Éditeur(s) : HAL CCSD
Résumé : Background Acute splenic sequestration is one of the major clinical forms of sickle cell disease. This potentially life-threatening complication is defined by a rapid sequestration of sickle red blood cells in the spleen. Approximately 30% of young patients will develop this complication and 49% of them will have recurrences. Methods The decision tree method is a statistical method that can act as a medical decision tool in the case of a complex biological problem. The decision tree method is used here to determine the variables involved in the severity and recurrence of acute splenic sequestration crises. Results A prior decision tree shows that platelet level, variation in spleen size, patient age and hygrometry also called relative humidity define acute splenic sequestration severity. A second one shows that spleen size variation, atmospheric pressure and patient age define recurrence. Conclusions For the first time, biological and environmental parameters are combined to discover some interesting rules which can lead to more accurate evaluations of acute splenic sequestration severity and recurrence. Thus, this method provides a sharp diagnostic tool which could improve medical treatment for better patient care.
https://hal.archives-ouvertes.fr/hal-00201460

hal-00201460
https://hal.archives-ouvertes.fr/hal-00201460
https://hal.archives-ouvertes.fr/hal-00201460v2/document
https://hal.archives-ouvertes.fr/hal-00201460/file/DT_Marianne_v2.pdf

Éditeur(s) : HAL CCSD Springer
Résumé : Third International Workshop, MLMI 2012, Held in Conjunction with MICCAI 2012
International audience
Universal Nearest Neighbours (unn) is a classifier recently proposed, which can also effectively estimates the posterior probability of each classification act. This algorithm, intrinsically binary, requires the use of a decomposition method to cope with multiclass problems, thus reducing their complexity in less complex binary subtasks. Then, a reconstruction rule provides the final classification. In this paper we show that the application of unn algorithm in conjunction with a reconstruction rule based on the posterior probabilities provides a classification scheme robust among different biomedical image datasets. To this aim, we compare unn performance with those achieved by Support Vector Machine with two different kernels and by a k Nearest Neighbours classifier, and applying two different reconstruction rules for each of the aforementioned classification paradigms. The results on one private and five public biomedical datasets show satisfactory performance.
Machine Learning in Medical Imaging
Nice, France

hal-00958909
https://hal.archives-ouvertes.fr/hal-00958909
https://hal.archives-ouvertes.fr/hal-00958909/document
https://hal.archives-ouvertes.fr/hal-00958909/file/Miccai.pdf
DOI : 10.1007/978-3-642-35428-1_15

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Background & Aims: The severity of liver diseases is exacerbated by the death of hepatocytes, which can be induced by the sensing of pathogen associated molecular patterns (PAMPs) derived from the gut microbiota. The molecular mechanisms regulating these cell death pathways are poorly documented. In this study, we investigated the role of the receptor interacting protein kinase 1 (RIPK1), a protein known to regulate cell fate decisions, in the death of hepatocytes using two in vivo models of PAMP-induced hepatitis. Methods: Hepatitis was induced in mice by independent injections of two different bacterial PAMPs: lipopolysaccharide (LPS) and unmethylated CpG oligodeoxynucleotide (CpG-DNA) motifs. The role of RIPK1 was evaluated by using mice specifically lacking RIPK1 in liver parenchymal cells (Ripk1(LPC-KO)). Administration of liposome-encapsulated clodronate served to investigate the role of Kupffer cells in the establishment of the disease. Etanercept, a tumor necrosis factor (TNF)-decoy receptor, was used to study the contribution of TNF-alpha during LPS-mediated liver injury. Results: Whereas RIPK1 deficiency in liver parenchymal cells did not trigger basal hepatolysis, it greatly sensitized hepatocytes to apoptosis and liver damage following a single injection of LPS or CpG-DNA. Importantly, hepatocyte death was prevented by previous macrophage depletion or by TNF inhibition. Conclusions: Our data highlight the pivotal function of RIPK1 in maintaining liver homeostasis in conditions of macrophage-induced TNF burst in response to PAMPs sensing. Lay summary: Excessive death of hepatocytes is a characteristic of liver injury. A new programmed cell death pathway has been described involving upstream death ligands such as TNF and downstream kinases such as RIPK1. Here, we show that in the presence of LPS liver induced hepatic injury was due to secretion of TNF by liver macrophages, and that RIPK1 acts as a powerful protector of hepatocyte death. This newly identified pathway in the liver may be helpful in the management of patients to predict their risk of developing acute liver failure. (C) 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
ISSN: 0168-8278

hal-01532060
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01532060
DOI : 10.1016/j.jhep.2017.01.005
PUBMED : 28088582

Éditeur(s) : HAL CCSD Wiley-VCH Verlag
Résumé : International audience
The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that mediates immunosuppression caused by a variety of environmental contaminants, such as polycyclic aromatic hydrocarbons or dioxins. Recent evidence suggests that AhR plays an important role in T-cell-mediated immune responses by affecting the polarization and differentiation of activated T cells. However, the regulation of AhR expression in activated T cells remains poorly characterized. In the present study, we used purified human T cells stimulated with anti-CD3 and anti-CD28 Abs to investigate the effect of T-cell activation on AhR mRNA and protein expression. The expression of AhR mRNA increased significantly and rapidly after T-cell activation, identifying AhR as an immediate-early activation gene. AhR upregulation occurred in all of the T-cell subtypes, and is associated with its nuclear translocation and induction of the cytochromes P-450 1A1 and 1B1 mRNA expression in the absence of exogenous signals. In addition, the use of an AhR antagonist or siRNA-mediated AhR knockdown significantly inhibited IL-22 expression, suggesting that expression and functional activation of AhR is necessary for the secretion of IL-22 by activated T cells. In conclusion, our data support the idea that AhR is a major player in T-cell physiology.
ISSN: 0014-2980

hal-01063944
https://hal.archives-ouvertes.fr/hal-01063944
DOI : 10.1002/eji.201343920
PUBMED : 24549985

Éditeur(s) : HAL CCSD
Résumé : International audience
Objective: To estimate the social cost of respiratory cancers attributable to occupational risk factors in France in 2010. Methods: We estimated the number of cases ofrespiratory cancers attributable to each identified occupational risk factor according to the attributable fractions method. We also estimated direct (costs of hospital stays, drugs, outpatient care) and indirect costs (production losses) related to morbidity (absenteeism and presenteeism) and mortality (years of lost production). Production losses for paid work and unpaid domestic activities were taken into account. Results: The social cost of respiratory cancers (lung, larynx, sinonasal, pleural mesothelioma) attributable to exposure to asbestos, chromium, diesel engine exhaust, polycyclic aromatic hydrocarbons, painting occupations (unidentified carcinogen), crystalline silica, wood and leather dust in France in 2010 was estimated to be between 960 and 1,866 million. The cost of lung cancer represents between 804 and 1,617 million. The three risk factors with the greatest impact are asbestos ((sic)530 to 890 million), diesel engine exhaust ((sic)227 to 394 million), and crystalline silica ( 116 to 268 million). Conclusion: These results provide a conservative estimate of the public health and economic burden of respiratory cancers attributable to occupational risk factors from a societal perspective.
ISSN: 0995-3914

hal-01659246
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01659246
DOI : 10.3917/spub.174.0509
PUBMED : 29034666

Éditeur(s) : HAL CCSD
Résumé : International audience
BACKGROUND: Africa faces a number of unique environmental challenges. Unfortunately, it lacks the infrastructure needed to support the comprehensive environmental studies that could provide the scientific basis to inform environmental policies. There are a number of known sources of endocrine-disrupting chemicals (EDCs) and other hazardous chemicals in Africa. However, a coordinated approach to identify and monitor these contaminants and to develop strategies for public health interventions has not yet been made. OBJECTIVES: This commentary summarizes the scientific evidence presented by experts at the First African Endocrine Disruptors meeting. We describe a "call to action" to utilize the available scientific knowledge to address the impact of EDCs on human and wildlife health in Africa. DISCUSSION: We identify existing knowledge gaps about exposures to EDCs in Africa and describe how well-designed research strategies are needed to address these gaps. A lack of resources for research and a lag in policy implementation slows down intervention strategies and poses a challenge to advancing future health in Africa. CONCLUSION: To address the many challenges posed by EDCs, we argue that Africans should take the lead in prioritization and evaluation of environmental hazards, including EDCs. We recommend the institution of education and training programs for chemical users, adoption of the precautionary principle, establishment of biomonitoring programs, and funding of community-based epidemiology and wildlife research programs led and funded by African institutes and private companies. https://doi.org/10.1289/EHP1774.
Environmental Health Perspectives

hal-01616487
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01616487
DOI : 10.1289/EHP1774
PUBMED : 28935616

Éditeur(s) : HAL CCSD Endocrine Society
Résumé : International audience
: Context:Masculinization depends on the fetal testis. Exposure of the human fetus during pregnancy to paracetamol or/and to other mild-analgesics is associated with an increased risk of cryptorchidism.Objective:We aimed at determining whether mild analgesics disrupted the morphology and endocrine function of the human testis.Design:We used an in vitro system based on the culture of human fetal testes exposed or not to paracetamol, its metabolite AM404, aspirin, indomethacin, ketoconazole at 10(-4) M to 10(-7) M.Setting:The study was conducted at the University of Rennes I.Patients/Participants:Human fetal testes were from pregnant women following induced abortion, between 7 and 12 weeks of gestation (GW).Main Outcome Measures:Testosterone (radioimmunoassay: RIA), Anti-Müllerian Hormone (AMH; ELISA), insulin-like factor 3 (INSL3; RIA), prostaglandin D2 and E2 (PGD2 and PGE2, respectively; ELISA), were assayed in the media. Testicular cells were counted using histology and image analysis. The possible nuclear receptor-mediated activities of the analgesics were investigated using reporter cell lines expressing estrogen (ERs), androgen (AR) and peroxysome proliferator-activated γ ( PPARγ) receptors.Results:Indomethacin and aspirin stimulated testosterone production, particularly by the younger testes (8-9 GW vs 10-12 GW). Paracetamol, AM404 and ketoconazole decreased INSL3 levels. Aspirin stimulated, whereas ketoconazole inhibited AMH production. PGE2 levels were inhibited by paracetamol, and aspirin in the 7-12 GW testes, and by indomethacin but only in 7-9.86 GW old testes. The inhibitory trends seen for PGD2 were not statistically significant.Conclusions:Analgesics at concentrations relevant to human exposure cause endocrine disturbances in the fetal testis. We suggest that the fetal human testis displays slight critical age windows for sensitivity to direct exposure to aspirin, indomethacin and paracetamol. The analgesic-induced inhibition of INSL3 may be the mechanism by which analgesics increase the risk of cryptorchidism. Greater caution is required concerning consumption of analgesics during pregnancy.
ISSN: 0021-972X

inserm-00876125
http://www.hal.inserm.fr/inserm-00876125
DOI : 10.1210/jc.2013-2531
PUBMED : 24030937

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
: Zebrafish, Danio rerio, is increasingly used as an animal model to study the effects of pharmaceuticals and environmental estrogens. As most of these estrogens have only been tested on human estrogen receptors (ERs), it is necessary to measure their effects on zebrafish ERs. In humans there are two distinct nuclear ERs (hERα and hERβ), whereas the zebrafish genome encodes three ERs, zfERα and two zfERβs (zfERβ1 and zfERβ2). In this study, we established HeLa-based reporter cell lines stably expressing each of the three zfERs. We first reported that estrogens more efficiently activate the zfERs at 28°C as compared to 37°C, thus reflecting the physiological temperature of zebrafish in wildlife. We then showed significant differences in the ability of agonist and antagonist estrogens to modulate activation of the three zfER isotypes in comparison to hERs. Environmental compounds (bisphenol A, alkylphenols, mycoestrogens) which are hER panagonists and hERβ selective agonists displayed greater potency for zfERα as compared to zfERβs. Among hERα selective synthetic agonists, PPT did not activate zfERα while 16α-LE2 was the most zfERα selective compound. Altogether, these results confirm that all hER ligands control in a similar manner the transcriptional activity of zfERs although significant differences in selectivity were observed among subtypes. The zfER subtype selective ligands that we identified thus represent new valuable tools to dissect the physiological roles of the different zfERs. Finally, our work also points out that care has to be taken in transposing the results obtained using the zebrafish as a model for human physiopathology.
ISSN: 0041-008X

inserm-01067804
http://www.hal.inserm.fr/inserm-01067804
http://www.hal.inserm.fr/inserm-01067804/document
http://www.hal.inserm.fr/inserm-01067804/file/pintot_et_al._manuscript.pdf
DOI : 10.1016/j.taap.2014.07.020

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Human hepatocytes cultured in a monolayer configuration represent a well-established in vitro model in liver toxicology, notably used in drug transporter studies. Polarized status of drug transporters, i.e., their coordinated location at sinusoidal or canalicular membranes, remains however incompletely documented in these cultured hepatocytes. The present study was therefore designed to analyze transporter expression and location in such cells. Most of drug transporters were first shown to be present at notable mRNA levels in monolayer-cultured human hepatocytes. Cultured human hepatocytes, which morphologically exhibited bile canaliculi-like structures, were next demonstrated, through immunofluorescence staining, to express the influx transporters organic anion transporting polypeptide (OATP) 1B1, OATP2B1 and organic cation transporter (OCT) 1 and the efflux transporter multidrug resistance-associated protein (MRP) 3 at their sinusoidal pole. In addition, the efflux transporters P-glycoprotein and MRP2 were detected at the canalicular pole of monolayer-cultured human hepatocytes. Moreover, canalicular secretion of reference substrates for the efflux transporters bile salt export pump, MRP2 and P-glycoprotein as well as sinusoidal drug transporter activities were observed. This polarized and functional expression of drug transporters in monolayer-cultured human hepatocytes highlights the interest of using this human in vitro cell model in xenobiotic transport studies.
ISSN: 0887-2333

hal-01141725
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01141725
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01141725/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01141725/file/Polarized%20location%20of%20SLC.pdf
DOI : 10.1016/j.tiv.2015.03.019

Éditeur(s) : HAL CCSD
Résumé : International audience
Tension wood, a tissue developed by angiosperm trees to actively recover their verticality, has long been defined by the presence of an unlignified cellulosic inner layer in the cell wall of fibres, called the G-layer. Although it was known that some species have no G-layer, the definition was appropriate since it enabled easy detection of tension wood zones using various staining techniques for either cellulose or lignin. For several years now, irrespective of its anatomical structure, tension wood has been defined by its high mechanical internal tensile stress. This definition enables screening of the diversity of cell walls in tension wood fibres. Recent results obtained in tropical species with tension wood with a delay in the lignification of the G-layer opened our eyes to the effective presence of large amounts of lignin in the G-layer of some species. This led us to review older literature mentioning the presence of lignin deposits in the G-layer and give them credit. Advances in the knowledge of tension wood fibres allow us to reconsider some previous classifications of the diversity in the organisation of the fibre walls of the tension wood.
ISSN: 0928-1541

hal-01636686
https://hal.archives-ouvertes.fr/hal-01636686
https://hal.archives-ouvertes.fr/hal-01636686/document
https://hal.archives-ouvertes.fr/hal-01636686/file/2017_Ghislain-Clair_IAWAJ_DiversityOrganisationLignificationTensionWoodFibreWalls-AReview.pdf
DOI : 10.1163/22941932-20170170

Éditeur(s) : HAL CCSD American Society for Biochemistry and Molecular Biology
Résumé : International audience
Chronic low grade inflammation is closely linked to obesity-associated insulin resistance. To examine how administration of the anti-inflammatory compound indomethacin, a general cyclooxygenase inhibitor, affected obesity development and insulin sensitivity, we fed obesity-prone male C57BL/6J mice a high fat/high sucrose (HF/HS) diet or a regular diet supplemented or not with indomethacin (±INDO) for 7 weeks. Development of obesity, insulin resistance, and glucose intolerance was monitored, and the effect of indomethacin on glucose-stimulated insulin secretion (GSIS) was measured in vivo and in vitro using MIN6 β-cells. We found that supplementation with indomethacin prevented HF/HS-induced obesity and diet-induced changes in systemic insulin sensitivity. Thus, HF/HS+INDO-fed mice remained insulin-sensitive. However, mice fed HF/HS+INDO exhibited pronounced glucose intolerance. Hepatic glucose output was significantly increased. Indomethacin had no effect on adipose tissue mass, glucose tolerance, or GSIS when included in a regular diet. Indomethacin administration to obese mice did not reduce adipose tissue mass, and the compensatory increase in GSIS observed in obese mice was not affected by treatment with indomethacin. We demonstrate that indomethacin did not inhibit GSIS per se, but activation of GPR40 in the presence of indomethacin inhibited glucose-dependent insulin secretion in MIN6 cells. We conclude that constitutive high hepatic glucose output combined with impaired GSIS in response to activation of GPR40-dependent signaling in the HF/HS+INDO-fed mice contributed to the impaired glucose clearance during a glucose challenge and that the resulting lower levels of plasma insulin prevented the obesogenic action of the HF/HS diet.
The journal of biological chemistry

hal-01063926
https://hal.archives-ouvertes.fr/hal-01063926
DOI : 10.1074/jbc.M113.525220

Éditeur(s) : HAL CCSD
Résumé : International audience
The main biological function of reaction wood is to act as “muscle” for trees, enabling them to control their posture and right stems when they are permanently disturbed from their set-point inclination by gravity or winds. The key property to achieve this function is the development of high mechanical stress during the formation of reaction wood cells, called “maturation strains”. Moreover, this function is basically performed through the asymmetric formation of wood (in quantity or quality) around the tree circumference. This asymmetry enables stems to bend upward or to compensate for the downward bending induced by gravity, as an asymmetric force associated to maturation strains creates a bending moment (i.e. one side of the stem “pulls” the other one). We will discuss the traits (cross sectional size and shape, wood features as G fibers or microfibril angle, eccentric growth even in usual or extreme cases as buttresses, total biomass growth and height of center of mass, stem lean and set-point angle) involved to understand how the posture control works. We will give simple formulas to estimate a “muscle efficiency” from biomechanical modeling. We will give practical methods to estimate all the involved traits, especially maturation strains from direct and indirect measurements, in peripheral functional wood or by retrospective dendrochronological analysis. Then, we will illustrate how tree stem tropisms and especially gravitropism, widely studied by physiologists, are key processes in natural ecosystems, through practical examples from tropical rainforest tree communities and regeneration of European mixed beech forests. Using the previous definition of postural control efficiency, we will show that the cross section size is rapidly a limiting factor, opposing the extreme strategies of flexible small stems, which bend easily but also right themselves quickly, to stiff big stems. Lastly, as wood in living trees ensures general storage, defence, vascular and skeletal functions, we will ask general questions about synergies and trade-offs between posture control and other functions.
Botany 2014 : new frontiers in botany
Boise, United States

hal-01627031
https://hal.archives-ouvertes.fr/hal-01627031

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
Plants often rely on external, mutualistic partners to survive and reproduce in resource-limited environments or for protection from enemies. Such interactions, including mycorrhizal symbioses and ant-plant associations, are widespread and play an important role at the ecosystem and community levels. In ant-plant mutualisms, the plants may benefit from both the protection provided by the presence of ants and from the nutrients absorbed from insect debris. However, the role of third partners in plant nutrition, particularly ant-associated fungi, has never before been demonstrated. 2. We investigate this issue in the ant-plant Hirtella physophora. In this model system, Allomerus decemarticulatus ants are involved in two, highly specific interactions: first, with their host plant, and, secondly, with a fungus that they actively manipulate. Moreover, the ants combine both plant trichomes and fungal hyphae to make a trap to capture prey. 3. We empirically demonstrate the existence of a third type of interaction between the fungus and the plant through the use of both experimental enrichments with stable isotopes (15N) and histological approaches. The fungus growing in the galleries plays a role in providing nutrients to the host plant, in addition to the structural role it plays for the ants. Fungus-facilitated nitrogen uptake occurs mainly in old domatia, where abundant hyphae are in close contact with the plant cells. Whether the fungi inside the domatia and those in the galleries are the same is still uncertain. 4. Synthesis. Together, our results show that a fungal partner in an ant-plant mutualism can benefit the plant by improving its nutrient uptake, and they demonstrate the existence of a true tripartite mutualismin this system. Our results add further evidence to the notion that interpretations of some ant-plant symbioses as purely protective mutualisms have overlooked these nutritional aspects.
ISSN: 0022-0477

hal-00818792
https://hal.archives-ouvertes.fr/hal-00818792

Éditeur(s) : HAL CCSD
Résumé : The ovary is not solely the unique source of oocytes necessary for fertilization but also a crucial conductor of endocrine regulations of the reproductive system. In the fetal ovary, oocytes grouped in clusters are surrounded by somatic pre-granulosa cells, altogether delineated by a basement membrane and constituting ovarian cords. The formation of the definitive ovarian functional units requires their fragmentation into follicles formed by a single oocyte surrounded by granulosa cells and delineated by a basement membrane. This partitioning occurs within a tiny period and is dependent on the correct timing of the meiotic process, on an apoptotic wave that specifically targets oocytes and the remodelling of the basement membrane. Follicle formation is a crucial event of ovarian development because the follicle stock formed at the end of this process is non-renewable. Therefore, any disturbance of this process can lead to reproductive abnormalities in adulthood. Recent data on endocrine disruptors displaying estrogenic activity have involved the fragile estrogenic homeostasis in the process. We aimed at better understanding how the endogen estrogen 17b-estradiol (E2) contributes to follicle formation. To assess it, Sprague-Dawley rats were treated with E2 at different doses during follicle formation, /i.e./ in the 3 days following birth. We show that although this treatment impairs the development of the hepatic and ovarian detoxification systems, the female neonate is able to increase its estrogen clearance capabilities. Nevertheless, E2 treatment within this critical period triggers a dose-dependent decrease of oocyte number per ovary. Regardless of the E2 dose, puberty is advanced. All treated females are at least transiently fertile, yet these reproductive capabilities rapidly decline. A high (10 µg/day) dose of E2 leads to a secondary infertility characterized by anovulation that probably result from a dysfunction of the whole reproductive tract. By contrast, a lower (0.1 µg/day) dose of E2, that does not significantly modify neonatal oocyte survival, leads to a progressive reproductive senescence likely due to ovarian failure. Long-term troubles may originate from precocious E2 impact on the ovary since it disturbs ovarian transcriptome and produces many lesions on ovarian cell DNA.
L'ovaire est au cœur de la physiologie de la reproduction féminine. Il est à la fois à l'origine des ovocytes nécessaires à la fécondation et acteur des régulations endocrines du système reproducteur. Les ovocytes de l'ovaire fœtal sont groupés en amas bordés de cellules somatiques et d'une membrane basale, formant les cordons ovariens. Ces cordons ovariens se fragmentent pour former les follicules ovariens: un ovocyte bordé de cellules somatiques et d'une membrane basale. Cette fragmentation se déroule sur une courte période (/in utero/ chez la femme et juste après la naissance chez les rongeurs) et fait intervenir une vague de mort cellulaire programmée touchant les ovocytes pendant leur méiose et un remodelage de la membrane basale. La formation des follicules est une période cruciale du développement ovarien puisque le stock de follicules formés à l'issue de ce processus est non renouvelable. Son altération peut donc être à l'origine de troubles de la fonction de reproduction chez le futur adulte. Il existe une fragile homéostasie œstrogénique en place au moment de la formation folliculaire: chez la femme, l'ovaire se développe /in utero/, sous l'influence des œstrogènes circulants maternels et la production ovarienne fœtale. Chez les rongeurs, les follicules se forment lors de la levée de l'imprégnation hormonale maternelle au moment de la naissance. Nous avons souhaité comprendre comment le 17b-œstradiol (E2), œstrogène endogène, pouvait contribuer à la mise en place des follicules. Pour cela, des rattes Sprague-Dawley ont été traitées pendant la période de formation des follicules avec de l'E2 à différentes doses entre 0.01 et 10 µg/jour. Nos travaux démontrent que le traitement de rattes par des œstrogènes entre leur naissance et 3 jours induit une réduction dose-dépendante de leur nombre d'ovocytes. Bien que le traitement entrave le développement normal du système de détoxication hépatique et ovarien, l'animal est capable d'accroître ses capacités d'élimination des œstrogènes. Ces capacités sont toutefois insuffisantes pour bloquer les effets du traitement. Quelle que soit la dose d'E2 utilisée (0.1 ou 10 µg/jour), la puberté est plus précoce chez les femelles exposées mais toutes sont fertiles, au moins transitoirement. Cependant le traitement induit une dégradation rapide des capacités reproductives. L'E2 modifie la dynamique folliculaire chez l'adulte, longtemps après l'arrêt du traitement. Si une forte dose d'E2 réduit la survie des ovocytes lors de la formation des follicules et conduit à une infertilité secondaire due à un dysfonctionnement général du tractus reproducteur, une dose faible n'affecte pas la survie des ovocytes à court terme mais conduit à une sénescence reproductive précoce vraisemblablement d'origine ovarienne. L'origine de ces troubles pourrait résider dans les effets précoces de l'exposition à E2 : cette molécule altère le transcriptome ovarien et induit de nombreuses lésions de l'ADN des cellules ovariennes.
https://tel.archives-ouvertes.fr/tel-00953657

NNT : 2013REN1S107
tel-00953657
https://tel.archives-ouvertes.fr/tel-00953657
https://tel.archives-ouvertes.fr/tel-00953657/document
https://tel.archives-ouvertes.fr/tel-00953657/file/CHALMEY_Clementine.pdf

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
Chlordecone (CLD) was an organochlorine insecticide whose previous use resulted in an extensive pollution of the environment with severe health effects and social consequences. A closely related compound, 5b-hydrochlordecone (5b-hydroCLD), has been searched for and often detected in environmental matrices from the geographical area where CLD was applied. The current consensus considered that its presence was not the result of a biotic or abiotic dechlorination of CLD in these matrices but rather the consequence of its presence as impurity (synthesis by-product) in the CLD released into the environment. The aim of the present study was to determine if and to what extent degradation of CLD into 5b-hydroCLD occurred in the field. To test this hypothesis, the ratios of 5b-hydroCLD and CLD concentrations in a dataset of 810 soils collected between 2006 and 2012 in Martinique were compared to the ratios measured in 3 samples of the CLD dust commercial formulations applied in the banana fields of French West Indies (FWI) and 1 sample of the technical-grade CLD corresponding to the active ingredient used in such formulations. Soil data were processed with a hierarchical Bayesian model to account for random measurement errors and data censoring. Any pathway of CLD transformation into 5b-hydroCLD occurring over the long term in FWI soils would indeed change the ratio of 5b-hydroCLD/CLD compared to what it was in the initially applied formulations. Results showed a significant increase of the 5b-hydroCLD/CLD ratio in the soils-25 times greater in soil than in commercial formulations-which suggested that natural CLD transformation into 5b-hydroCLD over the long term occurred in these soils. Results from this study may impact future decisions for the remediation of the polluted areas.
ISSN: 0944-1344

hal-01347150
https://hal.archives-ouvertes.fr/hal-01347150
https://hal.archives-ouvertes.fr/hal-01347150/document
https://hal.archives-ouvertes.fr/hal-01347150/file/Devault_15973.pdf
DOI : 10.1007/s11356-015-4865-0

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Epithelial-to-mesenchymal transition (EMT) promotes cell motility, which is important for the metastasis of malignant cells, and blocks CD95-mediated apoptotic signaling triggered by immune cells and chemotherapeutic regimens. CD95L, the cognate ligand of CD95, can be cleaved by metalloproteases and released as a soluble molecule (cl-CD95L). Unlike transmembrane CD95L, cl-CD95L does not induce apoptosis but triggers cell motility. Electron paramagnetic resonance was used to show that EMT and cl-CD95L treatment both led to augmentation of plasma membrane fluidity that was instrumental in inducing cell migration. Compaction of the plasma membrane is modulated, among other factors, by the ratio of certain lipids such as sphingolipids in the membrane. An integrative analysis of gene expression in NCI tumor cell lines revealed that expression of ceramide synthase-6 (CerS6) decreased during EMT. Furthermore, pharmacological and genetic approaches established that modulation of CerS6 expression/activity in cancer cells altered the level of C16-ceramide, which in turn influenced plasma membrane fluidity and cell motility. Therefore, this study identifies CerS6 as a novel EMT-regulated gene that has a pivotal role in the regulation of cell migration.Oncogene advance online publication, 17 March 2014; doi:10.1038/onc.2014.55.
ISSN: 0950-9232

hal-01063558
https://hal.archives-ouvertes.fr/hal-01063558
https://hal.archives-ouvertes.fr/hal-01063558/file/Down-regulation%20of%20ceramide_accepted.pdf
DOI : 10.1038/onc.2014.55
PUBMED : 24632610

Éditeur(s) : HAL CCSD
Résumé : International audience
Wound healing is important for sharks from the earliest life stages, for example, as the 'umbilical scar' in viviparous species heals, and throughout adulthood, when sharks can incur a range of external injuries from natural and anthropogenic sources. Despite anecdotal accounts of rapid healing in elasmobranchs, data regarding recovery and survival of individuals from different wound or injury types has not been systematically collected. The present study documented: (i) 'umbilical scar' healing in wild-caught, neonatal blacktip reef sharks while being reared for 30 days in flow-through laboratory aquaria in French Polynesia; (ii) survival and recovery of free-swimming blacktip reef sharks in Australia and French Polynesia following a range of injuries; and (iii) long-term survival following suspected shark-finning activities. Laboratory monitoring, tag-recapture records, telemetry data and photo-identification records suggest that blacktip reef sharks have a high capacity to survive and recover from small or even large and severe wounds. Healing rates, recovery and survival are important factors to consider when assessing impacts of habitat degradation and fishing stress on shark populations. The present study suggests that individual survival may depend more on handling practices and physiological stress rather than the extent of physical injury. These observations also contribute to discussions regarding the ethics of tagging practices used in elasmobranch research and provide baseline healing rates that may increase the accuracy in estimating reproductive timing inferred from mating scars and birth dates for neonatal sharks based on umbilical scar healing status. Cite as: Chin A, Mourier J, Rummer JL (2015) Blacktip reef sharks (Carcharhinus melanopterus) show high capacity for wound healing and recovery following injury. Conserv Physiol 3: doi:10.1093/conphys/cov062.
Conservation physiology

Droits : http://creativecommons.org/licenses/by/
hal-01250745
https://hal-univ-perp.archives-ouvertes.fr/hal-01250745
https://hal-univ-perp.archives-ouvertes.fr/hal-01250745/document
https://hal-univ-perp.archives-ouvertes.fr/hal-01250745/file/Conserv%20Physiol-2015-Chin-.pdf
DOI : 10.1093/conphys/cov062

Éditeur(s) : HAL CCSD Springer Verlag (Germany)
Résumé : International audience
Tight control of basal cytosolic Ca2+ concentration is essential for cell survival and to fine-tune Ca2+-dependent cell functions. A way to control this basal cytosolic Ca2+ concentration is to regulate membrane Ca2+ channels including store-operated Ca2+ channels and secondary messenger-operated channels linked to G-protein-coupled or tyrosine kinase receptor activation. Orai, with or without its reticular STIM partner and Transient Receptor Potential (TRP) proteins, were considered to be the main Ca2+ channels involved. It is well accepted that, in response to cell stimulation, opening of these Ca2+ channels contributes to Ca2+ entry and the transient increase in cytosolic Ca2+ concentration involved in intracellular signaling. However, in various experimental conditions, Ca2+ entry and/or Ca2+ currents can be recorded at rest, without application of any experimental stimulation. This led to the proposition that some plasma membrane Ca2+ channels are already open/activated in basal condition, contributing therefore to constitutive Ca2+ entry. This article focuses on direct and indirect observations supporting constitutive activity of channels belonging to the Orai and TRP families and on the mechanisms underlying their basal/constitutive activities.
ISSN: 0175-7571

inserm-01526286
http://www.hal.inserm.fr/inserm-01526286
http://www.hal.inserm.fr/inserm-01526286/document
http://www.hal.inserm.fr/inserm-01526286/file/EBJO-D-16-00056_R1-2%20%282%29.pdf
PUBMED : 28516266

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
Background - Pregnant women are a vulnerable population. Although regular follow-ups are recommended during pregnancy, not all pregnant women seek care. This pilot study wanted to assess whether the integration of data from administrative health information systems and socio-economic features allows identifying disparities in prenatal care trajectories.Methods - Prenatal care trajectories were extracted from the permanent sample of the French health insurance information system linked to the hospital discharge information system. The records of 2518 women who gave birth without complications in France in 2009 were analyzed. State sequence data analysis was performed to identify homogeneous groups of prenatal care trajectories. Socio-economic data were used to characterize their living environment.Results -We identified three groups of homogeneous prenatal care trajectories: (i) women with relatively high prenatal care consumption (~11 %), (ii) women with no prenatal care (~21 %), and (iii) women with an intermediate level of prenatal care (~66 %). Analysis of the socio-economic data demonstrated the association between disparities in prenatal care trajectories and the women’s living environment. Women with relatively high care consumption generally lived in socio-economically privileged areas (better education levels, employment status and housing conditions) compared with women with few or no prenatal care.Conclusions -Although ecological, our approach demonstrates that data from health administrative information systems could be used to describe prenatal care. However, more individual variables and an improvement of the data quality are needed to efficiently monitor the content and timing of prenatal care. Moreover, state sequence analysis, which was used in this context for the first time, proves to be an interesting approach to explore care trajectories. Finally, the integration of heterogeneous sources of data, including contextual information, might help identifying areas that require health promotion actions toward vulnerable populations, such as pregnant women.
ISSN: 1472-6963

hal-01169792
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01169792
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01169792/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01169792/file/Mining%20care%20trajectories%20using%20health%20administrative.pdf
DOI : 10.1186/s12913-015-0857-5

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
Mechanical forces influence the growth and shape of virtually all tissues and organs. Recent studies show that increased cell contractibility, growth and differentiation might be normalized by modulating cell tensions. Particularly, the role of these tensions applied by the extracellular matrix during liver fibrosis could influence the hepatocarcinogenesis process. The objective of this study is to determine if 3D stiffness could influence growth and phenotype of normal and transformed hepatocytes and to integrate extracellular matrix (ECM) stiffness to tensional homeostasis. We have developed an appropriate 3D culture model: hepatic cells within three-dimensional collagen matrices with varying rigidity. Our results demonstrate that the rigidity influenced the cell phenotype and induced spheroid clusters development whereas in soft matrices, Huh7 transformed cells were less proliferative, well-spread and flattened. We confirmed that ERK1 played a predominant role over ERK2 in cisplatin-induced death, whereas ERK2 mainly controlled proliferation. As compared to 2D culture, 3D cultures are associated with epithelial markers expression. Interestingly, proliferation of normal hepatocytes was also induced in rigid gels. Furthermore, biotransformation activities are increased in 3D gels, where CYP1A2 enzyme can be highly induced/activated in primary culture of human hepatocytes embedded in the matrix. In conclusion, we demonstrated that increasing 3D rigidity could promote proliferation and spheroid developments of liver cells demonstrating that 3D collagen gels are an attractive tool for studying rigidity-dependent homeostasis of the liver cells embedded in the matrix and should be privileged for both chronic toxicological and pharmacological drug screening.
ISSN: 0730-2312

hal-01196600
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01196600
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01196600/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01196600/file/Increasing%203D%20Matrix%20Rigidity_accepted.pdf
DOI : 10.1002/jcb.25356