Les tiques dures autre qu'Ixodes Ricinus dans le marais breton-vendéen (étude de leur distribution spatio-temporelle et des facteurs influant sur leur présence)

Cette étude a été menée dans 7 exploitations bovines situées dans le marais Breton-Vendéen (à l ouest de la France) dans lesquelles des pâtures (en majorité dans le marais) ont été sélectionnées. Des prélèvements de tiques par la méthode du drapeau ont été effectués à trois reprises dans chaque pâture entre avril et juin 2009. Le marais est apparu comme un milieu favorable à l implantation de Dermacentor marginatus, Ixodes ricinus et Haemaphysalis punctata. Dermacentor reticulatus a été collecté plus marginalement. Le marais se montre plus sensible à l assèchement que le bocage, ce qui se traduit par une saisonnalité des tiques différente dans ces deux milieux. Relativement peu de facteurs susceptibles d influer sur la présence des tiques sont apparus comme réellement prédictifs. Ces facteurs, à influence faible, semblent agir sur la présence des hôtes dans le marais, et donc indirectement sur les populations de tiques.TOULOUSE-EN Vétérinaire (315552301) / SudocNANTES-Ecole Nat.Vétérinaire (441092302) / SudocSudocFranceF

Identification of ebselen as a potent inhibitor of insulin degrading enzyme by a drug repurposing screening

International audienceInsulin-degrading enzyme, IDE, is a metalloprotease implicated in the metabolism of key peptides such as insulin, glucagon, β-amyloid peptide. Recent studies have pointed out its broader role in the cell physiology. In order to identify new drug-like inhibitors of IDE with optimal pharmacokinetic properties to probe its multiple roles, we ran a high-throughput drug repurposing screening. Ebselen, cefmetazole and rabeprazole were identified as reversible inhibitors of IDE. Ebselen is the most potent inhibitor (IC50 (insulin) = 14 nM). The molecular mode of action of ebselen was investigated by biophysical methods. We show that ebselen induces the disorder of the IDE catalytic cleft, which significantly differs from the previously reported IDE inhibitors. IDE inhibition by ebselen can explain some of its reported activities in metabolism as well as in neuroprotection

Modulators of hERAP2 discovered by High-Throughput Screening

International audienceEndoplasmic reticulum aminopeptidase 2, ERAP2, is an emerging pharmacological target in cancer immunotherapy and control of autoinflammatory diseases, as it is involved in antigen processing. It has been linked to the risk of development of spondyloarthritis, and it associates with the immune infiltration of tumours and strongly predicts the overall survival for patients receiving check-point inhibitor therapy. While some selective inhibitors of its homolog ERAP1 are available, no selective modulator of ERAP2 has been disclosed so far. In order to identify such compounds, we screened an in-house focused library of 1920 compounds designed to target metalloenzymes. Structure-Activity Relationships and docking around two hits led to the discovery of selective inhibitors of ERAP2. Amid those, some bind to yet untapped amino-acids in the S1 pocket. Importantly, we disclose also the first activator of small substrates hydrolysis by ERAP2. Inhibitors and activators identified in this study could serve as useful starting points for optimization

Reproducibility of fluorescent expression from engineered biological constructs in E. coli

We present results of the first large-scale interlaboratory study carried out in synthetic biology, as part of the 2014 and 2015 International Genetically Engineered Machine (iGEM) competitions. Participants at 88 institutions around the world measured fluorescence from three engineered constitutive constructs in E. coli. Few participants were able to measure absolute fluorescence, so data was analyzed in terms of ratios. Precision was strongly related to fluorescent strength, ranging from 1.54-fold standard deviation for the ratio between strong promoters to 5.75-fold for the ratio between the strongest and weakest promoter, and while host strain did not affect expression ratios, choice of instrument did. This result shows that high quantitative precision and reproducibility of results is possible, while at the same time indicating areas needing improved laboratory practices.Peer reviewe