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[
Worm Breeder's Gazette,
2003]
Previous work in our lab demonstrated that exposing C. elegans to the metabolic inhibitor sodium azide induces thermotolerance and the expression of the stress proteins
hsp70 and
hsp16 (Massie et al., 2003). We have continued our efforts to characterize further the physiological response of worms to sodium azide exposure. We sought to determine what effect, if any, sodium azide exposure had on the lifespan of the animal as well as on its reproductive viability since azide continues to be the anesthetic of choice for C. elegans researchers. In four separate double-blinded experiments consisting of 57 control and 50 experimental worms total (L1 and L2), a one hour exposure to sodium azide resulted in animals consistently showing a 7.1% decrease in lifespan. In our lab, the average age at death of control worms was 11.20.5 days, as compared to 10.41 days for azide treated worms (see Figure I). A two-tailed Z score demonstrated a confidence interval of p<0.001. We are also interested in determining whether azide exposure had an effect on the reproductive viability of the animal. For the reproductive viability study, we were concerned that the manual transfer of L1s and L2s may be quite traumatic for those animals and could be affecting their reproductive viability. As such, we decided to use L3 and L4 animals. Three separate experiments using L3 and L4 experimental worms (14 control and 15 azide exposed), failed to demonstrate a consistent effect on brood size or the number of days that the animals laid eggs. Our results demonstrate that the use of sodium azide as an anesthetic is not without immediate physiological consequences for the animal in terms of stress protein induction and a shortening of its lifespan.
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[
Eur J Clin Microbiol Infect Dis,
2013]
Methicillin-resistant Staphylococcus aureus (MRSA) strains from different geographic areas have different genetic backgrounds, suggesting independent clonal evolutions. To better understand the virulence of MRSA strains and the relationship to their clonal and geographic origins, we undertook an analysis of epidemiologic, molecular, and virulence characteristics of a large number of MRSA isolates from geographically diverse origins, in a Caenorhabditis elegans infection model. A total of 99 MRSA isolates collected between 1993 and 2010 at the Geneva University Hospitals from diverse global origins were characterized with Panton-Valentine leukocidin (PVL), toxic shock syndrome toxin (TSST), accessory gene regulator (agr) group, staphylococcal cassette chromosome mec (SCCmec), S. aureus protein A (spa), multilocus sequence typing (MLST), and pulsed-field gel electrophoresis (PFGE) typing. Epidemiologic data were provided from clinical records. The bacterial virulence was tested in a C. elegans host model. The inter-relationships of epidemiological/molecular characteristics in association with nematocidal activities were analyzed with univariate and two-factor analysis of variance (ANOVA). Community-associated MRSA (CA-MRSA) strains were more virulent than hospital-associated MRSA (HA-MRSA), with higher nematocidal activities in CA-MRSA strains (0.776 vs. 0.506, p = 0.0005). All molecular characteristics (PVL, TSST, spa, SCCmec, MLST, and PFGE types) showed a significant association with nematocidal activities on univariate analysis (p < 0.005). PVL was not a significant predictor after adjusting for genomic backgrounds using spa, MLST, or PFGE typing. The dominant CA-MRSA strains in North America showed higher nematocidal activities than strains from other regions (p < 0.0001). Strains with global origins containing distinct genetic backgrounds have different virulence in the C. elegans model. Nematocidal activities were most highly correlated with SCCmec, spa, MLST, and PFGE typing, suggesting that genomic background rather than a single exotoxin characteristic was the most discriminating predictor of virulence.
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[
Epigenomics,
2022]
In this interview, Professor Susan Gasser speaks with Storm Johnson, commissioning editor for <i>Epigenomics</i>, on her research on genome stability, epigenetic regulation and chromatin organization, as well as her work supporting women in research. Susan Gasser completed her BA at the University of Chicago, with an honors thesis in biophysics, and her PhD in biochemistry at the University of Basel in 1982, with Gottfried Schatz. She was a postdoc with Ulrich Laemmli at the University of Geneva, which initiated her career-long interest in chromosomes and chromatin structure. She established her own laboratory at the Swiss Institute for Experimental Cancer Research (ISREC) in 1986, focusing on chromatin organization in budding yeast, combining genetics, microscopy and biochemical approaches to understanding silent chromatin and telomeres. In 2001, she was named professor of molecular biology at the University of Geneva and expanded her laboratory's pioneering use of high-resolution time-lapse fluorescence microscopy to study single locus dynamics in the nucleus. From 2004 to 2019, Susan was the Director of the Friedrich Miescher Institute for Biomedical Research in Basel, where she also led a research group until the end of 2020. In Basel, she extended her research interests into heterochromatin in <i>Caenorhabditiselegans</i>. Her laboratory identified the mechanisms that position tissue-specific genesin the nuclei ofembryos and ofdifferentiated tissues, combining high throughput molecular analyses with cell biology to determine structure-function relationships in chromatin. Since January 2021, Susan Gasser has been <i>professor invite</i> at the University of Lausanne and Director of the ISREC Foundation, where she is helping shape the new Agora Institute of Translational Cancer Research. She was elected to the Academie de France, Leopoldina, European Molecular Biology Organization (EMBO), American Association for the Advancement of Science and Swiss Academy of Medical Sciences, and she received the French National Institute of Health and Medical Research (INSERM) International Prize in 2011, the Federation of European Biochemical Societies | EMBO Women in Science Award in 2012, the Weizmann Institute Women in Science Award in 2013 and honorary doctorates from the University of Lausanne, the University of Fribourg and Charles University in Prague. In Switzerland, she was the recipient of the Friedrich Miescher Award, the National Latsis Prize and the Otto Naegeli Award for the promotion of medical research. She participates in numerous review boards and advisory committees in Switzerland, across Europe and in Japan; she currently serves on the governing board of the Swiss Federal Institutes of Technology and the Swiss Science Council. From 2000 to 2004, she was vice chairperson, then chairperson of the EMBO Council. Susan led the Gender Committee of the Swiss National Science Foundation from 2014 to 2019 and initiated the Swiss National Science FoundationPrima program for the Promotion of women in academia. She has actively promotedthe careers of women scientists in Europe and Japan.
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Pennington PR, Heistad RM, Nyarko JNK, Barnes JR, Bolanos MAC, Parsons MP, Knudsen KJ, De Carvalho CE, Leary SC, Mousseau DD, Buttigieg J, Maley JM, Quartey MO
[
Sci Rep,
2021]
The pool of -Amyloid (A) length variants detected in preclinical and clinical Alzheimer disease (AD) samples suggests a diversity of roles for A peptides. We examined how a naturally occurring variant, e.g. A(1-38), interacts with the AD-related variant, A(1-42), and the predominant physiological variant, A(1-40). Atomic force microscopy, Thioflavin T fluorescence, circular dichroism, dynamic light scattering, and surface plasmon resonance reveal that A(1-38) interacts differently with A(1-40) and A(1-42) and, in general, A(1-38) interferes with the conversion of A(1-42) to a -sheet-rich aggregate. Functionally, A(1-38) reverses the negative impact of A(1-42) on long-term potentiation in acute hippocampal slices and on membrane conductance in primary neurons, and mitigates an A(1-42) phenotype in Caenorhabditis elegans. A(1-38) also reverses any loss of MTT conversion induced by A(1-40) and A(1-42) in HT-22 hippocampal neurons and APOE 4-positive human fibroblasts, although the combination of A(1-38) and A(1-42) inhibits MTT conversion in APOE 4-negative fibroblasts. A greater ratio of soluble A(1-42)/A(1-38) [and A(1-42)/A(1-40)] in autopsied brain extracts correlates with an earlier age-at-death in males (but not females) with a diagnosis of AD. These results suggest that A(1-38) is capable of physically counteracting, potentially in a sex-dependent manner, the neuropathological effects of the AD-relevant A(1-42).
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[
Worm Breeder's Gazette,
2003]
Wormgenes is a new resource for C.elegans offering a detailed summary about each gene and a powerful query system.
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[
Front Pharmacol,
2020]
Oligomeric assembly of Amyloid- (A) is the main toxic species that contribute to early cognitive impairment in Alzheimer's patients. Therefore, drugs that reduce the formation of A oligomers could halt the disease progression. In this study, by using transgenic <i>Caenorhabditis elegans</i> model of Alzheimer's disease, we investigated the effects of frondoside A, a well-known sea cucumber <i>Cucumaria frondosa</i> saponin with anti-cancer activity, on A aggregation and proteotoxicity. The results showed that frondoside A at a low concentration of 1 M significantly delayed the worm paralysis caused by A aggregation as compared with control group. In addition, the number of A plaque deposits in transgenic worm tissues was significantly decreased. Frondoside A was more effective in these activities than ginsenoside-Rg3, a comparable ginseng saponin. Immunoblot analysis revealed that the level of small oligomers as well as various high molecular weights of A species in the transgenic <i>C. elegans</i> were significantly reduced upon treatment with frondoside A, whereas the level of A monomers was not altered. This suggested that frondoside A may primarily reduce the level of small oligomeric forms, the most toxic species of A. Frondoside A also protected the worms from oxidative stress and rescued chemotaxis dysfunction in a transgenic strain whose neurons express A. Taken together, these data suggested that low dose of frondoside A could protect against A-induced toxicity by primarily suppressing the formation of A oligomers. Thus, the molecular mechanism of how frondoside A exerts its anti-A aggregation should be studied and elucidated in the future.
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[
International Journal of Developmental Biology,
1998]
Pleiotropy , a situation in which a single gene influences multiple phenotypic tra its, can arise in a variety of ways. This paper discusses possible underlying mechanisms and proposes a classification of the various phenomena involved.
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[
Curr Biol,
2011]
Recent work on a Caenorhabditis elegans transmembrane ATPase reveals a central role for the aminophospholipid phosphatidylethanolamine in the production of a class of extracellular vesicles.
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[
Naturwissenschaften,
2004]
Animals respond to signals and cues in their environment. The difference between a signal (e.g. a pheromone) and a cue (e.g. a waste product) is that the information content of a signal is subject to natural selection, whereas that of a cue is not. The model free-living nematode Caenorhabditis elegans forms an alternative developmental morph (the dauer larva) in response to a so-called 'dauer pheromone', produced by all worms. We suggest that the production of 'dauer pheromone' has no fitness advantage for an individual worm and therefore we propose that 'dauer pheromone' is not a signal, but a cue. Thus, it should not be called a pheromone.
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[
J Antibiot (Tokyo),
1990]
Cochlioquinone A, isolated from the fungus Helminthosporium sativum, was found to have nematocidal activity. Cochlioquinone A is a competitive inhibitor of specific [3H]ivermectin binding suggesting that cochlioquinone A and ivermectin interact with the same membrane receptor.