences black cutworm Agrotis ipsilon Hufnagel performance and susceptibility to the entomopathogenic nematode Steinernema carpocapsae (Weiser). Second-instar cutworm larvae were confined to greenhouse pots containing four different tall fescue Schedonorus phoenix (Scop.) Holub cultivars. After 1 wk, larvae were recovered from the pots, weighed, and individually exposed to 20 infective juvenile nematodes. Nematode-induced mortality was monitored for 72 h after exposure. Endophyte infection levels and ergot alkaloid concentrations varied between tall fescue cultivars, but endophyte infection level was not a significant predictor of ergot alkaloid concentrations in above-ground plant tissue. Larval survival also varied between cultivars, but neither endophyte infection level nor ergot alkaloid concentration was a significant covariate. Larval susceptibility to the entomopathogenic nematode varied between cultivars at 48 and 72 h after exposure. In all but one cultivar (Plantation), cumulative mortality at 72 h decreased significantly as ergot alkaloid concentrations increased. Neither larval biomass nor endophyte infection levels in tall fescue were significant predictors of larval susceptibility to the nematode. Results show that variation in endophyte-plant associations can influence black cutworm performance and susceptibility to entomopathogenic nematodes and that susceptibility to the nematode H. bacteriophora may be partially tied to ergot alkaloid levels in the insects' food. Findings further support the assertion that black cutworm may use certain endophyte-mediated toxins, particularly ergot alkaloids, as a form of acquired chemical defense against nematode-induced septicaemia.

PMID: 19689877 [PubMed - indexed for MEDLINE]

1033. Anal Bioanal Chem. 2009 Oct;395(3):809-17. Epub 2009 Aug 18.

Identification and quantification of glutathione and phytochelatins from Chlorella vulgaris by RP-HPLC ESI-MS/MS and oxygen-free extraction.

Simmons DB, Hayward AR, Hutchinson TC, Emery RJ.

Environmental & Life Sciences Graduate Program, Environmental Science Building, Trent University, Room A201, 1600 West Bank Drive, Peterborough, ON, K9J 7B8, Canada.

Phytochelatins are short, cysteine-containing, detoxification peptides produced by plants, algae, and fungi in response to heavy metal exposure. These peptides auto-oxidize easily. Current extraction protocols do not adequately address losses of phytochelatins because of their oxidation and the use of indirect methods for quantification. Method enhancements include the use of an argon environment during extraction to reduce auto-oxidation, the use of glycine-(13)C2-labeled glutathione as an internal standard, and an electrospray ionization source with a triple quadrupole mass spectrometer as a detector. The method-detection limits were 0.081 microM for glutathione, 0.440 microM for phytochelatin 2, and 0.120 microM for phytochelatin 3. These detection limits were comparable to similar studies and were not compromised incorporating these adjustments. The use of a labeled internal standard and an inert gaseous environment during sample preparation greatly improved calibration linearity and sensitivity. Furthermore, phytochelatin degradation was significantly reduced and more accurately tracked. Previous studies involving phytochelatin analyses have likely been subject to higher variability caused by this propensity for phytochelatins to degrade rapidly in air. The method adjustments were simple and cost-effective and allowed phytochelatin analyses to be performed for hours at a time with minimal auto-oxidation.

PMID: 19688341 [PubMed - indexed for MEDLINE]

1034. MLO Med Lab Obs. 2009 Jul;41(7):24, 26.

Address deficiencies in bloodborne pathogens exposure management.

Williams D.

Office of Health Enforcement, OSHA's Directorate of Enforcement Programs, Washington, DC, USA.

PMID: 19685692 [PubMed - indexed for MEDLINE]

1035. J Environ Health. 2009 Jul-Aug;72(1):59-61.

Responses to the efficacy of 'green' cleaning products article.

Barnett C, Bowles D, Culver A, Geiger C, Moore D, Earl J, Sutton R, Graham T.

Comment in J Environ Health. 2009 Sep;72(2):39-40.

Comment on J Environ Health. 2009 May;71(9):24-7; quiz 35.

PMID: 19685579 [PubMed - indexed for MEDLINE]

1036. Mol Biol Rep. 2010 Jun;37(5):2447-53. Epub 2009 Aug 15.

Cloning and characterization of a chitinase gene Lbchi31 from Limonium bicolor and identification of its biological activity.

Liu ZH, Wang YC, Qi XT, Yang CP.

Key Laboratory of Forest Tree Genetic Improvement and Biotechnology, Ministry of Education, Northeast Forestry University, Harbin 150040, China.

Chitinases are digestive enzymes that break down glycosidic bonds in chitin. In the current study, an endochitinase gene Lbchi31 was cloned from Limonium bicolor. The cDNA sequence of Lbchi31 was 1,107 bp in length, encoding 322 amino acid residues with a calculated molecular mass of 31.7 kDa. Clustal analysis showed that there was a highly conserved chitin-binding domains in Lbchi31 protein, containing four sulfide bridges. The Lbchi31 gene was inserted into the pPIC9 vector and transferred into yeast Pichia pastoris GS115 and KM71 for heterologous expression. The transformant harboring the Lbchi31 gene showed a clearly visible protein band with a molecular mass of more than 31 kDa in the SDS-PAGE gel, indicating that it had been translated in P. pastoris. Enzyme characterization showed that the optimal reaction condition for chitinase LbCHI31 activity was: 40 degrees C, pH of 5.0 and 5 mmol l(-1) of Mn(2+). The maximum enzyme activity was 0.88 U ml(-1) following exposure to the cell wall chitin of Valsa sordida. The LbCHI31 enzyme can efficiently degrade cell wall chitin of the phytopathogenic Rhizoctonia solani, Fusarium oxysporum, Sclerotinia sclerotiorum, V. sordida, Septoria tritici and Phytophthora sojae, suggesting that it has the biocontrol function to fungal phytopathogen.

PMID: 19685157 [PubMed - indexed for MEDLINE]

1037. Oral Dis. 2010 Apr;16(3):242-7. Epub 2009 Aug 4.

Melatonin in diseases of the oral cavity.

Gómez-Moreno G, Guardia J, Ferrera MJ, Cutando A, Reiter RJ.

School of Dentistry, University of Granada, Granada, Spain.

BACKGROUND: Melatonin is the principal secretory product of the pineal gland. It has immunomodulatory and antioxidant activities, stimulates the proliferation of collagen and osseous tissue and acts as a protector against cellular degeneration associated with aging and toxin exposure. Arising out of its antioxidant actions, melatonin protects against inflammatory processes and cellular damage caused by the toxic derivates of oxygen. As a result of these actions, melatonin may be useful as a co-adjuvant in the treatment of certain conditions of the oral cavity.
METHODS: An extensive review of the scientific literature was carried out using PubMed, Science Direct, ISI Web of Knowledge and the Cochrane base.
RESULTS: Melatonin, which is released into the saliva, may have important implications for oral diseases. Melatonin may have beneficial effects in certain oral pathologies including periodontal diseases, herpes viral infections and Candida, local inflammatory rocesses, xerostomia, oral ulcers and oral cancer.
CONCLUSIONS: Melatonin may play a role in protecting the oral cavity from tissue damage caused by oxidative stress. The experimental evidence suggests that melatonin may have utility in the treatment of several common diseases of the oral cavity. However, more specific studies are necessary to extend the therapeutic possibilities to other oral diseases.

PMID: 19682319 [PubMed - indexed for MEDLINE]

1038. Mol Microbiol. 2009 Sep;73(6):1032-42. Epub 2009 Aug 4.

Enhancer of decapping proteins 1 and 2 are important for translation during heat stress in Saccharomyces cerevisiae.

Neef DW, Thiele DJ.

Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.

In mammalian and Drosophila cells, heat stress strongly reduces general protein translation while activating cap-independent translation mechanisms to promote the expression of stress-response proteins. In contrast, in Saccharomyces cerevisiae general translation is only mildly and transiently reduced by heat stress and cap-independent translation mechanisms have not been correlated with the heat stress response. Recently we have identified direct target genes of the heat shock transcription factor (HSF), including genes encoding proteins thought to be important for general translation. One gene activated by HSF during heat stress encodes the enhancer of decapping protein, Edc2, previously shown to enhance mRNA decapping under conditions when the decapping machinery is limited. In this report we show that strains lacking Edc2, as well as the paralogous protein Edc1, are compromised for growth under persistent heat stress. This growth deficiency can be rescued by expression of a mutant Edc1 protein deficient in mRNA decapping indicative of a decapping independent function during heat stress. Yeast strains lacking Edc1 and Edc2 are also sensitive to the pharmacological inhibitor of translation paromomycin and exposure to heat stress and paromomycin functions synergistically to reduce yeast viability, suggesting that in the absence of Edc1 and Edc2 translation is compromised under heat stress conditions. Strains lacking Edc1 and Edc2 have significantly reduced rates of protein translation during growth under heat stress conditions, but not under normal growth conditions. We propose that Edc1 and the stress responsive isoform Edc2 play important roles in protein translation during stress.

PMCID: PMC2901857 PMID: 19682251 [PubMed - indexed for MEDLINE]

1039. J Environ Health. 2009 Jul-Aug;72(1):61.

Response to third-party review of cleaning products article.

Whittaker MH.

Comment on J Environ Health. 2009 May;71(9):20-3.

PMID: 19681391 [PubMed - indexed for MEDLINE]

1040. J Environ Health. 2009 Jul-Aug;72(1):59.

Responses to the efficacy of 'green' cleaning products article.

Petruzzi MT.

Comment in J Environ Health. 2009 Sep;72(2):39-40.

Comment on J Environ Health. 2009 May;71(9):24-7; quiz 35.

PMID: 19681390 [PubMed - indexed for MEDLINE]

1041. J Environ Health. 2009 Jul-Aug;72(1):58.

Responses to the efficacy of 'green' cleaning products article.

Weinberg J, Harrison R, Flattery J.

Comment in J Environ Health. 2009 Sep;72(2):39-40.

Comment on J Environ Health. 2009 May;71(9):24-7; quiz 35.

PMID: 19681389 [PubMed - indexed for MEDLINE]

1042. J Environ Health. 2009 Jul-Aug;72(1):57-8.

Responses to the efficacy of 'green' cleaning products article.

Ashkin S, Bishop M.

Comment in J Environ Health. 2009 Sep;72(2):39-40.

Comment on J Environ Health. 2009 May;71(9):24-7; quiz 35.

PMID: 19681388 [PubMed - indexed for MEDLINE]

1043. J Environ Health. 2009 Jul-Aug;72(1):24-8.

Mold growth on gypsum wallboard--a summary of three techniques.

Menetrez MY, Foarde KK, Webber TD, Dean TR, Betancourt DA.

U.S. Environmental Protection Agency, Office of Research and Development, National Risk Management Research Laboratory, Air Pollution Prevention and Control Division, Research Triangle Park, NC 27711, USA. menetrez.marc@epa.gov

Reducing occupant exposure to mold growing on damp gypsum wallboard and controlling mold contamination in the indoor environment was studied through 1) delineation of environmental conditions required to promote and avoid mold growth and 2) efficacy testing of antimicrobial products, specifically cleaners and paints, on gypsum wallboard (GWB) surfaces. The effects of moisture and relative humidity (RH) on mold growth and transport are important in avoiding and eliminating problems. These effects have been demonstrated on GWB and are discussed in this article for use as control guidance. The authors discuss the efficacy of antimicrobial cleaners and paints to remove, eliminate, or control mold growth on GWB. Research to control Stachybotrys chartarum growth using 13 separate antimicrobial cleaners and nine varieties of antimicrobial paint on contaminated GWB was performed in laboratory testing. GWB surfaces were subjected to high RH. GWB control measures are summarized and combined, and the antimicrobial product results are explained.

PMID: 19681385 [PubMed - indexed for MEDLINE]

1044. J Food Prot. 2009 Jul;72(7):1427-33.

Colletotrichum gloeosporioides growth-no-growth interface after selected microwave treatments.

Sosa-Morales ME, Garcia HS, López-Malo A.

Unidad de Investigación y Desarrollo de Alimentos, Instituto Tecnológico de Veracruz, M.A. de Quevedo 2779, Col. Formando Hogar, Veracruz, Ver. 91897, Mexico.

To study microwave heating for potential postharvest treatments against anthracnose disease, Colletotrichum gloeosporioides growth-no-growth response after selected microwave treatments (2,450 MHz) was fitted by using a logistic regression model. Evaluated variables were power level, exposure time, presence or absence of water in the medium during treatment, and incubation-observation time. Depending on the setting, the applied power ranged from 77.2 to 435.6 W. For the experiments on dry medium (mold spores over filter paper), exposure times were 1, 2, 3, or 4 min, whereas spores dispersed in potato dextrose agar, a wet medium, had exposure times of 3, 6, or 9 s. Growth (response = 1) or no growth (response = 0) was observed after two different incubation-observation times (4 or 10 days). As expected, high power levels and long exposure times resulted in complete inhibition of C. gloeosporioides spore germination. In a number of cases (such as low power levels and short treatment times), only a delay in mold growth was observed. Scanning electron micrographs showed signs of mycelia dehydration and structural collapse in the spores of the studied mold. Cell damage was attributed to heating during microwave exposure. Reduced logistic models included variables and interactions that significantly (P < 0.05) affected mold growth, and were able to predict the growth-no-growth response in at least 83% of the experimental conditions. Microwave treatments (4 min at any of the studied power levels in dry medium, and 9 s at power levels of 30% or more for wet medium) proved effective in the inhibition of C. gloeosporioides in model systems. These no-growth conditions will be tested further on fresh fruits in order to develop feasible postharvest microwave treatments.

PMID: 19681265 [PubMed - indexed for MEDLINE]

1045. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2008 Nov;25(11):1374-84.

Fate of Fusarium mycotoxins in maize flour and grits during extrusion cooking.

Scudamore KA, Guy RC, Kelleher B, MacDonald SJ.

KAS Mycotoxins, 6 Fern Drive, Taplow, Maidenhead SL60JS, UK. kasmyc@aol.com

Extrusion technology is used widely in the manufacture of a range of breakfast cereals and snacks for human consumption and animal feeds. To minimise consumer exposure to mycotoxins, the levels of deoxynivalenol (DON) and zearalenone (ZON) in cereals/cereal products and fumonisins B(1) and B(2) (FB(1) and FB(2)) in maize are controlled by European Union legislation. Relatively few studies, however, have examined the loss of Fusarium mycotoxins during processing. The behaviour of FB(1), FB(2) and fumonisin B(3) (FB(3)), DON and ZON during extrusion of naturally contaminated maize flour and maize grits is examined using pilot-scale equipment. DON and ZON are relatively stable during extrusion cooking but the fumonisins are lost to varying degrees. There is some loss of ZON when present in low concentrations and extruded at higher moisture contents. The presence of additives, such as reducing sugars and sodium chloride, can also affect mycotoxin levels. Moisture content of the cereal feed during extrusion is important and has a greater effect than temperature, particularly on the loss of fumonisins at the lower moistures. The effects are complex and not easy to explain, although more energy input to the extruder is required for drier materials. However, on the basis of these studies, the relationship between the concentration of Fusarium toxins in the raw and finished product is toxin- and process-dependent.

PMID: 19680845 [PubMed - indexed for MEDLINE]

1046. Expert Opin Investig Drugs. 2009 Sep;18(9):1279-95.

New generation azole antifungals in clinical investigation.

Girmenia C.

Dipartimento di Ematologia, Oncologia, Anatomia Patologica e Medicina Rigenerativa, Azienda Policlinico Umberto I, Via Benevento 6, 00161 Rome, Italy. girmenia@bce.uniroma1.it

Erratum in Expert Opin Investig Drugs. 2009 Dec;18(12):1967.

Considerable progress in treating systemic mycoses has been achieved in the past years through development of new drugs in association with more advanced diagnostic procedures. Here, we review the pharmacological, microbiological and clinical development progress with the so-called 'second generation' triazoles: voriconazole, posaconazole, ravuconazole, isavuconazole and albaconazole. All these drugs exhibit a favourable pharmacokinetic and toxicity profile and possess high activity against resistant and emerging pathogens. However, only voriconazole and posaconazole have been adequately investigated in Phase III studies and have been approved by the regulatory agencies in the treatment and prophylaxis of invasive fungal infections, respectively. On the contrary, ravuconazole, isavuconazole and albaconazole have not been investigated in adequate clinical trials and, in the absence of proper data, the real possibilities of these agents as competitors for the treatment and prevention of invasive mycoses in the clinical setting are still unknown. The drug interactions and the variability in the absorption and/or metabolism of the triazoles, in particular voriconazole and posaconazole, may determine an unpredictable exposure of the pathogens to the antifungal treatments. Literature evidences strongly support the use of therapeutic drug monitoring for these triazoles which may be crucial for the proper management of severe invasive fungal infections.

PMID: 19678798 [PubMed - indexed for MEDLINE]

1047. Plant Physiol. 2009 Oct;151(2):559-73. Epub 2009 Aug 12.

Multiple antibiotic resistance in Arabidopsis is conferred by mutations in a chloroplast-localized transport protein.

Conte S, Stevenson D, Furner I, Lloyd A.

Section of Molecular Cell and Developmental Biology, Institute for Cellular and Molecular Biology, University of Texas, Austin, Texas 78712, USA. conte@mail.utexas.edu

Comment in Plant Signal Behav. 2010 Jan;5(1):49-52.

Widespread antibiotic resistance is a major public health concern, and plants represent an emerging antibiotic exposure route. Recent studies indicate that crop plants fertilized with antibiotic-laden animal manure accumulate antibiotics; however, the molecular mechanisms of antibiotic entry and subcellular partitioning within plant cells remain unknown. Here, we report that mutations in the Arabidopsis (Arabidopsis thaliana) locus Multiple Antibiotic Resistance1 (MAR1) confer resistance, while MAR1 overexpression causes hypersensitivity to multiple aminoglycoside antibiotics. Additionally, yeast expressing MAR1 are hypersensitive to the aminoglycoside G418. MAR1 encodes a protein with 11 putative transmembrane domains with low similarity to ferroportin1 from Danio rerio. A MAR1:yellow fluorescent protein fusion localizes to the chloroplast, and chloroplasts from plants overexpressing MAR1 accumulate more of the aminoglycoside gentamicin, while mar1-1 mutant chloroplasts accumulate less than the wild type. MAR1 overexpression lines are slightly chlorotic, and chlorosis is rescued by exogenous iron. MAR1 expression is also down-regulated by low iron. These data suggest that MAR1 is a plastid transporter that is likely to be involved in cellular iron homeostasis and allows opportunistic entry of multiple antibiotics into the chloroplast.

PMCID: PMC2754617 PMID: 19675150 [PubMed - indexed for MEDLINE]

1048. Biol Lett. 2009 Dec 23;5(6):845-8. Epub 2009 Aug 12.

Crowded locusts produce hatchlings vulnerable to fungal attack.

Miller GA, Pell JK, Simpson SJ.

School of Biological Sciences, The University of Sydney, Heydon-Laurence Building A08, New South Wales 2006, Australia. gmiller@oeb.harvard.edu

Transgenerational effects of parental experience on offspring immunity are well documented in the vertebrate literature (where antibodies play an obligatory role), but have only recently been described in invertebrates. We have assessed the impact of parental rearing density upon offspring disease resistance by challenging day-old locust hatchlings (Schistocerca gregaria) from either crowd- or solitary-reared parents with the fungal pathogen Metarhizium anisopliae var. acridum. When immersed in standardized conidia suspensions, hatchlings from gregarious parents suffered greater pathogen-induced mortality than hatchlings from solitary-reared parents. This observation contradicts the basic theory of positive density-dependent prophylaxis and demonstrates that crowding has a transgenerational influence upon locust disease resistance.

PMCID: PMC2828005 PMID: 19675004 [PubMed - indexed for MEDLINE]

1049. Clin Microbiol Infect. 2009 Jul;15(7):602-12.

Antifungal pharmacokinetics and pharmacodynamics: bridging from the bench to bedside.

Hope WW, Drusano GL.

The University of Manchester, Manchester Academic Health Science Centre, NIHR Translational Research Facility in Respiratory Medicine, University Hospital of South Manchester NHS Foundation Trust, Manchester, UK. william.hope@manchester.ac.uk

This review considers a way in which experimental data can be used to identify safe and effective antifungal regimens for humans. The process begins with experimental models of invasive fungal infections that enable definition of optimal dosages and schedules of antifungal drug administration to be defined. These preclinical models also enable the identification of drug exposure targets that are associated with therapeutic outcomes of interest. Human pharmacokinetic variability results in a considerable range of drug exposures following the use of fixed antifungal drug regimens. This variability can be quantified using population pharmacokinetic modeling techniques. Monte Carlo simulation can then be used to simulate pharmacokinetic variability and thereby estimate the proportion of patients with a therapeutic outcome of interest. Effective and safe regimens can thus be studied appropriately in clinical settings. This approach can, and should, be used to optimize antifungal therapy for a large number of clinical scenarios.

PMID: 19673971 [PubMed - indexed for MEDLINE]

1050. Biochemistry. 2009 Sep 8;48(35):8312-21.

Occidiofungin, a unique antifungal glycopeptide produced by a strain of Burkholderia contaminans.

Lu SE, Novak J, Austin FW, Gu G, Ellis D, Kirk M, Wilson-Stanford S, Tonelli M, Smith L.

Mississippi State University, Department of Entomology, Mississippi State, Mississippi 39762, USA.

Bacterial strain Burkholderia contaminans MS14 was isolated from soil that suppressed brown patch disease of lawn grass. An antifungal compound was purified from the liquid culture of this bacterium. In this study, complete covalent structures of two purified closely related antifungal compounds were determined by the experiments of TOCSY, NOESY, ROESY, 13C HSQC 2D NMR, and ESI-MS and GC. The analysis of monoisotopic masses of the purified preparation indicated the presence of two related compounds with masses determined to be 1199.543 and 1215.518 Da; the difference corresponds to the mass of an oxygen atom. GC analysis identified a xylose sugar attached to the antifungal compound. NMR experiments revealed that the compound is cyclic and composed of eight amino acids, two of which are beta-hydroxy derivatives of Tyr and Asn, and one being a novel amino acid. The novel amino acid serves as the scaffold for the attachment of the xylose and a short acyl chain. The spectrum and concentration of antifungal activity were determined using a microtiter plate assay. The antifungal compound demonstrated potent antifungal activities against a broad panel of fungal plant and animal pathogens, as well as two Pythium spp. Microscopic observations showed that the antifungal compound disrupts normal membrane morphology. The cells fill with large inclusion bodies and the membrane becomes irregularly shaped and swollen following the exposure to subinhibitory concentrations of the antifungal compound. Our data support the identification of a novel fungicide and the compound has been named occidiofungin, meaning fungal killer.

PMCID: PMC2771368 PMID: 19673482 [PubMed - indexed for MEDLINE]

1051. Curr Allergy Asthma Rep. 2009 Sep;9(5):384-90.

Allergens and thunderstorm asthma.

Nasser SM, Pulimood TB.

Department of Allergy, Cambridge University Hospitals National Health Service Foundation Trust, Cambridge, United Kingdom. shuaib.nasser@addenbrookes.nhs.uk

Thunderstorm-related asthma is increasingly recognized in many parts of the world. This review focuses on important advances in the understanding of the mechanism of the role of allergens, in particular fungal spores such as Alternaria, in asthma epidemics associated with thunderstorms. From our observations, we have proposed that the prerequisites for this phenomenon are as follows: 1) a sensitized, atopic, asthmatic individual; 2) prior airway hyperresponsiveness before a sudden, large allergen exposure; 3) a large-scale thunderstorm with cold outflow occurring at a time and location during an allergen season in which large numbers of asthmatics are outdoors; and 4) sudden release of large amounts of respirable allergenic fragments, particularly fungal spores such as Alternaria.

PMID: 19671382 [PubMed - indexed for MEDLINE]

1052. Medicina (Kaunas). 2009;45(7):530-6.

[Professional biological risk factors of health care workers].

[Article in Lithuanian]

Gailiene G, Cenenkiene R.

Department of Infection Control, Hospital of Kaunas University of Medicine, Eiveniu 2, 50009 Kaunas, Lithuania. greta.gailiene@kmuk.lt

Health care workers are attributed to the group at highest risk of biological factors, as they are daily exposed to fluids of the human body. The risk of sharps injuries and exposure to blood is associated with bloodborne infections. The aim of this study was to determine the frequency and type of professional biological risk factors, to evaluate the use of personal protective devices, application of immunoprophylaxis to health care workers in the surgical departments. METHODS. A retrospective study was carried out from January to June 2006. Data were collected in the surgical departments of Hospital of Kaunas University of Medicine. An anonymous questionnaire survey was performed. RESULTS. More than half (51.4%) of the respondents experienced sharps injuries, 62.1% were exposed to biological fluids, and 39.6% of the workers experienced both injury and exposure. In all cases, the hands were injured during sharps injuries. Exposure of healthy skin and eyes to biological fluids occurred in 63% and 20% of the cases, respectively. Majority of exposures were blood splashes (60%). Physicians most frequently experienced sharps injury during the surgery (79.3%), nurses - during the preparation of instruments (35.1%), supporting staff - disposing the waste (75.8%). Commonly physicians were injured by surgical needles (72.4%), nurses - by needlestick (72.4%), and supporting staff - by glass waste (60.6%). Majority of the respondents (86%) were not vaccinated with HB vaccine. No personal protective equipment was used by 14.5% of the respondents during sharps injuries and 5% during exposures. CONCLUSIONS. More than half of the respondents experienced sharps injury or exposure to biological fluids during the study period. Physicians and nurses experience sharps injury and exposure to biological fluids more commonly as compared to supporting staff. Hepatitis B vaccination is insufficient among health care workers.

PMID: 19667747 [PubMed - indexed for MEDLINE]

1053. J Inorg Biochem. 2009 Oct;103(10):1355-65. Epub 2009 Jul 16.

Synthesis, characterization and biological activities of mononuclear Co(III) complexes as potential bioreductively activated prodrugs.

Souza ET, Castro LC, Castro FA, do Canto Visentin L, Pinheiro CB, Pereira MD, de Paula Machado S, Scarpellini M.

Departamento de Química Inorgânica, Instituto de Química, Universidade Federal do Rio de Janeiro, 21945-970 Rio de Janeiro, RJ, Brazil.

Aiming to investigate the use of tridentate ligands to develop new bireductively activated prodrugs, two N(2)O-donor ligands (HL1: [(2-hydroxybenzyl)(2-(imidazol-2-yl)ethyl)]amine; and HL2: [(2-hydroxybenzyl)(2-(pyridil-2-yl)ethyl]amine) were used to synthesize new Co(III) complexes, 1 and 2. Both complexes were characterized by X-ray crystallography, mass spectrometry, electrochemistry, IR, UV-visible and (1)H NMR spectroscopies. Electrochemical data in methanol revealed that the Co(III)-->Co(II) reduction of 1 (-0.84V vs. normal hydrogen electrode - NHE) is more positive than 2 (-1.13V vs. NHE), while it was expected to be more negative due to better sigma-donor ability of imidazole ring in HL1, compared to pyridine in HL2. Considering that reduction processes on Co(III) center may involve the lowest unoccupied molecular orbital (LUMO), it might play an important role on the electronic properties of the complexes, and could explain the observed redox potentials. Then, geometry optimizations of 1 and 2 were performed using the density functional theory (DFT), and different group participation in their LUMO is demonstrated. Using Saccharomyces cerevisiae cells as eukaryotic model, it is shown that in situ generated reduced species, 1(red) and 2(red), have high capacity to inhibit cellular growth, with IC50 (0.50mM for both complexes) lower than cisplatin IC50 (0.6mM) at the same time of exposure. Regarding to their ability to promote S. cerevisiae cells death, after 24 h, cells became susceptible only when exposed to 1(red) and 2(red): (i) at concentrations higher than 0.5mM in a non-dose dependence, and (ii) in anaerobic metabolism. These data reveal the potential of 1 and 2 as bioreductively activated prodrugs, since their oxidized forms do not present expressive activities when compared to their reduced forms.

PMID: 19665800 [PubMed - indexed for MEDLINE]

1054. Acta Trop. 2009 Nov;112(2):219-24. Epub 2009 Aug 7.

Evidence for high prevalence of Pneumocystis jirovecii exposure among Cameroonians.

Nkinin SW, Daly KR, Walzer PD, Ndzi ES, Asonganyi T, Respaldiza N, Medrano FJ, Kaneshiro ES.

Department of Biological Sciences, University of Cincinnati, Cincinnati, OH 45221-0006, USA.

Cameroon lacks the capacity for routine Pneumocystis pneumonia (PcP) diagnosis, thus, the prevalence of Cameroonian exposure to this microbe is unknown. It is known that Pneumocystis infecting different mammalian host species represent diverse phylogenetic backgrounds and are now designated as separate species. The highly sensitive nature of ELISA and the specificity afforded by using human-derived P. jirovecii Msg peptides has been shown to be useful for serological analysis of human sera. Thus, sera from patients in Yaoundé, the capital city of Cameroon, were analyzed for anti-P. jirovecii antibodies by enzyme-linked immunosorbent assay (ELISA) using three recombinant major surface glycoprotein (Msg) peptide fragments, MsgA1, MsgB, and MsgC1. Based on serum recognition of one or more of the three fragments, 82% of the total samples analyzed was positive for antibodies to P. jirovecii Msg, indicating high prevalence of P. jirovecii infection or colonization among Cameroonians. Different Msg fragments appear to be recognized more frequently by sera from different geographic regions of the globe. Antibodies in the Cameroonian serum samples recognized MsgA1>MsgC1>MsgB, suggesting that different P. jirovecii strains exist in different parts of the world and/or human populations differ in their response to P. jirovecii. Also, HIV(+) patients diagnosed with respiratory infections (such as TB and pneumonia) and maintained on trimethoprim/sulfamethoxazol prophylaxis had relatively lower anti-Msg titers. Whether PcP prophylaxis has significant effects on the quality of life among HIV(+) patients in Cameroon warrants further investigation.

PMCID: PMC2761101 PMID: 19665440 [PubMed - indexed for MEDLINE]

1055. AORN J. 2009 Aug;90(2):181.

Double-gloving recommendations.

Young J.

Comment on AORN J. 2009 Feb;89(2):322-8; quiz 329-32.

PMID: 19664411 [PubMed - indexed for MEDLINE]

1056. J Appl Microbiol. 2010 Jan;108(1):115-28.

Characterization of Metarhizium species and varieties based on molecular analysis, heat tolerance and cold activity.

Fernandes EK, Keyser CA, Chong JP, Rangel DE, Miller MP, Roberts DW.

Department of Biology, Utah State University, Logan, UT, USA.

AIMS: The genetic relationships and conidial tolerances to high and low temperatures were determined for isolates of several Metarhizium species and varieties. METHODS AND RESULTS: Molecular-based techniques [AFLP and rDNA (ITS1, ITS2 and 5.8S) gene sequencing] were used to characterize morphologically identified Metarhizium spp. isolates from a wide range of sources. Conidial suspensions of isolates were exposed to wet heat (45 + or - 0.2 degrees C) and plated on potato dextrose agar plus yeast extract (PDAY) medium. After 8-h exposure, the isolates divided clearly into two groups: (i) all isolates of Metarhizium anisopliae var. anisopliae (Ma-an) and Metarhizium from the flavoviride complex (Mf) had virtually zero conidial relative germination (RG), (ii) Metarhizium anisopliae var. acridum (Ma-ac) isolates demonstrated high heat tolerance (c. 70-100% RG). Conidial suspensions also were plated on PDAY and incubated at 5 degrees C for 15 days, during which time RGs for Ma-an and Ma-ac isolates were virtually zero, whereas the two Mf were highly cold active (100% RG).
CONCLUSIONS: Heat and cold exposures can be used as rapid tools to tentatively identify some important Metarhizium species and varieties. SIGNIFICANCE AND IMPACT OF THE STUDY: Identification of Metarhizium spp. currently relies primarily on DNA-based methods; we suggest a simple temperature-based screen to quickly obtain tentative identification of isolates as to species or species complexes.

PMID: 19664068 [PubMed - indexed for MEDLINE]

1057. Clin Infect Dis. 2009 Sep 15;49(6):919-23.

Expert opinion: what to do when there is Coccidioides exposure in a laboratory.

Stevens DA, Clemons KV, Levine HB, Pappagianis D, Baron EJ, Hamilton JR, Deresinski SC, Johnson N.

Department of Medicine, Santa Clara Valley Medical Center, San Jose, California 95128-2699, USA. stevens@stanford.edu

Inadvertent exposure to Coccidioides species by laboratory staff and others as a result of a mishap is not an uncommon cause of infection in clinical microbiology laboratories. These types of infection may occur in laboratories outside the endemic areas, because the etiologic agent is unexpected in the submitted specimens and because personnel may be unfamiliar with the hazards of dealing with Coccidioides species in the laboratory. Coccidioidal infections are often difficult to treat, and outcomes can be poor. Here, we emphasize prevention and an approach to a laboratory accident that minimizes the risk of exposure to laboratory staff and staff in adjacent areas. On the basis of an artificially large exposure to arthroconidia that may occur as a result of a laboratory accident, a conservative approach of close observation and early treatment of exposed staff is discussed.

PMID: 19663562 [PubMed - indexed for MEDLINE]

1058. Ann Allergy Asthma Immunol. 2009 Jul;103(1):26-30.

Household airborne Penicillium associated with peak expiratory flow variability in asthmatic children.

Bundy KW, Gent JF, Beckett W, Bracken MB, Belanger K, Triche E, Leaderer BP.

Department of Medicine, Division of Allergy/Immunology & Rheumatology, University of Rochester Medical Center, Rochester, New York 14642, USA. Kemp_Bundy@urmc.rochester.edu

BACKGROUND: Exposure to airborne fungi has been associated with increased airway hyperreactivity and asthma prevalence.
OBJECTIVE: To investigate the association between common indoor fungi and airway hyperreactivity measured by peak expiratory flow variability in asthmatic children.
METHODS: Children 6 to 12 years of age (n = 225) with a physician diagnosis of asthma were enrolled in the study to have their peak expiratory flow recorded twice daily during a 2-week period. Genus-specific, quantitative, in-home airborne mold concentrations were measured. Logistic regression models were used to examine the relationship between a mean peak expiratory flow variability greater than 18.5% (75th percentile) and any mold in the home (total mold, Cladosporium, Penicillium, Aspergillus, and Alternaria).
RESULTS: Mold was detected in 93% of the homes. The most common molds were Cladosporium in 72% and Penicillium in 42% of the samples. Controlling for sex, ethnicity, age, and winter season of sampling, Penicillium measured in the home was associated with a mean peak expiratory flow variability greater than 18.5% (odds ratio, 2.4; 95% confidence interval, 1.2-4.8). Greater peak expiratory flow variability was not associated with total mold or other mold measured in the home.
CONCLUSION: Exposure to airborne Penicillium is associated with increased peak expiratory flow variability in asthmatic children.

PMCID: PMC2746059 PMID: 19663123 [PubMed - indexed for MEDLINE]

1059. J Environ Monit. 2009 Aug;11(8):1513-7. Epub 2009 Jun 12.

Development of a new isotopically labeled internal standard for ergosterol measurement by GC/MS.

Sordillo J, Vespa D, Haggerty L, Youngs F, Gold D, Milton D.

Channing Laboratory, Boston, MA, USA.

Environmental exposure to fungi has been associated with a variety of adverse health effects. Ergosterol, a marker of total fungal biomass, can be used to quantify exposure to fungi. Unfortunately, environmental ergosterol measurement using published GC/MS/MS methods is prone to bias introduced by sample matrix effects, resulting in potential measurement inaccuracy. We developed an isotopically labeled internal standard ((13)C ergosterol) for ergosterol quantification by GC/MS/MS, to eliminate bias due to sample matrix effects and selective losses during preparation. To produce (13)C ergosterol, we grew Saccharomyces Cerevisiae on (13)C D-glucose under aerobic conditions at room temperature. The (13)C labeled ergosterol comprised 97.1% of the ergosterol in the dry yeast preparation. Ergosterol spike-recovery from house dust samples averaged 99.3% using the isotopically labeled yeast preparation as the internal standard (I.S.). By contrast, spike-recovery averaged 42.4% when 7-dehydrocholesterol (7-DHC) was the internal standard. Analysis of indoor house dust samples from a large epidemiologic study also showed the systematic underestimation of ergosterol when analyzed using 7-DHC as compared with using the yeast preparation containing the isotopically labeled authentic compound, (13)C-ergosterol.

PMID: 19657536 [PubMed - indexed for MEDLINE]

1060. J Clin Microbiol. 2009 Oct;47(10):3372-5. Epub 2009 Aug 5.

Atypical Aspergillus flavus isolates associated with chronic azole therapy.

Brandt ME, Gade L, McCloskey CB, Balajee SA.

Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA. mbb4@cdc.gov

A case of chronic sinus disease due to morphologically atypical Aspergillus flavus is described. Multiple fungal isolates sporulated poorly or not at all, displaying unusual color and microscopic morphology, including the absence of typical vesicles and phialides, which caused the isolates to resemble several other fungal genera superficially. The patient received multiple antifungal therapies over at least 10 years with various azole drugs, including voriconazole, itraconazole, and posaconazole. We speculate that this lengthy exposure to azole antifungal drugs may have caused or promoted the atypical morphology seen in these isolates.

PMCID: PMC2756908 PMID: 19656977 [PubMed - indexed for MEDLINE]

1061. J Antimicrob Chemother. 2009 Oct;64(4):764-73. Epub 2009 Aug 5.

The alternative oxidase of Candida albicans causes reduced fluconazole susceptibility.

Yan L, Li M, Cao Y, Gao P, Cao Y, Wang Y, Jiang Y.

Department of Pharmacology, College of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China.

OBJECTIVES: To evaluate the effect of Candida albicans mitochondrial respiratory status on antifungal azole susceptibility.
METHODS: The inhibitors cyanide and salicylhydroxamic acid (SHAM) were each combined with azoles to examine the effect of the combinations on C. albicans. C. albicans strains deleted for the alternative oxidase (Aox) were also examined for susceptibility to azoles and for the generation of intracellular reactive oxygen species (ROS). A chequerboard microdilution assay was performed on several C. albicans clinical strains including azole-resistant isolates to explore the combined effect of fluconazole and inhibitors of Aox.
RESULTS: The induction of the alternative respiratory pathway by cyanide decreased susceptibility to azoles, while the inhibition of alternative respiration by SHAM increased azole susceptibility. It was found that ROS production was increased in the absence of Aox in C. albicans upon treatment by antifungals such as miconazole and benomyl. The combination of fluconazole with SHAM resulted in a synergistic effect on the killing of C. albicans clinical isolates.
CONCLUSION: These results demonstrate that the induction of the alternative respiratory pathway confers reduced susceptibility to antifungal azoles, potentially through a mechanism that involves decreased intracellular ROS production during exposure to antifungal agents.

PMID: 19656781 [PubMed - indexed for MEDLINE]

1062. J Oral Pathol Med. 2010 Feb;39(2):182-7. Epub 2009 Jul 27.

Antifungal drug susceptibility of oral Candida albicans isolates may be associated with apoptotic responses to Amphotericin B.

Yang C, Gong W, Lu J, Zhu X, Qi Q.

Department of Oral Medicine School of Stomatology, Shandong University, Jinan, China.

BACKGROUND: Candida albicans is the important opportunistic fungal pathogens which can cause oral Candidiasis and even more seriously systemic infection. Apoptosis of C. albicans induced by environmental factor such as weak acid and antifungal drugs were studied recently. Illustrating the phenomenon of apoptosis in C. albicans may help us to discover new antifungal therapy by activating the fungal cells to suicide.
METHODS: Two oral C. albians clinical isolates which isolated respectively from healthy host [Strain 23C: minimal inhibition concentration (MIC) is 0.125 microg/ml for Amphotericin B (AmB)] and advanced cancer patient (Strain 28A: MIC is 2 microg/ml for AmB), were induced by 1 microg/ml AmB in vitro for 200 min, and then studied the apoptosis markers using terminal deoxynucletidyltransferase-mediated dUTP nick end labeling (TUNEL) (shown by diaminobenzidine and fluorescent isothiocyanate), and the ultrastructure of cell nuclear using transmission electron microscope (TEM), quantitative analysis using flow cytometry for the rapid exposure of phosphatidylserine at the outer membrane and propodium iodide (PI) double staining. C. albicans conference strain YEM30 was used as the control strain.
RESULTS: With TUNEL assay and TEM, we detected the typical characteristics of apoptosis. Strain 23C (with low MIC) showed significantly higher percentage of apoptosis (19.92%) compared with Strain 28A (with high MIC) which was isolated from the cancer patient (7.29%) (P < 0.01). In addition, 7.3% of early apoptosis cells of Strain 23C can form colonies on the plates, while 15% for Strain 28A. None of the PI+ cells can form colony.
CONCLUSIONS: Apoptosis of oral C. albicans isolates can be induced by AmB. The feature of antifungal drug susceptibility of the oral C. albicans clinical isolates may associate with the response of apoptosis inducing.

PMID: 19656268 [PubMed - indexed for MEDLINE]

1063. Cornea. 2009 Sep;28(8):914-7.

Hyphal penetration of worn hydrogel contact lenses by Fusarium.

Ahearn DG, Zhang S, Ward MA, Simmons RB, Stulting RD.

Department of Biology, Georgia State University, Atlanta, GA, USA. dgahearn@mindspring.com

PURPOSE: To determine the relative susceptibility of worn and unworn hydrogel contact lenses to penetration by hyphae of the Fusarium solani-Fusarium oxysporum species complex.
METHODS: Hydrogel contact lenses (lotrafilcon A, balafilcon A, senofilcon A, galyfilcon A, and etafilcon A) were removed from their original packages and placed directly on the eyes of 24 experienced contact lens wearers for 8-9 hours. Lenses were removed, each placed in 3.0 mL sterile phosphate buffered saline (PBS), and inoculated with 10 conidia of fusaria. Similar sets of unworn lenses were soaked in Sabouraud's dextrose broth for 2 hours prior to exposure to fusaria conidia in PBS. The entire surface of lenses was examined with microscopy for 14 days for the development of coiled hyphae in the lens matrix (ie, penetration pegs [PP]).
RESULTS: A total of 21 of 54 worn hydrogel lenses representing 4 types of silicone hydrogel and one type of hydroxyethylmethacrylate lens were penetrated by the fusaria. Compared to unworn lenses, 9 of the 21 PP-positive worn lenses showed earlier and more extensive penetration than seen with the unworn lenses. Several worn lenses compared to their unworn counterparts showed negligible or delayed penetration.
CONCLUSIONS: Worn hydrogel contact lenses without a history of exposure to disinfection solutions compared to unworn lenses of similar status may show enhanced or decreased susceptibilities to penetration by Fusarium. This suggests that tear characteristics are an additional factor in the invasive contamination of hydrogel contact lenses by Fusarium.

PMID: 19654522 [PubMed - indexed for MEDLINE]

1064. Nihon Ishinkin Gakkai Zasshi. 2009;50(3):139-45.

[Strategy of Aspergillus fumigatus to evade attacks from host--projectile weapons and armor].

[Article in Japanese]

Toyotome T, Watanabe A, Iwasaki A, Kamei K.

Division of Fungal Infection, Medical Mycology Research Center, Chiba University, Chiba, Japan.

Humans are continually inhaling environmental fungi. When the host immune system is competent, the inhaled fungi are cleared away from the lung by host defense mechanisms. But in immunocompromised individuals, the environmental fungi (e.g., Aspergillus fumigatus) sometimes cause infection. Pathogenic fungi possess various mechanisms to invade the host. A. fumigatus is no exception in possessing several virulence factors and defense mechanisms against host immune attack.One of the virulence factors is secondary metabolite. A. fumigatus produces a variety of secondary metabolites, and the fungal products in culture supernatant have a strong apoptosis-inducing activity to macrophages and alveolar epithelial cells. These data suggest that A. fumigatus is equipped with special projectile weapons for destroying host physical barriers and immunological barriers in lung.The fungal cell wall is an easy target for the host to recognize the pathogen. One of the fungal cell wall components, beta- (1,3) -glucan, is a major fungal PAMP (pathogen-associated molecular pattern), which is recognized by one of the pattern recognition receptors, dectin-1. The interaction induces activation of transcription factors and production of proinflammatory cytokines in the host cell. However, beta-glucan of A. fumigatus is strongly exposed to the surface only during the "swollen-conidia" phase. In the hyphal phase, the fungus is covered with "armor", i.e., other cell wall components to minimize the exposure of the beta-glucan structure. These findings suggest that A. fumigatus evades the recognition and the attack from host by masking beta-glucan. A. fumigatus has clever mechanisms to defend itself and to attack the host immune system.

PMID: 19654445 [PubMed - indexed for MEDLINE]

1065. Infect Control Hosp Epidemiol. 2009 Sep;30(9):928-9; author reply 929.

Is double gloving an effective barrier to protect surgeons against blood exposure due to needlestick injury?

Bouvet E, Pellissier G, Abiteboul D, L'Hériteau F; Group for the Prevention of Occupational Infections in Healthcare Workers.

Collaborators: Bouvet E, Pellissier G, Abiteboul D.

Comment on Infect Control Hosp Epidemiol. 2009 Jan;30(1):53-6.

PMID: 19653826 [PubMed - indexed for MEDLINE]

1066. Pediatrics. 2009 Aug;124(2):e329-38. Epub 2009 Jul 27.

Confirmed moisture damage at home, respiratory symptoms and atopy in early life: a birth-cohort study.

Karvonen AM, Hyvärinen A, Roponen M, Hoffmann M, Korppi M, Remes S, von Mutius E, Nevalainen A, Pekkanen J.

Environmental Health Department, National Institute for Health and Welfare, Kuopio, Finland. anne.karvonen@thl.fi

OBJECTIVES: Most previous studies on the association between moisture or mold problems in the home and respiratory symptoms in children were cross-sectional and based on self-reported exposure. The aim of this study was to evaluate the impact of objectively observed moisture damage and visible mold in the homes on early-life respiratory morbidity and atopic sensitization in a birth cohort.
METHODS: Building inspection was performed by building engineers in the homes of 396 children, and the children were followed up with questionnaires from birth to the age of 18 months. Specific immunoglobulin E levels were measured at the age of 1 year.
RESULTS: Doctor-diagnosed wheezing was associated with the severity of moisture damage in the kitchen and with visible mold in the main living area and especially in the bedroom of the child. The risk for parent-reported wheezing apart from cold increased with the severity of moisture damage in the kitchen. Moisture damage in the bathrooms or other interior spaces had no significant association with wheezing. No significant associations were observed for other end points, such as cough, or respiratory infections. There was a suggestion for an increased risk for sensitization to cat dander linked with moisture and mold exposure.
CONCLUSIONS: This birth-cohort study supports previous observations that moisture mold problems in the kitchen and in the main living area increase the risk for wheezing in early childhood. The results underline the importance of assessing separately the health effects of moisture and mold problems in different areas of the home.

PMID: 19651571 [PubMed - indexed for MEDLINE]

1067. Dokl Biol Sci. 2009 May-Jun;426:267-70.

The Biorisk experiment: 13-month exposure of resting forms of organism on the outer side of the Russian Segment of the International Space Station: preliminary results.

Baranov VM, Novikova ND, Polikarpov NA, Sychev VN, Levinskikh MA, Alekseev VR, Okuda T, Sugimoto M, Gusev OA, Grigor'ev AI.

Institute of Biomedical Problems, Russian Academy of Sciences, Khoroshevskoe sh. 76-a, Moscow, 123007 Russia.

PMID: 19650335 [PubMed - indexed for MEDLINE]

1068. FEBS Lett. 2009 Sep 3;583(17):2887-92. Epub 2009 Aug 3.

Kinetic and thermodynamic properties of the folding and assembly of formate dehydrogenase.

Ordu EB, Cameron G, Clarke AR, Karagüler NG.

Istanbul Technical University, Faculty of Science and Letters, Department of Molecular Biology and Genetics, Istanbul, Turkey.

The folding mechanism and stability of dimeric formate dehydrogenase from Candida methylica was analysed by exposure to denaturing agents and to heat. Equilibrium denaturation data yielded a dissociation constant of about 10(-13)M for assembly of the protein from unfolded chains and the kinetics of refolding and unfolding revealed that the overall process comprises two steps. In the first step a marginally stable folded monomeric state is formed at a rate (k(1)) of about 2x10(-3)s(-1) (by deduction k(-1) is about 10(-4)s(-1)) and assembles into the active dimeric state with a bimolecular rate constant (k(2)) of about 2x10(4)M(-1)s(-1). The rate of dissociation of the dimeric state in physiological conditions is extremely slow (k(-2) approximately 3x10(-7)s(-1)).

PMID: 19647736 [PubMed - indexed for MEDLINE]

1069. Biochim Biophys Acta. 2010 Feb;1800(2):190-201. Epub 2009 Jul 30.

Nucleocytoplasmic plant lectins.

Lannoo N, Van Damme EJ.

Department of Molecular Biotechnology, Laboratory of Biochemistry and Glycobiology, Ghent University, Coupure Links 653, 9000 Gent, Belgium.

During the last decade it was unambiguously shown that plants synthesize minute amounts of carbohydrate-binding proteins upon exposure to stress situations like drought, high salt, hormone treatment, pathogen attack or insect herbivory. In contrast to the 'classical' plant lectins, which are typically found in storage vacuoles or in the extracellular compartment this new class of lectins is located in the cytoplasm and the nucleus. Based on these observations the concept was developed that lectin-mediated protein-carbohydrate interactions in the cytoplasm and the nucleus play an important role in the stress physiology of the plant cell. Hitherto, six families of nucleocytoplasmic lectins have been identified. This review gives an overview of our current knowledge on the occurrence of nucleocytoplasmic plant lectins. The carbohydrate-binding properties of these lectins and potential ligands in the nucleocytoplasmic compartment are discussed in view of the physiological role of the lectins in the plant cell.

PMID: 19647040 [PubMed - indexed for MEDLINE]

1070. Respirology. 2009 May;14(4):617-20.

Coccidioidomycosis as a rare cause of pneumonia in non-endemic areas: a short exposure history should not be ignored.

Kwok HK, Chan JW, Li IW, Chu SY, Lam CW.

Hospital Authority Head Office, Queen Elizabeth Hospital, University of Hong Kong, Hong Kong, China. kwokkhh@ha.org.hk

Coccidioidomycosis is endemic in the south-western USA. Two cases of infection in travellers returning to Hong Kong are described. A previously healthy patient who had travelled to an endemic area for a short time was successfully treated with fluconazole. A second patient with comorbidities and more prolonged exposure had disseminated and eventually fatal disease, despite prolonged administration of anti-fungal agents. Although coccidioidomycosis is a rare disease in Hong Kong, it should always be considered when there is a relevant travel history. Even a short period of travel to an endemic area should alert clinicians to this possibility when managing patients with severe pneumonia, especially those with multi-organ involvement. On the other hand, in patients with comorbidities, even aggressive and prolonged anti-fungal therapy may not guarantee a successful outcome.

PMID: 19645872 [PubMed - indexed for MEDLINE]

1071. Liver Transpl. 2009 Aug;15(8):842-58.

Antifungal prophylaxis in liver transplant recipients.

Eschenauer GA, Lam SW, Carver PL.

University of Pittsburgh Medical Center, Pittsburgh, PA, USA. eschenauerg@upmc.edu

Erratum in Liver Transpl. 2010 Jun;16(6):797-805.

Although the overall incidence of fungal infections in liver transplant recipients has declined, these infections still contribute significantly to the morbidity and mortality of patients with risk factors for infection. Although antifungal prophylaxis has been widely studied and practiced, no consensus exists on which patients should receive prophylaxis, with which agent, and for what duration. Numerous studies have attempted to ascertain independent risk factors for invasive fungal infections in liver transplant patients, and these data, in addition to clinical trials, identify several patient groups at exceedingly high risk of fungal infection. These include retransplant patients, patients with renal failure requiring hemodialysis or renal replacement therapy, and those requiring reoperations after transplant. Because the majority of infections occur in the first month after transplantation, prophylaxis should be continued for 4-6 weeks. However, local epidemiology and research should guide decisions regarding choice of agent as well as overall development of interinstitutional guidelines, because the incidence and spectrum of infection may differ dramatically among institutions. Liver Transpl 15:842-858, 2009. (c) 2009 AASLD.

PMID: 19642130 [PubMed - indexed for MEDLINE]

1072. AAOHN J. 2009 Jul;57(7):275-80.

Evaluation of home health care nurses' practice and their employers' policies related to bloodborne pathogens.

Scharf BB, McPhaul KM, Trinkoff A, Lipscomb J.

University of Maryland, USA.

The purpose of this descriptive study was to assess home health care nurses' exposure to bloodborne pathogens, evaluate Medicare Certified Home Healthcare Agency (MCHHA) and hospice organization practices related to the Occupational Safety and Health Administration's (OSHA) Bloodborne Pathogens Standard and the Needlestick Safety and Prevention Act, and link the two to recommend safety improvements. This study evaluated the experiences of 355 home health care nurses and 30 MCHHA and hospice employers in one mid-Atlantic state regarding bloodborne pathogen programs and practices and blood and sharps contact. An index was developed to evaluate employer compliance with OSHA's Bloodborne Pathogens Standard. Employer policies and nurse practice related to the OSHA Bloodborne Pathogens Standard did not meet all requirements despite identified risk. Thirty-eight home health care nurses from 12 of the 30 employers reported needlestick injuries within the past year, yet employers reported only 18 nurse needlestick injuries within the same year. Using the bloodborne pathogen compliance index, employers can review and revise their exposure control plans to ensure compliance. This intervention should benefit both employer policies and nurse practice to improve safety and decrease the risks from bloodborne pathogens in the home health care setting.

PMID: 19639859 [PubMed - indexed for MEDLINE]

1073. Rev Iberoam Micol. 2009 Sep 30;26(3):202-5. Epub 2009 Jul 18.

Effect of phenotypic switching on expression of virulence factors by Candida albicans causing candidiasis in diabetic patients.

Antony G, Saralaya V, Gopalkrishna Bhat K, Shalini Shenoy M, Shivananda PG.

Department of Microbiology, Kasturba Medical College, Manipal University, Mangalore 575001, India.

A total of 110 strains belonging to seven species of Candida were isolated from various forms of candidiasis in diabetic patients. They were Candida albicans 53 (47%), Candida tropicalis 36 (33%), Candida glabrata 9 (8%), Candida parapsilosis 4 (4%), Candida guilliermondii 2 (2%), Candida krusei 5 (5%) and Candida kefyr 1 (1%). All 53 strains of C. albicans isolated were observed to express virulence factors such as cell surface hydrophobicity (CSH), adherence to human buccal epithelial cell (BEC) and proteinase activity (100%), while phospholipase activity was observed in 52 (98%). Phenotypic switching and its influence on the pathogenicity of C. albicans were studied. Two C. albicans strains isolated from oral and vaginal thrush, respectively, in diabetic individuals, and the control strain C. albicans NCPF 3153A were induced to undergo phenotypic switching by exposure to UV light and the degree of expression of virulence factors by the different morphological forms was determined. Three different morphological forms of C. albicans were obtained, namely Star (S), Wrinkled (W) and Ring (R) types from the original Smooth (O) variety. It was found that proteinase activity was greatest with the W type followed by the R type then the O type. The S type produced the least proteinase. The phospholipase activity was greatest with O type followed by R type. The W and S types produced the least phospholipase. Expression of CSH and adherence was greatest in the O type followed by the R and then the W type and finally the S type. Differential expression of virulence factors occurs with different phenotypic forms of C. albicans and this may provide a particular morphological type with a distinct advantage over other types in causing candidiasis.

PMID: 19635443 [PubMed - indexed for MEDLINE]

1074. Br J Nurs. 2009 Jul 23-Aug 12;18(14):860, 862-4.

Sharps management and the disposal of clinical waste.

Blenkharn JI.

Blenkharn Environmental, London.

Dangerous errors in clinical waste management continue to occur and inappropriate items find their way into clinical waste sacks that are not designed to hold sharp or heavy items, or fluids. Although great attention is given to the safe use of sharps, needles still find their way into waste sacks instead of a sharps bin. Sharps injuries among ancillary and support staff, and waste handlers working in the disposal sector, can occur at a rate greater than for health-care staff. Blood and body fluid exposures from carelessly packaged clinical waste are similarly common, with almost 100% of waste handlers having blood splashes on their clothing within four hours of starting a shift. Blood splashes are also common on the outside surfaces of sharps bins and on the frames supporting clinical waste sacks. Using forensic techniques, blood residues invisible to the naked eye can be detected on all surfaces of most sharps bins and on the bench top, walls and floor where the bins were positioned. Care is required when disposing of clinical waste, to protect and maintain the immediate environment from contamination, and to ensure the safety of those who come into contact with waste as it passes along the disposal chain.

PMID: 19633596 [PubMed - indexed for MEDLINE]

1075. Am J Infect Control. 2009 Oct;37(8):631-7. Epub 2009 Jul 23.

Influence of internal and outdoor factors on filamentous fungal flora in hematology wards.

Brenier-Pinchart MP, Lebeau B, Quesada JL, Mallaret MR, Borel JL, Mollard A, Garban F, Brion JP, Molina L, Bosson JL, Cahn JY, Grillot R, Pelloux H.

Parasitologie-Mycologie, Pôle de Biologie, Centre Hospitalier Universitaire, Grenoble, France. MPBrenierPinchart@chu-grenoble.fr

BACKGROUND: Nosocomial invasive filamentous fungi infections could result from inhalation of filamentous fungi conidia present in hospital environment.
METHODS: The environmental fungal flora in 3 different hospital wards with similar air conditioning was prospectively studied during 30 months and compared to internal (presence of agranulocytosis patient, behavioral practices, activity, cleaning work) and outdoor factors (meteorologic data, outdoor fungi). The general preventive measures differed from one unit to another.
RESULTS: The hematology wards with filamentous fungi preventive measures were significantly less contaminated than a conventional ward without specific measures. Internal and outdoor factors influenced the level of fungal flora. However, the influence of internal factors was greater in the conventional ward than in hematology wards. The variation of flora in the hospital environment was seasonal, and the level of this contamination in each ward was influenced by the meteorology. However, outdoor factors more readily explain the variations of fungal load in hematology than in the conventional ward.
CONCLUSION: This study highlights that specific preventive measures participate significantly in the control of the filamentous fungal flora intensity due to internal factors but not those due to outdoor factors, stressing the importance of high-efficiency particulate air filtration in high-risk units.

PMID: 19631408 [PubMed - indexed for MEDLINE]

1076. Genomics. 2009 Nov;94(5):294-307. Epub 2009 Jul 22.

A genome-wide screen in Saccharomyces cerevisiae reveals pathways affected by arsenic toxicity.

Zhou X, Arita A, Ellen TP, Liu X, Bai J, Rooney JP, Kurtz AD, Klein CB, Dai W, Begley TJ, Costa M.

Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, NY 10987, USA.

We have used Saccharomyces cerevisiae to identify toxicologically important proteins and pathways involved in arsenic-induced toxicity and carcinogenicity in humans. We performed a systemic screen of the complete set of 4733 haploid S. cerevisiae single-gene-deletion mutants to identify those that have decreased or increased growth, relative to wild type, after exposure to sodium arsenite (NaAsO(2)). IC(50) values for all mutants were determined to further validate our results. Ultimately we identified 248 mutants sensitive to arsenite and 5 mutants resistant to arsenite exposure. We analyzed the proteins corresponding to arsenite-sensitive mutants and determined that they belonged to functional categories that include protein binding, phosphate metabolism, vacuolar/lysosomal transport, protein targeting, sorting, and translocation, cell growth/morphogenesis, cell polarity and filament formation. Furthermore, these data were mapped onto a protein interactome to identify arsenite-toxicity-modulating networks. These networks are associated with the cytoskeleton, ubiquitination, histone acetylation and the MAPK signaling pathway. Our studies have potential implications for understanding toxicity and carcinogenesis in arsenic-induced human conditions, such as cancer and aging.

PMCID: PMC2763962 PMID: 19631266 [PubMed - indexed for MEDLINE]

1077. J Mol Biol. 2009 Oct 2;392(4):923-36. Epub 2009 Jul 21.

Structural-thermodynamic relationships of interactions in the N-terminal ATP-binding domain of Hsp90.

Nilapwar S, Williams E, Fu C, Prodromou C, Pearl LH, Williams MA, Ladbury JE.

Institute of Structural and Molecular Biology, University College London, Gower Street, London WC1E 6BT, UK.

Despite its importance as a target in anti-cancer therapeutics and the numerous rational-based inhibitor design efforts aimed at it, there are only limited data available on structural-thermodynamic relationships of interactions of the N-terminal ATP-binding domain of Hsp90 (N-Hsp90). Here, we redress this by presenting an investigation of binding of nucleotides and ansamycin compounds to this domain. Interactions of nucleotides with N-Hsp90 are relatively weak (>10 microM) and are strongly enthalpy driven over the temperature range 10-25 degrees C. Geldanamycin (GA) and its analogues 17-AAG [17-(allylamino)-17-demethoxy-GA] and 17-DMAG (17-N,N-dimethylaminoethylamino-17-demethoxy-GA) bind more strongly and have a dominant favourable enthalpic contribution over the temperature range investigated. We investigated the temperature dependence of the enthalpic contribution to binding. We found that while the ansamycin compounds have the commonly observed negative value, the nucleotides show a negligible or even a positive DeltaC(p) of binding. These data represent the first observation of a single binding site for which interactions with different ligands result in both negative and positive DeltaC(p) values. By addressing the likely impact of the potential contributions from protein-ligand interactions, we are able to attribute the anomalous DeltaC(p) for the nucleotides largely to a change in the conformation of the domain structure and local motion in the lid region of N-Hsp90 with the concomitant exposure of hydrophobic amino acid side chains.

PMID: 19631219 [PubMed - indexed for MEDLINE]

1078. Rev Iberoam Micol. 2009 Jun 30;26(2):155-60.

[Studies of viability and vitality after freezing of the probiotic yeast Saccharomyces boulardii: physiological preconditioning effect].

[Article in Spanish]

Pardo S, Galvagno MA, Cerrutti P.

Laboratorio de Microbiología Industrial, Departamento de Ingeniería Química, Facultad de Ingeniería, Universidad de Buenos Aires, Buenos Aires, Argentina.

The aim of this study was to evaluate the vitality and viability of the probiotic yeast Saccharomyces boulardii after freezing/thawing and the physiological preconditioning effect on these properties. The results indicate that the specific growth rate (0.3/h(-1)) and biomass (2-3 x10(8)cells/ml) of S. boulardii obtained in flasks shaken at 28 degrees C and at 37 degrees C were similar. Batch cultures of the yeast in bioreactors using glucose or sugar-cane molasses as carbon sources, reached yields of 0.28 g biomass/g sugar consumed, after 10h incubation at 28 degrees C; the same results were obtained in fed batch fermentations. On the other hand, in batch cultures, the vitality of cells recovered during the exponential growth phase was greater than the vitality of cells from the stationary phase of growth. Vitality of cells from fed-batch fermentations was similar to that of stationary growing cells from batch fermentations. Survival to freezing at -20 degrees C and subsequent thawing of cells from batch cultures was 0.31% for cells in exponential phase of growth and 11.5% for cells in stationary phase. Pre-treatment of this yeast in media with water activity (a(w)) 0.98 increased the survival to freezing of S. boulardii cells stored at -20 degrees C for 2 months by 10 fold. Exposure of the yeast to media of reduced a(w) and/or freezing/thawing process negatively affected cell vitality. It was concluded that stress conditions studied herein decrease vitality of S. boulardii. Besides, the yeast strain studied presented good tolerance to bile salts even at low pH values.

PMID: 19631167 [PubMed - indexed for MEDLINE]

1079. Rev Iberoam Micol. 2009 Jun 30;26(2):108-11.

[Colonization by yeasts in newborns and healthcare personnel in a neonatal intensive care unit at a university hospital in Bogotá, Colombia].

[Article in Spanish]

Orozco PA, Cortés JA, Parra CM.

Grupo de Enfermedades Infecciosas, Departamento de Microbiología, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá, Colombia.

Candida infections in the neonatal intensive care unit (NICU) are associated with high morbidity and mortality rates. The main objective of this work was to determine the risk factors for colonization by Candida species in the newborns in a hospital NICU in Bogota, Colombia, and to evaluate the colonization of intravascular devices and healthcare personnel. Fifty newborns at high risk (low birth-weight, gestational age under 35 weeks, previous exposure to antibiotics and eight days of stay in the NICU) were followed prospectively. Clinical specimens from conjunctiva, nasal orifices, oral cavity, inguinal skin, rectum, intravascular devices, and the resulting watery solution of the washing of hands of healthcare personnel were cultured. Samples were cultured on Sabouraud agar with chloramphenicol (50 ppm). Identification of yeasts was peformed using phenotypic and biochemical tests. A multivariate analysis of the risk factors for colonization in the newborns was performed. Growth of different Candida spp. was found in samples recovered from 38% of the newborns tested. However, no yeasts were obtained in cultures from intravascular devices. About 32% of the samples from healthcare personnel (paediatricians, undergraduate and postgraduate students, professional nurses and nurse assistants), showed presence of yeasts. In the multivariate regression analysis length of stay in the NICU was the only identified risk factor for colonization.

PMID: 19631159 [PubMed - indexed for MEDLINE]

1080. Biotechnol Prog. 2009 Sep-Oct;25(5):1260-6.

Augmented biosynthesis of cadmium sulfide nanoparticles by genetically engineered Escherichia coli.

Chen YL, Tuan HY, Tien CW, Lo WH, Liang HC, Hu YC.

Food Industry Research and Development Institute, Hsinchu, Taiwan.

Microorganisms can complex and sequester heavy metals, rendering them promising living factories for nanoparticle production. Glutathione (GSH) is pivotal in cadmium sulfide (CdS) nanoparticle formation in yeasts and its synthesis necessitates two enzymes: gamma-glutamylcysteine synthetase (gamma-GCS) and glutathione synthetase (GS). Hereby, we constructed two recombinant E. coli ABLE C strains to over-express either gamma-GCS or GS and found that gamma-GCS over-expression resulted in inclusion body formation and impaired cell physiology, whereas GS over-expression yielded abundant soluble proteins and barely impeded cell growth. Upon exposure of the recombinant cells to cadmium chloride and sodium sulfide, GS over-expression augmented GSH synthesis and ameliorated CdS nanoparticles formation. The resultant CdS nanoparticles resembled those from the wild-type cells in size (2-5 nm) and wurtzite structures, yet differed in dispersibility and elemental composition. The maximum particle yield attained in the recombinant E. coli was approximately 2.5 times that attained in the wild-type cells and considerably exceeded that achieved in yeasts. These data implicated the potential of genetic engineering approach to enhancing CdS nanoparticle biosynthesis in bacteria. Additionally, E. coli-based biosynthesis offers a more energy-efficient and eco-friendly method as opposed to chemical processes requiring high temperature and toxic solvents.

2009 American Institute of Chemical Engineers Biotechnol.

PMID: 19630084 [PubMed - indexed for MEDLINE]

1081. Toxicol Sci. 2009 Oct;111(2):437-46. Epub 2009 Jul 23.

Actin-mediated endocytosis limits intracellular Cr accumulation and Cr toxicity during chromate stress.

Holland SL, Avery SV.

School of Biology, Institute of Genetics, The University of Nottingham, University Park, Nottingham, UK.

Chromate toxicity is well documented, but the underlying toxic mechanism(s) has yet to be fully elucidated. Following a Cr toxicity screen against > 6000 heterozygous yeast mutants, here we show that Cr resistance requires normal function of the cortical actin cytoskeleton. Furthermore, Cr-stressed yeast cells exhibited an increased number of actin patches, the sites of endocytosis. This was coincident with a marked stimulation of endocytosis following Cr exposure. Genetic dissection of actin nucleation from endocytosis revealed that endocytosis, specifically, was required for Cr resistance. A series of further endocytosis mutants (sac6Delta, chc1Delta, end3Delta) exhibited elevated Cr sensitivity. These mutants also showed markedly elevated cellular Cr accumulation, explaining their sensitivities. In wild-type cells, an initial endocytosis-independent phase of Cr uptake was followed by an endocytosis-dependent decline in Cr accumulation. The results indicate that actin-mediated endocytosis is required to limit Cr accumulation and toxicity. It is proposed that this involves ubiquitin-dependent endocytic inactivation of a plasma membrane Cr transporter(s). We showed that such an action was not dependent on the transporters that have been characterized to date, the sulfate (and chromate) permeases Sul1p and Sul2p.

PMCID: PMC2742586 PMID: 19628586 [PubMed - indexed for MEDLINE]

1082. Med Mycol. 2010 Mar;48(2):298-302.

Determination of Alt a 1 (Alternaria alternata) in poultry farms and a sawmill using ELISA.

Prester L, Macan J.

Institute for Medical Research and Occupational Health, Zagreb, Croatia. prester@imi.hr

Farm and sawmill workers are exposed to high levels of allergenic fungi, such as Alternaria alternata, which are associated with respiratory diseases and asthma. The aim of this study was to measure the concentration of Alt a 1, a major allergen of A. alternata, in indoor dust samples collected in poultry farms and a sawmill using a monoclonal antibody-based enzyme immunoassay. A total of 45 dust samples were collected in poultry farms (30) and the sawmill (15) in Zagreb County (Croatia). The Alt a 1 allergen was detected in all dust samples (100%) collected in three poultry farms. The levels of Alt a 1 were in the range of 0.1-14 microg/g, and the median value was 0.37 microg/g. About 86% of dust samples contained Alt a 1 in the range of 0.1-1.0 microg/g. In the sawmill, no detectable level of Alt a 1 was found (limit of detection =0.12 microg/g). This study has shown that occupational exposure to Alt a 1 allergen in poultry farms deserves monitoring.

PMID: 19626544 [PubMed - indexed for MEDLINE]

1083. Int Arch Occup Environ Health. 2010 Jan;83(1):77-83. Epub 2009 Jul 22.

Occupational exposures to bloodborne viruses among German dental professionals and students in a clinical setting.

Wicker S, Rabenau HF.

Occupational Health Service, Hospital of the Johann Wolfgang Goethe-University of Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany. Sabine.Wicker@kgu.de

PURPOSE: Exposures to bloodborne pathogens pose a serious risk to dental healthcare workers (DHCW). Despite improved methods of preventing exposures like needlestick injuries (NSI), occupational exposures still continue to occur. The purpose of this study was to evaluate the incidence of occupational exposures to patient body fluids among German DHCW, to assess the rate of reporting of such incidents, and to evaluate the association of various factors with these exposures.
METHODS: Data was obtained through an anonymous questionnaire.
RESULTS: Our study confirms that occupational skills are an important factor concerning NSI. It turned out that dental students (0.74 NSI p. a.) had nearly twice the number of NSI compared with dentists with more or less than 10 years working experience (0.42, 0.49 NSI p. a., respectively, P < 0.0001). Overall, 54.3% (n = 144/265) of respondents had sustained at least one NSI in their professional life. Only 28.5% of injured dental students and DHCW reported all of their NSI, the main reason (19.1%) for not reporting NSI was little or no perception of risk on behalf of the respondent. One-fourth of respondents were not wearing a mask and 55.6% were not wearing protective goggles during their last occupational exposures.
CONCLUSIONS: Occupational exposure to blood or body fluids is a common problem among DHCW and dental students. Measures must be adopted by official institutions, public health service, occupational health association and universities in order to reverse this situation.

PMID: 19626335 [PubMed - indexed for MEDLINE]

1084. Lasers Med Sci. 2010 Nov;25(6):829-34. Epub 2009 Jul 22.

Argon ion laser and halogen lamp activation of a dark and light resin composite: microhardness after long-term storage.

Cassoni A, Ferla Jde O, Albino LG, Youssef MN, Shibli JA, Rodrigues JA.

Department of Restorative Dentistry, School of Dentistry, Guarulhos University, São Paulo, Brazil. acassoni@prof.ung.br

The objective of this study was to evaluate in vitro light activation of the nano-filled resin composite Vita shade A1 and A3 with a halogen lamp (QTH) and argon ion laser by Knoop microhardness profile. Materials and methods: Specimens of nanofilled composite resin (Z350-3 M-ESPE) Vita shade A1 and A3 were prepared with a single increment inserted in 2.0-mm-thick and 3-mm diameter disc-shaped Teflon mold. The light activation was performed with QTH for 20 s (with an intensity of approximately 1,000 mW/cm(2) and 700 mW/cm(2)) and argon ion laser for 10 s (with a power of 150 mW and 200 mW). Knoop microhardness test was performed after 24 h and 6 months. The specimens were divided into the 16 experimental groups (n = 10), according to the factors under study: photoactivation form, resin shade, and storage time. Knoop microhardness data was analyzed by a factorial ANOVA and Tukey s tests at the 0.05 level of significance. Results: Argon ion laser was not able to photo-activate the darker shade of the nanofilled resin composite evaluated but when used with 200 mW it can be as effective as QTH to photo-activate the lighter shade with only 50% of the time exposure. After 6 months storage, an increase in the means of Knoop microhardness values were observed. Conclusions: Light-activation significantly influenced the Knoop microhardness values for the darker nanofilled resin composite.

PMID: 19626274 [PubMed - indexed for MEDLINE]

1085. DNA Repair (Amst). 2009 Oct 2;8(10):1207-14. Epub 2009 Jul 21.

Cellular pathways for DNA repair and damage tolerance of formaldehyde-induced DNA-protein crosslinks.

de Graaf B, Clore A, McCullough AK.

Department of Molecular and Medical Genetics, Center for Research on Occupational and Environmental Toxicology, Oregon Health & Science University, Portland, 97239, USA.

Although it is well established that DNA-protein crosslinks are formed as a consequence of cellular exposure to agents such as formaldehyde, transplatin, ionizing and ultraviolet radiation, the biochemical pathways that promote cellular survival via repair or tolerance of these lesions are poorly understood. To investigate the mechanisms that function to limit DNA-protein crosslink-induced cytotoxicity, the Saccharomyces cerevisiae non-essential gene deletion library was screened for increased sensitivity to formaldehyde exposure. Following low dose, chronic exposure, strains containing deletions in genes mediating homologous recombination showed the greatest sensitivity, while under the same exposure conditions, deletions in genes associated with nucleotide excision repair conferred only low to moderate sensitivities. However, when the exposure regime was changed to a high dose acute (short-term) formaldehyde treatment, the genes that conferred maximal survival switched to the nucleotide excision repair pathway, with little contribution of the homologous recombination genes. Data are presented which suggest that following acute formaldehyde exposure, repair and/or tolerance of DNA-protein crosslinks proceeds via formation of nucleotide excision repair-dependent single-strand break intermediates and without a detectable accumulation of double-strand breaks. These data clearly demonstrate a differential pathway response to chronic versus acute formaldehyde exposures and may have significance and implications for risk extrapolation in human exposure studies.

PMCID: PMC2748227 PMID: 19625222 [PubMed - indexed for MEDLINE]

1086. Emerg Infect Dis. 2009 Jul;15(7):1068-76.

Frequency and evolution of Azole resistance in Aspergillus fumigatus associated with treatment failure.

Howard SJ, Cerar D, Anderson MJ, Albarrag A, Fisher MC, Pasqualotto AC, Laverdiere M, Arendrup MC, Perlin DS, Denning DW.

Regional Mycology Laboratory, Manchester, UK.

Azoles are the mainstay of oral therapy for aspergillosis. Azole resistance in Aspergillus has been reported infrequently. The first resistant isolate was detected in 1999 in Manchester, UK. In a clinical collection of 519 A. fumigatus isolates, the frequency of itraconazole resistance was 5%, a significant increase since 2004 (p<0.001). Of the 34 itraconazole-resistant isolates we studied, 65% (22) were cross-resistant to voriconazole and 74% (25) were cross-resistant to posaconazole. Thirteen of 14 evaluable patients in our study had prior azole exposure; 8 infections failed therapy (progressed), and 5 failed to improve (remained stable). Eighteen amino acid alterations were found in the target enzyme, Cyp51A, 4 of which were novel. A population genetic analysis of microsatellites showed the existence of resistant mutants that evolved from originally susceptible strains, different cyp51A mutations in the same strain, and microalterations in microsatellite repeat number. Azole resistance in A. fumigatus is an emerging problem and may develop during azole therapy.

PMCID: PMC2744247 PMID: 19624922 [PubMed - indexed for MEDLINE]

1087. Ann Occup Hyg. 2009 Oct;53(7):749-57. Epub 2009 Jul 20.

Airborne fungal and bacterial components in PM1 dust from biofuel plants.

Madsen AM, Schlünssen V, Olsen T, Sigsgaard T, Avci H.

The National Research Centre for the Working Environment, Lersø Parkallé 105, 2100 Copenhagen Ø, Denmark. amm@nrcwe.dk

Fungi grown in pure cultures produce DNA- or RNA-containing particles smaller than spore size (<1.5 microm). High exposures to fungi and bacteria are observed at biofuel plants. Airborne cultivable bacteria are often described to be present in clusters or associated with larger particles with an aerodynamic diameter (d(ae)) of 2-8 microm. In this study, we investigate whether airborne fungal components smaller than spore size are present in bioaerosols in working areas at biofuel plants. Furthermore, we measure the exposure to bacteria and fungal components in airborne particulate matter (PM) with a D(50) of 1 microm (called PM(1) dust). PM(1) was sampled using Triplex cyclones at a working area at 14 Danish biofuel plants. Millipore cassettes were used to sample 'total dust'. The PM(1) particles (29 samples) were analysed for content of 11 different components and the total dust was analysed for cultivable fungi, N-acetyl-beta-D-glucosaminidase (NAGase), and (1 --> 3)-beta-D-glucans. In the 29 PM(1) samples, cultivable fungi were found in six samples and with a median concentration below detection level. Using microscopy, fungal spores were identified in 22 samples. The components NAGase and (1 --> 3)-beta-D-glucans, which are mainly associated with fungi, were present in all PM(1) samples. Thermophilic actinomycetes were present in 23 of the 29 PM(1) samples [average = 739 colony-forming units (CFU) m(-3)]. Cultivable and 'total bacteria' were found in average concentrations of, respectively, 249 CFU m(-3) and 1.8 x 10(5) m(-3). DNA- and RNA-containing particles of different lengths were counted by microscopy and revealed a high concentration of particles with a length of 0.5-1.5 microm and only few particles >1.5 microm. The number of cultivable fungi and beta-glucan in the total dust correlated significantly with the number of DNA/RNA-containing particles with lengths of between 1.0 and 1.5 microm, with DNA/RNA-containing particles >1.5 microm, and with other fungal components in PM(1) dust. Airborne beta-glucan and NAGase were found in PM(1) samples where no cultivable fungi were present, and beta-glucan and NAGase were found in higher concentrations per fungal spore in PM(1) dust than in total dust. This indicates that fungal particles smaller than fungal spore size are present in the air at the plants. Furthermore, many bacteria, including actinomycetes, were present in PM(1) dust. Only 0.2% of the bacteria in PM(1) dust were cultivable.

PMCID: PMC2758667 PMID: 19620231 [PubMed - indexed for MEDLINE]

1088. Respir Res. 2009 Jul 21;10:68.

Candida soluble cell wall beta-glucan facilitates ovalbumin-induced allergic airway inflammation in mice: Possible role of antigen-presenting cells.

Inoue K, Takano H, Koike E, Yanagisawa R, Oda T, Tamura H, Adachi Y, Ishibashi K, Ohno N.

Environmental Health Sciences Division, National Institute for Environmental Studies, Tsukuba, Ibaraki 305-8506, Japan. inoue.kenichirou@nies.go.jp

BACKGROUND: Although fungi have been implicated as initiating/deteriorating factors for allergic asthma, their contributing components have not been fully elucidated. We previously isolated soluble beta-glucan from Candida albicans (CSBG) (Ohno et al., 2007). In the present study, the effects of CSBG exposure on airway immunopathology in the presence or absence of other immunogenic allergen was investigated in vivo, and their cellular mechanisms were analyzed both in vivo and in vitro.
METHODS: In vivo, ICR mice were divided into 4 experimental groups: vehicle, CSBG (25 microg/animal), ovalbumin (OVA: 2 microg/animal), and CSBG + OVA were repeatedly administered intratracheally. The bronchoalveolar lavage cellular profile, lung histology, levels of cytokines and chemokines in the lung homogenates, the expression pattern of antigen-presenting cell (APC)-related molecules in the lung digests, and serum immunoglobulin values were studied. In vitro, the impacts of CSBG (0-12.5 microg/ml) on the phenotype and function of immune cells such as splenocytes and bone marrow-derived dendritic cells (BMDCs) were evaluated in terms of cell proliferation, the surface expression of APC-related molecules, and OVA-mediated T-cell proliferating activity.
RESULTS: In vivo, repeated pulmonary exposure to CSBG induced neutrophilic airway inflammation in the absence of OVA, and markedly exacerbated OVA-related eosinophilic airway inflammation with mucus metaplasia in mice, which was concomitant with the amplified lung expression of Th2 cytokines and IL-17A and chemokines related to allergic response. Exposure to CSBG plus OVA increased the number of cells bearing MHC class II with or without CD80 in the lung compared to that of others. In vitro, CSBG significantly augmented splenocyte proliferation in the presence or absence of OVA. Further, CSBG increased the expression of APC-related molecules such as CD80, CD86, and DEC205 on BMDCs and amplified OVA-mediated T-cell proliferation through BMDCs.
CONCLUSION: CSBG potentiates allergic airway inflammation with maladaptive Th immunity, and this potentiation was associated with the enhanced activation of APCs including DC.

PMCID: PMC2731726 PMID: 19619338 [PubMed - indexed for MEDLINE]

1089. Public Health Rep. 2009 Jul-Aug;124 Suppl 1:169-79.

Hands-free technique in the operating room: reduction in body fluid exposure and the value of a training video.

Stringer B, Haines T, Goldsmith CH, Blythe J, Berguer R, Andersen J, De Gara CJ.

Department of Clinical Epidemiology and Biostatistics, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada.

OBJECTIVES: This study sought to determine if (1) using a hands-free technique (HFT)--whereby no two surgical team members touch the same sharp item simultaneously--> or = 75% of the time reduced the rate of percutaneous injury, glove tear, and contamination (incidents); and (2) if a video-based intervention increased HFT use to > or = 75%, immediately and over time.
METHODS: During three and four periods, in three intervention and three control hospitals, respectively, nurses recorded incidents, percentage of HFT use, and other information in 10,596 surgeries. The video was shown in intervention hospitals between Periods 1 and 2, and in control hospitals between Periods 3 and 4. HFT, considered used when > or = 75% passes were done hands-free, was practiced in 35% of all surgeries. We applied logistic regression to (1) estimate the rate reduction for incidents in surgeries when the HFT was used and not used, while adjusting for potential risk factors, and (2) estimate HFT use of about 75% and 100%, in intervention compared with control hospitals, in Period 2 compared with Period 1, and Period 3 compared with Period 2.
RESULTS: A total of 202 incidents (49 injuries, 125 glove tears, and 28 contaminations) were reported. Adjusted for differences in surgical type, length, emergency status, blood loss, time of day, and number of personnel present for > or = 75% of the surgery, the HFT-associated reduction in rate was 35%. An increase in use of HFT of > or = 75% was significantly greater in intervention hospitals, during the first post-intervention period, and was sustained five months later.
CONCLUSION: The use of HFT and the HFT video were both found to be effective.

PMCID: PMC2708668 PMID: 19618819 [PubMed - indexed for MEDLINE]

1090. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009 Aug;108(2):203-10.

Associations among the use of highly active antiretroviral therapy, oral candidiasis, oral Candida species and salivary immunoglobulin A in HIV-infected children.

Pomarico L, Cerqueira DF, de Araujo Soares RM, de Souza IP, de Araujo Castro GF, Socransky S, Haffajee A, Teles RP.

Department of Pediatric Dentistry and Orthodontics, School of Dentistry, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. lupomarico@superig.com.br

OBJECTIVES: The aim was to examine the impact of antiretroviral therapy on the prevalence of oral candidiasis, recovery of oral Candida spp. , and salivary levels of total secretory immunoglobulin A (SIgA) and Candida-specific SIgA in human immunodeficiency virus (HIV)-infected children. STUDY DESIGN: Sixty-six HIV+ and 40 HIV- children were cross-sectionally examined for the presence of oral lesions. Whole stimulated saliva samples were collected for the identification of Candida spp. using culture and measurement of total and specific SIgA using enzyme-linked immunosorbent assay (ELISA).
RESULTS: The HIV+ children had a higher prevalence of oral candidiasis (P < .05), higher frequency of detection of Candida spp. (P < .05), and higher levels of total (P < .05) and Candida-specific SIgA (P < .001) than the HIV- children. Among the HIV+ subjects, antiretroviral users had lower viral loads (P < .001) and lower levels of Candida spp. (P < .05) and total SIgA (P < .05) compared with antiretroviral nonusers.
CONCLUSIONS: The use of antiretroviral therapy was associated with decreases in the prevalence of oral candidiasis. This diminished exposure to Candida spp. was accompanied by decreases in levels of total and Candida-specific SIgA.

PMCID: PMC2758816 PMID: 19615660 [PubMed - indexed for MEDLINE]

1091. Clin Microbiol Infect. 2009 Jul;15(7):662-9. Epub 2009 Jul 15.

Candidaemia with uncommon Candida species: predisposing factors, outcome, antifungal susceptibility, and implications for management.

Chen SC, Marriott D, Playford EG, Nguyen Q, Ellis D, Meyer W, Sorrell TC, Slavin M; Australian Candidaemia Study.

Collaborators: McBride J, Coulter C, McCormack J, Walmsley K, Looke D, Johnson B, Nimmo G, Playford G, Drummond D, Forgan-Smith R, Preston E, Allworth A, Faoagali J, Gerns N, Botes J, Cherian S, Robson J, Vohra R, Norton R, O'Kane G, Robb D, Gottlieb T, Chambers I, DeWit D, Carroll M, Dobson P, Ferguson J, Graves S, Tierney L, Jozwiak F, Munro R, Tomasotos V, Pickles R, Holland J, Groenwald F, Hale K, Watson M, Vaz R, Hardiman R, Baleriola C, Ryan S, Pritchard R, Weeks K, Benn R, Lawrence R, Taylor P, Lindstrom S, Harkness J, Marriott D, Nguyen Q, Palasanthrian P, Grant R, McPetrie R, Johnson R, Chen S, Halliday C, Maszewska K, Meyer W, Sorrell T, Dennis N, Newton P, Franklin C, Morrisey O, Slavin M, Spelman D, Wesselingh S, Speed B, Hellsten J, Mayall B, Russell J, Broughton S, Woolley I, Coloe S, Sherman A, Korman T, Graves S, Slavin M, Huysmans M, Gordon D, Rowlands K, Shaw D, Ellis D, Ritchie B, Handke R, Beaman M, Chiam A, McCarthy J, Heath C, Altmann S, Arthur I, Speers D, Cox E, Cooley L, McGregor A, Currie B, Lum G, Fisher D, Collingnon P, Roberts J, Watson A.

Centre for Infectious Diseases and Microbiology, Westmead Hospital, University of Sydney, Sydney, Ausralia. Sharon.chen@swahs.health.nsw.gov.au

The risk factors for and clinical features of bloodstream infection with uncommon Candida spp. (species other than C. albicans, C. glabrata, C. parapsilosis, C. tropicals and C. krusei) are incompletely defined. To identify clinical variables associated with these species that might guide management, 57 cases of candidaemia resulting from uncommon Candida spp. were analysed in comparison with 517 episodes of Candida albicans candidaemia (2001-2004). Infection with uncommon Candida spp. (5.3% of candidaemia cases), as compared with C. albicans candidaemia, was significantly more likely to be outpatient-acquired than inpatient-acquired (15 of 57 vs. 65 of 517 episodes, p 0.01). Prior exposure to fluconazole was uncommon (n=1). Candida dubliniensis was the commonest species (n=22, 39%), followed by Candida guilliermondii (n=11, 19%) and Candida lusitaniae (n=7, 12%).C. dubliniensis candidaemia was independently associated with recent intravenous drug use (p 0.01) and chronic liver disease (p 0.03), and infection with species other than C. dubliniensis was independently associated with age<65 years (p 0.02), male sex (p 0.03) and human immunodeficiency virus infection (p 0.05). Presence of sepsis at diagnosis and crude 30-day mortality rates were similar for C. dubliniensis-related, non-C. dubliniensis-related and C. albicans-related candidaemia. Haematological malignancy was the commonest predisposing factor in C. guilliermondii (n=3, 27%) and C. lusitaniae (n=3, 43%) candidaemia. The 30-day mortality rate of C. lusitaniae candidaemia was higher than the overall death rate for all uncommon Candida spp. (42.9% vs. 25%, p not significant). All isolates were susceptible to amphotericin B, voriconazole, posaconazole, and caspofungin; five strains (9%) had fluconazole MIC values of 16-32 mg/L. Candidaemia due to uncommon Candida spp. is emerging among hospital outpatients; certain clinical variables may assist in recognition of this entity.

PMID: 19614718 [PubMed - indexed for MEDLINE]

1092. Biochem J. 2009 Sep 14;423(1):109-18.

Inositol pyrophosphates modulate hydrogen peroxide signalling.

Onnebo SM, Saiardi A.

Department of Cell and Developmental Biology, University College London, UK.

Inositol pyrophosphates are involved in a variety of cellular functions, but the specific pathways and/or downstream targets remain poorly characterized. In the present study we use Saccharomyces cerevisiae mutants to examine the potential roles of inositol pyrophosphates in responding to cell damage caused by ROS (reactive oxygen species). Yeast lacking kcs1 [the S. cerevisiae IP6K (inositol hexakisphosphate kinase)] have greatly reduced IP7 (diphosphoinositol pentakisphosphate) and IP8 (bisdiphosphoinositol tetrakisphosphate) levels, and display increased resistance to cell death caused by H2O2, consistent with a sustained activation of DNA repair mechanisms controlled by the Rad53 pathway. Other Rad53-controlled functions, such as actin polymerization, appear unaffected by inositol pyrophosphates. Yeast lacking vip1 [the S. cerevisiae PP-IP5K (also known as IP7K, IP7 kinase)] accumulate large amounts of the inositol pyrophosphate IP7, but have no detectable IP8, indicating that this enzyme represents the physiological IP7 kinase. Similar to kcs1Delta yeast, vip1Delta cells showed an increased resistance to cell death caused by H2O2, indicating that it is probably the double-pyrophosphorylated form of IP8 [(PP)2-IP4] which mediates the H2O2 response. However, these inositol pyrophosphates are not involved in directly sensing DNA damage, as kcs1Delta cells are more responsive to DNA damage caused by phleomycin. We observe in vivo a rapid decrease in cellular inositol pyrophosphate levels following exposure to H2O2, and an inhibitory effect of H2O2 on the enzymatic activity of Kcs1 in vitro. Furthermore, parallel cysteine mutagenesis studies performed on mammalian IP6K1 are suggestive that the ROS signal might be transduced by the direct modification of this evolutionarily conserved class of enzymes.

PMID: 19614566 [PubMed - indexed for MEDLINE]

1093. Infect Control Hosp Epidemiol. 2009 Sep;30(9):840-7.

Contaminated product water as the source of Phialemonium curvatum bloodstream infection among patients undergoing hemodialysis.

Rao CY, Pachucki C, Cali S, Santhiraj M, Krankoski KL, Noble-Wang JA, Leehey D, Popli S, Brandt ME, Lindsley MD, Fridkin SK, Arduino MJ.

Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA. cnr3@cdc.gov

OBJECTIVE: We investigated a cluster of cases of bloodstream infection (BSI) due to the mold Phialemonium at a hemodialysis center in Illinois and conducted a cohort study to identify risk factors. DESIGN: Environmental assessment and cohort study. SETTING: A hemodialysis center in a tertiary care hospital.
METHODS: A case patient was defined as a person who underwent dialysis at the center and had a blood sample that tested positive for Phialemonium curvatum on culture. We reviewed microbiology and medical records and tested water, surface, and dialysate samples by culture. Molds isolated from environmental and clinical specimens were identified by their morphological features and confirmed by sequencing DNA.
RESULTS: We identified 2 case patients with BSI due to P. curvatum. Both became febrile and hypotensive while undergoing dialysis on the same machine at the same treatment station, although on different days. Dialysis machines were equipped with waste handling option ports that are used to discard dialyzer priming fluid. We isolated P. curvatum from the product water (ie, water used for dialysis purposes) at 2 of 19 treatment stations, one of which was the implicated station.
CONCLUSION: The source of P. curvatum was likely the water distribution system. To our knowledge, this is the first report of patients acquiring a mold BSI from contaminated product water. The route of exposure in these cases of BSI due to P. curvatum may be related to the malfunction and improper maintenance of the waste handling option ports. Waste handling option ports have been previously implicated as the source of bacterial BSI due to the backflow of waste fluid into a patient's blood line. No additional cases of infection were noted after remediation of the water distribution system and after discontinuing use of waste handling option ports at the facility.

PMID: 19614543 [PubMed - indexed for MEDLINE]

1094. J Bioenerg Biomembr. 2009 Jun;41(3):239-49. Epub 2009 Jul 16.

Induction of a non-specific permeability transition in mitochondria from Yarrowia lipolytica and Dipodascus (Endomyces) magnusii yeasts.

Kovaleva MV, Sukhanova EI, Trendeleva TA, Zyl'kova MV, Ural'skaya LA, Popova KM, Saris NE, Zvyagilskaya RA.

A.N. Bach Institute of Biochemistry, Russian Academy of Sciences, Moscow, Russia.

In this study we used tightly-coupled mitochondria from Yarrowia lipolytica and Dipodascus (Endomyces) magnusii yeasts, possessing a respiratory chain with the usual three points of energy conservation. High-amplitude swelling and collapse of the membrane potential were used as parameters for demonstrating induction of the mitochondrial permeability transition due to opening of a pore (mPTP). Mitochondria from Y. lipolytica, lacking a natural mitochondrial Ca(2+) uptake pathway, and from D. magnusii, harboring a high-capacitive, regulated mitochondrial Ca(2+) transport system (Bazhenova et al. J Biol Chem 273:4372-4377, 1998a; Bazhenova et al. Biochim Biophys Acta 1371:96-100, 1998b; Deryabina and Zvyagilskaya Biochemistry (Moscow) 65:1352-1356, 2000; Deryabina et al. J Biol Chem 276:47801-47806, 2001) were very resistant to Ca(2+) overload. However, exposure of yeast mitochondria to 50-100 microM Ca(2+) in the presence of the Ca(2+) ionophore ETH129 induced collapse of the membrane potential, possibly due to activation of the fatty acid-dependent Ca(2+)/nH(+)-antiporter, with no classical mPTP induction. The absence of response in yeast mitochondria was not simply due to structural limitations, since large-amplitude swelling occurred in the presence of alamethicin, a hydrophobic, helical peptide, forming voltage-sensitive ion channels in lipid membranes. Ca(2+)- ETH129-induced activation of the Ca(2+)/H(+)-antiport system was inhibited and prevented by bovine serum albumin, and partially by inorganic phosphate and ATP. We subjected yeast mitochondria to other conditions known to induce the permeability transition in animal mitochondria, i.e., Ca(2+) overload (in the presence of ETH129) combined with palmitic acid (Mironova et al. J Bioenerg Biomembr 33:319-331, 2001; Sultan and Sokolove Arch Biochem Biophys 386:37-51, 2001), SH-reagents, carboxyatractyloside (an inhibitor of the ADP/ATP translocator), depletion of intramitochondrial adenine nucleotide pools, deenergization of mitochondria, and shifting to acidic pH values in the presence of high phosphate concentrations. None of the above-mentioned substances or conditions induced a mPTP-like pore. It is thus evident that the permeability transition in yeast mitochondria is not coupled with Ca(2+) uptake and is differently regulated compared to the mPTP of animal mitochondria.

PMID: 19609656 [PubMed - indexed for MEDLINE]

1095. J Biol Chem. 2009 Nov 6;284(45):30981-93. Epub 2009 Jul 16.

Good fat, essential cellular requirements for triacylglycerol synthesis to maintain membrane homeostasis in yeast.

Petschnigg J, Wolinski H, Kolb D, Zellnig G, Kurat CF, Natter K, Kohlwein SD.

Institute of Molecular Biosciences, University of Graz, Humboldtstrasse 50/II, A8010 Graz, Austria.

Storage triacylglycerols (TAG) and membrane phospholipids share common precursors, i.e. phosphatidic acid and diacylglycerol, in the endoplasmic reticulum. In addition to providing a biophysically rather inert storage pool for fatty acids, TAG synthesis plays an important role to buffer excess fatty acids (FA). The inability to incorporate exogenous oleic acid into TAG in a yeast mutant lacking the acyltransferases Lro1p, Dga1p, Are1p, and Are2p contributing to TAG synthesis results in dysregulation of lipid synthesis, massive proliferation of intracellular membranes, and ultimately cell death. Carboxypeptidase Y trafficking from the endoplasmic reticulum to the vacuole is severely impaired, but the unfolded protein response is only moderately up-regulated, and dispensable for membrane proliferation, upon exposure to oleic acid. FA-induced toxicity is specific to oleic acid and much less pronounced with palmitoleic acid and is not detectable with the saturated fatty acids, palmitic and stearic acid. Palmitic acid supplementation partially suppresses oleic acid-induced lipotoxicity and restores carboxypeptidase Y trafficking to the vacuole. These data show the following: (i) FA uptake is not regulated by the cellular lipid requirements; (ii) TAG synthesis functions as a crucial intracellular buffer for detoxifying excess unsaturated fatty acids; (iii) membrane lipid synthesis and proliferation are responsive to and controlled by a balanced fatty acid composition.

PMCID: PMC2781499 PMID: 19608739 [PubMed - indexed for MEDLINE]

1096. Sci Total Environ. 2009 Sep 15;407(19):5223-8. Epub 2009 Jul 15.

A longitudinal study of environmental risk factors for subjective symptoms associated with sick building syndrome in new dwellings.

Takigawa T, Wang BL, Sakano N, Wang DH, Ogino K, Kishi R.

Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, 700-8558 Okayama, Japan. ttomoko@md.okayama-u.ac.jp

This study was performed to explore possible environmental risk factors, including indoor chemicals, mold, and dust mite allergens, which could cause sick building syndrome (SBS)-type symptoms in new houses. The study was conducted in 2004 and 2005 and the final study population consisted of 86 men and 84 women residing in Okayama, Japan. The indoor concentrations of indoor aldehydes, volatile organic compounds, airborne fungi, and dust mite allergens in their living rooms were measured and the longitudinal changes in two consecutive years were calculated. A standardized questionnaire was used concomitantly to gather information on frequency of SBS-type symptoms and lifestyle habits. About 10% of the subjects suffered from SBS in the both years. Crude analyses indicated tendencies for aldehyde levels to increase frequently and markedly in the newly diseased and ongoing SBS groups. Among the chemical factors and molds examined, increases in benzene and in Aspergillus contributed to the occurrence of SBS in the logistic regression model. Indoor chemicals were the main contributors to subjective symptoms associated with SBS. A preventive strategy designed to lower exposure to indoor chemicals may be able to counter the occurrence of SBS.

PMID: 19608217 [PubMed - indexed for MEDLINE]

1097. Med Pr. 2009;60(1):1-5.

[Survivability of Candida fungi and workpost safety in the university mycological laboratory].

[Article in Polish]

Ejdys E.

Uniwersytet Warmińsko-Mazurski, Olsztyn, Katedra Mikologii, Wydział Biolog. elzbieta.ejdys@uwm.edu.pl

BACKGROUND: To ensure the security for persons using the laboratory for research purposes it was decided to determine the influence of the number of employees and the time of their work on the survivability and vitality of Candida albicans, C. dubliniensis and C. tropicalis. MATERIAL AND METHODS: Working time and the number of people in the room were monitored. Temperature and air relative humidity were checked. Every two weeks the vitality and survivability of fungi were assessed with the technique of intravital coloring in methylene blue.
RESULTS: During the observation of the examined species no 100% mortality was noted. After half a year of observation, the percentage of living cells in the smear did not exceed 10%. The greatest fluctuations in the survivability and its lowest value (5%) were found in C. albicans in the drop. The mortality rate in similar trials did not exceed 30% in C. dubliniensis and C. tropicalis isolates.
CONCLUSIONS: To secure the protection of employees one should limit the number of people entering the laboratory, use face masks, refresh archival isolate, and monitor hygiene procedures twice a year, depending on the frequency of changing objects and research team.

PMID: 19603690 [PubMed - indexed for MEDLINE]

1098. Environ Sci Technol. 2009 Jun 15;43(12):4606-11.

Photocatalytic oxidation of Escherischia coli, Aspergillus niger, and formaldehyde under different ultraviolet irradiation conditions.

Chen F, Yang X, Wu Q.

Department of Building Science, Tsinghua University, Beijing 100084, China.

Ultraviolet (UV) light irradiation, including the type of light source, light intensity, and irradiation dosage, directly affects the photocatalytic reaction rate and energy consumption. In this study, we investigated the photocatalysis effect of decomposing organic matter and inactivation bacteria and fungi under various conditions of UV sources (UVA and UVC) and light intensities (from 0.01 to 10 W/m2). The effect of light intensity was evaluated by photocatalytic reaction rate and UV dosage defined as a product of light intensity and irradiation time necessary to achieve a certain reduction. The results confirmed the positive effect of increased light intensity on photocatalytic reactions and suggested that within the light intensity range applied in this study low light intensity with long exposure time has higher light utilization efficiency compared to that of high light intensity with short exposure time. A conception for selection of the appropriate light intensity and dosage for effective degradation of pollutants, while saving energy, was provided.

PMID: 19603684 [PubMed - indexed for MEDLINE]

1099. Bioelectromagnetics. 2010 Jan;31(1):28-38.

Exposure to high static or pulsed magnetic fields does not affect cellular processes in the yeast Saccharomyces cerevisiae.

Anton-Leberre V, Haanappel E, Marsaud N, Trouilh L, Benbadis L, Boucherie H, Massou S, François JM.

University of Toulouse, INSA, UPS, INP & INRA, Toulouse, France. leberre@insa-toulouse.fr

We report results of a study of the effects of strong static (up to 16 T for 8 h) and pulsed (up to 55 T single-shot and 4 x 20 T repeated shots) magnetic fields on Saccharomyces cerevisiae cultures in the exponential phase of growth. In contrast to previous reports restricted to only a limited number of cellular parameters, we have examined a wide variety of cellular processes: genome-scale gene expression, proteome profile, cell viability, morphology, and growth, metabolic and fermentation activity after magnetic field exposure. None of these cellular activities were impaired in response to static or pulsed magnetic field exposure. Our results confirm and extend previous reports on the absence of magnetic field effects on yeast and support the hypothesis that magnetic fields have no impact on the transcriptional machinery and on the integrity of unicellular biological systems.

PMID: 19603479 [PubMed - indexed for MEDLINE]

1100. J Appl Microbiol. 2010 Jan;108(1):325-40.

The microbial signature of aerosols produced during the thermophilic phase of composting.

Le Goff O, Bru-Adan V, Bacheley H, Godon JJ, Wéry N.

INRA, UR50, Laboratoire de Biotechnologie de l'Environnement, Avenue des Etangs, Narbonne, France.

AIMS: The microbial diversity of bioaerosols released during operational activities at composting plants is poorly understood. Identification of bacteria and fungi present in such aerosols is the prerequisite for the definition of microbial indicators that could be used in dispersal and exposure studies. METHODS AND RESULTS: A culture-independent analysis of composting bioaerosols collected at five different industrial open sites during the turning of composting piles in fermentation was performed by building 16S rDNA and 18S rDNA libraries. More than 800 sequences were analysed. Although differences in the phylotypes distribution were observed from one composting site to another, similarities in the structure of microbial diversity were remarkable. The same phyla dominated in the five bioaerosols: Ascomycota among fungi, Firmicutes and Actinobacteria among bacteria. For each phylum, some dominant phylotypes were common to at least four bioaerosols. These common phylotypes belonged to Thermomyces, Aspergillus, Penicillium, Geobacillus, Planifilum, Thermoactinomyces, Saccharopolyspora, Thermobifida and Saccharomonospora.
CONCLUSIONS: The microbial signature of aerosols produced during the thermophilic phase of composting was determined. The similarities observed may be explained by the selection of thermophilic and sporulating species. SIGNIFICANCE AND IMPACT OF THE STUDY: Several bacteria and fungi identified in this study may represent potential indicators of composting bioaerosols in air.

PMID: 19602015 [PubMed - indexed for MEDLINE]

1101. Oecologia. 2009 Oct;161(4):781-90. Epub 2009 Jul 14.

Experimental evolution of resistance against a competing fungus in Drosophila melanogaster.

Wölfle S, Trienens M, Rohlfs M.

Department of Evolutionary Ecology and Genetics, Zoological Institute, Christian-Albrechts-University of Kiel, Am Botanischen Garten 1-9, 24098 Kiel, Germany.

Competition between microorganisms and arthropods has been shown to be an important ecological interaction determining animal development and spatial distribution patterns in saprophagous communities. In fruit-inhabiting Drosophila, variation in insect developmental success is not only determined by species-specific effects of various noxious filamentous fungi but, as suggested by an earlier study, also by additive genetic variation in the ability to successfully withstand the negative impact of the fungi. If this variation represents a direct adaptive response to the degree to which insect breeding substrates are infested with harmful fungi, genetic variation for successful development in the presence of fungi could be maintained by variation in infestation of resource patches with fungi. We selected for the ability to resist the negative influence of mould by maintaining replicated Drosophila melanogaster populations on substrates infested with Aspergillus nidulans. After five cycles of exposure to the fungus during the larval stage, the selected populations were compared with unselected control populations regarding adult survival and reproduction to reveal an evolved resistance against the fungal competitor. On fungus-infested larval feeding substrates, emerged adults from mould-selected populations had higher survival rates and higher early fecundity than the control populations. In the unselected populations, females had higher mortality rates than males, and a high proportion of both females and males appeared to be unable to lay eggs or fertilise eggs, respectively. When larvae developed on non-infested food we found indications of a loss of resistance to abiotic and starvation stress in the adult stage in flies from the selected populations. This suggests that there are costs associated with an increase in resistance against the microbial competitor. We discuss the underlying mechanisms that might have selected for increased resistance against harmful fungi.

PMID: 19597847 [PubMed - indexed for MEDLINE]

1102. J Microbiol Biotechnol. 2009 Jun;19(6):547-55.

Nanoscopic morphological changes in yeast cell surfaces caused by oxidative stress: an atomic force microscopic study.

Canetta E, Walker GM, Adya AK.

Condensed Matter Group and BIONTHE (Bio- and Nano- Technologies for Health and Environment) Centre, University of Abertay Dundee, Dundee DD1 1HG, U.K.

Nanoscopic changes in the cell surface morphology of the yeasts Saccharomyces cerevisiae (strain NCYC 1681) and Schizosaccharomyces pombe (strain DVPB 1354), due to their exposure to varying concentrations of hydrogen peroxide (oxidative stress), were investigated using an atomic force microscope (AFM). Increasing hydrogen peroxide concentration led to a decrease in cell viabilities and mean cell volumes, and an increase in the surface roughness of the yeasts. In addition, AFM studies revealed that oxidative stress caused cell compression in both S. cerevisiae and Schiz. pombe cells and an increase in the number of aged yeasts. These results confirmed the importance and usefulness of AFM in investigating the morphology of stressed microbial cells at the nanoscale. The results also provided novel information on the relative oxidative stress tolerance of S. cerevisiae and Schiz. pombe.

PMID: 19597311 [PubMed - indexed for MEDLINE]

1103. Mol Biol Evol. 2009 Oct;26(10):2387-95. Epub 2009 Jul 13.

Structural determinants of protein evolution are context-sensitive at the residue level.

Franzosa EA, Xia Y.

Boston University, Boston, USA.

Structural properties of a protein residue's microenvironment have long been implicated as agents of selective constraint. Although these properties are inherently quantitative, structure-based studies of protein evolution tend to rely upon coarse distinctions between "surface" and "buried" residues and between "interfacial" and "noninterfacial" residues. Using homology-mapped yeast protein structures, we explore the relationships between residue evolution and continuous structural properties of the residue microenvironment, including solvent accessibility, density and distribution of residue-residue contacts, and burial depth. We confirm the role of solvent exposure as a major structural determinant of residue evolution and also identify a weak secondary effect arising from packing density. The relationship between solvent exposure and evolutionary rate (d(N)/d(S)) is found to be strong, positive, and linear. This reinforces the notion that residue burial is a continuous property with quantitative fitness implications. Next, we demonstrate systematic variation in residue-level structure-evolution relationships resulting from changes in global physical and biological contexts. We find that increasing protein-core size yields a more rapid relaxation of selective constraint as solvent exposure increases, although solvent-excluded residues remain similarly constrained. Finally, we analyze the selective constraint in protein-protein interfaces, revealing two fundamentally different yet separable components: continuous structural constraint that scales with total residue burial and a more surprising fixed functional constraint that accompanies any degree of interface involvement. These discoveries serve to elucidate and unite structure-evolution relationships at the residue and whole-protein levels.

PMID: 19597162 [PubMed - indexed for MEDLINE]

1104. BMC Genet. 2009 Jul 13;10:36.

A strategy for constructing aneuploid yeast strains by transient nondisjunction of a target chromosome.

Anders KR, Kudrna JR, Keller KE, Kinghorn B, Miller EM, Pauw D, Peck AT, Shellooe CE, Strong IJ.

Biology Department, Gonzaga University, Spokane, WA 99258, USA. anders@gonzaga.edu

BACKGROUND: Most methods for constructing aneuploid yeast strains that have gained a specific chromosome rely on spontaneous failures of cell division fidelity. In Saccharomyces cerevisiae, extra chromosomes can be obtained when errors in meiosis or mitosis lead to nondisjunction, or when nuclear breakdown occurs in heterokaryons. We describe a strategy for constructing N+1 disomes that does not require such spontaneous failures. The method combines two well-characterized genetic tools: a conditional centromere that transiently blocks disjunction of one specific chromosome, and a duplication marker assay that identifies disomes among daughter cells. To test the strategy, we targeted chromosomes III, IV, and VI for duplication.
RESULTS: The centromere of each chromosome was replaced by a centromere that can be blocked by growth in galactose, and ura3::HIS3, a duplication marker. Transient exposure to galactose induced the appearance of colonies carrying duplicated markers for chromosomes III or IV, but not VI. Microarray-based comparative genomic hybridization (CGH) confirmed that disomic strains carrying extra chromosome III or IV were generated. Chromosome VI contains several genes that are known to be deleterious when overexpressed, including the beta-tubulin gene TUB2. To test whether a tubulin stoichiometry imbalance is necessary for the apparent lethality caused by an extra chromosome VI, we supplied the parent strain with extra copies of the alpha-tubulin gene TUB1, then induced nondisjunction. Galactose-dependent chromosome VI disomes were produced, as revealed by CGH. Some chromosome VI disomes also carried extra, unselected copies of additional chromosomes.
CONCLUSION: This method causes efficient nondisjunction of a targeted chromosome and allows resulting disomic cells to be identified and maintained. We used the method to test the role of tubulin imbalance in the apparent lethality of disomic chromosome VI. Our results indicate that a tubulin imbalance is necessary for disomic VI lethality, but it may not be the only dosage-dependent effect.

PMCID: PMC2725114 PMID: 19594932 [PubMed - indexed for MEDLINE]

1105. J Immunol. 2009 Aug 1;183(3):1732-8. Epub 2009 Jul 10.

IL-6 is required for airway mucus production induced by inhaled fungal allergens.

Neveu WA, Allard JB, Dienz O, Wargo MJ, Ciliberto G, Whittaker LA, Rincon M.

Department of Medicine, Division of Immunobiology, University of Vermont, Burlington, VT 05405, USA.

Allergic asthma is caused by inhaled allergens and is characterized by airway eosinophilia, as well as mucus hypersecretion, which can lead to airflow obstruction. Despite the association of increased IL-6 levels with human atopic asthma, the contribution of IL-6 to the development of allergic airway inflammation triggered by inhaled allergens remains unclear. In this study, we examined the role of IL-6 in a mouse model of allergic airway inflammation induced by direct airway exposure to extracts of Aspergillus fumigatus, a common allergen in humans. We show that inhaled A. fumigatus extracts rapidly trigger the production of IL-6 in the airways. IL-6 appears to be dispensable for the recruitment of eosinophils to the lung during the development of allergic airway inflammation. However, IL-6 is essential for mucus hypersecretion by airway epithelial cells triggered in response to inhaled A. fumigatus Ags. Impaired mucus production caused by IL-6 deficiency correlates with a severe reduction in the levels of IL-13, a major inducer of mucin glycoproteins. Thus, IL-6 is a key regulator of specific hallmark features of allergic airway inflammation and it could be a potential target for pulmonary diseases that are associated with goblet cell metaplasia and mucus hypersecretion.

PMCID: PMC2929571 PMID: 19592651 [PubMed - indexed for MEDLINE]

1106. BMC Microbiol. 2009 Jul 9;9:134.

Effect of lactoperoxidase on the antimicrobial effectiveness of the thiocyanate hydrogen peroxide combination in a quantitative suspension test.

Welk A, Meller Ch, Schubert R, Schwahn Ch, Kramer A, Below H.

Department of Restorative Dentistry, Periodontology and Endodontology, University of Greifswald, Germany. welk@uni-greifswald.de

BACKGROUND: The positive antimicrobial effects of increasing concentrations of thiocyanate (SCN-) and H2O2 on the human peroxidase defence system are well known. However, little is known about the quantitative efficacy of the human peroxidase thiocyanate H2O2 system regarding Streptococcus mutans and sanguinis, as well as Candida albicans. The aim of this study was to evaluate the effect of the enzyme lactoperoxidase on the bactericidal and fungicidal effectiveness of a thiocyanate-H2O2 combination above the physiological saliva level. To evaluate the optimal effectiveness curve, the exposure times were restricted to 1, 3, 5, and 15 min.
RESULTS: The bactericidal and fungicidal effects of lactoperoxidase on Streptococcus mutans and sanguinis and Candida albicans were evaluated by using two test mixtures of a 2.0% (w/v; 0.34 M) thiocyanate and 0.4% (w/v; 0.12 M) hydrogen peroxide solution, one without and one with lactoperoxidase. Following the quantitative suspension tests (EN 1040 and EN 1275), the growth of surviving bacteria and fungi in a nutrient broth was measured. The reduction factor in the suspension test without lactoperoxidase enzyme was < 1 for all three tested organisms. Thus, the mixtures of 2.0% (w/v; 0.34 M) thiocyanate and 0.4% (w/v; 0.12 M) hydrogen peroxide had no in vitro antimicrobial effect on Streptococcus mutans and sanguinis or Candida albicans. However, the suspension test with lactoperoxidase showed a high bactericidal and fungicidal effectiveness in vitro.
CONCLUSION: The tested thiocyanate and H2O2 mixtures showed no relevant antimicrobial effect. However, by adding lactoperoxidase enzyme, the mixtures became not only an effective bactericidal (Streptococcus mutans and sanguinis) but also a fungicidal (Candida albicans) agent.

PMCID: PMC2715409 PMID: 19589149 [PubMed - indexed for MEDLINE]

1107. Mol Plant Microbe Interact. 2009 Aug;22(8):942-52.

The YAP1 homolog-mediated oxidative stress tolerance is crucial for pathogenicity of the necrotrophic fungus Alternaria alternata in citrus.

Lin CH, Yang SL, Chung KR.

Citrus Research and Education Center, and Department of Plant Pathology, Institute of Food and Agricultural Sciences (IFAS), University of Florida, 700 Experiment Station Rd., Lake Alfred 33850, U.S.A.

Citrus brown spot disease is caused by the necrotrophic fungus Alternaria alternata. Its pathogenic capability has been thought to depend exclusively on the production of host-selective ACT toxin. However, circumvention of plant defenses is also likely to be important for the disease process. To investigate the fungal response to host-generated reactive oxygen species (ROS), we cloned and characterized the AaAP1 gene of A. alternata, which encodes a polypeptide resembling yeast YAP1-like transcriptional activators implicated in cellular responses to stress. Expression of the AaAP1 gene in a wild-type strain was primarily induced by H(2)O(2) or ROS-generating oxidants. Using a loss-of-function mutation in the AaAP1 gene, we demonstrated an essential requirement for oxidative tolerance during the host invasion step. Mutants lacking AaAP1 showed increased sensitivity to H(2)O(2) and loss of fungal pathogenicity. The DeltaAaAP1 null mutant did not cause any visible necrotic lesions on wounded or unwounded leaves of citrus cv. Minneola. Compared with the wild type, the null mutant displayed lower catalase, peroxidase, and superoxide dismutase activities. All mutant phenotypes were restored to the wild type in fungal strains expressing a functional copy of AaAP1. Upon exposure to H(2)O(2), the AaAP1::sGFP (synthetic green fluorescent protein) fusion protein became localized in the nucleus. Inoculation of the mutant with NADPH oxidase inhibitors partially restored fungal pathogenicity. Our results highlight the global regulatory role of a YAP1 homolog in response to oxidative stress in A. alternata and provide insights into the critical role of ROS detoxification in the pathogenicity of A. alternata.

PMID: 19589070 [PubMed - indexed for MEDLINE]

1108. Bull Environ Contam Toxicol. 2009 Oct;83(4):570-4. Epub 2009 Jul 9.

Toxicity assessment and clearance of Brazilian microbial pest control agents in mice.

Oliveira-Filho EC, Oliveira RS, Lopes MC, Ramos FR, Grisolia CK, Alves RT, Monnerat RG.

Laboratório de Ecotoxicologia, Embrapa Cerrados, Planaltina, DF 73310-970, Brazil. cyrino@cpac.embrapa.br

The environmental toxicology of chemical pesticides have increased interest in the development and use of microbial pest control agents. In the present study four new Brazilian strains of Bacillus and one fungus were tested to evaluate the acute oral toxicity and clearance of these microbials in C57BL6 mice. No mortality was observed after exposure for any of the microorganisms tested. Clearance was significant after 30 days but for one strain of B. thuringiensis and one of B. sphaericus this time was not enough to completely eliminate the spores.

PMID: 19588065 [PubMed - indexed for MEDLINE]

1109. N Engl J Med. 2009 Jul 9;361(2):161-9.

Investigation of the cause of death in a gene-therapy trial.

Frank KM, Hogarth DK, Miller JL, Mandal S, Mease PJ, Samulski RJ, Weisgerber GA, Hart J.

Department of Pathology, University of Chicago Medical Center, Chicago, IL 60637, USA. kfrank@uchicago.edu

Comment in N Engl J Med. 2009 Oct 29;361(18):1811. N Engl J Med. 2009 Jul 9;361(2):193-5. N Engl J Med. 2009 Oct 29;361(18):1811-2.

We present a case of disseminated histoplasmosis, complicated by retroperitoneal bleeding and leading to death, in a patient who was receiving systemic immunosuppressive therapy for rheumatoid arthritis and who was enrolled in a gene-therapy trial. This trial was designed to evaluate intraarticular delivery of a tumor necrosis factor alpha (TNF-alpha) antagonist, through an adeno-associated virus (AAV) type 2 delivery system, for inflammatory arthritis. The patient's receipt of concurrent anti-TNF-alpha therapy and other immunosuppressive therapy while she was living in an area where histoplasmosis was endemic was thought to be the most likely explanation for the infection; the evidence presented suggests that this fatal infection was unlikely to have been related to exposure to the agent administered in the gene-therapy trial. This case reinforces the importance of considering infectious complications, such as those from endemic mycoses, in patients receiving treatment with a TNF-alpha antagonist and the importance of having a well-designed monitoring plan when subjects in a research study become ill. (ClinicalTrials.gov number, NCT00126724.)

2009 Massachusetts Medical Society

PMID: 19587341 [PubMed - indexed for MEDLINE]

1110. Int J Hyg Environ Health. 2009 Nov;212(6):661-9. Epub 2009 Jul 7.

Health risks of the occupational exposure to microbiological and chemical pollutants in a municipal waste organic fraction treatment plant.

Nadal M, Inza I, Schuhmacher M, Figueras MJ, Domingo JL.

Laboratory of Toxicology and Environmental Health, School of Medicine, IISPV, Rovira i Virgili University, Sant Llorenç 21, 43201 Reus, Catalonia, Spain.

Composting is a good alternative for the treatment of organic waste. However, an important amount of hazardous agents such as bioaerosols and volatile organic compounds may be released during the process. Therefore, the presence of microbiological and chemical pollutants emitted to air may mean a risk for the health of composting plants workers. We here report the results of an investigation aimed at evaluating the occupational exposure to chemical and biological agents for workers of an organic waste treatment facility (Montcada i Reixac, Catalonia, Spain). Total concentrations of bacteria and fungi (at 25 degrees C and 37 degrees C), including Aspergillus fumigatus, were determined on a 3-month basis in 4 areas of the composting plant (reception, sorting, composting and cogeneration halls). Non-cancer and cancer risks were assessed. Workers in the sorting cabins seemed to be the most exposed to pollutants. Consequently, the use of preventive measures, such as integrated P3 filter masks and gloves are highly recommended. On the other hand, the emission and dispersion of bioaerosols and particles should be minimized during the process through the application of additional measures, such as the humectation of waste and the installation of biofilters. The results of this study can be useful to elaborate occupational risk prevention programs for workers in composting plants.

PMID: 19586797 [PubMed - indexed for MEDLINE]

1111. J Occup Environ Hyg. 2009 Sep;6(9):582-91.

Indoor allergens in Minnesota schools and child care centers.

Tranter DC, Wobbema AT, Norlien K, Dorschner DF.

Minnesota Department of Health, Division of Environmental Health, P.O. Box 64975, St. Paul, MN 55164-0975, USA. daniel.tranter@state.mn.us

Elevated concentrations of allergens in the indoor environment may cause allergic sensitization and symptoms. Occupant exposure to indoor allergens in educational facilities should and can be controlled. This study (1) assessed the presence of indoor allergens in Minnesota schools and child care centers, (2) characterized the distribution of allergens in different materials, and (3) evaluated the effect of building and maintenance interventions on allergen concentrations. Settled dust samples were collected from carpet, vinyl tile floors, and upholstered furniture in six schools and seven child care centers before and after interventions. Interventions included changes to cleaning, ventilation, entry mats, furnishings, flooring, and classroom items. The amount of total dust, culturable fungi, and indoor allergens--cockroach, dust mite, cat, and dog--were quantified in the dust samples. Cockroach and dust mite allergens were generally low and below the detection limit, but one dust mite allergen was detected in some areas. Cat and dog allergens were frequently detected at elevated levels, with half the samples above the provisional sensitization risk thresholds and a few samples above the symptom thresholds. Allergen concentrations were highest in upholstered furniture, followed by carpeting and then vinyl floor tile. Cat and dog allergens were lower after the interventions. Cat and dog allergens, but not dust mite and cockroach allergens, seem to be ubiquitous in child care and elementary schools of the U.S. Midwest. These allergens may contribute to sensitization in atopic individuals and occasionally cause symptoms in sensitized allergic individuals. Fleecy materials that are not adequately cleaned, such as upholstered furniture, appear to be the most significant allergen reservoirs. Modest environmental interventions can be implemented by building staff, which should result in lower allergen concentrations.

PMID: 19585331 [PubMed - indexed for MEDLINE]

1112. J Air Waste Manag Assoc. 2009 May;59(5):540-52.

Evaluation of bioaerosol components, generation factors, and airborne transport associated with lime treatment of contaminated sediment.

Barth EF, Reponen T, Succop P.

National Risk Management Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Cincinnati, OH 45268, USA. barth.ed@epa.gov

Lime treatment has been used in contaminated sediment management activities for many purposes such as dewatering, improvement of physical properties, and reducing contaminant mobility. Exothermic volatilization of volatile organic compounds from lime-treated sediment is well known, but potential aerosolization of bioaerosol components has not been evaluated. A physical model of a contaminated sediment treatment and airborne transport process and an experimental protocol were developed to identify specific bioaerosol components (bacteria, fungi, cell structural components, and particles) that may be aerosolized and transported. Key reaction variables (amount of lime addition, rate of lime addition, mixing energy supplied) that may affect the aerosolization of bioaerosol components were evaluated. Lime treatment of a sediment contaminated with heavy metals, petroleum-based organics, and microorganisms increased the sediment pH and solids content. Lime treatment reduced the number of water-extractable bacteria and fungi in the sediment from approximately 10(6) colony-forming units (CFU) x mL(-1) to less than the detection limit of 10(3) CFU x mL(-1). This reduction was seen immediately for bacteria and within 21 days for fungi. Lime treatment immediately reduced the amount of endotoxin in the sediment, but the effects of lime treatment on beta-D-glucan could not be determined. The temperature of the treated sediment was linearly related to the amount of lime added within the range of 0-25%. Bacteria were aerosolized during the treatment trials, but there was no culturable evidence of aerosolization of fungi, most likely because of either their particular growth stage or relatively larger particle size that reduced their aerosolization potential and their collection into the impingers. Nonbiological particles, endotoxin, and beta-D-glucan were not detected in air samples during the treatment trials. The amount of lime added to the reaction beaker and the relative amount of mixing energy supplied to the reaction significantly affected the aerosolization ratio of bacteria (amount of aerosolized bacteria divided by the amount of bacteria in untreated sediment) from the reaction beaker. The rate of lime addition did not significantly affect the aerosolization ratio of bacteria. The aerosolization results suggest that exposure to bacteria is possible with sediment treatment activities, but the hazard level could not be determined because speciation of the aerosolized bacteria for pathogen identification was not performed, and health and safety standards and criteria for bioaerosol components have not been developed. Quantitative scaling analysis and whether the system represents actual environmental conditions were not studied.

PMID: 19583154 [PubMed - indexed for MEDLINE]

1113. Lasers Med Sci. 2010 May;25(3):385-9. Epub 2009 Jul 5.

Comparison of the photodynamic fungicidal efficacy of methylene blue, toluidine blue, malachite green and low-power laser irradiation alone against Candida albicans.

Souza RC, Junqueira JC, Rossoni RD, Pereira CA, Munin E, Jorge AO.

Department of Biosciences and Oral Diagnosis, School of Dentistry of São José dos Campos, São Paulo State University (UNESP), Francisco José Longo 777, São Dimas, São José dos Campos 12245-000, SP, Brazil.

This study was to evaluate specific effects of photodynamic therapy (energy density 15.8 J/cm(2), 26.3 J/cm(2) and 39.5 J/cm(2)) using methylene blue, toluidine blue and malachite green as photosensitizers and low-power laser irradiation on the viability of Candida albicans. Suspensions of C. albicans containing 10(6) cells/ml were standardized in a spectrophotometer. For each dye, 120 assays, divided into four groups according to the following experimental conditions, were carried out: laser irradiation in the presence of the photosensitizer; laser irradiation only; treatment with the photosensitizer only; no exposure to laser light or photosensitizer. Next, serial dilutions were prepared and seeded onto Sabouraud dextrose agar for the determination of the number of colony-forming units per milliliter (CFU/ml). The results were subjected to analysis of variance and the Tukey test (P < 0.05). Photodynamic therapy using the photosensitizers tested was effective in reducing the number of C. albicans.. The number of CFU/ml was reduced by between 0.54 log(10) and 3.07 log(10) and depended on the laser energy density used. Toluidine blue, methylene blue and malachite green were effective photosensitizers in antimicrobial photodynamic therapy against C. albicans, as was low-power laser irradiation alone.

PMID: 19579004 [PubMed - indexed for MEDLINE]

1114. J Biotechnol. 2009 Aug 20;143(2):130-8. Epub 2009 Jul 3.

Isolation of cobalt hyper-resistant mutants of Saccharomyces cerevisiae by in vivo evolutionary engineering approach.

Cakar ZP, Alkim C, Turanli B, Tokman N, Akman S, Sarikaya M, Tamerler C, Benbadis L, François JM.

Department of Molecular Biology and Genetics, Faculty of Science & Letters, Istanbul Technical University, 34469 Maslak, Istanbul, Turkey. cakarp@itu.edu.tr

Cobalt is an important element with magnetic properties used in various industrial applications, but is also needed for biological activity. Very little is known about the cellular response of living systems to cobalt stress. Towards investigating this mechanism, we isolated individual Saccharomyces cerevisiae cells resistant to high cobalt concentrations up to 8 mmoll(-1), by employing four different 'in vivo' evolutionary engineering strategies: selection under constant or gradually increasing stress levels, and selection under continuous or pulse exposure to cobalt stress. Selection under continuous exposure to gradually increasing cobalt stress levels yielded the most resistant cell population to cobalt. However, the resistance was highly heterogeneous within the mutant populations ranging from 3- to 3700-fold survival rate of isolated individuals to 8 mmoll(-1) CoCl2 in the most resistant population. Moreover, cobalt-resistant individual colonies were associated with 2-4-times lower intracellular cobalt contents as compared to wild-type, and with cross-resistance to metals such as nickel, zinc, manganese, but not to copper and chromium ions. Contrary to mutants evolved under continuous exposure to cobalt, those isolated by pulse exposure strategy also exhibited resistance to heat shock and hydrogen peroxide stress. Taken together, this study reinforced the fact that evolutionary engineering is useful in selecting strains with very specific phenotypes, and further illustrated the importance of the strategy chosen to isolate the best evolved strain.

PMID: 19577596 [PubMed - indexed for MEDLINE]

1115. Toxicol In Vitro. 2009 Oct;23(7):1354-9. Epub 2009 Jun 30.

In ovo exposure of a Fusarium mycotoxin butenolide induces hepatic and renal oxidative damage in chick embryos, and antioxidants provide protections.

Wang YM, Wang HJ, Peng SQ.

Evaluation and Research Center for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, 20 Dongdajie Street, Fengtai District, Beijing 100071, PR China. wangyimei2006@126.com

Butenolide is a mycotoxin produced by several toxigenic Fusarium species. It frequently invades many important grains, and evokes a broad spectrum of toxic effects. For these reasons, butenolide poses a health risk to both humans and animals. However, many toxicology issues of butenolide including targets and mechanisms of toxicity remain to be elucidated so far. The present study therefore attempts to reveal the toxic profile of butenolide from a viewpoint of oxidative damage, using chick embryos as an in vitro model. A single in ovo injection of butenolide resulted in significant oxidative injuries in embryonic livers and kidneys, as manifested by a dose-dependent depletion of sulfhydryl groups, reduction of glutathione peroxidase activity, and increase of thiobarbituric acid reactive substances production, an indicator of lipid peroxidation. In contrast, co-injections of butenolide with antioxidants sodium selenite, vitamin C and a representative antioxidative enzyme superoxide dismutase markedly abated these oxidative toxicities. In conclusion, the present study suggests that oxidative damage may serve as a mediator in the toxicity of butenolide, and amelioration of antioxidant defense capacity by exogenous supplementation may play a role in the prevention and treatment of butenolide intoxication.

PMID: 19573587 [PubMed - indexed for MEDLINE]

1116. Ann Agric Environ Med. 2009 Jun;16(1):143-50.

Occupational exposure to organic dust, microorganisms, endotoxin and peptidoglycan among plants processing workers in Poland.

Góra A, Mackiewicz B, Krawczyk P, Golec M, Skórska C, Sitkowska J, Cholewa G, Larsson L, Jarosz M, Wójcik-Fatla A, Dutkiewicz J.

Department of Occupational Biohazards, Institute of Agricultural Medicine, ul. Jaczewskiego 2, 20-950 Lublin, Poland. angora@vp.pl

The objective of present work was to determine and compare the components of bioaerosol in several sectors of plant processing industries. The study was conducted in 10 facilities engaged in herb and grain processing, flax threshing, grain storing, baking, and cereals production. The air samples were taken on glass fibre filters with an AS-50 sampler. We determined the concentrations of airborne microorganisms, dust, endotoxin and peptidoglycan. Total concentrations of viable airborne microorganisms ranged from 0.18-861.4 x 10(3) cfu/m(3). The highest levels of microbial contamination of the air were observed at flax farms, in grain elevators and in a herb processing plant. Gram-positive bacteria and fungi were detected at all sampling sites and their median concentrations were respectively 18.1 x 10(3) cfu/m(3) and 0.66 x 10(3) cfu/m(3). The concentration of Gram-negative bacteria ranged from 0.0-168.0 x 10(3) cfu/m(3). The concentration of thermophilic actinomycetes ranged from 0.0-1.45 x 10(3) cfu/m(3). Qualitatively, Gram-positive bacteria constituted 23-93% of the total microbial count. The most common species were: Staphylococcus spp., Curtobacterium pusillum, Rhodococcus fascians, Aureobacterium testaceum, Sanguibacter keddieii, Microbacterium spp., and Bacillus spp. Gram-negative bacteria formed 0-48% of the total count. The species Pantoea agglomerans dominated in all examined air samples. Fungi constituted 2.5-76.9% of the total microbial count. Among them, Penicillium spp., Mucor spp., Alternaria spp., Aspergillus niger, and Aspergillus spp. were found. The dust concentration ranged from 0.18-86.9 mg/m(3). The concentration of endotoxin was large and ranged from 0.0041-1562.6 microg/m(3). Muramic acid, the chemical marker of peptidoglycan, was detected in 9 out of 13 (69.2%) collected samples. The concentration of peptidoglycan ranged from 1.93-416 ng/m(3). A highly significant correlation was found between the individual components of bioaerosol determined in this study. The concentration of endotoxin was correlated with the concentration of Gram-negative bacteria, total microorganisms, and peptidoglycan (R>0.9, p<0.001). The concentration of peptidoglycan was correlated with the concentration of Gram-positive bacteria, Gram-negative bacteria, and total microorganisms (R>0.9, p<0.001).

PMID: 19572487 [PubMed - indexed for MEDLINE]

1117. Int Arch Allergy Immunol. 2009;150(4):343-51. Epub 2009 Jul 1.

Human serum IgE reacts with a Metarhizium anisopliae fungal catalase.

Ward MD, Donohue MJ, Chung YJ, Copeland LB, Shoemaker JA, Vesper SJ, Selgrade MK.

United States Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Research Triangle Park, NC 27711, USA. ward.marsha@epa.gov

BACKGROUND: Previous studies have demonstrated that Metarhizium anisopliae extract can induce responses characteristic of human allergic asthma in a mouse model. The study objectives were (1) to identify and characterize the M. anisopliae mycelia extract (MYC) proteins that are recognized by mouse serum IgE, (2) to determine if human serum IgE reacts with these proteins, and (3) to determine if these IgE-reactive proteins are found in other fungi.
METHODS: Asthmatic human serum IgE, M. anisopliae crude antigen (MACA) immunized mouse serum IgE, and anti-catalase antibodies were used to probe one- and two-dimensional gel electrophoresis blots of MYC.
RESULTS: Mass spectrometry analysis identified catalase as a mouse IgE-reactive protein. This identification was confirmed by assaying catalase activity in the extract and extract immunoblots probed with anti-catalase antibody. Six adult asthmatic sera contained IgE, but not IgG, that was reactive with mycelia extract proteins. A similar protein profile was seen when blots were probed with either mouse anti-MACA IgE or anti-bovine liver catalase antibodies. Furthermore, these mouse anti-MACA and anti-catalase antibodies were cross-reactive with other mold extracts (skin prick testing mix) and Aspergillus niger catalase.
CONCLUSIONS: Some human asthmatics have developed IgE that reacts with an M. anisopliae catalase, most likely due to cross-reactivity (minimal IgG development). The cross-reactivity among fungal catalases suggests that IgE-reactive catalase might be useful for exposure assessment. Additionally, the similarity of protein profiles visualized with both human and mouse serum IgE suggests that allergy hazard identification can be facilitated using a mouse model.

PMID: 19571566 [PubMed - indexed for MEDLINE]

1118. FEMS Yeast Res. 2009 Sep;9(6):875-84. Epub 2009 Jun 3.

Investigations on light-induced stress in fluorescence microscopy using nuclear localization of the transcription factor Msn2p as a reporter.

Logg K, Bodvard K, Blomberg A, Käll M.

Department of Applied Physics, Chalmers University of Technology, Göteborg, Sweden. katarina.logg@chalmers.se

We utilized the nuclear localization of a stress-sensitive transcription factor, Msn2p, to study light-induced stress caused by time-lapse fluorescence imaging of green fluorescent protein (GFP) in budding yeast Saccharomyces cerevisiae. A range of exposure times, light intensities and intervals between exposures were tested in order to provide guidelines for noninvasive imaging. We found that the cellular response, revealed as an enhanced nuclear shuttling of Msn2p-GFP, is induced at significantly lower light exposures than those causing observable changes in cell morphology or cell growth. However, no stress induction was observed if the accumulated photon energy per area unit used to obtain an image was maintained at 0.16 J cm(-2) or below. Above this 'safe' level, the stress response is determined by both the intensity and the exposure time. In particular, for a given accumulated photon energy per area unit, a high intensity applied during a short exposure causes more stress than vice versa. Interestingly, no correlation was found between the degree of stress and the absolute fluorescence signal, indicating that light-induced cellular stress in the studied system is not specifically related to GFP excitation.

PMID: 19566686 [PubMed - indexed for MEDLINE]

1119. Genetics. 2009 Sep;183(1):185-94. Epub 2009 Jun 29.

Alternative splicing of PTC7 in Saccharomyces cerevisiae determines protein localization.

Juneau K, Nislow C, Davis RW.

Stanford Genome Technology Center, Department of Biochemistry, Stanford University School of Medicine, 855 California Ave., Palo Alto, California 94304, USA. kjuneau@stanford.edu

It is well established that higher eukaryotes use alternative splicing to increase proteome complexity. In contrast, Saccharomyces cerevisiae, a single-cell eukaryote, conducts predominantly regulated splicing through retention of nonfunctional introns. In this article we describe our discovery of a functional intron in the PTC7 (YHR076W) gene that can be alternatively spliced to create two mRNAs that code for distinct proteins. These two proteins localize to different cellular compartments and have distinct cellular roles. The protein translated from the spliced mRNA localizes to the mitochondria and its expression is carbon-source dependent. In comparison, the protein translated from the unspliced mRNA contains a transmembrane domain, localizes to the nuclear envelope, and mediates the toxic effects of Latrunculin A exposure. In conclusion, we identified a definitive example of functional alternative splicing in S. cerevisiae that confers a measurable fitness benefit.

PMCID: PMC2746143 PMID: 19564484 [PubMed - indexed for MEDLINE]

1120. J Exp Bot. 2009;60(11):3279-95. Epub 2009 Jun 29.

The beneficial endophyte Trichoderma hamatum isolate DIS 219b promotes growth and delays the onset of the drought response in Theobroma cacao.

Bae H, Sicher RC, Kim MS, Kim SH, Strem MD, Melnick RL, Bailey BA.

USDA-ARS-Beltsville Agricultural Research Center, Beltsville, MD 20705, USA.

Theobroma cacao (cacao) is cultivated in tropical climates and is exposed to drought stress. The impact of the endophytic fungus Trichoderma hamatum isolate DIS 219b on cacao's response to drought was studied. Colonization by DIS 219b delayed drought-induced changes in stomatal conductance, net photosynthesis, and green fluorescence emissions. The altered expression of 19 expressed sequence tags (ESTs) (seven in leaves and 17 in roots with some overlap) by drought was detected using quantitative real-time reverse transcription PCR. Roots tended to respond earlier to drought than leaves, with the drought-induced changes in expression of seven ESTs being observed after 7 d of withholding water. Changes in gene expression in leaves were not observed until after 10 d of withholding water. DIS 219b colonization delayed the drought-altered expression of all seven ESTs responsive to drought in leaves by > or = 3 d, but had less influence on the expression pattern of the drought-responsive ESTs in roots. DIS 219b colonization had minimal direct influence on the expression of drought-responsive ESTs in 32-d-old seedlings. By contrast, DIS 219b colonization of 9-d-old seedlings altered expression of drought-responsive ESTs, sometimes in patterns opposite of that observed in response to drought. Drought induced an increase in the concentration of many amino acids in cacao leaves, while DIS 219b colonization caused a decrease in aspartic acid and glutamic acid concentrations and an increase in alanine and gamma-aminobutyric acid concentrations. With or without exposure to drought conditions, colonization by DIS 219b promoted seedling growth, the most consistent effects being an increase in root fresh weight, root dry weight, and root water content. Colonized seedlings were slower to wilt in response to drought as measured by a decrease in the leaf angle drop. The primary direct effect of DIS 219b colonization was promotion of root growth, regardless of water status, and an increase in water content which it is proposed caused a delay in many aspects of the drought response of cacao.

PMCID: PMC2718224 PMID: 19564160 [PubMed - indexed for MEDLINE]

1121. J Immunol. 2009 Jul 15;183(2):1427-34. Epub 2009 Jun 26.

Proteases induce production of thymic stromal lymphopoietin by airway epithelial cells through protease-activated receptor-2.

Kouzaki H, O'Grady SM, Lawrence CB, Kita H.

Division of Allergic Diseases, Department of Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA.

Thymic stromal lymphopoietin (TSLP) is produced by epithelial cells and triggers dendritic cell-mediated Th2-type inflammation. Although TSLP is up-regulated in epithelium of patients with asthma, the factors that control TSLP production have not been studied extensively. Because mouse models suggest roles for protease(s) in Th2-type immune responses, we hypothesized that proteases from airborne allergens may induce TSLP production in a human airway epithelial cell line, BEAS-2B. TSLP mRNA and protein were induced when BEAS-2B cells were exposed to prototypic proteases, namely, trypsin and papain. TSLP induction by trypsin required intact protease activity and also a protease-sensing G protein-coupled receptor, protease-activated receptor (PAR)-2; TSLP induction by papain was partially dependent on PAR-2. In humans, exposure to ubiquitous airborne fungi, such as Alternaria, is implicated in the development and exacerbation of asthma. When BEAS-2B cells or normal human bronchial epithelial cells were exposed to Alternaria extract, TSLP was potently induced. The TSLP-inducing activity of Alternaria was partially blocked by treating the extract with a cysteine protease inhibitor, E-64, or by infecting BEAS-2B cells with small interfering RNA for PAR-2. Protease-induced TSLP production by BEAS-2B cells was enhanced synergistically by IL-4 and abolished by IFN-gamma. These findings demonstrate that TSLP expression is induced in airway epithelial cells by exposure to allergen-derived proteases and that PAR-2 is involved in the process. By promoting TSLP production in the airways, proteases associated with airborne allergens may facilitate the development and/or exacerbation of Th2-type airway inflammation, particularly in allergic individuals.

PMCID: PMC2706924 PMID: 19561109 [PubMed - indexed for MEDLINE]

1122. Ann Occup Hyg. 2009 Aug;53(6):595-603. Epub 2009 Jun 26.

Exposure to inhalable dust, endotoxins, beta(1->3)-glucans, and airborne microorganisms in horse stables.

Samadi S, Wouters IM, Houben R, Jamshidifard AR, Van Eerdenburg F, Heederik DJ.

Division of Environmental Epidemiology, Institute for Risk Assessment Sciences, Utrecht University, PO Box 80178, 3508 TD Utrecht, The Netherlands. S.Samadi@uu.nl

OBJECTIVES: Workers in horse stables are likely exposed to high levels of organic dust. Organic dusts play a role in increased risk of inflammatory reactions and are associated with respiratory diseases. The aim of this study was to investigate dust, endotoxin, beta(1-->3)-glucan, and culturable microorganisms exposure levels in horse stables.
METHODS: Ambient (n = 38) and personal (n = 42) inhalable dust samples were collected using PAS-6 sampling heads. As a special measurement, we included sampling near the horses' heads. Samples were analyzed for endotoxin and beta(1-->3)-glucan by Limulus amebocyte lysate assay and an inhibition enzyme immunoassay, respectively. Culturable bacteria and fungi were collected with an Anderson impactor.
RESULTS: Geometric means (GMs) of personal exposure to dust, endotoxin, and beta(1-->3)-glucan were 1.4 mg m(-3) (range 0.2-9.5), 608 EU m(-3) (20-9846), and 9.5 microg m(-3) (0.4-631 microg m(-3)), respectively. Exposure levels in the morning shift were higher compared to other shifts. The GMs (ranges) of culturable bacteria and fungi were 3.1 x 10(3) colony-forming unit (CFU) m(-3) (6.7 x 10 to 1.9 x 10(4)) and 1.9 x 10(3) CFU m(-3) (7.4 x 10 to 2.4 x 10(4)), respectively. Variance components for endotoxin and beta(1-->3)-glucan were considerably higher than for dust. Based on dummy variable in a mixed regression analysis, the predominant task explaining exposure levels of dust, endotoxin, and beta(1-->3)-glucan was sweeping the floor. For beta(1-->3)-glucan, feeding the horse was also an important determinant.
CONCLUSION: Dust, endotoxin, and beta(1-->3)-glucan exposure are considerable in horse stables. Bacterial and fungal exposure levels were moderate. Endotoxin exposures were above the Dutch proposed standard limits, suggesting workers in horse stables to be at risk of adverse health effects.

PMID: 19561032 [PubMed - indexed for MEDLINE]

1123. Chem Biol Interact. 2009 Dec 10;182(2-3):239-44. Epub 2009 Jun 25.

Tissue persistence of fumonisin B1 in ducks and after exposure to a diet containing the maximum European tolerance for fumonisins in avian feeds.

Tardieu D, Bailly JD, Benlashehr I, Auby A, Jouglar JY, Guerre P.

ENVT, Mycotoxicology Unit, 23 chemin des capelles, BP 87614, 31076 Toulouse Cedex 3, France.

Toxicity and persistence of fumonisin B1 (FB1) in liver, kidney and muscle were investigated in ducks fed 5, 10 and 20mg FB1+FB2/kg feed during force-feeding. Mortality and signs of toxicity were only obtained with 20mg/kg, whereas an increased Sa/So ratio was observed from 5mg/kg on. Persistence of FB1 was only found in liver (16 and 20 microg FB1/kg liver in ducks fed 10 and 20 mg FB1+FB2/kg feed, respectively). Toxicokinetic studies were conducted by the intravenous route (IV, single dose: 10mg FB1/kg body weight) and the oral route (single dose: 100mg FB1/kg body weight), in growing ducks and in ducks during force-feeding. After IV administration, serum concentration-time curves were described by a two-compartment open model. Elimination half-life and mean residence time of FB1 were 26 and 24 min, respectively, clearance was 19.3 ml/min/kg. After oral administration, bioavailability, elimination half-life, mean residence time and clearance varied during force-feeding and growth from 2-2.3%, 71-80 min, 200-188 min, 16.7-17 ml/min/kg, respectively. Taken together these results demonstrate that the risk of persistence of FB1 in ducks after force-feeding is very low, Sa/So being a good biomarker which increases before signs of toxicity and risk of persistence of FB1 in tissue (limit of detection 13 microg/kg).

PMID: 19559689 [PubMed - indexed for MEDLINE]

1124. Huan Jing Ke Xue. 2009 May 15;30(5):1292-7.

[Effect of abamectin insecticide on the microbial community in broccoli phyllosphere].

[Article in Chinese]

Zhang BG, Tang L, Li ZM, Wang HL, Xu WT, Zhang HX, Zhuang GQ, Bai ZH.

Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.

The indigenous microbial communities within the plant phyllosphere are highly diverse and include many different species of bacteria, filamentous fungi, yeasts and algae which play important ecological roles. This study was the first attempt to assess the impact of abamectin treatments on microbial communities of broccoli phyllosphere using two culture-independent techniques of phospholipid fatty acid analysis (PLFA) and terminal restriction fragment length polymorphism (T-RFLP). Results showed that low concentration of abamectin treatments did not affect the microbial biomass and microbial community structure of broccoli phyllosphere significantly. However, high concentration of abamectin treatments significantly change the microbial community structure including a decrease of total and bacterial biomass, and a decrease in the ratio of Gram-positive bacteria to Gram-negative bacteria, but did not change the fungal biomass. Moreover, PLFA suggested that the number of unsaturated and cyclopropane phospholipid fatty acids (PLFAs: 16: 1omega9t, 18: 1omega7, cy17:0 and cy19:0) increased with high concentration abamectin treatment, while the saturated PLFAs i15:0, a15:0, i16:0 and a17:0 decreased. The appearance terminal restriction fragments (T-RFs: 58, 96, 236 and 420 bp) indicated that some bacteria might play a significant role in abamectin degradation in broccoli phylosphere, while the disappeared T-RFs (51, 89, 99, 338, 66, 223 and 482 bp) implied some other bacteria might potentially serve as microbial indicator of abamectin exposure.

PMID: 19558092 [PubMed - indexed for MEDLINE]

1125. Can Respir J. 2009 May-Jun;16(3):e18-23.

Effects of the indoor environment on the fraction of exhaled nitric oxide in school-aged children.

Kovesi TA, Dales RE.

Department of Pediatrics, Children's Hospital of Eastern Ontario, University of Ottawa, Canada. kovesi@cheo.on.ca

BACKGROUND: The fractional concentration of exhaled nitric oxide (FeNO) appears to be a good marker for airway inflammation in children with asthma.
OBJECTIVE: To evaluate the effect of environmental exposures on exhaled nitric oxide in a community sample of children.
METHODS: The relationship among exhaled nitric oxide, underlying disease and home environmental exposures was examined using questionnaire data and measurement of exhaled nitric oxide in a cross-sectional study of 1135 children that included healthy children, and children with allergies and/or asthma who were attending grades 4 through 6 in Windsor, Ontario.
RESULTS: Among healthy children, there was a positive association between FeNO and occupancy (P<0.02). Compared with forced air and hot water radiant heat, electric baseboard heating was associated with a significant increase of FeNO in healthy children (P=0.007) and children with allergies (P=0.043). FeNO was not associated with environmental tobacco smoke exposure or reported surface mold. The presence of pet dog(s), but not cats, was associated with a significantly lower FeNO in healthy children (P<0.001) and in children with reported allergies (P<0.001).
CONCLUSIONS: The type of heating system, but not previously reported environmental tobacco smoke or mold exposure appears to affect exhaled nitric oxide in children. Exposure to different types of pets may have disparate effects on airway inflammation.

PMCID: PMC2706679 PMID: 19557209 [PubMed - indexed for MEDLINE]

1126. J Forensic Sci. 2009 Sep;54(5):979-84. Epub 2009 Jun 22.

Reconstructing the sequence of events surrounding body disposition based on color staining of bone*.

Huculak MA, Rogers TL.

Department of Anthropology, University of Toronto at Mississauga, Mississauga, Ontario, Canada. meaghan.huculak@utoronto.ca

Literature regarding bone color is limited to determining location of primary and secondary dispositions. This research is the first to use bone color to interpret the sequence of events surrounding body disposition. Two scenarios were compared-bones buried and then exposed on the ground surface and bones exposed then buried. Forty juvenile pig humeri with minimal tissue were used in each scenario with an additional 20 controls to determine if decomposing tissue affects bone color. Munsell Color Charts were used to record bone color of surface and 2.5 cm cross-sections. Results reveal five main surface colors attributed to soil, sun, hemolysis, decomposition, and fungi. Fungi on buried bones suggests prior surface exposure. Cross-sections of strictly buried bones are identical to buried then exposed bone, stressing the importance of bone surface analysis. Cross-sectioning may help verify remains have been exposed then buried. Decomposition of excess tissue creates minimal color staining.

PMID: 19549030 [PubMed - indexed for MEDLINE]

1127. Antimicrob Agents Chemother. 2009 Oct;53(10):4377-84. Epub 2009 Jun 22.

Biofilm formation and effect of caspofungin on biofilm structure of Candida species bloodstream isolates.

Ferreira JA, Carr JH, Starling CE, de Resende MA, Donlan RM.

Departamento de Microbiologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. jantgferr@hotmail.com

Candida biofilms are microbial communities, embedded in a polymeric matrix, growing attached to a surface, and are highly recalcitrant to antimicrobial therapy. These biofilms exhibit enhanced resistance against most antifungal agents except echinocandins and lipid formulations of amphotericin B. In this study, biofilm formation by different Candida species, particularly Candida albicans, C. tropicalis, and C. parapsilosis, was evaluated, and the effect of caspofungin (CAS) was assessed using a clinically relevant in vitro model system. CAS displayed in vitro activity against C. albicans and C. tropicalis cells within biofilms. Biofilm formation was evaluated after 48 h of antifungal drug exposure, and the effects of CAS on preformed Candida species biofilms were visualized using scanning electron microscopy (SEM). Several species-specific differences in the cellular morphologies associated with biofilms were observed. Our results confirmed the presence of paradoxical growth (PG) in C. albicans and C. tropicalis biofilms in the presence of high CAS concentrations. These findings were also confirmed by SEM analysis and were associated with the metabolic activity obtained by biofilm susceptibility testing. Importantly, these results suggest that the presence of atypical, enlarged, conical cells could be associated with PG and with tolerant cells in Candida species biofilm populations. The clinical implications of these findings are still unknown.

PMCID: PMC2764222 PMID: 19546368 [PubMed - indexed for MEDLINE]

1128. Biochem Biophys Res Commun. 2009 Aug 28;386(3):544-8. Epub 2009 Jun 21.

A DNA aptamer recognizes the Asp f 1 allergen of Aspergillus fumigatus.

Low SY, Hill JE, Peccia J.

Department of Chemical Engineering, Environmental Engineering Program, Yale University, New Haven, CT 06520, USA.

Allergies are caused by the binding of IgE antibodies onto specific sites on allergens. However, in the assessment of exposure to airborne allergens, current techniques such as whole spore counts fail to account for the presence of these allergenic epitopes that trigger allergic reactions. The objective of the research is to develop a DNA aptamer for the Asp f 1 allergen of the pathogenic fungus Aspergillus fumigatus, using an IgE-binding epitope of the allergen as the target for aptamer selection. Through in vitro SELEX, an aptamer has been produced that binds with nanomolar affinity to the Asp f 1 IgE-epitope. The aptamer is also able to recognize the native Asp f 1 allergen, and does not bind to allergenic proteins from non-target mold species such as Alternaria alternata. Production of this aptamer provides proof-of-principle that allergen measurement methods can be developed to indicate the potent fraction, or allergenicity, of allergens.

PMCID: PMC2727474 PMID: 19545545 [PubMed - indexed for MEDLINE]

1129. Mycopathologia. 2009 Nov;168(5):227-35. Epub 2009 Jun 21.

Enhancement of Candida albicans virulence after exposition to cigarette mainstream smoke.

Baboni FB, Barp D, Izidoro AC, Samaranayake LP, Rosa EA.

Laboratory of Stomatology, CCBS, Pontifical Catholic University of Paraná, Rua Imaculada Conceição 1155, Curitiba, 80215-901, Brazil.

The habit of cigarette smoking is associated with higher oral candidal carriage and possible predisposition to oral candidosis. The effects of exposure to smoke on the virulence properties of oral yeasts remain obscure. Hence, we showed in vitro the effect of cigarette smoke condensate (CSC) on ten clinical isolates of Candida albicans obtained from nonsmoking volunteers, as well the type-strain CBS562. CSC was generated by complete burn of five commercial cigarettes in an in-house smoking machine and used to prepare the culture broth in which the strains were grown. In 24-h intervals (T(24), T(48), and T(72)), the cells were harvested, washed, subcultured, and the resultant growth were evaluated for possible variations for secreted aspartyl protease, phospholipase, chondroitinase, and hemolysins, adhesion to acrylic and cell surface hydrophobicity (CSH). The results indicated a temporal increase in the secretion rates of enzymes, particularly when yeast cells were exposed to CSC for 48-72 h (P < 0.05). Similarly, adhesion to acrylic and CSH increased with exposure period (P < 0.05). Based on foregoing, we concluded that CSC may promote significant enhance in the secretion of candidal histolytic enzymes and adherence to denture surfaces, thereby promoting oral yeast carriage and possible infection.

PMID: 19544010 [PubMed - indexed for MEDLINE]

1130. Environ Monit Assess. 2010 Jul;166(1-4):677-86. Epub 2009 Jun 20.

Transfer of natural and anthropogenic radionuclides to ants, bryophytes and lichen in a semi-natural ecosystem.

Dragović S, Howard BJ, Caborn JA, Barnett CL, Mihailović N.

Institute for the Application of Nuclear Energy, Banatska 31b, 11080, Belgrade, Serbia. sdragovic@inep.co.rs

Few data are available to quantify the transfer of both natural and anthropogenic radionuclides to detritivorous invertebrates to facilitate estimation of the internal dose to such biota in models used to assess radiation exposure. To enhance the available data, activity concentrations of (137)Cs, (40)K, (90)Sr, (239 + 240)Pu, (241)Am, (235)U and (238)U were measured in ants (Formicidae) and corresponding undisturbed soil collected from the Zlatibor mountain in Serbia and ant/soil concentration ratios (CR) calculated. The (241)Am concentration ratios for ants were fourfold higher than those calculated for ants in a previous study whereas they are similar to the more numerous data previously reported for a range of detritivorous invertebrates in other studies. CR values for (137)Cs in ants were similar to the few other reported values and slightly lower than those for a range of detritivorous invertebrates. Those for (239 + 240)Pu were slightly higher than those for ants in two other studies but they were close to upper limit of a range of data reported for detritivorous invertebrates. All the CR values will be included in a future revision of the ERICA Tool database and will particularly improve the information available for uranium.

PMID: 19543994 [PubMed - indexed for MEDLINE]

1131. Rev Mal Respir. 2009 May;26(5):557-9.

[Allergic asthma due to sausage mould].

[Article in French]

Talleu C, Delourme J, Dumas C, Wallaert B, Fournier C.

Service de Pneumologie et Immuno-Allergologie, Pôle des Maladies Respiratoires, Hôpital Calmette, CHRU de Lille, France.

INTRODUCTION: Chronic cough is a common reason for consultation in respiratory medicine. The three most frequent causes of chronic cough are asthma, postnasal drip syndrome or rhinosinusitis, and gastro-oesophageal reflux disease. CASE REPORT: We describe a case of chronic cough related to occupational asthma with sensitivity to dry sausage mould (Penicillium nalgiovensis) in a worker in a semi-industrial pork butchers. The diagnosis was based on the history of symptoms, positive skin prick-tests, spirometry, a normal pulmonary CT-scan, and a favourable outcome after avoidance of the allergen. It was notified as a case of occupational disease.
CONCLUSION: A diagnosis of asthma should be considered in a worker exposed to dry sausage mould presenting with respiratory symptoms like chronic cough without evidence of hypersensitivity pneumonitis. Skin prick-tests and allergen avoidance are useful in the diagnosis.

PMID: 19543176 [PubMed - indexed for MEDLINE]

1132. J Immunol. 2009 Jul 1;183(1):533-42.

In vivo lipopolysaccharide exposure of human blood leukocytes induces cross-tolerance to multiple TLR ligands.

de Vos AF, Pater JM, van den Pangaart PS, de Kruif MD, van 't Veer C, van der Poll T.

Center of Infection and Immunity Amsterdam and Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, The Netherlands. a.f.devos@amc.uva.nl

In vitro and in vivo experiments in mice have shown that exposure of cells to the TLR4 ligand LPS induces tolerance toward a second exposure to LPS and induces cross-tolerance to certain other TLR ligands. Recently, we found that LPS tolerance in experimental human endotoxemia and Gram-negative sepsis is associated with elevated levels of IL-1R-associated kinase M, an intracellular negative regulator of MyD88-dependent TLR signaling. In the present study, we investigated whether in vivo exposure of humans to LPS induces tolerance in circulating leukocytes to other TLR agonists that rely either on MyD88- dependent or on MyD88-independent signaling. Analysis of TNF, IL-1beta, IL-6, and IL-10 levels in whole blood demonstrated that leukocytes were hyporesponsive to ex vivo LPS restimulation 3-8 h after i.v. LPS injection (4 ng/kg). Reduced cytokine release during the same interval was also observed in whole blood further stimulated with MyD88-dependent ligands for TLR2, TLR5, and TLR7 or with whole bacteria. Strikingly, blood leukocytes were also tolerant to a ligand for TLR3, which signals solely through a MyD88-independent (Toll IL-1R domain-containing adaptor-inducing IFN-beta (TRIF)-dependent) pathway. The hyporesponsiveness of leukocytes to TLR3 ligation was associated with reduced rather than increased levels of the recently identified TRIF inhibitor SARM. Taken together, these data indicate that systemic LPS challenge of human volunteers induces cross-tolerance to multiple TLR ligands that signal in a MyD88-dependent or MyD88-independent manner and suggest that LPS exposure of human blood leukocytes may hamper the inflammatory response to various microbial components.

PMID: 19542464 [PubMed - indexed for MEDLINE]

1133. Appl Environ Microbiol. 2009 Aug;75(16):5250-60. Epub 2009 Jun 19.

Genetic diversity and multihost pathogenicity of clinical and environmental strains of Burkholderia cenocepacia.

Springman AC, Jacobs JL, Somvanshi VS, Sundin GW, Mulks MH, Whittam TS, Viswanathan P, Gray RL, Lipuma JJ, Ciche TA.

Center for Microbial Pathogenesis, National Food Safety and Toxicology Center, Michigan State University, East Lansing, Michigan 48824, USA.

A collection of 54 clinical and agricultural isolates of Burkholderia cenocepacia was analyzed for genetic relatedness by using multilocus sequence typing (MLST), pathogenicity by using onion and nematode infection models, antifungal activity, and the distribution of three marker genes associated with virulence. The majority of clinical isolates were obtained from cystic fibrosis (CF) patients in Michigan, and the agricultural isolates were predominantly from Michigan onion fields. MLST analysis resolved 23 distinct sequence types (STs), 11 of which were novel. Twenty-six of 27 clinical isolates from Michigan were genotyped as ST-40, previously identified as the Midwest B. cenocepacia lineage. In contrast, the 12 agricultural isolates represented eight STs, including ST-122, that were identical to clinical isolates of the PHDC lineage. In general, pathogenicity to onions and the presence of the pehA endopolygalacturonase gene were detected only in one cluster of related strains consisting of agricultural isolates and the PHDC lineage. Surprisingly, these strains were highly pathogenic in the nematode Caenorhabditis elegans infection model, killing nematodes faster than the CF pathogen Pseudomonas aeruginosa PA14 on slow-kill medium. The other strains displayed a wide range of pathogenicity to C. elegans, notably the Midwest clonal lineage which displayed high, moderate, and low virulence. Most strains displayed moderate antifungal activity, although strains with high and low activities were also detected. We conclude that pathogenicity to multiple hosts may be a key factor contributing to the potential of B. cenocepacia to opportunistically infect humans both by increasing the prevalence of the organism in the environment, thereby increasing exposure to vulnerable hosts, and by the selection of virulence factors that function in multiple hosts.

PMCID: PMC2725458 PMID: 19542323 [PubMed - indexed for MEDLINE]

1134. J Hosp Infect. 2009 Aug;72(4):342-50. Epub 2009 Jun 21.

New hospital disinfection processes for both conventional and prion infectious agents compatible with thermosensitive medical equipment.

Lehmann S, Pastore M, Rogez-Kreuz C, Richard M, Belondrade M, Rauwel G, Durand F, Yousfi R, Criquelion J, Clayette P, Perret-Liaudet A.

CNRS, Institut de Génétique Humaine UPR 1142, Université Montpellier 1, France. Sylvain.Lehmann@igh.cnrs.fr

With the detection of prions in specific tissues in variant and sporadic Creutzfeldt-Jakob diseases, efficient decontamination for human transmissible spongiform encephalopathy (TSE) agents, that is compatible with medical equipment, has become a major issue. We previously described the cleavage of prions on exposure to copper (Cu) and hydrogen peroxide (H(2)O(2)) and have used this property to develop efficient prion decontamination processes. To validate this approach, in-vitro assays on genuine human and animal prions using both brain homogenates and steel wires to mimic contamination of medical equipment were conducted. In-vivo experiments using steel wire in the hamster 263 K model were then used to evaluate the effect on prion infectivity. Assays on classical pathogens following international norms completed these prion experiments. In-vitro data confirmed the full decontamination efficacy of H(2)O(2)/Cu on different TSE strains. Combination of Cu with peracetic acid, used for endoscope disinfection, also revealed improved prion decontamination. Animal assay demonstrated efficacy on TSE infectivity of H(2)O(2)/Cu alone or in combination with detergents (reduction factor > or =5.25 log(10)). Assays on classical pathogens confirmed the disinfection properties of the different processes. Taken together, these new disinfection processes are efficient for both conventional and prion infectious agents and are, compatible with thermosensitive medical equipment. They can be adapted to hospitals' and practitioners' routine use, and they present reduced risks for the environment and for healthcare professionals.

PMID: 19541387 [PubMed - indexed for MEDLINE]

1135. East Afr Med J. 2008 Sep;85(9):432-7.

Risk of conjunctival contamination from blood splashes during surgery at the Kenyatta National Hospital, Nairobi.

Ogendo SW, Awori MN, Omondi MA, Mulatya EM, Mugo PW.

Department of Surgery, College of Health Sciences, University of Nairobi, P. O. Box 19676-00202, Nairobi, Kenya.

OBJECTIVES: To determine the utilisation rate of design specific eye protection by surgeons and to assess the risk of conjunctival contamination with blood splashes during surgery. DESIGN: Cross sectional, observational study. SETTING: The theatre suite of Kenyatta National Hospital, Nairobi SUBJECTS: Surgeons from all specialties operating in the theatre suite.
RESULTS: The minority of surgeons, 5.2% utilised protective eye goggles compared to 3.5% of assistants. Prescription eye spectacles were the most common form of eye protection at 41.9 and 20.9% respectively for surgeons and their assistants. The contamination rate for provided protective eye wear was 53.1% with the average number of droplets being 2.48 per procedure for the principal surgeon. The duration of surgery and the use of power tools influenced the contamination rate.
CONCLUSIONS: The utilisation rate of design specific protective eye wear is low and with a significant risk of conjunctival contamination, changes in attitudes and practices are needed to increase utilisation.

PMID: 19537415 [PubMed - indexed for MEDLINE]

1136. Nature. 2009 Jul 9;460(7252):220-4. Epub 2009 Jun 17.

Adaptive prediction of environmental changes by microorganisms.

Mitchell A, Romano GH, Groisman B, Yona A, Dekel E, Kupiec M, Dahan O, Pilpel Y.

Department of Molecular Genetics, Weizmann Institute of Science Rehovot 76100, Israel.

Comment in Nature. 2009 Jul 9;460(7252):181.

Natural habitats of some microorganisms may fluctuate erratically, whereas others, which are more predictable, offer the opportunity to prepare in advance for the next environmental change. In analogy to classical Pavlovian conditioning, microorganisms may have evolved to anticipate environmental stimuli by adapting to their temporal order of appearance. Here we present evidence for environmental change anticipation in two model microorganisms, Escherichia coli and Saccharomyces cerevisiae. We show that anticipation is an adaptive trait, because pre-exposure to the stimulus that typically appears early in the ecology improves the organism's fitness when encountered with a second stimulus. Additionally, we observe loss of the conditioned response in E. coli strains that were repeatedly exposed in a laboratory evolution experiment only to the first stimulus. Focusing on the molecular level reveals that the natural temporal order of stimuli is embedded in the wiring of the regulatory network-early stimuli pre-induce genes that would be needed for later ones, yet later stimuli only induce genes needed to cope with them. Our work indicates that environmental anticipation is an adaptive trait that was repeatedly selected for during evolution and thus may be ubiquitous in biology.

PMID: 19536156 [PubMed - indexed for MEDLINE]

1137. J Expo Sci Environ Epidemiol. 2010 Sep;20(6):503-15. Epub 2009 Jun 17.

Indoor airborne fungi and wheeze in the first year of life among a cohort of infants at risk for asthma.

Rosenbaum PF, Crawford JA, Anagnost SE, Wang CJ, Hunt A, Anbar RD, Hargrave TM, Hall EG, Liu CC, Abraham JL.

Department of Public Health & Preventive Medicine, State University of New York Upstate Medical University, Syracuse, USA. rosenbap@upstate.edu

In studies worldwide, respiratory outcomes such as cough, wheeze and asthma have been consistently linked to mold exposure. Young children spend most of their time indoors and may be particularly vulnerable. We evaluated the associations between exposure to airborne fungal levels and episodes of wheezing in a cohort of 103 infants at risk for asthma (due to maternal history of asthma), living primarily in low-income urban settings. Using a new protocol that facilitates identification of rare and slow-growing fungi, we measured the type and concentration of cultured fungi in home air samples taken early in the infant's first year of life. We also inspected the homes for visible mold, water damage and other housing and environmental conditions. All homes had measurable indoor airborne fungi and 73%, had some sign of mold, water damage, dampness or a musty odor. One or more episodes of wheeze during the first year of life were observed in 38% of infants. Multiple logistic regression showed high indoor levels of Penicillium were a significant risk factor for wheeze (OR 6.18; 95% CI: 1.34-28.46) in the first year of life after controlling for season of sampling, smoking, endotoxin levels, day care attendance and confounders. Acrodontium, a rarely reported fungal genus, was detected in 18% of study homes, and was associated with wheeze in unadjusted models (OR 2.75; 95% CI 0.99-7.61), but not after adjustment for confounders. Total fungal levels, visually observed mold, dampness, water damage or musty odors were not significantly associated with wheeze.

PMID: 19536075 [PubMed - indexed for MEDLINE]

1138. Ecotoxicol Environ Saf. 2009 Nov;72(8):2153-7. Epub 2009 Jun 16.

Lack of pathogenicity and toxicity of the mycoinsecticide Metarhizium anisopliae var. acridum following acute gastric exposure in mice.

Toriello C, Pérez-Torres A, Vega-García F, Navarro-Barranco H, Pérez-Mejía A, Lorenzana-Jiménez M, Hernández-Velázquez V, Mier T.

Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México, México D.F. 04510, México. toriello@servidor.unam.mx

Metarhizium anisopliae var. acridum, monospore culture EH-502/8 (CNRCB MaPL40), isolated in Mexico from Schistocerca piceifrons ssp. piceifrons (Orthoptera: Acrididae) was tested for acute oral intragastric pathogenicity and toxicity in CD-1 mice. Animals were inoculated with one dose (10(8) conidia/animal) of viable (72 mice), non-viable (24 mice) conidia and compared to 18 control mice. Clinical observations were done daily; mycological and histological tests were performed during necropsies after the inoculation. No mice showed clinical symptoms of illness or died during the study. The fungus was able to persist in some organs until day 3, but did not cause any damage to the host. The gross pathology observed was splenomegaly in mice inoculated with viable and non-viable conidia. Non-germinated conidia, observed in several organs, suggest hematogenous spread, but without any histopathological tissue reaction. Results support the non-pathogenic and non-toxic status of this fungal strain when administered in a single intragastric dose to mice.

PMID: 19535139 [PubMed - indexed for MEDLINE]

1139. Chemosphere. 2009 Aug;76(9):1258-64. Epub 2009 Jun 16.

Intraspecific differences of arbuscular mycorrhizal fungi in their impacts on arsenic accumulation by Pteris vittata L.

Wu FY, Ye ZH, Wong MH.

Croucher Institute for Environmental Sciences, and Department of Biology, Hong Kong Baptist University, Kowloon Tong, Hong Kong SAR, PR China.

It has been shown that Pteris vittata, an arsenic hyperaccumulator, could be colonized by arbuscular mycorrhizal (AM) fungi either in controlled conditions or at field sites. However, physiological mechanisms of AM fungi influencing As accumulation and tolerance in the plant are not fully elucidated. Two predominant fungal species, Glomus mosseae and Glomus geosporum, and a rapidly sporulating fungal species, Glomus etunicatum, associated with P. vittata were isolated from As-contaminated soils. Two uncontaminated isolates, G. mosseae and G. etunicatum, served as reference isolates. Based on germination of spores exposed to elevated As, Pb and Zn concentrations, two contrasting isolates of G. mosseae were selected to investigate As accumulation in two populations of P. vittata [from an uncontaminated site of Hong Kong (HK) and an As-contaminated site located in Jinchuantang (JCT) of Hunan Province, China, respectively] under hydroponic culture and pot trials. At lower levels of As exposure (50-200 microM), both uncontaminated and metal-contaminated isolates of G. mosseae significantly increased short-term As influx into roots of P. vittata. However, at higher levels of As exposure (400-1000 microM), only uncontaminated isolates significantly increased short-term As influx into roots. When growing on 100mg As kg(-1) soils, uncontaminated isolates exhibited a higher level of colonization in roots of P. vittata than metal-contaminated isolates and only the former significantly increased As accumulation in roots of HK population and in fronds of JCT population. It was concluded that there were intraspecific differences of AM fungi in their impacts on As accumulation by P. vittata.

PMID: 19535126 [PubMed - indexed for MEDLINE]

1140. Mycopathologia. 2009 Oct;168(4):153-63. Epub 2009 Jun 16.

Adiaspiromycosis due to Emmonsia crescens is widespread in native British mammals.

Borman AM, Simpson VR, Palmer MD, Linton CJ, Johnson EM.

Mycology Reference Laboratory, Health Protection Agency South West Regional Laboratory, Bristol, UK. Andy.Borman@uhBristol.nhs.uk

Adiaspiromycosis caused by Emmonsia crescens is primarily a respiratory disease affecting small mammals, especially members of the Families Rodentia, Carnivora and Mustelidae. Although isolated reports exist of adiaspiromycosis in free-living British wildlife, the extent of infection in wild animals in the UK, and the significance of any associated pathology are unclear. Here, we report the results of histopathological examination of lungs of free-living wild mammals from the south-west UK coupled with digestion of lung material in potassium hydroxide followed by centrifugation and microscopic examination for the presence of adiaspores. The combined results showed that almost one-third (27/94, 28.7%) of animals examined had evidence of infection with E. crescens. Attempts to culture E. crescens from infected lungs were unsuccessful. However, E. crescens could be confirmed as the causative agent by PCR amplification and sequencing of DNA from adiaspores micro-dissected from animal lungs. The prevalence of adiaspiromycosis was largely independent of animal species or precise geography. Adiaspore burdens in most animals were low, consistent with transient exposure to E. crescens. However, burdens in several animals suggested heavy or repeated exposures to E. crescens, and were considered sufficient to have significantly impaired respiratory function. Finally, since E. crescens is apparently widespread in UK mammals and the first UK human case of adiaspiromycosis was reported recently, we present data obtained using a previous isolate of E. crescens demonstrating that both the mycelial and adiaspore phases of the organism are susceptible to amphotericin B, voriconazole, itraconazole and caspofungin.

PMID: 19533414 [PubMed - indexed for MEDLINE]

1141. Antonie Van Leeuwenhoek. 2009 Nov;96(4):413-22. Epub 2009 Jun 17.

Effect of ozone on spore germination, spore production and biomass production in two Aspergillus species.

Antony-Babu S, Singleton I.

Institute for Research on Environment and Sustainability, School of Biology, Newcastle University, Devonshire Building, NE17RU Newcastle, UK. Sanjay.Antony-Babu@ncl.ac.uk

The ability of ozone gas to reduce food spoilage is relatively well documented, but the developmental effects of the gas on food spoilage fungi are not well known. In this study two model aspergilli, Aspergillus nidulans and Aspergillus ochraceus were used to study the effects of ozone on spore germination, sporulation and biomass production. These effects were examined under three levels of ozone; two high level ozone exposures (200 and 300 micromol mol(-1)) and one low level exposure (0.2 micromol mol(-1)). The two species behaved noticeably different to each other. Ozone was more effective in reducing growth from spore inocula than mycelia. No spore production could be detected in A. nidulans exposed to continuous low level O3, whereas the same treatment reduced spores produced in A. ochraceus by 94%. Overall the work suggests that ozone exposure is an effective method to prevent spread of fungal spores in a food storage situation.

PMID: 19533409 [PubMed - indexed for MEDLINE]

1142. Appl Phys Lett. 2008 Oct 13;93(15):153105. Epub 2008 Oct 14.

Plasma fluorination of carbon-based materials for imprint and molding lithographic applications.

Schvartzman M, Mathur A, Hone J, Jahnes C, Wind SJ.

Diamondlike carbon nanoimprint templates are modified by exposure to a fluorocarbon-based plasma, yielding an ultrathin layer of a fluorocarbon material on the surface which has a very low surface energy with excellent antiwear properties. We demonstrate the use of these plasma fluorinated templates to pattern features with dimensions approximately 20 nm and below. Furthermore, we show that this process is extendable to other carbon-based materials. Plasma fluorination can be applied directly to nanoimprint resists as well as to molds used to form elastomer stamps for microcontact printing and other applications requiring easy mold release.

PMCID: PMC2684694 PMID: 19529791 [PubMed]

1143. Acta Trop. 2009 Aug;111(2):197-9. Epub 2009 Apr 11.

The suitability of clay pots for indoor sampling of mosquitoes in an arid area in northern Tanzania.

van den Bijllaardt W, ter Braak R, Shekalaghe S, Otieno S, Mahande A, Sauerwein R, Takken W, Bousema T.

Department of Medical Microbiology 268, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. wvandenbijl@hotmail.com

Comment in Acta Trop. 2009 Oct;112(1):88-9.

Water storage clay pots have been recently explored as method for outdoor mosquito sampling and as novel device for administrating insect-pathogenic fungi to mosquitoes. Their suitability for indoor mosquito sampling in natural conditions is unknown. We tested clay pots as indoor resting sites alongside catches by CDC light trap in an area of low malaria endemicity in northern Tanzania. Mosquitoes were caught by clay pots although the rate of female Anopheles mosquito catches was 22.64 (95% CI 11.26-45.52) times greater for CDC light traps. The proportion of fed female Anophelines was significantly higher for clay pots compared to CDC light trap (p<0.001), indicating these methods sample different populations of mosquitoes. Although we were able to identify households with a consistently higher exposure to mosquitoes by CDC light trap, there was no apparent heterogeneity in mosquito catches by clay pots. We conclude that clay pots are not a reliable tool to sample mosquitoes in the dry season in an area of low transmission intensity with Anopheles arabiensis as principle vector.

PMID: 19524083 [PubMed - indexed for MEDLINE]

1144. Microbiology. 2009 Sep;155(Pt 9):3134-41. Epub 2009 Jun 11.

Transcriptional analysis of the response of Neurospora crassa to phytosphingosine reveals links to mitochondrial function.

Videira A, Kasuga T, Tian C, Lemos C, Castro A, Glass NL.

IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal. avideira@ibmc.up.pt

Treatment of Neurospora crassa cells with phytosphingosine (PHS) induces programmed cell death (PCD) by an unknown mechanism. To determine the relationship between PHS treatment and PCD, we determined changes in global gene expression levels in N. crassa during a time-course of PHS treatment. Most genes having differential expression levels compared to untreated samples showed an increase in relative expression level upon PHS exposure. However, genes encoding mitochondrial proteins were highly enriched among approximately 100 genes that showed a relative decrease in expression levels after PHS treatment, suggesting that repression of these genes might be related to the death-inducing effects of PHS. Since mutants in respiratory chain complex I are more resistant to both PHS and hydrogen peroxide (H(2)O(2)) than the wild-type strain, possibly related to the production of reactive oxygen species, we also compared gene expression profiles of a complex I mutant (nuo14) and wild-type in response to H(2)O(2). Genes with higher expression levels in the mutant, in the presence of H(2)O(2), are also significantly enriched in genes encoding mitochondrial proteins. These data suggest that complex I mutants cope better with drug-induced decrease in expression of genes encoding mitochondrial proteins and may explain their increased resistance to both PHS and H(2)O(2). As a way of identifying new components required for PHS-induced death, we analysed the PHS sensitivity of 24 strains carrying deletions in genes that showed a significant alteration in expression pattern when the wild-type was exposed to the sphingolipid. Two additional mutants showing increased resistance to PHS were identified and both encode predicted mitochondrial proteins, further supporting the role of the mitochondria in PHS-induced PCD.

PMCID: PMC2888170 PMID: 19520721 [PubMed - indexed for MEDLINE]

1145. Am J Infect Control. 2009 Sep;37(7):534-40. Epub 2009 Jun 10.

Patient-days: a better measure of incidence of occupational bloodborne exposures.

Chen LF, Sexton DJ, Kaye KS, Anderson DJ.

Division of Infectious Diseases, Duke Infection Control Outreach Network, Duke University Medical Center, Durham, NC 27710, USA. Luke.Chen@duke.edu

BACKGROUND: There is currently no accepted standard denominator to calculate and to report the incidence of occupational exposures to bloodborne pathogens (OEBBPs) in health care.
METHODS: We performed a multicenter study of OEBBP injuries reported from 31 community hospitals in the southeastern United States from January 2003 to December 2006. A qualitative design was used to assess 4 commonly used denominators to calculate the incidence of OEBBP: patient-days; staffed beds; occupied beds and full-time employee equivalents (FTEs). Six criteria were used to assess the quality and suitability of each denominator as a standard method to calculate incidence of OEBBP. We also analyzed the correlation of hospital rankings produced by these 4 denominators.
RESULTS: During 4 years of study, a total of 3375 occupational exposures were reported. Patient-days outperformed others as a denominator to calculate rates of OEBBP when judged by 6 predefined criteria. Data for staffed beds, occupied beds, and FTE were manually collected, infrequently reported, and often subject to missing data. Furthermore, FTE and staffed beds data also captured unoccupied beds and non-clinical employee data that were not associated with risk of OEBBP.
CONCLUSION: Patient-days may be the most suitable and readily available denominator for standard reporting and benchmarking of incidence of OEBBP. Patient-days may be used as a standard method for comparing rates of OEBBP.

PMID: 19520459 [PubMed - indexed for MEDLINE]

1146. J Biol. 2009;8(5):51. Epub 2009 Jun 5.

Transcription in mosquito hemocytes in response to pathogen exposure.

Hillyer JF.

Department of Biological Sciences and Institute for Global Health, Vanderbilt University, VU Station B 35-1634, Nashville, TN 37235-1634, USA. julian.hillyer@vanderbilt.edu

Mosquito hemocytes are blood cells that are fundamental for combating systemic infection. A study published in BMC Genomics shows that hemocyte gene transcription in response to immune challenge is pathogen-specific and reaffirms the primary role of these cells in immunity.

PMCID: PMC2736665 PMID: 19519953 [PubMed - indexed for MEDLINE]

1147. J Immunotoxicol. 2009 Mar;6(1):62-73.

Differential allergy responses to Metarhizium anisopliae fungal component extracts in BALB/c mice.

Ward MD, Chung YJ, Haykal-Coates N, Copeland LB.

Intratracheal aspiration (IA) exposure to Metarhizium anisopliae crude antigen (MACA), which is composed of equal protein amounts of mycelium (MYC), conidia (CON) and inducible proteases/chitinases (IND) extracts/filtrates, has resulted in responses characteristic of human allergic asthma in mice. The study objective was to evaluate the potential of each component extract to induce allergic/asthma-like responses observed in this mouse model. BALB/c mice received 4 IA exposures to MACA, CON, MYC, IND, or bovine serum albumin (BSA; negative control) or appropriate vehicle control or inflammatory control over a 4-wk period. Mice were assessed by whole-body plethysmography for immediate airway responses and airway hyperresponsiveness to methacholine (Mch) challenge (PenH). Serum and bronchoalveolar lavage fluid (BALF) were collected 3 d after the final exposure. Additionally, BALF neurotrophin levels and extract protease and chitinase activity levels were evaluated. Western blot analysis showed that each component contained different IgE-reactive proteins. All fungal extract exposures resulted in elevated BALF total and differential cell counts, IgE and IgA and total serum IgE compared to HBSS and BSA controls. MYC-exposed mice had the highest responses except for neutrophil influx, which was highest in MACA and IND exposures. However, the MYC-exposed mice had significantly lower PenH values compared to other treatments. By comparison IND and MACA induced significantly higher PenH values. Additionally, IND had substantially higher protease activity levels but induced the lowest neurotrophin levels compared to the other fungal exposures. In this allergic asthma model extract chitinase activity was not associated with allergic responses. In summary, multiple exposures to any of the M. anisopliae component extracts induced allergic/asthma-like responses in BALB/c mice but the response magnitude was different for each component and each appears to contain unique IgE-reactive proteins. Therefore, hazard identification and/or risk assessment for molds must test both mycelia and conidia.

PMID: 19519164 [PubMed - indexed for MEDLINE]

1148. Duodecim. 2009;125(9):983-9.

[Mold problem in the work environment--an otorhinolaryngologist's view].

[Article in Finnish]

Ruoppi P.

KYS:n korva-, nenä- ja kurkkutautien klinikka, Kuopio.

A proportion of persons exposed to microbial growth and associated impurities of the air exhibit symptoms in buildings with moisture damage. Typical symptoms include irritation of the eyes, skin and respiratory passages such as rhinitis, voice problems, mucus production and dyspnea. Joint and muscle pain, headache, fatigue and low-grade fever are also common. In the case of rhinitis, investigational methods exist only for symptoms induced by allergy. If the respiratory symptoms are suspected to be caused by moisture damage, constructional technical investigations must be immediately commenced. The symptoms usually disappear upon reparation of the damage and ending of the exposure.

PMID: 19517867 [PubMed - indexed for MEDLINE]

1149. Klin Oczna. 2009;111(1-3):15-7.

In vitro photodynamic properties of methylene blue in a combination with laser illumination at 630 nm concerning Candida albicans.

Pasyechnikova N, Zborovskaya O, Kustrin T.

State Institution The Filatov' s Institute of Eye Diseases and Tissue Therapy of AMS of Ukraine, Laboratory of Microbiology, Department of Uveitis.

The study had to define influence of combined applications of laser radiation and methylene blue (MB) on pathogenic culture of Candida albicans in vitro. The experimental study was done at standard techniques of method of cultivations in a broth. The laser irradiation of cultures was done at once after addition of MB in concentration 0.05%, 0.1% and 0.2%. During studying action of MB in dark, influence of MB to the growth of test-shtam without laser radiation, were prepared fluid Gissa's broth with glucose without Andrede's indicator. Activation of MB was done by laser with wave length 630 nm during 3 or 5 min. All experiments were passed in 4 parallels and 3 repeats. Maximal suppression of growth of microorganisms was noted in group with using 0.1% MB with laser radiation 3 minutes without centrifugation after 24 hours. Maximal suppression of growth was noted in group after centrifugation with 0.05% MB with exposure of laser 3 min. after 48 hours. Sensitivity of pathogenic culture of Candida albicans to application of B and laser raises accordingly to increase of concentration of MB.

PMID: 19517838 [PubMed - indexed for MEDLINE]

1150. Mol Nutr Food Res. 2009 Jul;53(7):904-20.

Interactions between ABC-transport proteins and the secondary Fusarium metabolites enniatin and beauvericin.

Dornetshuber R, Heffeter P, Sulyok M, Schumacher R, Chiba P, Kopp S, Koellensperger G, Micksche M, Lemmens-Gruber R, Berger W.

Department of Pharmacology and Toxicology, University of Vienna, Vienna, Austria.

Enniatins (ENN) and beauvericin (BEA) exert cytotoxic properties. Here, we observed that their impact on Ca(2+)-homeostasis can be reversed by exogenous ATP. Thus, we investigated whether membrane-located ATP-binding cassette (ABC) transporters influence ENNs- and BEA-induced cytotoxicity. In short-term exposure assays breast cancer resistance protein (ABCG2)-overexpression weakly but significantly reduced the cytotoxic activity of BEA but not ENNs. In contrast, multidrug resistance-associated protein-1 (ABCC1)- and P-glycoprotein (ABCB1)-overexpression was not protective under identical conditions. ABCG2-mediated resistance against BEA was reversible by ABCG2 modulators. In long-term exposure assays, ABCG2 and ABCB1 significantly protected against ENNs- and to a lesser extent BEA-induced cytotoxicity. Moreover, both fusariotoxins potently inhibited the ABCG2- and ABCB1-mediated efflux of specific fluorescent substrates, with BEA being more effective. Additionally, ATPase and photoaffinity-labelling assays proofed interaction of both substances with ABCG2 and ABCB1. Remarkably, 2 years selection of KB-3-1 cells against both fusariotoxins resulted only in two-fold ENNs but negligible BEA resistance. Interestingly, the selected sublines displayed upregulation of multidrug resistance proteins and crossresistance to other chemotherapeutics. Summarizing, ABCG2 and ABCB1 slightly but significantly protect human cells against ENNs- and BEA-induced cytotoxicity. However, both mycotoxins potently interact with ABCB1 and ABCG2 transport functions suggesting influences on bioavailability of xenobiotics and pharmaceuticals.

PMID: 19517454 [PubMed - indexed for MEDLINE]

1151. J Trauma. 2009 Apr;66(4 Suppl):S62-8.

Occupational exposure to blood and other bodily fluids at a military hospital in Iraq.

Murray CK, Johnson EN, Conger NG, Marconi VC.

Infectious Disease Service, San Antonio Military Medical Center, Fort Sam Houston, Texas 78234, USA. clinton.murray@amedd.army.mil

BACKGROUND: Exposure to bloodborne pathogens, namely HIV, hepatitis B, and hepatitis C, remains a risk for healthcare workers. Given the austere and challenging environments in a combat zone, it is unclear to what extent blood and other bodily fluid occupational exposures pose a risk of infection for military healthcare workers deployed to a level III military treatment facility in support of Operation Iraqi Freedom.
METHODS: This is a retrospective review of electronic infection control records at the Air Force Theater Hospital in Iraq in which blood and other bodily fluid occupational exposure data were available: October 1, 2005 through May 31, 2006 and January 15, 2007 through April 30, 2007.
RESULTS: During the first study period, there were 46 exposures for an average monthly exposure of 5.8 (range, 2-16 per month). The majority of exposures were percutaneous fingersticks (74%), whereas the remainder were splashes (17%) or not documented (9%). During the second study period, there were 19 exposures with percutaneous device and splash exposure encompassing 68% and 32% of cases, respectively. The majority of occurrences were in the intensive care unit (53%) and primarily among nurses (37%). Overall, there were 65 exposures per 1,000 persons during the year review.
CONCLUSIONS: During the time periods evaluated, a substantial number of blood and other bodily fluid exposures occurred in a combat zone military healthcare facility. This finding is comparable to US civilian institutions. Maintaining programs for preventing, tracking, and implementing postexposure prophylaxis remain a worthy and achievable goal at every military treatment facility, regardless of the austerity of the environment.

PMID: 19359972 [PubMed - indexed for MEDLINE]

1152. Int J Immunopathol Pharmacol. 2009 Apr-Jun;22(2):287-97.

Pulmonary exposure to soluble cell wall beta-(1, 3)-glucan of aspergillus induces proinflammatory response in mice.

Inoue K, Koike E, Yanagisawa R, Adachi Y, Ishibashi K, Ohno N, Takano H.

Environmental Health Sciences Division, National Institute for Environmental Studies, Tsukuba, Ibaraki, Japan. inoue.kenichirou@nies.go.jp

Compared to the significant immunomodulation of cell wall component(s) of bacterium such as lipopolysaccharide (E. Coli), that of pathogenic fungi has not been well elucidated, especially in vivo. Furthermore, although it has been implied that beta-(1, 3)-glucan of fungi possesses various biological activities, the impacts of the component have not been properly clarified, possibly due to its insolubility in water and alkali solutions. Previously, we isolated a soluble type of beta-(1, 3) -glucan from Aspergillus (referred to as ASBG). The present study investigated the effects of a single pulmonary exposure to ASBG on the immune (proinflammatory) responses in naïve mice. ASBG (12.5-100micorg/animal) exposure Induced neutrophilic lung inflammation with an enhanced local expression of proinflammatory cytokines such as interleukin (IL)-1beta and chemokines such as macrophage inflammatory protein -1a, and keratinocyte-derived chemoattractant in a dose-dependent fashion with overall trends. On the other hand, ASBG at relatively lower doses significantly amplified the lung expression of IL-2, IL-6, and IL-12 as compared with vehicle. ASBG significantly induced pulmonary edema. Furthermore, ASBG augmented the nuclear translocation of nuclear factor (NF)-kB and its binding capacity to the promoter site of DNA in the lung homogenate. These results suggest that pulmonary exposure to ASBG confers lung inflammation, at least partly, via the enhanced local expression of proinflammatory cytokines, likely through NF-kB-dependent pathway.

PMID: 19505382 [PubMed - indexed for MEDLINE]

1153. PLoS One. 2009 Jun 8;4(6):e5830.

Comparative genome-wide screening identifies a conserved doxorubicin repair network that is diploid specific in Saccharomyces cerevisiae.

Westmoreland TJ, Wickramasekara SM, Guo AY, Selim AL, Winsor TS, Greenleaf AL, Blackwell KL, Olson JA Jr, Marks JR, Bennett CB.

Department of Surgical Sciences, Duke University Medical Center, Durham, North Carolina, United States of America.

The chemotherapeutic doxorubicin (DOX) induces DNA double-strand break (DSB) damage. In order to identify conserved genes that mediate DOX resistance, we screened the Saccharomyces cerevisiae diploid deletion collection and identified 376 deletion strains in which exposure to DOX was lethal or severely reduced growth fitness. This diploid screen identified 5-fold more DOX resistance genes than a comparable screen using the isogenic haploid derivative. Since DSB damage is repaired primarily by homologous recombination in yeast, and haploid cells lack an available DNA homolog in G1 and early S phase, this suggests that our diploid screen may have detected the loss of repair functions in G1 or early S phase prior to complete DNA replication. To test this, we compared the relative DOX sensitivity of 30 diploid deletion mutants identified under our screening conditions to their isogenic haploid counterpart, most of which (n = 26) were not detected in the haploid screen. For six mutants (bem1Delta, ctf4Delta, ctk1Delta, hfi1Delta,nup133Delta, tho2Delta) DOX-induced lethality was absent or greatly reduced in the haploid as compared to the isogenic diploid derivative. Moreover, unlike WT, all six diploid mutants displayed severe G1/S phase cell cycle progression defects when exposed to DOX and some were significantly enhanced (ctk1Delta and hfi1Delta) or deficient (tho2Delta) for recombination. Using these and other "THO2-like" hypo-recombinogenic, diploid-specific DOX sensitive mutants (mft1Delta, thp1Delta, thp2Delta) we utilized known genetic/proteomic interactions to construct an interactive functional genomic network which predicted additional DOX resistance genes not detected in the primary screen. Most (76%) of the DOX resistance genes detected in this diploid yeast screen are evolutionarily conserved suggesting the human orthologs are candidates for mediating DOX resistance by impacting on checkpoint and recombination functions in G1 and/or early S phases.

PMCID: PMC2688081 PMID: 19503795 [PubMed - indexed for MEDLINE]

1154. Nihon Eiseigaku Zasshi. 2009 May;64(3):665-71.

[Dampness, biological factors and sick house syndrome].

[Article in Japanese]

Saijo Y, Yoshida T, Kishi R.

Department of Health Science, Asahikawa Medical College, Midorigaoka-Higashi 2-1-1-1, Asahikawa 078-8510, Japan. y-saijo@asahikawa-med.ac.jp

Sick house syndrome is caused by not only chemicals but also dampness and biological factors. Many European and North American studies have shown that dampness associated with condensation, visible mold, moldy odor, and water-induced damage among others affects residents' health. Recent Japanese studies have also shown a similar significant relationship. Mold can cause infection and allergy, and can produce chemicals such as microbial volatile organic compounds (MVOCs) and (1-->3)-Beta-D-glucan. Mold exposure can be analyzed using culture-based (colony forming unit count) enumeration techniques. More recently, other nonculture-based methods of measuring mold concentrations in indoor environments have been described, which may provide more valid measures of exposure. These are based on measurement of specific mold markers in dust or air, such as ergosterol, genus-specific extracellular polysaccharides or (1-->3)-Beta-D-glucan. Mites are major indoor allergens. The gold standard for measuring exposure to mite allergens is enzyme-linked immunosorbent assay (ELISA), but it is relatively expensive and requires specialized techniques. Several simple semiquantitative dust mites allergen test have b available in Japan.

PMID: 19502762 [PubMed - indexed for MEDLINE]

1155. Biosci Biotechnol Biochem. 2009 Jun;73(6):1404-11. Epub 2009 Jun 7.

Activation of the oxidative stress regulator PpYap1 through conserved cysteine residues during methanol metabolism in the yeast Pichia pastoris.

Yano T, Yurimoto H, Sakai Y.

Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.

The methylotrophic yeast Pichia pastoris can grow on methanol as sole source of carbon and energy. The first reaction in yeast methanol metabolism, catalyzed by an abundant peroxisomal enzyme, alcohol oxidase, generates high levels of H(2)O(2), but the oxidative stress response during methanol metabolism has not been elucidated. In this study, we isolated the Yap1 homolog of P. pastoris (PpYap1) and analyzed the properties of a PpYAP1-disruption strain. The PpYap1 transcription factor is activated after exposure to various reactive agents, and therefore functions as a regulator of the redox system in P. pastoris. We have also identified PpGPX1, the unique glutathione peroxidase-encoding gene in P. pastoris whose expression is induced by PpYap1. PpGpx1, but not the ScTsa1 or SpTpx1 homolog PpTsa1, functions as a H(2)O(2) sensor and activates PpYap1. This study is the first demonstration of a yeast Yap1 family protein activated during conventional metabolism.

PMID: 19502720 [PubMed - indexed for MEDLINE]

1156. J Med Microbiol. 2009 Jul;58(Pt 7):936-44. Epub 2009 Jun 5.

Novel synergistic antibiofilm combinations for salvage of infected catheters.

Venkatesh M, Rong L, Raad I, Versalovic J.

Section of Neonatology, Department of Pediatrics, Texas Children's Hospital & Baylor College of Medicine, Houston, TX 77030, USA. mohanv@bcm.edu

Biofilms on catheters are responsible for catheter-related bloodstream infections (CRBSIs), which cause significant mortality and morbidity. Antimicrobial catheter-lock solutions may salvage precious catheters by eradicating biofilms. Staphylococcus epidermidis and Candida albicans are frequently isolated organisms in CRBSIs. We evaluated N-acetylcysteine (NAC), EDTA, ethanol and talactoferrin (TLF) individually and in combination with antibiotics against biofilms of S. epidermidis and C. albicans to identify effective catheter-lock solutions. Minimum biofilm-eradication concentrations causing 50% inhibition (MBEC(50)) for EDTA, NAC, ethanol and TLF were determined against biofilms of S. epidermidis and C. albicans formed on 96-well microtitre plates. Biomass, mean thickness and viability of S. epidermidis and C. albicans biofilms were evaluated after exposure to MBEC(50) concentrations of EDTA, NAC, ethanol and TLF. Antimicrobial combinations of EDTA, NAC, ethanol and TLF with nafcillin, vancomycin, fluconazole and amphotericin B were evaluated systematically for synergy using combination indices (CIs). EDTA, NAC, ethanol and TLF significantly reduced biofilm biomass and mean thickness (P<0.05, one-way ANOVA) of monomicrobial and polymicrobial biofilms as evaluated by confocal microscopy. CIs evaluated at equipotency ratios, and 50, 75 and 90 % effects, showed that EDTA, NAC, ethanol and TLF were synergistic (CI <1) with antibiotics (with few exceptions) against biofilms of S. epidermidis and C. albicans. EDTA, NAC, ethanol and TLF inhibit monomicrobial and polymicrobial biofilms of neonatal strains of S. epidermidis and C. albicans, and are synergistic with antibiotics. Catheter-lock solutions of EDTA, NAC and ethanol alone or in combination with antibiotics may be used to salvage infected catheters, which will directly impact on patient morbidity and health-care costs.

PMID: 19502361 [PubMed - indexed for MEDLINE]

1157. Indoor Air. 2009 Aug;19(4):280-90. Epub 2009 Jan 18.

Asthma and respiratory symptoms in hospital workers related to dampness and biological contaminants.

Cox-Ganser JM, Rao CY, Park JH, Schumpert JC, Kreiss K.

Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA. Jcoxganser@cdc.gov

The National Institute for Occupational Safety and Health investigated respiratory symptoms and asthma in relation to damp indoor environments in employees of two hospitals. A cluster of six work-related asthma cases from one hospital department, whose symptoms arose during a time of significant water incursions, led us to conduct a survey of respiratory health in 1171/1834 employees working in the sentinel cases hospital and a nearby hospital without known indoor environmental concerns. We carried out observational assessment of dampness, air, chair, and floor dust sampling for biological contaminants, and investigation of exposure-response associations for about 500 participants. Many participants with post-hire onset asthma reported diagnosis dates in a period of water incursions and renovations. Post-hire asthma and work-related lower respiratory symptoms were positively associated with the dampness score. Work-related lower respiratory symptoms showed monotonically increasing odds ratios with ergosterol, a marker of fungal biomass. Other fungal and bacterial indices, particle counts, cat allergen and latex allergen were associated with respiratory symptoms. Our data imply new-onset of asthma in relation to water damage, and indicate that work-related respiratory symptoms in hospital workers may be associated with diverse biological contaminants. PRACTICAL IMPLICATIONS: In healthcare facilities with indoor dampness and microbial contamination, possible associations between such conditions and respiratory health effects should be considered. Good building maintenance and housekeeping procedures should lead to improvements in employee respiratory health.

PMID: 19500175 [PubMed - indexed for MEDLINE]

1158. J Agric Food Chem. 2009 Jul 8;57(13):5707-12.

Bioactivity of latifolin and its derivatives against termites and fungi.

Sekine N, Ashitani T, Murayama T, Shibutani S, Hattori S, Takahashi K.

The United Graduate School Agricultural Science, Iwate University, 3-18-34 Ueda, Morioka 020-8550, Japan. abe10152@tds1.tr.yamagata-u.ac.jp

Latifolin (1) and its derivatives were investigated with the aim of confirming the correlation between bioactivity (antitermite and antifungal activity) and chemical structure. Termite mortality in response to the derivatives 2'-O-methyllatifolin (2), latifolin dimethyl ether (4), and latifolin diacetate (5) increased 2-fold compared to compound 1. The mortality rate from 5-O-methyllatifolin (3) was not different from 1. The mass loss (feed consumption by termite) in response to compounds 3-5 was 3 times greater than compound 1, and the mass loss from compound 2 was twice as great as compound 1. The mortality rate from compounds 4 and 5 increased sharply 7 days after initial exposure. In assessing the antifungal activity of these compounds, it was found that the inhibition rates of white- and brown-rot fungi in response to all derivatives were less than that for compound 1. Our findings indicate that the phenolic hydroxyl group at C-5 of the A ring provides antitermite activities (mortality and mass loss). In addition, both C-5 and C-2' phenolic hydroxyl groups in the A and B rings have antifungal activity against white- and brown-rot fungi. In conclusion, the bioactivity of compound 1 depends upon the position of phenolic hydroxyl groups.

PMID: 19499920 [PubMed - indexed for MEDLINE]

1159. Appl Biochem Biotechnol. 2010 Mar;160(6):1685-98. Epub 2009 Jun 5.

Toxicity of methanol and formaldehyde towards Saccharomyces cerevisiae as assessed by DNA microarray analysis.

Yasokawa D, Murata S, Iwahashi Y, Kitagawa E, Nakagawa R, Hashido T, Iwahashi H.

Department of Food Biotechnology, Hokkaido Food Processing Research Center, 589-4 Bunkyodai Midorimachi, Ebetsu, Hokkaido, 0690836, Japan. duke@foodhokkaido.gr.jp

To assess the toxicity of the C1 compounds methanol and formaldehyde, gene expression profiles of treated baker's yeast were analyzed using DNA microarrays. Among approximately 6,000 open reading frames (ORFs), 314 were repressed and 375 were induced in response to methanol. The gene process category "energy" comprised the greatest number of induced genes while "protein synthesis" comprised the greatest number of repressed genes. Products of genes induced by methanol were mainly integral membrane proteins or were localized to the plasma membrane. A total of 622 and 610 ORFs were induced or repressed by formaldehyde, respectively. More than one-third of the genes found to be strongly repressed by formaldehyde belonged to the "protein synthesis" functional category. Conversely, genes in the subcategory of "nitrogen, sulfur, and selenium metabolism" within "metabolism" and in the category of "cell rescue, defense, and virulence" were up-regulated by exposure to formaldehyde. Our data suggest that membrane structure is a major target of methanol toxicity, while proteins were major targets of formaldehyde toxicity.

PMID: 19499198 [PubMed - indexed for MEDLINE]

1160. Pest Manag Sci. 2009 Oct;65(10):1090-6.

Sensitivity to azoxystrobin in Didymella bryoniae isolates collected before and after field use of strobilurin fungicides.

Keinath AP.

Clemson University, Coastal Research and Education Center, Charleston, SC 29414-5329, USA. tknth@clemson.edu

BACKGROUND: Isolates of Didymella bryoniae (Auersw.) Rehm, causal agent of gummy stem blight on cucurbits, developed insensitivity to azoxystrobin in the eastern United States 2 years after first commercial use in 1998. Baseline sensitivity of this fungus to azoxystrobin has never been reported. The objectives were to compare baseline sensitivities of D. bryoniae from South Carolina and other locations to sensitivities of isolates exposed to azoxystrobin for one or more seasons, and to compare sensitivity in vitro and in vivo.
RESULTS: Sixty-one isolates of D. bryoniae collected before 1998 were sensitive. Median EC50 was 0.055 mg L(-1) azoxystrobin (range 0.005 to 0.81). Forty isolates collected after exposure during 1998 also were sensitive. Fifty-three of 64 isolates collected in South and North Carolina between 2000 and 2006 were insensitive to 10 mg L(-1) azoxystrobin. Sensitive and insensitive isolates were distinguished by disease severity on Cucumis melo L. seedlings treated with azoxystrobin (20 or 200 mg L(-1)).
CONCLUSIONS: An azoxystrobin baseline sensitivity distribution was established in vitro for isolates of D. bryoniae never exposed to strobilurins. Baseline values were comparable with those of other ascomycetes. Insensitive isolates were found in fields with a history of strobilurin applications. An in vivo method distinguished sensitive and insensitive isolates.

PMID: 19488995 [PubMed - indexed for MEDLINE]

1161. Toxicon. 2009 Sep 15;54(4):513-8. Epub 2009 May 30.

The role of oxidative stress in deoxynivalenol-induced DNA damage in HepG2 cells.

Zhang X, Jiang L, Geng C, Cao J, Zhong L.

Department of Toxicology, Dalian Medical University, No. 9, Dalian 116044, Liaoning, China.

Deoxynivalenol (DON) is a trichothecene mycotoxin and a cereals contamination, whose cytotoxicity has been shown in animals and various cells. However, with respect to the deoxynivalenol-induced DNA damage, especially in humans, are not well understood. The aim of this study was to assess the role of oxidative stress in deoxynivalenol-induced DNA damage, using human hepatoma HepG2 cells. Exposure of the cells to DON caused significant increase of DNA migration in comet assay at concentrations of 3.75-30 microM, which suggests that DON caused DNA strand breaks. To elucidate the role of antioxidation in those effects, DNA migration was monitored by pre-treatment with hydroxytyrosol (HT) as an antioxidant in comet assay. It was found that DNA migration with pre-treatment of HT was dramatically decreased. The DNA damage induced by DON was almost completely prevented. In order to clarify the underlying mechanisms, we evaluated the level of reactive oxygen species (ROS) production with the 2,7-dichlorofluorescein diacetate (DCFH-DA) assay. Significant increase in the level of ROS was observed in HepG2 cells at a higher concentration (60 microM). The involvement of lipid peroxidation in the DNA damage of DON was confirmed by using immunoperoxidase staining for 8-hydroxydeoxyguanosine (8-OHdG) and by measuring levels of thiobarbituric acid-reactive substances (TBARS), the doses being 7.5-60 microM and 3.75-15 microM, respectively. These results indicate that the DNA damage induced by DON in HepG2 cells is probably related to the oxidative stress.

PMID: 19486909 [PubMed - indexed for MEDLINE]

1162. J Prosthodont. 2009 Jul;18(5):411-6. Epub 2009 Mar 26.

Microhardness of a resin cement polymerized by light-emitting diode and halogen lights through ceramic.

Hooshmand T, Mahmoodi N, Keshvad A.

Department of Dental Materials, School of Dentistry/Research Center for Science and Technology in Medicine, Tehran University of Medical Sciences, Tehran, Iran. hoshmand@sina.tums.ac.ir

PURPOSE: This study evaluated the curing efficiency of light-emitting diode (LED) and halogen [quartz tungsten halogens (QTH)] lights through ceramic by determining the surface microhardness of a highly filled resin cement. MATERIALS AND METHODS: Resin cement specimens (Variolink Ultra; with and without catalyst) (5-mm diameter, 1-mm thick) were condensed in a Teflon mold. They were irradiated through a ceramic disc (IPS Empress 2, diameter 5 mm, thickness 2 mm) by high-power light-curing units as follows: (1) QTH for 40 seconds (continuous), (2) LED for 20 seconds, and (3) LED for 40 seconds (5-second ramp mode). The specimens in control groups were cured under a Mylar strip. Vickers microhardness was measured on the top and bottom surfaces by a microhardness tester. Data were analyzed using analysis of variance (ANOVA) and a post hoc Bonferroni test at a significance level of p < 0.05.
RESULTS: The mean microhardness values of the top and bottom surfaces for the dual-cured cement polymerized beneath the ceramic by QTH or LED (40 seconds) were significantly higher than that of light-cured cement (p < 0.05). The top and bottom surface microhardness of dual-cured cement polymerized beneath the ceramic did not show a statistically significant difference between the LED and QTH for 40 seconds (p > 0.05).
CONCLUSIONS: The efficiency of high-power LED light in polymerization of the resin cement used in this study was comparable to the high-power QTH light only with a longer exposure time. A reduced curing time of 20 seconds with high-power LED light for photopolymerizing the dual-cured resin cement under ceramic restorations with a minimum 2-mm thickness is not recommended.

PMID: 19486456 [PubMed - indexed for MEDLINE]

1163. Mycopathologia. 2009 Oct;168(4):165-73. Epub 2009 May 31.

Candidal onychomycosis: a mini-review.

Jayatilake JA, Tilakaratne WM, Panagoda GJ.

Division of Microbiology, Department of Oral Medicine and Periodontology, Faculty of Dental Sciences, University of Peradeniya, Peradeniya, Sri Lanka. sumedhaj@pdn.ac.lk

Onychomycosis is a common fungal infection affecting nails. The primary cause for onychomycosis is dermatophytes, while Candida species have emerged as second-line pathogens. Onychomycosis due to Candida (candidal onychomycosis) is increasingly found in individuals having defective immunity consequential to aging, diabetes mellitus, vascular diseases, HIV infection and drug therapies such as immunosuppressives and broad-spectrum antibiotics. Breached local immunity at the nail complex due to trauma, chronic exposure to moisture and chemicals including smoke, detergents, soap, etc., also contribute to candidal onychomycosis. Adhesion, filamentation, secretion of extracellular enzymes and the development of antifungal resistance are some of the virulence mechanisms of Candida species associated with onychomycosis. Diagnosis of onychomycosis depends on history and clinical examination, direct microscopic investigation, mycological culture and histopathology. Restoration of immune defenses, elimination of fungi using appropriate drug therapy and improvement of nail hygiene with the removal of predisposing factors are key aspects in the management of candidal onychomycosis.

PMID: 19484505 [PubMed - indexed for MEDLINE]

1164. Gastroenterology. 2009 Sep;137(3):914-23. Epub 2009 May 29.

Saccharomyces boulardii inhibits EGF receptor signaling and intestinal tumor growth in Apc(min) mice.

Chen X, Fruehauf J, Goldsmith JD, Xu H, Katchar KK, Koon HW, Zhao D, Kokkotou EG, Pothoulakis C, Kelly CP.

Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.

BACKGROUND & AIMS: Saccharomyces boulardii (Sb) is a probiotic yeast with anti-inflammatory and anti-microbial activities and has been used for decades in the prevention and treatment of a variety of human gastrointestinal disorders. We reported previously that Sb modulates host inflammatory responses through down-regulation of extracellular signal-regulated kinase (Erk)1/2 activities both in vitro and in vivo. The aim of this study was to identify upstream mediators responsible for extracellular signal-regulated kinase (Erk)1/2 inactivation and to examine the effects of Sb on tumor development in Apc(Min) mice.
METHODS: Signaling studies of colon cancer cells were done by western blot. Cell proliferation was measured by MTS and BrdU assay. Apoptosis was examined by flow cytometry, tunel assay and caspase assay. Apc(Min) mice were orally given Sb for 9 weeks before sacrifice for tumor analysis.
RESULTS: We found that the epidermal growth factor receptor (EGFR) was deactivated upon exposure to Sb, leading to inactivation of both the EGFR-Erk and EGFR-Akt pathways. In human colonic cancer cells, Sb prevented EGF-induced proliferation, reduced cell colony formation, and promoted apoptosis. HER-2, HER-3, and insulin-like growth factor-1 receptor were also found to be inactivated by Sb. Oral intake of Sb reduced intestinal tumor growth and dysplasia in C57BL/6J Min/+ (Apc(Min)) mice.
CONCLUSIONS: Thus, in addition to its anti-inflammatory effects, Sb inhibits EGFR and other receptor tyrosine kinase signaling and thereby may also serve a novel therapeutic or prophylactic role in intestinal neoplasia.

PMCID: PMC2777664 PMID: 19482027 [PubMed - indexed for MEDLINE]

1165. Early Hum Dev. 2009 Aug;85(8):531-5. Epub 2009 May 28.

Oxidative burst and phagocytosis of neonatal neutrophils confronting Candida albicans and Candida parapsilosis.

Destin KG, Linden JR, Laforce-Nesbitt SS, Bliss JM.

Department of Pediatrics, Women & Infants Hospital of Rhode Island, Warren Alpert Medical School of Brown University, Providence, RI 02905, USA.

BACKGROUND: Candida albicans and Candida parapsilosis are important causes of sepsis among premature neonates. The neutrophil is a key element in the control of Candida infections, yet specific neutrophil mechanisms that may contribute to the susceptibility of the premature neonate to candidiasis are not well understood. AIMS: The hypothesis for this study is that neonatal neutrophils have a developmental deficiency in their capacity to generate an oxidative burst in response to Candida species. STUDY DESIGN: Neutrophils were isolated from cord blood of term and preterm infants and from peripheral blood of adult volunteers. Neutrophils were exposed to Candida species, and assays of oxidative burst and phagocytosis were conducted.
RESULTS: Oxidative burst of neutrophils from term and preterm (22-29 weeks) neonates exposed to C. albicans hyphae was similar to adult neutrophils. No detectable burst was induced in either group by exposure to C. parapsilosis yeast, and was attenuated by exposure to C. albicans yeast. Because no deficiency in oxidative burst was seen, phagocytosis was also studied. Phagocytosis of unopsonized C. albicans yeast was low in both adult and neonatal neutrophils (10-12%), but was more efficient with C. parapsilosis as target (76-88%). Neutrophils from both term and preterm infants were capable of phagocytosis equivalent to adults.
CONCLUSION: A deficiency in generation of an oxidative burst or phagocytosis may not contribute to the increased susceptibility of preterm neonates to infections with Candida.

PMCID: PMC2752422 PMID: 19481378 [PubMed - indexed for MEDLINE]

1166. J Dent. 2009 Sep;37(9):666-72. Epub 2009 May 4.

Denture disinfection by microwave irradiation: a randomized clinical study.

Ribeiro DG, Pavarina AC, Dovigo LN, Palomari Spolidorio DM, Giampaolo ET, Vergani CE.

R. Humaitá n degrees 1680, CEP 14801-903, Department of Dental Materials and Prosthodontics, São Paulo State University, UNESP, Araraquara Dental School, Araraquara, São Paulo, Brazil.

OBJECTIVE: This study evaluated the clinical effectiveness of two exposure times of microwave irradiation on the disinfection of complete dentures.
METHODS: Biofilm samples were collected from dentures of 30 patients, who were randomly divided into two experimental groups of 15 subjects each: Group 1-patients had their maxillary denture microwaved for 3 min (650W); Group 2-patients had their maxillary denture microwaved for 2 min (650W). Denture biofilm samples were taken with swabs, before (left side surfaces) and after (right side surfaces) microwave irradiation. All microbial material was plated on selective media for Candida spp., Staphylococcus spp., mutans streptococci and a non-selective media. After incubation (48 h/37 degrees C), the number of colony-forming units (cfu/mL) was counted. Microorganisms which grew on selective media were identified using biochemical methods. The data were statistically analyzed by Kruskal-Wallis test, followed by Dunn's post-test (alpha=0.05).
RESULTS: Microwave irradiation for 3 min (Group 1) resulted in sterilization of all dentures evaluated. After microwave irradiation for 2 min (Group 2), a significant decrease in Candida spp. (P=0.0062), Staphylococcus spp. (P=0.0178), mutans streptococci (P=0.0047) and non-identified species (P<0.0001) was achieved in comparison with the cfu/mL obtained before irradiation. The colonies grown after 2 min of microwave irradiation were identified as Candida albicans, non-aureus Staphylococci and Streptococcus mutans.
CONCLUSION: Microwave irradiation for 3 min may be a potential treatment to prevent cross-contamination.

PMID: 19481327 [PubMed - indexed for MEDLINE]

1167. BMC Infect Dis. 2009 May 29;9:78.

Impact of infection control activities on the rate of needle stick injuries at a tertiary care hospital of Pakistan over a period of six years: an observational study.

Zafar A, Habib F, Hadwani R, Ejaz M, Khowaja K, Khowaja R, Irfan S.

Department of Pathology and Microbiology, Aga Khan University Hospital, Karachi, Pakistan. afia.zafar@aku.edu

BACKGROUND: Accidental exposure to blood and body fluids is frequent among health care workers. They are at high risk of nosocomial transmission of blood borne pathogens due to injuries caused by used sharps. We are reporting impact of surveillance and educational program on the rate of needle stick injuries among health care workers at a tertiary care hospital in Pakistan.
METHODS: At Aga Khan University Hospital sharp injuries are reported to infection control office. To reduce these incidents a quality improvement project was inducted in the year 2005. Health care workers were educated; surveillance data from 2002 to 2007 was analyzed and compared with various risk factors.
RESULTS: During study period 1382 incidents were reported. Junior doctors sustained highest number of injuries (n = 394; 28.5%) followed by registered nurses (n = 283; 20.4%). Highest number of incidents was reported during blood collection (19%). An increasing trend was observed in the pre intervention years (2002-04). However noticeable fall was noted in the post intervention period that is in year 2006 and 2007. Major decline was noted among nurses (from 13 to 5 NSI/100 FTE/year). By relating and comparing the rates with various activities directly linked with the use of syringes a significant reduction in incidents were found including; hospital admissions (p-value 0.01), surgeries and procedures performed (p = 0.01), specimens collected in the laboratory (p = 0.001) and patients visits in clinics (p = 0.01).
CONCLUSION: We report significant reduction in needle stick injuries especially during post intervention study period. This is being achieved by constant emphasis on improving awareness by regular educational sessions, implemented as a quality improvement project.

PMCID: PMC2692861 PMID: 19480683 [PubMed - indexed for MEDLINE]

1168. Clin Infect Dis. 2009 Jul 1;49(1):142-7.

Laboratory-acquired infections.

Singh K.

Department of Pathology and Infectious Diseases, Rush University Medical Center, Chicago, Illinois 60612, USA. Kamaljit_Singh@rush.edu

Laboratory-acquired infections due to a wide variety of bacteria, viruses, fungi, and parasites have been described. Although the precise risk of infection after an exposure remains poorly defined, surveys of laboratory-acquired infections suggest that Brucella species, Shigella species, Salmonella species, Mycobacterium tuberculosis, and Neisseria meningitidis are the most common causes. Infections due to the bloodborne pathogens (hepatitis B virus, hepatitis C virus, and human immunodeficiency virus) remain the most common reported viral infections, whereas the dimorphic fungi are responsible for the greatest number of fungal infections. Because of the increasing attention on the role of the laboratory in bioterrorism preparation, I discuss the risk of laboratory-acquired infection with uncommon agents, such as Francisella tularensis and Bacillus anthracis. Physicians who care for a sick laboratory worker need to consider the likelihood of an occupationally acquired infection while advising exposed laboratory workers about postexposure prophylaxis. In addition, physicians should be aware of the importance of alerting the laboratory if infection with a high-risk agent is suspected.

PMID: 19480580 [PubMed - indexed for MEDLINE]

1169. Am J Ind Med. 2009 Jul;52(7):563-70.

Occupational blood exposure among unlicensed home care workers and home care registered nurses: are they protected?

Lipscomb J, Sokas R, McPhaul K, Scharf B, Barker P, Trinkoff A, Storr C.

School of Nursing, University of Maryland, Baltimore, Maryland 21201, USA. lipscomb@son.umaryland.edu

BACKGROUND: Little is known about the risk of blood exposure among personnel providing care to individual patients residing at home. The objective of this study was to document and compare blood exposure risks among unlicensed home care personal care assistants (PCAs) and home care registered nurses (RNs).
METHODS: PCAs self-completed surveys regarding blood and body fluid (BBF) contact in group settings (n = 980), while RNs completed mailed surveys (n = 794).
RESULTS: PCAs experience BBF contact in the course of providing care for home-based clients at a rate approximately 1/3 the rate experienced by RNs providing home care (8.1 and 26.7 per 100 full time equivalent (FTE), respectively), and the majority of PCA contact episodes did not involve direct sharps handling. However, for PCAs who performed work activities such as handling sharps and changing wound dressings, activities much more frequently performed by RNs, PCAs were at increased risk of injury when compared with RNs (OR = 7.4 vs. 1.4) and (OR = 6.3 vs. 2.5), respectively.
CONCLUSION: Both PCAs and RNs reported exposures to sharps, blood, and body fluids in the home setting at rates that warrant additional training, prevention, and protection. PCAs appear to be at increased risk of injury when performing nursing-related activities for which they are inexperienced and/or lack training. Further efforts are needed to protect home care workers from blood exposure, namely by assuring coverage and enforcement of the Occupational Safety and Health Administration (OSHA) Bloodborne Pathogen Standard [Occupational Safety and Health Administration. 1993. Frequently Asked Questions Concerning the Bloodborne Pathogens Standard. Available at: http://www.osha.gov/pls/oshaweb/owadisp.show_document?p_table=INTERPRETATIONS &p_id=21010#Scope. Accessed May 30, 2008].

PMID: 19479817 [PubMed - indexed for MEDLINE]

1170. Disabil Rehabil. 2009;31(23):1963-9.

The psychological consequences of occupational blood and body fluid exposure injuries.

Wald J.

Department of Psychiatry, University of British Columbia, 2255 Wesbrook Mall, Vancouver, British Columbia, Canada. jwald@interchange.ubc.ca

PURPOSE: This article describes the psychological impact of occupational blood and body fluid (BBF) exposure injuries and provides suggestions for improving clinical practice. METHOD: A literature review was conducted to search for articles relating to the psychological consequences and management of these work injuries.
RESULTS: Acute psychological symptoms including posttraumatic stress, anxiety and depression are frequently experienced postexposure, which appear to be the major contributing factors of time loss from work. Furthermore, a subgroup is at risk for chronic symptoms and disability that persists beyond notification that no disease transmission occurred. Distressed workers often go unrecognised and untreated, and their assistance needs are largely unknown. Accordingly, this article draws upon the posttraumatic stress literature to offer suggestions for advancing the postexposure management of these injuries.
CONCLUSIONS: This clinical commentary underscores the serious yet understudied secondary psychological effects of occupational BBF exposure injuries. Postexposure management programmes need to place greater emphasis on psychosocial and educational initiatives to improve the identification and treatment of symptomatic workers.

PMID: 19479544 [PubMed - indexed for MEDLINE]

1171. Bull Environ Contam Toxicol. 2009 Dec;83(6):852-8.

Monitoring of traffic-related pollution in a province of central Italy with transplanted lichen Pseudovernia furfuracea.

Guidotti M, Stella D, Dominici C, Blasi G, Owczarek M, Vitali M, Protano C.

Agenzia Regionale per la Protezione Ambientale del Lazio, Sezione di Rieti, Via Salaria per l'Aquila, 8, 02100 Rieti, Italy.

The ability of transplanted lichen Pseudevernia furfuracea to biomonitor specific airborne pollutants (heavy metals and polycyclic aromatic hydrocarbons—PAHs) was investigated at five stations with different traffic densities in Viterbo, Italy. Exposed lichen showed high levels of all analysed pollutants; greatest values were for Zn (147–252 μg/g dw), Pb (24.9–34.6 μg/g dw), fluoranthene (37–107 ng/g dw), pyrene (23–124 ng/g dw). Comparison between contaminants concentration in lichens before and after exposure showed "accumulation" or "severe accumulation" rates in more than 90% of each substance. Besides, Pseudevernia furfuracea accumulated airborne PAHs in a manner that was proportional to traffic density.

PMID: 19479172 [PubMed - indexed for MEDLINE]

1172. Mol Biol Cell. 2009 Aug;20(15):3572-82. Epub 2009 May 28.

The stress-activated protein kinase Hog1 mediates S phase delay in response to osmostress.

Yaakov G, Duch A, García-Rubio M, Clotet J, Jimenez J, Aguilera A, Posas F.

Cell Signaling Unit, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, 08003 Barcelona, Spain.

Control of cell cycle progression by stress-activated protein kinases (SAPKs) is essential for cell adaptation to extracellular stimuli. Exposure of yeast to osmostress activates the Hog1 SAPK, which modulates cell cycle progression at G1 and G2 by the phosphorylation of elements of the cell cycle machinery, such as Sic1 and Hsl1, and by down-regulation of G1 and G2 cyclins. Here, we show that upon stress, Hog1 also modulates S phase progression. The control of S phase is independent of the S phase DNA damage checkpoint and of the previously characterized Hog1 cell cycle targets Sic1 and Hsl1. Hog1 uses at least two distinct mechanisms in its control over S phase progression. At early S phase, the SAPK prevents firing of replication origins by delaying the accumulation of the S phase cyclins Clb5 and Clb6. In addition, Hog1 prevents S phase progression when activated later in S phase or cells containing a genetic bypass for cyclin-dependent kinase activity. Hog1 interacts with components of the replication complex and delays phosphorylation of the Dpb2 subunit of the DNA polymerase. The two mechanisms of Hog1 action lead to delayed firing of origins and prolonged replication, respectively. The Hog1-dependent delay of replication could be important to allow Hog1 to induce gene expression before replication.

PMCID: PMC2719575 PMID: 19477922 [PubMed - indexed for MEDLINE]

1173. Innate Immun. 2009 Jun;15(3):155-68.

Activation of Toll-like receptors 2 and 4 in Aspergillus fumigatus keratitis.

Jie Zhao, Wu XY, Yu FS.

Department of Ophthalmology, Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan, China.

Toll-like receptor (TLR) 2 and TLR4 are major receptors of Aspergillus fumigatus. Aspergillus fumigatus signaling in cornea induces the production of many pro-inflammatory molecules. In this study, we have shown that exposure of telomerase-immortalized human corneal epithelial cells (HCECs) to A. fumigatus antigens resulted in up-regulation of TLR2 and TLR4, and release of IL-1beta and IL-10 in HCECs, effects that could be inhibited by treatment with TLR2, and TLR4 antibodies. In addition, the A. fumigatus antigens-induced production of IL-1beta and IL-10 in supernatants of corneal epithelial cells was also attenuated by NF-kappaB inhibitor. Aspergillus fumigatus keratitis developed in Wistar rats, as evidenced by high SLE scores, influx of polymorphonuclear leukocytes (PMNs), activation of TLR2 and TLR4, and production of IL-1beta and IL-10 over controls. These findings indicate that the cornea has functional TLR2 and TLR4, and activation of TLR2 and TLR4 through NF-kappaB may contribute to pathogenesis of keratomycosis.

PMID: 19474209 [PubMed - indexed for MEDLINE]

1174. Genome Biol. 2009;10(5):R57. Epub 2009 May 26.

The histone deacetylase Rpd3p is required for transient changes in genomic expression in response to stress.

Alejandro-Osorio AL, Huebert DJ, Porcaro DT, Sonntag ME, Nillasithanukroh S, Will JL, Gasch AP.

Department of Biomolecular Chemistry, University of Wisconsin-Madison, University Avenue, Madison, WI 53706, USA. adriana.alejandro@gmail.com

BACKGROUND: Yeast responding to stress activate a large gene expression program called the Environmental Stress Response that consists of approximately 600 repressed genes and approximately 300 induced genes. Numerous factors are implicated in regulating subsets of Environmental Stress Response genes; however, a complete picture of Environmental Stress Response regulation remains unclear. We investigated the role of the histone deacetylase Rpd3p, previously linked to the upstream regions of many Environmental Stress Response genes, in producing Environmental Stress Response gene expression changes in response to stress.
RESULTS: We found that the Rpd3-Large complex is required for proper expression of both induced and repressed Environmental Stress Response genes under multiple stress conditions. Cells lacking RPD3 or the Rpd3-Large subunit PHO23 had a major defect in Environmental Stress Response initiation, particularly during the transient phase of expression immediately after stress exposure. Chromatin-immunoprecipitation showed a direct role for Rpd3-Large at representative genes; however, there were different effects on nucleosome occupancy and histone deacetylation at different promoters. Computational analysis implicated regulators that may act with Rpd3p at Environmental Stress Response genes. We provide genetic and biochemical evidence that Rpd3p is required for binding and action of the stress-activated transcription factor Msn2p, although the contribution of these factors differs for different genes.
CONCLUSIONS: Our results implicate Rpd3p as an important co-factor in the Environmental Stress Response regulatory network, and suggest the importance of histone modification in producing transient changes in gene expression triggered by stress.

PMCID: PMC2718523 PMID: 19470158 [PubMed - indexed for MEDLINE]

1175. Pol J Microbiol. 2009;58(1):29-36.

Production and characterization of alpha-amylase from Aspergillus niger JGI 24 isolated in Bangalore.

Varalakshmi KN, Kumudini BS, Nandini BN, Solomon J, Suhas R, Mahesh B, Kavitha AP.

Department of Biotechnology, Centre for Post-Graduate Studies, Shri Bhagawan Mahaveer Jain College, Jayanagar, Bangalore. varalakshmikn@yahoo.co.in

Five fungal isolates were screened for the production of alpha-amylase using both solid-state and submerged fermentations. The best amylase producer among them, Aspergillus niger JGI 24, was selected for enzyme production by solid-state fermentation (SSF) on wheat bran. Different carbon and nitrogen supplements were used to enhance enzyme production and maximum amount of enzyme was obtained when SSF was carried out with soluble starch and beef extract (1% each) as supplements. Further attempts to enhance enzyme production by UV induced mutagenesis were carried out. Survival rate decreased with increase in duration of UV exposure. Partial purification of the enzyme using ammonium sulphate fractionation resulted in 1.49 fold increase in the enzyme activity. The enzyme showed a molecular weight of 43 kDa by SDS-PAGE. Metal ions Ca2+ and Co2+ increased the enzyme activity. The enzyme was optimally active at 30 degrees C and pH 9.5.

PMID: 19469283 [PubMed - indexed for MEDLINE]

1176. Plant Physiol Biochem. 2009 Sep;47(9):796-806. Epub 2009 May 9.

Roles of a membrane-bound caleosin and putative peroxygenase in biotic and abiotic stress responses in Arabidopsis.

Partridge M, Murphy DJ.

Biotechnology Unit, Division of Biological Sciences, University of Glamorgan, Treforest, CF37 1DL, United Kingdom.

We report here the localisation and properties of a new membrane-bound isoform of caleosin and its putative role as a peroxygenase involved in oxylipin metabolism during biotic and abiotic stress responses in Arabidopsis. Caleosins are a family of lipid-associated proteins that are ubiquitous in plants and true fungi. Previous research has focused on lipid-body associated, seed-specific caleosins that have peroxygenase activity. Here, we demonstrate that a separate membrane-bound constitutively expressed caleosin isoform (Clo-3) is highly upregulated following exposure to abiotic stresses, such as salt and drought, and to biotic stress such as pathogen infection. The Clo-3 protein binds one atom of calcium per molecule, is phosphorylated in response to stress, and has a similar peroxygenase activity to the seed-specific Clo-1 isoform. Clo-3 is present in microsomal and chloroplast envelope fractions and has a type I membrane orientation with about 2 kDa of the C terminal exposed to the cytosol. Analysis of Arabidopsis ABA and related mutant lines implies that Clo-3 is involved in the generation of oxidised fatty acids in stress related signalling pathways involving both ABA and salicylic acid. We propose that Clo-3 is part of an oxylipin pathway induced by multiple stresses and may also generate fatty acid derived anti-fungal compounds for plant defence.

PMID: 19467604 [PubMed - indexed for MEDLINE]

1177. J Occup Med Toxicol. 2009 May 25;4:10.

Influence of horse stable environment on human airways.

Elfman L, Riihimäki M, Pringle J, Wålinder R.

Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University Hospital, SE-751 85 Uppsala, Sweden. lena.elfman@medsci.uu.se.

BACKGROUND: Many people spend considerable amount of time each day in equine stable environments either as employees in the care and training of horses or in leisure activity. However, there are few studies available on how the stable environment affects human airways. This study examined in one horse stable qualitative differences in indoor air during winter and late summer conditions and assessed whether air quality was associated with clinically detectable respiratory signs or alterations to selected biomarkers of inflammation and lung function in stable personnel.
METHODS: The horse stable environment and stable-workers (n = 13) in one stable were investigated three times; first in the winter, second in the interjacent late summer and the third time in the following winter stabling period. The stable measurements included levels of ammonia, hydrogen sulphide, total and respirable dust, airborne horse allergen, microorganisms, endotoxin and glucan. The stable-workers completed a questionnaire on respiratory symptoms, underwent nasal lavage with subsequent analysis of inflammation markers, and performed repeated measurements of pulmonary function.
RESULTS: Measurements in the horse stable showed low organic dust levels and high horse allergen levels. Increased viable level of fungi in the air indicated a growing source in the stable. Air particle load as well as 1,3-beta-glucan was higher at the two winter time-points, whereas endotoxin levels were higher at the summer time-point. Two stable-workers showed signs of bronchial obstruction with increased PEF-variability, increased inflammation biomarkers relating to reported allergy, cold or smoking and reported partly work-related symptoms. Furthermore, two other stable-workers reported work-related airway symptoms, of which one had doctor's diagnosed asthma which was well treated.
CONCLUSION: Biomarkers involved in the development of airway diseases have been studied in relation to environmental exposure levels in equine stables. Respirable dust and 1,3-beta-glucan levels were increased at winter stabling conditions. Some employees (3/13) had signs of bronchial obstruction, which may be aggravated by working in the stable environment. This study contributes to the identification of suitable biomarkers to monitor the indoor horse stable environment and the personnel. An improved management of the stable climate will be beneficial for the health of both stable workers and horses.

PMCID: PMC2693518 PMID: 19467158 [PubMed]

1178. J Invertebr Pathol. 2009 Jul;101(3):234-41. Epub 2009 May 20.

Cellular encapsulation in the eastern subterranean termite, Reticulitermes flavipes (Isoptera), against infection by the entomopathogenic fungus Metarhizium anisopliae.

Chouvenc T, Su NY, Robert A.

Department of Entomology and Nematology, Ft. Lauderdale Research and Education Center, University of Florida, Institute of Food and Agricultural Sciences, Davie, FL 33314, USA. tomchouv@ufl.edu

Reticulitermes flavipes workers were topically inoculated with approximately 10,000 conidia of the entomopathogenic fungus Metarhizium anisopliae. After being kept in groups of 20 individuals for 1-9 d, histopathological examination showed that termites had an individual immune reaction. The nodule formation at the point of entrance of the fungal hyphae was identified as a cellular encapsulation and the different steps in the nodule formation are described. The relative number of hemocytes per termite increased 24h after fungal exposure and remained high in the hemolymph for at least 3 d before decreasing back to pre-exposure levels. The role of an individual immune cellular reaction in social insects is discussed.

PMID: 19463828 [PubMed - indexed for MEDLINE]

1179. Infect Genet Evol. 2009 Jul;9(4):493-500. Epub 2009 Jan 30.

Distribution of mutations distinguishing the most prevalent disease-causing Candida albicans genotype from other genotypes.

Zhang N, Upritchard JE, Holland BR, Fenton LE, Ferguson MM, Cannon RD, Schmid J.

Institute for Molecular Biosciences, Massey University, Palmerston North, New Zealand.

Candida albicans is a major opportunistic pathogen of humans. Previous work has demonstrated the existence of a general-purpose genotype (GPG; equivalent to clade 1 as defined by multi-locus sequence typing data) that is more frequent than other genotypes as an agent of human disease and commensal colonization. We undertook a genomic screen which indicated that a large number of mutations differentiate GPG strains from other strains and that such mutations are scattered throughout the genome. GPG-specific mutations are non-synonymous more frequently than expected by chance, and are not randomly distributed across functional and structural gene categories. Our analysis has identified three categories of genes in which GPG-specific mutations are over-represented, namely genes for which expression changes during the yeast-hyphal transition, genes for which expression changes as a result of exposure to antifungal agents and repeat-containing ORFs. Although we have no direct evidence that the individual polymorphisms identified confer selective advantages to GPG strains, the results support our contention that the high prevalence of GPG strains is not merely due to genetic drift but that GPG strains have reached a high prevalence because they possess a multitude of fitness-enhancing traits. They also indicate that the distribution of genes marked by GPG-specific mutations across functional and structural categories could identify physiological traits that are of particular importance to the success of GPG strains in their interactions with the human host.

PMID: 19460314 [PubMed - indexed for MEDLINE]

1180. MLO Med Lab Obs. 2009 Apr;41(4):40.

Prepare for occupational bloodborne pathogen exposure.

Harty-Golder B.

toadehall@comcast.net

PMID: 19456064 [PubMed - indexed for MEDLINE]

1181. FEMS Microbiol Ecol. 2009 Jul;69(1):132-41. Epub 2009 Apr 27.

Weathering of chrysotile asbestos by the serpentine rock-inhabiting fungus Verticillium leptobactrum.

Daghino S, Turci F, Tomatis M, Girlanda M, Fubini B, Perotto S.

Interdepartmental Centre G. Scansetti for Studies on Asbestos and Other Toxic Particulates, University of Torino, 10125 Turin, Italy.

Verticillium leptobactrum, a rare fungal species, has repeatedly been isolated from serpentinic rocks in the Western Alps, thus suggesting that it adapts easily to this selective mineral substrate. The rRNA internal transcribed spacer region of several isolates has been sequenced to confirm their identity and taxonomic position within Verticillium, a recently revised polyphyletic entity. Isolates of V. leptobactrum have also been investigated to establish their ability to weather asbestos chrysotile, the most common mineral in the isolation sites. The results of solubilization assays on magnesium and silicon, as well as measurement of the Mg/Si ratio in the asbestos fibres after exposure to fungal mycelia, indicate a high bioweathering activity of V. leptobactrum towards chrysotile. Comparison with data on Fusarium oxysporum shows differences among species, with V. leptobactrum being more active than F. oxysporum in removing structural ions from chrysotile. Asbestos weathering by fungi could be envisaged as a bioremediation strategy for hazardous asbestos-rich soils (e.g. abandoned mines). Fungi that have adapted to live in serpentine sites could be good candidates for this purpose.

PMID: 19453742 [PubMed - indexed for MEDLINE]

1182. Annu Rev Microbiol. 2009;63:119-31.

Lipid signaling in pathogenic fungi.

Rhome R, Del Poeta M.

Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina 29425, USA. rhome@musc.edu

Lipid signaling in pathogenic fungi has been studied to determine the role of these pathways in fungal biology and human infections. Owing to their unique nature, they may represent targets for future antifungal treatments. Farnesol signaling was characterized as a quorum-sensing molecule, with exposure inhibiting filamentation. Research has shown involvement in both the Ras1-adenylate cyclase and MAP kinase pathways. In species of Aspergillus, farnesol exposure induces apoptosis-like changes and alterations in ergosterol synthesis. Eicosanoid production has been characterized in several pathogenic fungi, utilizing host lipids in some cases. The role in virulence is not known yet, but it may involve modulation of host lipids. Sphingolipid signaling pathways seem to center around the production of diacylglycerol in the formation of inositol phosphorylceramide. Diacylglycerol activates both melanin production through laccase and transcription of antiphagocytic protein, both of which are involved in virulence.

PMID: 19450140 [PubMed - indexed for MEDLINE]

1183. IET Syst Biol. 2009 May;3(3):203-18.

Discrete dynamical system modelling for gene regulatory networks of 5-hydroxymethylfurfural tolerance for ethanologenic yeast.

Song M, Ouyang Z, Liu ZL.

Department of Computer Science, New Mexico State University, Las Cruces, NM 88003, USA. joemsong@cs.nmsu.edu

Composed of linear difference equations, a discrete dynamical system (DDS) model was designed to reconstruct transcriptional regulations in gene regulatory networks (GRNs) for ethanologenic yeast Saccharomyces cerevisiae in response to 5-hydroxymethylfurfural (HMF), a bioethanol conversion inhibitor. The modelling aims at identification of a system of linear difference equations to represent temporal interactions among significantly expressed genes. Power stability is imposed on a system model under the normal condition in the absence of the inhibitor. Non-uniform sampling, typical in a time-course experimental design, is addressed by a log-time domain interpolation. A statistically significant DDS model of the yeast GRN derived from time-course gene expression measurements by exposure to HMF, revealed several verified transcriptional regulation events. These events implicate Yap1 and Pdr3, transcription factors consistently known for their regulatory roles by other studies or postulated by independent sequence motif analysis, suggesting their involvement in yeast tolerance and detoxification of the inhibitor.

PMID: 19449980 [PubMed - indexed for MEDLINE]

1184. J Immigr Minor Health. 2010 Oct;12(5):617-25.

Housing environments and child health conditions among recent Mexican immigrant families: a population-based study.

Litt JS, Goss C, Diao L, Allshouse A, Diaz-Castillo S, Bardwell RA, Hendrikson E, Miller SL, DiGuiseppi C.

Department of Environmental & Occupational Health, Colorado School of Public Health, University of Colorado Denver, Denver, CO 80045, USA. jill.litt@ucdenver.edu

The influx of immigrants to urban areas throughout the United States has raised concerns about accessibility of safe, affordable housing and the health consequences of poor-quality housing, particularly among immigrant children. We conducted a population-based study of home environmental conditions among recently immigrated Mexican families (weighted n = 473), generally of low socioeconomic status, and the health conditions of their children, in an urban industrial area north of Denver, Colorado. The majority of recent immigrants had low socioeconomic status; virtually all had household incomes below the Colorado median ($50,841). Approximately one quarter of homes were overcrowded. Adverse environmental conditions were present across recent immigrant homes. These conditions include dampness or mold (44%), pests (28%), and minimal to no ventilation potential (26%), all of which are associated with asthma and atopic diseases. At least one of these three environmental hazards was found in 67% of homes; multiple hazards were present in 27% of homes. Children of recent immigrant families had active symptoms within the past 12 months suggestive of asthma (4%) and atopic disorders (10%); however, fewer than 2% had been diagnosed with these conditions. The prevalence of asthma and atopic symptoms among Mexican immigrant children, albeit lower than in other low income and minority communities, is partially explained by housing conditions. Many of the conditions identified (e.g., pest infestation, mold resulting from plumbing leaks, and lack of exhaust fans) are amenable to low cost interventions. Solutions to address unhealthy housing conditions among recent immigrants must be multi-faceted and include strategies that target household-level improvements and access to health care.

PMID: 19449207 [PubMed - indexed for MEDLINE]

1185. J Environ Radioact. 2009 Dec;100(12):1034-52. Epub 2009 May 17.

Assessing radiation impact at a protected coastal sand dune site: an intercomparison of models for estimating the radiological exposure of non-human biota.

Wood MD, Beresford NA, Barnett CL, Copplestone D, Leah RT.

Institute for Sustainable Water Integrated Management and Ecosystem Research (SWIMMER), Nicholson Building, University of Liverpool, Liverpool, Merseyside L69 3GP, United Kingdom. mwood@liv.ac.uk

This paper presents the application of three publicly available biota dose assessment models (the ERICA Tool, R&D128/SP1a and RESRAD-BIOTA) to an assessment of the Drigg coastal sand dunes. Using measured (90)Sr, (99)Tc, (137)Cs, (238)Pu, (239+240)Pu and (241)Am activity concentrations in sand dune soil, activity concentration and dose rate predictions are made for a range of organisms including amphibians, birds, invertebrates, mammals, reptiles, plants and fungi. Predicted biota activity concentrations are compared to measured data where available. The main source of variability in the model predictions is the transfer parameters used and it is concluded that developing the available transfer databases should be a focus of future research effort. The value of taking an informed user approach to investigate the way in which models may be expected to be applied in practice is highlighted and a strategy for the future development of intercomparison exercises is presented.

PMID: 19447531 [PubMed - indexed for MEDLINE]

1186. FEBS Lett. 2009 Jun 18;583(12):2015-20. Epub 2009 May 15.

The yeast MAPK Hog1 is not essential for immediate survival under osmostress.

Maayan I, Engelberg D.

Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.

The yeast HOG pathway is activated in response to increased osmolarity and affects many cellular activities. As cells lacking Hog1 are osmo-sensitive it is believed that Hog1 is essential for survival under osmostress. We show, however, that hog1Delta cells survive and even proliferate to some degree under high osmostress for many hours. If forced to enter G1/G0 prior the exposure to osmostress, hog1Delta cells survive for at least 6days. We suggest that the primary role of Hog1 is not to preserve viability upon exposure to stress. We discuss the possibility that Hog1 is needed for proliferation under osmostress.

PMID: 19447106 [PubMed - indexed for MEDLINE]

1187. Biochim Biophys Acta. 2009 Aug;1790(8):770-7. Epub 2009 May 13.

Plagiochin E, an antifungal bis(bibenzyl), exerts its antifungal activity through mitochondrial dysfunction-induced reactive oxygen species accumulation in Candida albicans.

Wu XZ, Cheng AX, Sun LM, Sun SJ, Lou HX.

School of Pharmaceutical Sciences, Shandong University, No. 44 West Wenhua Road, Jinan 250012, PR China.

BACKGROUND: Plagiochin E (PLE) is an antifungal macrocyclic bis(bibenzyl) isolated from liverwort Marchantia polymorpha L. Its antifungal mechanism is unknown. To elucidate the mechanism of action, its effect on mitochondria function in Candida albicans was studied.
METHODS: We assayed the mitochondrial membrane potential (mtDeltapsi) using rhodamine 123, measured ATP level in mitochondria by HPLC, and detected the activities of mitochondrial F(0)F(1)-ATPase and dehydrogenases. Besides, the mitochondrial dysfunction-induced reactive oxygen species (ROS) production was determined by a fluorometric assay, and the effects of antioxidant L-cysteine on PLE-induced ROS production and the antifungal effect of PLE on C. albicans were also investigated.
RESULTS: Exposure to PLE resulted in an elevation of mtDeltapsi, and a decrease of ATP level in mitochondria. The ATP depletion owed to PLE-induced enhancement of mitochondrial F(0)F(1)-ATPase and inhibition of the mitochondrial dehydrogenases. These dysfunctions of mitochondria caused ROS accumulation in C. albicans, and this increase in the level of ROS production and PLE-induced decrease in cell viability were prevented by addition of L-cysteine, indicating that ROS was an important mediator of the antifungal action of PLE.
CONCLUSIONS: PLE exerts its antifungal activity through mitochondrial dysfunction-induced ROS accumulation in C. albicans.
GENERAL SIGNIFICANCE: The effect of PLE on the mitochondria function in C. albicans was assayed for the first time. These results would conduce to elucidate its underlying antifungal mechanism.

PMID: 19446008 [PubMed - indexed for MEDLINE]

1188. Neurotoxicology. 2009 Jul;30(4):666-76. Epub 2009 May 13.

Proteome response to ochratoxin A-induced apoptotic cell death in mouse hippocampal HT22 cells.

Yoon S, Cong WT, Bang Y, Lee SN, Yoon CS, Kwack SJ, Kang TS, Lee KY, Choi JK, Choi HJ.

College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju 500-757, South Korea.

Mycotoxins are commonly encountered natural products, and are capable of poisoning animals or humans that inhale mold particles from mycotoxin-contaminated foods. Ochratoxin A (OTA) is produced by Aspergillu ochracus and Penicillium verrucosum, and is often found in cereals and agricultural products. Although previous studies have focused on the potent nephrotoxicity and renal carcinogenicity of OTA, more recent studies suggest that it accumulates in the brain and causes oxidative stress and DNA damage in various brain regions and neuronal populations. In the present study, we undertook to investigate the potential harm caused by environmental exposure to OTA in terms of its effects on neuronal cell viability and proteome profiles. OTA was found to significantly reduce the viabilities of human neuroblastoma SH-SY5Y and mouse hippocampal HT22 cells, as assessed by lactic dehydrogenase release into culture media. Generation of reactive oxygen species was detected in OTA-treated SH-SY5Y and HT22 cells, however, caspase activation and increase in p53 phosphorylation were only detected in HT22 cells, and the expressions of several proteins were found to be significantly altered after treating HT22 cells with OTA. Valosin containing protein, prolyl 4-hydroxylase, Atp5b protein, nucleophosmin 1, eukaryotic translation elongation factor 1 delta isoform, ornithine aminotransferase, prohibitin, and peroxiredoxin 6, which have been suggested to be implicated in the pathogenesis of neurodegenerative disorders, were up-regulated. Our findings suggest that coordinated regulations of molecular networks are involved in the OTA-induced cytotoxicity and that proteome response can be an indicative for neurodegeneration.

PMID: 19445961 [PubMed - indexed for MEDLINE]

1189. Public Health Rep. 2009 May-Jun;124(3):436-41.

Do obese adults have a higher risk of asthma attack when exposed to indoor mold? A study based on the 2005 Behavioral Risk Factor Surveillance System.

Wen XJ, Balluz L, Mokdad A.

Behavioral Surveillance Branch, National Center for Chronic Diseases/Division of Adult and Community Health, Centers for Disease Control and Prevention, 4770 Buford Hwy., MS-K66, Atlanta, GA 30341, USA.

OBJECTIVE: Some studies show an association between asthma and obesity, but it is unknown whether exposure to mold will increase the risk of asthma attacks among obese people. This study examined whether obese adults have a higher risk of asthma attacks than non-obese adults when exposed to indoor mold.
METHODS: We used data from the 2005 Behavioral Risk Factor Surveillance System to conduct a cross-sectional analysis among 9,668 respondents who reported exposure to indoor mold.
RESULTS: With exposure to indoor mold, weighted prevalence of asthma attacks among obese respondents was 11.4% (95% confidence interval [CI] 6.0, 20.6], which was 2.3 times as high as among the exposed non-obese respondents (5.0%, 95% CI 2.8, 8.8). This ratio was almost the same as the ratio of 2.0:1 between the obese respondents (5.7%, 95% CI 4.6, 7.2) and the non-obese respondents (2.8%, 95% CI 2.3, 3.9) when neither group had exposure to mold. The odds ratio of asthma attack among obese people was 3.10 (95% CI 1.10, 8.67) for those with exposure to mold and 2.21 (95% CI 1.54, 3.17) for those without exposure to mold after adjusting for age, sex, race/ethnicity, and smoking status.
CONCLUSION: Our study suggests that obese adults who have been exposed to indoor mold may not necessarily have a higher risk of asthma attack than obese adults who have not been exposed, even though obesity and exposure to indoor mold are both major risk factors for asthma attack. Medical professionals should not only incorporate weight-control or weight-reduction measures as the components of asthma treatment plans, but also advise asthma patients to avoid exposure to indoor mold.

PMCID: PMC2663880 PMID: 19445420 [PubMed - indexed for MEDLINE]

1190. Guang Pu Xue Yu Guang Pu Fen Xi. 2009 Feb;29(2):428-31.

[Investigation on low power microwave irradiation-assisted enzymatic esterification in organic solvent by fluorescence spectroscopy].

[Article in Chinese]

Min R, Fang Y, Xia YM.

School of Chemical & Materical Engineering, Jiangnan University, Wuxi 214122, China.

The authors studied the fluorescence change of immobilized lipase from Rhizomucor miehei in the microwave assisted enzymatic esterification of caprylic acid and butanol in organic medium by investigating the fluorescence spectra in solvent or aqueous buffer after incubating the lipase with the solvent, caprylic acid and butanol under microwave irradiation, respectively. A comparison was made with the conventional heated enzymatic esterification in the solvents. Both of the heating modes, the microwave irradiation and conventional heating, can enhance the fluorescence intensity without shifting the emission wavelength of the lipase. In the circumstance that the irradiation can accelerate the esterification, the irradiation can enhance the exposure of the lipase protein molecules in the aqueous environment after incubating the lipase with solvents or the substrates. The effect of the reaction mixture on the fluorescence intensity was dominated by the solvents. The trend of the plot of log P versus the initial reaction rate was similar to that of log P versus fluorescence intensity of lipase in aqueous buffer after esterification; but was different from that of log P versus fluorescence intensity of lipase in organic medium.

PMID: 19445220 [PubMed - indexed for MEDLINE]

1191. J Hosp Infect. 2009 Aug;72(4):285-91. Epub 2009 May 13.

Occupational transmission of bloodborne diseases to healthcare workers in developing countries: meeting the challenges.

Lee R.

Nuffield Centre for International Health and Development, Leeds, UK. beckilee@doctors.org.uk

Healthcare workers have increased chance of acquiring bloodborne pathogens through occupational exposure in developing countries due to a combination of increased risk and fewer safety precautions. As loss of workers can seriously undermine developing health systems, it is important that risks are minimised. A literature search was conducted to investigate the risks of transmission of three pathogens: human immunodeficiency virus, hepatitis B and hepatitis C viruses; and to identify factors that influenced the risk with reference to developing countries. There are many difficulties faced by developing countries in minimising the risk of occupational exposure. Efforts have been made to address the problems both on international and national levels. It is imperative that all healthcare workers are protected in order to prevent the loss of such a crucial component of developing healthcare systems.

PMID: 19443081 [PubMed - indexed for MEDLINE]

1192. Arch Bronconeumol. 2009 Jun;45(6):304-5. Epub 2009 May 12.

[Hypersensitivity pneumonitis caused by Trichoderma viride].

[Article in Spanish]

Enríquez-Matas A, Quirce S, Cubero N, Sastre J, Melchor R.

Departamento de Alergia, Fundación Jiménez Díaz, Madrid, España. aenriquezmatas@hotmail.com

Hypersensitivity pneumonitis (HP) can be induced by exposure to indoor molds contaminating humidifiers and heating or ventilation systems. A 54-year-old woman with dyspnea, cough, chest pain, and fever was seen in the emergency room. A chest radiograph revealed interstitial infiltrates and blood tests showed leukocytosis with neutrophilia and severe hypoxemia. A diagnosis of HP was made by a combination of clinical, radiologic, physiologic, and immunologic studies. Trichoderma viride was isolated in cultures of water samples from an ultrasonic humidifier installed in the patient's home a year earlier. Precipitating immunoglobulin G antibodies to T viride were detected in the patient's serum by enzyme-linked immunosorbent assay. The patient remained symptom free after the humidifier was removed from her home. Our findings strongly suggest that the patient developed HP due to T viride from the humidifier. To our knowledge, this is the first report of such a case.

PMID: 19442428 [PubMed - indexed for MEDLINE]

1193. J Nanosci Nanotechnol. 2009 Jan;9(1):562-6.

Effect of post exposure bake in inorganic electron beam resist and utilizing for nanoimprint mold.

Shizuno M, Taniguchi J, Ogino K, Ishikawa K.

Department of Applied Electronics, Tokyo University of Science, 2461 Yamazaki, Noda, Chiba, 278-8510, Japan.

A high-aspect-ratio structural mold has been fabricated using a simple process that comprises of electron beam lithography (EBL) and post exposure bake (PEB) of inorganic resist. Using developed inorganic resist for mold, pattern transfer to a photo-curable polymer was carried out by ultraviolet nanoimprint lithography (UV-NIL). The developed inorganic resist has enough hardness to be used for mold because this resist structure is almost equivalent to that of quartz. The aspect ratio of the fabricated mold with PEB was 2.59; this value is twice the size of aspect ratio of fabricated mold without PEB (1.16). Thus, PEB is very effective in fabricating high-aspect ratio pattern in inorganic resist. The size of the fabricated mold with PEB was 1004 nm developed depth and 388 nm line and 252 nm space. Using the mold, UV-NIL was carried out. The size of replicated pattern was 942 nm height and 278 nm line and 241 nm space. The replicated height and line width were slightly smaller than mold depth and line width because of volume shrinkage of photo-curable polymer by UV irradiation. The aspect ratio of the replicated pattern using the mold with PEB was 3.39; thus, high-aspect-ratio transfer was also possible. This process is useful for rapid fabrication of quarter wavelength plates.

PMID: 19441350 [PubMed]

1194. Microb Ecol. 2009 Nov;58(4):715-27. Epub 2009 May 14.

Do botanical pesticides alter the structure of the soil microbial community?

Spyrou IM, Karpouzas DG, Menkissoglu-Spiroudi U.

School of Agriculture, Laboratory of Pesticide Science, Aristotle University of Thessaloniki, Thessaloniki, 54124, Greece.

The effects of synthetic pesticides on the soil microbial community have been thoroughly investigated in the past mostly by culture-dependent methods and only few recent studies have used culture-independent approaches for this purpose. However, it should be noted that most of these studies have been conducted in microcosms where the soil microbial community is exposed to unrealistic concentrations of the pesticides, providing an unrealistic exposure scheme for soil microorganism. On the other hand, little is known regarding the potential impact of botanical pesticides on the soil microbial community. Therefore, a laboratory study and a field study were conducted to investigate the effects of synthetic (metham sodium [MS], sodium tetrathiocarbonate [SoTe], and fosthiazate) and botanical pesticides (azadirachtin, quillaja, and pulverized Melia azedarach fruits [PMF]) on the soil microbial community using phospholipid fatty acids (PLFA) analysis. Principal component analysis (PCA) on the results of the laboratory study indicated that the application of PMF resulted in significant changes in the soil microbial community. This was obvious by the proportional increase in the abundance of fatty acids 18:1omega9cis, 18:1omega9trans, which are common in gram-negative bacteria and saprotrophic fungi, and 18:2omega6,9, which is a fungal indicator. This response was attributed to the release of copious amounts of organic carbon and nutrients in the soil by the PMF. On the other hand, MS inhibited fungi and gram-negative bacteria, while fosthiazate and the botanical pesticides quillaja and azadirachtin did not impose significant changes in the soil microbial community. Similar results were obtained by the field study where application of the fumigants MS and SoTe significantly altered the structure of the soil microbial community with the former having a more prominent effect. Fosthiazate imposed mild changes in the soil microbial community, whereas quillaja and azadirachtin again did not show a significant effect. Overall, botanical pesticides, at their recommended dose, did not alter the structure of the soil microbial community compared to synthetic nonfumigant and fumigant pesticides which induced significant changes.

PMID: 19440648 [PubMed - indexed for MEDLINE]

1195. Pest Manag Sci. 2009 Sep;65(9):949-55.

A laboratory evaluation to determine the compatibility of microbiological control agents with the pollinator Bombus terrestris.

Mommaerts V, Sterk G, Hoffmann L, Smagghe G.

Laboratory of Cellular Genetics, Department of Biology, Free University of Brussels, Brussels, Belgium. Veerle.Mommaerts@vub.ac.be

BACKGROUND: This study was undertaken to identify any potential adverse side effects of the use of seven microbiological control agents (MCAs) on the bumblebee, Bombus terrestris L., in the context of combined use in integrated pest management (IPM). AQ10 (Ampelomyces quisqualis), Binab-T-vector (Hypocrea parapilulifera + T. atroviride; 1/1), Prestop-Mix (Gliocladium catenulatum J1446), Serenade (Bacillus subtilis QST713), Trianum-P (Trichoderma harzianum T22), Botanigard (Beauveria bassiana GHA) and Granupom (Cydia pomonella granulovirus), comprising five biofungicides and two bioinsecticides, were investigated. Bumblebee workers were exposed under laboratory conditions to each MCA at its maximum field recommended concentration (MFRC) via three different routes of exposure: dermal contact and orally via either treated sugar water or pollen.
RESULTS: The tested MCAs were found to be safe for workers of B. terrestris, with the exception of Botanigard and Serenade. Exposure to Botanigard via contact at its MFRC caused 92% mortality after 11 weeks, while the 1/10 MFRC killed 46% of exposed workers. For Serenade, topical contact and oral delivery via sugar water resulted in 88 and 100% worker mortality respectively. With lower concentrations (1/2, 1/5 and 1/10 MFRC) the toxicity decreased, but the effect depended on the route of exposure. In addition to lethal effects, nests were also evaluated for sublethal effects after treatment with the seven MCAs at their respective MFRCs over 11 weeks. In these bioassays, only Botanigard and Serenade gave rise to a significant (P < 0.05) decrease in drone production. Sublethal effects on foraging behaviour were also evaluated, and only Botanigard at its MFRC delivered via treated sugar water induced negative effects.
CONCLUSION: The results demonstrated that most of the MCAs tested can be considered safe for use in combination with B. terrestris, based on the International Organisation for Biological Control of Noxious Animals and Plants (IOBC) classification. However, some can be harmful, such as the biofungicide Serenade and the bioinsecticide Botanigard. Therefore, it is recommended that all should be tested before use in combination with pollinators. In this context, it is also advisable that these MCAs should be evaluated in more realistic field situations for the assessment of potentially deleterious effects on foraging behaviour.

PMID: 19437453 [PubMed - indexed for MEDLINE]

1196. Int J Epidemiol. 2009 Dec;38(6):1642-9. Epub 2009 May 11.

Climate and acute/subacute paracoccidioidomycosis in a hyper-endemic area in Brazil.

Barrozo LV, Mendes RP, Marques SA, Benard G, Silva ME, Bagagli E.

Department of Geography, School of Philosophy, Literature and Human Sciences, University of São Paulo, CEP 05508-900, São Paulo, Brazil. lija@usp.br

Comment in Int J Epidemiol. 2009 Dec;38(6):1649-50.

BACKGROUND: Paracoccidioidomycosis (PCM) is Latin America's most prevalent systemic mycosis, carrying an important social burden. Its agent, Paracoccidioides brasiliensis, has rarely been identified in nature. Studies characterizing acute/subacute PCM incidence and their relationship with climate variables are not available. This work analysed a series of acute/subacute cases that occurred in the Botucatu area, São Paulo State, Brazil, from 1969 to 1999, as an outcome of weather variability.
METHODS: Stepwise regression of annual data was applied to model incidence, calculated based on 91 cases, from lagged variables: antecedent precipitation, air temperature, soil water storage, absolute and relative air humidity, and Southern Oscillation Index (SOI).
RESULTS: Multiple regression analyses resulted in a model, which explains 49% of the incidence variance, taking into account the absolute air humidity in the year of exposure, soil water storage and SOI of the previous 2 years.
CONCLUSIONS: The correlations may reflect enhanced fungal growth after increase in soil water storage in the longer term and greater spore release with increase in absolute air humidity in the short term.

PMID: 19433518 [PubMed - indexed for MEDLINE]

1197. Nihon Ishinkin Gakkai Zasshi. 2009;50(2):57-66.

[The mechanisms of resistance to echinocandin class of antifungal drugs].

[Article in Japanese]

Niimi K, Niimi M.

Department of Oral Sciences, University of Otago, Dunedin, New Zealand.

The echinocandin (candin) class of antifungal drugs inhibit beta-1,3-glucan synthase and block synthesis of beta-1,3-glucan , an important polysaccharide in fungal cell walls. Candins are used widely for treatment of systemic infections caused by Candida and Aspergillus because of their high potency and low toxicity to humans. The incidence of candin resistance has been rare compared to that of azole resistance, although candin-resistant clinical isolates of C. albicans, C. glabrata, C. krusei and C. tropicalis have been reported in the USA and Europe in recent years. These isolates possess hundred-fold higher MIC values for candins than sensitive strains, as well as candin-resistant beta-1,3-glucan synthase activities. Their candin resistance is associated with amino acid substitutions in the echinocandin resistant region (Ech) of the FKS gene that encodes a catalytic subunit of the beta-1,3-glucan synthase. However, the effect of these amino acid substitutions on the drug-protein interaction and the molecular basis for the resistance is unknown. The exposure of fungi to candin drugs induces stress responses that activate networks involving transcriptional regulators and components controlling signal transduction of the pathways responsible for maintenance of fungal cell wall integrity. The fungal cell wall is still an attractive drug target and further investigation into the mechanisms of candin resistance and structural analysis of the beta-1,3-glucan synthase protein complex will facilitate the development of broad spectrum inhibitors of fungal cell wall synthesis.

PMID: 19430179 [PubMed - indexed for MEDLINE]

1198. J Biotechnol. 2009 Apr 20;141(1-2):26-30. Epub 2009 Mar 17.

Expression of an alkalo-tolerant fungal xylanase enhanced by directed evolution in Pichia pastoris and Escherichia coli.

McHunu NP, Singh S, Permaul K.

Department of Biotechnology and Food Technology, Durban University of Technology, Durban, South Africa. nokuthula@dut.ac.za

The alkaline stability of the xylanase from Thermomyces lanuginosus was further improved by directed evolution using error-prone PCR mutagenesis. Positive clones were selected by their ability to produce zones of clearing on pH 9 and 12 xylan agar plates. Variant NC38 was able to withstand harsh alkaline conditions retaining 84% activity after exposure at pH 10 for 90 min at 60 degrees C, while the parent enzyme had 22% activity after 60 min. The alkaline stable variant NC38 was cloned into pBGP1 under the control GAP promoter and pET22b(+) for expression in Pichia pastoris and Escherichia coli BL21, respectively. Best extracellular expression of the recombinant xylanase was observed in P. pastoris (261.7+/-0.61 U ml(-1)) whereas intracellular activity was observed in E. coli (47.9+/-0.28 U ml(-1)) was low. Total activity obtained in P. pastoris was 545-fold higher than E. coli. The mutated alkaline stable xylanase from P. pastoris was secreted into the culture medium with little or no contamination by host proteins, which favours the application of this enzyme in the pulp and paper industry.

PMID: 19428727 [PubMed - indexed for MEDLINE]

1199. Water Res. 2009 Jun;43(11):2841-51. Epub 2009 Apr 14.

Determination of emitted airborne microorganisms from a BIO-PAK wastewater treatment plant.

Korzeniewska E, Filipkowska Z, Gotkowska-Płachta A, Janczukowicz W, Dixon B, Czułowska M.

Department of Environmental Microbiology, Faculty of Environmental Sciences and Fisheries, University of Warmia and Mazury in Olsztyn, R. Prawocheńskiego Street 1, 10-957 Olsztyn-Kortowo, Poland. ewa.korzeniewska@uwm.edu.pl

Results of a study conducted to assess the degree of airborne microbial contamination generated by a wastewater treatment plant (WWTP) with bioreactor "BIO-PAK" closed treatment system and evaluation of the dispersion of potential pathogens are described. Over the year aerosol samples were collected simultaneously with sedimentation and impact methods from several plant sites and the surroundings. External upwind sites were used as control. Total colony-forming counts of heterotrophic psychrophilic, psychrotrophic, mesophilic, haemolytic bacteria, as well as members of the Enterobacteriaceae family, Staphylococcus, Enterococcus and Pseudomonas genera, actinomycetes and fungi (moulds, yeasts and yeast-like fungi) were determined. Their highest concentrations ranged up to 10(1)-10(3)CFU/m(3) (with the exception of moulds exceeding 2x10(4)) were determined in air sampled inside the bioreactor, its vicinity, and near the grate chamber. Higher species diversity of the family Enterobacteriaceae (including Shigella spp., Yersinia enterocolitica, Escherichia coli, Klebsiella pneumoniae ozaenae) in the air sampled inside or near the bioreactor may imply a health risk for staff exposed for longer periods of time. Notwithstanding, no increased emission of the analysed groups of microorganisms, including faecal bacteria, were found outside the WWTP.

PMID: 19428042 [PubMed - indexed for MEDLINE]

1200. BMC Infect Dis. 2009 May 8;9:56.

Modeling microbial survival in buildup biofilm for complex medical devices.

Alfa MJ, Howie R.

Department of Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada. malfa@sbgh.mb.ca

BACKGROUND: Flexible endoscopes undergo repeated rounds of patient-use and reprocessing. Some evidence indicates that there is an accumulation or build-up of organic material that occurs over time in endoscope channels. This "buildup biofilm" (BBF) develops as a result of cyclical exposure to wet and dry phases during usage and reprocessing. This study investigated whether the BBF matrix represents a greater challenge to disinfectant efficacy and microbial eradication than traditional biofilm (TBF), which forms when a surface is constantly bathed in fluid.
METHODS: Using the MBEC (Minimum Biofilm Eradication Concentration) system, a unique modelling approach was developed to evaluate microbial survival in BBF formed by repetitive cycles of drying, disinfectant exposure and re-exposure to the test organism. This model mimics the cumulative effect of the reprocessing protocol on flexible endoscopes. Glutaraldehyde (GLUT) and accelerated hydrogen peroxide (AHP) were evaluated to assess the killing of microbes in TBF and BBF.
RESULTS: The data showed that the combination of an organic matrix and aldehyde disinfection quickly produced a protective BBF that facilitated high levels of organism survival. In cross-linked BBF formed under high nutrient conditions the maximum colony forming units (CFU) reached ~6 Log(10)CFU/peg. However, if an oxidizing agent was used for disinfection and if organic levels were kept low, organism survival did not occur. A key finding was that once established, the microbial load of BBF formed by GLUT exposure had a faster rate of accumulation than in TBF. The rate of biofilm survival post high-level disinfection (HLD) determined by the maximum Log(10)CFU/initial Log(10)CFU for E. faecalis and P. aeruginosa in BBF was 10 and 8.6 respectively; significantly different compared to a survival rate in TBF of ~2 for each organism. Data from indirect outgrowth testing demonstrated for the first time that there is organism survival in the matrix. Both TBF and BBF had surviving organisms when GLUT was used. For AHP survival was seen less frequently in BBF than in TBF.
CONCLUSION: This BBF model demonstrated for the first time that survival of a wide range of microorganisms does occur in BBF, with significantly more rapid outgrowth compared to TBF. This is most pronounced when GLUT is used compared to AHP. The data supports the need for meticulous cleaning of reprocessed endoscopes since the presence of organic material and microorganisms prevents effective disinfection when GLUT and AHP are used. However, cross-linking agents like GLUT are not as effective when there is BBF. The data from the MBEC model of BBF suggest that for flexible endoscopes that are repeatedly used and reprocessed, the assurance of effective high-level disinfection may decrease if BBF develops within the channels.

PMCID: PMC2689233 PMID: 19426471 [PubMed - indexed for MEDLINE]

1201. J Infect Dis. 2009 Jun 15;199(12):1891-8.

Expression of Candida glabrata adhesins after exposure to chemical preservatives.

Mundy RD, Cormack B.

Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2185, USA.

Adherence of Candida glabrata, an opportunistic yeast pathogen, to host cells is mediated in part by the Epa family of adhesins, which are encoded largely at subtelomeric loci, where they are subject to transcriptional silencing. In analyzing the regulation of the subtelomeric EPA6 gene, we found that its transcription is highly induced after exposure to methylparaben, propylparaben, or sorbate. These weak acid-related chemicals are widely used as antifungal preservatives in many consumer goods, including over-the-counter vaginal products. Culture of C. glabrata with a variety of vaginal products induced expression of EPA6, leading to increased adherence to cultured human cells as well as primary human vaginal epithelial cells. We present evidence that paraben/sorbate induction of EPA6 expression involves both preservative stress and growth under hypoxic conditions. We further show that activation of EPA6 transcription depends on the Flo8 and Mss11 transcription factors and does not require the classic weak-acid transcription factors War1 or Msn2/Msn4. We conclude that exposure of C. glabrata to commonly used preservatives can alter the expression of virulence-related genes.

PMID: 19426114 [PubMed - indexed for MEDLINE]

1202. Ecohealth. 2009 Mar;6(1):6-10. Epub 2009 May 7.

Chytridiomycosis, amphibian extinctions, and lessons for the prevention of future panzootics.

Kriger KM, Hero JM.

Centre for Innovative Conservation Strategies, School of Environment, Griffith University, Gold Coast, QLD, Australia. kerry@savethefrogs.com

Comment in Ecohealth. 2009 Mar;6(1):148-51; author reply 152.

The human-mediated transport of infected amphibians is the most plausible driver for the intercontinental spread of chytridiomycosis, a recently emerged infectious disease responsible for amphibian population declines and extinctions on multiple continents. Chytridiomycosis is now globally ubiquitous, and it cannot be eradicated from affected sites. Its rapid spread both within and between continents provides a valuable lesson on preventing future panzootics and subsequent erosion of biodiversity, not only of amphibians, but of a wide array of taxa: the continued inter-continental trade and transport of animals will inevitably lead to the spread of novel pathogens, followed by numerous extinctions. Herein, we define and discuss three levels of amphibian disease management: (1) post-exposure prophylactic measures that are curative in nature and applicable only in a small number of situations; (2) pre-exposure prophylactic measures that reduce disease threat in the short-term; and (3) preventive measures that remove the threat altogether. Preventive measures include a virtually complete ban on all unnecessary long-distance trade and transport of amphibians, and are the only method of protecting amphibians from disease-induced declines and extinctions over the long-term. Legislation to prevent the emergence of new diseases is urgently required to protect global amphibian biodiversity.

PMID: 19421815 [PubMed - indexed for MEDLINE]

1203. Chirality. 2010 Feb;22(2):183-92.

Integration of metabolomics and in vitro metabolism assays for investigating the stereoselective transformation of triadimefon in rainbow trout.

Kenneke JF, Ekman DR, Mazur CS, Konwick BJ, Fisk AT, Avants JK, Garrison AW.

U.S. Environmental Protection Agency, National Exposure Research Laboratory, Ecosystems Research Division, Athens, Georgia.

Triadimefon is a systemic agricultural fungicide of the triazole class whose major metabolite, triadimenol, also a commercial fungicide, provides the majority of the actual fungicidal activity, i.e., inhibition of steroid demethylation. Both chemicals are chiral: triadimefon has one chiral center with two enantiomers while its enzymatic reduction to triadimenol produces a second chiral center and two diastereomers with two enantiomers each. All six stereoisomers of the two fungicides were separated from each other using a chiral BGB-172 column on a GC-MS system so as to follow stereospecificity in metabolism by rainbow trout hepatic microsomes. In these microsomes the S-(+) enantiomer of triadimefon was transformed to triadimenol 27% faster than the R-(-) enantiomer, forming the four triadimenol stereoisomers at rates different from each other. The most fungi-toxic stereoisomer (1S,2R) was produced at the slowest rate; it was detectable after 8 h, but below the level of method quantitation. The triadimenol stereoisomer ratio pattern produced by the trout microsomes was very different from that of the commercial triadimenol standard, in which the most rat-toxic pair of enantiomers (known as "Diastereomer A") is about 85% of the total stereoisomer composition. The trout microsomes produced only about 4% of "Diastereomer A". Complementary metabolomic studies with NMR showed that exposure of the separate triadimefon enantiomers and the racemate to rainbow trout for 48 h resulted in different metabolic profiles in the trout liver extracts, i.e., different endogenous metabolite patterns that indicated differences in effects of the two enantiomers.

2009 Wiley-Liss, Inc.

PMID: 19418553 [PubMed - indexed for MEDLINE]

1204. FEMS Microbiol Rev. 2009 Sep;33(5):833-54. Epub 2009 Apr 17.

Fungal apoptosis: function, genes and gene function.

Sharon A, Finkelstein A, Shlezinger N, Hatam I.

Department of Plant Sciences, Tel Aviv University, Tel Aviv, Israel. amirsh@ex.tau.ac.il

Cells of all living organisms are programmed to self-destruct under certain conditions. The most well known form of programmed cell death is apoptosis, which is essential for proper development in higher eukaryotes. In fungi, apoptotic-like cell death occurs naturally during aging and reproduction, and can be induced by environmental stresses and exposure to toxic metabolites. The core apoptotic machinery in fungi is similar to that in mammals, but the apoptotic network is less complex and of more ancient origin. Only some of the mammalian apoptosis-regulating proteins have fungal homologs, and the number of protein families is drastically reduced. Expression in fungi of animal proteins that do not have fungal homologs often affects apoptosis, suggesting functional conservation of these components despite the absence of protein-sequence similarity. Functional analysis of Saccharomyces cerevisiae apoptotic genes, and more recently of those in some filamentous species, has revealed partial conservation, along with substantial differences in function and mode of action between fungal and human proteins. It has been suggested that apoptotic proteins might be suitable targets for novel antifungal treatments. However, implementation of this approach requires a better understanding of fungal apoptotic networks and identification of the key proteins regulating apoptotic-like cell death in fungi.

PMID: 19416362 [PubMed - indexed for MEDLINE]

1205. FEMS Yeast Res. 2009 May;9(3):365-71.

The role of acetaldehyde and glycerol in the adaptation to ethanol stress of Saccharomyces cerevisiae and other yeasts.

Vriesekoop F, Haass C, Pamment NB.

Institute for Food and Crop Science, School of Science and Engineering, University of Ballarat, Ballarat, Victoria, Australia.

Ethanol inhibition is a commonly encountered stress condition during typical yeast fermentations and often results in reduced fermentation rates and production yields. While past studies have shown that acetaldehyde addition has a significant ameliorating effect on the growth of ethanol-stressed Saccharomyces cerevisiae, this study investigated the potential ameliorating effect of acetaldehyde on a wide range of ethanol-stressed yeasts. Acetaldehyde does not appear to be a universal ameliorating agent for yeasts exposed to ethanol stress. It is also shown that as a result of an ethanol stress, most yeasts rapidly produce glycerol as an alternative means of NAD(+) regeneration rather than having a specific requirement for glycerol. The results strongly suggest that both ethanol and acetaldehyde exposure have a direct effect on the cellular NAD(+)/NADH ratio, which can manifest itself as modulations in glycerol production.

PMID: 19416102 [PubMed - indexed for MEDLINE]

1206. Antimicrob Agents Chemother. 2009 Jul;53(7):2804-15. Epub 2009 May 4.

Heteroresistance to fluconazole in Cryptococcus neoformans is intrinsic and associated with virulence.

Sionov E, Chang YC, Garraffo HM, Kwon-Chung KJ.

Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

In 1999, heteroresistance to triazoles was reported in Cryptococcus neoformans strains isolated from an azole therapy failure case of cryptococcosis in an AIDS patient and in a diagnostic strain from a non-AIDS patient. In this study, we analyzed 130 strains of C. neoformans isolated from clinical and environmental sources before 1979, prior to the advent of triazoles, and 16 fluconazole (FLC)-resistant strains isolated from AIDS patients undergoing FLC maintenance therapy during 1990 to 2000. All strains isolated prior to 1979 manifested heteroresistance (subset of a population that grows in the presence of FLC) at concentrations between 4 and 64 microg/ml, and all 16 FLC-resistant AIDS isolates manifested heteroresistance at concentrations between 16 and 128 microg/ml. Upon exposure to stepwise increases in the concentration of FLC, subpopulations that could grow at higher concentrations emerged. Repeated transfer on drug-free media caused the highly resistant subpopulations to revert to the original level of heteroresistance. The reversion pattern fell into four categories based on the number of transfers required. The strains heteroresistant at > or =32 microg/ml were significantly more resistant to other xenobiotics and were also more virulent in mice than were those heteroresistant at < or =8 microg/ml. During FLC treatment of mice infected by strains with low levels of heteroresistance, subpopulations exhibiting higher levels of heteroresistance emerged after a certain period of time. The ABC transporter AFR1, known to efflux FLC, was unrelated to the heteroresistance mechanism. Our study showed that heteroresistance to azole is universal and suggests that heteroresistance contributes to relapse of cryptococcosis during azole maintenance therapy.

PMCID: PMC2704677 PMID: 19414582 [PubMed - indexed for MEDLINE]

1207. Aust N Z J Public Health. 2009 Apr;33(2):194-5.

The Malaysian Medical Association's role in public health control for reduction of bird dropping hazards in Sarawak.

Hock RH.

PMID: 19413867 [PubMed - indexed for MEDLINE]

1208. J Korean Acad Nurs. 2009 Apr;39(2):298-309.

[Application and evaluation of a web-based education program on blood-borne infection control for nurses].

[Article in Korean]

Choi JS, Kim KS.

Department of Nursing Science, Konyang University, Daejeon, Korea. jschoi408@empal.com

PURPOSE: To develop a web-based program on blood-borne infection control and to examine the effect of the newly developed program on perceived threat of diseases, knowledge, preventive health behaviors for blood-borne infections, and incidence rates of accidental needle sticks and other sharp object injuries in nurses.
METHODS: The program was developed through the processes of analysis, design, development, implementation, and evaluation. The research design involved a nonequivalent control group for pretest and posttest experiments. The setting was a 745-bed general hospital located in Korea.
RESULTS: The program was designed and developed after consulting previous studies. After development of the program was completed, it was evaluated and revised by a panel of experts. The total score for perceived threat of diseases, knowledge, preventive health behaviors in the experimental group was significantly higher compared to the control group (p<.05). The incidence rates for needle sticks and other sharp object injuries in the experimental group were significantly lower compared to the control group (p<.05).
CONCLUSION: Application of a Web-based, blood-borne infection control program is effective, and can be expanded to other healthcare workers who also have a high risk of blood-borne infections.

PMID: 19411801 [PubMed - indexed for MEDLINE]

1209. Sci Total Environ. 2009 Jul 1;407(14):4283-8. Epub 2009 May 2.

Mixtures of zinc and phosphate affect leaf litter decomposition by aquatic fungi in streams.

Fernandes I, Duarte S, Cássio F, Pascoal C.

Centre of Molecular and Environmental Biology, Department of Biology, University of Minho, Campus de Gualtar, Braga, Portugal.

To better understand the impacts of multiple stressors in freshwaters, we investigated the effects of mixtures of zinc and inorganic phosphorus on microbial decomposition of leaf litter. Alder leaves were colonized in a stream and placed in microcosms with stream water supplemented or not with 3 concentrations of zinc (Zn up to 9.8 mg/l) or phosphate (P-PO(4)(3-) up to 0.5 mg/l), alone and in all possible combinations. We measured leaf mass loss, and fungal biomass, reproduction and diversity. In control microcosms, 23 species of aquatic hyphomycetes were identified on leaves, and the exposure to the highest zinc concentration reduced diversity to 14 species. Articulosporatetracladia was the dominant species followed by Flagellospora sp. and Alatosporaacuminata. The exposure to phosphate increased the contribution of A.acuminata, but this species was negatively affected by zinc. Under high zinc stress, Varicosporiumelodeae increased its contribution to the total conidial production. The exposure to high zinc concentration, alone or in mixtures with phosphate, led to shifts in fungal community structure, as indicated by cluster analysis based on sporulation data and denaturing gradient gel electrophoresis (DGGE) fingerprints of fungal DNA. These changes were accompanied by a reduction in leaf decomposition, particularly in mixtures with high Zn concentration, in which leaf mass loss was 30% lower than in the control. This suggests that the co-occurrence of zinc and phosphate may have negative effects on stream ecosystem functioning. However, we did not detect decreased leaf-associated fungal biomass and sporulation, probably because a delay in fungal colonization occurred due to the presence of stressors.

PMID: 19411090 [PubMed - indexed for MEDLINE]

1210. Toxicol Lett. 2009 Aug 25;189(1):21-6. Epub 2009 May 3.

Pro-apoptotic effects of nivalenol and deoxynivalenol trichothecenes in J774A.1 murine macrophages.

Marzocco S, Russo R, Bianco G, Autore G, Severino L.

Department of Pharmaceutical Sciences, School of Pharmacy, University of Salerno, Fisciano (SA) 84084, Italy. smarzocco@unisa.it

Nivalenol (NIV) and deoxynivalenol (DON) are trichothecenes mycotoxins produced by Fusarium fungi that occur in cereal grains alone or in combination. Several studies have shown that exposure to high concentrations of these mycotoxins resulted in decreased cell proliferation; however, the molecular mechanism underlying their activities are still partially known. In this study, we evaluated the effects of NIV and DON, alone and in combination, on J7741.A macrophages viability. The results of the current study show that both NIV and DON (10-100 microM) significantly stimulate apoptosis in J774A.1 macrophages in a concentration-dependent manner; in particular, NIV results a stronger pro-apoptotic effect than DON on cultured J774A.1 murine macrophages. No interactive effects were observed by exposing J774A.1 cells to both NIV and DON simultaneously. Pro-apoptotic activity induced by both mycotoxins seems to be essentially mediated by caspase-3 and is associated with a cell cycle blocking in G0/G1 phase. Moreover, our results show that NIV and DON are able to influence apoptotic pathway by ERK, pro-apoptotic protein Bax, caspase-3 and poly-ADP-ribose synthase (PARP), DNA repairing enzyme.

PMID: 19410639 [PubMed - indexed for MEDLINE]

1211. S Afr J Surg. 2009 Feb;47(1):7-9.

Risk of blood splashes to the eye during surgery.

De Silva R, Mall A, Panieri E, Stupart D, Kahn D.

Department of Surgery and Medical Research Council Liver Research Centre, University of Cape Town and Groote Schuur Hospital, Cape Town.

BACKGROUND: With the advent of a new infectious era involving the HIV and hepatitis B and C viruses, concern has arisen about transmission of these viruses through ocular blood splashes during surgery. The purpose of the study was to determine the risk of ocular blood splashes to surgeons and their assistants during surgery. METHOD: Surgeons and assistants in several surgical disciplines were requested to wear facemasks with a transparent plastic visor. The visors were collected postoperatively and inspected for macroscopic and microscopic blood splashes.
RESULTS: Fifty-nine per cent of the surgeons and assistants refused to wear facemasks with a visor. The incidence of blood splashes in those who participated was 45%. There was a trend for blood splashes to be more common during major surgery and during elective surgery. Surgeons and assistants were subject to similar risk.
CONCLUSION: This study confirms the significant risk of ocular blood splashes during surgery, while also suggesting that both surgeons and assistants lack appreciation of the risk.

PMID: 19405330 [PubMed - indexed for MEDLINE]

1212. Biochimie. 2009 Aug;91(8):951-60. Epub 2009 May 3.

Effect of alkyl alcohols on partially unfolded state of proteinase K: Differential stability of alpha-helix and beta-sheet rich regions of the enzyme.

Tomar R, Dubey VK, Jagannadham MV.

Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.

Proteinase K (E.C. 3.4.21.64), a serine proteinase from fungus Tritirachium album, has been used as a model system to investigate the conformational changes induced by monohydric alcohols at low pH. Proteinase K belongs to alpha/beta class of proteins and maintains structural integrity in the range of pH 7.0-3.0. Enzyme acquires partially unfolded conformation (U(P)) at pH 2.5 with lower activity, partial loss of tertiary structure and exposure of some hydrophobic patches. Proteinase K in stressed state at pH 2.5 is chosen and the conformational changes induced by alkyl alcohols (methanol/ethanol/isopropanol) are studied. At critical concentration of alcohol, conformational switch occurs in the protein structure from alpha/beta to beta-sheet driving the protein into O-state. Complete loss of tertiary contacts and proteolytic activity in O-sate emphasize the involvement of alpha regions in maintaining the active site of the enzyme. Moreover, isopropanol induced unfolding of proteinase K in U(P) state occurred in two steps with the formation of beta state at low alcohol concentration followed by stabilization of beta state at high alcohol concentration. GuHCl and temperature induced unfolding of proteinase K in O-state (in 50% isopropanol) is non-cooperative as the transition curves are biphasic. This suggests that the structure of proteinase K in O-state has melted alpha regions and stabilized beta regions and that these differentially stabilized regions unfold sequentially. Further, the O-state of proteinase K can be attained from complete unfolded protein by the addition of 50% isopropanol. Hence the alcohol-induced O-state is different from native state or completely unfolded state and shows characteristics of the molten globule-like state. Thus, this state may be functioning as an intermediary in the folding pathway of proteinase K.

PMID: 19403104 [PubMed - indexed for MEDLINE]

1213. Dis Aquat Organ. 2009 Feb 25;83(3):187-93.

Effects of the pathogenic water mold Saprolegnia ferax on survival of amphibian larvae.

Romansic JM, Diez KA, Higashi EM, Johnson JE, Blaustein AR.

Department of Zoology, 3029 Cordley Hall, Oregon State University, Corvallis, Oregon 97331, USA. jromansi@cas.usf.edu

Infectious diseases are a significant threat to worldwide biodiversity. Amphibian declines, a significant part of current biodiversity losses, are in many cases associated with infectious disease. Water molds are one group of pathogens affecting amphibians on a worldwide basis. Although water molds have been studied extensively for their effects on host embryos, little information is available about how they affect post-embryonic amphibians. We tested the effects of one species of water mold, Saprolegnia ferax, in a comparative study of larvae of 4 amphibian species: Pseudacris regilla (Pacific treefrog), Rana cascadae (Cascades frog), Ambystoma macrodactylum (long-toed salamander), and R. aurora (red-legged frog). S. ferax can kill amphibians at the embryonic and juvenile life history stages, depending on the amphibian species. In the present study, a 1 wk exposure to S. ferax killed P. regilla larvae and a 2 wk exposure killed R. aurora larvae. Larvae of the other host species were unaffected after 1 wk of exposure to S. ferax. Our results suggest that S. ferax can kill amphibian larvae and further suggest that evaluation of how pathogens affect amphibians at the population level requires investigation at various life stages.

PMID: 19402452 [PubMed - indexed for MEDLINE]

1214. J Cell Biol. 2009 May 4;185(3):423-37. Epub 2009 Apr 27.

Cdc28/Cdk1 positively and negatively affects genome stability in S. cerevisiae.

Enserink JM, Hombauer H, Huang ME, Kolodner RD.

Department of Medicine, Cancer Center, Ludwig Institute for Cancer Research, University of California, San Diego School of Medicine, La Jolla, CA 92093, USA.

We studied the function of the cyclin-dependent kinase Cdc28 (Cdk1) in the DNA damage response and maintenance of genome stability using Saccharomyces cerevisiae. Reduced Cdc28 activity sensitizes cells to chronic DNA damage, but Cdc28 is not required for cell viability upon acute exposure to DNA-damaging agents. Cdc28 is also not required for activation of the DNA damage and replication checkpoints. Chemical-genetic analysis reveals that CDC28 functions in an extensive network of pathways involved in maintenance of genome stability, including homologous recombination, sister chromatid cohesion, the spindle checkpoint, postreplication repair, and telomere maintenance. In addition, Cdc28 and Mre11 appear to cooperate to prevent mitotic catastrophe after DNA replication arrest. We show that reduced Cdc28 activity results in suppression of gross chromosomal rearrangements (GCRs), indicating that Cdc28 is required for formation or recovery of GCRs. Thus, we conclude that Cdc28 functions in a genetic network that supports cell viability during DNA damage while promoting the formation of GCRs.

PMCID: PMC2700387 PMID: 19398760 [PubMed - indexed for MEDLINE]

1215. Radiat Res. 2009 Apr;171(4):454-63.

Ionizing radiation induces microhomology-mediated end joining in trans in yeast and mammalian cells.

Scuric Z, Chan CY, Hafer K, Schiestl RH.

David Geffen School of Medicine at UCLA, Department of Pathology, Los Angeles, California, USA.

DNA double-strand breaks repaired through nonhomologous end joining require no extended sequence homology as a template for the repair. A subset of end-joining events, termed microhomology-mediated end joining, occur between a few base pairs of homology, and such pathways have been implicated in different human cancers and genetic diseases. Here we investigated the effect of exposure of yeast and mammalian cells to ionizing radiation on the frequency and mechanism of rejoining of transfected unirradiated linear plasmid DNA. Cells were exposed to gamma radiation prior to plasmid transfection; subsequently the rejoined plasmids were recovered and the junction sequences were analyzed. In irradiated yeast cells, 68% of recovered plasmids contained microhomologies, compared to only 30% from unirradiated cells. Among them 57% of events used>or=4 bp of microhomology compared to only 11% from unirradiated cells. In irradiated mammalian cells, 54% of plasmids used>or=4 bp of microhomology compared to none from unirradiated cells. We conclude that exposure of yeast and mammalian cells to radiation prior to plasmid transfection enhances the frequency of microhomology-mediated end-joining events in trans. If such events occur within genomic locations, they may be involved in the generation of large deletions and other chromosomal aberrations that occur in cancer cells.

PMCID: PMC2709764 PMID: 19397446 [PubMed - indexed for MEDLINE]

1216. Can J Microbiol. 2009 Apr;55(4):437-49.

Dibutylphthalate and Tween 80 alter ultrastructure in Candida albicans: implications for peroxisome proliferation.

Blaize J, L'amoreaux WJ, Downey M, McCoy EC.

Department of Biology, College of Staten Island, The City University of New York, 2800 Victory Blvd., Staten Island, NY 10314, USA.

Phthalates are ubiquitous environmental pollutants associated with endocrine disruption and peroxisome proliferation in experimental animals. In yeasts exposed to environmental chemicals, including phthalates, alterations in cell growth, cellular morphology, and H2O2 detoxification occur. Nutrient availability also influences diverse cellular processes. Differences in responses to environmental stress between Candida albicans and the model yeast, Saccharomyces cerevesiae, have been reported. In this study, we chose C. albicans as an alternate model for testing estrogen-like chemicals because of its high affinity estrogen-binding protein and, in contrast to S. cerevesiae, estrogens are not growth inhibitory for C. albicans. Cultures were grown in either yeast nitrogen dextrose (YND; phosphate limiting) or YNDP (YND plus 100 mmol/L inorganic phosphate). For chemical testing, 0.5% dibutylphthalate (DBP), 0.05% Tween 80, or a combination of the two (DBPT) were incorporated in growth media to investigate the effects of these estrogenic agents on cell proliferation, morphology, and catalase demonstration. We observed significant differences in cell growth related to DBP and changes in cell wall thickness related to both Tween 80 and phosphate. We describe ultrastructural changes including detachment of the outer yeast cell wall layer and presence of putative peroxisomes. Our findings support the proposal that C. albicans may be particularly suitable for use in studies involving cellular responses associated with exposure to estrogenic chemicals contained in complex mixtures.

PMID: 19396244 [PubMed - indexed for MEDLINE]

1217. Nursing. 2009 May;39(5):22-8; quiz 28-9.

How to protect yourself after body fluid exposure.

Davenport A, Myers F.

Scripps Mercy Hospital, San Diego, CA, USA.

An accidental exposure to blood or other potentially infectious material (OPIM) such as cerebrospinal or pleural fluid can be a life changing experience. Among the bloodborne and OPIM pathogens are HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV). Postexposure prophylaxis (PEP) exists for HBV and HIV, but not for HCV, which is the most common chronic bloodborne infection in the United States; approximately 3.2 million persons are chronically infected. Fortunately, however, exposure to blood or OPIM usually doesn't translate into disease transmission. In this article, we'll discuss how you can minimize the risk of disease transmission if you or a coworker is accidentally exposed to blood or another potentially infectious body fluid. But first, let's review some key definitions.

PMID: 19395929 [PubMed - indexed for MEDLINE]

1218. Plant Physiol. 2009 Jun;150(2):924-41. Epub 2009 Apr 24.

The wound-, pathogen-, and ultraviolet B-responsive MYB134 gene encodes an R2R3 MYB transcription factor that regulates proanthocyanidin synthesis in poplar.

Mellway RD, Tran LT, Prouse MB, Campbell MM, Constabel CP.

Centre for Forest Biology and Department of Biology, University of Victoria, Victoria, British Columbia, Canada V8W 3N5.

Comment in Plant Signal Behav. 2009 Aug;4(8):790-2.

In poplar (Populus spp.), the major defense phenolics produced in leaves are the flavonoid-derived proanthocyanidins (PAs) and the salicin-based phenolic glycosides. Transcriptional activation of PA biosynthetic genes leading to PA accumulation in leaves occurs following herbivore damage and mechanical wounding as well as infection by the fungal biotroph Melampsora medusae. In this study, we have identified a poplar R2R3 MYB transcription factor gene, MYB134, that exhibits close sequence similarity to the Arabidopsis (Arabidopsis thaliana) PA regulator TRANSPARENT TESTA2 and that is coinduced with PA biosynthetic genes following mechanical wounding, M. medusae infection, and exposure to elevated ultraviolet B light. Overexpression of MYB134 in poplar resulted in transcriptional activation of the full PA biosynthetic pathway and a significant plant-wide increase in PA levels, and electrophoretic mobility shift assays showed that recombinant MYB134 protein is able to bind to promoter regions of PA pathway genes. MYB134-overexpressing plants exhibited a concomitant reduction in phenolic glycoside concentrations and other minor alterations to levels of small phenylpropanoid metabolites. Our data provide insight into the regulatory mechanisms controlling stress-induced PA metabolism in poplar, and the identification of a regulator of stress-responsive PA biosynthesis constitutes a valuable tool for manipulating PA metabolism in poplar and investigating the biological functions of PAs in resistance to biotic and abiotic stresses.

PMCID: PMC2689947 PMID: 19395405 [PubMed - indexed for MEDLINE]

1219. Plant J. 2009 Jul;59(2):292-302. Epub 2009 Mar 14.

Signal signature of aboveground-induced resistance upon belowground herbivory in maize.

Erb M, Flors V, Karlen D, de Lange E, Planchamp C, D'Alessandro M, Turlings TC, Ton J.

Laboratory for Fundamental and Applied Research in Chemical Ecology (FARCE), University of Neuchâtel, Switzerland.

Erratum in Plant J. 2009 Dec;60(5):929.

Comment in Plant Signal Behav. 2009 Jul;4(7):636-8.

Plants activate local and systemic defence mechanisms upon exposure to stress. This innate immune response is partially regulated by plant hormones, and involves the accumulation of defensive metabolites. Although local defence reactions to herbivores are well studied, less is known about the impact of root herbivory on shoot defence. Here, we examined the effects of belowground infestation by the western corn rootworm Diabrotica virgifera virgifera on aboveground resistance in maize. Belowground herbivory by D. v. virgifera induced aboveground resistance against the generalist herbivore Spodoptera littoralis, and the necrotrophic pathogen Setosphaeria turcica. Furthermore, D. v. virgifera increased shoot levels of 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA), and primed the induction of chlorogenic acid upon subsequent infestation by S. littoralis. To gain insight into the signalling network behind this below- and aboveground defence interaction, we compiled a set of 32 defence-related genes, which can be used as transcriptional marker systems to detect activities of different hormone-response pathways. Belowground attack by D. v. virgifera triggered an ABA-inducible transcription pattern in the shoot. The quantification of defence hormones showed a local increase in the production of oxylipins after root and shoot infestation by D. v. virgifera and S. littoralis, respectively. On the other hand, ABA accumulated locally and systemically upon belowground attack by D. v. virgifera. Furthermore, D. v. virgifera reduced the aboveground water content, whereas the removal of similar quantities of root biomass had no effect. Our study shows that root herbivory by D. v. virgifera specifically alters the aboveground defence status of a maize, and suggests that ABA plays a role in the signalling network mediating this interaction.

PMID: 19392694 [PubMed - indexed for MEDLINE]

1220. Yeast. 2009 May;26(5):273-85.

Catalytic isoforms Tpk1 and Tpk2 of Candida albicans PKA have non-redundant roles in stress response and glycogen storage.

Giacometti R, Kronberg F, Biondi RM, Passeron S.

Cátedra de Microbiología, Facultad de Agronomía, Universidad de Buenos Aires, IBYF-CONICET, Avda. San Martín 4453, C1417DSE Buenos Aires, Argentina.

Candida albicans cAMP-dependent protein kinase (PKA) is coded by two catalytic subunits (TPK1 and TPK2) and one regulatory subunit (BCY1). In this organism the cAMP/PKA signalling pathway mediates basic cellular processes, such as the yeast-to-hyphae transition and cell cycle regulation. In the present study, we investigated the role of C. albicans PKA in response to saline, heat and oxidative stresses as well as in glycogen storage. To fine-tune the analysis, we performed the studies on several C. albicans PKA mutants having heterozygous or homozygous deletions of TPK1 and/or TPK2 in a different BCY1 genetic background. We observed that tpk1Delta/tpk1Delta strains developed a lower tolerance to saline exposure, heat shock and oxidative stress, while wild-type and tpk2Delta/tpk2Delta mutants were resistant to these stresses, indicating that both isoforms play different roles in the stress response pathway. We also found that regardless of the TPK background, heterozygous and homozygous BCY1 mutants were highly sensitive to heat treatment. Surprisingly, we observed that those strains devoid of one or both TPK1 alleles were defective in glycogen storage, while strains lacking Tpk2 accumulated higher levels of the polysaccharide, indicating that Tpk1 and Tpk2 have opposite roles in carbohydrate metabolism.

PMID: 19391100 [PubMed - indexed for MEDLINE]

1221. Infection. 2009 Aug;37(4):370-3. Epub 2009 Apr 23.

Cryptococcus gattii meningoencephalitis in an immunocompetent person 13 months after exposure.

Georgi A, Schneemann M, Tintelnot K, Calligaris-Maibach RC, Meyer S, Weber R, Bosshard PP.

Department of Medicine, University Hospital Zurich, Zurich, Switzerland.

A 53-year old immunocompetent Swiss female is described who developed severe meningoencephalitis due to infection with Cryptococcus gattii 13 months following exposure on Vancouver Island, Canada. Diagnosis was based on cerebrospinal fluid (CSF) examination, i.e., positive India-ink staining, positive latex particle agglutination, and positive culture. Species identification was performed by growth on L-canavanine-glycine-bromthymol blue medium and by sequencing of the intergenic and internal transcribed spacer regions of the rRNA genes. After initial therapy with fluconazole by which the patient did not improve, therapy was changed to amphotericin B and flucytosine and later to high-dose fluconazole and amphotericin B. Despite long-term treatment and external drainage of the CSF, the patient's condition improved only slowly. The patient was discharged after 132 days of hospitalization.

PMID: 19390780 [PubMed - indexed for MEDLINE]

1222. Wei Sheng Wu Xue Bao. 2009 Jan 4;49(1):44-8.

[Breeding of arachidonic acid producing Mortierella sabellina by ultraviolet mutation].

[Article in Chinese]

Yu C, Li L.

College of Food Science, Heilongjiang August First Land Reclamation University, Daqing 163319, China. spxyycq@126.com

OBJECTIVE: We obtained a new mutant with higher growth rate and high capability of producing arachidonic acid after protoplast ultraviolet mutation.
METHODS: Using dry weight of biomass, microbial total lipid and total arachidonic acid production as evaluation index, we determined time of ultraviolet irradiation by single factor experiment and measured the content of the arachidonic acid by gas chromatography.
RESULTS: When the power of viltalight lamp was set at 20W,exposure distance at 30 cm and exposure time at 80 s, lethality of spores of Mortierella isabellina was 76.4%.
CONCLUSION: After ultraviolet mutation and repeatedly screening, a mutat of Mortierella isabellina YZ-124 whose arachidonic acid concentration in biomass was 5.76 times of the control strains was obtained.

PMID: 19388263 [PubMed - indexed for MEDLINE]

1223. Arch Pharm Res. 2009 Mar;32(3):367-73. Epub 2009 Apr 23.

Inhibitory effects of arbutin on melanin biosynthesis of alpha-melanocyte stimulating hormone-induced hyperpigmentation in cultured brownish guinea pig skin tissues.

Lim YJ, Lee EH, Kang TH, Ha SK, Oh MS, Kim SM, Yoon TJ, Kang C, Park JH, Kim SY.

Department of Medical Science, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, 449-701, Korea.

Arbutin has been used as a whitening agent in cosmetic products. Melanin, the major pigment that gives color to skin, may be over-produced with sun exposure or in conditions such as melasma or hyperpigmentary diseases. Tyrosinase is a key enzyme that catalyzes melanin synthesis in melanocytes; therefore, inhibitors of the tyrosinase enzyme could be used for cosmetic skin whitening. A recent study has reported that arbutin decreases melanin biosynthesis through the inhibition of tyrosinase activity. However, this inhibitory mechanism of arbutin was not sufficiently demonstrated in skin tissue models. We found that arbutin both inhibits melanin production in B16 cells induced with alpha-MSH and decreases tyrosinase activity in a cell-free system. Furthermore, the hyperpigmentation effects of alpha-MSH were abrogated by the addition of arbutin to brownish guinea pig and human skin tissues. These results suggest that arbutin may be a useful agent for skin whitening.

PMID: 19387580 [PubMed - indexed for MEDLINE]

1224. FEMS Yeast Res. 2009 Jun;9(4):626-33. Epub 2009 Apr 6.

Dynamics of in vitro acquisition of resistance by Candida parapsilosis to different azoles.

Pinto e Silva AT, Costa-de-Oliveira S, Silva-Dias A, Pina-Vaz C, Rodrigues AG.

Department of Microbiology, Faculty of Medicine, University of Porto, Porto, Portugal. anatpsilva@hotmail.com

Candida parapsilosis is a common isolate from clinical fungal infectious episodes. Resistance of C. parapsilosis to azoles has been increasingly reported. To analyse the development of resistance in C. parapsilosis, four azole-susceptible clinical strains and one American Type Culture Collection type strain were cultured in the presence of fluconazole, voriconazole and posaconazole at different concentrations. The isolates developed variable degrees of azole resistance according to the antifungal used. Fluconazole was the fastest inducer while posaconazole was the slowest. Fluconazole and voriconazole induced resistance to themselves and each other, but not to posaconazole. Posaconazole induced resistance to all azoles. Developed resistance was stable; it could be confirmed after 30 days of subculture in drug-free medium. Azole-resistant isolates revealed a homogeneous population structure; the role of azole transporter efflux pumps was minor after evaluation by microdilution and cytometric assays with efflux pump blockers (verapamil, ibuprofen and carbonyl cyanide 3-chloro-phenylhydrazone). We conclude that the rapid development of azole resistance occurs by a mechanism that might involve mutation of genes responsible for ergosterol biosynthesis pathway, stressed by exposure to antifungals.

PMID: 19385998 [PubMed - indexed for MEDLINE]

1225. Sarcoidosis Vasc Diffuse Lung Dis. 2008 Dec;25(2):125-32.

HLA and environmental interactions in sarcoidosis.

Rossman MD, Thompson B, Frederick M, Iannuzzi MC, Rybicki BA, Pander JP, Newman LS, Rose C, Magira E, Monos D; ACCESS Group.

Collaborators: Weinberger SE, Finn P, Garpestad E, Moran A, Yeager H Jr, Rabin DL, Stein S, Iannuzzi MC, Rybicki B, Major M, Maliarik M, Popovich J Jr, Moller DR, Johns CJ, Rand C, Steimel J, Judson MA, D'Alessandro S, Heister N, Johnson T, Lackland DT, Pandey J, Sahn S, Strange C, Teirstein AS, DePalo L, Brown S, Lesser M, Padilla ML, Marshall M, Newman LS, Rose C, Barnard J, Baughman RP, Lower EE, Winget DB, McLennan G, Hunninghake G, Dayton C, Powers L, Rossman MD, Bresnitz EA, Daniele R, Regovich J, Sexauer W, Musson R, Deshler J, Sorlie P, Wu M, Cherniack R, Newman L, Knatterud GL, Terrin ML, Thompson BW, Brown K, Frederick M, LoPresti F, Wilkins P, Canner M, Dotson J, Lindenfelser S, Cosentino M.

Division of Pulmonary, Allergy and Critical Care, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania 19104-6160, USA. rossmanm@mail.med.upenn.edu

Sarcoidosis is a systemic granulomatosis of unknown etiology despite being described over 100 years ago. While both genetic predisposition and environmental exposures have been proposed as playing a role in this disease, there have not been any systematic investigations of gene-environmental interaction in this disease. In the ACCESS dataset, detailed environmental histories and high resolution HLA class II typing were performed on 476 cases of newly diagnosed sarcoidosis and 476 matched controls from the patients' community. We evaluated gene-environmental interactions in exposures or HLA class II alleles that were present in > 5% of the population and had an odd ratio of > 1.0. Four exposures and four HLA Class II alleles met these criteria and were evaluated. Significant interaction was observed between HLA DRB1*1101 and insecticide exposure at work (p < 0.10) and suggestive interaction was observed between HLA DRB1*1101 and exposure to mold and musty odors and DRB1*1501 and insecticide exposure at work (P < 0.15). In addition, HLA DRB1*1101 and insecticide exposure at work was associated with extrapulmonary sarcoidosis, specifically cardiac sarcoidosis and hypercalcemia (p<0.05) and HLA DRB1*1101 and exposure to molds and musty odors was associated with pulmonary only sarcoidosis (P < 0.05). These studies suggest that sarcoidosis is due to an interaction of genetic predisposition and environmental exposure in at least some cases of sarcoidosis. Future studies in defined phenotypes of sarcoidosis may be necessary to define environmental and genetic associations with sarcoidosis.

PMID: 19382531 [PubMed - indexed for MEDLINE]

1226. Environ Toxicol. 2010 Jun;25(3):213-20.

Descriptive and mechanistic toxicity of conazole fungicides using the model test alga Dunaliella tertiolecta (Chlorophyceae).

Baird TD, DeLorenzo ME.

Grice Marine Biological Laboratory, College of Charleston, 205 Fort Johnson Rd., Charleston, SC 29412, USA.

Conazole fungicides are commonly used to prevent fungal growth on turf grass and agricultural crops. As many of these sites are adjacent to coastal waterways and estuaries, there exists the potential for nontarget effects of runoff on marine organisms. This study reports 96 h EC(50) values for four selected conazole fungicides (triadimefon = 5.98 mg/L; triadimenol = 5.51 mg/L; propiconazole = 2.33 mg/L; hexaconazole = 0.91 mg/L) to the model test alga Dunaliella tertiolecta. We further investigated possible mechanisms of toxicity by examining sublethal effects of exposure on cell morphology, osmoregulatory function, and lipid composition. These mechanistic studies revealed that conazole exposure does not inhibit synthesis of the cell's glycerol osmolyte, but does result in an overall increase in cellular volume and total lipid content. Both fungi and chlorophytes rely on ergosterol to maintain membrane structure and fluidity, and we provide evidence that the sterol-inhibiting conazoles may interfere with ergosterol biosynthesis in the cell membrane of Dunaliella. These findings suggest that green algae may be especially susceptible to nontarget effects of sterol-inhibiting fungicides in marine systems.

Published 2009 by Wiley Periodicals, Inc.

PMID: 19382186 [PubMed - indexed for MEDLINE]

1227. Analyst. 2009 May;134(5):939-44. Epub 2009 Mar 6.

A new PCR-based bioassay strategy for the detection of type A trichothecenes in food.

Bowens P, Lancova K, Dip R, Povilaityte V, Stroka J, Naegeli H.

Institute of Pharmacology and Toxicology, University of Zürich-Vetsuisse, CH-8057 Zürich, Switzerland.

Type A trichothecenes (primarily T-2 and HT-2 toxins) are common fungal metabolites found in a wide range of grains and other field crops grown in temperate climatic zones. By acting as potent inhibitors of protein synthesis, T-2 and HT-2 exert adverse effects particularly against rapidly proliferating tissues, including the bone marrow, the immune system and epithelial cells. Based on toxicity studies in laboratory and farm animals, a temporary tolerable daily intake for the sum of T-2 and HT-2 has been issued in the European Union. However, exposure assessments suggest that the combined intake of these natural compounds exceeds in many cases the proposed threshold. To further protect the consumers, it is therefore necessary to screen a large number of food samples for parts per billion levels of both T-2 and HT-2. Towards that goal, we are the first to report that these two type A trichothecenes induce fast and high-amplitude transcriptional changes in cultured human breast cancer cells. This specific response involving marker gene inductions by more than 1000-fold has been exploited to develop a real-time PCR-based screening method that displays a limit of detection of 5 ng g(-1) for T-2 and 10 ng g(-1) for HT-2. The practicability of this bioassay is demonstrated by its application to the detection of type A trichothecenes in different food matrices.

PMID: 19381388 [PubMed - indexed for MEDLINE]

1228. J Hosp Infect. 2009 Jun;72(2):189-90. Epub 2009 Apr 19.

Biological hazards among police workers: a hospital-based prevention programme.

Bonoli F, Poissonnet CM.

PMID: 19380183 [PubMed - indexed for MEDLINE]

1229. Appl Environ Microbiol. 2009 Jun;75(12):3937-43. Epub 2009 Apr 17.

Susceptibility of Diabrotica virgifera virgifera (Coleoptera: Chrysomelidae) to the entomopathogenic fungus Metarhizium anisopliae when feeding on Bacillus thuringiensis Cry3Bb1-expressing maize.

Meissle M, Pilz C, Romeis J.

Agroscope Reckenholz-Tänikon Research Station ART, Zurich, Switzerland.

Genetically engineered maize producing the insecticidal protein Cry3Bb1 from Bacillus thuringiensis (Bt maize) is protected against corn rootworms (Diabrotica spp.), which are serious maize pests in North America and Europe. The aim of the present study was to investigate the interaction of Bt maize (event MON88017) and the entomopathogenic fungus Metarhizium anisopliae for controlling the western corn rootworm, Diabrotica virgifera virgifera. Exposure to Cry3Bb1 expressed in Bt maize seedlings resulted in decreased weight gain in D. v. virgifera larvae but did not influence susceptibility to M. anisopliae. Adult beetles were not affected by Cry3Bb1 in their food, but mortality when feeding on maize leaves was higher than when feeding on silk. Adults were more susceptible to the fungus than larvae. The results indicate that the effects of Bt maize and M. anisopliae on D. v. virgifera are additive and that Bt maize does not interfere with the biological control provided by entomopathogenic fungi.

PMCID: PMC2698357 PMID: 19376921 [PubMed - indexed for MEDLINE]

1230. Appl Environ Microbiol. 2009 Jun;75(12):4053-7. Epub 2009 Apr 17.

Possible environmental origin of resistance of Aspergillus fumigatus to medical triazoles.

Snelders E, Huis In 't Veld RA, Rijs AJ, Kema GH, Melchers WJ, Verweij PE.

Department of Medical Microbiology, Radboud University Nijmegen Medical Center, The Netherlands.

We reported the emergence of resistance to medical triazoles of Aspergillus fumigatus isolates from patients with invasive aspergillosis. A dominant resistance mechanism was found, and we hypothesized that azole resistance might develop through azole exposure in the environment rather than in azole-treated patients. We investigated if A. fumigatus isolates resistant to medical triazoles are present in our environment by sampling the hospital indoor environment and soil from the outdoor environment. Antifungal susceptibility, resistance mechanisms, and genetic relatedness were compared with those of azole-resistant clinical isolates collected in a previous study. Itraconazole-resistant A. fumigatus (five isolates) was cultured from the indoor hospital environment as well as from soil obtained from flower beds in proximity to the hospital (six isolates) but never from natural soil. Additional samples of commercial compost, leaves, and seeds obtained from a garden center and a plant nursery were also positive (four isolates). Cross-resistance was observed for voriconazole, posaconazole, and the azole fungicides metconazole and tebuconazole. Molecular analysis showed the presence of the dominant resistance mechanism, which was identical to that found in clinical isolates, in 13 of 15 environmental isolates, and it showed that environmental and clinical isolates were genetically clustered apart from nonresistant isolates. Patients with azole-resistant aspergillosis might have been colonized with azole-resistant isolates from the environment.

PMCID: PMC2698372 PMID: 19376899 [PubMed - indexed for MEDLINE]

1231. Arch Bronconeumol. 2009 Aug;45(8):405-7. Epub 2009 Apr 18.

[Hypersensitivity pneumonitis caused by Mucor species in a cork worker].

[Article in Spanish]

Villar A, Muñoz X, Cruz MJ, Morell F.

Servei de Pneumologia, Hospital Vall d'Hebron, Departamento de Medicina, Universitat Autònoma de Barcelona, Barcelona, España.

Suberosis is a type of hypersensitivity pneumonitis caused by exposure to cork proteins and molds such as Aspergillus fumigatus and Penicillium frequentans. We present the case of a man with suberosis caused by Mucor species, a mold that has been rarely reported to cause hypersensitivity pneumonitis. Furthermore, the patient had symptoms and lung function tests indicating bronchial obstruction-an atypical presentation of hypersensitivity pneumonitis. No imaging abnormalities were observed. A diagnosis was made on the basis of bronchoalveolar lavage and transbronchial biopsy findings. Mucor species was identified as the causative agent using a specific bronchial challenge test.

PMID: 19376624 [PubMed - indexed for MEDLINE]

1232. Clin Chest Med. 2009 Jun;30(2):217-25, v.

Histoplasmosis.

Kauffman CA.

Division of Infectious Diseases, Veterans Affairs Ann Arbor Healthcare System, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48105, USA. ckauff@umich.edu

Histoplasmosis is the most common endemic mycosis causing human infection. Large outbreaks have been ascribed to histoplasmosis, but most infections are sporadic. Similar to the other fungi in this category, initial exposure to Histoplasma capsulatum is by way of the respiratory tract, but once inhaled into the alveoli, the organism readily spreads in macrophages throughout the reticuloendothelial system. Compared with a decade ago, improvements in diagnostic tests have made it feasible to more quickly establish a diagnosis of histoplasmosis, thus allowing appropriate antifungal therapy to be started promptly. Treatment guidelines have been updated recently and are reviewed for the various forms of histoplasmosis.

PMID: 19375629 [PubMed - indexed for MEDLINE]

1233. J Med Microbiol. 2009 May;58(Pt 5):563-6.

Evaluation of laccases and melanization in clinical and environmental Cryptococcus neoformans samples by non-denaturing PAGE.

Pereira CB, Bueno FL, Dias AL, Brigagão MR, Paula CR, Siqueira AM.

Departamento de Ciências Biológicas, Laboratório de Microbiologia e Imunologia, Universidade Federal de Alfenas, Alfenas, MG, Brazil.

The increased incidence of infections caused by the opportunistic pathogen Cryptococcus neoformans, which mainly affects immunocompromised patients but can also infect immunocompetent individuals, has needed additional studies on this micro-organism's pathogenicity and factors related to virulence, such as enzyme production, for a better understanding of the aetiology of cryptococcosis. The aim of this study was to verify the applicability of non-denaturing PAGE for analysis of laccases by quantification of the amount of melanin pigment produced by clinical and environmental strains of C. neoformans. After incubation of the gel with the substrate L-dopa, strains produced melanin spots of a bright brown to black colour. Quantification of these spots was performed by densitometry analysis and the amount of melanin produced was calculated and compared among the strains. All strains showed laccase activity. Serotype B strains showed a higher melanin intensity than serotype A strains. Over half of the clinical strains (56.2%) showed the lowest melanin intensities, suggesting that melanin production may not be the main virulence factor against host defence. The clinical strain ICB 88 revealed two melanin spots on the gel, indicating the presence of two laccase isoforms. The environmental strains showed the highest values of melanin intensity, which may be related to previous exposure to environmental stress conditions.

PMID: 19369516 [PubMed - indexed for MEDLINE]

1234. Environ Sci Technol. 2009 Mar 15;43(6):2144-50.

Endocrine disrupting effects of herbiicides and pentachlorophenol: in vitro and in vivo evidence.

Orton F, Lutz I, Kloas W, Routledge EJ.

Institute for the Environment, Brunel University, Kingston Lane, Uxbridge UB8 3PH, UK. francesorton@googlemail.com

The potential for agricultural chemicals to cause endocrine disruption (ED) in humans and wildlife is an increasing concern; however, the effects of commonly used pesticides at environmentally relevant concentrations are largely unknown. Therefore, 12 environmentally relevant pesticides (11 herbicides and pentachlorophenol (PCP)) were tested for their endocrine disrupting potential in two in vitro assays. A recombinant yeast screen was used to detect receptor mediated (anti-) estrogenic and (anti-) androgenic activity (concentration range: 0.01-1000 microM), and cultured Xenopus oocytes were used to measure effects on the ovulatory response and ovarian steroidogenesis (concentration range: 0.00625-62.5 microM). Eleven pesticides were active in at least one assay (isoproturon, diuron, linuron, 4-chloro-2-methylphenoxy acetic acid (MCPA), mecoprop, atrazine, simazine, PCP, trifluralin, chlorpropham, bentazone), and one had no effect (2,4-dichlorophenoxy acetic acid (2,4,-D)). The most common effects were antiestrogenic/ antiandrogenic activity in the yeast screen, and inhibition of ovulation in vitro, accompanied by decreased testosterone production. Estrogenic activity was never observed. In addition, the most potent compound identified in vitro (PCP) was tested for ED activity in vivo. A short-term exposure (6 days) of adult female Xenopus to low concentrations (0.1 or 1 microg/L; 0.375 or 3.75 nM) resulted in minor alterations in plasma hormone levels and toxic effects on the ovary. Changes in in vitro human chorionic gonadotropin (hCG) stimulated hormone production in ovarian follicles from exposed individuals was also observed. In conclusion, novel effects of herbicides and PCP at environmentally relevant concentrations were found, and the effects of these compounds on humans and/or wildlife warrant further investigation.

PMID: 19368227 [PubMed - indexed for MEDLINE]

1235. Occup Environ Med. 2009 Aug;66(8):543-9. Epub 2009 Apr 13.

Effect of an intervention aimed at reducing the risk of allergic respiratory disease in bakers: change in flour dust and fungal alpha-amylase levels.

Meijster T, Tielemans E, Heederik D.

TNO Quality of Life, Department of Food and Chemical Risk Analysis, Zeist, The Netherlands. tim.meijster@tno.nl

INTRODUCTION: We evaluated the effect on exposure of an intervention programme, which focused on risk education and providing information on good work practices. This intervention programme was enrolled as part of a Dutch covenant in the flour processing industry (industrial bakeries, flour mills, ingredient producers).
METHODS: Data from several measurement surveys collected pre- and post-intervention were used to evaluate changes in exposure over time. All datasets contained personal measurements analysed for flour dust and fungal alpha-amylase contents, and contextual information was available on process characteristics, work practice, and use of control measures.
RESULTS: Changes in exposure over time varied substantially between sectors and jobs. For bakeries a modest downward annual trend of -2% was found for flour dust and -8% for amylase. For flour mills the annual trend for flour dust was -12%; no significant trend was observed for amylase. For ingredient producers results were generally non-significant but indicated a reduction in flour dust exposure and increase in fungal alpha-amylase exposure. Modest increase in use of control measures and proper work practices were reported in most sectors, especially the use of local exhaust ventilation and decreased use of compressed air.
CONCLUSIONS: The magnitude of the observed reductions in exposure levels indicates that the sector-wide intervention strategy implemented during the covenant period had a limited overall effect. This indicates that a more rigorous approach is needed to substantially decrease the exposure levels to flour dust and related allergens and, respectively, the prevalence of associated occupational diseases.

PMID: 19366713 [PubMed - indexed for MEDLINE]

1236. J Biol Chem. 2009 Jun 5;284(23):15668-75. Epub 2009 Apr 14.

Motogenic sites in human fibronectin are masked by long range interactions.

Vakonakis I, Staunton D, Ellis IR, Sarkies P, Flanagan A, Schor AM, Schor SL, Campbell ID.

Department of Biochemistry, University of Oxford, Oxford OX1 3QU , UK. ioannis.vakonakis@bioch.ox.ac.uk

Fibronectin (FN) is a large extracellular matrix glycoprotein important for development and wound healing in vertebrates. Recent work has focused on the ability of FN fragments and embryonic or tumorigenic splicing variants to stimulate fibroblast migration into collagen gels. This activity has been localized to specific sites and is not exhibited by full-length FN. Here we show that an N-terminal FN fragment, spanning the migration stimulation sites and including the first three type III FN domains, also lacks this activity. A screen for interdomain interactions by solution-state NMR spectroscopy revealed specific contacts between the Fn N terminus and two of the type III domains. A single amino acid substitution, R222A, disrupts the strongest interaction, between domains (4-5)FnI and (3)FnIII, and restores motogenic activity to the FN N-terminal fragment. Anastellin, which promotes fibril formation, destabilizes (3)FnIII and disrupts the observed (4-5)FnI-(3)FnIII interaction. We discuss these findings in the context of the control of cellular activity through exposure of masked sites.

PMCID: PMC2708863 PMID: 19366708 [PubMed - indexed for MEDLINE]

1237. Bull Entomol Res. 2010 Feb;100(1):99-103. Epub 2009 Apr 14.

Mortality of Atta sexdens rubropilosa (Hymenoptera: Formicidae) workers in contact with colony waste from different plant sources.

Lacerda FG, Della Lucia TM, Pereira OL, Peternelli LA, Tótola MR.

Departamento de Biologia Animal, Universidade Federal de Viçosa,Viçosa, MG 36570-000, Brazil. tdlucia@ufv.br

The objective of this work was to study the effect of colony waste on the mortality of workers of Atta sexdens rubropilosa Forel colonies fed with different plant substrates. Eight nests were used; two colonies each were fed with Acalypha wilkesiana Müller.Arg, Ligustrum japonicum Thunb, Eucalyptus urophylla S.T. Blake or a mixture of the three substrates in equal proportions. Irrespective of diet, being kept with waste led to higher mortality. However, workers that were kept in contact with waste produced by colonies fed Acalypha had higher average survival rate and later death when compared with workers from the other treatments. Workers from the Eucalyptus-fed colonies had the lowest survival rate and 50% of them died within four days of exposure to Eucalyptus waste. Trichoderma viride Pers. ex Gray, a fungus garden antagonist, and the entomopathogen Aspergillus flavus Link. ex Gray were present in the colonies supplied with all plants. The largest fungus diversity was verified in the waste of colonies fed Acalypha and the mixture of Acalypha, Ligustrum and Eucalyptus. Therefore, antibiotic properties of Acalypha did not reduce contaminant diversity but apparently minimized effects of pathogenic microorganisms present in the waste such as Asp. flavus. This may explain the highest survival rate of workers in this treatment.

PMID: 19366474 [PubMed - indexed for MEDLINE]

1238. Pediatrics. 2009 Mar;123 Suppl 3:S160-7.

Complex interactions of pollutant and allergen exposures and their impact on people with asthma.

Eggleston PA.

Johns Hopkins Hospital, CMSC 1105, Department of Pediatrics, Division of Allergy and Immunology, 600 North Wolfe St, Baltimore, MD 21287, USA. pegglest@jhmi.edu

Pediatric asthma has many causes and can manifest differently in different children and at different times. Understanding the many factors related to the development and exacerbation of asthma is complicated by the complexity of the many environmental exposures related to asthma development and morbidity. Furthermore, the same environmental exposures that may cause increased symptoms at 1 point in time may be protective when the exposure occurs earlier or at high enough levels. We know that environmental exposures such as allergens, irritants, and pollutants are quite complex in their composition; further examination of this complexity may improve our understanding of this complex and highly prevalent disease.

PMID: 19221159 [PubMed - indexed for MEDLINE]

1239. Antimicrob Agents Chemother. 2009 Jun;53(6):2392-401. Epub 2009 Apr 13.

Farnesol-induced apoptosis in Candida albicans.

Shirtliff ME, Krom BP, Meijering RA, Peters BM, Zhu J, Scheper MA, Harris ML, Jabra-Rizk MA.

Department of Microbial Pathogenesis, Dental School, University of Maryland, Baltimore, MD 21201, USA.

Farnesol, a precursor in the isoprenoid/sterol pathway, was recently identified as a quorum-sensing molecule produced by the fungal pathogen Candida albicans. Farnesol is involved in the inhibition of germination and biofilm formation by C. albicans and can be cytotoxic at certain concentrations. In addition, we have shown that farnesol can trigger apoptosis in mammalian cells via the classical apoptotic pathways. In order to elucidate the mechanism behind farnesol cytotoxicity in C. albicans, the response to farnesol was investigated, using proteomic analysis. Global protein expression profiles demonstrated significant changes in protein expression resulting from farnesol exposure. Among the downregulated proteins were those involved in metabolism, glycolysis, protein synthesis, and mitochondrial electron transport and the respiratory chain, whereas proteins involved in folding, protection against environmental and oxidative stress, actin cytoskeleton reorganization, and apoptosis were upregulated. Cellular changes that accompany apoptosis (regulated cell death) were further analyzed using fluorescent microscopy and gene expression analysis. The results indicated reactive oxygen species accumulation, mitochondrial degradation, and positive terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) in the farnesol-exposed cells concurrent with increased expression of antioxidant-encoding and drug response genes. More importantly, the results demonstrated farnesol-induced upregulation of the caspase gene MCA1 and the intracellular presence of activated caspases. In conclusion, this study demonstrated that farnesol promotes apoptosis in C. albicans through caspase activation, implying an important physiological role for farnesol in the fungal cell life cycle with important implications for adaptation and survival.

PMCID: PMC2687256 PMID: 19364863 [PubMed - indexed for MEDLINE]

1240. Antimicrob Agents Chemother. 2009 Aug;53(8):3347-52. Epub 2009 Apr 13.

Anidulafungin is fungicidal and exerts a variety of postantifungal effects against Candida albicans, C. glabrata, C. parapsilosis, and C. krusei isolates.

Nguyen KT, Ta P, Hoang BT, Cheng S, Hao B, Nguyen MH, Clancy CJ.

Department of Medicine, University of Florida College of Medicine, Gainesville, Florida, USA.

Anidulafungin targets the cell walls of Candida species by inhibiting beta-1,3-glucan synthase, thereby killing isolates and exerting prolonged postantifungal effects (PAFEs). We performed time-kill and PAFE experiments on Candida albicans (n = 4), C. glabrata (n = 3), C. parapsilosis (n = 3), and C. krusei (n = 2) isolates and characterized the PAFEs in greater detail. MICs were 0.008 to 0.125 microg/ml against C. albicans, C. glabrata, and C. krusei and 1.0 to 2.0 microg/ml against C. parapsilosis. During time-kill experiments, anidulafungin caused significant kills at 16x MIC (range, log 2.68 to 3.89) and 4x MIC (log 1.87 to 3.19), achieving fungicidal levels (>or=log 3) against nine isolates. A 1-hour drug exposure during PAFE experiments resulted in kills ranging from log 1.55 to 3.47 and log 1.18 to 2.89 (16x and 4x MIC, respectively), achieving fungicidal levels against four isolates. Regrowth of all 12 isolates was inhibited for >or=12 h after drug washout. Isolates of each species collected 8 h after a 1-hour exposure to anidulafungin (16x and 4x MIC) were hypersusceptible to sodium dodecyl sulfate (0.01 to 0.04%) and calcofluor white (40 microg/ml). Moreover, PAFEs were associated with major cell wall disturbances, as evident in electron micrographs of viable cells, and significant reductions in adherence to buccal epithelial cells (P

PMCID: PMC2715634 PMID: 19364856 [PubMed - indexed for MEDLINE]

1241. Sci Am. 2009 Apr;300(4):40-7.

Saving the honeybee.

Cox-Foster D, vanEngelsdorp D.

Pennsylvania State University, USA.

PMID: 19363919 [PubMed - indexed for MEDLINE]

1242. Am J Infect Control. 2009 Sep;37(7):541-4. Epub 2009 Apr 10.

Accidental exposures to blood and body fluid in the operation room and the issue of underreporting.

Nagao M, Iinuma Y, Igawa J, Matsumura Y, Shirano M, Matsushima A, Saito T, Takakura S, Ichiyama S.

Department of Infection Control and Prevention, Kyoto University Hospital, Kyoto, Japan. mnagao@kuhp.kyoto-u.ac.jp

Comment in Am J Infect Control. 2010 Mar;38(2):163-5.

A retrospective review of all exposure injuries affecting members of the operative care line at a single university hospital between January 2000 and December 2007 was performed. A questionnaire survey on current status of adherence to barrier precautions was also completed by 164 staff members. Of 136 exposure injuries, 87 (64.0%) were in surgeons, and 49 (36.0%) were in scrub nurses. Surgeons were most commonly injured during suturing (49, 56%), followed by "handing over sharps" (7, 8%), whereas scrub nurses were most commonly injured during "counting and sorting of sharps" (15, 41%), followed by "handing over sharps," and "splash." The questionnaire survey revealed that compliance with goggles, face shields, and double gloving was poor, and only 9% of respondents routinely used the hands-free technique. Only 22% of staff who had experienced exposure injuries reported every incident. Because circumstances of exposure injuries in operating rooms differ by profession, appropriate preventive measures should address individual situations. To reduce exposure injuries in the operating room, further efforts are required including education, mentoring, and competency training for operation personnel.

PMID: 19362389 [PubMed - indexed for MEDLINE]

1243. J Infect Dis. 2009 May 1;199(9):1399-406.

Increased virulence of Zygomycetes organisms following exposure to voriconazole: a study involving fly and murine models of zygomycosis.

Lamaris GA, Ben-Ami R, Lewis RE, Chamilos G, Samonis G, Kontoyiannis DP.

Department of Infectious Diseases, Infection Control and Employee Health, University of Texas MD Anderson Cancer Center, University of Houston, Houston, TX 77030, USA.

BACKGROUND: Breakthrough zygomycosis is increasingly observed among patients at high risk for fungal infection who are receiving voriconazole, reflecting either selective pressure or voriconazole-associated alterations in Zygomycetes virulence. We tested the latter hypothesis, using 2 phylogenetically disparate zygomycosis models.
METHODS: Three Zygomycetes strains were exposed to voriconazole by serial passages on voriconazole-containing medium. The virulence of voriconazole-exposed Zygomycetes strains was compared with that of voriconazole-nonexposed strains in Drosophila and murine models of zygomycosis by assessment of survival curves, pulmonary fungal burdens, and expression of inflammation-associated genes.
RESULTS: Among Toll-deficient (Tl(-/-)) and wild-type fruit flies, infection with Zygomycetes isolates that had been exposed to voriconazole yielded significantly lower survival rates than infection with Zygomycetes strains grown in drug-free media. In contrast, exposure of Rhizopus oryzae to itraconazole, amphotericin B, or caspofungin and exposure of Aspergillus fumigatus to voriconazole did not alter the virulence of these isolates in fruit flies. In the murine model, infection with a R. oryzae strain preexposed to voriconazole was associated with decreased survival rates and increased pulmonary fungal burdens, compared with infection with a voriconazole-nonexposed R. oryzae strain. In addition, enhanced angioinvasion, inflammation, and expression of genes involved in stress response and tissue repair were found in mouse lungs infected with voriconazole-exposed R. oryzae.
CONCLUSIONS: Exposure of Zygomycetes organisms to voriconazole selectively enhanced their virulence. The mechanisms underlying these phenotypic changes should be studied further.

PMID: 19358672 [PubMed - indexed for MEDLINE]

1244. Am J Ind Med. 2009 Jul;52(7):534-8.

Cluster of presumed organic dust toxic syndrome cases among urban landscape workers-Colorado, 2007.

Boehmer TK, Jones TS, Ghosh TS, McCammon CS, Vogt RL.

Tri-County Health Department, Greenwood Village, Colorado 80111, USA. tboehmer@cdc.gov

BACKGROUND: Organic dust toxic syndrome (ODTS) is an influenza-like illness typically affecting agricultural workers exposed to organic dusts. In July 2007, Tri-County Health Department investigated a cluster of acute respiratory illnesses among urban landscape workers with known mulch exposure.
METHODS: An epidemiologic study of landscape workers was conducted. Employees were interviewed regarding illness and occupational exposures. Medical records were reviewed. Mulch samples were tested for fungi and endotoxins.
RESULTS: Five (12%) of 43 employees experienced respiratory illness compatible with ODTS. Illness was associated with prolonged mulch exposure (>or=6 vs. <6 hr/day; relative risk = 24.7; 95% confidence interval = 3.3-184.9). Mulch samples contained high levels of Aspergillus spores and endotoxin.
CONCLUSIONS: Contaminated mulch was implicated as the source of presumed ODTS among landscape workers, highlighting that ODTS is not limited to rural agricultural settings. Education of employers, safety officers, and clinicians is necessary to improve recognition and prevention of ODTS within urban occupational groups.

PMID: 19358224 [PubMed - indexed for MEDLINE]

1245. Ann Allergy Asthma Immunol. 2009 Mar;102(3):210-5.

Low tumor necrosis factor alpha levels and neutrophil counts in nasal lavage after mold exposure.

Hellgren UM, Leino M, Aarnisalo AA, Mussalo-Rauhamaa H, Alenius H, Reijula K.

Finnish Institute of Occupational Health, Helsinki, Finland. ulla-maija.hellgren@ttl.fi

BACKGROUND: The results of allergy tests against molds usually remain negative in patients with upper respiratory tract and conjunctival symptoms after microbial exposure in a water-damaged building. Most mold-exposed persons report nasal irritation. Immune mechanisms of the nasal symptoms have not been fully elucidated.
OBJECTIVE: To investigate local inflammatory responses after mold exposure in the upper respiratory tract and the feasibility of nasal lavage in diagnosing work-related exposure.
METHODS: Altogether, 26 mold-exposed and 20 nonexposed workers from the same hospital were selected for the present study. The work premises of the exposed workers had detectable moisture and microbial problems. All exposed workers and their nonexposed controls underwent clinical examination, laboratory tests to detect allergy to molds, and nasal lavage. Inflammatory cells and proinflammatory cytokines were measured in the nasal lavage fluid. Nasal lavages were performed again 6 months after a thorough renovation of the building.
RESULTS: In the nasal lavage, the neutrophil count and the level of tumor necrosis factor alpha in the exposed employees were lower, whereas the macrophage and epithelial cell counts were higher than in the control group. After the renovation, no difference was found in inflammatory response between the study group and the control group. The mean concentration of serum IgG to Stachybotrys chartarum was higher in the exposed workers.
CONCLUSIONS: These results suggest that exposure to toxin-producing microbial growth in a water-damaged building caused immunosuppression in nasal mucosa, leading to a decrease in neutrophil counts and tumor necrosis factor alpha levels. Nasal lavage is a suitable method for examining inflammatory responses in work-related mold exposure.

PMID: 19354067 [PubMed - indexed for MEDLINE]

1246. Phytopathology. 2009 May;99(5):472-9.

Diversity, virulence, and 2,4-diacetylphloroglucinol sensitivity of Gaeumannomyces graminis var. tritici isolates from Washington state.

Kwak YS, Bakker PA, Glandorf DC, Rice JT, Paulitz TC, Weller DM.

Department of Plant Pathology, Washington State University, Pullman, WA 99164-6430, USA.

We determined whether isolates of the take-all pathogen Gaeumannomyces graminis var. tritici become less sensitive to 2,4-diacetylphloroglucinol (2,4-DAPG) during wheat monoculture as a result of exposure to the antibiotic over multiple growing seasons. Isolates of G. graminis var. tritici were baited from roots of native grasses collected from noncropped fields and from roots of wheat from fields with different cropping histories near Lind, Ritzville, Pullman, and Almota, WA. Isolates were characterized by using morphological traits, G. graminis variety-specific polymerase chain reaction and pathogenicity tests. The sensitivity of G. graminis var. tritici isolates to 2,4-DAPG was determined by measuring radial growth of each isolate. The 90% effective dose value was 3.1 to 4.4 microg ml(-1) for 2,4-DAPG-sensitive isolates, 4.5 to 6.1 microg ml(-1) for moderately sensitive isolates, and 6.2 to 11.1 microg ml(-1) for less sensitive isolates. Sensitivity of G. graminis var. tritici isolates to 2,4-DAPG was normally distributed in all fields and was not correlated with geographic origin or cropping history of the field. There was no correlation between virulence on wheat and geographical origin, or virulence and sensitivity to 2,4-DAPG. These results indicate that G. graminis var. tritici does not become less sensitive to 2,4-DAPG during extended wheat monoculture.

PMID: 19351242 [PubMed - indexed for MEDLINE]

1247. J Biol Chem. 2009 May 29;284(22):15233-45. Epub 2009 Apr 6.

Thioredoxin-related Protein 32 is an arsenite-regulated Thiol Reductase of the proteasome 19 S particle.

Wiseman RL, Chin KT, Haynes CM, Stanhill A, Xu CF, Roguev A, Krogan NJ, Neubert TA, Ron D.

Kimmel Center for Biology and Medicine of the Skirball Institute , New York University School of Medicine, New York, New York 10016, USA.

Perturbation of the cytoplasmic protein folding environment by exposure to oxidative stress-inducing As(III)-containing compounds challenges the ubiquitin-proteasome system. Here we report on mass spectrometric analysis of As(III)-induced changes in the proteasome's composition in samples prepared by stable isotope labeling with amino acids in cell culture, using mammalian cells in which TRP32 (thioredoxin-related protein of 32 kDa; also referred to as TXNL1) was identified as a novel subunit of the 26 S proteasome. Quantitative genetic interaction mapping, using the epistatic miniarray profiling approach, identified a functional connection between TRP32 and the proteasome. Deletion of txl1, the Schizosaccharomyces pombe homolog of TRP32, results in a slow growth phenotype when combined with deletion of cut8, a gene required for normal proteasome localization. Deletion analysis in vivo, chemical cross-linking, and manipulation of the ATP concentration in vitro during proteasome immunopurification revealed that the C-terminal domain of mammalian TRP32 binds the 19 S regulatory particle in proximity to the proteasome substrate binding site. Thiol modification with polyethylene glycol-maleimide showed disulfide bond formation at the active site of TRP32 in cells exposed to As(III). Pulse-chase labeling showed that TRP32 is a stable protein whose half-life of >6 h is surprisingly reduced to 1 h upon exposure of cells to As(III). These findings reveal a previously undescribed thiol reductase at the proteasome's regulatory particle.

PMCID: PMC2685704 PMID: 19349280 [PubMed - indexed for MEDLINE]

1248. J Allergy Clin Immunol. 2009 Apr;123(4):925-32.e11.

Combined sensitization of mice to extracts of dust mite, ragweed, and Aspergillus species breaks through tolerance and establishes chronic features of asthma.

Goplen N, Karim MZ, Liang Q, Gorska MM, Rozario S, Guo L, Alam R.

Department of Medicine, Division of Allergy and Immunology, National Jewish Health, University of Colorado Denver Health Sciences Center, Denver, CO 80206, USA.

BACKGROUND: Existing asthma models develop tolerance when chronically exposed to the same allergen.
OBJECTIVE: We sought to establish a chronic model that sustains features of asthma long after discontinuation of allergen exposure.
METHODS: We immunized and exposed mice to a combination of single, double, or triple allergens (dust mite, ragweed, and Aspergillus species) intranasally for 8 weeks. Airway hyperreactivity (AHR) and morphologic features of asthma were studied 3 weeks after allergen exposure. Signaling effects of the allergens were studied on dendritic cells.
RESULTS: Sensitization and repeated exposure to a single allergen induced tolerance. Sensitization to double and especially triple allergens broke through tolerance and established AHR, eosinophilic inflammation, mast cell and smooth muscle hyperplasia, mucus production, and airway remodeling that persisted at least 3 weeks after allergen exposure. Mucosal exposure to triple allergens in the absence of an adjuvant was sufficient to induce chronic airway inflammation. Anti-IL-5 and anti-IL-13 antibodies inhibited inflammation and AHR in the acute asthma model but not in the chronic triple-allergen model. Multiple allergens produce a synergy in p38 mitogen-activated protein kinase signaling and maturation of dendritic cells, which provides heightened T-cell costimulation at a level that cannot be achieved with a single allergen.
CONCLUSIONS: Sensitivity to multiple allergens leads to chronic asthma in mice. Multiple allergens synergize in dendritic cell signaling and T-cell stimulation that allows escape from the single allergen-associated tolerance development.

PMCID: PMC2683988 PMID: 19348928 [PubMed - indexed for MEDLINE]

1249. Waste Manag. 2009 Sep;29(9):2454-61. Epub 2009 Apr 5.

Baseline levels of bioaerosols and volatile organic compounds around a municipal waste incinerator prior to the construction of a mechanical-biological treatment plant.

Vilavert L, Nadal M, Inza I, Figueras MJ, Domingo JL.

Laboratory of Toxicology and Environmental Health, School of Medicine,Rovira i Virgili University, Sant Llorenç 21, 43201 Reus, Catalonia, Spain.

New waste management programs are currently aimed at developing alternative treatment technologies such as mechanical-biological treatment (MBT) and composting plants. However, there is still a high uncertainty concerning the chemical and microbiological risks for human health, not only for workers of these facilities, but also for the population living in the neighborhood. A new MBT plant is planned to be constructed adjacently to a municipal solid waste incinerator (MSWI) in Tarragona (Catalonia, Spain). In order to evaluate its potential impact and to differentiate the impacts of MSWI from those of the MBT when the latter is operative, a pre-operational survey was initiated by determining the concentrations of 20 volatile organic compounds (VOCs) and bioaerosols (total bacteria, gram-negative bacteria, fungi and Aspergillus fumigatus) in airborne samples around the MSWI. The results indicated that the current concentrations of bioaerosols (ranges: 382-3882, 18-790, 44-926, and <1-7 CFU/m(3) for fungi at 25 degrees C, fungi at 37 degrees C, total bacteria, and gram-negative bacteria, respectively) and VOCs (ranging from 0.9 to 121.2 microg/m(3)) are very low in comparison to reported levels in indoor and outdoor air in composting and MBT plants, as well in urban and industrial zones. With the exception of total bacteria, no correlations were observed between the environmental concentrations of biological agents and the direction/distance from the facility. However, total bacteria presented significantly higher levels downwind. Moreover, a non-significant increase of VOCs was detected in sites closer to the incinerator, which means that the MSWI could have a very minor impact on the surrounding environment.

PMID: 19346120 [PubMed - indexed for MEDLINE]

1250. Fungal Genet Biol. 2009 Apr;46(4):333-41.

The basidiomycetous mushroom Lentinula edodes white collar-2 homolog PHRB, a partner of putative blue-light photoreceptor PHRA, binds to a specific site in the promoter region of the L. edodes tyrosinase gene.

Sano H, Kaneko S, Sakamoto Y, Sato T, Shishido K.

Department of Life Science, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Midori-ku, Yokohama, Japan. sano.h.aa@m.titech.ac.jp

We isolated a cDNA homolog of Neurospora crassa wc-2 from the basidiomycetous mushroom Lentinula edodes and termed it phrB cDNA. The deduced PHRB (313 amino acid residues) contained a PAS domain and a zinc-finger motif. Random binding-site selection analysis of the PHRB produced in Escherichia coli revealed that it bound to a 7-bp sequence with the consensus sequence 5'GATA/TTG/T/AC3'. Electrophoretic mobility-shift assay showed that it also bound to the consensus sequence 5'GATATTC3' in the promoter region of the L. edodes tyrosinase gene (Le.tyr). In vitro GST-pulldown immunoblot analysis disclosed that PHRB interacts with a putative blue-light photoreceptor of L. edodes (PHRA), the homolog of N. crassa WC-1, through the PAS B- and/or PAS C domain of PHRA. The expression of phrB and Le.tyr genes in pre-primordial mycelia of L. edodes is induced by light exposure, suggesting that PHRB can regulate the expression of the Le.tyr gene in a light-dependent manner.

PMID: 19344689 [PubMed - indexed for MEDLINE]

1251. Proteomics. 2009 May;9(9):2578-88.

A proteomic-based approach for the identification of immunodominant Cryptococcus neoformans proteins.

Young M, Macias S, Thomas D, Wormley FL Jr.

Department of Biology, The University of Texas at San Antonio, San Antonio, TX 78249-0062, USA.

Cryptococcus neoformans is an opportunistic fungal pathogen that can cause life-threatening meningoencephalitis in immune compromised patients. Previous, studies in our laboratory have shown that prior exposure to an IFN-gamma-producing C. neoformans strain (H99gamma) elicits protective immunity against a second pulmonary C. neoformans challenge. Here, we characterized the antibody response produced in mice protected against experimental pulmonary C. neoformans infection compared to nonprotected mice. Moreover, we evaluated the efficacy of using serum antibody from protected mice to detect immunodominant C. neoformans proteins. Protected mice were shown to produce significantly more C. neoformans-specific antibodies following a second experimental pulmonary cryptococcal challenge compared to nonprotected mice. Immunoblot analysis of C. neoformans proteins resolved by 2-DE using serum from nonprotected mice failed to show any reactivity. In contrast, serum from protected mice was reactive with several cryptococcal protein spots. Analysis of these spots by capillary HPLC-ESI-MS/MS identified several cryptococcal proteins shown to be associated with the pathogenesis of cryptococcosis. Our studies demonstrate that mice immunized with C. neoformans strain H99gamma produce antibodies that are immune reactive against specific cryptococcal proteins that may provide a basis for the development of immune based therapies that induce protective anticryptococcal immune responses.

PMCID: PMC2754056 PMID: 19343717 [PubMed - indexed for MEDLINE]

1252. J Biophotonics. 2008 Sep;1(4):299-309.

Versatile laser-based cell manipulator.

Maghelli N, Tolić-Nørrelykke IM.

Max-Planck-Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany. maghelli@mpi-cbg.de

Here we describe a two-photon microscope and laser ablation setup combined with optical tweezers. We tested the setup on the fission yeast Schizosaccharomyces pombe, a commonly used model organism. We show that long-term imaging can be achieved without significant photo-bleaching or damage of the sample. The setup can precisely ablate sub-micrometer structures, such as microtubules and mitotic spindles, inside living cells, which remain viable after the manipulation. Longer exposure times lead to ablation, while shorter exposures lead to photo-bleaching of the target structure. We used optical tweezers to trap intracellular particles and to displace the cell nucleus. Two-photon fluorescence imaging of the manipulated cell can be performed simultaneously with trapping. The combination of techniques described here may help to solve a variety of problems in cell biology, such as positioning of organelles and the forces exerted by the cytoskeleton.

PMID: 19343653 [PubMed - indexed for MEDLINE]

1253. Mycopathologia. 2009 Dec;168(6):283-97. Epub 2009 Apr 3.

Invasive fungal infection in haematopoietic stem cell transplant recipients: epidemiology from the transplant physician's viewpoint.

Bow EJ.

Sections of Infectious Diseases and Haematology/Oncology, Department of Internal Medicine, The University of Manitoba, Winnipeg, MB, Canada. ebow@hsc.mb.ca

The practice of hematopoietic stem cell transplantation (HSCT) has undergone many changes that affect the likelihood that a given patient would develop an invasive fungal infection (IFI). The risks for IFI and the types of IFI that may occur are not continuous over the time course after transplantation. IFIs vary with the events that occur during the pre-engraftment neutropenic period, the early post-engraftment period until approximately day 100 post-transplant, and those in the late post-engraftment period after day 100. A number of well-recognized transplant recipient-, transplant procedure-, and transplant complication-related factors play a role in the likelihood of IFI. Important recipient-related factors include age, state of the underlying disease for which the HSCT is being done, and treatment-related history. Transplant procedure-related factors include the type of transplant (autologous or allogeneic), the use of and timing of anti-fungal prevention strategies including whether or not the transplant was conducted in a protected environment to minimize environmental exposure to mould conidia, the choice of conditioning (myeloablative or non-myeloablative), human leucocyte antigen-relatedness [autologous, matched related, mismatched related (including haploidentical pairings), unrelated (matched or mismatched)], stem cell source (bone marrow, peripheral, or cord blood), stem cell dosing, and stem cell product processing (red cell, plasma, or T-lymphocyte depletions, or CD34 selections). Transplant-related complications include duration of pre-engraftment period of neutropenia, graft failure or rejection, the degree of cytotoxic conditioning therapy-related intestinal mucosal damage, acute and chronic graft-versus-host disease (GvHD), the use of corticosteroids for the prevention or management of GvHD, the presence of cytomegalovirus infection and disease. The interaction of these factors over a given patient's journey through HSCT conspires to promote or reduce the overall IFI risk and set the conditions for the development of any given IFI. The following discussion attempts to look at this from the perspective of the transplant physician struggling to account for these interactions and their attendant risks for IFI.

PMID: 19343534 [PubMed - indexed for MEDLINE]

1254. J Photochem Photobiol B. 2009 Jun 3;95(3):156-61. Epub 2009 Mar 5.

Photoprotective role of carotenoids in yeasts: Response to UV-B of pigmented and naturally-occurring albino strains.

Moliné M, Libkind D, Diéguez Mdel C, van Broock M.

Instituto de Investigaciones en Biodiversidad y Medio Ambiente, CONICET-UNComahue, Bariloche, Argentina. martinmoline@crub.uncoma.edu.ar

In this work, the photoprotective role of carotenoids in yeasts was analysed by contrasting the responses to UV-B of pigmented and naturally occurring albino strains of Sporobolomyces ruberrimus and Cystofilobasidium capitatum in different conditions. Albino and pigmented strains were confirmed to be conspecific by PCR fingerprinting and rDNA sequencing. Experimental exposure to UV-B conducted with both yeast species showed that the pigmented strains were more tolerant to UV-B than the albino strains and that the increment in carotenoid contents during the stationary growth phase enhance survivorship. These results indicated that carotenoid pigments afford UV-B protection in yeasts.

PMID: 19342251 [PubMed - indexed for MEDLINE]

1255. Semin Cutan Med Surg. 2009 Mar;28(1):44-8.

New tools in nail disorders.

Richert B, Lateur N, Theunis A, Andre J.

Dermatology Department, University of Liège, Belgium. bertrand.richert@skynet.be

Tumors of the nail unit may be difficult to diagnose because of the screening effect of the nail plate. In longitudinal melanonychia, several new promising techniques assist with early diagnosis of melanoma (in vivo matrix dermoscopy and immunohistochemistry) as well as sparing as much of the healthy tissues as is possible (shave biopsy technique). Diagnosing nail disorders is in some instances difficult both for the clinician and the pathologist. New tools such as polymerase chain reaction have been proposed for onychomycosis, which accounts for more than half of nail conditions, will allow quick and accurate diagnosis. However, polymerase chain reaction analysis remains expensive and is not routinely used by clinicians. Scoring nail dystrophy by clinical observation remains very subjective; therefore, severity indexes have been proposed. Another emerging noninvasive technique is forensic analysis of nail clippings for detection of drug intake and abuse, as well as exposure to environmental pollution.

PMID: 19341942 [PubMed - indexed for MEDLINE]

1256. FEMS Immunol Med Microbiol. 2009 Jun;56(1):88-93. Epub 2009 Apr 1.

Innate responses of corneal epithelial cells against Aspergillus fumigatus challenge.

Guo H, Wu X.

Department of Ophthalmology, Qilu Hospital of Shandong University, Jinan, Shandong Province, China.

Toll-like receptors (TLRs) are key components of the innate immune system that detects microbial infection and triggers host defensive responses. To determine the roles of TLR2 and TLR4 in corneal epithelial cells in mediating innate responses against Aspergillus fumigatus, telomerase-immortalized human corneal epithelial cells (THCE) were challenged by TLR2 ligand zymosan, TLR4 ligand lipopolysaccharide and A. fumigatus hyphae, respectively. Culture media were collected at different time points and enzyme-linked immunosorbent assay was performed to detect the levels of inflammatory cytokines interleukin-1beta (IL-1beta) and IL-6. We found that THCE responded to the challenge of TLR2 or TLR4 ligand by expressing and secreting inflammatory cytokines into the culture media. And exposure of THCE to A. fumigatus hyphae resulted in the upregulation of IL-1beta and IL-6. Treatment with TLR2- or TLR4-siRNA plasmid reduced TLR2 or TLR4 expression level in THCE when compared with controls, and caused a significant decrease in A. fumigatus-induced IL-1beta and IL-6 production. Our results suggested that THCE can respond to TLR2 and TLR4 ligand challenge by secreting IL-1beta and IL-6. They recognize A. fumigatus hyphae via TLR2 and TLR4 and initiate innate immune responses. Corneal epithelial cells play a role in innate defense against fungal infection through the mediation of inflammatory cytokines production.

PMID: 19341426 [PubMed - indexed for MEDLINE]

1257. Mycorrhiza. 2009 Aug;19(6):365-74. Epub 2009 Apr 2.

Fenpropimorph slows down the sterol pathway and the development of the arbuscular mycorrhizal fungus Glomus intraradices.

Campagnac E, Fontaine J, Lounès-Hadj Sahraoui A, Laruelle F, Durand R, Grandmougin-Ferjani A.

Laboratoire de Mycologie Phytopathologie Environnement, Université du Littoral Côte d'Opale, B.P. 699, 62228, Calais Cedex, France.

The direct impact of fenpropimorph on the sterol biosynthesis pathway of Glomus intraradices when extraradical mycelia alone are in contact with the fungicide was investigated using monoxenic cultures. Bi-compartmental Petri plates allowed culture of mycorrhizal chicory roots in a compartment without fenpropimorph and exposure of extraradical hyphae to the presence of increasing concentrations of fenpropimorph (0, 0.02, 0.2, 2, 20 mg l(-1)). In the fungal compartment, sporulation, hyphal growth, and fungal biomass were already reduced at the lowest fungicide concentration. A decrease in total sterols, in addition to an increase in the amount of squalene and no accumulation of abnormal sterols, suggests that the sterol pathway is severely slowed down or that squalene epoxidase was inhibited by fenpropimorph in G. intraradices. In the root compartment, neither extraradical and intraradical development of the arbuscular mycorrhizal (AM) fungus nor root growth was affected when they were not in direct contact with the fungicide; only hyphal length was significantly affected at 2 mg l(-1) of fenpropimorph. Our results clearly demonstrate a direct impact of fenpropimorph on the AM fungus by a perturbation of its sterol metabolism.

PMID: 19340463 [PubMed - indexed for MEDLINE]

1258. Can Vet J. 2009 Jan;50(1):93.

Inhalation pneumonitis in a dog from spores of puffball mushrooms.

Rubensohn M.

PMCID: PMC2603663 PMID: 19337622 [PubMed - indexed for MEDLINE]

1259. J Microsc. 2009 Apr;234(1):1-8.

Intracellular nanosurgery and cell enucleation using a picosecond laser.

Raabe I, Vogel SK, Peychl J, Tolić-Nørrelykke IM.

Max Planck Institute of Molecular Cell Biology & Genetics, Pfotenhauerstrasse 108, Dresden, Germany.

Living cells are highly organized in space and time, which makes spatially and temporally confined manipulations an indispensable tool in cell biology. Laser-based nanosurgery is an elegant method that allows precise ablation of intracellular structures. Here, we show cutting of fluorescently labelled microtubules and mitotic spindles in fission yeast, performed with a picosecond laser coupled to a confocal microscope. Diverse effects from photo-bleaching to partial and complete breakage are obtained by varying the exposure time, while simultaneously imaging the structures of interest. Using this system we developed an efficient technique to generate enucleated cells without perturbing the distribution of other organelles. This enucleation method can be used to study the cytoskeleton in a nucleus-free environment, as well as the role of the nucleus in cell growth and a variety of cellular functions.

PMID: 19335451 [PubMed - indexed for MEDLINE]

1260. Int J Mol Sci. 2008 Dec;9(12):2543-58. Epub 2008 Dec 10.

Species-specific fungal DNA in airborne dust as surrogate for occupational mycotoxin exposure?

Halstensen AS.

National Institute of Occupational Health, Department of Chemical and Biological Working Environment, Oslo, Norway. anne.s.halstensen@stami.no

Possible health risks associated with occupational inhalation of mycotoxin-containing dust remain largely unknown, partly because methods for mycotoxin detection are not sensitive enough for the small dust masses obtained by personal sampling, which is needed for inhalable exposure measurements. Specific and sensitive PCR detection of fungi with mycotoxin-producing potential seem to be a good surrogate for occupational exposure measurements that include all fungal structures independent of morphology and cultivability. Results should, however, be interpreted with caution due to variable correlations with mycotoxin concentrations.

PMCID: PMC2635655 PMID: 19330091 [PubMed]

1261. Curr Biol. 2009 Apr 28;19(8):621-9. Epub 2009 Mar 26.

Hsp90 orchestrates temperature-dependent Candida albicans morphogenesis via Ras1-PKA signaling.

Shapiro RS, Uppuluri P, Zaas AK, Collins C, Senn H, Perfect JR, Heitman J, Cowen LE.

Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.

Comment in Curr Biol. 2009 Apr 28;19(8):R333-4.

BACKGROUND: Hsp90 is an environmentally contingent molecular chaperone that influences the form and function of diverse regulators of cellular signaling. Hsp90 potentiates the evolution of fungal drug resistance by enabling crucial cellular stress responses. Here we demonstrate that in the leading fungal pathogen of humans, Candida albicans, Hsp90 governs cellular circuitry required not only for drug resistance but also for the key morphogenetic transition from yeast to filamentous growth that is crucial for virulence. This transition is normally regulated by environmental cues, such as exposure to serum, that are contingent upon elevated temperature to induce morphogenesis. The basis for this temperature dependence has remained enigmatic.
RESULTS: We show that compromising Hsp90 function pharmacologically or genetically induces a transition from yeast to filamentous growth in the absence of external cues. Elevated temperature relieves Hsp90-mediated repression of the morphogenetic program. Hsp90 regulates morphogenetic circuitry by repressing Ras1-PKA signaling. Modest Hsp90 compromise enhances the phenotypic effects of activated Ras1 signaling whereas deletion of positive regulators of the Ras1-PKA cascade blocks the morphogenetic response to Hsp90 inhibition. Consistent with the requirement for morphogenetic flexibility for virulence, depletion of C. albicans Hsp90 attenuates virulence in a murine model of systemic disease.
CONCLUSIONS: Hsp90 governs the integration of environmental cues with cellular signaling to orchestrate fungal morphogenesis and virulence, suggesting new therapeutic strategies for life-threatening infectious disease. Hsp90's capacity to govern a key developmental program in response to temperature change provides a new mechanism that complements the elegant repertoire that organisms utilize to sense temperature.

PMCID: PMC2735497 PMID: 19327993 [PubMed - indexed for MEDLINE]

1262. Immunobiology. 2009;214(4):321-30. Epub 2008 Oct 17.

Zymosan treatment of mouse mast cells enhances dectin-1 expression and induces dectin-1-dependent reactive oxygen species (ROS) generation.

Yang Z, Marshall JS.

Atlantic Baptist University, N.B., Canada.

Dectin-1 is a major beta-glucan receptor expressed in the innate immune cells such as macrophages, neutrophils and dendritic cells. It can mediate pro-inflammatory mediator release and other cellular responses such as phagocytosis and respiratory burst in response to pathogens. Mast cells are sentinel cells of the immune system found in greater numbers at sites of pathogen exposure such as the skin and airways than in other body sites. Dectin-1 on human mast cells has been shown to mediate the production of leukotrienes in response to yeast zymosan. In this study, using RT-PCR and FACS analysis, we examined both mRNA and protein expression of dectin-1 on bone marrow-derived cultured mast cells (BMMC) from either C57BL/6 or TLR2 deficient mice. Low levels of surface dectin-1 were detected on the mast cell surface, which could be up-regulated by zymosan activation. Neither mouse plasma nor decomplemented plasma (56 degrees C, 30 min) induced altered dectin-1 protein expression although zymosan-activated C57BL/6 BMMCs expressed two dectin-1 mRNA isoforms. Addition of laminarin, a well-established dectin-1 inhibitor, significantly inhibited surface expression of dectin-1 (p < 0.05), which further confirmed that dectin-1 surface expression was up-regulated by non-opsonized zymosan activation. Further studies showed that zymosan stimulated both C57BL/6 and TLR2(-/-) deficient BMMCs to generate intracellular oxidative burst. Pretreatment of BMMCs with laminarin inhibited ROS generation significantly (p < 0.05) after 2 h zymosan activation. Therefore, intracellular ROS generation in murine mast cells in response to zymosan is dependent on dectin-1 receptors.

PMID: 19327548 [PubMed - indexed for MEDLINE]

1263. Curr Opin Allergy Clin Immunol. 2009 Apr;9(2):128-35.

The role of indoor allergens in the development of asthma.

Gaffin JM, Phipatanakul W.

Department of Pediatrics, Boston Children's Hospital, Massachusetts, USA.

PURPOSE OF REVIEW: Asthma prevalence has markedly increased over the past 30 years. Although atopy and exposure to environmental allergens are known to exacerbate asthma, recent literature supports a causal role of indoor allergens in disease development.
RECENT FINDINGS: High-risk birth cohorts continue to point to atopy as the main risk factor for developing asthma. Exposure to perennial allergens has also been linked to the development of asthma, though with less consistency. Intervention at the level of allergen exposure and allergic immune response is promising. SUMMARY: The current model of atopic asthma, the predominant phenotype, incorporates genetic and environmental factors in the development of disease. Although genetic factors are less malleable, the environmental component lends itself to analysis and modification.For many, the development of asthma starts with allergen exposure leading to atopic sensitization and subsequent disease. Several studies support the progression from exposure to sensitization with the potential of extremely high levels of exposure leading to tolerance. Likewise, the progression from atopy to asthma is well documented,especially in genetically predisposed children. Recent intervention trials confirm these findings and begin to show promise for the prevention of asthma by interrupting the allergen exposure==>allergen sensitization==>atopic asthma pathway.

PMCID: PMC2674017 PMID: 19326507 [PubMed - indexed for MEDLINE]

1264. Occup Med (Lond). 2009 Jun;59(4):237-42. Epub 2009 Mar 26.

Occupational exposure and sensitization to fungi among museum workers.

Wiszniewska M, Walusiak-Skorupa J, Pannenko I, Draniak M, Palczynski C.

Department of Occupational Diseases and Toxicology, Nofer Institute of Occupational Medicine, 91-348 Lodz, Poland. martaz@imp.lodz.pl

BACKGROUND: Museum employees are exposed to fungi and storage mites in the workplace. AIMS: To evaluate the prevalence and risk factors of sensitization to moulds, as well as clinical symptoms associated with allergy in museum workers.
METHODS: A total of 103 employees of the Polish National Museum (NM) in Warsaw, potentially exposed to fungi during their work, were assessed using a questionnaire and skin prick tests to common allergens and fungal extracts. The level of total and serum-specific IgE to moulds was evaluated, and spirometry was performed in all subjects. Mycological analysis of the workplace was also performed.
RESULTS: Penicillium, Aspergillus, Cladosporium, Alternaria, Trichoderma, Acremonium and Paecilomyces were the most frequent species isolated from investigated exhibits of NM. Thirty per cent of museum employees were sensitized to at least one of the fungal allergens. Logistic regression analysis revealed that duration of occupational exposure lasting >5 years, family history of atopy, presence of a cat at home, sinusitis, allergic rhinitis and a history of frequent respiratory infections were risk factors for the development of sensitization to fungi in this working group.
CONCLUSIONS: This study suggests an important role of fungi as occupational allergens for museum workers. The prevalence of allergic symptoms among employees of NM was relatively high. Further studies are necessary to elucidate the importance of particular fungal species in the development of occupational allergy.

PMID: 19325162 [PubMed - indexed for MEDLINE]

1265. Fungal Genet Biol. 2009 Jun-Jul;46(6-7):461-72. Epub 2009 Mar 24.

Reactive oxygen species and autophagy play a role in survival and differentiation of the phytopathogen Moniliophthora perniciosa.

Pungartnik C, Melo SC, Basso TS, Macena WG, Cascardo JC, Brendel M.

Laboratório de Biologia de Fungos, Centro de Biotecnologia e Genética, Universidade Estadual de Santa Cruz (UESC), Rodovia Ilhéus-Itabuna, CEP, Brazil.

The hemibiotrophic basidiomycete Moniliophthora perniciosa causes "witches' broom disease" in cacao (Theobroma cacao). During plant infection, M. perniciosa changes from mono to dikaryotic life form, an event which could be triggered by changes in plant nutritional offer and plant defense molecules, i.e., from high to low content of glycerol and hydrogen peroxide. We have recently shown that in vitro glycerol induces oxidative stress resistance in dikaryotic M. perniciosa. In order to understand under which conditions in parasite-plant interaction M. perniciosa changes from intercellular monokaryotic to intracellular dikaryotic growth phase we studied the role of glycerol on mutagen-induced oxidative stress resistance of basidiospores and monokaryotic hyphae; we also studied the role of H(2)O(2) as a signaling molecule for in vitro dikaryotization and whether changes in nutritional offer by the plant could be compensated by inducible fungal autophagy. Mono-/dikaryotic glycerol or glucose-grown cells and basidiospores were exposed to the oxidative stress-inducing mutagens H(2)O(2) and Paraquat as well as to pre-dominantly DNA damaging 4-nitroquinoline-1-oxide and UVC irradiation. Basidiospores showed highest resistance to all treatments and glycerol-grown monokaryotic hyphae were more resistant than dikaryotic hyphae. Monokaryotic cells exposed to 1microM of H(2)O(2) in glycerol-media induced formation of clamp connections within 2 days while 1mM H(2)O(2) did not within a week in the same medium; no clamp connections were formed in H(2)O(2)-containing glucose media within a week. Lower concentrations of H(2)O(2) and glycerol, when occurring in parallel, are shown to be two signals for dikaryotization in vitro and may be also during the course of infection. Q-PCR studies of glycerol-grown dikaryotic cells exposed to oxidative stress (10mM H(2)O(2)) showed high expression of MpSOD2 and transient induction of ABC cytoplasmic membrane transporter gene MpYOR1 and autophagy-related gene MpATG8. Expression of a second ABC transporter gene MpSNQ2 was 14-fold induced after H(2)O(2) exposure in glucose as compared to glycerol-grown hyphae while MpYOR1 did not show strong variation of expression under similar conditions. Glucose-grown dikaryotic cells showed elevated expression of MpATG8, especially after exposure to H(2)O(2) and 4-nitroquinoline-1-oxide. During different stages preceding basidiocarp formation MpATG8 and the two catalase-encoding genes MpCTA1 and MpCTT1 were expressed continuously. We have compiled our results and literature data in a model graph, which compares the in vitro and in planta development and differentiation of M. perniciosa with the help of physiological and morphological landmarks.

PMID: 19324099 [PubMed - indexed for MEDLINE]

1266. Chin Med J (Engl). 2009 Mar 5;122(5):496-501.

Insoluble beta-glucan from the cell wall of Candida albicans induces immune responses of human THP-1 monocytes through Dectin-1.

Li M, Liu ZH, Chen Q, Zhou WQ, Yu MW, Lü GX, Lü XL, Shen YN, Liu WD, Wu SX.

Department of Medical Mycology, Institute of Dermatology, Chinese Academy of Medical Science & Peking Union Medical College, Nanjing, China. minli08@gmail.com

Comment in Chin Med J (Engl). 2009 Mar 5;122(5):483-5.

BACKGROUND: beta-glucan is the major structure component of Candida albicans (C. albicans) cell wall. It has been demonstrated that Dectin-1 as the principal C-type lectin pattern-recognition receptor (PRR) can recognize fungal beta-glucan and induce immune responses. In this study, we sought to clarify whether insoluble beta-glucan from the cell wall of C. albicans (CaIG) could induce immune responses in human THP-1 monocytes (a human acute monocytic leukemia cell line) and to determine the underlying mechanisms.
METHODS: Human THP-1 monocytes were challenged with CaIG in vitro. The mRNA expression of Dectin-1, Toll-like receptors (TLR2), proinflammatory cytokine (TNF-alpha) and chemokine (IL-8) was assayed by real-time reverse transcription polymerase chain reaction (RT-PCR). The secretion of TNF-a and IL-8 were measured by enzyme-linked immunosorbent assay (ELISA). H(2)O(2) release was determined by microplate fluorescent assay. Western blotting was used to analyze IkappaB-a phosphorylation and degradation.
RESULTS: Exposure of THP-1 monocytes to CaIG led to increased gene expression and secretion of TNF-alpha and IL-8. CaIG induced H(2)O(2) release in a time-dependent manner. CaIG hydrolyzed with zymolyase failed to induce gene expression and secretion of TNF-alpha, IL-8 and H(2)O(2) release. CaIG up-regulated the mRNA of Dectin-1, whereas the mRNA level of TLR2 was not altered. THP-1 monocytes challenged with CaIG resulted in the activation of NF-kappaB in a time-dependent manner. Dectin-1 inhibitor laminarin blocked the CaIG-induced production of TNF-alpha and H(2)O(2) in THP-1 monocytes, but no such effect was observed in pretreatment with anti-TLR2 neutralizing antibody and the LPS inhibitor (polymyxin B).
CONCLUSION: CaIG may play a role in activation of immune responses in human THP-1 cells through Dectin-1, not TLR2.

PMID: 19323897 [PubMed - indexed for MEDLINE]

1267. J Food Sci. 2009 Mar;74(2):H83-7.

Effect of soybean volatile compounds on Aspergillus flavus growth and aflatoxin production.

Cleveland TE, Carter-Wientjes CH, De Lucca AJ, Boué SM.

US Dept of Agriculture, Southern Regional Research Center, Agricultural Research Service, New Orleans, LA 70179, USA.

Soybean homogenates produced volatile compounds upon exposure to lipase. These induced volatiles were identified by SPME. Seventeen volatile compounds identified by SPME were chosen for determination of their ability to inhibit Aspergillus flavus growth and aflatoxin B(1) (AFB1) production in a solid media assay. These volatiles included aldehydes, alcohols, ketones, and furans. Of the tested compounds, the aldehydes showed the greatest inhibition of fungal growth and AFB1 production. These compounds inhibited up to 100% of the observed growth and AFB1 production as compared to the controls. The greatest activity by the aldehydes to disrupt growth was ranked as follows: 2,4 hexadienal > benzaldehyde > 2-octenal > (E)-2-heptenal > octanal > (E)-2-hexenal > nonanal > hexanal. The greatest activity by the aldehydes to reduce AFB1 was ranked as follows: (E)-2-hexenal > 2,4 hexadienal > (E)-2-heptenal > hexanal > nonanal. (E)-2-hexenal and (E)-2-heptenal were tested further in an A. flavus-inoculated corn kernel assay. Both compounds prevented colonization by A. flavus and eliminated AFB1 production when exposed to compound volumes < 10 muL as also shown in the solid media assay. The results suggest that soybeans react to lipase by production of potent antifungal volatiles.

PMID: 19323756 [PubMed - indexed for MEDLINE]

1268. Mol Biochem Parasitol. 2009 Apr;164(2):147-52.

The complementation of yeast with human or Plasmodium falciparum Hsp90 confers differential inhibitor sensitivities.

Wider D, Péli-Gulli MP, Briand PA, Tatu U, Picard D.

Département de Biologie Cellulaire, Université de Genève, Sciences III, 30 quai Ernest-Ansermet, Geneva, Switzerland.

Developing novel drugs against the unicellular parasite Plasmodium is complicated by the paucity of simple screening systems. Heat-shock proteins are an essential class of proteins for the parasite's cyclical life style between different cellular milieus and temperatures. The molecular chaperone Hsp90 assists a large variety of proteins, but its supporting functions for many proteins that are important for cancer have made it into a well-studied drug target. With a better understanding of the differences between Hsp90 and of the malarial parasite and Hsp90 of its human host, new therapeutic options might become available. We have generated a set of isogenic strains of the budding yeast Saccharomyces cerevisiae where the essential yeast Hsp90 proteins have been replaced with either of the two human cytosolic isoforms Hsp90alpha or Hsp90beta, or with Hsp90 from Plasmodium falciparum (Pf). All strains express large amounts of the Flag-tagged Hsp90 proteins and are viable. Even though the strain with Pf Hsp90 grows more poorly, it provides a tool to reconstitute additional aspects of the parasite Hsp90 complex and its interactions with substrates in yeast as a living test tube. Upon exposure of the set of Hsp90 test strains to the two Hsp90 inhibitors radicicol (Rd) and geldanamycin (GA), we found that the strain with Pf Hsp90 is relatively more sensitive to GA than to Rd compared to the strains with human Hsp90's. This indicates that this set of yeast strains could be used to screen for new Pf Hsp90 inhibitors with a wider therapeutic window.

PMID: 19320098 [PubMed - indexed for MEDLINE]

1269. J Invertebr Pathol. 2009 Mar;100(3):160-8.

Real-time quantitative PCR for analysis of candidate fungal biopesticides against malaria: technique validation and first applications.

Bell AS, Blanford S, Jenkins N, Thomas MB, Read AF.

School of Biological Sciences, University of Edinburgh, West Mains Road, Edinburgh EH93JT, UK. asb15@psu.edu

Recent research has indicated that fungal biopesticides could augment existing malaria vector control tools. Here we present a set of methodologies to monitor the in vivo kinetics of entomopathogenic fungi in Anopheles in the presence or absence of malaria parasites using quantitative real-time PCR. Three qPCR assays were successfully developed for counting fungal genomes: "specific" assays capable of distinguishing two well characterized fungal entomopathogens Beauveria bassiana isolate IMI391510 and Metarhizium anisopliae var. acridum isolate IMI330189, both of which have previously been shown to be virulent to Anopheles mosquitoes, and a "generic" fungal assay for determining any fungal burden. A fourth assay to Plasmodium chabaudi enabled quantification of co-infecting malarial parasites. All qPCR assays provide sensitive, target-specific, and robust quantification over a linear range of greater than five orders of magnitude (seven orders of magnitude for the fungal assays). B. bassiana growth within mosquitoes exposed to three different conidial challenge doses was monitored using the B. bassiana-specific assay and represents the first description of entomopathogenic fungal replication within an insect host. This revealed that, irrespective of challenge dose, after several days of relatively little replication, a sudden on-set of substantial nuclear division occurs, accompanied by physical fungal growth (hyphae) within the mosquito haemocoel shortly before death. Exposure to higher densities of conidia resulted in significantly greater pick-up by mosquitoes and to elevated fungal burdens at each time point sampled. High fungal burdens, comparable to those identified in cadavers, were attained more rapidly and mortalities occurred earlier post-exposure with increasing challenge dose. The lines of research made possible by the qPCR assays described here will contribute to optimization of fungal biopesticides against malaria and other vector-borne diseases.

PMCID: PMC2666797 PMID: 19320043 [PubMed - indexed for MEDLINE]

1270. J Photochem Photobiol B. 2009 Jun 3;95(3):148-55. Epub 2009 Feb 20.

Slt2 (Mpk1) MAP kinase is involved in the response of Saccharomyces cerevisiae to 8-methoxypsoralen plus UVA.

Dardalhon M, Agoutin B, Watzinger M, Averbeck D.

Institut Curie Section de Recherche, UMR CNRS/I.C., INSERM, Centre Universitaire d'Orsay, France. michele.dardalhon@curie.u-psud.fr

The bifunctional furocoumarin 8-methoxypsoralen (8-MOP) is a well established drug in the photochemotherapy of psoriasis and other skin diseases. In eukaryotic cells, this compound intercalates into DNA and undergoes photocycloaddition with pyrimidines to form monoadducts and interstrand crosslinks initiating a cascade of events leading to cytotoxic, mutagenic and carcinogenic responses. In yeast cells, exposure to 8-MOP plus UVA induces transcription of a large set of genes, and cellular reaction is different from an overall DNA damage response and specific to 8-MOP/UVA [M. Dardalhon, W. Lin, A. Nicolas, D. Averbeck, Specific transcriptional responses induced by 8-methoxypsoralen and UVA in yeast, FEMS Yeast Res. 7 (2007) 866-878]. To further define the relationship between induced genes and genotoxic consequences after 8-MOP/UVA treatment, the survival responses of mutants deleted for genes that are specifically induced by 8-MOP plus UVA were analysed in terms of survival. Six mutants deleted for RAD51, RAD54, DUN1, DIN7, already known to be implicated in DNA damage responses, and for SLT2/MPK1 and PDE2 involved in cell wall stress responses, were found sensitive to 8-MOP plus UVA treatment. Further characterization of slt2 mutant provides evidence for the existence of an 8-MOP/UVA response in yeast in which the yeast Slt2 MAPK pathway is implicated. Activation by 8-MOP plus UVA of this MAP kinase previously observed at the transcriptional level is now confirmed at the protein level. In addition to sensitivity to 8-MOP/UVA, yeast cells lacking SLT2 show reduced survival after 3-carbethoxypsoralen plus UVA and 1,6-dioxapyrene plus UVA. Osmotic support could suppress the sensitivities to these genotoxic agents, suggesting that these sensitivities are related to cell integrity defects and/or cell wall defects.

PMID: 19318276 [PubMed - indexed for MEDLINE]

1271. Med Vet Entomol. 2009 Jun;23(2):141-7. Epub 2009 Feb 27.

Enhanced ovicidal activity of an oil formulation of the fungus Metarhizium anisopliae on the mosquito Aedes aegypti.

Albernaz DA, Tai MH, Luz C.

Departmento de Microbiologia, Immunologia, Parasitologia e Patologia, Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.

The effect of humidity on the activity of Metarhizium anisopliae IP 46 (Metsch.) Sorokin (Hypocreales: Clavicipitaceae) formulated in sunflower oil against Aedes aegypti (L.) (Diptera: Culicidae) eggs was examined. After exposure of eggs at 75% relative humidity (RH) for 98% RH, eclosion was 98% RH, followed by: (a) a 12-day exposure at 75% RH before submersion in water; (b) a minimal 5-day exposure at > 98% RH and direct subsequent transfer of treated eggs to water, or (c) a minimal daily 20-h exposure at > 98% RH alternating with 4 h at 75% RH for 10 days. We demonstrate that oil-based formulations of conidia of M. anisopliae enhance ovicidal activity at high humidities and conclude that these formulations have potential in the integrated control of Ae. aegypti.

PMID: 19309438 [PubMed - indexed for MEDLINE]

1272. Infect Immun. 2009 Jun;77(6):2436-46. Epub 2009 Mar 23.

Cryptococcus neoformans directly stimulates perforin production and rearms NK cells for enhanced anticryptococcal microbicidal activity.

Marr KJ, Jones GJ, Zheng C, Huston SM, Timm-McCann M, Islam A, Berenger BM, Ma LL, Wiseman JC, Mody CH.

Department of Medical Science, University of Calgary, Calgary, Alberta, Canada.

NK cells, in addition to possessing antitumor and antiviral activity, exhibit perforin-dependent microbicidal activity against the opportunistic pathogen Cryptococcus neoformans. However, the factors controlling this response, particularly whether the pathogen itself provides an activation or rearming signal, are largely unknown. The current studies were performed to determine whether exposure to this fungus alters subsequent NK cell anticryptococcal activity. NK cells lost perforin and mobilized lysosome-associated membrane protein 1 to the cell surface following incubation with the fungus, indicating that degranulation had occurred. Despite a reduced perforin content during killing, NK cells acquired an enhanced ability to kill C. neoformans, as demonstrated using auxotrophs that allowed independent assessment of the killing of two strains. De novo protein synthesis was required for optimal killing; however, there was no evidence that a soluble factor contributed to the enhanced anticryptococcal activity. Exposure of NK cells to C. neoformans caused the cells to rearm, as demonstrated by increased perforin mRNA levels and enhanced loss of perforin when transcription was blocked. Degranulation alone was insufficient to provide the activation signal as NK cells lost anticryptococcal activity following treatment with strontium chloride. However, NK cells regained the activity upon prolonged exposure to C. neoformans, which is consistent with activation by the microbe. The enhanced cytotoxicity did not extend to tumor killing since NK cells exposed to C. neoformans failed to kill NK-sensitive tumor targets (K562 cells). These studies demonstrate that there is contact-mediated microbe-specific rearming and activation of microbicidal activity that are necessary for optimal killing of C. neoformans.

PMCID: PMC2687353 PMID: 19307209 [PubMed - indexed for MEDLINE]

1273. Eukaryot Cell. 2009 May;8(5):768-78. Epub 2009 Mar 20.

Oxidative stress function of the Saccharomyces cerevisiae Skn7 receiver domain.

He XJ, Mulford KE, Fassler JS.

Department of Biology, University of Iowa, Iowa City, IA 52242, USA.

The bifunctional Saccharomyces cerevisiae Skn7 transcription factor regulates osmotic stress response genes as well as oxidative stress response genes; however, the mechanisms involved in these two types of regulation differ. Skn7 osmotic stress activity depends on the phosphorylation of the receiver domain aspartate, D427, by the Sln1 histidine kinase. In contrast, D427 and the SLN1-SKN7 phosphorelay are dispensable for the oxidative stress response, although the receiver domain is required. The majority of oxidative stress response genes regulated by Skn7 also are regulated by the redox-responsive transcription factor Yap1. It is therefore possible that the nuclearly localized Skn7 does not itself respond to the oxidant but simply cooperates with Yap1 when it translocates to the nucleus. We report here that oxidative stress leads to a phosphatase-sensitive, slow-mobility Skn7 variant. This suggests that Skn7 undergoes a posttranslational modification by phosphorylation following exposure to oxidant. Oxidant-dependent Skn7 phosphorylation was eliminated in strains lacking the Yap1 transcription factor. This suggests that the phosphorylation of Skn7 is regulated by Yap1. Mutations in the receiver domain of Skn7 were identified that affect its oxidative stress function. These mutations were found to compromise the association of Yap1 and Skn7 at oxidative stress response gene promoters. A working model is proposed in which the association of Yap1 with Skn7 in the nucleus is a prerequisite for Skn7 phosphorylation and the activation of oxidative stress response genes.

PMCID: PMC2681607 PMID: 19304952 [PubMed - indexed for MEDLINE]

1274. J Appl Microbiol. 2009 Jul;107(1):280-6. Epub 2009 Mar 10.

The assessment of the antibacterial and antifungal activities of aspirin, EDTA and aspirin-EDTA combination and their effectiveness as antibiofilm agents.

Al-Bakri AG, Othman G, Bustanji Y.

University of Jordan, Faculty of Pharmacy, Amman-11942, Jordan. agbakri@ju.edu.jo

AIMS: To evaluate the antimicrobial activities of aspirin, EDTA and an aspirin-EDTA (A-EDTA) combination against Pseudomonas aeruginosa, Escherichia coli and Candida albicans in planktonic and biofilm cultures. METHODS AND RESULTS: Minimal inhibitory concentrations (MIC) and minimal biocidal concentrations (MBC) were determined using twofold broth microdilution and viable counting methods, respectively. Aspirin's recorded MIC values ranged from 1.2 to 2.7 mg ml(-1). Checkerboard assay demonstrated a synergism in antimicrobial activity upon combination. Aspirin's minimal biofilm eradication concentration values (MBEC) against the established biofilms ranged between 1.35 and 3.83 mg ml(-1). A complete eradication of bacterial biofilms was achieved after a 4-h treatment with the A-EDTA combination.
CONCLUSION: Both aspirin and EDTA possess broad-spectrum antimicrobial activity for both planktonic and biofilm cultures. Aspirin used at the MBEC for 24 h was successful in eradicating P. aeruginosa, E. coli and C. albicans biofilms established on abiotic surfaces. Moreover, the exposure to the A-EDTA combination (4 h) effected complete bacterial biofilm eradication. SIGNIFICANCE AND IMPACT OF THE STUDY: There is a continuous need for the discovery of new antimicrobial agents. Aspirin and EDTA are 'nonantibiotic drugs', the combination of which can be used successfully to treat and eradicate biofilms established on abiotic surfaces.

PMID: 19302313 [PubMed - indexed for MEDLINE]

1275. Aquat Toxicol. 2009 May 17;92(4):264-70. Epub 2009 Feb 27.

Metal stress induces programmed cell death in aquatic fungi.

Azevedo MM, Almeida B, Ludovico P, Cássio F.

Centre of Molecular and Environmental Biology (CBMA), Department of Biology, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal.

Aquatic hyphomycetes are a group of fungi that play a key role in organic matter turnover in both clean and metal-polluted streams. We examined the ability of Cu or Zn to induce programmed cell death (PCD) in three aquatic hyphomycete species through the evaluation of typical apoptotic markers, namely reactive oxygen species (ROS) accumulation, caspase-like activity, nuclear morphological alterations, and the occurrence of DNA strand breaks assessed by TUNEL assay. The exposure to both metals induced apoptotic events in all tested aquatic fungi. The most tolerant fungi either to Zn (Varicosporium elodeae) or Cu (Heliscussubmersus) exhibited higher levels of PCD markers, suggesting that PCD processes might be linked to fungal resistance/tolerance to metal stress. Moreover, different patterns of apoptotic markers were found, namely a PCD process independent of ROS accumulation in V. elodeae exposed to Cu, or independent of caspase-like activity in Flagellospora curta exposed to Zn, or even without the occurrence of DNA strand breaks in F. curta exposed to Cu. This suggests that a multiplicity of PCD pathways might be operating in aquatic hyphomycetes. The occurrence of a tightly regulated cell death pathway, such as PCD, in aquatic hyphomycetes under metal stress might be a part of the mechanisms underlying fungal acclimation in metal-polluted streams, because it would allow the rapid removal of unwanted or damaged cells sparing nutrients and space for the fittest ones.

PMID: 19297034 [PubMed - indexed for MEDLINE]

1276. J Toxicol Environ Health A. 2009;72(9):585-98.

The concentration of no toxicologic concern (CoNTC) and airborne mycotoxins.

Hardin BD, Robbins CA, Fallah P, Kelman BJ.

Veritox Inc, Redmond, WA 98052, USA. BHardin@Veritox.com

The threshold of toxicologic concern (TTC) concept was developed as a method to identify a chemical intake level that is predicted to be without adverse human health effects assuming daily intake over the course of a 70-yr life span. The TTC values are based on known structure-activity relationships and do not require chemical-specific toxicity data. This allows safety assessment (or prioritization for testing) of chemicals with known molecular structure but little or no toxicity data. Recently, the TTC concept was extended to inhaled substances by converting a TTC expressed in micrograms per person per day to an airborne concentration (ng/m(3)), making allowance for intake by routes in addition to inhalation and implicitly assuming 100% bioavailability of inhaled toxicants. The resulting concentration of no toxicologic concern (CoNTC), 30 ng/m(3), represents a generic airborne concentration that is expected to pose no hazard to humans exposed continuously throughout a 70-yr lifetime. Published data on the levels of mycotoxins in agricultural dusts or in fungal spores, along with measured levels of airborne mycotoxins, spores, or dust in various environments, were used to identify conditions under which mycotoxin exposures might reach the CoNTC. Data demonstrate that airborne concentrations of dusts and mold spores sometimes encountered in agricultural environments have the potential to produce mycotoxin concentrations greater than the CoNTC. On the other hand, these data suggest that common exposures to mycotoxins from airborne molds in daily life, including in the built indoor environment, are below the concentration of no toxicologic concern.

PMID: 19296408 [PubMed - indexed for MEDLINE]

1277. Bioresour Technol. 2009 Jul;100(14):3657-62. Epub 2009 Mar 16.

Kinetics of an extracellular exo-inulinase production from a 5-flourocytosine resistant mutant of Geotrichum candidum using two-factorial design.

Mughal MS, Ali S, Ashiq M, Talish AS.

Department of Zoology, GC University Lahore, Pakistan.

In the present study, eight different strains of Geotrichum candidum were isolated and screened for an extracellular exo-inulinase production using chemically enriched sucrose-mineral media. The isolate (Zool-3i) with a better enzyme activity (1.38 IU/ml) was subjected to induced mutagenesis using methyl methane sulphonate (MMS) and a mutant with an enzyme activity of 32.06 IU/ml was obtained. Further exposure to ethyl methane sulphonate (EMS) and ultraviolet (UV) radiations yielded a mutant exhibiting an improved activity of 39.34 IU/ml. The potential mutant was cultured overnight and plated on 5fc-YPR agar medium and thus made resistant against 5-flourocytocine. Over 50-fold enhancement in enzyme production (71.85 IU/ml) was achieved when the process parameters including incubation period (48 h), sucrose concentration (5.0 g/L), pH (6.0), inoculum size (2.0%, 16 h old) and urea (0.2%) were identified using Plackett-Burman design. On the basis of kinetic variables, notably Q(p) (0.723 U/g/h), Y(p/s) (2.036U/g) and q(p) (0.091U/g cells/h), the mutant MEU-5fc-6 was found to be a hyper producer of exo-inulinase (HS, LSD 0.045, p< or =0.05).

PMID: 19289278 [PubMed - indexed for MEDLINE]

1278. Chemosphere. 2009 Jun;76(1):114-9. Epub 2009 Mar 16.

Determination of microbial volatile organic compounds (MVOCs) by passive sampling onto charcoal sorbents.

Matysik S, Herbarth O, Mueller A.

Department of Human Exposure Research and Epidemiology, Helmholtz Centre for Environmental Research-UFZ, Leipzig, Germany. silke.matysik@ufz.de

Passive sampling combined with GC-MS was applied for the detection of microbial volatile organic compounds (MVOCs) emitted by mould cultures. The fungi species Penicillium expansum, Penicillium chrysogenum, Penicillium brevicompactum, Aspergillus fumigatus, Aspergillus versicolor, Aspergillus niger, and Cladosporium cladosporoides were cultivated on dichloran glycerol agar. The emitted volatiles were collected by charcoal-based passive diffusion monitors during the first four weeks of growth. Several alcohols, mainly 2-methyl-1-propanol and 3-methyl-1-butanol, alkenes, ketones, ethers and esters could be identified and quantified after external calibration. Species-specific compounds like 1,3-dimethoxybenzene for A. versicolor could be proposed. Associations between the concentrations of some of the identified MVOCs (e.g. methylfurans and dimethyldisulfide) and indoor mould exposure in dwellings were found in a field study comprising more than 500 dwellings in Leipzig/Germany. It could be concluded that passive sampling onto charcoal adsorbents for the determination of MVOCs is particularly suitable in epidemiological studies with a high number of participants.

PMID: 19289243 [PubMed - indexed for MEDLINE]

1279. Mol Cell. 2009 Mar 13;33(5):581-90.

Functionally distinct isoforms of Cik1 are differentially regulated by APC/C-mediated proteolysis.

Benanti JA, Matyskiela ME, Morgan DO, Toczyski DP.

Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94115, USA. jbenanti@cc.ucsf.edu

Cik1, in association with the kinesin Kar3, controls both the mitotic spindle and nuclear fusion during mating. Here, we show that there are two Cik1 isoforms, and that the mitotic form includes an N-terminal domain required for ubiquitination by the Anaphase-Promoting Complex/Cyclosome (APC/C). During vegetative growth, Cik1 is expressed during mitosis and regulates the mitotic spindle, allowing for accurate chromosome segregation. After mitosis, APC/C(Cdh1) targets Cik1 for ubiquitin-mediated proteolysis. Upon exposure to the mating pheromone alpha factor, a smaller APC/C-resistant Cik1 isoform is expressed from an alternate transcriptional start site. This shorter Cik1 isoform is stable and cannot be ubiquitinated by APC/C(Cdh1). Moreover, the two Cik1 isoforms are functionally distinct. Cells that express only the long isoform have defects in nuclear fusion, whereas cells expressing only the short isoform have an increased rate of chromosome loss. These results demonstrate a coupling of transcriptional regulation and APC/C-mediated proteolysis.

PMCID: PMC2883288 PMID: 19285942 [PubMed - indexed for MEDLINE]

1280. BMC Genomics. 2009 Mar 12;10:105.

Genetic basis of arsenite and cadmium tolerance in Saccharomyces cerevisiae.

Thorsen M, Perrone GG, Kristiansson E, Traini M, Ye T, Dawes IW, Nerman O, Tamás MJ.

Department of Cell and Molecular Biology/Microbiology, University of Gothenburg, S-405 30 Gothenburg, Sweden. mthorsen@bio.ku.dk

BACKGROUND: Arsenic and cadmium are widely distributed in nature and pose serious threats to the environment and human health. Exposure to these nonessential toxic metals may result in a variety of human diseases including cancer. However, arsenic and cadmium toxicity targets and the cellular systems contributing to tolerance acquisition are not fully known.
RESULTS: To gain insight into metal action and cellular tolerance mechanisms, we carried out genome-wide screening of the Saccharomyces cerevisiae haploid and homozygous diploid deletion mutant collections and scored for reduced growth in the presence of arsenite or cadmium. Processes found to be required for tolerance to both metals included sulphur and glutathione biosynthesis, environmental sensing, mRNA synthesis and transcription, and vacuolar/endosomal transport and sorting. We also identified metal-specific defence processes. Arsenite-specific defence functions were related to cell cycle regulation, lipid and fatty acid metabolism, mitochondrial biogenesis, and the cytoskeleton whereas cadmium-specific defence functions were mainly related to sugar/carbohydrate metabolism, and metal-ion homeostasis and transport. Molecular evidence indicated that the cytoskeleton is targeted by arsenite and that phosphorylation of the Snf1p kinase is required for cadmium tolerance.
CONCLUSION: This study has pin-pointed core functions that protect cells from arsenite and cadmium toxicity. It also emphasizes the existence of both common and specific defence systems. Since many of the yeast genes that confer tolerance to these agents have homologues in humans, similar biological processes may act in yeast and humans to prevent metal toxicity and carcinogenesis.

PMCID: PMC2660369 PMID: 19284616 [PubMed - indexed for MEDLINE]

1281. J Allergy Clin Immunol. 2009 Mar;123(3):575-8.

Advances in environmental and occupational disorders in 2008.

Bush RK, Peden DB.

Department of Medicine, Section of Allergy, Immunology, Pulmonary, Critical Care, and Sleep Medicine, University of Wisconsin, Madison, Wis, USA. rkb@medicine.wisc.edu.

Substantial progress in understanding the role of environmental factors in allergic disease and asthma has been made in the past year. A number of new allergens have been described, and the impact of exposure to indoor allergens in the development of allergic respiratory disease is further confirmed. Exposures to environmental pollutants, particularly tobacco smoke in children, have furthered our knowledge of the detrimental effects of these exposures. This review highlights key advances in environmental and occupational exposures that contribute to the burden of allergic respiratory disease.

PMID: 19281905 [PubMed - indexed for MEDLINE]

1282. J Agric Food Chem. 2009 Apr 22;57(8):3351-5.

Vitamin D2 formation and bioavailability from Agaricus bisporus button mushrooms treated with ultraviolet irradiation.

Koyyalamudi SR, Jeong SC, Song CH, Cho KY, Pang G.

Centre for Plant and Food Science, College of Health and Science, University of Western Sydney, Penrith South DC, NSW 1797, Australia.

Agaricus bisporus mushrooms contain an abundance of ergosterol, which on exposure to UV irradiation is converted to vitamin D2. The present study evaluated the effects UV-C irradiation on vitamin D2 formation and its bioavailability in rats. Fresh button mushrooms were exposed to UV-C irradiation at mean intensities of 0.403, 0.316, and 0.256 mW/cm(2) from respective distances of 30, 40, and 50 cm for periods ranging from 2.5 to 60 min. Vitamin D2 and ergosterol were measured by HPLC-MS/MS. The stability and retention of vitamin D2 were assessed including the extent of discoloration during storage at 4 degrees C or at room temperature. Exposure to UV-C irradiation at 0.403 mW/cm(2) intensity from 30 cm distance resulted in a time-dependent increase in vitamin D2 concentrations that was significantly higher than those produced at intensities of 0.316 and 0.256 mW/cm(2) from distances of 40 and 50 cm, respectively. Furthermore, the concentrations of vitamin D2 produced after exposure to UV-C irradiation doses of 0.125 and 0.25 J/cm(2) for, 2.5, 5, and 10 min were 6.6, 15.6, and 23.1 microg/g solids, equivalent to 40.6, 95.4, and 141 microg/serving, respectively. The data showed a high rate of conversion from ergosterol to vitamin D2 at short treatment time, which is required by the mushroom industry. The stability of vitamin D2 remained unchanged during storage at 4 degrees C and at room temperature over 8 days (P = 0.36), indicating no degradation of vitamin D2. By visual assessment or using a chromometer, no significant discoloration of irradiated mushrooms, as measured by the degree of "whiteness", was observed when stored at 4 degrees C compared to that observed with mushrooms stored at room temperature over an 8 day period (P < 0.007). Vitamin D2 was well absorbed and metabolized as evidenced by the serum response of 25-hydroxyvitamin D in rats fed the irradiated mushrooms. Taken together, the data suggest that commercial production of button mushrooms enriched with vitamin D2 for improving consumer health may be practical.

PMID: 19281276 [PubMed - indexed for MEDLINE]

1283. J Biochem. 2009 Jul;146(1):13-21. Epub 2009 Mar 11.

PCNA mono-ubiquitination and activation of translesion DNA polymerases by DNA polymerase {alpha}.

Suzuki M, Niimi A, Limsirichaikul S, Tomida S, Miao Huang Q, Izuta S, Usukura J, Itoh Y, Hishida T, Akashi T, Nakagawa Y, Kikuchi A, Pavlov Y, Murate T, Takahashi T.

Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Japan. msuzuki@med.nagoya-u.ac.jp

Erratum in J Biochem. 2010 Aug;148(2):261.

Translesion DNA synthesis (TLS) involves PCNA mono-ubiquitination and TLS DNA polymerases (pols). Recent evidence has shown that the mono-ubiquitination is induced not only by DNA damage but also by other factors that induce stalling of the DNA replication fork. We studied the effect of spontaneous DNA replication errors on PCNA mono-ubiquitination and TLS induction. In the pol1L868F strain, which expressed an error-prone pol alpha, PCNA was spontaneously mono-ubiquitinated. Pol alpha L868F had a rate-limiting step at the extension from mismatched primer termini. Electron microscopic observation showed the accumulation of a single-stranded region at the DNA replication fork in yeast cells. For pol alpha errors, pol zeta participated in a generation of +1 frameshifts. Furthermore, in the pol1L868F strain, UV-induced mutations were lower than in the wild-type and a pol delta mutant strain (pol3-5DV), and deletion of the RAD30 gene (pol eta) suppressed this defect. These data suggest that nucleotide misincorporation by pol alpha induces exposure of single-stranded DNA, PCNA mono-ubiquitination and activates TLS pols.

PMID: 19279190 [PubMed - indexed for MEDLINE]

1284. Appl Biochem Biotechnol. 2009 Nov;159(2):453-63. Epub 2009 Mar 10.

Enhanced production of an extracellular beta-D-fructofuranosidase fructohydrolase from a 2-deoxy-D-glucose stabilized mutant of Candida utilis.

Ali S, Ashiq M.

Institute of Industrial Biotechnology (IIB), Government College University, Lahore, Pakistan.

The enzyme beta-D-fructofuranosidase fructohydrolase (FFH) cleaves the alpha-1,4 glycosidic linkage between alpha-D-glucose and beta-D: -fructose molecules of sucrose, releasing monosaccharides by hydrolysis. In the present study, FFH production in Candida utilis GC-46, a lipolytic wild yeast strain was improved by exposure to N-methyl N-nitro N-nitroso guanidine (NG) and 2-deoxy-D-glucose (2dg) at various levels. The mutant strain NG-5 was obtained after exposure to 0.06 mg/ml of NG for 20 min. NG-5 offers improved extracellular FFH production (34 +/- 2.6 U/ml/min) when compared to the wild strain (1.15 +/- 0.01 U/ml/min). A 40-fold increase of FFH (45.65 +/- 2.0 U/ml/min) was achieved when the process parameters, including incubation period (48 h), sucrose concentration (5.0 g/l), initial pH (6.0), inoculum size (2.0% v/v, 16 h old), and urea concentration (0.2%, w/v) were identified using Plackett-Burman design. The kinetic parameters viz. Q (p) (0.723 U/g/h), Y (p/s) (2.036 U/g), and q (p) (0.091 U/g yeast cells/h) indicate that NG-5 is a hyperproducer of extracellular FFH with a concomitant increase in growth rate. The volumetric productivity of NG-5 was over sixfold improved over the parental strain. The enzyme production improvement is highly significant (HS, LSD 0.042, p < or = 0.05), indicating commercial utility.

PMID: 19277487 [PubMed - indexed for MEDLINE]

1285. Vet Pathol. 2009 Jul;46(4):604-13. Epub 2009 Mar 9.

Clara cell secretory protein is reduced in equine recurrent airway obstruction.

Katavolos P, Ackerley CA, Viel L, Clark ME, Wen X, Bienzle D.

Department of Pathobiology, University of Guelph, Guelph, ON, N1G 2W1, Canada.

Horses are prone to recurrent airway obstruction (RAO), an inflammatory lung disease induced by repeated exposure to environmental mold, dust, and bacterial components. Active disease manifests with mucus hyperproduction, neutrophilic inflammation, bronchoconstriction, and coughing. Chronically affected animals have lung remodeling characterized by smooth muscle hyperplasia, collagen deposition, lymphoid hyperplasia, and impaired aerobic performance. Clara cell secretory protein (CCSP) counters inflammation in the lung, hence we hypothesized that CCSP depletion is a key feature of RAO in horses. Recombinant equine CCSP and specific antiserum were produced, and percutaneous lung biopsies were obtained from 3 healthy horses and from 3 RAO-affected horses before and after induction of RAO. CCSP relative gene expression in tissue, as well as protein concentration in lung lavage fluid, was determined. Immunocytochemical analysis, using both light and immunogold ultrastructural methods, demonstrated reduced CCSP staining in lung tissue of animals with RAO. Immunogold label in Clara cell granules was less in animals with chronic RAO than in normal animals, and absent in animals that had active disease. Median lung lavage CCSP concentration was 132 and 129 ng/ml in healthy horses, and 62 and 24 ng/ml in RAO horses before and after challenge, respectively. CCSP lung gene expression was significantly higher in healthy animals than in animals with chronic RAO. Together, these preliminary findings suggest that reduced production of CCSP and subcellular changes in Clara cells are features of chronic environmentally induced lung inflammation in horses.

PMID: 19276063 [PubMed - indexed for MEDLINE]

1286. Drugs. 2009;69(3):361-92. doi: 10.2165/00003495-200969030-00010.

Liposomal amphotericin B: a review of its use as empirical therapy in febrile neutropenia and in the treatment of invasive fungal infections.

Moen MD, Lyseng-Williamson KA, Scott LJ.

Wolters Kluwer Health | Adis, Auckland, New Zealand. demail@adis.co.nz

Liposomal amphotericin B (AmBisome) is a lipid-associated formulation of the broad-spectrum polyene antifungal agent amphotericin B. It is active against clinically relevant yeasts and moulds, including Candida spp., Aspergillus spp. and filamentous moulds such as Zygomycetes, and is approved for the treatment of invasive fungal infections in many countries worldwide. It was developed to improve the tolerability profile of amphotericin B deoxycholate, which was for many decades considered the gold standard of antifungal treatment, despite being associated with infusion-related events and nephrotoxicity. In well controlled trials, liposomal amphotericin B had similar efficacy to amphotericin B deoxycholate and amphotericin B lipid complex as empirical therapy in adult and paediatric patients with febrile neutropenia. In addition, caspofungin was noninferior to liposomal amphotericin B as empirical therapy in adult patients with febrile neutropenia. For the treatment of confirmed invasive fungal infections, liposomal amphotericin B was more effective than amphotericin B deoxycholate treatment in patients with disseminated histoplasmosis and AIDS, and was noninferior to amphotericin B deoxycholate in patients with acute cryptococcal meningitis and AIDS. In adults, micafungin was shown to be noninferior to liposomal amphotericin B for the treatment of candidaemia and invasive candidiasis. Data from animal studies suggested that higher dosages of liposomal amphotericin B might improve efficacy; however, in the AmBiLoad trial in patients with invasive mould infection, there was no statistical difference in efficacy between the standard dosage of liposomal amphotericin B 3 mg/kg/day and a higher 10 mg/kg/day dosage, although the standard dosage was better tolerated. Despite being associated with fewer infusion-related adverse events and less nephrotoxicity than amphotericin B deoxycholate and amphotericin B lipid complex, liposomal amphotericin B use is still limited to some extent by these adverse events. Both echinocandins were better tolerated than liposomal amphotericin B. The cost of liposomal amphotericin B therapy may also restrict its use, but further pharmacoeconomic studies are required to fully define its cost effectiveness compared with other antifungal agents. Based on comparative data from well controlled trials, extensive clinical experience and its broad spectrum of activity, liposomal amphotericin B remains a first-line option for empirical therapy in patients with febrile neutropenia and in those with disseminated histoplasmosis, and is an option for the treatment of AIDS-associated cryptococcal meningitis, and for invasive Candida spp. or Aspergillus spp. infections. Amphotericin B, a macrocyclic, polyene antifungal agent, is thought to act by binding to ergosterol, the principal sterol in fungal cell membranes and Leishmania cells. This results in a change in membrane permeability, causing metabolic disturbance, leakage of small molecules and, as a consequence, cell death. In vitro and in vivo studies have shown that liposomal amphotericin B remains closely associated with the liposomes in the circulation, thereby reducing the potential for nephrotoxicity and infusion-related toxicity associated with conventional amphotericin B. Amphotericin B shows very good in vitro activity against a broad spectrum of clinically relevant fungal isolates, including most strains of Candida spp. and Aspergillus spp., and other filamentous fungi such as Zygomycetes. Liposomal amphotericin B has proven effective in various animal models of fungal infections, including those for candidiasis, aspergillosis, fusariosis and zygomycosis. Liposomal amphotericin B also shows immunomodulatory effects, although the mechanisms involved are not fully understood, and differ from those of amphotericin B deoxycholate and amphotericin B colloidal dispersion. In adult patients with febrile neutropenia, intravenous liposomal amphotericin B has nonlinear pharmacokinetics, with higher than dose-proportional increases in exposure being consistent with reticuloendothelial saturation and redistribution of amphotericin B in the plasma compartment. Liposomal amphotericin B is rapidly and extensively distributed after single and multiple doses, with steady-state concentrations of amphotericin B attained within 4 days and no clinically relevant accumulation of the drug following multiple doses of 1-7.5 mg/kg/day. In autopsy tissue, the highest concentrations of the drug were found in the liver and spleen, followed by the kidney, lung, myocardium and brain tissue. Elimination of liposomal amphotericin B, like that of amphotericin B deoxycholate, is poorly understood; its route of metabolism is not known and its excretion has not been studied. The terminal elimination half-life is about 7 hours. No dosage adjustment is required based on age or renal impairment. In several randomized, double-blind trials (n = 73-1095) in adult and/or paediatric patients, liposomal amphotericin B was effective as empirical therapy or as treatment for confirmed invasive fungal infections, including invasive candidiasis, candidaemia, invasive mould infection (mainly aspergillosis), histoplasmosis and cryptococcal meningitis. All agents were administered as an intravenous infusion; the typical dosage for liposomal amphotericin B was 3 mg/kg/day. Treatment was generally given for 1-2 weeks. Participants in trials evaluating empirical therapy had neutropenia and a persistent fever despite antibacterial treatment and had received chemotherapy or undergone haematopoietic stem cell transplantation. As empirical therapy in adult and paediatric patients, liposomal amphotericin B appeared to be as effective as amphotericin B deoxycholate (approximately 50% of patients in each group achieved treatment success) or amphotericin B lipid complex (approximately 40% of liposomal amphotericin B recipients experienced treatment success). Of note, in the first trial, results of the statistical test to determine equivalence between treatments were not reported. In the second trial, efficacy was assessed as an 'other' endpoint. In another trial, caspofungin was shown to be noninferior to liposomal amphotericin B, with approximately one-third of patients in each group experiencing treatment success. Liposomal amphotericin B was significantly more effective than amphotericin B deoxycholate for the treatment of moderate to severe disseminated histoplasmosis in patients with AIDS, with 88% and 64% of patients, respectively, having a successful response. Liposomal amphotericin B was noninferior to amphotericin B deoxycholate for the treatment of cryptococcal meningitis in terms of mycological success. Micafungin therapy was shown to be noninferior to liposomal amphotericin B for the treatment of adult patients with candidaemia or invasive candidiasis. In a substudy in paediatric patients, which was not powered to determine noninferiority, liposomal amphotericin B was as effective as micafungin for the treatment of candidaemia or invasive candidiasis. In this patient population, within each trial, 90% of adult patients and approximately three-quarters of paediatric patients in both treatment groups experienced a successful response. In patients with invasive mould infection (mainly aspergillosis), there was no difference in efficacy between a higher dosage of liposomal amphotericin B (10 mg/kg/day) and the standard dosage (3 mg/kg/day), with 46% and 50% of patients experiencing a favourable overall response. In well designed clinical trials, liposomal amphotericin B was generally at least as well tolerated as other lipid-associated formulations of amphotericin B and better tolerated than amphotericin B deoxycholate in adult and paediatric patients. Compared with other amphotericin B formulations, liposomal amphotericin B treatment was associated with a lower incidence of infusion-related adverse events and nephrotoxicity. A higher than recommended dosage of liposomal amphotericin B (10 mg/kg/day) was associated with an increased incidence of nephrotoxicity compared with the standard dosage (3 mg/kg/day), although the incidence of infusion-related reactions did not differ between treatment groups. In general, liposomal amphotericin B treatment was not as well tolerated as echinocandin therapy in well designed clinical trials. As empirical therapy or for the treatment of confirmed invasive fungal infections in adult patients, liposomal amphotericin B recipients experienced more infusion-related events and nephrotoxicity than caspofungin or micafungin recipients. There was no difference in the incidence of these adverse events between the liposomal amphotericin B and micafungin groups in a study in paediatric patients.

PMID: 19275278 [PubMed - indexed for MEDLINE]

1287. Environ Sci Pollut Res Int. 2009 May;16(3):278-86. Epub 2009 Mar 10.

Endocrine disruptors in bottled mineral water: total estrogenic burden and migration from plastic bottles.

Wagner M, Oehlmann J.

Department of Aquatic Ecotoxicology, Johann Wolfgang Goethe University, Siesmayerstr. 70 A, 60054, Frankfurt am Main, Germany. wagner@bio.uni-frankfurt.de

BACKGROUND, AIM, AND SCOPE: Food consumption is an important route of human exposure to endocrine-disrupting chemicals. So far, this has been demonstrated by exposure modeling or analytical identification of single substances in foodstuff (e.g., phthalates) and human body fluids (e.g., urine and blood). Since the research in this field is focused on few chemicals (and thus missing mixture effects), the overall contamination of edibles with xenohormones is largely unknown. The aim of this study was to assess the integrated estrogenic burden of bottled mineral water as model foodstuff and to characterize the potential sources of the estrogenic contamination. MATERIALS, METHODS, AND RESULTS: In the present study, we analyzed commercially available mineral water in an in vitro system with the human estrogen receptor alpha and detected estrogenic contamination in 60% of all samples with a maximum activity equivalent to 75.2 ng/l of the natural sex hormone 17beta-estradiol. Furthermore, breeding of the molluskan model Potamopyrgus antipodarum in water bottles made of glass and plastic [polyethylene terephthalate (PET)] resulted in an increased reproductive output of snails cultured in PET bottles. This provides first evidence that substances leaching from plastic food packaging materials act as functional estrogens in vivo. DISCUSSION AND CONCLUSIONS: Our results demonstrate a widespread contamination of mineral water with xenoestrogens that partly originates from compounds leaching from the plastic packaging material. These substances possess potent estrogenic activity in vivo in a molluskan sentinel. Overall, the results indicate that a broader range of foodstuff may be contaminated with endocrine disruptors when packed in plastics.

PMID: 19274472 [PubMed - indexed for MEDLINE]

1288. Mol Cell Biol. 2009 May;29(9):2346-58. Epub 2009 Mar 9.

Role of the histone variant H2A.Z/Htz1p in TBP recruitment, chromatin dynamics, and regulated expression of oleate-responsive genes.

Wan Y, Saleem RA, Ratushny AV, Roda O, Smith JJ, Lin CH, Chiang JH, Aitchison JD.

Institute for Systems Biology, 1441 N 34th St., Seattle, WA 98103, USA.

The histone variant H2A.Z (Htz1p) has been implicated in transcriptional regulation in numerous organisms, including Saccharomyces cerevisiae. Genome-wide transcriptome profiling and chromatin immunoprecipitation studies identified a role for Htz1p in the rapid and robust activation of many oleate-responsive genes encoding peroxisomal proteins, in particular POT1, POX1, FOX2, and CTA1. The Swr1p-, Gcn5p-, and Chz1p-dependent association of Htz1p with these promoters in their repressed states appears to establish an epigenetic marker for the rapid and strong expression of these highly inducible promoters. Isw2p also plays a role in establishing the nucleosome state of these promoters and associates stably in the absence of Htz1p. An analysis of the nucleosome dynamics and Htz1p association with these promoters suggests a complex mechanism in which Htz1p-containing nucleosomes at fatty acid-responsive promoters are disassembled upon initial exposure to oleic acid leading to the loss of Htz1p from the promoter. These nucleosomes reassemble at later stages of gene expression. While these new nucleosomes do not incorporate Htz1p, the initial presence of Htz1p appears to mark the promoter for sustained gene expression and the recruitment of TATA-binding protein.

PMCID: PMC2668375 PMID: 19273605 [PubMed - indexed for MEDLINE]

1289. Food Microbiol. 2009 May;26(3):340-6. Epub 2008 Dec 10.

Selectivity and antimicrobial action of bovine lactoferrin derived peptides against wine lactic acid bacteria.

Enrique M, Manzanares P, Yuste M, Martínez M, Vallés S, Marcos JF.

Departamento de Biotecnología de Alimentos, Instituto de Agroquímica y Tecnología de Alimentos, Consejo Superior de Investigaciones Científicas PO Box 73, 46100 Burjassot, Valencia, Spain.

In this study, the antibacterial activities of a bovine Lactoferrin pepsin hydrolysate (LFH) and a synthetic peptide derived from bovine lactoferricin (LfcinB(17-31)) have been evaluated against Oenococcus oeni and three additional lactic acid bacteria (LAB) known to cause spoilage during winemaking processes. Inhibition of bacterial growth was demonstrated in vitro in synthetic broth media (MRS) for both LFH and LfcinB(17-31). The bactericidal activity of the synthetic peptide was also assayed and found to vary depending on the bacterial species and the matrix in which exposure to peptide occurred (either MRS broth or white must). Specificity of LfcinB(17-31) for Lactobacillus brevis, Pediococcus damnosus, and O. oeni was demonstrated in must fermentation experiments in which these three LAB co-existed with the winemaking Saccharomyces cerevisiae T73 in the presence of the peptide. Finally, fermentation experiments also showed that LfcinB(17-31) at inhibitory concentrations did not alter either fermentation kinetics or specific enological parameters.

PMID: 19269579 [PubMed - indexed for MEDLINE]

1290. Int J Occup Environ Health. 2009 Jan-Mar;15(1):115-7.

Literature on mycotoxins and human health at the time of the ACOEM report.

Hodgson MJ, Dearborn DG.

Comment on Int J Occup Environ Health. 2008 Oct-Dec;14(4):283-98.

PMID: 19267132 [PubMed - indexed for MEDLINE]

1291. Int J Occup Environ Health. 2009 Jan-Mar;15(1):114; author reply 114-5.

Mold science and conflict of interest.

Orford RR.

Comment on Int J Occup Environ Health. 2008 Oct-Dec;14(4):283-98.

PMID: 19267131 [PubMed - indexed for MEDLINE]

1292. Eye Contact Lens. 2009 Mar;35(2):88-91.

Multipurpose solutions and rates of biocidal efficacy.

Scheuer C, Zhao F, Erb T, Orsborn G.

Lens Care for Bausch & Lomb, Rochester, NY 14609, USA. catherine.a.scheuer@bausch.com

OBJECTIVE: To investigate the hypothesis that reasonable levels of disinfection are achievable over relatively short exposure durations of microorganisms to multipurpose solutions, this study examined the stand-alone disinfection efficacy at 10, 20, and 30 min of five different multipurpose solutions products, each against five different pathogens eye care practitioners may encounter in their contact lens practice.
METHODS: ReNu MultiPlus, ReNu Multi-Purpose, AQuify, OptiFree Express, and OptiFree RepleniSH were evaluated for their microbiocidal efficacy using the stand-alone method at 10, 20, and 30 min of exposure to either Fusarium solani, Candida albicans, Staphylococcus aureus, Serratia marcescens, or Pseudomonas aeruginosa.
RESULTS: Solutions which showed significantly higher rates of disinfection at 30 min were ReNu MultiPlus against Fusarium solani and Candida albicans, and both ReNu MultiPlus and AQuify against Staphylococcus aureus and Serratia marcescens. There were no statistically significant differences at 30 min amongst solutions against Pseudomonas aeruginosa.
CONCLUSIONS: The product attribute of rapid rate of disinfection may give a greater level of assurance to practitioners when patients are noncompliant and do not follow the recommended time period for lens disinfection. The results of this study, however, should not be interpreted as a recommendation to use any of the solutions tested for a disinfection period less than the recommended soak time. Patient compliance with recommended lens care regimens is essential in minimizing the risk of contamination of contact lenses and lens care accessories.

PMID: 19265330 [PubMed - indexed for MEDLINE]

1293. J Virol. 2009 May;83(10):4861-70. Epub 2009 Mar 4.

A yeast glycoprotein shows high-affinity binding to the broadly neutralizing human immunodeficiency virus antibody 2G12 and inhibits gp120 interactions with 2G12 and DC-SIGN.

Luallen RJ, Fu H, Agrawal-Gamse C, Mboudjeka I, Huang W, Lee FH, Wang LX, Doms RW, Geng Y.

ProSci Inc., 12170 Flint Place, Poway, CA 92064, USA.

The human immunodeficiency virus type 1 (HIV-1) envelope (Env) protein contains numerous N-linked carbohydrates that shield conserved peptide epitopes and promote trans infection by dendritic cells via binding to cell surface lectins. The potent and broadly neutralizing monoclonal antibody 2G12 binds a cluster of high-mannose-type oligosaccharides on the gp120 subunit of Env, revealing a conserved and highly exposed epitope on the glycan shield. To find an effective antigen for eliciting 2G12-like antibodies, we searched for endogenous yeast proteins that could bind to 2G12 in a panel of Saccharomyces cerevisiae glycosylation knockouts and discovered one protein that bound weakly in a Delta pmr1 strain deficient in hyperglycosylation. 2G12 binding to this protein, identified as Pst1, was enhanced by adding the Delta mnn1 deletion to the Delta pmr1 background, ensuring the exposure of terminal alpha1,2-linked mannose residues on the D1 and D3 arms of high-mannose glycans. However, optimum 2G12 antigenicity was found when Pst1, a heavily N-glycosylated protein, was expressed with homogenous Man(8)GlcNAc(2) structures in Delta och1 Delta mnn1 Delta mnn4 yeast. Surface plasmon resonance analysis of this form of Pst1 showed high affinity for 2G12, which translated into Pst1 efficiently inhibiting gp120 interactions with 2G12 and DC-SIGN and blocking 2G12-mediated neutralization of HIV-1 pseudoviruses. The high affinity of the yeast glycoprotein Pst1 for 2G12 highlights its potential as a novel antigen to induce 2G12-like antibodies.

PMCID: PMC2682088 PMID: 19264785 [PubMed - indexed for MEDLINE]

1294. J Clin Microbiol. 2009 May;47(5):1325-32. Epub 2009 Mar 4.

Strain-dependent variation in 18S ribosomal DNA Copy numbers in Aspergillus fumigatus.

Herrera ML, Vallor AC, Gelfond JA, Patterson TF, Wickes BL.

Department of Microbiology and Immunology, the University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229-3900, USA.

Enumerating Aspergillus fumigatus CFU can be challenging since CFU determination by plate count can be difficult. CFU determination by quantitative real-time PCR (qPCR), however, is becoming increasingly common and usually relies on detecting one of the subunits of the multicopy rRNA genes. This study was undertaken to determine if ribosomal DNA (rDNA) copy number was constant or variable among different A. fumigatus isolates. FKS1 was used as a single-copy control gene and was validated against single-copy (pyrG and ARG4) and multicopy (arsC) controls. The copy numbers of the 18S rDNA subunit were then determined for a variety of isolates and were found to vary with the strain, from 38 to 91 copies per genome. Investigation of the stability of the 18S rDNA copy number after exposure to a number of different environmental and growth conditions revealed that the copy number was stable, varying less than one copy across all conditions, including in isolates recovered from an animal model. These results suggest that while the ribosomal genes are excellent targets for enumeration by qPCR, the copy number should be determined prior to using them as targets for quantitative analysis.

PMCID: PMC2681831 PMID: 19261786 [PubMed - indexed for MEDLINE]

1295. Micron. 2009 Jun;40(4):439-43. Epub 2009 Feb 6.

In situ TEM and SEM studies on the antimicrobial activity and prevention of Candida albicans biofilm by Cassia spectabilis extract.

Sangetha S, Zuraini Z, Suryani S, Sasidharan S.

School of Distance Education, Universiti Sains Malaysia, Minden, Penang, Malaysia.

The inhibitory effect of Cassia spectabilis methanol leaf extract was evaluated against biofilm forming Candida albicans, which was sensitive to 6.25 mg/ml concentration of the extract. Transmission (TEM) and scanning electron microscope (SEM) observations were used to study the anticandidal activity and prevention of biofilm formation by the C. spectabilis extract. SEM analysis further revealed reduction in C. albicans biofilm in response to the extract. The main abnormalities noted via TEM study was the alterations in morphology and complete collapse of the yeast cells after 36 h of exposure to the extract. The significant antifungal activity shown by this methanol extract of C. spectabilis suggests its potential against infections caused by C. albicans.

PMID: 19261482 [PubMed - indexed for MEDLINE]

1296. Med Mycol. 2009;47 Suppl 1:S369-75. Epub 2009 Feb 28.

Paradoxical echinocandin activity: a limited in vitro phenomenon?

Wiederhold NP.

University of Texas at Austin College of Pharmacy, Austin, Texas 78229, USA. wiederholdn@uthscsa.edu

The echinocandins have been a welcome addition for the treatment of invasive fungal infections. Despite their excellent safety profile and clinical efficacy, concerns exist regarding an attenuation of activity at higher concentrations, known as the paradoxical effect. In vitro studies have reported this phenomenon against both Candida and Aspergillus species. Recent data have also demonstrated this effect to be species-related and echinocandin specific. Although not completely understood, studies have pointed towards involvement of the protein kinase C cell wall integrity pathway as well as increases in cell wall chitin content as potential mechanisms responsible for this phenomenon. Increases in galactomannan have been reported in vitro and in vivo following echinocandin exposure. Although some in vivo studies of invasive aspergillosis have also reported a paradoxical increase in other markers of invasive disease and fungal burden with echinocandin therapy, these observations are inconsistent. The paradoxical effect has also not been demonstrated clinically. Thus, the clinical implications of the paradoxical attenuation of echinocandin activity at elevated concentrations remain unknown. A complete understanding of this effect may further our knowledge of fungal responses to echinocandin cell wall damage and potentially improve treatment strategies.

PMID: 19255904 [PubMed - indexed for MEDLINE]

1297. Environ Monit Assess. 2010 Mar;162(1-4):291-9. Epub 2009 Mar 3.

Comparison of the suitability of two lichen species and one higher plant for monitoring airborne heavy metals.

Aprile GG, Di Salvatore M, Carratù G, Mingo A, Carafa AM.

Dipartimento di Arboricoltura, Botanica, Patologia Vegetale-Sez. di Botanica, Federico II Facoltà di Agraria, Università degli Studi di Napoli, via Università, 100-80055, Portici, Naples, Italy. gaprile@unina.it

We compared the capacity to accumulate airborne heavy metals of two lichens (Flavoparmelia caperata and Parmotrema chinense) and one higher plant (Nerium oleander) at a very densely populated urban site near Naples. After 15, 45, 75, and 120 days of exposure at four sites with different levels of air pollution, equal portions of thalli and 20 leaves were collected, and four environmentally significant elements, Fe, Cu, Zn, and Pb, were measured by inductively coupled plasma analysis. To compare the accumulation rates of lichens and the vascular plant, we determined an index of relative accumulation rate of pollutants during time and the ratio between the concentrations of each element in exposed samples to that of control samples (exposed-to-control ratio). Our data indicate F. caperata as being the most suitable bioaccumulator, followed by P. chinense. N. oleander was also found to be a useful heavy metal biomonitor though not suitable as a bioaccumulator.

PMID: 19255863 [PubMed - indexed for MEDLINE]

1298. J Econ Entomol. 2009 Feb;102(1):43-9.

Efficacy of the biofumigant fungus Muscodor albus (Ascomycota: Xylariales) for control of codling moth (Lepidoptera: Tortricidae) in simulated storage conditions.

Lacey LA, Horton DR, Jones DC, Headrick HL, Neven LG.

USDA-ARS, Yakima Agricultural Research Laboratory, 5230 Konnowac Pass Road, Wapato, WA 98951, USA. lerry.lacey@ars.usda.gov

Codling moth, Cydia pomonella (L.) (Lepidoptera: Tortricidae), a serious pest of pome fruit, is a threat to exportation of apples (Malus spp.) because of the possibility of shipping infested fruit. The need for alternatives to fumigants such as methyl bromide for quarantine security of exported fruit has encouraged the development of effective fumigants with reduced side effects. The endophytic fungus Muscodor albus Worapong, Strobel and Hess (Ascomycota: Xylariales) produces volatile compounds that are biocidal for several pest organisms, including plant pathogens and insect pests. The objectives of our research were to determine the effects of M. albus volatile organic compounds (VOCs) on codling moth adults, neonate larvae, larvae in infested apples, and diapausing cocooned larvae in simulated storage conditions. Fumigation of adult codling moth with VOCs produced by M. albus for 3 d and incubating in fresh air for 24 h at 25 degrees C resulted in 81% corrected mortality. Four- and 5-d exposures resulted in higher mortality (84 and 100%, respectively), but control mortality was also high due to the short life span of the moths. Exposure of neonate larvae to VOCs for 3 d on apples and incubating for 7 d resulted in 86% corrected mortality. Treated larvae were predominantly first instars, whereas 85% of control larvae developed to second and third instars. Exposure of apples that had been infested for 5 d, fumigated with M. albus VOCs for 3 d, and incubated as described above resulted in 71% corrected larval mortality. Exposure of diapausing cocooned codling moth larvae to VOCs for 7 or 14 d resulted in 31 and 100% mortality, respectively, with negligible control mortality. Our data on treatment of several stages of codling moth with M. albus VOCs indicate that the fungus could provide an alternative to broad spectrum chemical fumigants for codling moth control in storage and contribute to the systems approach to achieve quarantine security of exported apples.

PMID: 19253616 [PubMed - indexed for MEDLINE]

1299. Intern Med. 2009;48(5):363-7. Epub 2009 Mar 2.

Cladosporium species-related hypersensitivity pneumonitis in household environments.

Chiba S, Okada S, Suzuki Y, Watanuki Z, Mitsuishi Y, Igusa R, Sekii T, Uchiyama B.

South Miyagi Medical Center, Miyagi.

Home-related chronic hypersensitivity pneumonitis (HP) is sometimes difficult to discriminate because patients do not have an obvious history of antigen exposure. We report two HP cases which developed in an office area and in a home: a 47-year-old woman with acute-onset HP and a 72-year-old woman with chronic HP followed up as idiopathic pulmonary fibrosis following isolation of Cladosporium cladosporioides and Cladosporium herbarum, respectively. Lymphocyte stimulating activity and antibody titer to these fungi were increased in these patients. Since Cladosporium spp. and several other fungi are present ubiquitously in our living environment, it is difficult to eliminate the antigen from the patients' environment to control the disease. Cladosporium spp. can be key antigens in inducing chronic HP in the home environment.

PMID: 19252363 [PubMed - indexed for MEDLINE]

1300. Environ Sci Technol. 2009 Feb 1;43(3):623-9.

Urban/peri-urban aerosol survey by determination of the concentration and isotopic composition of Pb collected by transplanted lichen Hypogymnia physodes.

Cloquet C, De Muynck D, Signoret J, Vanhaecke F.

CRPG, Nancy-Université, CNRS, 15 rue Notre-Dame-des-Pauvres B.P. 20, 54501 Vandoeuvre lès Nancy, France. cloquet@crpg.cnrs-nancy.fr

In the northeastern part of France, around the city of Metz, lichens (Hypogymnia physodes) have been transplanted from a single reference site to five different sites: (i) the reference site itself, (ii and iii) two peri-urban sites, (iv) a site in the proximity of a highway, and (v) a final one close to an industrial site. The dynamics of two different system set-ups (one covered and one uncovered) were evaluated. Samples have been collected 14, 34, and 68 days after transplantation. Lead concentrations already accumulated in the thallus, and the corresponding Pb isotopic compositions have been measured by quadrupole-based ICP-mass spectrometry. A systematic difference between the two setups is found for Pb concentrations, with the higher concentrations measured in lichens from the uncovered devices. Lead concentrations in lichens from the covered devices were found to be lower than or equal to the original concentration. Also the Pb isotopic compositions show a systematic difference between the devices, with the Pb isotopic composition present in lichens from the uncovered device being more radiogenic. Substantial changes in the isotopic composition of Pb are recorded for lichens from the uncovered device (from about 1.15 up to 1.22 for the 206Pb/207Pb ratio), in some cases already after only 34 days of exposure. The increases in the Pb concentration and the 206pb/207Pb ratio and the differences between the devices are explained by hypothesizing that (i) different Pb sources give rise to a different size distribution of aerosol particles and (ii) in the lichens present in the covered setup, a part of the aerosol particles cannot be incorporated. Also the influence of the source of the aerosols to lichens after transplantation is evaluated and the potential influence of biological reactions is discussed.

PMID: 19244993 [PubMed - indexed for MEDLINE]

1301. Nutr Clin Pract. 2009 Feb-Mar;24(1):33-40.

The use of probiotics in the prevention and treatment of antibiotic-associated diarrhea with special interest in Clostridium difficile-associated diarrhea.

Rohde CL, Bartolini V, Jones N.

RML Specialty Hospital, Food and Nutrition Services, 5601 South County Line Rd, Hinsdale, IL 60321, USA. crohde@rmlspecialtyhospital.org

Antimicrobials are effective agents used to combat virulent bacterial, yeast, and fungal infections that may otherwise cause rampant disease leading to skyrocketing social/economic costs and possible epidemic morbidity and mortality rates. Antibiotics are designed to attack specific bacterial pathogens but, in the process, indiscreetly reduce the number of beneficial human microbiota that is part of the gut-associated lymphatic tissue. Broad-spectrum antibiotics can upset this uniquely balanced gut ratio, allowing pathogens to propagate in a largely unrestrained environment, which may result in antibiotic-induced diarrhea. Critical illness, age, immunosuppression, exposure to nosocomial microorganisms, and the length of hospitalization are additional factors that contribute to the overgrowth of opportunistic pathogens. In mild to moderate cases of diarrhea, absorptive impairment may occur, thereby reducing micro/macronutrient assimilation, resulting in malnutrition and growth issues in children. In severe cases, infectious diarrhea can have devastating complications. Of particular interest is the bacterium Clostridium difficile, which has the potential to cause a host of symptoms ranging from mild diarrhea to severe life-threatening conditions. C. difficile infection can increase mortality rates by 10%-30%. Probiotic supplementation may prevent and treat antibiotic-associated diarrhea. Specific probiotics may modulate the intestinal mucosa by antagonizing pathogens through the production of antimicrobial compounds and chemicals, thereby reducing the rate of nosocomial infection and recurrence of C. difficile.

PMID: 19244146 [PubMed - indexed for MEDLINE]

1302. Plant Cell. 2009 Feb;21(2):655-67. Epub 2009 Feb 24.

A bacterial-type ABC transporter is involved in aluminum tolerance in rice.

Huang CF, Yamaji N, Mitani N, Yano M, Nagamura Y, Ma JF.

Research Institute for Bioresources, Okayama University, Kurashiki 710-0046, Japan.

Aluminum (Al) toxicity is a major factor limiting crop production in acidic soil, but the molecular mechanisms of Al tolerance are poorly understood. Here, we report that two genes, STAR1 (for sensitive to Al rhizotoxicity1) and STAR2, are responsible for Al tolerance in rice. STAR1 encodes a nucleotide binding domain, while STAR2 encodes a transmembrane domain, of a bacterial-type ATP binding cassette (ABC) transporter. Disruption of either gene resulted in hypersensitivity to aluminum toxicity. Both STAR1 and STAR2 are expressed mainly in the roots and are specifically induced by Al exposure. Expression in onion epidermal cells, rice protoplasts, and yeast showed that STAR1 interacts with STAR2 to form a complex that localizes to the vesicle membranes of all root cells, except for those in the epidermal layer of the mature zone. When expressed together in Xenopus laevis oocytes, STAR1/2 shows efflux transport activity specific for UDP-glucose. Furthermore, addition of exogenous UDP-glucose rescued root growth in the star1 mutant exposed to Al. These results indicate that STAR1 and STAR2 form a complex that functions as an ABC transporter, which is required for detoxification of Al in rice. The ABC transporter transports UDP-glucose, which may be used to modify the cell wall.

PMCID: PMC2660611 PMID: 19244140 [PubMed - indexed for MEDLINE]

1303. Am J Infect Control. 2009 Sep;37(7):609-11. Epub 2009 Feb 25.

Adherence to management after occupational exposure to bloodborne pathogen among health care workers in Taiwan.

Ko NY, Yeh SH, Tsay SL, Pan SM, Feng MC, Chiang MC, Lee YW, Chang LH, Jang JF.

Department of Nursing and Center of Infection Control, College of Medicine, National Cheng Kung University and Hospital, Tainan, Taiwan. nyko@mail.ncku.edu.tw

The study purpose was to investigate the adherence to postexposure management of health care workers (HCWs) in Taiwan. A total of 685 HCWs of 1164 HCWs who had reported exposure incidents during 2003-2005 completed questionnaires. Only 33% of the 567 exposed HCWs adhered to the postexposure management. Adherence was associated with percutaneous injury and knowledge of the seropositive status of source patients. Regular follow-ups for seroconversion testing are essential to improving the quality of postexposure management.

PMID: 19243861 [PubMed - indexed for MEDLINE]

1304. Int J Food Microbiol. 2009 May 31;131(2-3):246-50. Epub 2009 Feb 4.

Detection of viable Zygosaccharomyces bailii in fruit juices using ethidium monoazide bromide and real-time PCR.

Rawsthorne H, Phister TG.

Department of Bioscience and Biotechnology, 3141 Chestnut Street, Stratton Hall, Drexel University, Philadelphia, PA 19104, USA.

In this study, we use ethidium monoazide (EMA) a dye commonly used to differentiate viable and nonviable populations of bacteria in real-time PCR (QPCR) assays to eliminate the nonviable cells from the Z. bailii population. Thus we are able to determine the viable Z. bailii population using QPCR plus EMA. To do this we first, optimized the EMA exposure conditions; EMA concentration of 50 microg/ml with an incubation at 30 degrees C in the dark for 5 min. Followed by light exposure on ice, for 5 min using a 500 W halogen lamp at a distance of 12 cm. Using these optimized conditions, we determined that the assay could detect as few as 12.5 viable Z. bailii cells in the presence of 10(5) CFU/ml of heat killed-cells. The EMA assay was also more consistent at determining viable cell counts when compared to plating than fluorescent microscopy viable cell counts. Finally, we used the assay to determine the viable population in heat-treated (72 degrees C, 2 min), ethanol-treated and raspberry cranberry juice Z. bailii cultures. When examining Z. bailii cells treated with 70% ethanol the QPCR assay with EMA (1.22 x 10(2)) showed a better correlation with plating (4.5 x 10(1) CFU/ml) compared to the QPCR assay without EMA (5.31 x 10(6) CFU/ml) and this was also seen in the other two injured populations. Thus we feel that we have designed an assay which will be useful for the detection of viable spoilage yeasts in various fruit juices.

PMID: 19243848 [PubMed - indexed for MEDLINE]

1305. Thorax. 2009 Apr;64(4):353-8. Epub 2009 Feb 24.

Fungi and pollen exposure in the first months of life and risk of early childhood wheezing.

Harley KG, Macher JM, Lipsett M, Duramad P, Holland NT, Prager SS, Ferber J, Bradman A, Eskenazi B, Tager IB.

Center for Children's Environmental Health Research, School of Public Health, University of California, Berkeley, 2150 Shattuck Ave, Suite 600, Berkeley, CA 94704, USA. kharley@berkeley.edu

BACKGROUND: Many studies have found that the risk of childhood asthma varies by month of birth, but few have examined ambient aeroallergens as an explanatory factor. A study was undertaken to examine whether birth during seasons of elevated ambient fungal spore or pollen concentrations is associated with risk of early wheezing or blood levels of Th1 and Th2 type cells at 24 months of age.
METHODS: 514 children were enrolled before birth and followed to 24 months of age. Early wheezing was determined from medical records, and Th1 and Th2 type cells were measured in peripheral blood using flow cytometry. Ambient aeroallergen concentrations were measured throughout the study period and discrete seasons of high spore and pollen concentrations were defined.
RESULTS: A seasonal pattern was observed, with birth in autumn to winter (the spore season) associated with increased odds of early wheezing (adjusted odds ratio 3.1; 95% confidence interval 1.3 to 7.4). Increasing mean daily concentrations of basidiospores and ascospores in the first 3 months of life were associated with increased odds of wheeze, as were increasing mean daily concentrations of total and specific pollen types. Levels of Th1 cells at age 24 months were positively associated with mean spore concentrations and negatively associated with mean pollen concentrations in the first 3 months of life.
CONCLUSIONS: Children with higher exposure to spores and pollen in the first 3 months of life are at increased risk of early wheezing. This association is independent of other seasonal factors including ambient levels of particulate matter of aerodynamic diameter

PMID: 19240083 [PubMed - indexed for MEDLINE]

1306. FEMS Immunol Med Microbiol. 2009 Jun;56(1):32-40. Epub 2009 Feb 23.

Purification and immunological characterization of a 12-kDa allergen from Epicoccum purpurascens.

Kukreja N, Sridhara S, Singh BP, Gaur SN, Arora N.

Allergy and Immunology Section, Institute of Genomics and Integrative Biology (CSIR), Delhi University Campus, Delhi, India.

Exposure to Epicoccum purpurascens is implicated in respiratory allergies and asthma. Several allergens of clinical importance were identified in Epicoccum extract (EE), but only one allergen has been isolated and characterized. In the present study, a 12-kDa allergen was isolated from an Epicoccum spore-mycelial extract by concanavalin-A sepharose, reverse-phase hydrophobic and gel filtration chromatography. The purified protein was recognized as a single 12-kDa allergen on immunoblot with a serum pool of Epicoccum-sensitive patients. Of the 94 respiratory allergy patients tested intradermally, 17 showed marked positive skin reactions to EE and 12 of them reacted with the 12-kDa protein, indicating a diagnostic sensitivity of 70%. More than 80% patients' sera showed immunoglobulin E (IgE) reactivity to the purified protein in enzyme-linked immunosorbent assay and immunoblot, identifying it as a major allergen. Preincubation of pooled serum with the protein led to inhibition of IgE binding to solid-phase-bound EE (effective concentration 50%=180 ng). Twelve of the 17 serum samples showed significant basophil histamine release upon stimulation with purified protein. The protein induced significant proliferation of peripheral blood mononuclear cells of 13 patients. A high level of interleukin-4 in the culture supernatant of these cells indicated induction of a T-helper type 2 response. The purified 12-kDa protein is a clinically relevant allergen and has potential for the diagnosis and therapy of Epicoccum allergies.

PMID: 19239492 [PubMed - indexed for MEDLINE]

1307. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2008 Sep;25(9):1158-65.

Genomic analysis of Fusarium verticillioides.

Brown DW, Butchko RA, Proctor RH.

Mycotoxin Research Unit, US Department of Agriculture-ARS, Peoria, IL, USA. browndw@ncaur.usda.gov

Fusarium verticillioides (teleomorph Gibberella moniliformis) can be either an endophyte of maize, causing no visible disease, or a pathogen-causing disease of ears, stalks, roots and seedlings. At any stage, this fungus can synthesize fumonisins, a family of mycotoxins structurally similar to the sphingolipid sphinganine. Ingestion of fumonisin-contaminated maize has been associated with a number of animal diseases, including cancer in rodents, and exposure has been correlated with human oesophageal cancer in some regions of the world, and some evidence suggests that fumonisins are a risk factor for neural tube defects. A primary goal of the authors' laboratory is to eliminate fumonisin contamination of maize and maize products. Understanding how and why these toxins are made and the F. verticillioides-maize disease process will allow one to develop novel strategies to limit tissue destruction (rot) and fumonisin production. To meet this goal, genomic sequence data, expressed sequence tags (ESTs) and microarrays are being used to identify F. verticillioides genes involved in the biosynthesis of toxins and plant pathogenesis. This paper describes the current status of F. verticillioides genomic resources and three approaches being used to mine microarray data from a wild-type strain cultured in liquid fumonisin production medium for 12, 24, 48, 72, 96 and 120h. Taken together, these approaches demonstrate the power of microarray technology to provide information on different biological processes.

PMID: 19238625 [PubMed - indexed for MEDLINE]

1308. Pediatr Allergy Immunol. 2009 Dec;20(8):748-56. Epub 2009 Feb 13.

Indoor environmental risk factors and seasonal variation of childhood asthma.

Han YY, Lee YL, Guo YL.

Department of Environmental and Occupational Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.

Seasonality of asthma may result from varying exposures. This cross-sectional study was designed to examine the relationship between indoor environmental factors and seasonal childhood asthma. Study subjects were participants from the International Study of Asthma and Allergies in Childhood (ISAAC) in 2004, a population-based surveillance, which included school children aged 6-15 yr in south Taiwan. Cases included 1725 children who experienced asthma symptoms in the past 12 months and the references consisted of 19,646 children who reportedly have no asthma history. By using a moving average and principal component analysis, asthmatic children were grouped into four asthma subtypes: winter, spring, summer/fall, and perennial. Multivariate logistic regression was used to evaluate the effect of indoor environmental factors on seasonality of childhood asthma. For all asthma prevalence, a peak occurred in the winter and a nadir appeared in summer. Contributing factors of asthma for children, regardless of seasonality, included younger age, parental atopy, maternal smoking during pregnancy, breast feeding, and perceived air pollution. After adjusted for salient risk factors, water damage was significantly associated with all subtypes of asthma. Presence of cockroaches was related to the summer/fall asthma (adjusted odds ratio [aOR] = 1.65, 95% confidence interval [CI] = 1.12-2.55). Visible mold on the walls was associated with an increased occurrence of winter and spring asthma (aOR = 1.53, 95% CI = 1.26-1.85 and aOR = 1.34, 95% CI = 1.10-1.62, respectively). Passive smoking was shown to be related to spring and summer/fall asthma. Water damage is a possible risk for childhood asthma year-round. Cockroaches and visible mold on the walls may play essential roles for seasonality of childhood asthma in Taiwan. Plausible mechanisms and allergic effects should be further determined. Elimination of these allergens is necessary to help prevent the development of asthma.

PMID: 19236600 [PubMed - indexed for MEDLINE]

1309. Yeast. 2009 Feb;26(2):111-24.

Genome-wide expression profiling of the osmoadaptation response of Debaryomyces hansenii.

Gonzalez NA, Vázquez A, Ortiz Zuazaga HG, Sen A, Olvera HL, Peña de Ortiz S, Govind NS.

Department of Marine Sciences, University of Puerto Rico, Mayagüez, Puerto Rico.

The euryhaline marine yeast Debaromyces hansenii is a model system for the study of processes related to osmoadaptation. In this study, microarray-based gene expression analyses of the entire genome of D. hansenii was used to study its response to osmotic stress. Differential gene expression, compared to control, was examined at three time points (0.5, 3 and 6 h) after exposure of D. hansenii cultures to high salt concentration. Among the 1.72% of genes showing statistically significant differences in expression, only 65 genes displayed at least three-fold increases in mRNA levels after treatment with 2 M NaCl. On the other hand, 44 genes showed three-fold repression. Upregulated as well as the downregulated genes were grouped into functional categories to identify biochemical processes possibly affected by osmotic stress and involved in osmoadaptation. The observation that only a limited number of genes are upregulated in D. hansenii in response to osmotic stress supports the notion that D. hansenii is pre-adapted to survive in extreme saline environments. In addition, since more than one-half of the upregulated genes encode for ribosomal proteins, it is possible that a translational gene regulatory mechanism plays a key role in D. hansenii's osmoregulatory response. Validation studies for ENA1 and for hyphal wall/cell elongation protein genes, using real-time PCR, confirmed patterns of gene expression observed in our microarray experiments. To our knowledge, this study is the first of its kind in this organism and provides the foundation for future molecular studies assessing the significance of the genes identified here in D. hansenii's osmoadaptation.

PMID: 19235772 [PubMed - indexed for MEDLINE]

1310. Appl Microbiol Biotechnol. 2009 Apr;82(6):1123-30. Epub 2009 Feb 24.

Transcriptional profiles of response to terbinafine in Trichophyton rubrum.

Zhang W, Yu L, Yang J, Wang L, Peng J, Jin Q.

State Key Laboratory for Molecular Virology and Genetic Engineering, Beijing 100176, China.

Trichophyton rubrum is a good model for the study of human pathogenic filamentous fungi. The antifungal agent terbinafine (TRB) shows specific activity against T. rubrum. To identify the transcriptional profiles of response to TRB in T. rubrum, a cDNA microarray was constructed from the expressed sequence tags of different phase cDNA libraries and transcriptional profiles of the response to TRB were determined. Exposure to TRB decreased the transcription of some genes involved in the ergosterol biosynthesis pathway, including ERG2, ERG4, ERG24, and ERG25, and induced the expression of some genes involved in lipid metabolism such as ERG10, ERG13, and INO1. TRB affected transcription of multidrug-resistance genes and some genes encoding ribosomal proteins.

PMID: 19234875 [PubMed - indexed for MEDLINE]

1311. J Comp Physiol A Neuroethol Sens Neural Behav Physiol. 2009 May;195(5):445-51. Epub 2009 Feb 21.

No evidence for melatonin-linked immunoenhancement over the annual cycle of an avian species.

Buehler DM, Koolhaas A, Van't Hof TJ, Schwabl I, Dekinga A, Piersma T, Tieleman BI.

Animal Ecology Group, Centre for Ecological and Evolutionary Studies, University of Groningen, P.O. Box 14, 9750 AA, Haren, The Netherlands. d.m.buehler@rug.nl

The winter immunoenhancement hypothesis associates long nights and increased exposure to melatonin with enhanced immune function in winter when resource availability is low and the chances of becoming ill are high. Thus, increased exposure to melatonin in the winter could be adaptive for species facing difficult winter conditions. This idea has found some support in studies of resident mammals. In birds, the link between day length and melatonin over the annual cycle is weaker, and contributions of melatonin to seasonal timing are unclear. Furthermore, many species, especially migrants, do not experience the most difficult conditions of their annual cycle in winter. In this study, we tested whether the winter immunoenhancement hypothesis holds in an avian species, the red knot Calidris canutus. We found that melatonin duration and amplitude varied significantly over the annual cycle with the highest values occurring in winter. However, peaks did not correspond to the winter solstice or with annual variation in immune function. Our findings do not support the winter immunoenhancement hypothesis in knots and question whether the idea that immune function should be bolstered in winter can be generalized to systems where winter is not the most difficult time of the year.

PMID: 19234709 [PubMed - indexed for MEDLINE]

1312. Mol Biol Evol. 2009 May;26(5):1155-61. Epub 2009 Feb 20.

Solvent exposure imparts similar selective pressures across a range of yeast proteins.

Conant GC, Stadler PF.

Division of Animal Sciences and Informatics Institute, University of Missouri-Columbia, USA. conantg@missouri.edu

We study how an amino acid residue's solvent exposure influences its propensity for substitution by analyzing multiple alignments of 61 yeast genes for which the crystal structure is known. We find that the selective constraint on the interior residues is on average 10 times that of residues on the surface. Surprisingly, there is no correlation between the overall selective constraint observed for a protein alignment and the ratio of constraints on interior and surface residues. By modeling the selective constraint on several amino acid properties, we show that although residue volume and hydropathy are strongly conserved across most alignments, there is little variation in interior versus surface conservation for these two properties. By contrast, residue charge (isoelectric point) is less generally conserved when considering the protein as a whole but shows a strong constraint against the introduction of charged residues into the protein interior.

PMID: 19233963 [PubMed - indexed for MEDLINE]

1313. Occup Med (Lond). 2009 Mar;59(2):107-13.

Exposures to blood and body fluids in Brazilian primary health care.

Garcia LP, Facchini LA.

Department of Health Surveillance, Brazilian Ministry of Health, Brasília, Brazil.

BACKGROUND: Primary health care workers (HCWs) represent a growing occupational group worldwide. They are at risk of infection with blood-borne pathogens because of occupational exposures to blood and body fluids (BBF). AIM: To investigate BBF exposure and its associated factors among primary HCWs.
METHODS: Cross-sectional study among workers from municipal primary health care centres in Florianópolis, Southern Brazil. Workers who belonged to occupational categories that involved BBF exposures during the preceding 12 months were interviewed and included in the data analysis.
RESULTS: A total of 1077 workers participated. The mean incidence rate of occupational BBF exposures was 11.9 per 100 full-time equivalent worker-years (95% confidence interval: 8.4-15.3). The cumulative prevalence was 7% during the 12 months preceding the interview. University-level education, employment as a nurse assistant, dental assistant or dentist, higher workload score, inadequate working conditions, having sustained a previous occupational accident and current smoking were associated with BBF exposures (P CONCLUSIONS: Primary Health Care Centres are working environments in which workers are at risk of BBF exposures. Exposure surveillance systems should be created to monitor their occurrence and to guide the implementation of preventive strategies.

PMID: 19233830 [PubMed - indexed for MEDLINE]

1314. J Insect Physiol. 2009 Jun;55(6):525-31. Epub 2009 Feb 14.

Humoral immune response of Galleria mellonella larvae after infection by Beauveria bassiana under optimal and heat-shock conditions.

Wojda I, Kowalski P, Jakubowicz T.

Department of Invertebrate Immunology, Institute of Biology, Maria Curie-Sklodowska University, Lublin, Poland. wojda@hektor.umcs.lublin.pl

Natural infection of Galleria mellonella larvae with the entomopathogenic fungus Beauveria bassiana led to antifungal, but not antibacterial host response. This was manifested by induction of gallerimycin and galiomicin gene expression and, consequently, the appearance of antifungal activity in the hemolymph of the infected larvae. The activity of lysozyme increased at the beginning of infection and dropped while infection progressed. Exposure of the naturally infected animals to 43 degrees C for 15 min extended their life time. Galleria mellonella larvae were injected with 10(4), 10(5) and 10(6) fungal blastospores, resulting in the appearance of strong antifungal activity and a significant increase in lysozyme activity in larval hemolymph after 24h. Antibacterial activity was detectable only when 10(5) and increased when 10(6) blastospores were injected. The number of the injected B. bassiana blastospores also determined the survival rate of animals. We found that exposure of the larvae to 38 degrees C for 30 min before infection extended their life time when 10(3) and 10(4) spores were injected. The increase in the survival rate of the pre-heat-shocked animals may be explained by higher expression of antimicrobial peptides and higher antifungal and lysozyme activities in their hemolymph in comparison to non-heat-shocked animals.

PMID: 19232408 [PubMed - indexed for MEDLINE]

1315. Int J Med Microbiol. 2009 Aug;299(6):453-64. Epub 2009 Feb 20.

Role of trehalose-6P phosphatase (TPS2) in stress tolerance and resistance to macrophage killing in Candida albicans.

Martínez-Esparza M, Martínez-Vicente E, González-Párraga P, Ros JM, García-Peñarrubia P, Argüelles JC.

Departamento de Bioquímica y Biología Molecular B e Inmunología, Facultad de Medicina, Universidad de Murcia, E-30100 Murcia, Spain.

Disruption of the TPS2 gene encoding the only trehalose-6P phosphatase activity in Candida albicans caused a pleiotropic defective phenotype, maintaining the cell wall integrity and the ability to form chlamydospores. A homozygous tps2Delta/tps2Delta showed reduced growth at high temperatures and a marked sensitivity to heat shock (42 degrees C) and severe oxidative exposure (50mM H(2)O(2)). Reintroduction of the TPS2 gene reversed these alterations. A more detailed study of the antioxidant response showed that exponential tps2Delta null cells displayed an adaptive response to oxidative stress as well as cross-tolerance between temperature and oxidative stress. Differential measurement of trehalose and trehalose-6P, using reliable new HPLC methodology, revealed a significant accumulation of trehalose-6P in tps2Delta cells, which was enhanced after oxidative exposure. In contrast, the level of trehalose-6P in parental cells was virtually undetectable, and oxidative treatment only induced the synthesis of free trehalose. A transitory increase in the expression of TPS2 and TPS1 genes was promoted in wild-type cells in response to acute (50mM) but not gentle (5mM) oxidative exposure. TPS1 and TPS2 oxidative-induced transcriptions were completely absent from the tps2Delta mutant. Exponential blastoconidia from both parental and tps2Delta/tps2Delta strains were completely phagocytosed by murine and human macrophages, triggering a subsequent proinflammatory response manifested by the release of TNF-alpha. Reflecting the lower resistance to oxidative stress displayed by the tps2Delta mutant, intracellular survival in resting and IFN-gamma and LPS-stimulated macrophages was also diminished. Taken together, our results confirm the mainly protective role played by the trehalose biosynthetic pathway in the cellular response to oxidative stress and subsequently in the resistance to phagocytosis in C. albicans, a defensive mechanism in which TPS2 would be involved.

PMID: 19231283 [PubMed - indexed for MEDLINE]

1316. Ann Allergy Asthma Immunol. 2009 Feb;102(2):131-7.

Mold exposure during infancy as a predictor of potential asthma development.

Iossifova YY, Reponen T, Ryan PH, Levin L, Bernstein DI, Lockey JE, Hershey GK, Villareal M, LeMasters G.

Department of Environmental Health, University of Cincinnati, Cincinnati, Ohio 45267-0056, USA.

BACKGROUND: Exposure to mold has been associated with exacerbation of asthma symptoms in children.
OBJECTIVE: To report how the presence of visible mold and exposure to (1-3)-beta-D-glucan in infancy affects the risk of asthma at the age of 3 years as defined by an Asthma Predictive Index (API).
METHODS: Visible mold was evaluated by means of home inspection. (1-3)-beta-D-glucan levels were measured in settled dust. Children were considered to be at high risk for asthma at later ages if they reported recurrent wheezing at the age of 3 years and met at least 1 of 3 major or 2 of 3 minor API criteria.
RESULTS: Children aged 3 years with high visible mold in the home during infancy were 7 times more likely to have a positive API than were those with no visible mold (adjusted odds ratio [aOR], 7.1; 95% confidence interval [CI], 2.2-12.6). In contrast, at low (1-3)-beta-D-glucan levels (< 22 microg/g), children were at increased risk of a positive API (aOR, 3.4; 95% CI, 0.5-23.5), whereas those with high (1-3)-beta-D-glucan levels (> 133 microg/g) were at decreased risk (aOR, 0.6; 95% CI, 0.2-1.6). Of the other covariates, mother's smoking was the strongest significant risk factor for the future development of asthma based on a positive API (aOR, 4.4; 95% CI, 1.7-11.6).
CONCLUSIONS: The presence of high visible mold and mother's smoking during infancy were the strongest risk factors for a positive API at the age of 3 years, suggesting an increased risk of asthma. High (1-3)-beta-D-glucan exposure seems to have an opposite effect on API than does visible mold.

PMID: 19230464 [PubMed - indexed for MEDLINE]

1317. Respir Res. 2009 Feb 19;10:10.

Pneumocystis murina colonization in immunocompetent surfactant protein A deficient mice following environmental exposure.

Linke MJ, Ashbaugh AD, Demland JA, Walzer PD.

Research Service, Veterans Affairs Medical Center, Cincinnati, OH, USA. michael.linke@va.gov

BACKGROUND: Pneumocystis spp. are opportunistic pathogens that cause pneumonia in immunocompromised humans and animals. Pneumocystis colonization has also been detected in immunocompetent hosts and may exacerbate other pulmonary diseases. Surfactant protein A (SP-A) is an innate host defense molecule and plays a role in the host response to Pneumocystis.
METHODS: To analyze the role of SP-A in protecting the immunocompetent host from Pneumocystis colonization, the susceptibility of immunocompetent mice deficient in SP-A (KO) and wild-type (WT) mice to P. murina colonization was analyzed by reverse-transcriptase quantitative PCR (qPCR) and serum antibodies were measured by enzyme-linked immunosorbent assay (ELISA).
RESULTS: Detection of P. murina specific serum antibodies in immunocompetent WT and KO mice indicated that the both strains of mice had been exposed to P. murina within the animal facility. However, P. murina mRNA was only detected by qPCR in the lungs of the KO mice. The incidence and level of the mRNA expression peaked at 8-10 weeks and declined to undetectable levels by 16-18 weeks. When the mice were immunosuppressed, P. murina cyst forms were also only detected in KO mice. P. murina mRNA was detected in SCID mice that had been exposed to KO mice, demonstrating that the immunocompetent KO mice are capable of transmitting the infection to immunodeficient mice. The pulmonary cellular response appeared to be responsible for the clearance of the colonization. More CD4+ and CD8+ T-cells were recovered from the lungs of immunocompetent KO mice than from WT mice, and the colonization in KO mice depleted CD4+ cells was not cleared.
CONCLUSION: These data support an important role for SP-A in protecting the immunocompetent host from P. murina colonization, and provide a model to study Pneumocystis colonization acquired via environmental exposure in humans. The results also illustrate the difficulties in keeping mice from exposure to P. murina even when housed under barrier conditions.

PMCID: PMC2650685 PMID: 19228388 [PubMed - indexed for MEDLINE]

1318. Med Pr. 2008;59(5):373-9.

[Occupational exposure to mesophilic microorganisms associated with commercial processing of compost for mushroom production].

[Article in Polish]

Buczyńska A, Sowiak M, Szadkowska-Stańczyk I.

Instytut Medycyny Pracy im. prof. J. Nofera, Lódź, Zakład Srodowiskowych Zagrozeń Zdrowia. alina@imp.lodz.pl

BACKGROUND: The aim of the study was to assess the occupational exposure to mesophilic microorganisms associated with commercial processing of compost for mushroom production. MATERIALS AND METHODS: The air samples for microbiological analysis were collected directly on Petri dishes with Malt Extract Agar medium using Burkard Air Sampler. The quantitative and qualitative identification of mesophilic bacteria and mesophilic fungi were performed using the standard microbiological procedures.
RESULTS: Considerable variation in exposure to bioaerosols within the sectors of compost production were observed. The highest level of mesophilic bacteria in the air (4.17 x 10(4) cfu/m3) was measured during the mixing of raw materials with water and loading of the final compost piles to the pasteurization tunnels (3.54 x 10(4) cfu/m3). The highest concentration of mesophilic fungi was found in the air samples collected during the manual unrolling of straw (1.62 x 10(4) cfu/m3) and dosing of mycelium to the compost (1.15 x 10(4) cfu/m3). Among 33 identified bacteria and fungi species, Pasteurella sp, Proteus mirabilis, Streptomyces sp, Corynebacterium sp and Aspergillusfumigatus create the potential risk for health of exposed workers.
CONCLUSIONS: The presence of microorganisms found in the air creats the potential risk for human health, therefore the use of personal equipment, protecting the respiratory tract and skin of exposed workers is strongly recommended.

PMID: 19227882 [PubMed - indexed for MEDLINE]

1319. Med Pr. 2008;59(5):365-71.

[Assessment of occupational exposure to fungal aerosols in wastewater treatment plants].

[Article in Polish]

Cyprowski M, Sowiak M, Soroka PM, Buczyrńska A, Kozajda A, Szadkowska-Stańczyk I.

Instytut Medycyny Pracy im. prof. J. Nofera, Lódź, Zakład Srodowiskowych Zagrozeń Zdrowia. marc@imp.lodz.pl

BACKGROUND: The quantitative assessment and qualitative identification of moulds at workplaces in wastewater treatment plants were the aim of the study. MATERIALS AND METHODS: The study was carried out in four wastewater treatment plants, where 15 stationary points were selected according to mechanical, biological and sewage sludge treatment processes. In addition, background level samples from the city area were also collected. Bioaerosols were sampled with use of a Burkard Aerosol Sampler and directly put on Malt Extract Agar plates. Identification of moulds was based on morphological properties described in the professional literature.
RESULTS: The identified concentrations of moulds were low and ranged between 0.11 and 16.75 x 10(2) cfu/m3. The highest mean levels of fungal microflora were found during sewage sludge treatment processes. In total, there were 65 fungal isolates, of which 80% were found in wastewater treatment plants. In bioaerosol samples of the occupational origin, the highest (40%) amount of isolates originated from sewage sludge treatment processes and the lowest (25%) from biological treatment stages. In wastewater treatment plants, moulds of Aspergillus genus predominated and represented nearly 35% of all identified fungi. Comparing to background levels, the content of this genus was almost 4.5 times higher. Pathogenic Aspergillus fumigatus was found at all stages of wastewater treatment and Trichophyton genus at the stage of mechanical treatment. Moreover, there were numerous moulds of Mucor, Penicillium and Alternaria genera. In background samples moulds of Penicillium genus predominated and no pathogenic species were found.
CONCLUSIONS: The obtained results reveal that the sewage sludge is the main source of mould emission into the air at workplaces in wastewater treatment plants. On account of the presence of moulds with the evidenced infectious and allergic activity it is suggested that personal protective equipment should be used by employees.

PMID: 19227881 [PubMed - indexed for MEDLINE]

1320. Eur J Immunol. 2009 Mar;39(3):776-88.

Th2 allergic immune response to inhaled fungal antigens is modulated by TLR-4-independent bacterial products.

Allard JB, Rinaldi L, Wargo MJ, Allen G, Akira S, Uematsu S, Poynter ME, Hogan DA, Rincon M, Whittaker LA.

Department of Medicine, Division of Pulmonary Disease and Critical Care, Vermont Lung Center, University of Vermont, Burlington, VT, USA.

Allergic airway disease is characterized by eosinophilic inflammation, mucus hypersecretion and increased airway resistance. Fungal antigens are ubiquitous within the environment and are well known triggers of allergic disease. Bacterial products are also frequently encountered within the environment and may alter the immune response to certain antigens. The consequence of simultaneous exposure to bacterial and fungal products on the lung adaptive immune response has not been explored. Here, we show that oropharyngeal aspiration of fungal lysates (Candida albicans, Aspergillus fumigatus) promotes airway eosinophilia, secretion of Th2 cytokines and mucus cell metaplasia. In contrast, oropharyngeal exposure to bacterial lysates (Pseudomonas aeruginosa) promotes airway inflammation characterized by neutrophils, Th1 cytokine secretion and no mucus production. More importantly, administration of bacterial lysates together with fungal lysates deviates the adaptive immune response to a Th1 type associated with neutrophilia and diminished mucus production. The immunomodulatory effect that bacterial lysates have on the response to fungi is TLR4 independent but MyD88 dependent. Thus, different types of microbial products within the airway can alter the host's adaptive immune response and potentially impact the development of allergic airway disease to environmental fungal antigens.

PMCID: PMC2750775 PMID: 19224641 [PubMed - indexed for MEDLINE]

1321. Antimicrob Agents Chemother. 2009 Jun;53(6):2599-604. Epub 2009 Feb 17.

Metabolism of an alkyl polyamine analog by a polyamine oxidase from the microsporidian Encephalitozoon cuniculi.

Bacchi CJ, Yarlett N, Faciane E, Bi X, Rattendi D, Weiss LM, Woster PM.

Haskins Laboratories, Pace University, 41 Park Row, New York, NY 10038, USA. cbacchi@pace.edu

Encephalitozoon cuniculi is a microsporidium responsible for systemic illness in mammals. In the course of developing leads to new therapy for microsporidiosis, we found that a bis(phenylbenzyl)3-7-3 analog of spermine, 1,15-bis{N-[o-(phenyl)benzylamino}-4,12-diazapentadecane (BW-1), was a substrate for an E. cuniculi amine oxidase activity. The primary natural substrate for this oxidase activity was N'-acetylspermine, but BW-1 had activity comparable to that of the substrate. As the sole substrate, BW-1 gave linear reaction rates over 15 min and K(m) of 2 microM. In the presence of N'-acetylspermine, BW-1 acted as a competitive inhibitor of oxidase activity and may be a subversive substrate, resulting in increased peroxide production. By use of (13)C-labeled BW-1 as a substrate and nuclear magnetic resonance analysis, two products were determined to be oxidative metabolites, a hydrated aldehyde or dicarboxylate and 2(phenyl)benzylamine. These products were detected after exposure of (13)C-labeled BW-1 to E. cuniculi preemergent spore preparations and to uninfected host cells. In previous studies, BW-1 was curative in a rodent model of infection with E. cuniculi. The results in this study demonstrate competitive inhibition of oxidase activity by BW-1 and support further studies of this oxidase activity by the parasite and host.

PMCID: PMC2687184 PMID: 19223636 [PubMed - indexed for MEDLINE]

1322. Semin Respir Crit Care Med. 2008 Dec;29(6):670-9. Epub 2009 Feb 16.

Exposures and idiopathic lung disease.

Taskar V, Coultas D.

Department of Medicine, The University of Texas Health Science Center at Tyler, Tyler, Texas 75708, USA.

Of the idiopathic lung diseases, idiopathic pulmonary fibrosis (IPF) and sarcoidosis have been the focus of a growing number of epidemiological investigations on the risk of environmental and occupational exposures. To date, the consistency of epidemiological evidence is suggestive of a causal relationship between several environmental exposures and IPF, with the strongest evidence for cigarette smoking and metal dust. Current knowledge about pathogenesis provides further support for a causal link. However, scant epidemiological evidence for dose-response and temporality weaken the case for making causal inferences. In contrast to IPF, the quantity of epidemiological evidence for environmental exposures and sarcoidosis is smaller. Two studies provide consistent evidence for exposures to agricultural dust and musty odor/mold/mildew, and studies among military personnel and firefighters suggest mixed dust and fume exposures as risk factors for sarcoidosis. Although studies of the pathogenesis of sarcoidosis also provide evidence supporting environmental causation, more epidemiological studies are needed to establish consistency of associations, dose-response, and temporality. Future investigations, of gene-environment interaction offer the potential for strengthening the evidence of causation between several environmental and occupational exposures and idiopathic lung diseases.

PMID: 19221965 [PubMed - indexed for MEDLINE]

1323. Oecologia. 2009 May;160(2):335-42. Epub 2009 Feb 17.

Relative importance of tree genetics and microhabitat on macrofungal biodiversity on coarse woody debris.

Barbour RC, Storer MJ, Potts BM.

School of Plant Science and Cooperative Research Centre for Forestry, University of Tasmania, Private Bag 55, Hobart, Tasmania 7001, Australia. rbarbour@utas.edu.au

Understanding the contribution of genetic variation within foundation species to community-level pattern and diversity represents the cornerstone of the developing field of community genetics. We assessed the relative importance of intraspecific genetic variation, spatial variation within a forest and microhabitat variation on a macrofungal decay community developing on logs of the Australian forest tree, Eucalyptus globulus. Uniform logs were harvested from trees from eight geographic races of E. globulus growing in a 15-year-old genetic trial. Logs were placed as designed grids within a native E. globulus forest and after 3 years of natural colonisation the presence of 62 macrofungal taxa were recorded from eight microhabitats on each log. The key factor found to drive macrofungal distribution and biodiversity on structurally uniform coarse woody debris was log-microhabitat, explaining 42% of the total variation in richness. Differences between log-microhabitats appeared to be due to variation in aspect, substrate (bark vs wood) and area/time of exposure to colonisation. This findings demonstrates the importance of considering fine-scale (within substrate) variation in the conservation and management of macrofungal biodiversity, an area that has received little previous attention. While a number of recent studies have demonstrated that the genetics of foundation tree species can influence dependent communities, this was not found to be the case for the early log decay community associated with E. globulus. Despite genetic variation in wood and bark properties existing within this species, there was no significant effect of tree genetics on macrofungal community richness or composition. This finding highlights the variation that may exist among guilds of organisms in their response to genetic variation within foundation species, an important consideration in a promising new area of research.

PMID: 19221804 [PubMed - indexed for MEDLINE]

1324. FEMS Yeast Res. 2009 Mar;9(2):202-16.

The RIM101 pathway has a role in Saccharomyces cerevisiae adaptive response and resistance to propionic acid and other weak acids.

Mira NP, Lourenço AB, Fernandes AR, Becker JD, Sá-Correia I.

IBB, Centre for Biological and Chemical Engineering, Instituto Superior Técnico, Lisboa, Portugal.

The physiological function of the Saccharomyces cerevisiae RIM101 signaling pathway is extended in this study beyond alkaline pH-induced responses. The transcription factor Rim101p is demonstrated to be required for maximal tolerance to weak acid-induced stress, at pH 4.0, but does not exert protection against low pH itself (range 4.5-2.5), when a strong acid is used as the acidulant. The Rim101p-dependent alterations of the yeast transcriptome following exposure to propionic acid stress (at pH 4.0) include genes of the previously described Rim101p regulon but also new target genes, in particular KNH1, involved in cell wall beta-1,6-glucan synthesis and the uncharacterized ORF YIL029c, both required for maximal propionic acid resistance. Clustering of the genes that provide resistance to propionic acid reveals the enrichment of those involved in protein catabolism through the multivesicular body pathway and in the homeostasis of internal pH and vacuolar function. The analysis of the network of interactions established among all the identified propionic acid resistance determinants shows an enrichment of interactions around the RIM101 gene and highlights the role of proteins involved in Rim101p proteolytic processing. RIM101 expression is shown to be required to counteract propionic acid-induced cytosolic acidification and for proper vacuolar acidification and cell wall structure, these having positive implications for a robust adaptive response and resistance to stress promoted by this food preservative.

PMID: 19220866 [PubMed - indexed for MEDLINE]

1325. Allergy. 2009 Jul;64(7):1068-73. Epub 2009 Feb 13.

High levels of grass pollen inside European dairy farms: a role for the allergy-protective effects of environment?

Sudre B, Vacheyrou M, Braun-Fahrländer C, Normand AC, Waser M, Reboux G, Ruffaldi P, von Mutius E, Piarroux R; PASTURE study group.

Collaborators: Weiss G, Ublagger E, Humer C, Russegger M, Riedler J, Juntunen R, Tiihonen R, Tiittanen P, Hirvonen MR, Huttunen K, Virtanen S, Kauppila T, Nevalainen A, Hyvärinen A, Tuomainen TP, Karvonen A, Roponen M, Remes S, Pekkanen J, Vuitton DA, Dalphin JC, Dalphin ML, Roussel S, Ege MJ, Büchele G, Schmid S, Illi S, Korherr N, Genuneit J, Peter R, Sel S, Blümer N, Pfefferle P, Herzum I, Krauss-Etschmann S, Renz H, Gehring U, Brunekreef B, Bitter S, Sennhauser FH, Loeliger S, Steinle J, Frei R, Lauener RP.

CNRS-Université de Franche-Comté/UMR 6249 Laboratoire Chrono-environnement, Parasitology-Mycology departement, University Hospital of Besançon, France.

BACKGROUND: There is evidence of an allergy protective effect in children raised on farm. It has been assumed that microbial exposure may confer this protection. However in farm, little attention has been given to the pollen level and to concomitant microbiological exposure, and indoor pollen concentrations have never been precisely quantified.
METHODS: The kinetics of pollen in dairy farms have been studied in a pilot study (n = 9), and exposure in a sub-sample of the ongoing European birth cohort PASTURE (n = 106). Measurements of viable microorganisms and pollen were performed in air samples. To identify factors that modulate the pollen concentration multivariate regression analyses were run.
RESULTS: Indoor pollen (95% of Poaceae fragments and grains) were significantly higher in winter than in summer (P = 0.001) and ranged between 858 to 11 265 counts/m(3) during feeding in winter, thus exceeding typical outdoor levels during the pollen season. Geometric mean in French farms was significantly higher than in German and Swiss farms (7 534, 992 and 1 079 count/m(3), respectively). The presence of a ventilation system and loose housing systems significantly reduced indoor pollen levels. This pollen concentration rise after feeding was accompanied by an increase in fungal and actinomycetal levels, whereas the concentration of bacteria was not associated with feeding.
CONCLUSIONS: Farmers and their children who attend cowsheds during the feeding sessions are exposed perennially to high pollen concentrations. It might be speculated that the combined permanent exposure to microbes from livestock and grass pollen may initiate tolerance in children living on a farm.

PMID: 19220219 [PubMed - indexed for MEDLINE]

1326. Int J Hyperthermia. 2009 Feb;25(1):72-8.

Some peculiarities of the sequential action of heat and ionizing radiation on yeast cells.

Petin VG, Kim JK, Zhurakovskaya GP, Kim SH.

Biophysical Laboratory, Medical Radiological Research Centre, Obninsk, Kaluga Region, Russia.

The dependence of the thermal enhancement ratio after a sequential action of heat and ionizing radiation on the dose and dose rate of ionizing radiation as well as on the temperature and duration of its application was studied for yeast cells. The combined effect of heat and ionizing radiation on cell killing depended on both the sequence of application (i.e. whether heat is applied prior to or following irradiation) and the temperature. The effectiveness of treatment with heat and ionizing radiation was greatly dependent on the duration of heat exposure. For an equal amount of cell killing from heat alone, long action of heat (50 degrees C) was more effective for radiosensitization than a short acute action of high heat (58 degrees C). For heating at 50 degrees C, heating after irradiation produced more radiosensitization than heating before irradiation. However, high heating at 58 degrees C before irradiation gave the same radiosensitization as heating after irradiation. These data confirm similar observations for mammalian cells. The results were interpreted by means of a mathematical model in which the synergistic effect of the sequential application of heat and ionizing radiation results from the additional lethal damage arising from the interaction of sublesions induced by both agents. These sublesions are not lethal after the action of these modalities, each taken alone. The model appears to be appropriate and the conclusions are valid.

PMID: 19219703 [PubMed - indexed for MEDLINE]

1327. Am J Infect Control. 2009 Sep;37(7):525-33. Epub 2009 Feb 12.

The prevalence and risk factors for percutaneous injuries in registered nurses in the home health care sector.

Gershon RR, Pearson JM, Sherman MF, Samar SM, Canton AN, Stone PW.

Mailman School of Public Health, Columbia University, New York, NY 10032, USA. rg405@columbia.edu

BACKGROUND: Patients continue to enter home health care (HHC) "sicker and quicker," often with complex health problems that require extensive intervention. This higher level of acuity may increase the risk of percutaneous injury (PI), yet information on the risk and risk factors for PI and other types of exposures in this setting is exceptionally sparse. To address this gap, a large cross-sectional study of self-reported exposures in HHC registered nurses (RNs) was conducted.
METHODS: A convenience sample of HHC RNs (N=738) completed a survey addressing 5 major constructs: (1) worker-centered characteristics, (2) patient-related characteristics, (3) household characteristics, (4) organizational factors, and (5) prevalence of PIs and other blood and body fluid exposures. Analyses were directed at determining significant risk factors for exposure.
RESULTS: Fourteen percent of RNs reported one or more PIs in the past 3 years (7.6 per 100 person-years). Nearly half (45.8%) of all PIs were not formally reported. PIs were significantly correlated with a number of factors, including lack of compliance with Standard Precautions (odds ratio [OR], 1.72; P=.019; 95% confidence interval [CI]: 1.09-2.71); recapping of needles (OR, 1.78; P=.016; 95% CI: 1.11-2.86); exposure to household stressors (OR, 1.99; P=.005; 95% CI: 1.22-3.25); exposure to violence (OR, 3.47; P=.001; 95% CI: 1.67-7.20); mandatory overtime (OR, 2.44; P=.006; 95% CI: 1.27-4.67); and safety climate (OR, 1.88; P=.004; 95% CI: 1.21-2.91) among others.
CONCLUSION: The prevalence of PI was substantial. Underreporting rates and risk factors for exposure were similar to those identified in other RN work populations, although factors uniquely associated with home care were also identified. Risk mitigation strategies tailored to home care are needed to reduce risk of exposure in this setting.

PMID: 19216006 [PubMed - indexed for MEDLINE]

1328. Med Mycol. 2009 Dec;47(8):796-801.

In vitro pharmacodynamic characteristics of griseofulvin against dermatophyte isolates of Trichophyton tonsurans from tinea capitis patients.

Gupta AK, Williams JV, Zaman M, Singh J.

Mycology Section, Mediprobe Research Inc., London, Ontario, Canada.

Tinea capitis is the most commonly observed fungal infection in childhood and is primarily caused by the dermatophyte species Trichophyton tonsurans, Microsporum canis, and Trichophyton violaceum. In North America and the United Kingdom T. tonsurans is responsible for more than 90% of cases. Griseofulvin has been the treatment of choice for tinea capitis for more than 40 years and is the sole oral antifungal agent approved by the FDA for the management of tinea capitis. Some researchers have expressed concern about the possibility of emerging resistance in tinea capitis isolates, especially when there is clinical failure to treatment. A total of 151 isolates of T. tonsurans (142), M. canis (7), and T. violaceum (2) collected from tinea capitis patients were evaluated for their susceptibility to griseofulvin using the CLSI M38-A method. MIC ranges and geometric means in parenthesis were observed for T. tonsurans 0.125-16 microg/ml (1.1 microg/ml), M. canis 0.25-2 microg/ml (0.61 microg/ml), and T. violaceum 2-4 microg/ml (2.82 microg/ml), respectively. In a time kill assay with T. tonsurans UAMH 9334, 50% and 90% reduction was observed in the number of colony forming units with >2x MIC after 6 h and 12 h of exposure to the griseofulvin, respectively. Of 142 T. tonsurans isolates studied, only three could grow on SDA containing 4 times to their griseofulvin MIC, representing resistance frequencies of 1.3 x 10(-6), 6.9 x 10(-7), and 9.7 x 10(-7). Furthermore a two-fold increase in MIC was observed in isolates collected at two time intervals in only one of eight patients. Interestingly, these isolates did not show the same increase in their in vitro resistance as exhibited by the three isolated mentioned above. In light of this data, we could not confirm any correlation between increased MIC and therapy failure.

PMID: 19212895 [PubMed - indexed for MEDLINE]

1329. Environ Pollut. 2009 May;157(5):1581-8. Epub 2009 Feb 10.

Cd-tolerant Suillus luteus: a fungal insurance for pines exposed to Cd.

Krznaric E, Verbruggen N, Wevers JH, Carleer R, Vangronsveld J, Colpaert JV.

Environmental Biology Group, Centre for Environmental Sciences, Hasselt University, Agoralaan, Gebouw D, 3590 Diepenbeek, Belgium.

Soil metal pollution can trigger evolutionary adaptation in soil-borne organisms. An in vitro screening test showed cadmium adaptation in populations of Suillus luteus (L.: Fr.) Roussel, an ectomycorrhizal fungus of pine trees. Cadmium stress was subsequently investigated in Scots pine (Pinus sylvestris L.) seedlings inoculated with a Cd-tolerant S. luteus, isolated from a heavy metal contaminated site, and compared to plants inoculated with a Cd-sensitive isolate from a non-polluted area. A dose-response experiment with mycorrhizal pines showed better plant protection by a Cd-adapted fungus: more fungal biomass and a higher nutrient uptake at high Cd exposure. In addition, less Cd was transferred to aboveground plant parts. Because of the key role of the ectomycorrhizal symbiosis for tree fitness, the evolution of Cd tolerance in an ectomycorrhizal partner such as S. luteus can be of major importance for the establishment of pine forests on Cd-contaminated soils.

PMID: 19211178 [PubMed - indexed for MEDLINE]

1330. Respirology. 2009 Apr;14(3):360-70. Epub 2009 Feb 4.

Chronic intranasal administration of Aspergillus fumigatus spores leads to aggravation of airway inflammation and remodelling in asthmatic rats.

Gao FS, Qiao JO, Zhang Y, Jin XQ.

Department of Respiratory Medicine, First People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China.

BACKGROUND AND OBJECTIVE: Epidemiological evidence indicates a close link between exposure to fungi and deterioration of asthma. However, the role of fungi as an exogenous precipitant for initiation and progression of asthma has been incompletely explored. In this study, the effects of Aspergillus fumigatus exposure on airway inflammation and remodelling in a rat model of chronic asthma were investigated.
METHODS: The rat model of chronic asthma was established by systemic sensitization and repeated challenge with ovalbumin (OVA). The asthmatic rats were exposed to chronic intranasal inhalation of A. fumigatus spores. Changes in airway inflammation, remodelling and BHR were measured after exposure to the fungus.
RESULTS: Chronic inhalation of A. fumigatus spores elevated the production of T helper 2 (Th2) cytokines, increased the concentration of total serum IgE, and resulted in the recruitment of eosinophils and lymphocyte infiltration into the airways of asthmatic rats. Goblet cell hyperplasia, mucus hyperproduction and subepithelial collagen deposition were also induced by inhalation of the fungus. The remodelling changes induced by inhalation of the fungus paralleled the changes in BHR in this rat model of asthma.
CONCLUSIONS: Chronic exposure to A. fumigatus aggravated Th2 airway inflammation, promoted airway remodelling and increased BHR in OVA-sensitized and -challenged rats.

PMID: 19207119 [PubMed - indexed for MEDLINE]

1331. Crit Rev Toxicol. 2009;39(2):139-93.

Microbial volatile organic compounds.

Korpi A, Järnberg J, Pasanen AL.

University of Kuopio, Department of Environmental Science, Kuopio, Finland. anne.korpi@uku.fi

Microbial volatile organic compounds (MVOCs) are a variety of compounds formed in the metabolism of fungi and bacteria. Of more than 200 compounds identified as MVOCs in laboratory experiments, none can be regarded as exclusively of microbial origin or as specific for certain microbial species. Thus, the recognition of microbially contaminated areas by MVOC measurements is not successful with current methods. In this review, the basic physical and chemical properties of 96 typical MVOCs have been summarised. Of these, toxicological and exposure data were gathered for the 15 MVOCs most often analysed and reported in buildings with moisture and microbial damage. The most obvious health effect of MVOC exposure is eye and upper-airway irritation. However, in human experimental exposure studies, symptoms of irritation have appeared at MVOC concentrations several orders of magnitude higher than those measured indoors (single MVOC levels in indoor environments have ranged from a few ng/m(3) up to 1 mg/m(3)). This is also supported by dose-dependent sensory-irritation response, as determined by the American Society for Testing and Materials mouse bioassay. On the other hand, the toxicological database is poor even for the 15 examined MVOCs. There may be more potent compounds and other endpoints not yet evaluated.

PMID: 19204852 [PubMed - indexed for MEDLINE]

1332. J Environ Sci (China). 2008;20(11):1356-62.

Effect of cypermethrin insecticide on the microbial community in cucumber phyllosphere.

Zhang B, Zhang H, Jin B, Tang L, Yang J, Li B, Zhuang G, Bai Z.

Research Centre for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China. baoguozhang521@yahoo.com.cn

Cucumber (Cucumis sativus) is one of the most widely used vegetable in the world, and different pesticides have been extensively used for controlling the insects and disease pathogens of this plant. However, little is known about how the pesticides affect the microbial community in cucumber phyllosphere. This study was the first attempt to assess the impact of pyrethroid insecticide cyperemethrin on the microbial communities of cucumber phyllosphere using biochemical and genetic approaches. Phospholipid fatty acid (PLFA) assay indicated that cyperemethrin insecticide treatment led to a significant increase in both total and bacterial biomass and a decrease in fungal biomass and the ratio of Gram-positive (GP) bacteria to Gram-negative (GN) bacteria within the cucumber phyllosphere. Principal-component analyses (PCA) suggested that the number of unsaturated and cyclopropane PLFAs (16:1 omega 9t, 18:1 omega 7, cy17:0, cy19:0) increased with the insecticide treatment, whereas the saturated PLFA i16:0, i17:0 decreased. The increase of GN bacteria implied that the cypermethrin insecticide might be a nutrient for the growth of these phyllosphere microbes. Terminal restriction fragment length polymorphism (T-RFLP) reinforced the PLFA results. A significant change of bacterial community structure was observed in the separate dendrogram cluster between control and treated samples with the cucumber phyllosphere following cypermethrin insecticide treatment. Moreover, the increased terminal restriction fragments (T-RFs) (58, 62, 89, 99, 119, 195, 239, 311, 340, and 473 bp) indicated that some bacteria might play a significant role in the insecticide degradation within the cucumber phylosphere, whereas the disappeared T-RFs (44, 51, 96, 223, 306, and 338 bp) implied that some other bacteria might potentially serve as microbial indicator of cyperemethrin insecticide exposure.

PMID: 19202876 [PubMed - indexed for MEDLINE]

1333. Mycologia. 2008 Nov-Dec;100(6):956-61.

Durianella, a new gasteroid genus of boletes from Malaysia.

Desjardin DE, Wilson AW, Binder M.

Department of Biology, San Francisco State University, 1600 Holloway Avenue, San Francisco, California 94132, USA. ded@sfsu.edu

Hydnangium echinulatum, described originally from a single specimen collected in Malaysia, has been recollected, and based on morphological and molecular characters is recognized as representing a new gasteroid genus of boletes with affinities to the Boletineae, herein named Durianella. Diagnostic features include an epigeous, ovoid, pyramidal-warted, durian fruit-like basidiome with gelatinized glebal locules and a columella that turns indigo blue upon exposure, and subglobose basidiospores with long, curved, thin-walled and collapsible spines. A redescription, phylogenetic analysis and comparison with allied taxa are presented.

PMID: 19202849 [PubMed - indexed for MEDLINE]

1334. Mycologia. 2008 Nov-Dec;100(6):833-42.

Nondormancy in Entomophaga maimaiga azygospores: effects of isolate and cold exposure.

Hajek AE, Burke AE, Nielsen C, Hannam JJ, Bauer LS.

Department of Entomology, Comstock Hall, Garden Avenue, Cornell University, Ithaca, New York 14853-2601, USA. aeh4@cornell.edu

Azygospores (resting spores) of the fungal pathogen Entomophaga maimaiga are produced in later larval instars of the gypsy moth Lymantria dispar and normally enter constitutive dormancy. In the laboratory cadavers of recently dead larvae containing immature azygospores were placed on 1.0% water agar at 20 C for 2 wk after host death, allowing time for azygospore maturation. We found that some azygospores produced in this way did not enter dormancy. To investigate nondormancy, suspensions of azygospores from individual cadavers were transferred to moist, sterile soil at 15 C. Groups of gypsy moth larvae were exposed sequentially to azygospores for consecutive 4 d periods for 196 d. Infections first were seen among larvae exposed 24-28 d after bioassays began, and infection potential continued 196 d. Germination tests confirmed azygospore germination. Additional cadavers containing azygospores produced under the same conditions were maintained at 4 C for 1-8 mo, and each month new sequential bioassays were initiated. There was a general trend of earlier initiation of infection with longer durations of 4 C exposure; after 6-8 mo at 4 C first infections occurred 6-10 d after bioassays began. With 5-8 mo at 4 C infection levels declined after 96 d of sequential bioassays. Activity of azygospores differed by the individual larval cadaver in which they were produced; azygospores from 29.2% of cadavers yielded only 0-0.3% infection. Infection from nondormant azygospores did not differ among three Japanese isolates and two North American isolates, although azygospores from a third North American isolate caused no infections in 84 d, suggesting that dormancy had not been prevented.

PMID: 19202838 [PubMed - indexed for MEDLINE]

1335. Appl Environ Microbiol. 2009 May;75(9):2742-9. Epub 2009 Feb 6.

Treatment of fungal bioaerosols by a high-temperature, short-time process in a continuous-flow system.

Jung JH, Lee JE, Lee CH, Kim SS, Lee BU.

Center for Environmental Technology Research, Korea Institute of Science and Technology, Hawolgok-dong, Seongbuk-gu, Seoul 136-791, Republic of Korea.

Airborne fungi, termed fungal bioaerosols, have received attention due to the association with public health problems and the effects on living organisms in nature. There are growing concerns that fungal bioaerosols are relevant to the occurrence of allergies, opportunistic diseases in hospitals, and outbreaks of plant diseases. The search for ways of preventing and curing the harmful effects of fungal bioaerosols has created a high demand for the study and development of an efficient method of controlling bioaerosols. However, almost all modern microbiological studies and theories have focused on microorganisms in liquid and solid phases. We investigated the thermal heating effects on fungal bioaerosols in a continuous-flow environment. Although the thermal heating process has long been a traditional method of controlling microorganisms, the effect of a continuous high-temperature, short-time (HTST) process on airborne microorganisms has not been quantitatively investigated in terms of various aerosol properties. Our experimental results show that the geometric mean diameter of the tested fungal bioaerosols decreased when they were exposed to increases in the surrounding temperature. The HTST process produced a significant decline in the (1-->3)-beta-d-glucan concentration of fungal bioaerosols. More than 99% of the Aspergillus versicolor and Cladosporium cladosporioides bioaerosols lost their culturability in about 0.2 s when the surrounding temperature exceeded 350 degrees C and 400 degrees C, respectively. The instantaneous exposure to high temperature significantly changed the surface morphology of the fungal bioaerosols.

PMCID: PMC2681678 PMID: 19201954 [PubMed - indexed for MEDLINE]

1336. J Immunol. 2009 Feb 15;182(4):2502-10.

Asthma-related environmental fungus, Alternaria, activates dendritic cells and produces potent Th2 adjuvant activity.

Kobayashi T, Iijima K, Radhakrishnan S, Mehta V, Vassallo R, Lawrence CB, Cyong JC, Pease LR, Oguchi K, Kita H.

Division of Allergic Diseases, Department of Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA.

Asthma is thought to result from dysregulated Th2-like airway inflammatory responses to the environment. Although the etiology of asthma is not fully understood in humans, clinical and epidemiological evidence suggest a potential link between exposure to environmental fungi, such as Alternaria, and development and/or exacerbation of asthma. The goal of this project was to investigate the mechanisms of airway Th2 responses by using Alternaria as a clinically relevant model for environmental exposure. Airway exposure of naive animals to an experimental Ag, OVA, or a common allergen, short ragweed pollen, induced no or minimal immune responses to these Ags. In contrast, mice developed strong Th2-like immune responses when they were exposed to these Ags in the presence of Alternaria extract. Extracts of other fungi, such as Aspergillus and Candida, showed similar Th2 adjuvant effects, albeit not as potently. Alternaria stimulated bone marrow-derived dendritic cells (DCs) to express MHC class II and costimulatory molecules, including OX40 ligand, in vitro. Importantly, Alternaria inhibited IL-12 production by activated DCs, and DCs exposed to Alternaria enhanced Th2 polarization of CD4(+) T cells. Furthermore, adoptive airway transfer of DCs, which had been pulsed with OVA in the presence of Alternaria, showed that the recipient mice had enhanced IgE Ab production and Th2-like airway responses to OVA. Thus, the asthma-related environmental fungus Alternaria produces potent Th2-like adjuvant effects in the airways. Such immunogenic properties of certain environmental fungi may explain their strong relationships with human asthma and allergic diseases.

PMCID: PMC2653279 PMID: 19201906 [PubMed - indexed for MEDLINE]

1337. J Immunol. 2009 Feb 15;182(4):2416-24.

IgE influences the number and function of mature mast cells, but not progenitor recruitment in allergic pulmonary inflammation.

Mathias CB, Freyschmidt EJ, Caplan B, Jones T, Poddighe D, Xing W, Harrison KL, Gurish MF, Oettgen HC.

Division of Immunology, Children's Hospital, Boston, MA 02115, USA.

Studies performed using cultured cells indicate that IgE functions not only to trigger degranulation of mast cells following allergen exposure, but also to enhance their survival. Such an influence of IgE on mast cell homeostasis during allergic responses in vivo has not been established. In this study, we show that inhalation of Aspergillus fumigatus extract in mice induced a dramatic rise in IgE accompanied by an increase in airway mast cells. These had an activated phenotype with high levels of FcepsilonRI. Plasma mast cell protease-1 was also increased, indicating an elevated systemic mast cell load. In addition, enhanced levels of IL-5 and eosinophils were observed in the airway. Both mast cell expansion and activation were markedly attenuated in IgE(-/-) animals that are incapable of producing IgE in response to A. fumigatus. The recruitment of eosinophils to the airways was also reduced in IgE(-/-) mice. Analyses of potential cellular targets of IgE revealed that IgE Abs are not required for the induction of mast cell progenitors in response to allergen, but rather act by sustaining the survival of mature mast cells. Our results identify an important role for IgE Abs in promoting mast cell expansion during allergic responses in vivo.

PMCID: PMC2653867 PMID: 19201896 [PubMed - indexed for MEDLINE]

1338. Environ Res. 2009 Apr;109(3):215-24. Epub 2009 Feb 8.

Aerosolization of fungi, (1-->3)-beta-D glucan, and endotoxin from flood-affected materials collected in New Orleans homes.

Adhikari A, Jung J, Reponen T, Lewis JS, DeGrasse EC, Grimsley LF, Chew GL, Grinshpun SA.

Center for Health-Related Aerosol Studies, Department of Environmental Health, University of Cincinnati, P.O. Box 670056, 3223 Eden Avenue, Cincinnati, OH 45267-0056, USA.

Standing water and sediments remaining on flood-affected materials were the breeding ground for many microorganisms in flooded homes following Hurricane Katrina. The purpose of this laboratory study was to examine the aerosolization of culturable and total fungi, (1-->3)-beta-D glucan, and endotoxin from eight flood-affected floor and bedding materials collected in New Orleans homes, following Hurricane Katrina. Aerosolization was examined using the Fungal Spore Source Strength Tester (FSSST) connected to a BioSampler. Dust samples were collected by vacuuming. A two-stage cyclone sampler was used for size-selective analysis of aerosolized glucan and endotoxin. On average, levels of culturable fungi ranged from undetectable (lower limit=8.3 x 10(4)) to 2.6 x 10(5) CFU/m(2); total fungi ranged from 2.07 x 10(5) to 1.6 x 10(6) spores/m(2); (1-->3)-beta-D glucan and endotoxin were 2.0 x 10(3) - 2.9 x 10(4) ng/m(2) and 7.0 x 10(2) - 9.3 x 10(4) EU/m(2), respectively. The results showed that 5-15 min sampling is sufficient for detecting aerosolizable biocontaminants with the FSSST. Smaller particle size fractions (<1.0 and <1.8 microm) have levels of glucan and endotoxin comparable to larger (>1.8 microm) fractions, which raises additional exposure concerns. Vacuuming was found to overestimate inhalation exposure risks by a factor of approximately 10(2) for (1-->3)-beta-D glucan and by 10(3)-10(4) for endotoxin as detected by the FSSST. The information generated from this study is important with respect to restoration and rejuvenation of the flood-affected areas in New Orleans. We believe the findings will be significant during similar disasters in other regions of the world including major coastal floods from tsunamis.

PMID: 19201399 [PubMed - indexed for MEDLINE]

1339. Pest Manag Sci. 2009 Jun;65(6):624-8.

Nanodisks protect amphotericin B from ultraviolet light and oxidation-induced damage.

Tufteland ML, Selitrennikoff CP, O Ryan R.

Children's Hospital Oakland Research Institute, Oakland, CA 94609, USA.

BACKGROUND: Macrolide polyene antibiotics possess potent broad-spectrum antifungal properties. Use of these agents in the field or in controlled environments is impeded by their poor water solubility and susceptibility to oxidation- and/or light-induced degradation. While typically used for human disease therapy, there is potential to expand the utility of polyene macrolide antibiotics, such as amphotericin B, for control of fungal disease infestation in agricultural settings. Thus, the susceptibility of this antibiotic to exposure-induced activity loss was evaluated.
RESULTS: Incubation of the prototype polyene amphotericin B (AMB) with phospholipid vesicles and apolipoprotein A-I results in the formation of nanoscale complexes, termed nanodisks (NDs), capable of solubilizing significant quantities of AMB. To evaluate whether AMB incorporation into NDs conferred protection against light- or oxidation-induced damage, yeast growth inhibition assays were conducted. Compared with AMB solubilized in detergent micelles, AMB incorporated into NDs was protected from damage caused by exposure to UV light as well as by KMnO(4)-induced oxidation. Furthermore, AMB-NDs inhibited growth of the turfgrass fungus Marasmius oreades Fr.
CONCLUSION: Results suggest that this water-soluble formulation of a natural, biodegradable, antifungal agent represents a potential cost-effective, non-toxic and environmentally friendly substitute for chemical agents currently employed to control a range of fungal infestations.

PMCID: PMC2893591 PMID: 19198012 [PubMed - indexed for MEDLINE]

1340. Exp Dermatol. 2009 Jul;18(7):603-10. Epub 2008 Dec 19.

Candida albicans phospholipomannan triggers inflammatory responses of human keratinocytes through Toll-like receptor 2.

Li M, Chen Q, Shen Y, Liu W.

Institute of Dermatology, Chinese Academy of Medical Science & Peking Union Medical College, 12 Jiangwangmiao St., Nanjing 210042, China. minli08@gmail.com

The Toll-like receptors (TLRs) play an important role in the recognition of Candida albicans components and activation of innate immunity. Phospholipomannan (PLM), a glycolipid, is expressed at the surface of C. albicans cell wall, which acts as a member of the pathogen-associated molecular patterns family. In this study, we sought to clarify whether C. albicans-native PLM could induce an inflammation response in human keratinocytes and to determine the underlying mechanisms. Exposure of cultured human primary keratinocytes to PLM led to the increased gene expression and secretion of proinflammatory cytokines (IL-6) and chemokines (IL-8). PLM hydrolysed with beta-d-mannoside mannohydrolase failed to induce gene expression and secretion of IL-6 and IL-8. PLM up-regulated the mRNA and protein levels of TLR2, whereas the mRNA level of TLR4 was not altered. Keratinocytes challenged with PLM resulted in the activation of NF-kappaB and mitogen-activated protein kinase (MAPKs) including p38. Anti-TLR2 neutralizing antibody, NFkappaB and p38MAPK inhibitors blocked the PLM-induced secretion of IL-6, IL-8 in keratinocytes, but no such effect was observed in pretreatment with anti-TLR4-neutralizing antibody and lipopolysaccharide inhibitor (polymyxin B). These data suggest C. albicans-native PLM may contribute to the inflammatory responses of cutaneous candidiasis in the TLR2-NF-kappaB and p38MAPK signalling pathway dependent manner.

PMID: 19196344 [PubMed - indexed for MEDLINE]

1341. Med Mycol. 2010 Feb;48(1):79-84.

Clinical Candida krusei isolates remain susceptible during extensive exposure to antifungal drugs.

Hautala T, Kakko S, Siitonen T, Säily M, Koistinen P, Koskela M.

Department of Internal Medicine, Oulu University Hospital, Oulu, Finland. timo.hautala@oulu.fi

We have previously reported a Candida krusei outbreak during which a number of our patients were infected or colonized by several different closely related Candida krusei genotypes. The treatment response in many of our patients was at best modest and the patients remained positive for Candida krusei. We speculated that extended exposure to antifungals in patients with an incomplete treatment response might lead to the conditions for selection of drug resistance in the multiple Candida krusei clones. Therefore, we followed the in vitro susceptibility of the Candida krusei isolates taken from our patients before and during the antifungal treatment. A total of 28 Candida krusei isolates from 11 patients with prolonged exposure to antifungal medication were analyzed for their in vitro susceptibility to commonly used drugs. We found that MIC(50) values of all Candida krusei isolates was 12 microg/ml for fluconazole, 0.19 microg/ml for voriconazole, 1.0 microg/ml for amphotericin B, and 1.0 microgt/ml for caspofungin with the corresponding MIC(90) values being 16 microg/ml, 0.5 microg/ml, 2.0 microg/ml, and 1.0 micro/ml, respectively. Extended antifungal exposure did not change these MIC values. We conclude that resistance development in Candida krusei during prolonged antifungal treatment may not be common and the treatment failure of our patients was not likely due to the development of drug resistance by the etiologic agent.

PMID: 19194820 [PubMed - indexed for MEDLINE]

1342. PLoS One. 2009;4(2):e4376. Epub 2009 Feb 5.

A newly identified essential complex, Dre2-Tah18, controls mitochondria integrity and cell death after oxidative stress in yeast.

Vernis L, Facca C, Delagoutte E, Soler N, Chanet R, Guiard B, Faye G, Baldacci G.

Régulation de la Réplication de l'ADN des Eucaryotes, UMR2027 CNRS/Institut Curie, INSERM, Université Paris-Sud, Orsay, France. laurence.vernis-beringue@curie.u-psud.fr

A mutated allele of the essential gene TAH18 was previously identified in our laboratory in a genetic screen for new proteins interacting with the DNA polymerase delta in yeast [1]. The present work shows that Tah18 plays a role in response to oxidative stress. After exposure to lethal doses of H(2)O(2), GFP-Tah18 relocalizes to the mitochondria and controls mitochondria integrity and cell death. Dre2, an essential Fe/S cluster protein and homologue of human anti-apoptotic Ciapin1, was identified as a molecular partner of Tah18 in the absence of stress. Moreover, Ciapin1 is able to replace yeast Dre2 in vivo and physically interacts with Tah18. Our results are in favour of an oxidative stress-induced cell death in yeast that involves mitochondria and is controlled by the newly identified Dre2-Tah18 complex.

PMCID: PMC2633045 PMID: 19194512 [PubMed - indexed for MEDLINE]

1343. Environ Sci Technol. 2008 Dec 1;42(23):8849-57.

Investigation of bioaerosols released from swine farms using conventional and alternative waste treatment and management technologies.

Ko G, Simmons OD 3rd, Likirdopulos CA, Worley-Davis L, Williams M, Sobsey MD.

Department of Environmental Health and Institute of Health and Environment, Seoul National University, Seoul, Korea. gko@snu.ac.kr

Microbial air pollution from concentrated animal feeding operations (CAFOs) has raised concerns about potential public health and environmental impacts. We investigated the levels of bioaerosols released from two swine farms using conventional lagoon-sprayfield technology and ten farms using alternative waste treatment and management technologies in the United States. In total, 424 microbial air samples taken at the 12 CAFOs were analyzed for several indicator and pathogenic microorganisms, including culturable bacteria and fungi, fecal coliform, Escherichia coli, Clostridium perfringens, bacteriophage, and Salmonella. At all of the investigated farms, bacterial concentrations at the downwind boundary were higher than those at the upwind boundary, suggesting that the farms are sources of microbial air contamination. In addition, fecal indicator microorganisms were found more frequently near barns and treatmenttechnology sites than upwind or downwind of the farms. Approximately 4.5% (19/424), 1.2% (5/424), 22.2% (94/424), and 12.3% (53/424) of samples were positive for fecal coliform, E. coli, Clostridium, and total coliphage, respectively. Based on statistical comparison of airborne fecal indicator concentrations at alternative treatment technology farms compared to control farms with conventional technology, three alternative waste treatment technologies appear to perform better at reducing the airborne release of fecal indicator microorganisms during on-farm treatment and management processes. These results demonstrate that airborne microbial contaminants are released from swine farms and pose possible exposure risks to farm workers and nearby neighbors. However, the release of airborne microorganisms appears to decrease significantly through the use of certain alternative waste management and treatment technologies.

PMID: 19192808 [PubMed - indexed for MEDLINE]

1344. J Environ Health. 2009 Jan-Feb;71(6):43-9; quiz 51-2.

Environmental health risks associated with off-campus student-tenant housing.

Johnson E, Cole EC, Merrill R.

erinjohnson8@gmail.com

While previous studies have established an association between poor housing conditions and adverse health effects, none has specifically addressed health and safety risks to the college student population in rental housing. A needs-assessment survey was conducted to determine the prevalence of adverse health and safety conditions in off-campus student housing associated with a large university in the western United States. Results from 1959 student-tenant surveys revealed problems with installed appliances (39.6%); visible mold (39.3%); heating/cooling systems (31.9%); indoor dampness/water damage (24.9%); security locks (23.4%); ants (17.1%); electrical wiring (11.3%); malfunctioning or missing smoke alarms (11.2%); broken steps/handrails (7.8%); and mice (4.8%), among other problems. Reported health effects associated with housing included headaches, coughing, sneezing, nausea, and dizziness, and these effects were found to significantly correlate with increased environmental problems. The results of this study indicate a need to inform college students about environmental health and safety problems in leased housing, to promote responsibility of landlords to provide safe and healthful environments, and to raise awareness of this issue for public health and housing officials in university communities across the country.

PMID: 19192743 [PubMed - indexed for MEDLINE]

1345. Indoor Air. 2009 Apr;19(2):153-8. Epub 2009 Jan 28.

Molds and mycotoxins in dust from water-damaged homes in New Orleans after hurricane Katrina.

Bloom E, Grimsley LF, Pehrson C, Lewis J, Larsson L.

Laboratory Medicine, Division of Medical Microbiology, Lund University, Sölvegatan 23, Lund, Sweden.

Dust collected in New Orleans homes mold-contaminated because of the flooding after hurricane Katrina was analyzed for molds and mycotoxins. The mycoflora was studied by cultivation and quantitative PCR for selected molds. The most commonly found mold taxa were Aspergillus, Cladosporium, and Penicillium. Verrucarol, a hydrolysis product of macrocyclic trichothecenes predominately produced by Stachybotrys spp. was identified in three dust samples by gas chromatography-tandem mass spectrometry, and sterigmatocystin (produced by various Aspergillus spp.) was found in two samples by high pressure liquid chromatography-tandem mass spectrometry. This is the first demonstration of mycotoxins in Katrina-associated dust samples. The analytical methods used represent valuable tools in further studies on bioaerosol exposure and health risks. PRACTICAL IMPLICATIONS: In the aftermath of natural disasters like hurricane Katrina water-damages on infrastructure and public and private property are often associated with health risks for remediation workers and returning residents. In the case of New Orleans evaluations of health hazards, health studies, and assessments of bioaerosol have been conducted previously. However, until now mycotoxins have not been addressed. Our study shows, for the first time, the presence of mycotoxins in dust collected in houses in New Orleans mold-contaminated because of the hurricane Katrina. The results may highlight the potential health threats posed by mold aerosols in post-disaster inhabited areas.

PMID: 19191921 [PubMed - indexed for MEDLINE]

1346. Oecologia. 2009 May;160(1):9-14. Epub 2009 Feb 3.

Pre-hatching exposure to water mold reduces size at metamorphosis in the moor frog.

Uller T, Sagvik J, Olsson M.

Department of Zoology, Edward Grey Institute, University of Oxford, Oxford, UK. tobias.uller@zoo.ox.ac.uk

Developmental plasticity is increasingly recognized as important for ecological and evolutionary processes. However, few studies consider the potential for delayed effects of early environments. Here, we show that tadpoles hatching from clutches exposed to water mold (Saprolegnia) have 20% decreased mass at metamorphosis, despite no further exposure subsequent to hatching. The effects were consistent across four populations that have previously been shown to vary in their resistance to infection during embryonic development. Contrary to expectations, time to hatching or metamorphosis was not affected, suggesting that the results do not reflect an evolved escape strategy from infected waters triggered by embryonic conditions. Instead, decreased mass at metamorphosis may arise from carry-over effects of impaired embryo development. Such strong links across developmental stages have potential consequences for the evolution of plasticity and the responses of populations to emergent infections.

PMID: 19189128 [PubMed - indexed for MEDLINE]

1347. J Epidemiol Community Health. 2009 May;63(5):373-8. Epub 2009 Feb 2.

HIV prone occupational exposures: epidemiology and factors associated with initiation of post-exposure prophylaxis.

Zenner D, Tomkins S, Charlett A, Wellings K, Ncube F.

Health Protection Agency, Centre for Infections, London, UK. dominik.zenner@lshtm.ac.uk

BACKGROUND: Occupational exposures to bloodborne viruses are very common. Whilst occupational HIV transmissions are rare, the serious physical, psychological and cost implications of potential transmission make this an important public health topic. European and UK guidelines recommend HIV post-exposure prophylaxis (PEP) as a valuable tool of preventing occupational HIV infection. Yet one in five UK healthcare workers did not initiate PEP despite having been exposed to an HIV-positive source patient. The aim of the study is to examine factors associated with PEP uptake behaviour.
METHODS: The study is based on an analysis of the UK Health Protection Agency surveillance database of 'Significant Occupational Exposures to Bloodborne Viruses in Healthcare Workers'. Associations between possible predicting factors and PEP-uptake have been examined with univariate analysis and logistic regression modelling.
RESULTS: Univariate analysis and logistic regression found significant associations between PEP-uptake and visible blood on the device (p<0.0001) and a linear relationship with increasing injury depth (p<0.0001). Doctors were significantly more likely to start PEP than nurses (OR 1.88, 1.16; 3.02). Multiple imputation of missing values did not significantly alter these results.
CONCLUSIONS: PEP-uptake was associated with known transmission risk factors, suggesting awareness of current guidelines. The significant differences in PEP-uptake across occupation categories may be due to differential risk perceptions or other underlying factors. This is the first national study to examine PEP-uptake following occupational exposures to HIV. Further research and exploration of these findings are warranted, to understand the role of PEP-uptake behaviour in preventing occupational HIV transmission.

PMID: 19188197 [PubMed - indexed for MEDLINE]

1348. FEBS Lett. 2009 Feb 18;583(4):739-42. Epub 2009 Jan 29.

Probing the orientation of yeast VDAC1 in vivo.

McDonald BM, Wydro MM, Lightowlers RN, Lakey JH.

The Institute for Cell and Molecular Biosciences, Newcastle University, Framlington Place, Newcastle-upon-Tyne NE2 4HH, UK.

Voltage dependent anion channel (VDAC) is a vital ion channel in mitochondrial outer membranes and its structure was recently shown to be a 19 stranded beta-barrel. However the orientation of VDAC in the membrane remains unclear. We probe here the topology and membrane orientation of yeast Saccharomyces cerevisiae in vivo. Five FLAG-epitopes were independently inserted into scVDAC1 and their surface exposure in intact and disrupted mitochondria detected by immunoprecipitation. Functionality was confirmed by measurements of respiration. Two epitopes suggest that VDAC (scVDAC) has its C-terminus exposed to the cytoplasm whilst two others are more equivocal and, when combined with published data, suggest a dynamic behavior.

PMID: 19185576 [PubMed - indexed for MEDLINE]

1349. Med Mycol. 2009 Dec;47(8):814-23.

Oxidative stress response of Inonotus obliquus induced by hydrogen peroxide.

Zheng W, Zhao Y, Zhang M, Wei Z, Miao K, Sun W.

Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, Xuzhou Normal University, Xuzhou, China. zheng.weifa@gmail.com

While the medicinal fungus Inonotus obliquus produces polyphenols as one of its main metabolites in natural habitats, it accumulates less polyphenols under laboratory conditions. In this study we found that the continuous addition of 1 mM H(2)O(2) at a rate of 1.6 ml/h into a submerged culture of the fungus enhanced its production of mycelia, melanins, flavonoids and hispidin analogs (HA). Simultaneous exposure of the fungus to both H(2)O(2) and arbutin resulted in reduced production of mycelia, glycosylated flavonoids (GF) and HA, and inhibition of melanogenesis. However, superoxide dismutases (SOD) and catalase (CAT) activity were enhanced following the addition of H(2)O(2) or H(2)O(2) plus arbutin. The maximum levels of SOD and CAT activities reached 355.2 U/mg protein and 39.8 U/mg protein respectively in H(2)O(2)-added medium, and 264 U/mg protein and 35.9 U/mg protein respectively in H(2)O(2) plus arbutin medium. Thus, detoxification of H(2)O(2) is conducted mainly by polyphenols under normal physiological conditions, and by both polyphenols and antioxidant enzymes under oxidative stress when melanogenesis is inhibited. Although enhanced HA production occurred after melanogenesis inactivation, total extracellular polyphenol levels were reduced. These findings suggest that enzymatic activities convert superoxide to H(2)O(2), and non-enzymatic mechanisms are largely responsible for detoxifying H(2)O(2). Enhanced production of melanins is the most important non-enzymatic response of this fungus against oxidative stress.

PMID: 19184774 [PubMed - indexed for MEDLINE]

1350. Curr Microbiol. 2009 May;58(5):504-10. Epub 2009 Jan 31.

Monitoring oxidative stress and DNA damage induced by heavy metals in yeast expressing a redox-sensitive green fluorescent protein.

Yu S, Qin W, Zhuang G, Zhang X, Chen G, Liu W.

The State Key Laboratory of Microbial Technology, School of Life Science, Shandong University, Jinan, Shandong, PR China.

Reactive oxygen species (ROS) has been proposed to play an important role in heavy metal-associated toxicity and pathology. Conventional methods for determining ambient redox state in cells are usually labor-intensive, precluding real-time or single-cell monitoring changes in intracellular redox poise resulting from either metabolic processes or environmental influences. Redox-sensitive green fluorescent protein (roGFP) was expressed in Saccharomyces cerevisiae and recombinant cells were evaluated in monitoring the changes in the redox state of living cells when challenged with toxicologically relevant metal ions. roGFP expressed in yeast responded not only to typical membrane-permeant oxidants and reductants, but also to toxicological metal ion-induced intracellular redox changes. Moreover, exposure of yeast cells to NaAsO(2) or Pb(NO(3))(2) at concentrations that induced redox changes reported by roGFP caused up to two- to three-fold increases in DNA mutation frequency. This mutagenic effect was largely caused by oxidative stress since blocking the production of hydryl radicals significantly reduced the mutation rate as well as delayed the cell death.

PMID: 19184609 [PubMed - indexed for MEDLINE]

1351. Nat Genet. 2009 Mar;41(3):308-15. Epub 2009 Feb 1.

Alpha-synuclein is part of a diverse and highly conserved interaction network that includes PARK9 and manganese toxicity.

Gitler AD, Chesi A, Geddie ML, Strathearn KE, Hamamichi S, Hill KJ, Caldwell KA, Caldwell GA, Cooper AA, Rochet JC, Lindquist S.

Whitehead Institute for Biomedical Research and Howard Hughes Medical Institute, Cambridge, Massachusetts 02142, USA.

Parkinson's disease (PD), dementia with Lewy bodies and multiple system atrophy, collectively referred to as synucleinopathies, are associated with a diverse group of genetic and environmental susceptibilities. The best studied of these is PD. alpha-Synuclein (alpha-syn) has a key role in the pathogenesis of both familial and sporadic PD, but evidence linking it to other predisposition factors is limited. Here we report a strong genetic interaction between alpha-syn and the yeast ortholog of the PD-linked gene ATP13A2 (also known as PARK9). Dopaminergic neuron loss caused by alpha-syn overexpression in animal and neuronal PD models is rescued by coexpression of PARK9. Further, knockdown of the ATP13A2 ortholog in Caenorhabditis elegans enhances alpha-syn misfolding. These data provide a direct functional connection between alpha-syn and another PD susceptibility locus. Manganese exposure is an environmental risk factor linked to PD and PD-like syndromes. We discovered that yeast PARK9 helps to protect cells from manganese toxicity, revealing a connection between PD genetics (alpha-syn and PARK9) and an environmental risk factor (PARK9 and manganese). Finally, we show that additional genes from our yeast screen, with diverse functions, are potent modifiers of alpha-syn-induced neuron loss in animals, establishing a diverse, highly conserved interaction network for alpha-syn.

PMCID: PMC2683786 PMID: 19182805 [PubMed - indexed for MEDLINE]

1352. Cell Cycle. 2009 Feb 15;8(4):639-42. Epub 2009 Feb 8.

Phylogenetic conservation of the preapoptotic calreticulin exposure pathway from yeast to mammals.

Madeo F, Durchschlag M, Kepp O, Panaretakis T, Zitvogel L, Fröhlich KU, Kroemer G.

Institute of Molecular Biosciences, University of Graz, Graz, Austria.

The pre-apoptotic exposure of calreticulin (CRT) on the cell surface determines the efficient engulfment of mouse or human tumor cells by antigen-presenting dendritic cells. CRT exposure is rapidly induced by anthracyclins and ionizing irradiation and follows a complex signal transduction pathway that is interrupted by depletion of PERK, caspase-8, BAP31, Bax, Bak or SNAREs, as well as by knock-in mutation of eIF2alpha (to make it non-phosphorylable by PERK) or BAP31 (to render it uncleavable by caspase-8). Here, we show that yeast (Saccharomyces cerevisiae) can expose the CRT orthologue CNE1 on the surface in response to cell death induced by the anthracylin mitoxantrone (MTX). This MTX-triggered CNE1 translocation is abolished by knockout of the yeast orthologues of PERK (Gcn2), BAP31 (Yet3) and SNAREs (Nyv1, Sso1). Altogether, our data point to the existence of an ancestral and cell death-related CRT exposure pathway with conserved elements shared between unicellular fungi and mammals.

PMID: 19182525 [PubMed - indexed for MEDLINE]

1353. J Occup Environ Hyg. 2009 Apr;6(4):211-20.

Concentrations of bioaerosols, odors, and hydrogen sulfide inside and downwind from two types of swine livestock operations.

Thorne PS, Ansley AC, Perry SS.

Department of Occupational and Environmental Health, University of Iowa, Iowa City, Iowa 52242-5000, USA. peter-thorne@uiowa.edu

Few data on in-barn and downwind concentrations of endotoxin, bioaerosols, and odors from livestock facilities are available, and no studies have compared conventional confinement operations with the more animal-friendly hoop operations. Hoops are open to the environment and use a composted bedding system rather than housing pigs on slatted floors over pits holding manure slurry as in conventional confinements. We assessed airborne toxicants upwind, in barns, and downwind and evaluated determinants of exposure. Inhalable particulate matter, endotoxin, odor threshold, hydrogen sulfide, culturable mesophilic bacteria, culturable fungi, and total airborne microbes, along with wind speed, temperature, and humidity were measured at separate midsized livestock facilities (one hoop, one confinement) in Central Iowa on 10 occasions over 2 years. Significant differences in contaminants were observed between hoops and confinement buildings and across seasons for endotoxin, odors, airborne microorganisms, and hydrogen sulfide. For hoops and confinements, respectively, geometric mean in-barn concentrations were 3250 and 3100 EU/m(3) for endotoxin; 1400 and 1910 microg/m(3) for particulates; 19.6 and 146 ppb for hydrogen sulfide; 137 and 428 dilutions for odor threshold; and 3.0 x 10(6) and 1.5 x 10(6) organisms/m(3) for total microbes. Endotoxin, odor, and culturable microorganisms exceeded recommended exposure limits. Reduced analysis of variance models for these contaminants demonstrated differences by barn type, season, number of pigs, and, in some cases, temperature and humidity. Both types of swine operations produced high airborne concentrations of endotoxin, odor, hydrogen sulfide, bacteria, and fungi. Endotoxin and odors were found downwind at concentrations previously associated with adverse health effects.

PMID: 19177273 [PubMed - indexed for MEDLINE]

1354. Allergy Asthma Proc. 2008 Nov-Dec;29(6):575-9.

Indoor allergens, environmental avoidance, and allergic respiratory disease.

Bush RK.

Section of Allergy, Immunology, Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, University of Wisconsin-Madison, Madison, WI 53792, USA. rkb@medicine.wisc.edu

Indoor allergen exposure to sources such as house-dust mites, pets, fungi, and insects plays a significant role in patients with allergic rhinitis and asthma. The identification of the major allergens has led to methods that can quantitate exposure, e.g., immunoassays for Der p 1 in settled dust samples. Sensitization and the development of allergic respiratory disease result from complex genetic and environmental interactions. New paradigms that examine the role of other environmental factors, including exposure to proteases that can activate eosinophils and initiate Th2 responses, and epigenetics, are being explored. Recommendations for specific environmental allergen avoidance measures are discussed for house-dust mites, cockroaches, animal dander, and fungi. Specific measures to reduce indoor allergen exposure when vigorously applied may reduce the risk of sensitization and symptoms of allergic respiratory disease, although further research will be necessary to establish cost-effective approaches.

PMID: 19173784 [PubMed - indexed for MEDLINE]

1355. Biotechnol Bioeng. 2009 Jun 1;103(2):341-52.

Engineering of the yeast antioxidant enzyme Mpr1 for enhanced activity and stability.

Iinoya K, Kotani T, Sasano Y, Takagi H.

Graduate School of Biological Sciences, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-0192, Japan.

The budding yeast Saccharomyces cerevisiae Sigma1278b has the MPR1 gene, which confers resistance to the proline analogue azetidine-2-carboxylate (AZC). This gene encodes an N-acetyltransferase Mpr1 that detoxifies AZC, and the homologous genes have been found in many yeasts. Recently, we found that Mpr1 protects yeast cells by reducing the intracellular reactive oxygen species (ROS) levels under oxidative stresses, such as heat-shock, freezing, or ethanol treatment. Unlike the known antioxidant enzymes, Mpr1 is thought to acetylate toxic metabolite(s) involved in ROS generation via oxidative events. To improve the enzymatic functions of Mpr1, we applied PCR random mutagenesis to MPR1. The mutagenized plasmid library was introduced into the S. cerevisiae S288C strain lacking MPR1, and we successfully isolated two Mpr1 variants with higher AZC resistance (K63R and F65L/L117V). Interestingly, overexpression of the K63R variant was found to increase cell viability or decrease intracellular ROS levels after exposure to H(2)O(2) or ethanol compared with the wild-type Mpr1. In vitro studies with the recombinant enzymes showed that the catalytic efficiency of the K63R variant for AZC and acetyl-CoA was higher than that of the wild-type Mpr1 and that the F65L mutation greatly enhanced the thermal stability. The mutational analysis and molecular modeling suggest that an alpha-helix containing Lys63 and Phe65 has important roles in the function of Mpr1. In addition, the wild-type and K63R variant Mpr1 reduced intracellular ROS levels under ethanol stress conditions on haploid sake yeast cells. These results suggest that engineering Mpr1 might be useful in breeding oxidative stress-tolerant yeast strains.

PMID: 19170243 [PubMed - indexed for MEDLINE]

1356. Phytopathology. 2009 Feb;99(2):167-75.

Ultrastructural alterations in Fusarium sambucinum and Heterobasidion annosum treated with aluminum chloride and sodium metabisulfite.

Avis TJ, Rioux D, Simard M, Michaud M, Tweddell RJ.

Department of Chemistry, Carleton University, 1125 Colonel By Drive, Ottawa (On), Canada, K1S 5B6. tyler_avis@carleton.ca

Aluminum chloride (AlCl(3)) and sodium metabisulfite (Na(2)S(2)O(5)) have received increasing attention as antifungal agents for the control of plant diseases. In an effort to understand their toxic action on fungi, ultrastructural changes and membrane damage in Fusarium sambucinum (Ascomycota) and Heterobasidion annosum (Basidiomycota) in response to salt exposure was investigated using transmission electron microscopy. Conidial membrane damage was quantified using SYTOX Green stain, which only enters altered membranes. The results showed that mortality of the conidia was generally closely associated with SYTOX stain absorption in F. sambucinum treated with Na(2)S(2)O(5) and in H. annosum treated with AlCl(3) or Na(2)S(2)O(5), suggesting that these salts cause membrane alterations. For both fungi, ultrastructural alterations in conidia treated with AlCl(3) and Na(2)S(2)O(5) included membrane retraction, undulation, and invagination. At higher concentrations or exposure periods to the salts, loss of membrane integrity, cytoplasmic leakage, and cell rupture were observed. Ultrastructural alterations and increased SYTOX stain absorption in salt-treated conidia appear consistent with a mode of action where AlCl(3) and Na(2)S(2)O(5) alter membrane integrity and permeability.

PMID: 19159309 [PubMed - indexed for MEDLINE]

1357. Phytopathology. 2009 Feb;99(2):152-9.

Interaction of the mite Aceria mangiferae with Fusarium mangiferae, the causal agent of mango malformation disease.

Gamliel-Atinsky E, Freeman S, Sztejnberg A, Maymon M, Ochoa R, Belausov E, Palevsky E.

Department of Plant Pathology and Microbiology, Faculty of Agricultural, Food and Environmental Quality Sciences, The Hebrew University of Jerusalem, P.O. Box 12, Rehovot 76100, Israel.

The role of the mango bud mite, Aceria mangiferae, in carrying conidia of Fusarium mangiferae, vectoring them into potential infection sites, and assisting fungal infection and dissemination was studied. Following the mite's exposure to a green fluorescent protein-marked isolate, conidia were observed clinging to the mite's body. Agar plugs bearing either bud mites or the pathogen were placed on leaves near the apical buds of potted mango plants. Conidia were found in bud bracts only when both mites and conidia were co-inoculated on the plant, demonstrating that the mite vectored the conidia into the apical bud. Potted mango plants were inoculated with conidia in the presence or absence of mites. Frequency and severity of infected buds were significantly higher in the presence of mites, revealing their significant role in the fungal infection process. Conidia and mite presence were monitored with traps in a diseased orchard over a 2-year period. No windborne bud mites bearing conidia were found; however, high numbers of windborne conidia were detected in the traps. These results suggest that A. mangiferae can carry and vector conidia between buds and assist in fungal penetration but does not play a role in the aerial dissemination of conidia between trees.

PMID: 19159307 [PubMed - indexed for MEDLINE]

1358. Mol Biol Cell. 2009 Mar;20(6):1683-94. Epub 2009 Jan 21.

Esc2 and Sgs1 act in functionally distinct branches of the homologous recombination repair pathway in Saccharomyces cerevisiae.

Mankouri HW, Ngo HP, Hickson ID.

Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, United Kingdom.

Esc2 is a member of the RENi family of SUMO-like domain proteins and is implicated in gene silencing in Saccharomyces cerevisiae. Here, we identify a dual role for Esc2 during S-phase in mediating both intra-S-phase DNA damage checkpoint signaling and preventing the accumulation of Rad51-dependent homologous recombination repair (HRR) intermediates. These roles are qualitatively similar to those of Sgs1, the yeast ortholog of the human Bloom's syndrome protein, BLM. However, whereas mutation of either ESC2 or SGS1 leads to the accumulation of unprocessed HRR intermediates in the presence of MMS, the accumulation of these structures in esc2 (but not sgs1) mutants is entirely dependent on Mph1, a protein that shows structural similarity to the Fanconi anemia group M protein (FANCM). In the absence of both Esc2 and Sgs1, the intra-S-phase DNA damage checkpoint response is compromised after exposure to MMS, and sgs1esc2 cells attempt to undergo mitosis with unprocessed HRR intermediates. We propose a model whereby Esc2 acts in an Mph1-dependent process, separately from Sgs1, to influence the repair/tolerance of MMS-induced lesions during S-phase.

PMCID: PMC2655263 PMID: 19158388 [PubMed - indexed for MEDLINE]

1359. PLoS One. 2009;4(1):e4224. Epub 2009 Jan 19.

Conidiation color mutants of Aspergillus fumigatus are highly pathogenic to the heterologous insect host Galleria mellonella.

Jackson JC, Higgins LA, Lin X.

Department of Biology, Texas A & M University, College Station, Texas, United States of America.

The greater wax moth Galleria mellonella has been widely used as a heterologous host for a number of fungal pathogens including Candida albicans and Cryptococcus neoformans. A positive correlation in pathogenicity of these yeasts in this insect model and animal models has been observed. However, very few studies have evaluated the possibility of applying this heterologous insect model to investigate virulence traits of the filamentous fungal pathogen Aspergillus fumigatus, the leading cause of invasive aspergillosis. Here, we have examined the impact of mutations in genes involved in melanin biosynthesis on the pathogenicity of A. fumigatus in the G. mellonella model. Melanization in A. fumigatus confers bluish-grey color to conidia and is a known virulence factor in mammal models. Surprisingly, conidial color mutants in B5233 background that have deletions in the defined six-gene cluster required for DHN-melanin biosynthesis caused enhanced insect mortality compared to the parent strain. To further examine and confirm the relationship between melanization defects and enhanced virulence in the wax moth model, we performed random insertional mutagenesis in the Af293 genetic background to isolate mutants producing altered conidia colors. Strains producing conidia of previously identified colors and of novel colors were isolated. Interestingly, these color mutants displayed a higher level of pathogenicity in the insect model compared to the wild type. Although some of the more virulent color mutants showed increased resistance to hydrogen peroxide, overall phenotypic characterizations including secondary metabolite production, metalloproteinase activity, and germination rate did not reveal a general mechanism accountable for the enhanced virulence of these color mutants observed in the insect model. Our observations indicate instead, that exacerbated immune response of the wax moth induced by increased exposure of PAMPs (pathogen-associated molecular patterns) may cause self-damage that results in increased mortality of larvae infected with the color mutants. The current study underscores the limitations of using this insect model for inferring the pathogenic potential of A. fumigatus strains in mammals, but also points to the importance of understanding the innate immunity of the insect host in providing insights into the pathogenicity level of different fungal strains in this model. Additionally, our observations that melanization defective color mutants demonstrate increased virulence in the insect wax moth, suggest the potential of using melanization defective mutants of native insect fungal pathogens in the biological control of insect populations.

PMCID: PMC2625396 PMID: 19156203 [PubMed - indexed for MEDLINE]

1360. Plant J. 2009 May;58(3):499-510. Epub 2008 Jan 18.

The ABC transporter BcatrB from Botrytis cinerea exports camalexin and is a virulence factor on Arabidopsis thaliana.

Stefanato FL, Abou-Mansour E, Buchala A, Kretschmer M, Mosbach A, Hahn M, Bochet CG, Métraux JP, Schoonbeek HJ.

Department of Biology, University of Fribourg, Chemin du Musée 8, CH-1700 Fribourg, Switzerland.

Arabidopsis thaliana is known to produce the phytoalexin camalexin in response to abiotic and biotic stress. Here we studied the mechanisms of tolerance to camalexin in the fungus Botrytis cinerea, a necrotrophic pathogen of A. thaliana. Exposure of B. cinerea to camalexin induces expression of BcatrB, an ABC transporter that functions in the efflux of fungitoxic compounds. B. cinerea inoculated on wild-type A. thaliana plants yields smaller lesions than on camalexin-deficient A. thaliana mutants. A B. cinerea strain lacking functional BcatrB is more sensitive to camalexin in vitro and less virulent on wild-type plants, but is still fully virulent on camalexin-deficient mutants. Pre-treatment of A. thaliana with UV-C leads to increased camalexin accumulation and substantial resistance to B. cinerea. UV-C-induced resistance was not seen in the camalexin-deficient mutants cyp79B2/B3, cyp71A13, pad3 or pad2, and was strongly reduced in ups1. Here we demonstrate that an ABC transporter is a virulence factor that increases tolerance of the pathogen towards a phytoalexin, and the complete restoration of virulence on host plants lacking this phytoalexin.

PMID: 19154205 [PubMed - indexed for MEDLINE]

1361. Int J Antimicrob Agents. 2009 May;33(5):494-5. Epub 2009 Jan 18.

Triazole-resistant candidaemia following posaconazole exposure.

Weiler S, Lass-Flörl C, Auberger J, Bellmann-Weiler R, Stein M, Joannidis M, Bellmann R.

PMID: 19153033 [PubMed - indexed for MEDLINE]

1362. DNA Repair (Amst). 2009 May 1;8(5):600-11. Epub 2009 Jan 17.

Damage recognition by UV damage endonuclease from Schizosaccharomyces pombe.

Paspaleva K, Moolenaar GF, Goosen N.

Laboratory of Molecular Genetics, Leiden Institute of Chemistry, Gorlaeus Laboratories, Leiden University, Einsteinweg 55, 2300 RA Leiden, The Netherlands.

UV damage endonuclease (UVDE) from Schizosaccharomyces pombe initiates repair of UV lesions and abasic sites by nicking the DNA 5' to the damaged site. In this paper we show that in addition UVDE incises DNA containing a single-strand nick or gap, but that the enzymatic activity on these substrates as well as on abasic sites strongly depends on the presence of a neighbouring pyrimidine residue. This indicates that, although UVDE may have been derived from an ancestral AP endonuclease its major substrate is a UV lesion and not an AP site. We propose that UVDE rotates two nucleotides into a pocket of the protein in order to bring the scissile bond close to the active site and that purine bases are excluded from this pocket. We also show that in the DNA complex residue Tyr-358 of UVDE penetrates the DNA helix causing unstacking of two residues opposite the lesion, thereby stabilizing the protein-DNA interaction, most likely by promoting bending of the DNA. In the absence of Tyr-358 the enzyme exhibits an increased catalytic activity on UV-induced lesions, but only at a lower pH of 6.5. At physiological conditions (pH 7.5) the mutant protein completely looses its catalytic activity although it can still bind to the DNA. We propose that in addition to stabilizing the bend in the DNA the hydrophobic side chain of Tyr-358 shields the active site from exposure to the solvent.

PMID: 19152795 [PubMed - indexed for MEDLINE]

1363. Peptides. 2009 Apr;30(4):638-46. Epub 2008 Dec 27.

Cloning and expression of a hepcidin gene from a marine fish (Pseudosciaena crocea) and the antimicrobial activity of its synthetic peptide.

Wang KJ, Cai JJ, Cai L, Qu HD, Yang M, Zhang M.

Xiamen University, Fujian, China. wkjian@xmu.edu.cn

Hepcidin gene is widely expressed in various fish, suggesting that this antimicrobial peptide is a very important component in the innate immune system. Large yellow croaker (Pseudosciaena crocea) is one of the important economic species of marine-cultured fish but knowledge of its innate immune mechanism is lacking. In this study, we characterize a P. crocea hepcidin gene named as PC-hepc. It consists of an open reading frame of 258 bases encoding 85 amino acids and has a conserved sequence in common with other known hepcidins. The genomic DNA of PC-hepc contains three exons and two introns, the same organization as other reported hepcidins, indicating that PC-hepc is one member of the hepcidin family in fish. The tissue-specific expression of PC-hepc gene in normal fish and the expression pattern in LPS-challenged fish at the time course of stimulation were investigated. The expression of PC-hepc mRNA was significantly increased in the spleen, heart and stomach but not significantly induced in the liver after LPS challenge. An interesting finding is the demonstration of high amounts of PC-hepc transcripts in the kidney in normal fish and their maintenance through 48h exposure to LPS challenge. The synthetic PC-hepc demonstrated a rather wide spectrum of antimicrobial activity in vitro against bacteria and fungi tested, and particularly showed strong activity against the principal fish pathogens, Aeromonas hydrophila, Vibrio parahaemloyticus, Vibrio alginolyticus and Vibrio harvryi. The study indicates that PC-hepc may play a role with a tissue-specific mode in the innate immunity of P. crocea.

PMID: 19150638 [PubMed - indexed for MEDLINE]

1364. Dis Aquat Organ. 2008 Nov 20;82(2):97-104.

Survival of the amphibian chytrid fungus Batrachochytrium dendrobatidis on bare hands and gloves: hygiene implications for amphibian handling.

Mendez D, Webb R, Berger L, Speare R.

Amphibian Diseases Ecology Group, School of Public Health, Tropical Medicine and Rehabilitation Sciences, James Cook University, Townsville, Queensland 4811, Australia. diana.mendez@jcu.edu.au

Hygiene protocols for handling amphibians in the field and in laboratories have been proposed to decrease the transmission of chytridiomycosis caused by infection with the amphibian chytrid fungus Batrachochytrium dendrobatidis, which is responsible for global amphibian declines. However, these protocols are mainly based on theoretical principles. The aim of this study was to develop an evidence-based approach to amphibian handling hygiene protocols by testing the survival of B. dendrobatidis on human hands and various gloves. Bare or gloved human fingers were exposed to cultured zoospores and zoosporangia of B. dendrobatidis. Survival of B. dendrobatidis on hands and gloves was tested for up to 10 min post-exposure by inoculation onto tryptone/gelatin hydrolysate/lactose (TGhL) agar plates. The effects of repeated hand washings with water and with 70% ethanol and of washing gloves with water were also tested. Bare human skin demonstrated a fungicidal effect on B. dendrobatidis by 2 min and killed 100% of cells by 6 min, but this killing effect was reduced by repeated washing with water and ethanol. Nitrile gloves killed all B. dendrobatidis on contact, but washing in water decreased this effect. Latex and polyethylene gloves had no killing effect, and B. dendrobatidis survived for over 6 min. The killing effect of vinyl gloves varied with brands and batches. These results support the use of an unused pair of gloves for each new amphibian handled in either the field or the laboratory, and if this is not possible, bare hands are a preferable, although imperfect, alternative to continual use of the same pair of gloves.

PMID: 19149372 [PubMed - indexed for MEDLINE]

1365. Oncol Rep. 2009 Feb;21(2):321-7.

Chemopreventive effects of fermented brown rice and rice bran against 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumorigenesis in female A/J mice.

Phutthaphadoong S, Yamada Y, Hirata A, Tomita H, Taguchi A, Hara A, Limtrakul PN, Iwasaki T, Kobayashi H, Mori H.

Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.

The most common cause of human lung cancer is suggested to be exposure to the carcinogens in tobacco smoke. Among the multiple chemicals in tobacco smoke, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) has been regarded as one of the important agents for generation of lung cancers. Previously, our studies proved that fermented brown rice and rice bran (FBRA) has chemopreventive effects against carcinogenesis of the colon, liver, stomach, bladder and esophagus. In the present study, we examined possible chemopreventive effects of FBRA on the NNK-induced lung tumorigenesis in mice. Six-week-old female A/J mice were divided into 8 groups, and groups 1-5 were given NNK (10 mmol) by i.p. injection at week 7. Groups 2 and 3 were fed with diet containing 5 and 10% FBRA during the initiation phase, respectively. Groups 4 and 5 were fed with 5% and 10% FBRA during the post-initiation phase. Groups 1 and 6 were given control diet throughout the experiment. Groups 7 and 8 were given the diet containing 5 and 10% FBRA throughout the experiment, respectively. In both initiation (group 3) and post-initiation phase (group 5), 10% FBRA exposure significantly reduced the multiplicity of lung tumor (group 3, 2.35+/-2.13; group 5, 3.00+/-1.52; group 1, 4.08+/-1.85; p<0.006 and 0.04, respectively). Furthermore, administration of FBRA during the post-initiation phase significantly decreased the tumor size in comparison with that of control mice (0.66+/-0.32 vs. 0.77+/-0.33 mm). Treatment of 10% FBRA significantly reduced the mRNA expression levels of cytochrome P450 2A5 (Cyp2a5), which is known to be closely related to the human CYP2A6 enzyme that is involved in the mutagenic activation of NNK, in the lung but not liver tissues. A significantly reduced index of Ki67 positivity of lung tumors in group 5 was confirmed when compared with tumors of the control group (0.065+/-0.016 vs. 0.114+/-0.025). These findings suggest that FBRA has inhibitory effects on NNK-induced pulmonary tumorigenesis in A/J mice in both during initiation and post-initiation treatment, which is possibly associated with the induction of Cyp2a5 in the lung and the reduced proliferation rate of tumor cells. FBRA may be a promising chemopreventive agent for human lung cancers.

PMID: 19148502 [PubMed - indexed for MEDLINE]

1366. J Biosci Bioeng. 2009 Jan;107(1):42-8.

Comparative study of antioxidant activity and antiproliferative effect of hot water and ethanol extracts from the mushroom Inonotus obliquus.

Hu H, Zhang Z, Lei Z, Yang Y, Sugiura N.

Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba 305-8572, Japan.

The medicinal mushroom Inonotus obliquus is a traditional and widely used multi-functional fungus. Hot water (50 degrees C, 70 degrees C, and 80 degrees C) and ethanol crude extracts of I. obliquus were investigated for their antioxidant activity with superoxide dismutase (SOD) and (1,1-diphenyl-2-picryhydrazyl) (DPPH) radical-scavenging activity assays. We also investigated the antiproliferative effects and ability of the extracts to induce apoptosis in human colon cancer DLD-1 cells. Among the four extracts, the ethanol extract (EE) exhibited the strongest SOD-like activity and antiproliferative effect on DLD-1 cells, and exposure to the EE resulted in the induction of apoptosis, whereas no apoptosis was observed in DLD-1 cells exposed to the hot water extracts (HWEs). HWE at 70 degrees C (HWE70) exhibited the strongest DPPH radical-scavenging activity (EC50, 126 microg/ml), whereas the EE showed the weakest activity (EC50, 224 microg/ml). The different biological activities among the four extracts may be attributed to differences in their chemical composition, partially supported by polysaccharide, protein and phenolic content, and the 1H-NMR spectra.

PMID: 19147108 [PubMed - indexed for MEDLINE]

1367. Mutat Res. 2009 Feb 19;673(1):53-8. Epub 2008 Dec 25.

Comet assay on tetraploid yeast cells.

Rank J, Syberg K, Jensen K.

Department of Environmental, Social and Spatial Change (ENSPAC), Roskilde University, DK-4000 Roskilde, Denmark. jr@ruc.dk

Tetraploid yeast cells (Saccharomyces cerevisiae) were used in the comet assay with the intention of developing a new, fast and easy assay for detecting environmental genotoxic agents without using higher organisms. Two DNA-damaging chemicals, H(2)O(2) and acrylamide, together with wastewater from three municipal treatment plants were tested for their effect on the yeast-cell DNA. The main problem with using yeast in the comet assay is the necessity to degrade the cell wall. This was achieved by using Zymolase 100 T twice during the procedure, since Zymolase 20 T did not open the cell wall. Analytical problems that arose due to the small amount of DNA in the yeast nuclei in haploid and diploid cells, which contain 13 Mbp and 26 Mbp DNA per cell, respectively, were solved by using tetraploid yeast cells (52 Mbp) instead. DNA damage was shown after exposure to H(2)O(2) and acrylamide. The lowest dose causing significant DNA damage was 20 microM for H(2)O(2) and 200mg/l for acrylamide. Tertiary-treated wastewater from the outlets of three municipal wastewater-treatment plants was tested, but did not cause DNA damage. Even though it is possible to produce comets with tetraploid yeast cells, the amount of DNA is likely too small for a proper comet assay.

PMID: 19146983 [PubMed - indexed for MEDLINE]

1368. Prehosp Emerg Care. 2009 Jan-Mar;13(1):6-13.

Blood or body fluid exposures and HIV postexposure prophylaxis utilization among first responders.

Merchant RC, Nettleton JE, Mayer KH, Becker BM.

Department of Emergency Medicine, Warren Alpert Medical School, Brown University, Providence, Rhode Island, USA. rmerchant@lifespan.org

OBJECTIVES: To estimate the incidence of first-responder visits to emergency departments (EDs) for blood or body fluid exposures, elucidate any temporal patterns of these visits, and quantify human immunodeficiency virus (HIV) postexposure prophylaxis (PEP) utilization for these exposures.
METHODS: This was a retrospective study of first responders presenting to Rhode Island EDs for blood or body fluid exposures from 1995 to 2001. Incidence rates for exposures with 95% confidence intervals (CIs) were estimated. Temporal trends for visits were modeled. Factors associated with HIV PEP utilization were identified using logistic regression. Odds ratios (ORs) with 95% CIs were estimated.
RESULTS: The average incidence rate of ED visits for blood or body fluid exposures was 23.29 (20.07-26.52) ED visits per 100,000 ambulance runs. The incidence rose between 1995 and 1999 and then decreased. First-responder ED visits were lowest in October and highest in April and were lowest at 7 am and highest at 7 pm. First responders presenting with a percutaneous or blood-to-mucous membrane exposure had a 4.13 (1.82-8.89) greater odds and those exposed to a known HIV-infected source had a 9.03 (1.59-51.26) greater odds of being offered HIV PEP. First responders presenting to a teaching hospital had a 2.21 (1.02-4.77) greater odds of being offered prophylaxis and a 4.20 (1.08-16.32) greater odds of accepting prophylaxis when it was offered.
CONCLUSIONS: First responders face a risk of blood or body fluid exposure that varies over the course of the day and the year. HIV PEP is more likely to be used if the exposures are percutaneous, or blood-to-mucous membrane, or if the source is known to be HIV-infected. Standardization of protocols across EDs for administering HIV prophylaxis appears to be needed.

PMID: 19145518 [PubMed - indexed for MEDLINE]

1369. J Med Microbiol. 2009 Feb;58(Pt 2):174-9.

Aspergillus fumigatus germ tube growth and not conidia ingestion induces expression of inflammatory mediator genes in the human lung epithelial cell line A549.

Bellanger AP, Millon L, Khoufache K, Rivollet D, Bièche I, Laurendeau I, Vidaud M, Botterel F, Bretagne S.

UMR 6249 CNRS, Laboratoire de Parasitologie-Mycologie, Hôpital Jean Minjoz, Besançon, France.

Inhalation of conidia is the main cause of invasive pulmonary aspergillosis (IPA) and the respiratory epithelium is the first line of defence. To explore the triggering factor for the inflammatory response to Aspergillus fumigatus, the species mainly responsible for IPA, this study analysed the differential expression of three inflammatory genes in A549 cells after challenge with live and killed conidia. The influence of steroids, one of the main risk factors for developing IPA, was also investigated. Quantification of mRNAs of the inflammatory mediator genes encoding interleukin (IL)-8, tumour necrosis factor (TNF)-alpha and granulocyte-monocyte colony-stimulating factor (GM-CSF) was carried out using real-time PCR. Ingestion rates were studied for the conidia of A. fumigatus and Penicillium chrysogenum using a fluorescence brightener. Similar results were obtained for both species, with ingestion rates ranging from 35 to 40 %. Exposure of A549 cells to live A. fumigatus conidia only induced a four- to fivefold increase in the mRNA levels of the three genes, starting 8 h after the initial contact. Both inactivation of live A. fumigatus conidia and treatment by dexamethasone (10(-7) M) prevented the overexpression of TNF-alpha, IL-8 and GM-CSF. Fungal growth, rather than conidia ingestion, appears to be the main stimulus for the production of inflammatory mediators by epithelial cells, and this production is inhibited by steroid therapy. These results underline the role that the epithelium plays in the innate response against IPA.

PMID: 19141733 [PubMed - indexed for MEDLINE]

1370. Aviakosm Ekolog Med. 2008 Jul-Aug;42(4):66-70.

[Role of some species of Ficus in amelioration of environment].

[Article in Russian]

Seraia AS, Tsybulia NV, Dul'tseva GG.

Laboratory investigation of gas-absorbing and antimicrobial (phytoncide) activity of Ficus species was carried out. It was demonstrated that some species of Ficus genus possessing gas-absorbing and phytoncide properties can be used to improve the sanitary characteristics of indoor air. The highest ability to absorb formaldehyde were exhibited by F. benjamina, F. retusa, F. binnendijkii, F. lyrata. The phytoncide action was revealed for all the investigated Ficus species against Escherichia coli, while only F. benjamina was active against Staphylococcus epidermidis. No activity against yeastlike fungi Candida albicans was revealed.

PMID: 19140478 [PubMed - indexed for MEDLINE]

1371. Mol Biol (Mosk). 2008 Nov-Dec;42(6):1030-9.

[Nucleosome positioning within neomycinphosphotransferase gene (NPTII) on yeast plasmid in repressed and active state].

[Article in Russian]

Kir'ianov GI, Isaeva LV, Kintsurashvili LN, Zakharova MG.

Yeast recombinant plasmid containing FRT-sequence flanked by hybrid GAL-CYC promoter and NPTII gene was developed. GAL-CYC promoter contains four UAS sequences and two closely associated TATA-boxes in CYC part. This construct provides galactose-inducible synthesis of neomycinphosphotransferase from NPTII gene, and, thus, resistance of transformed cells to G418 antibiotic. Nucleosome positioning within NPTII gene in repressed and active states was studied. Under repressive conditions (growth on glucose) stable positioning of three nucleosomes was detected. Two nucleosomes are localized in CYC-part. One of them encompasses both TATA-boxes. The third nucleosome overlaps FRT sequence and start of NPTII gene coding sequence. All three nucleosomes show multiple positioning. It suggests possibility of nucleosome sliding along DNA. After induction of NPTII expression by galactose sliding of two nucleosomes is detected. Sliding leads to exposure of TATA-box and long promoter segment. Sliding results in stable repositioning of nucleosomes at new sites. 5'-distal nucleosome moves closer to UAS-sequences. As a results UAS becomes spatially closer to TATA-box. This proximity facilitates assembly of preinitiation complex. Nucleosomes slides independently from each other. The second nucleosome moves towards FRT-sequence and repositions at its nucleosome positioning signal. Galactose-induced expression does not affect nucleosome positioning with coding region of NPTII gene. Unidirectional sliding and repositioning are detected without induction after deacetylase inhibition with trichostatine A. Basal expression of NPTII gene was shown without activation of GAL-CYC promoter and after spatial uncoupling of coding sequence and promoter by gene inversion. In these cases it seems that expression is driven by TATA-like element in FRT-sequence. This element is located in permanently exposed area (in vivo data).

PMID: 19140324 [PubMed - indexed for MEDLINE]

1372. Biometals. 2009 Feb;22(1):99-108. Epub 2009 Jan 13.

Di-iron proteins of the Ric family are involved in iron-sulfur cluster repair.

Justino MC, Baptista JM, Saraiva LM.

Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Oeiras, Portugal.

A key element in eukaryotic immune defenses against invading microbes is the production of reactive oxygen and nitrogen species. One of the main targets of these species are the iron-sulfur clusters, which are essential prosthetic groups that confer to proteins the ability to perform crucial roles in biological processes. Microbes have developed sophisticated systems to eliminate nitrosative and oxidative species and promote the repair of the damages inflicted. The Ric (Repair of Iron Centers) proteins constitute a novel family of microbial di-iron proteins with a widespread distribution among microbes, including Gram-positive and Gram-negative bacteria, protozoa and fungi. The Ric proteins are encoded by genes that are up-regulated by nitric oxide and hydrogen peroxide. Recent studies have shown that the active di-iron center is involved in the restoration of Fe-S clusters damaged by exposure to nitric oxide and hydrogen peroxide.

PMID: 19140014 [PubMed - indexed for MEDLINE]

1373. Proteomics. 2009 Feb;9(3):657-70.

Insights into yeast adaptive response to the agricultural fungicide mancozeb: a toxicoproteomics approach.

Santos PM, Simões T, Sá-Correia I.

IBB-Institute for Biotechnology and Bioengineering, Centre for Biological and Chemical Engineering, Instituto Superior Técnico, Lisboa, Portugal.

Toxicogenomics has the potential to elucidate gene-environment interactions to identify genes that are affected by a particular chemical at the early stages of the toxicological response and to establish parallelisms between different organisms. The fungicide mancozeb, widely used in agriculture, is an ethylene-bis-dithiocarbamate complex with manganese and zinc. Exposure to this pesticide has been linked to the development of idiopathic Parkinson's disease and cancer. Given that many signalling pathways and their molecular components are substantially conserved among eukaryotic organisms, we used Saccharomyces cerevisiae to get insights into the molecular mechanisms of mancozeb toxicity and adaptation based on expression proteomics. The early global response to mancozeb was analysed by quantitative proteomics using 2-DE. The target genes (e.g. TSA1, TSA2, SOD1, SOD2, AHP1, GRE2, GRX1, CYS3, PRE3, PRE6, PRE8, PRE9, EFT1, RPS5, TIF11, HSP31, HSP26, HSP104, HSP60, HSP70-family) and the putative main transcription activators (e.g. Yap1, Msn2/Msn4, Met4, Hsf1, Aft1, Pdr1, Skn7, Rpn4p, Gcn4) of the complex mancozeb-induced expression changes are related with yeast response to stress, in particular to oxidative stress, protein translation initiation and protein folding, disassembling of protein aggregates and degradation of damaged proteins. Our results also suggest that this study provided powerful indications that may be useful to expand the knowledge obtained in yeast not only to the global response to mancozeb toxicity in phytopathogenic fungi but also to humans.

PMID: 19137554 [PubMed - indexed for MEDLINE]

1374. J Occup Environ Hyg. 2009 Mar;6(3):165-73.

Working conditions and exposure to dust and bioaerosols in sisal processing factories in Tanzania.

Kayumba AV, Bråtveit M, Mashalla Y, Baste V, Eduard W, Moen BE.

Department for Public Health and Primary Health Care, Research Group on Occupational and Environmental Medicine, University of Bergen, Bergen, Norway.

Information was collected on working conditions and personal exposures to dust, bacteria, and fungi in sisal fiber processing factories in Tanzania to identify health hazards and possible needs for preventive measures. Walkthrough surveys were performed in the brushing and decorticating departments of six sisal factories. The number of departments showing adequate scores for ergonomics and work organization, physical working environment, and occupational health items were determined. Personal thoracic dust samples were collected during sisal processing and analyzed for concentration of dust (n = 24) and for fungi and bacteria (n = 32). In both departments, most items considered to be a prerequisite for a good working environment were either missing or inadequate. Ergonomic and physical hazards were observed. Repetitive strenuous tasks, awkward work postures, and high noise levels were found. Visible dust and inadequate ventilation were seen in the brushing departments, and wet floors were observed in the decortication departments. Personal protective equipment was hardly used. The arithmetic mean exposure of sisal processors was 1.2 mg thoracic dust/m(3), 43 x 10(6) bacteria/ m(3), and 2.35 x 10(6) fungal spores/m(3). The highest exposure levels were measured in the decortication departments when machines were cleaned of waste. Significant differences were found for mean thoracic dust exposure and bacteria counts between the brushing and decortication departments and the security guards. Within individual departments, there were no significant differences in exposures between the different work tasks. A linear mixed effect model of thoracic dust including department as fixed effect explained 65% of the between-worker variability for thoracic dust exposure. The study shows that workers in sisal processing in Tanzania are exposed to bioaerosols, and suitable control measures should be implemented. More exposure studies are needed in this type of industry.

PMID: 19137457 [PubMed - indexed for MEDLINE]

1375. J Occup Environ Med. 2009 Jan;51(1):80-6.

Screening tools to estimate mold burdens in homes.

Vesper S, McKinstry C, Bradham K, Ashley P, Cox D, Dewalt G, Lin KT.

United States Environmental Protection Agency, National Exposure Research Laboratory, Cincinnati, Ohio, USA. vesper.stephen@epa.gov

OBJECTIVE: The objective of this study was to develop screening tools that could be used to estimate the mold burden in a home which would indicate whether more detailed testing might be useful.
METHODS: Two possible screening methods were considered for mold analysis: use of vacuum cleaner bag dust rather than the standard protocol dust samples and reducing the number of molds needed to be quantified resulting in the creation of an alternative mold burden scale.
RESULTS: Vacuum bag dust analysis placed the estimate of mold burden into the upper or lower half of the Environmental Relative Moldiness Index scale. Mold burdens estimated by only 12 species produced an index, the American Relative Moldiness Index, with a correlation of rho = 0.80 with the Environmental Relative Moldiness Index.
CONCLUSIONS: Two screening tools were developed for estimating the mold burden in homes.

PMID: 19136876 [PubMed - indexed for MEDLINE]

1376. Chem Biol Interact. 2009 May 15;179(2-3):94-102. Epub 2008 Dec 24.

Cumene hydroperoxide debilitates macrophage physiology by inducing oxidative stress: possible protection by alpha-tocopherol.

Kaur G, Alam MS, Athar M.

Department of Medical Elementology & Toxicology, Faculty of Science, Jamia Hamdard, Hamdard Nagar, New Delhi 110062, India.

Macrophages, the major phagocytes of body, are largely dependent on membrane for their apposite functioning. Cum-OOH, a catalyst used in chemical and pharmaceutical industry, is a peroxidative agent, which may induce oxidative stress in macrophages hampering the integrity of their membrane. Alpha-tocopherol is known to protect the membrane from oxidative modulation and preserve its integrity. In the present study, we investigated the effect of Cum-OOH on physiology of macrophages and evaluated the protective effect of alpha-tocopherol against Cum-OOH-induced functional impairment. An in vitro exposure to 10-200 microM Cum-OOH altered redox balance of murine peritoneal macrophages and led to a severe physiological impairment. It markedly augmented the release of proinflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta and prostaglandin E(2)), lipopolysaccharide primed nitric oxide release and inducible nitric oxide synthase expression, and lysosomal hydrolases secretion. It mitigated respiratory burst and phagocytosis and intracellular killing of yeast (Saccharomyces cerevisiae). Mannose receptor, a major macrophage phagocytic receptor (also implicated in S. cerevisiae phagocytosis), exhibited a hampered recycling with its number being reduced to about 54% of the untreated, control cells following Cum-OOH exposure. A 24-h pretreatment of macrophages with 25 microM alpha-tocopherol preserved most of the assessed functions close to their corresponding control values. These data suggest that exposure to Cum-OOH may impair the physiology of immune cells such as macrophages and that supplementation with alpha-tocopherol can safeguard these cells against Cum-OOH toxicity.

PMID: 19135433 [PubMed - indexed for MEDLINE]

1377. J Microbiol Biotechnol. 2008 Dec;18(12):1997-2003.

Induction of apoptosis by aqueous extract of Cordyceps militaris through activation of caspases and inactivation of Akt in human breast cancer MDA-MB-231 Cells.

Jin CY, Kim GY, Choi YH.

Department of Biomaterial Control (BK21 Program), Dongeui University Graduate School and Department of Biochemistry,Dongeui University College of Oriental Medicine, Busan 614-052, Korea.

Cordyceps militaris is well known as a traditional medicinal mushroom and has been shown to exhibit immunostimulatory and anticancer activities. In this study, we investigated the apoptosis induced by an aqueous extract of C. militaris (AECM) via the activation of caspases and altered mitochondrial membrane permeability in human breast cancer MDA-MB-231 cells. Exposure to AECM induced apoptosis, as demonstrated by a quantitative analysis of nuclear morphological change and a flow cytometric analysis. AECM increased hyperpolarization of mitochondrial membrane potential and promoted the activation of caspases. Both the cytotoxic effect and apoptotic characteristics induced by AECM treatment were significantly inhibited by z-DEVD-fmk, a caspase-3 inhibitor, which demonstrates the important role of caspase-3 in the observed cytotoxic effect. AECM-induced apoptosis was associated with the inhibition of Akt activation in a time-dependent manner, and pretreatment with LY294002, a PI3K/Akt inhibitor, significantly increased AECM-induced apoptosis. The results indicated that AECM-induced apoptosis may relate to the activation of caspase-3 and mitochondria dysfunctions that correlate with the inactivation of Akt.

PMID: 19131705 [PubMed - indexed for MEDLINE]

1378. Environ Res. 2009 Feb;109(2):135-42. Epub 2009 Jan 7.

Assessment of airborne microorganism contamination in an industrial area characterized by an open composting facility and a wastewater treatment plant.

Grisoli P, Rodolfi M, Villani S, Grignani E, Cottica D, Berri A, Picco AM, Dacarro C.

Department of Experimental and Applied Pharmacology, Laboratory of Microbiology, University of Pavia, Pavia, Italy. pietro.grisoli@unipv.it

In order to assess the potential exposure hazard to workers and people living in the immediate surroundings of an area characterized by an open composting facility and a wastewater treatment plant, a quantitative and a qualitative analysis of airborne microorganisms were carried out. Air sampling was performed once a week for four consecutive weeks in summer and winter. Six sites were selected as air sampling sites: one was upwind at approximately 40 m from the facilities; the other five were downwind at increasing distances from the facilities, with the furthest at 100 m away. Monitoring permitted us to verify the influence that the composting activities and wastewater treatment had on the bacterial and fungal contamination of the air. The results obtained have been expressed by means of contamination indexes that have already been used in previous works: a major microbiological contamination near the plants was evidenced. Near the facilities, mesophilic bacteria, psychrophilic bacteria and microfungi showed the highest median concentrations, respectively, of 307.5, 327.5 and 257.5 CFU/m(3). Moreover, the season generally influenced the concentration of the bacteria as well as of the fungi; higher in summer than in winter. The contamination index global index of microbial contamination (GIMC/m(3)) showed mean values of 4058.9 in summer and 439.7 in winter and the contamination index-amplification index (AI) showed values of 4.5 and 1.1 in the same seasons, respectively. Controlling the seasonal effect, mesophilic bacteria, Pseudomonas spp. and Enterobacteriaceae showed a significant decline in concentration with respect to upwind air samples and with increasing distance. Both GIMC and AI showed a significant decline with respect to upwind air samples by increasing the distance from facilities after adjusting for the seasonal effect. In conclusion, even if these plants do not represent a potential risk for nearby populations, they may pose a potential health risk for workers.

PMID: 19131053 [PubMed - indexed for MEDLINE]

1379. Biochem Biophys Res Commun. 2009 Feb 6;379(2):621-5. Epub 2009 Jan 4.

Human trehalase is a stress responsive protein in Saccharomyces cerevisiae.

Ouyang Y, Xu Q, Mitsui K, Motizuki M, Xu Z.

Department of Biochemistry 2, University of Yamanashi, Faculty of Medicine, 1110, Shimokato, Chuo, Yamanashi 409-3898, Japan.

Three trehalases ATH1, NTH1, and NTH2 have been identified in Saccharomyces cerevisiae. ATH1, and NTH1 hydrolyze trehalose to glucose to provide energy and assist in recovery from stress. Human trehalase (TREH) is expressed in the intestine and kidney and probably hydrolyzes ingested trehalose in the intestine and acts as marker of renal tubular damage in kidney. Since trehalose is not present in circulation or kidney tubules, its renal effect suggests it has other yet unidentified actions. Here we examined the function of human trehalase in budding yeast. We constructed three yeast trehalase mutants (NTH1Delta, NTH2Delta, and ATH1Delta) and then transformed TREH into these mutants. NTH1Delta did not grow on media containing trehalose as the carbon source, and TREH did not rectify NTH1Delta dysfunction and also did not grow on trehalose medium, suggesting that TREH is not responsible for utilization of exogenous trehalose in yeast. In experiments involving exposure to heat, osmotic and oxidative stresses, NTH1Delta showed no recovery. Interestingly, ATH1Delta-TREH showed high sensitivity to all three stressors. ATH1Delta and NTH2Delta showed very low neutral trehalase activity and NTH1Delta did not show any neutral trehalase activity, and trehalose concentrations were higher. Increased neutral trehalase activity (equivalent to the wild type), reduction of trehalose content and brisk sensitivity to stressors were noted in TREH-ATH1Delta strain, but not in TREH-NTH1Delta or -NTH2Delta. Our results suggest that TREH acts as a stress-response protein in the kidney rather than involved in utilization of exogenous trehalose.

PMID: 19126402 [PubMed - indexed for MEDLINE]

1380. Asia Pac J Public Health. 2008;20(2):139-47.

Sharps injury and body fluid exposure among health care workers in an Australian tertiary hospital.

Peng Bi, Tully PJ, Boss K, Hiller JE.

Discipline of Public Health, The University of Adelaide, Adelaide, South Australia 5005, Australia. peng.bi@adelaide.edu.au

To examine sharps injury and body fluid exposure among health care workers, a descriptive epidemiological study was conducted in a 1000-bed tertiary hospital between 2000 and 2003 using surveillance data of all reported sharps injuries and body fluid exposures. A total of 640 sharps injuries and body fluid exposures were reported from hospital and nonhospital staff, although no seroconversions to HIV, hepatitis B virus, or hepatitis C virus were observed during the study period. Nurses reported 47% of sharps injuries and 68% of body fluid exposures, medical staff reported 38% and 16%, and other nonmedical staff notified 5% and 4%, respectively, while nonhospital staff reported the rest. Hollow-bore needles accounted for 56% of sharps injuries, while 11% of the incidents were sustained during recapping and inappropriate disposal. Further research into Australian work practices, disposal systems, education strategies, and the use of safety sharps should be emphasized to implement strategies to reduce work-related injuries among health care workers.

PMID: 19124307 [PubMed - indexed for MEDLINE]

1381. Occup Med (Lond). 2009 Mar;59(2):101-6. Epub 2009 Jan 2.

Accidental blood and body fluid exposure among doctors.

Naghavi SH, Sanati KA.

Department of Occupational Health, Imperial College Healthcare NHS Trust, London, UK. hamidreza_naghavi@yahoo.com

AIM: To study the epidemiology and time trends of blood and body fluids (BBF) exposures among hospital doctors.
METHODS: A 3-year study was carried out using data from the Exposure Prevention Information Network of four teaching hospitals in the UK.
RESULTS: One hundred and seventy-five cases of BBF exposures in doctors were reported over the 3-year study period. Eighty-one (46%) occurred in senior doctors and 94 (54%) in junior doctors. Junior doctors had a higher rate of BBF exposures compared to senior doctors: 13 versus 4 incidents per 100 person-years, respectively (relative risk 3, 95% confidence interval 2-4). The most frequent setting for BBF exposures among senior doctors was the operating theatre/recovery (59%). Among junior doctors, it was the patient room (48%). The commonest original reason for use of sharps by junior doctors was the taking of blood samples (42%). Among senior doctors, it was suturing (41%).
CONCLUSION: While ongoing training efforts need to be directed towards both junior and senior doctors, our data suggest that junior doctors are at higher risk of BBF exposures and may need particular attention in prevention strategies. An improvement in the safety culture in teaching hospitals can be expected to reduce the number of BBF exposures.

PMID: 19122191 [PubMed - indexed for MEDLINE]

1382. J Appl Microbiol. 2008 Dec;105(6):1919-28.

Isolation of Saccharomyces cerevisiae strains from different food matrices and their preliminary selection for a potential use as probiotics.

Pennacchia C, Blaiotta G, Pepe O, Villani F.

Dipartimento di Scienza degli Alimenti, Università degli Studi di Napoli Federico II, Portici, Italy.

AIMS: To isolate acid- and bile-resistant Saccharomyces cerevisiae strains directly from food samples and to preliminarily select them on the basis of fundamental probiotic properties. METHODS AND RESULTS: A rapid screening method allowed the isolation and selection of 20 acid- and bile-resistant yeasts from foods, avoiding time-consuming isolation steps. The strains were characterized for their specific survival in simulated gastric juice and in intestinal fluid after pre-exposure at low pH. Ten isolates demonstrated a satisfactory survival percentage in intestinal fluid after pre-exposure to gastric juice and appreciable lipolytic and proteolytic properties, as demonstrated by the API-ZYM test. By using molecular methods five strains were identified as Saccharomyces cerevisiae, three as Candida spp., one as Candida pararugosa and one as Pichia spp. The Saccharomyces cerevisiae strains showed considerable probiotic properties, achieving a 80< % <90 survival through the simulated gastrointestinal tract, as well as interesting glucosidase activities.
CONCLUSIONS: The research represents an efficient strategy to select and identify Saccharomyces cerevisiae strains with desirable acid and bile resistances. SIGNIFICANCE AND IMPACT OF THE STUDY: This paper reports the direct selection of potentially probiotic yeasts from foods and provides indications about the ability of Saccharomyces cerevisiae strains to survive conditions simulating the human gastrointestinal tract.

PMID: 19120638 [PubMed - indexed for MEDLINE]

1383. Ann N Y Acad Sci. 2008 Dec;1149:384-7.

Virulence of Metarhizium anisopliae to eggs and immature stages of Stomoxys calcitrans.

Moraes AP, Angelo Ida C, Fernandes EK, Bittencourt VR, Bittencourt AJ.

Universidade Federal Rural do Rio de Janeiro, Instituto de Veterinária, Seropédica, Rio de Janeiro, Brazil.

Stomoxys calcitrans control is primarily based on the use of chemical products; however, new methods for control have been investigated. Biological control has been proposed as a promising alternative to traditional chemicals. The current study evaluated three methods in vitro to treat S. calcitrans eggs with the fungus Metarhizium anisopliae and assessed the virulence of this fungus to immature stages of this fly. In the first method of egg exposure, eggs were immersed in conidial suspensions and transferred to Petri plates with high humidity. A high mortality was observed in both treated and control groups. In the second method, the eggs were transferred to rearing medium right after immersion in conidial suspensions; the suspensions with highest conidial concentrations, 10(7) and 10(8) conidia mL(-1), caused 96.25% and 100% mortality, respectively. In the third method, the eggs were sprayed with conidial suspensions on the rearing medium. A high mortality was observed at 10(7) and 10(8) conidia mL(-1), 78.3% and 100%, respectively. The second method had the lowest mortality in the control group and was considered the most useful method for evaluating the effect of entomopathogenic fungi on S. calcitrans eggs. While eggs were very susceptible to M. anisopliae infection, larvae and pupae were not.

PMID: 19120256 [PubMed - indexed for MEDLINE]

1384. Ann N Y Acad Sci. 2008 Dec;1149:239-41.

Fungal formulations to control Rhipicephalus sanguineus engorged females.

Reis RC, Fernandes EK, Bittencourt VR.

Departamento Zootecnia, Uinversidade Federal de Roraima (UFRR), Campus Cauamé Boa Vista, RR, Brazil.

Entomopathogenic fungi are promising alternatives to chemical acaricides in controlling tick populations; however, biological formulations are required to improve conidial performance of these pathogens in the field. This study evaluated the effect of in vitro treatment of Rhipicephalus sanguineus with conidial formulations of Beauveria bassiana (Bb) or Metarhizium anisopliae (Ma). Conidia were formulated (at 10(8) conidia mL(-1)) in (1) emulsifiable concentrate (EC), (2) polymerized cellulose gel (PCG), or both (3) emulsifiable concentrate and polymerized cellulose gel combined (EC+PCG). Engorged females were weighed and exposed to one of six treatment groups: EC+Bb, EC+Ma, PCG+Bb, PCG+Ma, EC+PCG+Bb, EC+PCG+Ma; or to control groups: C1 (untreated) or (C2) treated with Tween 80 aqueous solution, EC or PCG. After exposure, ticks were placed in petri plates and kept at 27 +/- 1 degrees C and 80% relative humidity (RH). Ticks treated with formulated conidia of entomopathogenic fungi showed significantly higher control percentage in comparison to that of control groups. The formulation of B. bassiana with EC and PCG combined (EC+PCG+Bb) caused the highest control percentage (86.79%) of R. sanguineus. This study concludes that entomopathogenic fungus conidial formulations are important to ensure effective tick control.

PMID: 19120220 [PubMed - indexed for MEDLINE]

1385. Ann Agric Environ Med. 2008 Dec;15(2):251-61.

Endotoxin exposure in sewage treatment workers: investigation of exposure variability and comparison of analytical techniques.

Spaan S, Smit LA, Eduard W, Larsson L, Arts HJ, Wouters IM, Heederik DJ.

Institute for Risk Assessment Sciences, division of Environmental Epidemiology, Utrecht University, Utrecht, The Netherlands. suzanne.spaan@tno.nl

INTRODUCTION: Objectives were to give an overview of endotoxin exposure and its determinants in sewage treatment workers, and to study exposure to culturable and non-culturable microorganisms and the applicability of the LAL assay in this work environment. MATERIAL AND METHODS: In 43 Dutch sewage treatment plants 470 full-shift, 123 task-based personal and 54 stationary inhalable dust samples were collected. Endotoxin concentration was determined with the LAL-assay. Mixed effects models were used to investigate possible determinants of exposure. Simultaneous parallel filter samples, impinger samples and viable total bacteria and Gram-negative bacterial samples were taken to compare analytical techniques. Filter and impinger samples were analyzed with the LAL-assay, gas chromatography-mass spectrometry (GC-MS) and fluorescence microscopy.
RESULTS: Endotoxin exposure levels were moderate to low (geometric mean personal exposure 27 EU/m(3), stationary 33 EU/m(3), task-based 64 EU/m(3)), yet differences between jobs and sources and some determinants of exposure were identified. Exposure varied more from day to day than between workers. Concentrations in filter samples were higher and more consistent than in impinger samples. Fungi and Gram-positive bacteria were found in higher levels than Gram-negative bacteria. The LAL assay and GC-MS showed comparable endotoxin levels. DISCUSSION AND CONCLUSION: Endotoxin exposure in Dutch sewage treatment workers was relatively low. Comparison of sampling and analytical techniques suggests that the LAL-assay did not result in much exposure misclassification. It thus seems justified to perform filter measurements in combination with the LAL-assay to measure endotoxin exposure in sewage treatment plants.

PMID: 19118445 [PubMed - indexed for MEDLINE]

1386. Mycopathologia. 2009 Apr;167(4):187-90. Epub 2009 Jan 1.

Serologic detection of coccidioidomycosis antibodies in northeast Brazil.

Cordeiro Rde A, Fechine MA, Brilhante RS, Rocha MF, da Costa AK, Nagao MA, de Camargo ZP, Sidrim JJ.

Specialized Medical Mycology Center, Federal University of Ceará, Fortaleza, Ceará, Brazil. ross@uece.br

Coccidioidomycosis is a systemic infection caused by Coccidioides spp. The disease is endemic in Brazil but its incidence is underreported as it is not a notifiable disease. This article presents the results of a serologic survey carried out with 229 volunteers in northeast Brazil by the immunodiffusion (ID) test with commercial Coccidioides spp. antigens. The commercial ID test detected 15 individuals without clinical diagnosis of the disease and two individuals in treatment for coccidioidomycosis. Regarding the epidemiological data, most of the positive individuals were male, between 18 and 65 years of age and were engaged in armadillo hunting. Three women who had never participated in armadillo hunts also displayed positive results for coccidioidal antibodies. Besides armadillo hunts, exposure to environmental dust in endemic areas may account for the serologic response detected in the study. The data from this study suggest the importance of performing epidemiological surveys for coccidioidomycosis in order to understand the prevalence of this disease in Brazil.

PMID: 19116771 [PubMed - indexed for MEDLINE]

1387. J Microw Power Electromagn Energy. 2009;43(4):17-27.

Interaction of radio-frequency, high-strength electric fields with harmful insects.

Ponomaryova IA, Niño de Rivera y Oyarzabal L, Ruíz Sánchez E.

SEPI ESIME-CULHUACAN, Instituto Politécnico Nacional, Mexico, D. F. iripon76@yahoo.com.mx

The objective of the research reported here is to investigate the influence of radio-frequency electric fields of high strength on insect mortality. The experiments were accomplished at the frequencies 47.5, 900 and 2,450 MHz for the pulse modulated radiation treatment and the continuous wave RF radiation. Two types of systems, which are the coaxial irradiation chamber and the irradiation chamber with plane capacitor are presented in this work. The experiments in the coaxial type radiation chamber on granary weevil (Sitophilus granarius L.) at voltages U = 5.5-10.5 kV frequency 47.5 MHz, electric field intensity 180-350 kV/m and exposures 5-60 seconds give 40-90% of insect mortality that mainly depends on voltage increase. The experiments in the irradiation chamber with plane capacitor are presented for the pulse modulated regime at a frequency of 47.5 MHz and field intensities 350-2000 kV/m. 100% of insect mortality is reached at the exposures of 1-30 seconds, at field intensity of 2000 kV/m. The RF radiation of granary weevil (Sitophilus granarius L.) in the coaxial irradiation chamber in stationary mode reaches 100% insect mortality at major exposure times for the frequencies 900 and 2,450 MHz. Stationary generator mode also permits 21-97% fungi (Cladosporium cladosporioides, Aspergillus candidus) control at voltage U = 10.5 kV frequencies 900 and 2,450 MHz and exposures of 120-180 seconds. Further investigation is needed for microscopic fungi control to understand the fungi reproduction mechanism during the RF-radiation treatment for Aspergillus fumigatus.

PMID: 21384727 [PubMed - indexed for MEDLINE]

1388. Wiad Parazytol. 2009;55(4):425-8.

[Mapping of environmental mycologic hazards using GIS method].

[Article in Polish]

Lonc E, Wieliczko A, Plewa K.

Zakład Ekologii Drobnoustrojów i Ochrony Srodowiska Instytutu Genetyki i Mikrobiologii, Uniwersytet Wrocławski, ul. Przybyszewskiego 63/77, 51-148 Wrocław. lonc@microb.uni.wroc.pl

Intensive poultry production is associated with extreme densities of birds crammed into industrial-scale hen houses. Consequently, the bird keepers are exposed to elevated concentrations of dust. Exposure to dust, containing pathogenic mycological agents, may cause exacerbate asthma, allergic alveolitis, as well as organic dust toxic syndrome. Geographic Information System (GIS) allows to view, understand, question, interpret, and visualize biological data, among them mycological threats. The aim of the presently reported study was to create the mycological database from the chicken farms and their visualization on the map of Lower Silesia, Poland. Field data for Aspergillus fumigatus, A. flavus, Candida sp. were collected in Wrocław laboratory in 2008. GIS database was formed using ArcView 9.2. computer software. The visualization data on the digital maps were analyzed for the Health and Safety Executive.

PMID: 20209819 [PubMed - indexed for MEDLINE]

1389. Int J Occup Med Environ Health. 2009;22(4):343-54.

Is the risk of allergic hypersensitivity to fungi increased by indoor exposure to moulds?

Wiszniewska M, Walusiak-Skorupa J, Gutarowska B, Krakowiak A, Pałczyński C.

Department of Occupational Diseases and Toxicology, Nofer Institute of Occupational Medicine, Łódź, Poland. martaz@imp.lodz.pl

OBJECTIVES: Moulds are frequently found in the indoor environment of residential houses. An association between domestic mould contamination and respiratory symptoms has been reported, but mould exposure as a risk factor for allergy to moulds is not well documented. The aim of the study was to evaluate the prevalence and associated factors of allergic hypersensitivity to moulds. MATERIALS AND METHODS: A group of 243 participants was examined. Of these 118 lived in dwellings with evident signs of fungal contamination (study group) and 125 in non-contaminated sites (controls). An interview, skin prick tests to common and fungal allergens, evaluation of total serum IgE and specific IgE to moulds, resting spirometry as well as mycological analysis in building were performed for each participant.
RESULTS: 19.8% subjects were sensitized to at least one mould allergen. Logistic regression analysis revealed that the history of respiratory and skin symptoms, smoking cigarettes in the past and positive skin prick tests (SPT) to common allergens (dust mite and grass pollens) or the presence of a cat as a pet animal were the significant associated factors of hypersensitivity to moulds.
CONCLUSIONS: The association between indoor fungal exposure and the development of fungal allergy was not confirmed in our study.

PMID: 20197261 [PubMed - indexed for MEDLINE]

1390. Med Pr. 2009;60(6):483-90.

[Waste sorting plants--recognition of exposure to biological agents (moulds)].

[Article in Polish]

Kozajda A, Sowiak M, Piotrowska M, Szadkowska-Stańczyk I.

Instytut Medycyny Pracy im. prof. J. Nofera, Łódź Zakład Srodowiskowych Zagrozeń Zdrowia. anias@imp.lodz.pl

BACKGROUND: The aim of the study was to recognize exposure to biological agents in the air of waste sorting plants. This publication contains the characteristics of technical solutions in use during sorting of waste and the results of quantitative analysis in terms of the presence of moulds and inhalable dust in the air. MATERIAL AND METHODS: The study was conducted in the summertime inside two waste sorting plants with different production capacity ("big" and "small"). To evaluate inhalable dust in the air, 53 samples were collected using personal samplers on glass fiber filters. To assess mycological contamination of the air, 30 triple samples were directly collected on Petri dishes (Malt Extract Agar medium), using the volumetric impact method in the worker's respiratory zone. Samples were incubated for 5 days at 30 degrees C. Outcomes of the total number of moulds were provided in cfu/m3 (cfu--colony forming units).
RESULTS: The mean concentration of inhalable dust, determined in the "big" waste sorting plant, was 2.38 mg/m3 and in the "small" plant 1.12 mg/m3. The quantitative analysis revealed the following values of the total number of moulds present in the air: 1) "big" waste sorting plant, 2.9 x 10(4) cfu/m3 (work premises) and 3.6 x 10(3) jtk/m3 (office premises); 2) "small" waste sorting plant, 7.8 x 10(4) cfu/m3 (work premises) and 2.5 x 10(3) jtk/m3 (office premises).
CONCLUSIONS: Mould concentrations determined in the environment of waste sorting plants were high. To protect health of workers in this kind of plants, preventive programs focused on the protection of the skin and respiratory system should be implemented. Offices should be properly isolated from work premises to minimize spreading of inhalable dust.

PMID: 20187496 [PubMed - indexed for MEDLINE]

1391. Eukaryot Cell. 2009 Mar;8(3):262-70. Epub 2008 Dec 29.

Hypovirus-responsive transcription factor gene pro1 of the chestnut blight fungus Cryphonectria parasitica is required for female fertility, asexual spore development, and stable maintenance of hypovirus infection.

Sun Q, Choi GH, Nuss DL.

Center for Biosystems Research, University of Maryland Biotechnology Institute, Shady Grove Campus, Rockville, Maryland 20850, USA.

We report characterization of the gene encoding putative transcription factor PRO1, identified in transcriptional profiling studies as being downregulated in the chestnut blight fungus Cryphonectria parasitica in response to infection by virulence-attenuating hypoviruses. Sequence analysis confirmed that pro1 encodes a Zn(II)(2)Cys(6) binuclear cluster DNA binding protein with significant sequence similarity to the pro1 gene product that controls fruiting body development in Sordaria macrospora. Targeted disruption of the C. parasitica pro1 gene resulted in two phenotypic changes that also accompany hypovirus infection, a significant reduction in asexual sporulation that could be reversed by exposure to high light intensity, and loss of female fertility. The pro1 disruption mutant, however, retained full virulence. Although hypovirus CHV1-EP713 infection was established in the pro1 disruption mutant, infected colonies continually produced virus-free sectors, suggesting that PRO1 is required for stable maintenance of hypovirus infection. These results complement the recent characterization of the hypovirus-responsive homologue of the Saccharomyces cerevisiae Ste12 C(2)H(2) zinc finger transcription factor gene, cpst12, which was shown to be required for C. parasitica female fertility and virulence.

PMCID: PMC2653244 PMID: 19114501 [PubMed - indexed for MEDLINE]

1392. J Occup Health. 2009;51(1):64-73. Epub 2008 Dec 19.

Oral lead exposure induces dysbacteriosis in rats.

Sadykov R, Digel I, Artmann AT, Porst D, Linder P, Kayser P, Artmann G, Savitskaya I, Zhubanova A.

Kazakh National University Named after Al-Farabi, Republic of Kazakhstan.

OBJECTIVES: Lead's (Pb(II)) possible role in intestinal pathologies of microbial etiology remains mostly unknown. The aim of this study was to examine the effects of lead on the gut microbial community and its interactions with rat intestinal epithelium.
METHODS: The lead-induced changes in different intestinal microbial groups (lactose-positive lac(+) and -negative lac(-) E.coli strains, lactobacilli and yeasts) were followed separately by the colony-forming unit (CFU) method. Samples were taken from outbred white rats subjected to different exposure schedules. Additionally, the impact of different lead doses on microbial adhesion to cultured intestinal cells (IEC-6) was investigated. Finally, the lead accumulation and distribution were measured by means of atomic absorption spectrometry.
RESULTS: For the first time it was shown that oral lead exposure causes drastic changes in the gut microbial community. Proportional to the lead dose received, the relative number of lactose-negative E.coli cells increased dramatically (up to 1,000-fold) in comparison to the other microbial groups during 2 wk of exposure. Considering the number of microbes in the intestine, such a shift in intestinal microflora (dysbacteriosis) is very significant. Adhesion studies showed certain stimulating effects of lead on E. coli attachment to rat intestinal epithelium as compared to Lactobacillus attachment.
CONCLUSIONS: The mechanisms providing the apparent competitive success of the lac(-) group are unclear but could be related to changes in surface interactions between microbial and host cells. This study may provide important clues for understanding the pathological effects of metal dietary toxins in human beings.

PMID: 19096199 [PubMed - indexed for MEDLINE]

1393. Eur J Nutr. 2009 Mar;48(2):75-83. Epub 2008 Dec 17.

Dietary calcium and vitamin D2 supplementation with enhanced Lentinula edodes improves osteoporosis-like symptoms and induces duodenal and renal active calcium transport gene expression in mice.

Lee GS, Byun HS, Yoon KH, Lee JS, Choi KC, Jeung EB.

Laboratory of Veterinary Biochemistry and Molecular Biology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea.

The two main sources of vitamin D3 are de novo synthesis induced by exposure to ultraviolet (UV) light from the sun, and diet. Vitamin D3 deficiency causes rickets or osteoporosis. Oak mushrooms (Lentinula edodes) that are exposed to UV radiation contain enhanced vitamin D2 and have much higher calcium content than unmodified (non-irradiated) mushrooms. Such modified edible mushrooms have been proposed as a natural alternative source of dietary vitamin D. In the current study, we have examined whether modified oak mushrooms could improve or prevent osteoporosis-like symptoms in mice fed with low calcium and vitamin D3-deficient diet. Four-week-old male mice were fed low calcium, vitamin D3-deficient diets supplemented with 5, 10, or 20% unmodified, calcium-enhanced, or calcium plus vitamin D2-enhanced oak mushrooms for 4 weeks. To assess the effects of the supplemented diets, we evaluated femur density and length, bone histology, the expression of active calcium transport genes, and serum calcium levels. Mice fed with low calcium and vitamin D3-deficient diet developed osteoporosis-like symptoms within 4 weeks. Femur density and tibia thickness were significantly higher in mice fed calcium plus vitamin D2-enhanced mushrooms, and the expression of duodenal and renal calcium transport genes was significantly induced. These results indicate that in mice, vitamin D2 and/or calcium derived from irradiated oak mushrooms may improve bone mineralization through a direct effect on the bone, and by inducing the expression of calcium-absorbing genes in the duodenum and kidney.

PMID: 19093162 [PubMed - indexed for MEDLINE]

1394. Vet Parasitol. 2009 Mar 23;160(3-4):279-84. Epub 2008 Nov 13.

The use of a semiochemical bait to enhance exposure of Amblyomma variegatum (Acari: Ixodidae) to Metarhizium anisopliae (Ascomycota: Hypocreales).

Nchu F, Maniania NK, Touré A, Hassanali A, Eloff JN.

International Centre of Insect Physiology and Ecology, African Insect Sciences for Food and Health, Nairobi, Kenya.

Experiments were conducted to explore the use of a semiochemical bait to enhance exposure of Amblyomma variegatum Fabricius (Acari: Ixodidae) to different formulations of the entomopathogenic fungus Metarhizium anisopliae (Metsch.) Sorok. (Ascomycota: Hypocreales). Initially, the relative efficacies of attraction-aggregation-attachment pheromone (AAAP), made up of o-nitrophenol, methyl salicylate and nonanoic acid in the ratio 2:1:8, 1-octen-3-ol and butyric acid, were evaluated in an olfactometer. Only AAAP and 1-octen-3-ol were found to elicit attractive responses to the tick. Simultaneous release of 1-octen-3-ol and AAAP together with CO(2) from a trap in semifield plots attracted up to 94.0+/-6% of adult ticks from a distance of 6m, and up to 24.0+/-5.1% from 8m. Formulations of M. anisopliae (dry powder, oil, and emulsifiable) applied within the trap baited with AAAP, 1-octen-3-ol and CO(2) resulted in high levels of contamination of the ticks attracted to the traps. However, 48h after autoinoculation, 89.1 and 33.3% of conidia were lost in dry powder and oil formulations, respectively. Emulsifiable formulation showed least loss of propagules (17.1%). Samples of ticks attracted to the baited traps were transferred to plastic basins containing grass and maintained for 5 weeks. The experiment was conducted in rainy and dry seasons. Emulsifiable formulation gave the highest relative tick reduction in both seasons: 54.7 and 46.5% in rainy and dry seasons, respectively, followed by oil formulation (32.0 and 23.8%) and powder formulation (38.0 and 24.4%).

PMID: 19091474 [PubMed - indexed for MEDLINE]

1395. Cancer Lett. 2009 Dec 1;286(1):9-14. Epub 2008 Dec 16.

Liver cancer: descriptive epidemiology and risk factors other than HBV and HCV infection.

Chuang SC, La Vecchia C, Boffetta P.

Lifestyle, Environment and Cancer Group, International Agency for Research on Cancer, 150 cours Albert Thomas, 69008 Lyon, France.

The incidence of liver cancer is high in all low-resource regions of the world, with the exception of Northern Africa and Western Asia. The estimated worldwide number of new cases of liver cancer in 2002 is 600,000, of which 82% are from developing countries. Given the poor survival from this disease, the estimated number of deaths is similar to that of new cases. Hepatocellular carcinoma (HCC) is the main form of liver cancer. A part from chronic infections with Hepatitis B and Hepatitis C viruses, which are the main causes of HCC, contamination of foodstuff with aflatoxins, a group of mycotoxins produced by the fungi Aspergillus flavus and Aspergillus parasiticus, is an important contributor to HCC burden in many low-income country. Alcoholic cirrhosis is an important risk factor for HCC in populations with low prevalence of HBV and HCV infection, and the association between tobacco smoking and HCC is now established. Diabetes is also related to an excess risk of HCC and the increased prevalence of overweight and obesity likely contributes to it. The second most important type of liver cancer is cholangiocarcinoma, whose main known cause is infestation with the liver flukes, Opistorchis viverrini and Clonorchis sinensis, which is frequent in some areas in South-East Asia. Angiosarcoma is a rare form of liver cancer whose occurence is linked to occupational exposure to vinyl chloride.

PMID: 19091458 [PubMed - indexed for MEDLINE]

1396. J Appl Oral Sci. 2007 Dec;15(6):470-4.

The effect of different light-curing units on tensile strength and microhardness of a composite resin.

Franco EB, dos Santos PA, Mondelli RF.

Department of Endodontics, Dentistry and Dental Materials, Bauru School of Dentistry, São Paulo State University, Bauru, SP, Brazil. ebfranco@fob.usp.br

The aim of this study was to evaluate the influence of different light-curing units on the tensile bond strength and microhardness of a composite resin (Filtek Z250 - 3M/ESPE). Conventional halogen (Curing Light 2500 - 3M/ESPE; CL) and two blue light emitting diode curing units (Ultraled - Dabi/Atlante; UL; Ultrablue IS - DMC; UB3 and UB6) were selected for this study. Different light intensities (670, 130, 300, and 600 mW/cm(2), respectively) and different curing times (20s, 40s and 60s) were evaluated. Knoop microhardness test was performed in the area corresponding to the fractured region of the specimen. A total of 12 groups (n=10) were established and the specimens were prepared using a stainless steel mold composed by two similar parts that contained a cone-shaped hole with two diameters (8.0 mm and 5.0 mm) and thickness of 1.0 mm. Next, the specimens were loaded in tensile strength until fracture in a universal testing machine at a crosshead speed of 0.5 mm/min and a 50 kg load cell. For the microhardness test, the same matrix was used to fabricate the specimens (12 groups; n=5). Microhardness was determined on the surfaces that were not exposed to the light source, using a Shimadzu HMV-2 Microhardness Tester at a static load of 50 g for 30 seconds. Data were analyzed statistically by two-way ANOVA and Tukey's test (p<0.05). Regarding the individual performance of the light-curing units, there was similarity in tensile strength with 20-s and 40-s exposure times and higher tensile strength when a 60-s light-activation time was used. Regarding microhardness, the halogen lamp had higher results when compared to the LED units. For all light-curing units, the variation of light-exposure time did not affect composite microhardness. However, lower irradiances needed longer light-activation times to produce similar effect as that obtained with high-irradiance light-curing sources.

PMID: 19089182 [PubMed]

1397. Auris Nasus Larynx. 2009 Aug;36(4):422-6. Epub 2008 Dec 11.

Mouse model of Aspergillus and Alternaria induced rhinosinusitis.

Ahn BH, Park YH, Shin SH.

Department of Otolaryngology, School of Medicine, Keimyung University, South Korea.

OBJECTIVE: Fungi are known to induce the production of chemical mediators from respiratory epithelial cells and have been increasingly recognized as important pathogens in sinusitis. However, the exact role of fungi in the pathogenesis of rhinosinusitis has not been clearly established. This study was performed to improve our understanding of the role of fungi in the pathogenesis of rhinosinusitis by developing an animal model of fungus induced rhinosinusitis.
METHODS: Fifty mice (C57BL6/J) were divided into five groups. Sham-operated group was the first group. In the second group, Aspergillus versicolor (Group IIa) and Alternaria alternata (Group IIb) (10(6)spores/ml) were inoculated into the nasal cavity. In the third group, fungi were inoculated into the nasal cavity in the presence of mucosal scratch (Group IIIa,b) and the fourth group was a nasal mucosal scratch only (Group IV). The fifth was a negative control (Group V). The fungi were inoculated once a week on six occasions and then the animals were sacrificed at 7 weeks. The histological sections were examined in a blind manner for the appearance of neutrophil clusters and epithelial thickness with hematoxylin-eosin stain, and mucus secreting glands using the Alcian blue/periodic acid Schiff stain.
RESULTS: Non-invasive fungal sinusitis had been induced with increased numbers of neutrophil clusters after Aspergillus and Alternaria exposure. The mice with the mucosal scratch wounds had significantly more inflammatory cell infiltration and epithelial thickening; but eosinophils were not commonly found. The mice with fungal sinusitis had goblet cell hyperplasia and increased mucus secretion in the sinonasal cavity.
CONCLUSIONS: Inoculation of fungi in the nasal cavity induced rhinosinusitis in C57BL6/J mice. This mouse model may be used for better understanding of the role of fungi in the pathogenesis of rhinosinusitis.

PMID: 19084360 [PubMed - indexed for MEDLINE]

1398. Am J Infect Control. 2008 Dec;36(10):e27-31.

Risk of infection in health care workers following occupational exposure to a noninfectious or unknown source.

Kuruuzum Z, Yapar N, Avkan-Oguz V, Aslan H, Ozbek OA, Cakir N, Yuce A.

Department of Infectious Diseases and Clinical Microbiology, School of Medicine, University of Dokuz Eylul, Izmir, Turkey. ziya.kuruuzum@deu.edu.tr

BACKGROUND: The major concern after occupational exposures is the possible transmission of blood-borne pathogens, especially hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV). This study was undertaken to evaluate the risk of infection after exposure to blood or body fluids of an unknown or an HBV-, HCV-, and HIV-negative source and to determine the epidemiologic characteristics of these incidents in health care workers.
METHODS: The survey was conducted over a 6-year period at a university hospital in Turkey, using a questionnaire to elicit demographic and epidemiologic information. Serologic tests for HBV, HCV, and HIV were performed and repeated after 3 months.
RESULTS: Of the 449 incidents, complete follow-up was achieved in 320 (71.3%), and no seroconversion was observed for HBV, HCV and HIV. Most of the incidents occurred in medical (34.7%) and surgical (25.4%) work areas. The most frequent type of exposure was percutaneous injury (94%), most commonly caused by handling of garbage bags (58.4%), needle recapping (16.5%), and invasive interventions (13.4%).
CONCLUSION: Infection risk seems to be extremely low for HCV and HIV, because of low endemicity, and for HBV in groups immunized against HBV.

PMID: 19084160 [PubMed - indexed for MEDLINE]

1399. Nature. 2009 Jan 29;457(7229):612-5. Epub 2008 Dec 14.

RAD6-RAD18-RAD5-pathway-dependent tolerance to chronic low-dose ultraviolet light.

Hishida T, Kubota Y, Carr AM, Iwasaki H.

Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan. hishida@biken.osaka-u.ac.jp

In nature, organisms are exposed to chronic low-dose ultraviolet light (CLUV) as opposed to the acute high doses common to laboratory experiments. Analysis of the cellular response to acute high-dose exposure has delineated the importance of direct DNA repair by the nucleotide excision repair pathway and for checkpoint-induced cell cycle arrest in promoting cell survival. Here we examine the response of yeast cells to CLUV and identify a key role for the RAD6-RAD18-RAD5 error-free postreplication repair (RAD6 error-free PRR) pathway in promoting cell growth and survival. We show that loss of the RAD6 error-free PRR pathway results in DNA-damage-checkpoint-induced G2 arrest in CLUV-exposed cells, whereas wild-type and nucleotide-excision-repair-deficient cells are largely unaffected. Cell cycle arrest in the absence of the RAD6 error-free PRR pathway was not caused by a repair defect or by the accumulation of ultraviolet-induced photoproducts. Notably, we observed increased replication protein A (RPA)- and Rad52-yellow fluorescent protein foci in the CLUV-exposed rad18Delta cells and demonstrated that Rad52-mediated homologous recombination is required for the viability of the rad18Delta cells after release from CLUV-induced G2 arrest. These and other data presented suggest that, in response to environmental levels of ultraviolet exposure, the RAD6 error-free PRR pathway promotes replication of damaged templates without the generation of extensive single-stranded DNA regions. Thus, the error-free PRR pathway is specifically important during chronic low-dose ultraviolet exposure to prevent counter-productive DNA checkpoint activation and allow cells to proliferate normally.

PMID: 19079240 [PubMed - indexed for MEDLINE]

1400. Indoor Air. 2009 Apr;19(2):102-12. Epub 2008 Oct 15.

Effects on perceived air quality and symptoms of exposure to microbially produced metabolites and compounds emitted from damp building materials.

Claeson AS, Nordin S, Sunesson AL.

National Institute for Working Life, Umeå, Sweden.

This work investigated perceived air quality and health effects from exposure to low to high levels of volatile organic compounds (VOCs) emitted from damp building materials and a mixture of molds growing on the materials. A mixture of Wallemia sebi, Fusarium culmorum, Penicillium chrysogenum, Ulocladium botrytis, and Aspergillus versicolor was inoculated on pine wood and particle board. In Study 1, each of 27 participants took part in two exposure conditions, one with air from molds growing on building materials (low levels of emissions from the building materials and the mold mixture) and one with blank air, both conditions during 60 min. In Study 2, each of 24 participants was exposed (10 min) four times in a 2 x 2 design randomly to air from moldy building materials (high levels) and blank, with and without nose-clip. The participants rated air quality and symptoms before, during, and after each exposure. Self-reported tear-film break-up time and attention and processing speed (Study 1) was also measured. Exposure to high VOC levels increased the reports of perceived poor air quality, and in the condition without nose-clip enhanced skin symptoms were also noted. No such outcome was observed when exposing the participants to low VOC levels.
PRACTICAL IMPLICATIONS: Emissions from building materials caused by dampness and microbial growth may be involved in indoor air health problems. This study showed that exposure to high levels of VOC emitted from damp building materials and a mixture of mold may cause perceived poor air quality. It also indicated that stimulation of chemical warning systems (the nasal chemosensory part of the trigeminal system and the olfactory system) may enhance skin symptoms.

PMID: 19077173 [PubMed - indexed for MEDLINE]

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