A Benchmark of Parametric Methods for Horizontal Transfers Detection

Horizontal gene transfer (HGT) has appeared to be of importance for prokaryotic species evolution. As a consequence numerous parametric methods, using only the information embedded in the genomes, have been designed to detect HGTs. Numerous reports of incongruencies in results of the different methods applied to the same genomes were published. The use of artificial genomes in which all HGT parameters are controlled allows testing different methods in the same conditions. The results of this benchmark concerning 16 representative parametric methods showed a great variety of efficiencies. Some methods work very poorly whatever the type of HGTs and some depend on the conditions or on the metrics used. The best methods in terms of total errors were those using tetranucleotides as criterion for the window methods or those using codon usage for gene based methods and the Kullback-Leibler divergence metric. Window methods are very sensitive but less specific and detect badly lone isolated gene. On the other hand gene based methods are often very specific but lack of sensitivity. We propose using two methods in combination to get the best of each category, a gene based one for specificity and a window based one for sensitivity

Lead, mercury, and selenium alter physiological functions in wild caimans (Caiman crocodilus)

International audienceEnvironmental contaminants affect ecosystems worldwide and have deleterious effects on biota. Non-essentialmercury (Hg) and lead (Pb) concentrations are well documented in some taxa and are described to cause multipledetrimental effects on human and wildlife. Additionally, essential selenium (Se) is known to be toxic at highconcentrations but, at lower concentrations, Se can protect organisms against Hg toxicity. Crocodilians areknown to bioaccumulate contaminants. However, the effects of these contaminants on physiological processesremain poorly studied. In the present study, we quantified Hg, Pb and Se concentrations in spectacled caimans(Caiman crocodilus) and investigated the effects of these contaminants on several physiological processes linkedto osmoregulatory, hepatic, endocrine and renal functions measured through blood parameters in 23 individuals.Mercury was related to disruption of osmoregulation (sodium levels), hepatic function (alkaline phosphataselevels) and endocrine processes (corticosterone levels). Lead was related to disruption of hepatic functions(glucose and alanine aminotransferase levels). Selenium was not related to any parameters, but the Se:Hg molarratio was positively related to the Na+ and corticosterone concentrations, suggesting a potential protective effectagainst Hg toxicity. Overall, our results suggest that Hg and Pb alter physiological mechanisms in wild caimansand highlight the need to thoroughly investigate the consequences of trace element contamination incrocodilians

Low-dose interleukin-2 fosters a dose-dependent regulatory T cell tuned milieu in T1D patients

International audienceMost autoimmune diseases (AID) are linked to an imbalance between autoreactive effector T cells (Teffs) and regulatory T cells (Tregs). While blocking Teffs with immunosuppression has long been the only therapeutic option, activating/expanding Tregs may achieve the same objective without the toxicity of immunosuppression. We showed that low-dose interleukin-2 (ld-IL-2) safely expands/activates Tregs in patients with AID, such HCV-induced vasculitis and Type 1 Diabetes (T1D). Here we analyzed the kinetics and dose-relationship of IL-2 effects on immune responses in T1D patients. Ld-IL-2 therapy induced a dose-dependent increase in CD4+Foxp3+ and CD8+Foxp3+ Treg numbers and proportions, the duration of which was markedly dose-dependent. Tregs expressed enhanced levels of activation markers, including CD25, GITR, CTLA-4 and basal pSTAT5, and retained a 20-fold higher sensitivity to IL-2 than Teff and NK cells. Plasma levels of regulatory cytokines were increased in a dose-dependent manner, while cytokines linked to Teff and Th17 inflammatory cells were mostly unchanged. Global transcriptome analyses showed a dose-dependent decrease in immune response signatures. At the highest dose, Teff responses against beta-cell antigens were suppressed in all 4 patients tested. These results inform of broader changes induced by ld-IL-2 beyond direct effects on Tregs, and relevant for further development of ld-IL-2 for therapy and prevention of T1D, and other autoimmune and inflammatory diseases