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 Wiley
Résumé : International audience
With the growing use of selective serotonin reuptake inhibitor medications (SSRIs) for the treatment of depression during the perinatal period, questions have been raised about the longterm impact of these medications on development. We aimed to investigate how developmental SSRI exposure may alter affect-related behaviors and associated molecular processes in offspring using a rodent model of maternal stress and depression. For this purpose, prenatally stressed or non-stressed male offspring were exposed to fluoxetine (5 mg/kg/day) or vehicle, via lactation, until weaning. Primary results show that postnatal fluoxetine exposure differentially altered anxiety-like behavior by increasing anxiety in non-stressed offspring and decreasing anxiety in prenatally stressed offspring. In the hippocampus, developmental fluoxetine exposure decreased BDNF IV and TrkB mRNA expression. Prenatal stress alone also decreased escape behaviors and decreased hippocampal BDNF IV mRNA expression. These data provide important evidence for the long-term programming effects of early-life exposure to SSRIs on brain and behavior.
ISSN: 0012-1630

hal-01305478
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01305478
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01305478/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01305478/file/Developmental%20SSRIs%2C%20anxiety%20and%20BDNF_accepted.pdf
DOI : 10.1002/dev.21385

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
ODP (Ocean Drilling Program)/IODP (Integrated Ocean Drilling Program) Site 1256 is located on the Cocos Plate in the Eastern Equatorial Pacific Ocean, in a 15 Ma old oceanic lithosphere formed at the EPR during a period of superfast spreading (>200 mm/yr). ODP/IODP Hole 1256D reached for the first time the contact between sheeted dikes and underlying gabbros. It consequently offers a unique opportunity to study in situ, in present-day oceanic crust, the root zone of the sheeted dike complex. This root zone is a thin, 100 m thick boundary layer between the magmatic system (i.e., the axial melt lens, similar to 1100 degrees C), and the overlying high temperature hydrothermal system (<= 450 degrees C). The understanding of interactions within this boundary layer is critical to that of crustal processes along mid-ocean ridges.;This work focuses on the petrophysical characterization of the root zone of the sheeted dike complex in order to further constrain the hydrothermal circulation system in the vicinity of the axial melt lens, as recorded in non-granoblastic dikes, granoblastic dikes, and varitextured gabbros. The petrophysical properties were determined from sample measurements in the laboratory and were compared to in situ downhole geophysical probing. The porosity structure is bipolar, depending on lithology, resulting in a layered system. Non-granoblastic dikes are generally altered in the greenschist fades (similar to>250 degrees C) with relatively high and interconnected (cementation index m similar to 1.72, electrical tortuosity tau similar to 28.3) porosity (1.5%). In contrast, gabbros are retrogressively metamorphosed in the amphibolite (similar to>450 degrees C) and greenschist facies, with lower porosity (1.3%) that involves numerous fissures and cracks, resulting in a more connected medium (m similar to 1.58, tau similar to 11.8) than non-granoblastic dikes. These cracks are more abundant but also tend to close with increasing depth as indicated in downhole geophysical data. Porosity and alteration, as viewed from surface electrical conductivity, appear to be directly correlated.
ISSN: 0040-1951

hal-00544556
https://hal.archives-ouvertes.fr/hal-00544556
DOI : 10.1016/j.tecto.2010.07.013

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
STUDY QUESTION: Is prenatal exposure to persistent organic pollutants (POPs) associated with variations of sex hormone levels in cord blood? SUMMARY ANSWER: Prenatal exposure to a number of POPs is associated with a disruption of hormone levels in cord blood, with sex specificities. WHAT IS KNOWN ALREADY: Epidemiological studies have reported disorders of reproductive health, in relation with POPs exposure during early life and the endocrine disruption properties of these chemicals have been suggested as possible mechanisms. STUDY DESIGN, SIZE, DURATION: A subset of 282 mother-child pairs was selected from the prospective population-based PELAGIE birth cohort (n = 3421, 2002-2006, Brittany, France). Pregnant women were recruited before 19 weeks of gestation and followed until delivery. PARTICIPANTS/MATERIALS, SETTING, METHODS: Sex hormone levels including sex hormone-binding globulin (SHBG), estradiol (E2), total testosterone (T), free testosterone (fT = T/SHBG) and the aromatase index (AI = T/E2) were measured in 282 cord blood samples. Anti-Müllerian hormone (AMH) was measured in male newborns only. Pesticide concentrations of α-endosulfan, β-hexachlorocyclohexane (β-HCH), γ-HCH, dieldrin, pp'-dichlorodiphenyldichloroethylene (p,p'-DDE), hexachlorobenzene (HCB), heptachlor epoxide (HCE), as well as PCBs (congeners 153, 187 and the sum of anti-estrogenic PCBs 118, 138, and 170) and decabrominated diphenyl ether (BDE209) were also measured in cord blood. Associations between sex hormones and POPs exposure were explored using multiple linear regressions adjusted for potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE: High PCB levels were associated with an increase of SHBG (P-trend extless 0.01) and AMH (P-trend extless 0.05) and a decrease of fT (P-trend extless 0.05) and AI (P-trend extless 0.01). High pesticide levels, particularly α-endosulfan and HCE, were associated with an increase of SHBG (P extless 0.05) and E2 (P extless 0.01) and a decrease of fT (P extless 0.05) and AI (P extless 0.01). Several of these associations were stronger, or specific, among male or female newborns. The associations were not altered in the sensitivity analyses. LIMITATIONS, REASONS FOR CAUTION: The study population was of relatively small sample size, and some compounds rarely detected in cord blood. The high level of correlation between POPs makes it difficult to identify the most contributing POPs. Hormone measurements were performed at birth (in cord blood) and may not adequately represent the infant endocrine system. Multiple statistical testing may have led to false-positive associations. WIDER IMPLICATIONS OF THE FINDINGS: Our results are in discordance with those reported in the only published study of the kind but in accordance with studies about prenatal exposure to other endocrine disruptors such as phthalates. These findings may help understanding the pathways involved in adverse reproductive outcomes associated with POPs exposure. STUDY FUNDING/COMPETING INTERESTS: The PELAGIE cohort is funded by Inserm, French Ministry of Health, French Ministry of Labor, InVS, ANR, ANSES, and French Ministry of Ecology. None of the authors has any competing interest to declare
ISSN: 0268-1161

hal-01220641
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01220641
DOI : 10.1093/humrep/dev260
PUBMED : 26493407

Éditeur(s) : HAL CCSD Oxford University Press
Résumé : International audience
The epigenetic events imposed during germline reprogramming and affected by harmful exposure can be inherited and transferred to subsequent generations via gametes inheritance. In this study, we examine the transgenerational effects promoted by widely used herbicide atrazine (ATZ). We exposed pregnant outbred CD1 female mice and the male progeny was crossed for three generations with untreated females. We demonstrate here that exposure to ATZ affects meiosis, spermiogenesis and reduces the spermatozoa number in the third generation (F3) male mice. We suggest that changes in testis cell types originate from modified transcriptional network in undifferentiated spermatogonia. Importantly, exposure to ATZ dramatically increases the number of transcripts with novel transcription initiation sites, spliced variants and alternative polyadenylation sites. We found the global decrease in H3K4me3 occupancy in the third generation males. The regions with altered H3K4me3 occupancy in F3 ATZ-derived males correspond to altered H3K4me3 occupancy of F1 generation and 74% of changed peaks in F3 generation are associated with enhancers. The regions with altered H3K4me3 occupancy are enriched in SP family and WT1 transcription factor binding sites. Our data suggest that the embryonic exposure to ATZ affects the development and the changes induced by ATZ are transferred up to three generations.
ISSN: 0305-1048

hal-01477213
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01477213
DOI : 10.1093/nar/gkw840
PUBMED : 27655631

Éditeur(s) : Université des Antilles Études caribéennes
Résumé : This paperdiscusses approaches to cultural alterity in the context of tourism, with an emphasis on food consumption.Tourism as a field of study is ideal for the observation and analysis of the strategies adopted by individuals facing the unknown, the other.Food consumption, although universal,is deeplycultural, and it anchors social norms in the body.Studyingfood inthe context of tourismallows us tohighlightthese normsas well ascertain individual identification processes. Roseau’s cruise port, Commonwealth of Dominica, serves as the empirical basis for my analysis. In 2006, 470 830 cruise passengers disembarked on the Island, which represented over 80% of visitors to the island, as well as more than six times the national population. In consideration of these impressive statistics, analyzing food strategies can give us insights into larger patterns of negotiation, between fear and attraction to the unknown.
Ce texte propose de développer la question de la relation à l’altérité culturelle en jeu dans la pratique touristique sous l’angle de l’alimentation. Le tourisme a l’avantage d’offrir un terrain d’étude privilégié pour observer les stratégies identitaires des individus face à l’inconnu. La consommation alimentaire, bien qu’universelle, est profondément culturelle, et ancre dans les corps des normes sociales. Etudier l’alimentation dans le contexte touristique donne l’occasion de mettre en évidence ces normes de même que certaines logiques identitaires des individus. Le port de croisière de Roseau, Commonwealth of Dominica, sert de base empirique au développement. En 2006, 470 830 passagers de croisières ont débarqués sur l’île, ce qui représentait plus de 80 % des visiteurs de l’île, de même que plus de six fois la population nationale. Face à ces impressionnantes statistiques, s’intéresser aux stratégies alimentaires permet de mettre en évidence des schémas plus larges : entre peur et attrait de l’inconnu.
Dominique

Droits : info:eu-repo/semantics/openAccess
urn:doi:10.4000/etudescaribeennes.5655
http://journals.openedition.org/etudescaribeennes/5655

Éditeur(s) : HAL CCSD Oxford University Press (OUP): Policy B - Oxford Open Option A Oxford University Press (OUP)
Résumé : International audience
Peridotites exhumed in the footwall of axial detachment faults at slow-spreading ridges are highly serpentinized. Most mid-ocean ridge detachment settings are magmatically active and hydrous fluid circulation in and near the fault has been shown to be influenced by the presence of melt or magmatic lithologies. Our working area along the Southwest Indian Ridge (62–65°E) is nearly amagmatic and represents an end-member to study the hydrous alteration of exhumed peridotites without these magmatic influences. We use an integrated petrological approach combining microstructural, mineralogical and chemical observations to unravel the sequence of serpentinization in 272 dredged samples of variably serpentinized peridotites and to document the circulation of serpentinizing fluids in and near the exhumation faults. We find that serpentine recrystallization and veins overprint the initial serpentinite mesh texture in ∼25% of the samples. Oxygen isotope data suggest that this sequence developed at relatively high temperatures (271–336°C) and under increasing fluid–rock ratios, from near stoichiometry for mesh texture formation to >10 during recrystallization. Increasing fluid supersaturation relative to serpentine favors the replacement of mesh texture lizardite by chrysotile and polygonal or polyhedral serpentine. We attribute local recrystallization into antigorite to moderate Si-metasomatism, possibly following pyroxene serpentinization. We do not observe the more pronounced Si-metasomatism leading to talc replacing serpentine that is reported for the more magmatically active Mid-Atlantic Ridge detachment settings and is attributed to prior leaching of magmatic rocks. Scales of preferential fluid pathways in our samples evolved from pervasive and close-spaced (<500 µm) microfractures during the formation of the initial serpentine mesh texture, to centimeter-thick planar domains of enhanced fluid flux, spaced at ∼10 cm intervals and probably grouped in corridors that may be up to ∼100 m across. Serpentine minerals are enriched in some fluid-mobile elements (Cl, B, U) relative to the peridotite protolith, and several elements (Al, Fe, Si, Cu, As, Sb, REE) are redistributed at the millimeter to decimeter scale. Serpentinizing fluids were seawater-derived, probably mildly alkaline (small to no europium anomalies), reducing and H2-enriched (formation of magnetite). These fluids may have been similar to, though warmer than, those venting at the ultramafic-hosted Lost City hydrothermal fluid (30°N, Mid-Atlantic Ridge).
ISSN: 0022-3530

hal-01174047
https://hal.archives-ouvertes.fr/hal-01174047
DOI : 10.1093/petrology/egv014

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Cigarette smoke condensate (CSC) has previously been shown to impair activity and expression of hepatic drug transporters. In the present study, we provided evidence that CSC also hinders activity of organic anion transporters (OATs), notably expressed at the kidney level. CSC thus cis-inhibited OAT substrate uptake in OAT1- and OAT3-transfected HEK293 cells, in a concentration-dependent manner (IC50=72.1μg/mL for OAT1 inhibition and IC50=27.3μg/mL for OAT3 inhibition). By contrast, OAT4 as well as the renal organic cation transporter (OCT) 2 were less sensitive to the inhibitory effect of CSC (IC50=351.5μg/mL and IC50=226.2μg/mL, for inhibition of OAT4 and OCT2, respectively). OAT3 activity was further demonstrated to be blocked by some single chemicals present in cigarette smoke such as the heterocyclic amines AαC (IC50=11.3μM) and PhIP (IC50=1.9μM), whereas other major cigarette smoke components used at 100μM, like nicotine, the nitrosamine NNK and the polycyclic aromatic hydrocarbons benzo(a)pyrene and phenanthrene, were without effect. AαC and PhIP however failed to trans-stimulate activity of OAT3, suggesting that they were not substrates for this transporter. Taken together, these data establish OAT1 and OAT3 transporters as targets of cigarette smoke chemicals, which may contribute to smoking-associated pharmacokinetics alterations.
ISSN: 0887-2333

hal-01579604
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01579604
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01579604/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01579604/file/Sayyed%20et%20al.%20-%20Inhibition%20of%20organic%20anion%20transporter%20%28OAT%29%20acti.pdf
DOI : 10.1016/j.tiv.2017.06.014

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Serpentinites form by hydration of mantle peridotite and constitute the largest potential reservoir of fluid-mobile elements entering subduction zones. Isotope ratios of one such element, boron, distinguish fluid contributions from crustal versus serpentinite sources. Despite 85% of boron hosted within abyssal peridotite being lost at the onset of subduction at the lizardite-to-antigorite transition, a sufficient cargo of boron to account for the composition of island arc magma is retained (c. 7 μg g− 1, with a δ11B of + 22‰) until the down-going slab reaches the antigorite-out isograd. At this point a 11B-rich fluid, capable of providing the distinctive δ11B signature of island arc basalts, is released. Beyond the uniquely preserved antigorite-out isograd in serpentinites from Cerro del Almirez, Betic Cordillera, Spain, the prograde lithologies (antigorite–chlorite–orthopyroxene–olivine serpentinite, granofels-texture chlorite-harzburgite and spinifex-texture chlorite-harzburgite) have very different boron isotope signatures (δ11B = − 3 to + 6‰), but with no significant difference in boron concentration compared to the antigorite-serpentinite on the low P–T side of the isograd. 11B-rich fluid, which at least partly equilibrated with pelagic sediments, is implicated in the composition of these prograde lithologies, which dehydrated under open-system conditions. Serpentinite-hosted boron lost during the early stages of dehydration is readily incorporated into forearc peridotite. This, in turn, may be dragged to sub-arc depths as a result of subduction erosion and incorporated in a mélange comprising forearc serpentinite, altered oceanic crust and pelagic sediment. At the antigorite-out isograd it dehydrates, thus potentially providing an additional source of 11B-rich fluids.
ISSN: 0009-2541

hal-01172276
https://hal.archives-ouvertes.fr/hal-01172276
DOI : 10.1016/j.chemgeo.2014.03.015

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
: Until recently, synonymous mutations (which do not change amino acids) have been much neglected. Some evidence suggests that this kind of mutations could affect mRNA secondary structure or stability, translation kinetics and protein structure. To explore deeper the role of synonymous mutations, we studied their consequence on the functional activity of the estrogen receptor alpha (ERα). The ERα is a ligand-inducible transcription factor that orchestrates pleiotropic cellular effects, at both genomic and non-genomic levels in response to estrogens. In this work we analyzed in transient transfection experiments, the activity of ERα carrying the synonymous mutation Ala87, a polymorphism involving about 5-10% of the population. In comparison to the wild type receptor, our results show that ERαA87 mutation reduces the transactivation efficiency of ERα on an ERE reporter gene while its expression level remains similar. This mutation enhances 4-OHT-induced transactivation of ERα on an AP1 reporter gene. Finally, the mutation affects the subcellular localization of ERα in a cell type specific manner. It enhances the cytoplasmic location of ERα without significant changes in non-genomic effects of E2. The functional alteration of the ERαA87 determined in this work highlights the relevance of synonymous mutations for biomedical and pharmacological points of view.
Journal of steroid biochemistry and molecular biology

inserm-01015532
http://www.hal.inserm.fr/inserm-01015532
DOI : 10.1016/j.jsbmb.2014.02.016
PUBMED : 24607813

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Inorganic arsenic is a toxic environmental contaminant to which humans are mainly exposed through drinking water. This metalloid impairs functions of several key immune cells. Particularly, it reduces IL-2 secretion and proliferation of blood peripheral mononuclear cells stimulated by lectins that, however, do not mimic physiological T cell activation. The present study used isolated human T cells activated, in a more physiological manner, through stimulation with CD3/CD28 antibodies, to carefully analyze the impact of arsenic on T cell proliferation and cytokine expression. We demonstrate that non cytotoxic concentrations of sodium arsenite (As(III), 0.25-2μM) significantly reduce T cell proliferation by increasing the percentage of non dividing cells blocked in G1 phase and by preventing cyclin D3 and CDC25A expression. They also markedly, although not totally, reduces IL-2 expression at both mRNA and protein levels; however, metalloid-dependent inhibition of T cells could not be reversed by addition of recombinant IL-2. In addition, As(III) markedly reduces secretion of interferon-γ without impairing that of IL-4 and IL-13; it also decreases interferon-γ mRNA levels but increases those of IL-13. Finally, simultaneously to its immune effects, As(III) rapidly and potently increases expression of the redox-sensitive genes HMOX1, NQO1 and GCLM in activated T cells without altering the levels of reactive oxygen species. In conclusion, our results demonstrate that As(III) inhibits T cell proliferation, independently of IL-2, and alters the Th balance of cytokines secreted by co-stimulated T cells which thus constitute direct targets of this major environmental contaminant.
ISSN: 0300-483X

inserm-00872848
http://www.hal.inserm.fr/inserm-00872848
DOI : 10.1016/j.tox.2012.05.025
PUBMED : 22683347

Éditeur(s) : Oxford Univ Press
Résumé : Biological reference points are important tools for fisheries management. Reference points are not static, butmay change when a population's environment or the population itself changes. Fisheries-induced evolution is one mechanism that can alter population characteristics, leading to "shifting" reference points by modifying the underlying biological processes or by changing the perception of a fishery system. The former causes changes in "true" reference points, whereas the latter is caused by changes in the yardsticks used to quantify a system's status. Unaccounted shifts of either kind imply that reference points gradually lose their intended meaning. This can lead to increased precaution, which is safe, but potentially costly. Shifts can also occur in more perilous directions, such that actual risks are greater than anticipated. Our qualitative analysis suggests that all commonly used reference points are susceptible to shifting through fisheries-induced evolution, including the limit and "precautionary" reference points for spawning-stock biomass, B-lim and B-pa, and the target reference point for fishing mortality, F-0.1. Our findings call for increased awareness of fisheries-induced changes and highlight the value of always basing reference points on adequately updated information, to capture all changes in the biological processes that drive fish population dynamics.
Ices Journal Of Marine Science (1054-3139) (Oxford Univ Press), 2013-07 , Vol. 70 , N. 4 , P. 707-721

Droits : 2013 International Council for the Exploration of the Sea. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com
http://archimer.ifremer.fr/doc/00151/26228/24302.pdf
DOI:10.1093/icesjms/fst077
http://archimer.ifremer.fr/doc/00151/26228/

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
BACKGROUND: Early in life, cystic fibrosis (CF) patients are infected with microorganisms. The role of macrophages has largely been underestimated in literature, whereas the focus being mostly on neutrophils and epithelial cells. Macrophages may however play a significant role in the initiating stages of this disease, via an inability to act as a suppressor cell. Yet macrophage dysfunction may be the first step in cascade of events leading to chronic inflammation/infection in CF. Moreover, reports have suggested that CFTR contribute to altered inflammatory response in CF by modification of normal macrophage functions. OBJECTIVES: In order to highlight possible intrinsic macrophage defects due to impaired CFTR, we have studied inflammatory cytokines secretions, recognition of pathogens and phagocytosis in peripheral blood monocyte-derived macrophages from stable adult CF patients and healthy subjects (non-CF). RESULTS: In CF macrophage supernatants, concentrations of sCD14, IL-1β, IL-6, TNF-α and IL-10 were strongly raised. Furthermore expression of CD11b and TLR-5 were sorely decreased on CF macrophages. Beside, no difference was observed for mCD14, CD16, CD64, TLR-4 and TLR1/TLR-2 expressions. Moreover, a strong inhibition of phagocytosis was observed for CF macrophages. Elsewhere CFTR inhibition in non-CF macrophages also led to alterations of phagocytosis function as well as CD11b expression. CONCLUSIONS: Altogether, these findings demonstrate excessive inflammation in CF macrophages, characterized by overproduction of sCD14 and inflammatory cytokines, with decreased expression of CD11b and TLR-5, and impaired phagocytosis. This leads to altered clearance of pathogens and non-resolution of infection by CF macrophages, thereby inducing an exaggerated pro-inflammatory response.
ISSN: 1932-6203

inserm-00872278
http://www.hal.inserm.fr/inserm-00872278
http://www.hal.inserm.fr/inserm-00872278/document
http://www.hal.inserm.fr/inserm-00872278/file/Impaired_Functions.accepted.pdf
DOI : 10.1371/journal.pone.0075667

Éditeur(s) : HAL CCSD
Résumé : Inorganic arsenic is an environmental human carcinogen, but is also studied these days because of its potential effectiveness in curing chronic inflammatory disease. Indeed, this metalloid possesses immunosuppressive properties which can dysregulate physiological mechanisms involved in immune defense, or reduce inflammation associated with those inflammatory diseases. Inorganic arsenic is known mainly to alter functions of T cells and macrophages. However, it is unknown whether arsenic targets dendritic cells (DCs). Yet, this antigen presenting cells plays a major role in the immunosurveillance, and is involved in the physiopathology of chronic inflammatory diseases. So, the aim of my thesis work was to study the effects of inorganic arsenic on in vitro differenciation and maturation of dendritic cells from human monocytes. Our results mainly shows that concentrations corresponding to those measured in environmentally exposed people, inhibits DCs secretion of proinflammatory cytokines, which plays a major role in activation and polarization of T cells. Particularly, arsenic strongly impairs expression and secretion of interleukine 12 (IL-12) by an underlying molecular mechanism involving Nrf2. Finally, this work shows that inorganic arsenic has immunosuppressive properties on the physiology in vitro of human dendritic cells. Immunotoxicity may then contribute to the metalloid toxicity in environmentally exposed people. This element could be taken into account when determining arsenic effects in curing some chronic inflammatory diseases.
L’arsenic inorganique est un contaminant environnemental, cancérogène pour l’homme, mais également un métalloïde étudié, aujourd’hui, dans le traitement de maladies inflammatoires chroniques. Il possède des propriétés immunosuppressives pouvant déréguler les mécanismes physiologiques de défense ou bloquer l’exacerbation de réponses inflammatoires chroniques. L’arsenic inorganique altère principalement les fonctions des lymphocytes T et des macrophages. En revanche, l’impact du métalloïde sur la physiologie des cellules dendritiques (DCs) est peu connu. Pourtant, ces cellules présentatrices d’antigène jouent un rôle fondamental dans les processus d’immunosurveillance et sont très impliquées dans la physiopathologie des maladies inflammatoires chroniques. Dans ce contexte, les objectifs de mon travail de thèse étaient d’étudier les effets de l’arsenic inorganique sur la différenciation et la maturation in vitro de DCs générées à partir de monocytes humains. Nos résultats démontrent principalement que des concentrations de métalloïde, compatibles avec les taux plasmatiques d’arsenic mesurés chez les individus exposés, répriment la capacité des DCs à sécréter différentes cytokines pro-inflammatoires jouant un rôle essentiel dans l’activation et la polarisation des lymphocytes T. En particulier, l’arsenic inhibe l’expression et la sécrétion de l’interleukine-12 par un mécanisme moléculaire impliquant le facteur de transcription Nrf2. Au total, ces travaux de thèse démontrent que l’arsenic inorganique possède des propriétés immunosuppressives sur la physiologie in vitro des DCs humaines. Cette immunotoxicité pourrait contribuer à la toxicité du métalloïde chez l’homme exposé par voie environnementale, et être prise en compte pour déterminer les effets de l’arsenic dans le traitement de certaines maladies inflammatoires chroniques
https://tel.archives-ouvertes.fr/tel-01135887

NNT : 2013REN1B013
tel-01135887
https://tel.archives-ouvertes.fr/tel-01135887
https://tel.archives-ouvertes.fr/tel-01135887/document
https://tel.archives-ouvertes.fr/tel-01135887/file/pdf2star-1392896105-Th--se-M--linda-Macoch2.pdf

Éditeur(s) : HAL CCSD American Chemical Society
Résumé : Experiments were conducted to assess the potential impact of fractured well-cement degradation on leakage rate. Permeability was monitored while CO2-enriched reservoir-equilibrated brine was flowed at constant rate through a single fracture in a class G cement core under conditions mimicking geologic sequestration environments (temperature 60 °C, pressure 10 MPa). The results demonstrate that, at least for the conditions used in the experiment, an initial leakage in a 42 μm aperture fracture (permeability = 1.5 × 10-10 m2) can be self-mitigated due to the decrease of the fracture hydraulic aperture after about 15 h. This decrease results from the development of continuous highly hydrated amorphous Si-rich alteration products at the edge of the fracture and the dense carbonation of the bulk cement that mitigate the penetration of the alteration front.
ISSN: 0013-936X

hal-00950088
https://hal.archives-ouvertes.fr/hal-00950088
DOI : 10.1021/es401317c

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : National audience
Introduction Les télomérases sont les enzymes assurant la synthèse des télomères, séquences d’ADN essentiels dans la protection des chromosomes. Les mutations des télomérases sont responsables, entre autres, d’anomalies hématologiques, pulmonaires (fibrose pulmonaire idiopathique) et hépatiques. Il n’y a que peu de données dans la littérature concernant les résultats des transplantations pulmonaires chez ces patients mutés. Cas clinique Nous rapportons le cas d’un jeune homme de 39 ans, souffrant de syndrome myélodysplasique associé à une fibrose pulmonaire, permettant de poser le diagnostic de téloméropathie (mutation de la sous-unité ARN ou TERC ; r.182delG, pseudoknot area). L’insuffisance médullaire est sévère : leucopénie à 1,3 G/L dont 0,54 G/L de PNN, anémie macrocytaire (Hb à 10,3 g/dL ; VGM à 120 fL) et thombopénie à 27 G/L. Le syndrome restrictif est également sévère avec une CPT à 60 % et une CVF à 82 % de la valeur prédite (% pred). Il s’associe à une altération de la membrane alvéolo-capillaire (DLCO corrigée sur l’hémoglobine à 31 % pred). Le patient a été récusé à la fois pour la transplantation médullaire et pour la transplantation pulmonaire malgré son jeune âge. La prise en charge est donc palliative : réhabilitation respiratoire, oxygénothérapie, puis nintedanib. Discussion Dans la littérature, les transplantations médullaires chez les patients présentant une mutation des télomérases s’associent à une dégradation de la fonction respiratoire, en lien avec la toxicité des traitements immunosuppresseurs, même en l’absence d’atteinte pulmonaire initiale. Par ailleurs, les complications infectieuses et hématologiques post-transplantations pulmonaires chez ces patients mutés semblent plus fréquentes et nécessitent souvent une adaptation des traitements anti-rejets. Ces risques post-transplantations paraissent plus importants en présence d’une thrombopénie sévère préopératoire. Ces données sont cependant limitées à trois études rétrospectives de petites tailles. Au total, ce jeune patient a été jugé inéligible à la transplantation médullaire et à la transplantation pulmonaire, respectivement à cause de l’insuffisance respiratoire et de l’insuffisance médullaire. Il est émis l’hypothèse que l’allègement de la thérapie immunosuppressive pourrait améliorer le devenir des patients mutés transplantés, sans majorer le risque de rejet, illustrant le concept d’immunosénescence. Mais cette hypothèse reste à être validée. Ce cas clinique souligne l’importance de reconnaître les signes évocateurs de téloméropathie, dans la mesure où le diagnostic impacte la prise en charge de la fibrose pulmonaire
ISSN: 0761-8425

hal-01334065
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01334065
DOI : 10.1016/j.rmr.2016.04.018

Éditeur(s) : Wiley-blackwell
Résumé : Managing fisheries resources to maintain healthy ecosystems is one of the main goals of the ecosystem approach to fisheries (EAF). While a number of international treaties call for the implementation of EAF, there are still gaps in the underlying methodology. One aspect that has received substantial scientific attention recently is fisheries-induced evolution (FIE). Increasing evidence indicates that intensive fishing has the potential to exert strong directional selection on life-history traits, behaviour, physiology, and morphology of exploited fish. Of particular concern is that reversing evolutionary responses to fishing can be much more difficult than reversing demographic or phenotypically plastic responses. Furthermore, like climate change, multiple agents cause FIE, with effects accumulating over time. Consequently, FIE may alter the utility derived from fish stocks, which in turn can modify the monetary value living aquatic resources provide to society. Quantifying and predicting the evolutionary effects of fishing is therefore important for both ecological and economic reasons. An important reason this is not happening is the lack of an appropriate assessment framework. We therefore describe the evolutionary impact assessment (EvoIA) as a structured approach for assessing the evolutionary consequences of fishing and evaluating the predicted evolutionary outcomes of alternative management options. EvoIA can contribute to EAF by clarifying how evolution may alter stock properties and ecological relations, support the precautionary approach to fisheries management by addressing a previously overlooked source of uncertainty and risk, and thus contribute to sustainable fisheries.
Fish And Fisheries (1467-2960) (Wiley-blackwell), 2014-03 , Vol. 15 , N. 1 , P. 65-96

Droits : 2012 John Wiley & Sons Ltd
http://archimer.ifremer.fr/doc/00124/23522/21409.pdf
DOI:10.1111/faf.12007
http://archimer.ifremer.fr/doc/00124/23522/

Éditeur(s) : HAL CCSD
Résumé : International audience
A prospective study on randomized patients was conducted to determine how morphokinetic parameters are altered in embryos grown in sequential versus global culture media. Eleven morphokinetic parameters of 160 single embryos transferred were analyzed by time lapse imaging involving two University-affiliated in vitro fertilization (IVF) centers. We found that the fading of the two pronuclei occurred earlier in global (22.56±2.15 hpi) versus sequential media (23.63±2.71 hpi; p=0.0297). Likewise, the first cleavage started earlier at 24.52±2.33 hpi vs 25.76±2.95 hpi (p=0.0158). Also, the first cytokinesis was shorter in global medium, lasting 18±10.2 minutes in global versus 36±37.8 minutes in sequential culture medium (p <0.0001). We also observed a significant shortening in the duration of the 2-cell stage in sequential medium: 10.64 h±2.75 versus 11.66 h±1.11 in global medium (p=0.0225) which suggested a faster progression of the embryos through their first mitotic cell cycle. In conclusion, morphokinetic analysis of human embryos by Time lapse imaging reveals significant differences in five kinetic variables according to culture medium. Our study highlights the need to adapt morphokinetic analysis accordingly to the type of media used to best support human early embryo development.
Annales de Biologie Clinique

hal-01579406
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01579406
DOI : 10.1684/abc.2017.1259
PUBMED : 28751285

Éditeur(s) : HAL CCSD AGU and the Geochemical Society
Résumé : Mid-ocean ridges magmatism is, by and large, considered to be mostly dry. Nevertheless, numerous works in the last decade have shown that a hydrous component is likely to be involved in ocean ridges magmas genesis and/or evolution. The petrology and geochemistry of peculiar coarse grained gabbros sampled in the upper part of the gabbroic sequence from the northern Oman ophiolite (Wadi Rajmi) provide information on the origin and fate of hydrous melts in fast-spreading oceanic settings. Uncommon crystallization sequences for oceanic settings (clinopyroxene crystallizing before plagioclase), extreme mineral compositions (plagioclase An% up to 99, and clinopyroxene Mg # up to 96), and the presence of magmatic amphibole, imply the presence of a high water activity during crystallization. Various petrological and geochemical constraints point to hydration, resulting from the recycling of hydrothermal fluids. This recycling event may have occurred at the top of the axial magma chamber where assimilation of anatectic hydrous melts is recurrent along mid-ocean ridges or close to segments ends where fresh magma intrudes previously hydrothermally altered crust. In ophiolitic settings, hydration and remelting of hydrothermally altered rocks producing hydrous melts may also occur during the obduction process. Although dry magmatism dominates oceanic magmatism, the dynamic behavior of fast-spreading ocean ridge magma chambers has the potential to produce the observed hydrous melts (either in ophiolites or at spreading centers), which are thus part of the general mid-ocean ridges lineage.
ISSN: 1525-2027

hal-00939400
https://hal.archives-ouvertes.fr/hal-00939400
DOI : 10.1002/ggge.20137

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Diesel exhaust particles (DEPs) are common environmental air pollutants primarily affecting the lung. DEPs or chemicals adsorbed on DEPs also exert extra-pulmonary effects, including alteration of hepatic drug detoxifying enzyme expression. The present study was designed to determine whether organic DEP extract (DEPe) may target hepatic drug transporters that contribute in a major way to drug detoxification. Using primary human hepatocytes and transporter-overexpressing cells, DEPe was first shown to strongly inhibit activities of the sinusoidal solute carrier (SLC) uptake transporters organic anion-transporting polypeptides (OATP) 1B1, 1B3 and 2B1 and of the canalicular ATP-binding cassette (ABC) efflux pump multidrug resistance-associated protein 2, with IC50 values ranging from approximately 1 to 20 μg/mL and relevant to environmental exposure situations. By contrast, 25 μg/mL DEPe failed to alter activities of the SLC transporter organic cation transporter (OCT) 1 and of the ABC efflux pumps P-glycoprotein and bile salt export pump (BSEP), whereas it only moderately inhibited those of sodium taurocholate co-transporting polypeptide and of breast cancer resistance protein (BCRP). Treatment by 25 μg/mL DEPe was next demonstrated to induce expression of BCRP at both mRNA and protein level in cultured human hepatic cells, whereas it concomitantly repressed mRNA expression of various transporters, including OATP1B3, OATP2B1, OCT1 and BSEP. Such changes in transporter expression were found to be highly correlated to those caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a reference activator of the aryl hydrocarbon receptor (AhR) pathway. This suggests that DEPe, which is enriched in known ligands of AhR like polycyclic aromatic hydrocarbons, alters drug transporter expression via activation of the AhR cascade. Taken together, these data established human hepatic transporters as targets of organic chemicals containing in DEPs, which may contribute to their systemic effects through impairing hepatic transport of endogenous compound or drug substrates of these transporters.
ISSN: 1932-6203

Droits : http://creativecommons.org/licenses/by/
hal-01138535
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01138535
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01138535/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01138535/file/Regulation%20of%20human%20hepatic%20drug.pdf
DOI : 10.1371/journal.pone.0121232