Éditeur(s) : HAL CCSD Impact journals
Résumé : International audience
Interleukin (IL)-33 has been recently reported to be strongly pro-fibrogenic in various models of liver disease. Our aim was to study the role of endogenous IL-33 in a diet-induced model of steatohepatitis. IL-33 deficient mice and wild type (WT) littermates received a high-fat diet (HFD), or a standard diet for 12 weeks. The HFD-induced steatohepatitis was associated with an upregulation of IL-33 transcripts and protein. An insulin tolerance test revealed lower systemic insulin sensitivity in IL33-/-HFD mice than in WT-HFD mice. Nevertheless, IL-33 deficiency did not affect the severity of liver inflammation by histological and transcriptomic analyses, nor the quantity of liver fibrosis. Livers from HFD mice had more myeloid populations, markedly fewer NKT cells and higher proportion of ST2+ Treg cells and ST2+ type 2 innate lymphoid cells (ILC2), all unaffected by IL-33 deficiency. In conclusion, deficiency of endogenous IL-33 does not affect the evolution of experimental diet-induced steatohepatitis towards liver fibrosis.
ISSN: 1949-2553

hal-01578584
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01578584
DOI : 10.18632/oncotarget.18335
PUBMED : 28611297

Éditeur(s) : HAL CCSD Landes Bioscience
Résumé : International audience
In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
Autophagy

hal-00735751
https://hal.archives-ouvertes.fr/hal-00735751
PUBMED : 22966490

Éditeur(s) : 3e Rencontres Scientifiques Internationales du contrat de baie de la rade de Brest. Brest 14-16 mars 1995
Résumé : Aquaculture production of scallop has been identified by a series of technical operations during the past ten years programme under a partnership involving the fishermen organizations with regional and national grants. 3 million juveniles have been produced annually, giving a potential recapture by fishing of 100 to 120 tonnes 3 years later. Results in terms of technical and economical approach have pointed out the principal unknown factors responsable for high costs. 7he pilot programme aims to increase the production to reach a level of 5 million juveniles to support the fishery of the rade de Brest and induce new management of the resources. Two priorities were selected, control of the reproduction in the hatchery to obtain reliable larval and postlarval rearing during a larger period of the year, mainly during summer, and improvement of survival rate of the juveniles by minimizing stress when manipulating the animals. But biological and ecological mechanisms are still poorly understoodfor scallop and generally bibvalves and the last two years have shown unchanged results. The technical pathways shows interactions between the different steps of the production of juveniles where different teams operate separately. Management of the livestock has to be developed to increase the survival rate by better breeding but also to reduce the loss by adapted and coordinated practices. Recapture results indicate that fishery strategies depend also on the production of juvenile, and could orientate the management of the hatchery.

Droits : info:eu-repo/semantics/openAccess
http://archimer.ifremer.fr/doc/00044/15494/12860.pdf
http://archimer.ifremer.fr/doc/00044/15494/

Éditeur(s) : HAL CCSD Société Géologique de France
Résumé : International audience
The seaward extension of onshore formations and structures were previously almost unknown in Provence. The interpretation of 2D high-resolution marine seismic profiles together with the integration of sea-bottom rock samples provides new insights into the stratigraphic, structural and paleogeographic framework of pre-Messinian Salinity Crisis (MSC) deposits of the Provence continental shelf. Seven post-Jurassic seismic units have been identified on seismic profiles, mapped throughout the offshore Provence area and correlated with the onshore series. The studied marine surface and sub-surface database provided new insights into the mid and late Cretaceous paleogeography and structural framework as well as into the syn-and post-rift deformation in Provence. Thick (up to 2000 m) Aptian-Albian series whose deposition is controlled by E-W-trending faults are evidenced offshore. The occurrence and location of the Upper Cretaceous South-Provence basin is confirmed by the thick (up to 1500 m) basinal series downlaping the Aptian-Albian unit. This basin was fed in terrigenous sediments by a southern massif (" Massif Méridional ") whose present-day relict is the Paleozoic basement and its sedimentary cover from the Sicié imbricate. In the bay of Marseille, thick syn-rift (Rupelian to Aquitanian) deposition occurred (>1000 m). During the rifting phase, syn-sedimentary deformations consist of dominant N040 to N060 sub-vertical faults with a normal component and N050 drag-synclines and anticlines. The syn-rift and early post-rift units (Rupelian to early Burdigalian) are deformed and form a set of E-W-trending en echelon folds that may result from sinistral strike-slip reactivation of N040 to N060 normal faults during a N-S com-pressive phase of early-to-mid Burdigalian age (18-20 Ma). Finally, minor fault reactivation and local folding affect post-rift deposits within a N160-trending corridor localized south of La Couronne, and could result from a later, post-Burdigalian and pre-Pliocene compressive phase.
Cadre tectonostratigraphique des formations anté-pliocènes du plateau continental de Provence (golfe du Lion oriental, SE France) Mots-clés. – Géologie marine, Tectonostratigraphie, Stratigraphie sismique, Paléogéographie crétacée, Rifting oligo-miocène, Compression post-rift Résumé. – Le prolongement en mer des formations et des structures provençales était jusqu'alors largement inconnu.L'interprétation de profils de sismique-réflexion marine 2D et l'intégration de dragages et carottages du fond-marin ont permis d'apporter des éléments nouveaux concernant le cadre stratigraphique, structural et paléogéographique des dé-pôts anté-Messiniens du plateau continental de Provence. Sept unités sismiques post-jurassiques ont été identifiées sur les profils sismiques, cartographiées à travers le plateau continental et corrélées avec les séries affleurant à terre. Une épaisse unité apto-albienne (jusqu'à 2000 m) dont le dépôt est contrôlé par des failles E-W a été mise en évidence en mer. L'existence d'un bassin subsident au Crétacé supérieur sur le plateau continental de Provence a été confirmée par le développement d'une épaisse série de bassin (jusqu'à 1500 m) reposant en downlap sur l'Apto-Albien. Le socle mé-tamorphique de l'écaille de Sicié et sa couverture sédimentaire peut être considéré comme une relique allochtone du « Massif Méridional » ayant alimenté le Bassin sud-provençal en éléments terrigènes au Crétacé supérieur. Dans la rade de Marseille, une épaisse unité syn-rift (Rupélien à Aquitanien) a été mise en évidence (>1000 m), structurée en une série de synformes en échelon d'axe E-W et affectée par des failles d'orientation dominante N040 à N060. Sur le flanc sud des synformes, la formation de plis d'axe N050 est associée à une déformation syn-sédimentaire. La formation des synformes en échelon d'axe E-W résulterait d'une réactivation en décrochement des failles N040 à N060 pendant une phase de compression N-S dont l'âge est compris entre le Burdigalien inférieur et moyen (18-20 Ma). Enfin, les dépôts post-rift sont affectés par des déformations mineures (réactivation de failles et plis associés), le long d'un couloir d'orientation N160 à l'ouest de la baie de Marseille, attribuables à une phase de compression post-burdigalienne et anté-pliocène.
ISSN: 0037-9409

hal-01463727
https://hal-amu.archives-ouvertes.fr/hal-01463727
https://hal-amu.archives-ouvertes.fr/hal-01463727/document
https://hal-amu.archives-ouvertes.fr/hal-01463727/file/Fournier_et_al_Provence_2016.pdf
DOI : 10.2113/gssgfbull.187.4-5.187

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Chlordecone is a persistent organochlorine pesticide that was used in the French West Indies until the early 1990s for banana weevil borer control. Human exposure to this chemical in this area still occurs nowadays due to consumption of contaminated food. Although adverse effects on neurodevelopment, including tremors and memory deficits, have been documented in experimental studies conducted with rodents exposed during the gestational and neonatal periods, no study has been conducted yet to determine if chlordecone alters child development. This study examines the relation of gestational and postnatal exposure to chlordecone to infant development at 18 months of age in a birth-cohort of Guadeloupean children. In a prospective longitudinal study conducted in Guadeloupe (Timoun mother-child cohort study), exposure to chlordecone was measured at birth from an umbilical cord blood sample (n=141) and from a breast milk sample collected at 3 months postpartum (n=75). Toddlers were assessed using an adapted version of the Ages and Stages Questionnaire. Higher chlordecone concentrations in cord blood were associated with poorer fine motor scores. When analyses were conducted separately for boys and girls, this effect was only observed among boys. These results suggest that prenatal exposure to chlordecone is associated with specific impairments in fine motor function in boys, and add to the growing evidence that exposure to organochlorine pesticides early in life impairs child development.
ISSN: 0161-813X

hal-00875907
https://hal.archives-ouvertes.fr/hal-00875907
PUBMED : 23376090
DOI : 10.1016/j.neuro.2013.01.007

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
CONTEXT: Chlordecone, an environmentally persistent organochlorine insecticide used intensively in banana culture in the French West Indies until 1993, has permanently polluted soils and contaminated foodstuffs. Consumption of contaminated food is the main source of exposure nowadays. We sought to identify main contributors to blood chlordecone concentration (BCC) and to validate an exposure indicator based on food intakes. MATERIAL AND METHODS: We used a food frequency questionnaire (FFQ) completed by a sample of 194 pregnant women to estimate their dietary exposure to chlordecone and compared it to blood levels. In a first approach, chlordecone daily intake was estimated as the product of daily eaten quantity of 214 foodstuffs, multiplied by their chlordecone content, and summed over all items. We then predicted individual blood chlordecone concentration with empirical weight regression models based on frequency of food consumption, and without contamination data. RESULTS: Among the 191 subjects who had BCC determination, 146 (76%) had detectable values and mean BCC was 0.86 ng/mL (range < LOD-13.2). Mean per capita dietary intake of chlordecone was estimated at 3.3 microg/day (range: 0.1-22.2). Blood chlordecone levels were significantly correlated with food exposure predicted from the empirical weight models (r=0.47, p<0.0001) and, to a lesser extent, with chlordecone intake estimated from food consumption and food contamination data (r=0.20, p=0.007). Main contributors to chlordecone exposure included seafood, root vegetables, and Cucurbitaceous. CONCLUSION: These results show that the Timoun FFQ provides valid estimates of chlordecone exposure. Estimates from empirical weight models correlated better with blood levels of chlordecone than did estimates from the dietary intake assessment.
ISSN: 0013-9351

inserm-00517109
http://www.hal.inserm.fr/inserm-00517109
http://www.hal.inserm.fr/inserm-00517109/document
http://www.hal.inserm.fr/inserm-00517109/file/Pesticide_exposureofpregnantwomeninGuadeloupe.pdf
DOI : 10.1016/j.envres.2009.10.015

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Collisional mountain belts grow as a consequence of continental plate convergence and eventuallydisappear under the combined effects of gravitational collapse and erosion. Using a decade ofGPS data, we show that the western Alps are currently characterized by zero horizontal velocityboundary conditions, offering the opportunity to investigate orogen evolution at the time ofcessation of plate convergence. We find no significant horizontal motion within the belt, but GPS andlevelling measurements independently show a regional pattern of uplift reaching ~2.5 mm/yr in thenorthwestern Alps. Unless a low viscosity crustal root under the northwestern Alps locally enhancesthe vertical response to surface unloading, the summed effects of isostatic responses to erosion andglaciation explain at most 60% of the observed uplift rates. Rock-uplift rates corrected from transientglacial isostatic adjustment contributions likely exceed erosion rates in the northwestern Alps. In theabsence of active convergence, the observed surface uplift must result from deep-seated processes.
ISSN: 2045-2322

hal-01357450
https://hal.archives-ouvertes.fr/hal-01357450
https://hal.archives-ouvertes.fr/hal-01357450/document
https://hal.archives-ouvertes.fr/hal-01357450/file/noquet2016.pdf
DOI : 10.1038/srep28404

Éditeur(s) : Soc General Microbiology
Résumé : The Plasmodium falciparum kinome includes a family of four protein kinases (Pfnek-1 to -4) related to the NIMA (never-in-mitosis) family, members of which play important roles in mitosis and meiosis in eukaryotic cells. Only one of these, Pfnek-1, which we previously characterized at the biochemical level, is expressed in asexual parasites. The other three (Pfnek-2, -3 and -4) are expressed predominantly in gametocytes, and a role for nek-2 and nek-4 in meiosis has been documented. Here we show by reverse genetics that Pfnek-1 is required for completion of the asexual cycle in red blood cells and that its expression in gametocytes in detectable by immunofluorescence in male (but not in female) gametocytes, in contrast with Pfnek-2 and Pfnek-4. This indicates that the function of Pfnek-1 is non-redundant with those of the other members of the Pfnek family and identifies Pfnek-1 as a potential target for antimalarial chemotherapy. A medium-throughput screen of a small-molecule library provides proof of concept that recombinant Pfnek-1 can be used as a target in drug discovery.
Microbiology-sgm (1350-0872) (Soc General Microbiology), 2011-10 , Vol. 157 , P. 2785-2794

Droits : 2011 SGM Printed in Great Britain / This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
http://archimer.ifremer.fr/doc/00175/28578/26965.pdf
DOI:10.1099/mic.0.049023-0
http://archimer.ifremer.fr/doc/00175/28578/

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
Retreatment with pegylated interferon (peg-IFN) and ribavirin (RBV) results in poor sustained virological response (SVR) rates in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients. There are limited data regarding the use of telaprevir plus peg-IFN/RBV in this population. HIV type 1-infected patients who previously failed ≥12 weeks of peg-IFN/RBV for HCV genotype 1 coinfection were enrolled in a single-arm, phase 2 trial. Patients with cirrhosis and previous null response were excluded. Authorized antiretrovirals were tenofovir, emtricitabine, efavirenz, atazanavir, and raltegravir. All patients received peg-IFN alfa-2a (180 µg/week) plus RBV (1000-1200 mg/day) for 4 weeks, followed by telaprevir (750 mg or 1125 mg every 8 hours with efavirenz) plus peg-IFN/RBV for 12 weeks and peg-IFN/RBV for 32-56 weeks according to virological response at week 8. The primary endpoint was the SVR rate at 24 weeks after the end of treatment (SVR24). Sixty-nine patients started treatment; SVR24 was achieved in 55 (80% [95% confidence interval, 68%-88%). SVR24 was not influenced by baseline fibrosis stage, IL28B genotype, antiretroviral regimen, HCV subtype, CD4 cell count, previous response to HCV treatment, HCV RNA level, or HCV RNA decline at week 4. HCV treatment was discontinued for adverse events (AEs) in 20% of patients, including cutaneous (4%), psychiatric (4%), hematological (6%), and other AEs (6%). Peg-IFN or RBV dose reduction was required in 23% and 43% of patients, respectively. Seventy percent of patients required erythropoietin, blood transfusions, or RBV dose reduction for anemia. Two patients died during the study. No HIV breakthrough was observed. Despite a high discontinuation rate related to toxicity, a substantial proportion of treatment-experienced HIV-coinfected patients achieved SVR24 with a telaprevir-based regimen. Clinical Trials Registration. NCT01332955.
ISSN: 1058-4838

hal-01118447
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118447
PUBMED : 25139963
DOI : 10.1093/cid/ciu659

Droits : 2010 Ifremer/Observatoire du Patrimoine Naturel de Bretagne
http://archimer.ifremer.fr/doc/00026/13737/10865.pdf
http://archimer.ifremer.fr/doc/00026/13737/

Éditeur(s) : HAL CCSD CNRS éditions
Résumé : International audience
Die antike Siedlung von Mandeure und Mathay (Epomanduodurum), welche durch ihre Größe und ihre monumentale Ausstattung als die zweitwichtigste Stadt der Sequaner hinter der Civitashauptstadt Besançon betrachtet wird, ist Gegenstand eines interdisziplinarischen Forschungsprogramms. Dieser Artikel stellt eine Bilanz der Ergebnisse der zwischen 2001 und 2004 durchgeführten Forschungen dar. Im Mittelpunkt der Forschungen der ersten Phase stand der zentralen Teil der Siedlung mit dem Bereich Heiligtum-Theater-spätrömische Befestigung, der für die Problematik der Entstehung, der Entwicklung und dem Ende der römischen Besiedlung besonders interessant ist. Verschiedene, sich ergänzende Projekte wurden eingeleitet: Erforschung des alten Dokumentarbestandes, geophysikalische Prospektionen, geoarchäologische Sondierungen, Plangrabungen, architektonische Untersuchunge. Durch diese Projekte war es möglich, die Kenntnisse über die drei wichtigen Großbauten (Heiligtum-Theater-spätrömische Befestigung) grundsätzlich zu vertiefen und insbesondere die geophysikalischen Prospektionsergebnisse lassen in bemerkenswerter Weise einen dichten Baubestand dieses Stadtteils erkennen. Schließlich konnte die Funktion und die Entwicklung der Flußebene des Doubs in diesem Bereich besser verstanden werden als auch die Art und Weise in welcher die antike Monumentalanlage in diesen einzigartigen natürlichen Rahmen einbezogen wurde.
Since 2001, a collective pluridisciplinary research programme is being undertaken on the antique town of Epomanduodurum in the communes of Mandeure and Mathay. This site is considered like the second one of the Sequani, for its dimensions and the monuments, after the civitas capital, Besançon. This article is an assessment of the investigations conducted between 2001 and 2004. During this period, the central part of the site was studied (sanctuary, theatre, Late fortification area), considered as the most significant for the question of the birth, development and decline of the town. Various complementary approaches have been carried out: study of archives, geophysical and geoarchaeological survey, extent excavations, architectural analyses. They lead to a better understanding of the three main buildings (the Celtic and Gallo-Roman sanctuary, the theatre of the Principate, the Late Antique fortification) and they add considerable informations about the pattern of settlement of this area; so it is possible to detect more precisely the spatial organization and finally to understand how the alluvial plain of the Doubs river was functioning and how the monumental complex has been integrated in such a peculiar landscape.
L'agglomération antique d'Epomanduodurum, située sur les communes de Mandeure et Mathay, et considérée comme la seconde du pays séquane par la taille et la parure monumentale, derrière la capitale de cité, Besançon, fait l'objet d'un programme collectif de recherche, pluridisciplinaire, depuis 2001. Cet article dresse un bilan des résultats des fouilles réalisées entre 2001 et 2004. Dans cette première phase, les investigations ont porté principalement sur la partie centrale du site (secteur sanctuaire-théâtrefortification tardive), perçue comme particulièrement intéressante pour la problématique de la naissance, du développement et du déclin de l'agglomération. Différentes approches complémentaires ont été lancées : étude du fond documentaire ancien, prospections géophysiques, sondages géoarchéologiques, fouilles extensives, études architecturales. Elles ont permis d'approfondir la connaissance des trois principaux édifices (sanctuaire laténien et gallo-romain, théâtre du Haut-Empire, fortification du Bas-Empire), de compléter de façon très notable la trame de l'occupation de ce secteur, et donc d'en mieux percevoir l'organisation spatiale, enfin de mieux comprendre le fonctionnement de la plaine alluviale du Doubs et l'insertion dans ce contexte naturel particulier d'un complexe monumental antique.
ISSN: 0016-4119

halshs-00718356
https://halshs.archives-ouvertes.fr/halshs-00718356

Éditeur(s) : HAL CCSD WB Saunders
Résumé : International audience
OBJECTIVE: We hypothesized that, in Human Immunodeficiency Virus and Hepatitis C Virus (HIV/HCV) co-infected patients who did not respond to peg-interferon and ribavirin, a maintenance therapy with peg-interferon could induce fibrosis regression. METHODS: This was a randomized study with two parallel groups. HIV/HCV co-infected patients received peg-interferon α-2a at 180 μg/week or remained on observation for 96 weeks. The primary endpoint was the percentage of patients who experienced a decrease of at least one point in their Metavir fibrosis score between initial and final liver biopsies. Secondary endpoints included plasma fibrosis markers at week 96, occurrence of HCV-related complications, and survival. RESULTS: A total of 52 patients were randomized (peg-interferon: 25; control: 27) including 18 with cirrhosis. The median (interquartile range) age was 44 (40-46) years, and 69% were male. A total of 64% had ALT levels >1.5 normal values, and the CD4 cell count was 391 (296-537) cells/mm(3); 67% of patients had HIV RNA <200 copies/mL at entry. The main endpoint was assessed in 41 patients. Response rates were 3/20 (15%) and 4/21 (19%) in the peg-interferon and control groups, respectively (p = 0.99). There was no significant difference between peg-interferon and control groups on plasma fibrosis markers at the final visit. Severe liver-related complications were observed in 2 and 5 patients in peg-interferon and control groups, respectively. Three deaths were observed, all in the control group. CONCLUSIONS: A maintenance therapy with peg-interferon α-2a over 96 weeks in HIV/HCV co-infected patients, who were non-responders to HCV treatment, did not change liver fibrosis. ClinicalTrials.gov Identifier: NCT00122616.
ISSN: 0163-4453

hal-00875067
https://hal.archives-ouvertes.fr/hal-00875067
DOI : 10.1016/j.jinf.2013.05.007
PUBMED : 23800784

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
OBJECTIVE: The WEGENT trial and other short-term studies suggested that azathioprine or methotrexate could effectively maintain granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) remission. Whether differences in relapse or adverse event rates would appear after discontinuation of those 2 maintenance regimens and longer follow-up remains unknown. METHODS: Long-term outcomes for the patients enrolled in the WEGENT trial were analyzed according to their randomization group. Parameters at trial entry were evaluated as potential prognostic factors for death, relapse or damage in multivariate models. RESULTS: Data were returned for 88.8% of the 126 original participants. Median [95% confidence interval] followup was 11.9 [11.3-12.5] years. For the azathioprine and methotrexate arms, respectively, the 10-year overall survival rates were 75.1% [64.8-86.9] and 79.9% [70.3-90.8] (P = 0.56), and relapse-free survival rates 26.3% [17.3-40.1] and 33.5% [23.5-47.7] (P = 0.29). No between-arm differences were observed for relapse, adverse events, damage, survival rates without severe side effects and survival rates without relapse and severe side effects. Considering only the 97 GPA patients, no between-arm survival differences were observed. Relapse-free survival was shorter for GPA than MPA patients but the multivariate analysis retained anti-PR3-ANCA-positivity, and not GPA, as being independently associated with relapse. CONCLUSION: This long-term analysis confirms that azathioprine and methotrexate are comparable options for maintaining GPA or MPA remission. Despite good overall survival, relapses, adverse events and damage remain matters of concern and further studies are needed to reduce them.
ISSN: 2326-5205

hal-01217989
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01217989
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01217989/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01217989/file/Long-term%20outcomes%20of%20the%20WEGENT%20trial_accepted.pdf
DOI : 10.1002/art.39450

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Few studies have explored the consequences of environmental exposure to organochlorine pesticides for gestational hypertension (GH), preeclampsia (PE) and gestational diabetes mellitus (GDM). Chlordecone is a persistent organochlorine pesticide that was used intensively, and almost exclusively, in the French West Indies until 1993. We investigated the impact of prenatal exposure to chlordecone on the occurrence of GDM, GH and PE by studying 779 pregnant women enrolled in a prospective mother-child cohort (Timoun Study) in Guadeloupe between 2004 and 2007. Chlordecone exposure was determined by assaying maternal plasma and information about pregnancy complications was obtained from midwives, pediatricians and hospital medical records after delivery. The risks of GH (n=65), PE (n=31) and GDM (n=71) were estimated by multiple logistic regression including potential confounders. Levels of chlordecone plasma concentration in the third (OR=0.2; 95% confidence interval (CI): 0.1, 0.5) and fourth quartiles (OR=0.3; 95% CI: 0.2, 0.7) were associated with a statistically significant decrease in the risk of GH. A log10 increase in chlordecone concentration was significantly associated with lower risk of GH (OR=0.4; 95% CI: 0.2, 0.6). No significant associations were observed between the chlordecone exposure and the risk of PE or GDM. This study suggests an inverse association between chlordecone exposure during pregnancy and GH. Further studies are required to determine the underlying mechanism, or the potential unknown confounding factors, resulting in this association.
ISSN: 0160-4120

hal-01061391
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01061391
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01061391/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01061391/file/Saunders_et_al._Final_version_main_manuscript.pdf
DOI : 10.1016/j.envint.2014.03.024

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
BACKGROUND: The insecticide chlordecone was extensively used in the French West Indies to control banana root borer. Its persistence in soils has led to the widespread pollution of the environment, and human beings are still exposed to this chemical. Chlordecone has been shown to impair neurological and behavioural functions in rodents when exposed gestationally or neonatally. OBJECTIVES: The aim of the study was to evaluate the impact of prenatal and postnatal exposure to chlordecone on the cognitive, visual, and motor development of 7-month-old infants from Guadeloupe. METHODS: Infants were tested at 7 months (n=153). Visual recognition memory and processing speed were assessed with the Fagan Tests of Infant Intelligence (FTII), visual acuity with the Teller Acuity Card, and fine motor development with the Brunet-Lezine. Samples of cord blood and breast milk at 3 months (n=88) were analyzed for chlordecone concentrations. Postnatal exposure was determined through breast feeding and frequency of contaminated food consumption by the infants. RESULTS: Cord chlordecone concentrations in tertiles were associated with reduced novelty preference on the FTII in the highly exposed group (β=-0.19, p=0.02). Postnatal exposure through contaminated food consumption was marginally related to reduced novelty preference (β=-0.14, p=0.07), and longer processing speed (β=0.16, p=0.07). Detectable levels of chlordecone in cord blood were associated with higher risk of obtaining low scores on the fine motor development scale (OR=1.25, p<0.01). CONCLUSION: These results suggest that pre- and postnatal low chronic exposure to chlordecone is associated with negative effects on cognitive and motor development during infancy.
ISSN: 0013-9351

hal-00875939
https://hal.archives-ouvertes.fr/hal-00875939
DOI : 10.1016/j.envres.2012.07.006
PUBMED : 22910562

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Treacher Collins/Franceschetti syndrome (TCS; OMIM 154500) is a disorder of craniofacial development belonging to the heterogeneous group of mandibulofacial dysostoses. TCS is classically characterized by bilateral mandibular and malar hypoplasia, downward-slanting palpebral fissures, and microtia. To date, three genes have been identified in TCS:,TCOF1, POLR1D, and POLR1C. We report a clinical and extensive molecular study, including TCOF1, POLR1D, POLR1C, and EFTUD2 genes, in a series of 146 patients with TCS. Phenotype-genotype correlations were investigated for 19 clinical features, between TCOF1 and POLR1D, and the type of mutation or its localization in the TCOF1 gene. We identified 92/146 patients (63%) with a molecular anomaly within TCOF1, 9/146 (6%) within POLR1D, and none within POLR1C. Among the atypical negative patients (with intellectual disability and/or microcephaly), we identified four patients carrying a mutation in EFTUD2 and two patients with 5q32 deletion encompassing TCOF1 and CAMK2A in particular. Congenital cardiac defects occurred more frequently among patients with TCOF1 mutation (7/92, 8%) than reported in the literature. Even though TCOF1 and POLR1D were associated with extreme clinical variability, we found no phenotype-genotype correlation. In cases with a typical phenotype of TCS, 6/146 (4%) remained with an unidentified molecular defect.
ISSN: 1098-3600

hal-01134364
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01134364
DOI : 10.1038/gim.2015.29
PUBMED : 25790162

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Plio-Pleistocene diatomitic sequences in the Shamb paleo-lake (South Armenia, Lesser Caucasus) offer a rare opportunity to give new insights on the paleo-climate of Western Asia. We present an integrated palynological, 40Ar/39Ar geochronologic and magnetostratigraphic study for the most complete section in the sedimentary deposits of the Shamb paleo-lake. 40Ar/39Ar dating of two volcaniclastic layers provided ages of 1.24 ± 0.03 and 1.16 ± 0.02 Ma (2. Magnetostratigraphic data show that the entire Shamb section is of reversed polarity which, combined with 40Ar/39Ar dating, suggests that the entire section correlates with part of the Matuyama period (1.785-1.070 Ma). Pollen assemblages and macroremains diversity clearly show an alternation of glacial and interglacial phases. Age calibrations and accumulation rate extrapolation allow a direct correlation of climate changes with the global isotopic curve, and show that the Shamb section probably ranges from approximately 1.300 to 1.080 Ma (marine isotopic stages 40 to 31). The vegetation of the Lesser Caucasus developed in a mosaic pattern in a Pleistocene continental, mostly arid climate, comparable to the present-day climate. The observed vegetation changes record a dominant climate response to the obliquity orbital parameter, but the influence of precession could not be established from the Shamb data. Pollen and macroflora both indicate that glacial periods were cold and dry and that interglacials were warm with local humidity. The early Pleistocene climatic model for Western Asia is thus similar to the climatic model for the Mediterranean area.
ISSN: 0012-821X

hal-00470353
https://hal.archives-ouvertes.fr/hal-00470353
DOI : 10.1016/j.epsl.2010.01.007

Éditeur(s) : HAL CCSD Lippincott, Williams & Wilkins
Résumé : International audience
OBJECTIVE: To evaluate the incidence and determinants of diabetes in a cohort of HIV-infected adults initiated with combination antiretroviral treatment (cART) in 1997-1999 and followed up to 2009. DESIGN: Prospective study of 1046 patients at 47 French clinical sites. METHODS: Potential determinants of diabetes occurrence, defined by confirmed increased glycemia and/or initiation of antidiabetic treatment, were assessed by a proportional hazards model, including time-updated metabolic parameters and ART exposure. RESULTS: Among the cohort, representing 7846 person-years of follow-up (PYFU), 54% received indinavir, 75% stavudine and 52% didanosine. Overall, 111 patients developed diabetes, with an incidence of 14.1/1000 PYFU (14.6 in men, 12.6 in women). Incidence peaked in 1999-2000 (23.2/1000 PYFU) and decreased thereafter. The incidence of diabetes was associated [adjusted hazard ratio (aHR), all P<0.02] with older age (hazard ratio = 2.13 when 40-49 years, hazard ratio = 3.63 when ≥50 years), overweight (hazard ratio = 1.91 for a BMI 25-29 kg/m(2), hazard ratio = 2.85 >30 kg/m(2)), waist-to-hip ratio (hazard ratio = 3.87 for ≥0.97 male/0.92 female), time-updated lipoatrophy (hazard ratio = 2.14) and short-term exposure to indinavir (0-1 year: hazard ratio = 2.53), stavudine (0-1 year: hazard ratio = 2.56, 1-2 years: hazard ratio = 2.65) or didanosine (2-3 years: hazard ratio = 3.16). Occurrence of diabetes was not associated with HIV-related markers, hepatitis C, hypertension or family history of diabetes. Insulin resistance was predictive for incident diabetes. CONCLUSIONS: In this nationwide cohort, followed for 10 years after cART initiation, diabetes incidence peaked in 1990-2000, was markedly higher than that reported for European uninfected or other HIV-infected populations (4-6/1000 PYFU) and linked with age and adiposity. Adiposity and glycemic markers should be monitored in aging HIV-infected patients.
ISSN: 0269-9370

hal-00875222
https://hal.archives-ouvertes.fr/hal-00875222
DOI : 10.1097/QAD.0b013e32834e8776
PUBMED : 22089377

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Pyrethroids are insecticides frequently used in agriculture and in the home; exposure occurs through dietary and non-dietary pathways, including indoor and outdoor environmental contamination. Our objective was to study the potential determinants of pyrethroid metabolite concentrations measured in children's urine samples and in the dust of their homes. Specifically, we measured urinary metabolites from morning spot samples of 245 six-year- old children living in Brittany (France) in 2009-2012 and from dust vacuumed from the floor of their homes. Mothers reported home insecticide use, dietary habits, sociodemographic data; residential and school proximity to agricultural crops was assessed with spatialized data. The metabolites cis-DBCA, trans-DCCA, cisDCCA, 3-PBA, and F-PBA were detected in 84, 95, 64, 63, and 16% of the urine samples, respectively. Permethrin, cypermethrin, cyfluthrin, deltamethrin, and tetramethrin pyrethroids were detected in 100, 56, 9, 15, and 26% of the dust samples, respectively. Multiple regression analysis suggested diet plays a role in children's exposure, in particular, the food groups "pasta, rice or semolina" (for cis-DCCA and F-PBA), fruit (3-PBA), "breakfast cereals and whole grain bread" (cis-DBCA), and the global proportion of organic food in diet (for cis-DBCA, trans-DCCA). Children with a parent occupationally exposed to pesticides were about 3-times more likely to have higher urinary concentrations of 3-PBA (OR = 2.8, 95% CI [1.2; 6.5]). Dust content was correlated mainly with household insecticide use: higher mean concentrations of permethrin (beta = 0.8 [0.3; 1.3], in mu g/g) and an increased risk of a detectable level of cyfluthrin (OR = 4.7 [1.7; 12.9]) were observed in home dust, for indoor use of at least twice a year. Outdoor insecticide use at least once a year was associated with detection in dust of cypermethrin (OR = 3.0 [1.3; 6.7]) and tetramethrin (OR = 3.7 [1.6; 8.3]). Three positive and one negative correlations (out of 11) between urinary metabolite concentrations and home dust contents of their possible corresponding parent compounds were observed. The strength of this study lies in its concurrent use of biomarkers, environmental measurements, and potential sources of exposure. Its limitations include the use of a single urine sample and imprecise data about pyrethroid use in local agriculture.
ISSN: 0160-4120

hal-01560147
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01560147
DOI : 10.1016/j.envint.2017.04.007
PUBMED : 28453973

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
Are bisphenol A (BPA) and BPA analogs (BPA-A) safe for male human reproductive function? The endocrine function of human testes explants [assessed by measuring testosterone and insulin-like factor 3 (INSL3)] was impacted by exposure of the human adult testis explants to BPA/BPA-A. The few epidemiologic studies performed suggest that bisphenols have potential endocrine disruptive properties, but they did not identify clear and direct patterns of endocrine disruption. Adult human testis explants in culture were exposed to BPA and the analogs bisphenol F (BPF), bisphenol S (BPS), bisphenol E (BPE), bisphenol B (BPB) and bisphenol A diglycidyl ether (BADGE) at 10(-9)-10(-5) M for 24 or 48 h. Human adult testes were obtained from prostate cancer patients who had no hormone therapy, or from multiorgan donors. After ex vivo exposure to the investigated bisphenols, the measured outcomes were related to histopathology (gross morphology and germ cell viability determined by anti-caspase three immunohistochemistry), and the levels of testosterone, INSL3 and inhibin B were measured using immunoassays. The levels of mRNA encoding key enzymes of bisphenol biotransformation were investigated by quantitative PCR: UGT2B15 UDP (glucuronosyltransferase two family, polypeptide B15), GUSB (glucuronidase beta), SULT1A1 and 3 (sulfotransferase family 1 A member 1 and 3) and STS (steroid sulfatase). A significant dose-dependent inhibition was found between testosterone levels measured in the culture medium and concentrations of BPA (P = 0.00778 at 24 h and P = 0.0291 at 48 h), BPE (P = 0.039) and BPF (P = 0.00663). The observed BPA and BPA-A-induced inhibition of testosterone production varied according to duration of exposure and BPA/BPA-A concentrations. BPA (10(-9) M; P < 0.05), BPB (10(-9) M; P < 0.05), BPS (10(-9) and 10(-8) M; P < 0.05) and BADGE (10(-5) M; P < 0.05) increased Leydig cell INSL3 production. By contrast, BPE dose dependently inhibited INSL3 (P = 0.0372). Conversely, Sertoli cell function (inhibin B) and germ cell viability were not significantly affected by either bisphenols. N/A. Environmental compounds cannot be deliberately administered to men, justifying the use of an ex vivo approach. A relatively low number of testes samples were available for analysis (n = 3, except for testosterone secretion with n = 5). The active concentrations of BPA and BPA-A used in the study were higher than those found in human biological fluids. Under our experimental conditions, direct exposure to BPA or BPA-A can result in endocrine disturbance in the adult human testis.
ISSN: 0268-1161

hal-01578582
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01578582
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01578582/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01578582/file/Parallel%20assessment%20of%20the%20effects%20of%20bisphenol%20A_accepted.pdf
DOI : 10.1093/humrep/dex093