BABESIA, MEPRON, MALARONE, ARTEMISININ, ZHANG, COWDEN, IGENEX, ILADS, JAMES SCHALLER, LYMEINFO, INFORMATION, LAB, DIAGNOSIS, SYMPTOMS, CAMERON
main page books and articles schaller health creed facebook testimonies search
menu main page what's new second opinion new patient meet doctor schaller location, travel

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.

Copyright © 2011 Elsevier Ltd. All rights reserved.

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.

2011 Elsevier B.V. All rights reserved.

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.

Copyright © 2011 Elsevier Inc. All rights reserved.

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.

Copyright © 2011 Elsevier Ltd. All rights reserved.

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.

Copyright © 2011. Published by Elsevier Inc.

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.

© 2011 The Authors. Letters in Applied Microbiology © 2011 The Society for Applied Microbiology.

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.

© 2011 The Authors. Journal of Evolutionary Biology © 2011 European Society For Evolutionary Biology.

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.

Allergy and Clinical Immunology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, 1095 Willowdale Road, Morgantown, WV 26505, USA.

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.

Copyright © 2011 John Wiley & Sons, Ltd.

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.

Copyright © 2011. Published by Elsevier Inc.

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.

Copyright © 2011 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

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.

Copyright © 2011 Elsevier B.V. All rights reserved.

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).

Copyright © 2011 Elsevier B.V. All rights reserved.

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.

Copyright © 2011 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

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.

Copyright © 2011 Elsevier Ltd. All rights reserved.

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.

Copyright © 2011 Elsevier Inc. All rights reserved.

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.

Copyright © 2011 S. Karger AG, Basel.

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.

Copyright © 2011 Elsevier Ltd. All rights reserved.

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.

Copyright © 2011 Elsevier Ltd. All rights reserved.

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.

Copyright © 2011 Wiley Periodicals, Inc.

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.

Copyright © 2011 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

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.

Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

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.

Copyright © 2011 Elsevier GmbH. All rights reserved.

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.

Copyright © 2010 Elsevier Ltd. All rights reserved.

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.

Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

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.

Copyright © 2011 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.

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.

Copyright © 2011 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

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.

Copyright © 2011 Elsevier Ltd. All rights reserved.

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.

Copyright © 2011 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

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.

Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

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.

Copyright © 2011 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

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.

Copyright © 2011 Elsevier B.V. All rights reserved.

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.

© 2011 ISHAM

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.

Copyright © 2011 Elsevier Ltd. All rights reserved.

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.

Copyright © 2011 Elsevier B.V. All rights reserved.

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.

Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

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.

Copyright © 2010 the Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

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.

© 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

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.

© 2011 by Radiation Research Society

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.

© 2011 The Authors. Scandinavian Journal of Immunology © 2011 Blackwell Publishing Ltd.

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.

© 2011 Mount Sinai School of Medicine.

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.

© 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

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.

2011 Elsevier B.V. All rights reserved.

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.

Copyright © 2011 Elsevier Ltd. All rights reserved.

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.

Copyright © 2010 Elsevier B.V. All rights reserved.

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.

© 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

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.

2010 Elsevier B.V. All rights reserved.

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.

Copyright © 2010 Elsevier B.V. All rights reserved.

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.

Copyright © 2011 Elsevier Inc. All rights reserved.

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.

© 2011 The Authors. Photochemistry and Photobiology © 2011 The American Society of Photobiology.

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.

© 2011 John Wiley & Sons A/S.

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.

© 2011 John Wiley & Sons A/S.

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.

© 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

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.

© 2011 The Authors. Letters in Applied Microbiology © 2011 The Society for Applied Microbiology.

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.

© 2011 Blackwell Publishing Ltd.

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.

© 2010 Society for Applied Microbiology and Blackwell Publishing Ltd.

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.

© 2010 The Authors. Journal compilation © 2010 by the Molecular Biology Society of Japan/Blackwell Publishing Ltd.

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.

© 2010 The Authors. Journal compilation © 2010 The Association of Anaesthetists of Great Britain and Ireland.

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.

Copyright © 2010 Elsevier B.V. All rights reserved.

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.

Copyright © 2010 Elsevier Ltd. All rights reserved.

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.

2010 Elsevier B.V. All rights reserved.

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.

Copyright © 2010 SPLF. Published by Elsevier Masson SAS. All rights reserved.

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.

Copyright © 2010 Wiley-Liss, Inc.

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.

Copyright © 2010 Elsevier Ltd. All rights reserved.

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.

© 2011 The Authors. Clinical and Experimental Ophthalmology © 2011 Royal Australian and New Zealand College of Ophthalmologists.

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.

Copyright © 2010 Elsevier Inc. All rights reserved.

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.

Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

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.

Copyright © 2010 Elsevier B.V. All rights reserved.

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.

© 2010 Blackwell Publishing Ltd.

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%.

© 2010 The Authors. Photochemistry and Photobiology © 2010 The American Society of Photobiology.

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.

Copyright © 2011 Elsevier Inc. All rights reserved.

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.

Copyright © 2010 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.

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.

Copyright © 2010 Elsevier Masson SAS. All rights reserved.

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.

© 2011 Blackwell Publishing Ltd.

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.

Copyright © 2010 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.

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.

Copyright © 2010 Elsevier Ltd. All rights reserved.

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.

© Springer Science+Business Media B.V. 2010

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.

Copyright © 2009 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.

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.

Copyright © 2010 Elsevier B.V. All rights reserved.

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.

Copyright © 2010 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.

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.

Copyright © 2010 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.

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.

Copyright © 2009 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.

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.

Copyright © 2010 Elsevier Inc. All rights reserved.

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.

Copyright © 2010 Elsevier Ltd. All rights reserved.

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.

Copyright © 2010 Elsevier Inc. All rights reserved.

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.

© 2010 The Authors. Journal Compilation. The American Society of Photobiology.

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.

© The Royal Society of Chemistry and Owner Societies 2011

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.

Copyright © 2010 Elsevier GmbH. All rights reserved.

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.

Copyright © 2011 Mosby, Inc. All rights reserved.

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.

Copyright © 2010 Elsevier B.V. All rights reserved.

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.

Copyright © 2010 Elsevier Ltd. All rights reserved.

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.

(c) 2009 SETAC.

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.

Copyright © 2010 Elsevier B.V. All rights reserved.

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.

© 2010 Blackwell Publishing Ltd.

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.

Copyright © 2010 Elsevier B.V. All rights reserved.

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.

Copyright © 2010 Elsevier Inc. All rights reserved.

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.

Copyright © 2010 Elsevier Inc. All rights reserved.

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.

Copyright © 2010 Elsevier Inc. All rights reserved.

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.

Copyright © 2010 Elsevier B.V. All rights reserved.

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.

Copyright © 2010 Elsevier Inc. All rights reserved.

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.

Journal compilation © 2010 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. No claim to original French government works.

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.

Copyright © 2010 John Wiley & Sons, Ltd.

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.

Copyright © 2010 John Wiley & Sons, Ltd.

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.

2010 Elsevier Ltd. All rights reserved.

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.

Copyright © 2010 Elsevier B.V. All rights reserved.

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.

© 2010 Japanese Cancer Association.

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.

Copyright © 2010 Elsevier Inc. All rights reserved.

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.

Copyright © 2010 Elsevier B.V. All rights reserved.

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.

Copyright © 2010 Elsevier Ltd. All rights reserved.

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.

Copyright 2010 Elsevier Inc. All rights reserved.

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.

Copyright (c) 2010 Elsevier B.V. All rights reserved.

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.

Crown Copyright 2010. Published by Elsevier B.V. All rights reserved.

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.

© 2009 Society for Applied Microbiology and Blackwell Publishing Ltd.

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.

© 2010 The Authors. Journal Compilation. The American Society of Photobiology.

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.

Copyright © 2010 Elsevier B.V. All rights reserved.

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.

Copyright 2010 Elsevier B.V. All rights reserved.

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.

Copyright © 2010 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

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.

Copyright © 2010 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

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.

Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

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.

© 2010 John Wiley & Sons A/S.

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.

Copyright © 2010 Elsevier B.V. All rights reserved.

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.

Copyright (c) 2010 Elsevier B.V. All rights reserved.

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.

Copyright 2010 Elsevier B.V. All rights reserved.

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.

Copyright 2010 Elsevier Inc. All rights reserved.

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.

Copyright 2010 Elsevier B.V. All rights reserved.

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.

© 2010 Wiley-Liss, Inc.

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.

© 2010 Blackwell Verlag GmbH.

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.

© 2010 The Authors. Journal compilation © 2010 The Society for Applied Microbiology.

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.

Copyright 2010 Elsevier Ltd. All rights reserved.

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.

Copyright 2010 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved.

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.

Copyright (c) 2010 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

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.

Copyright © 2010 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

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.

Copyright © 2011 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

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.

Copyright 2010 Elsevier Inc. All rights reserved.

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.

© 2010 Blackwell Publishing Ltd.

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.

Copyright 2010 Elsevier Ltd. All rights reserved.

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.

Copyright 2010 Elsevier Ltd. All rights reserved.

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.

Copyright 2010 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

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