Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Necroptosis is a programmed cell death pathway that has been shown to be of central pathophysiological relevance in multiple disorders (hepatitis, brain and cardiac ischemia, pancreatitis, viral infection and inflammatory diseases). Necroptosis is driven by two serine threonine kinases, RIPK1 (Receptor Interacting Protein Kinase 1) and RIPK3, and a pseudo-kinase MLKL (Mixed Lineage Kinase domain-Like) associated in a multi-protein complex called necrosome. In order to find new inhibitors for use in human therapy, a chemical library containing highly diverse chemical structures was screened using a cell-based assay. The compound 6E11, a natural product derivative, was characterized as a positive hit. Interestingly, this flavanone compound: inhibits necroptosis induced by death receptors ligands TNF-α (Tumor Necrosis Factor) or TRAIL (TNF-Related Apoptosis-Inducing Ligand); is an extremely selective inhibitor, among kinases, of human RIPK1 enzymatic activity with a nM Kd; has a non-ATP competitive mode of action and a novel putative binding site; is weakly cytotoxic towards human primary blood leukocytes or retinal pigment epithelial cells at effective concentrations; protects human aortic endothelial cells (HAEC) from cold hypoxia/reoxygenation injury more effectively than necrostatin-1 (Nec-1) and Nec-1s. Altogether, these data demonstrate that 6E11 is a novel potent small molecular inhibitor of RIPK1-driven necroptosis.
ISSN: 2045-2322

hal-01616456
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01616456
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01616456/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01616456/file/s41598-017-12788-4.pdf
DOI : 10.1038/s41598-017-12788-4

Éditeur(s) : HAL CCSD American Chemical Society
Résumé : Ants have evolved venoms rich in peptides and proteins used for predation, defense, and communication. However, they remain extremely understudied due to the minimal amount of venom secreted by each ant. The present study investigated the differences in the proteome and peptidome of the venom from the bullet ant, Paraponera clavata. Venom samples were collected from a single colony either by manual venom gland dissection or by electrical stimulation and were compared using proteomic methods. Venom proteins were separated by 2D-PAGE and identified by nanoLC-ESI-QTOF MS/MS. Venom peptides were initially separated using C18 reversed-phase high-performance liquid chromatography, then analyzed by MALDI-TOF MS. The proteomic analysis revealed numerous proteins that could be assigned a biological function (total 94), mainly as toxins, or roles in cell regulation and transport. This investigation found that ca. 73% of the proteins were common to venoms collected by the two methods. The peptidomic analysis revealed a large number of peptides (total 309) but with <20% shared by the two collection methods. There was also a marked difference between venoms obtained by venom gland dissection from different ant colonies. These findings demonstrate the rich composition and variability of P. clavata venom.
ISSN: 1535-3893

hal-01603415
https://hal.archives-ouvertes.fr/hal-01603415
DOI : 10.1021/acs.jproteome.6b00948
PRODINRA : 406775
PUBMED : 28118015

Éditeur(s) : HAL CCSD
Résumé : International audience
Necroptosis is a regulated form of cell death involved in several disease models including in particular liver diseases. Receptor-interacting protein kinases, RIPK1 and RIPK3, are the main serine/threonine kinases driving this cell death pathway. We screened a noncommercial, kinase-focused chemical library which allowed us to identify Sibiriline as a new inhibitor of necroptosis induced by tumor necrosis factor (TNF) in Fas-associated protein with death domain (FADD)-deficient Jurkat cells. Moreover, Sib inhibits necroptotic cell death induced by various death ligands in human or mouse cells while not protecting from caspase-dependent apoptosis. By using competition binding assay and recombinant kinase assays, we demonstrated that Sib is a rather specific competitive RIPK1 inhibitor. Molecular docking analysis shows that Sib is trapped closed to human RIPK1 adenosine triphosphate-binding site in a relatively hydrophobic pocket locking RIPK1 in an inactive conformation. In agreement with its RIPK1 inhibitory property, Sib inhibits both TNF-induced RIPK1-dependent necroptosis and RIPK1-dependent apoptosis. Finally, Sib protects mice from concanavalin A-induced hepatitis. These results reveal the small-molecule Sib as a new RIPK1 inhibitor potentially of interest for the treatment of immune-dependent hepatitis. © 2017 Federation of European Biochemical Societies
ISSN: 1742464X

hal-01616420
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01616420
DOI : 10.1111/febs.14176
PUBMED : 28715128

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
ISSN: 0933-7407

hal-01632369
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01632369

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Estrogens are known as steroid hormones affecting the brain in many different ways and a wealth of data now document effects on neurogenesis. Estrogens are provided by the periphery but can also be locally produced within the brain itself due to local aromatization of circulating androgens. Adult neurogenesis is described in all vertebrate species examined so far, but comparative investigations have brought to light differences between vertebrate groups. In teleost fishes, the neurogenic activity is spectacular and adult stem cells maintain their mitogenic activity in many proliferative areas within the brain. Fish are also quite unique because brain aromatase expression is limited to radial glia cells, the progenitor cells of adult fish brain. The zebrafish has emerged as an interesting vertebrate model to elucidate the cellular and molecular mechanisms of adult neurogenesis, and notably its modulation by steroids. The main objective of this review is to summarize data related to the functional link between estrogens production in the brain and neurogenesis in fish. First, we will demonstrate that the brain of zebrafish is an endogenous source of steroids and is directly targeted by local and/or peripheral steroids. Then, we will present data demonstrating the progenitor nature of radial glial cells in the brain of adult fish. Next, we will emphasize the role of estrogens in constitutive neurogenesis and its potential contribution to the regenerative neurogenesis. Finally, the negative impacts on neurogenesis of synthetic hormones used in contraceptive pills production and released in the aquatic environment will be discussed
ISSN: 0960-0760

hal-01174214
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01174214
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01174214/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01174214/file/Steroid%20modulation%20of%20neurogenesis.pdf
DOI : 10.1016/j.jsbmb.2015.06.011

Éditeur(s) : HAL CCSD Spandidos Publications
Résumé : International audience
ISSN: 1107-3756

hal-01122662
https://hal.archives-ouvertes.fr/hal-01122662

Éditeur(s) : Elsevier Sci Ltd
Résumé : A detailed morphological analysis of the outer shelf and continental slope of the Western Gulf of Lion is presented, based on swath bathymetry data together with sub-bottom profiles and high resolution seismic reflection profiles. These data reveal two main erosive features, of very different dimensions: the axial incision and the canyon's major valley. The height of axial incisions' flanks with respect to the canyon deepest point (the thalweg) ranges from 40 to 150 m. It creates a small axial erosive path within the canyon's major valley, which is typically bounded by flanks of more than 700 m in height. We interpret the axial incision observed in the sea floor as the imprint of turbidity currents that eroded the floor of canyons during phases of connection to rivers (hyperpycnal turbidity current). Such currents are most likely to have formed during the Last Glacial Maximum (LGM) as both proximity of the shoreline (due to the lowstand of sea level) and high detrital sediment supply (due to glacial abrasion upstream) increased the flow of sediments delivered to the canyon heads. Fossil axial incisions, observed in seismic lines, are related to equivalent conditions. The axial incision, however, has a key influence on canyon evolution as it triggers mass wasting of different sizes that affect the canyon's major valley (head and flanks). We interpret the geometry of the canyon's major valley as the result of recurrent activity of axial incisions. These periods of activity occurred during low sea levels at glacial maxima and show a cyclicity of 100,000 years for the last 400,000 years.
Marine And Petroleum Geology (0264-8172) (Elsevier Sci Ltd), 2005-06 , Vol. 22 , N. 6-7 , P. 805-826

Droits : 2005 Elsevier Ltd All rights reserved
http://archimer.ifremer.fr/doc/2005/publication-353.pdf
DOI:10.1016/j.marpetgeo.2005.03.011
http://archimer.ifremer.fr/doc/00000/353/

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
The CoPanFlu-France cohort of households was set up in 2009 to study the risk factors for infection by the pandemic influenza virus (H1N1pdm) in the French general population. The authors developed an integrative data-driven approach to identify individual, collective and environmental factors associated with the post-seasonal serological H1N1pdm geometric mean titer, and derived a nested case-control analysis to identify risk factors for infection during the first season. This analysis included 1377 subjects (601 households). The GMT for the general population was 47.1 (95% confidence interval (CI): 45.1, 49.2). According to a multivariable analysis, pandemic vaccination, seasonal vaccination in 2009, recent history of influenza-like illness, asthma, chronic obstructive pulmonary disease, social contacts at school and use of public transports by the local population were associated with a higher GMT, whereas history of smoking was associated with a lower GMT. Additionally, young age at inclusion and risk perception of exposure to the virus at work were identified as possible risk factors, whereas presence of an air humidifier in the living room was a possible protective factor. These findings will be interpreted in light of the longitudinal analyses of this ongoing cohort.
ISSN: 1932-6203

Droits : http://creativecommons.org/licenses/by-sa/
hal-01122215
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01122215
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01122215/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01122215/file/journal.pone.0060127.pdf
PUBMED : 23613718

Éditeur(s) : HAL CCSD Taylor & Francis
Résumé : International audience
The functional organization of the circadian system and the location of the main circadian oscillators vary through phylogeny. Present study investigates by in situ hybridization the anatomical location of the clock gene gPer1b in forebrain and midbrain, pituitary, and in two peripheral locations, the anterior intestine and liver, in a teleost fish, the goldfish (Carassius auratus). Moreover, the daily expression profiles of this gene were also studied by quantitative Real Time-PCR. Goldfish were maintained under a 12L–12D photoperiod and fed daily at 2 h after lights were switched on. A wide distribution of gPer1b mRNA in goldfish brain and pituitary was found in telencephalon, some hypothalamic nuclei (including the homologous to mammalian SCN), habenular nucleus, optic tectum, cerebellum and torus longitudinalis. Moreover, gPer1b expression was observed, for the first time in teleosts, in the pituitary, liver and anterior intestine. Day/night differences in gper1b mRNA abundance were found by in situ hybridization, with higher signal at nighttime that correlates with the results obtained by RT-PCR, where a rhythmic gPer1b expression was found in all tissues with acrophases at the end of the night. Amplitudes of gper1b rhythms vary among tissues, being higher in liver and intestine than in the brain, maybe because different cues entrain clocks in these locations. These results support the existence of functional clocks in many central and peripheral locations in goldfish coordinated, ticking at the same time
ISSN: 0742-0528

hal-01197353
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01197353
DOI : 10.3109/07420528.2015.1049615
PUBMED : 26171989

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : National audience
Introduction L’objectif de cette étude est de disposer de données qualitatives et quantitatives sur la contamination de l’environnement intérieur hospitalier, microbiologique et chimique, afin d’évaluer l’exposition du personnel, des visiteurs et des patients et la variabilité spatio-temporelle de la contamination. Méthodes L’étude s’est déroulée dans différents lieux des CHU de Rennes et de Nancy : hall d’accueil, salle de soins infirmiers, salle de réveil post-opératoire, chambre d’un patient, unité de désinfection des endoscopes, laboratoire de parasitologie et salle de découpe de plâtres. Deux campagnes de prélèvement ont eu lieu en été 2014 et en hiver 2015. Les méthodes de prélèvement étaient nombreuses et complémentaires (Fig. 1). L’analyse des données a été réalisée sous IBM SPSS grâce au test de Mann-Whitney et le coefficient de corrélation de Pearson. Résultats Les concentrations d’aldéhydes, de composés organiques volatils (COV) et semi-volatils étaient faibles à très faibles dans les 2 établissements. Étaient détectables, mais sans différences globales entre les 2 établissements : la contamination fongique (m = 226 UFC/m3 ; p = 0,97) ou bactérienne (m = 352 UFC/m3 ; p = 0,14), les particules PM2,5 (m = 2,1 μg/m3 ; p = 0,97) et PM10 (m = 6,6 μg/m3 ; p = 0,84). Sur le plan saisonnier, la contamination fongique était plus importante en été pour les 2 établissements (p = 0,002). La contamination bactérienne ne varie pas significativement entre les locaux (p = 0,14) contrairement à la contamination fongique (p = 0,02) et particulaires PM2,5 (p = 0,01) ou PM10 (p = 0,01). Cette dernière est plus importante dans le hall (m = 879 UFC/m3), le laboratoire de parasitologie (m = 333 UFC/m3) et la salle de plâtre (m = 310 UFC/m3). Nous ne retrouvons pas de corrélation significative entre le nombre de personnes, le taux de CO2, l’humidité relative et le dénombrement bactérien ou fongique. Néanmoins nous retrouvons une relation forte entre la température du local et la contamination bactérienne (r = 0,7, p = 0,008) ou la contamination fongique (r = 0,56, p = 0,045) d’une part, et entre la contamination fongique et les PM10 (r = 0,52, p = 0,022) d’autre part. Conclusion Notre étude montre une très faible contamination par les aldéhydes, COV et sCOV comparativement à d’autres lieux publics. La forte variabilité spatio-temporelle de la contamination fongique et particulaire est liée à la saison, à l’activité et à la ventilation
ISSN: 1156-5233

hal-01334070
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01334070
DOI : 10.1016/j.mycmed.2016.04.026