Éditeur(s) : HAL CCSD
Résumé : International audience
Antiviral proteins that recognize pathogen-specific or aberrantly located molecular motifs are perfectly positioned to act as pattern-recognition receptors and signal to the immune system. Here we investigated whether the interferon-induced viral restriction factor tetherin (CD317/BST2), which is known to inhibit HIV-1 particle release by physically tethering virions to the cell surface, has such a signaling role. We find that upon restriction of Vpu-defective HIV-1, tetherin acts as a virus sensor to induce NFκB-dependent proinflammatory gene expression. Signaling requires both tetherin's extracellular domain involved in virion retention and determinants in the cytoplasmic tail, including an endocytic motif, although signaling is independent of virion endocytosis. Furthermore, recruitment of the TNF-receptor-associated factor TRAF6 and activation of the mitogen-activated protein kinase TAK1 are critical for signaling. Human tetherin's ability to mediate efficient signaling may have arisen as a result of a five amino acid deletion that occurred in hominids after their divergence from chimpanzees.
ISSN: 1934-6069

hal-01121777
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01121777
PUBMED : 23159053
DOI : 10.1016/j.chom.2012.10.007
PUBMEDCENTRAL : PMC3556742

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Coral reef resource systems are complex adaptive social-ecological systems providing vital and valuableecosystem services for human societies such as food provision, coastal protection and recreational activities.Their sustainability is questioned in many places around the world as they experience combined effects ofmultiple chronic anthropogenic and natural drivers at local to global scales. From a management perspective,there is a crucial need to understand how the impact of these drivers cascade through the social-ecologicalsystem components. This study develops a transdisciplinary and participatory approach to investigating thesocial-ecological dynamics of a Polynesian coral reef coastal system. A preliminary conceptual model using theDriver-Pressure-State-Impact (DPSI) framework is first being built through participatory modeling workshops.Then, pressure-state relationships are assessed with the help of empirical datasets as a first step towards thevalidation of the DPSI model. Results shows striking social-ecological interactions with different patterns in thelagoon and in the fore reef. Local management should be: (1) less resource-focused to account more specificallyto the existing typology of actors; (2) more spatially-explicit to better distinguish management objectives andactions for the lagoon and the fore reef sub-systems; and (3) more coordinated with terrestrial agencies for acoherent land-sea connection and integration that would both (i) account for existing land-sea interactions and(ii) better reflect the Polynesian cultural heritage that considers nature from ridge to reef as a whole. Suchconceptual models of social-ecological systems are a useful tool to build exploratory scenarios to ultimatelysupport planning decision-making processes.
ISSN: 0308-597X

hal-01491968
https://hal-univ-perp.archives-ouvertes.fr/hal-01491968
DOI : 10.1016/j.marpol.2017.01.014

Éditeur(s) : HAL CCSD Elsevier Elsevier Masson
Résumé : International audience
Prostate cancer is the most frequent cancer affecting men in most Western countries. Certain risk factors have been identified (age, family history, ethnic origin), but the aetiology of this cancer remains largely unknown. However, a role for environmental factors is strongly suspected. Questions have been raised concerning the role of the chemical substances generated by human activities in the occurrence of this disease. Diverse studies have consistently demonstrated a higher risk of prostate cancer in agricultural populations than in the general population. The hypothesis that this higher risk is linked to the use of pesticides has been tested in a number of studies, mostly in North America and Europe. However, to date, with a few possible exceptions, it has been impossible to demonstrate a significant association between exposure to pesticides or a chemical family of pesticides and prostate cancer. Studies have also been carried out on the role of exposure to trace metals, such as cadmium, or to pollutants from industry, such as polychlorobiphenyls. However, no firm conclusions have been drawn. Finally, the effect of chemical substances with endocrine disruptor activity on the occurrence of prostate cancer remains largely unexplored in epidemiological studies. In the face of these uncertainties, rigorous studies are required, with objective measurements of exposure, taking into account confounding factors and individual risk factors, making it possible to assess gene-environment interactions.
ISSN: 1297-9589

inserm-00524579
http://www.hal.inserm.fr/inserm-00524579
DOI : 10.1016/j.gyobfe.2008.07.005
PUBMED : 18693059

Éditeur(s) : HAL CCSD National Institute of Environmental Health Sciences
Résumé : International audience
Safe drinking water is essential for well-being. Although microbiological contamination remains the largest cause of water-related morbidity and mortality globally, chemicals in water supplies may also cause disease, and evidence of the human health consequences is limited or lacking for many of them. We aimed to summarize the state of knowledge, identify gaps in understanding, and provide recommendations for epidemiological research relating to chemicals occurring in drinking water. Assessing exposure and the health consequences of chemicals in drinking water is challenging. Exposures are typically at low concentrations, measurements in water are frequently insufficient, chemicals are present in mixtures, exposure periods are usually long, multiple exposure routes may be involved, and valid biomarkers reflecting the relevant exposure period are scarce. In addition, the magnitude of the relative risks tends to be small. Research should include well-designed epidemiological studies covering regions with contrasting contaminant levels and sufficient sample size; comprehensive evaluation of contaminant occurrence in combination with bioassays integrating the effect of complex mixtures; sufficient numbers of measurements in water to evaluate geographical and temporal variability; detailed information on personal habits resulting in exposure (e.g., ingestion, showering, swimming, diet); collection of biological samples to measure relevant biomarkers; and advanced statistical models to estimate exposure and relative risks, considering methods to address measurement error. Last, the incorporation of molecular markers of early biological effects and genetic susceptibility is essential to understand the mechanisms of action. There is a particular knowledge gap and need to evaluate human exposure and the risks of a wide range of emerging contaminants.
ISSN: 0091-6765

hal-01118530
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118530
PUBMED : 24380896
DOI : 10.1289/ehp.1206229
PUBMEDCENTRAL : PMC3948022

Éditeur(s) : HAL CCSD Oxford University Press
Résumé : International audience
Type IB DNA topoisomerases can eliminate torsional stresses produced during replication and transcription. These enzymes are found in all eukaryotes and a short version is present in some bacteria and viruses. Among prokaryotes, the long eukaryotic version is only observed in archaea of the phylum Thau-marchaeota. However, the activities and the roles of these topoisomerases have remained an open question. Here, we demonstrate that all available thaumar-chaeal genomes contain a topoisomerase IB gene that defines a monophyletic group closely related to the eukaryotic enzymes. We show that the topIB gene is expressed in the model thaumarchaeon Ni-trososphaera viennensis and we purified the recom-binant enzyme from the uncultivated thaumarchaeon Candidatus Caldiarchaeum subterraneum. This enzyme is active in vitro at high temperature, making it the first thermophilic topoisomerase IB characterized so far. We have compared this archaeal type IB enzyme to its human mitochondrial and nuclear counterparts. The archaeal enzyme relaxes both negatively and positively supercoiled DNA like the eukaryotic enzymes. However, its pattern of DNA cleavage specificity is different and it is resistant to camptothecins (CPTs) and non-CPT Top1 inhibitors, LMP744 and lamellarin D. This newly described ther-mostable topoisomerases IB should be a promising new model for evolutionary, mechanistic and structural studies.
ISSN: 0305-1048

Droits : http://creativecommons.org/licenses/by/
hal-01327354
http://hal.upmc.fr/hal-01327354
http://hal.upmc.fr/hal-01327354/document
http://hal.upmc.fr/hal-01327354/file/Nucl.%20Acids%20Res.-2016-Dahmane-2795-805.pdf
DOI : 10.1093/nar/gkw097

Éditeur(s) : HAL CCSD Oxford University Press
Résumé : International audience
Enhancers are developmentally controlled transcriptional regulatory regions whose activities are modulated through histone modifications or histone variant deposition. In this study, we show by genome-wide mapping that the newly discovered deoxyribonucleic acid (DNA) modification 5-hydroxymethylcytosine (5hmC) is dynamically associated with transcription factor binding to distal regulatory sites during neural differentiation of mouse P19 cells and during adipocyte differentiation of mouse 3T3-L1 cells. Functional annotation reveals that regions gaining 5hmC are associated with genes expressed either in neural tissues when P19 cells undergo neural differentiation or in adipose tissue when 3T3-L1 cells undergo adipocyte differentiation. Furthermore, distal regions gaining 5hmC together with H3K4me2 and H3K27ac in P19 cells behave as differentiation-dependent transcriptional enhancers. Identified regions are enriched in motifs for transcription factors regulating specific cell fates such as Meis1 in P19 cells and PPARγ in 3T3-L1 cells. Accordingly, a fraction of hydroxymethylated Meis1 sites were associated with a dynamic engagement of the 5-methylcytosine hydroxylase Tet1. In addition, kinetic studies of cytosine hydroxymethylation of selected enhancers indicated that DNA hydroxymethylation is an early event of enhancer activation. Hence, acquisition of 5hmC in cell-specific distal regulatory regions may represent a major event of enhancer progression toward an active state and participate in selective activation of tissue-specific genes.
ISSN: 0305-1048

inserm-00716879
http://www.hal.inserm.fr/inserm-00716879
http://www.hal.inserm.fr/inserm-00716879/document
http://www.hal.inserm.fr/inserm-00716879/file/nar.gks595.full.pdf
DOI : 10.1093/nar/gks595

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
The Southwest Indian Ocean (SWIO) is a striking marine biodiversity hotspot. Coral reefs in this region host a high proportion of endemics compared to total species richness and they are particularly threatened by human activities. The island archipelagos with their diverse marine habitats constitute a natural laboratory for studying diversification processes. Rocky shores in the SWIO region have remained understudied. This habitat presents a high diversity of molluscs, in particular gastropods. To explore the role of climatic and geological factors in lineage diversification within the genus Nerita, we constructed a new phylogeny with an associated chronogram from two mitochondrial genes [cytochrome oxidase sub-unit 1 and 16S rRNA], combining previously published and new data from eight species sampled throughout the region. All species from the SWIO originated less than 20 Ma ago, their closest extant relatives living in the Indo-Australian Archipelago (IAA). Furthermore, the SWIO clades within species with Indo-Pacific distribution ranges are quite recent, less than 5 Ma. These results suggest that the regional diversification of Nerita is closely linked to tectonic events in the SWIO region. The Reunion mantle plume head reached Earth's surface 67 Ma and has been stable and active since then, generating island archipelagos, some of which are partly below sea level today. Since the Miocene, sea-level fluctuations have intermittently created new rocky shore habitats. These represent ephemeral stepping-stones, which have likely facilitated repeated colonization by intertidal gastropods, like Nerita populations from the IAA, leading to allopatric speciation. This highlights the importance of taking into account past climatic and geological factors when studying diversification of highly dispersive tropical marine species. It also underlines the unique history of the marine biodiversity of the SWIO region.
ISSN: 1932-6203

hal-01185713
https://hal.archives-ouvertes.fr/hal-01185713
https://hal.archives-ouvertes.fr/hal-01185713/document
https://hal.archives-ouvertes.fr/hal-01185713/file/PLoS%20ONE%202014%20Postaire.pdf
DOI : 10.1371/journal.pone.0095040

Éditeur(s) : HAL CCSD
Résumé : Hepatitis C virus (HCV) is one of the leading causes of hepatocellular carcinoma. Therapeutic treatment against the virus has been recently improved by a tritherapy including pegylated interferon, ribavirin and antiviral protease. Nevertheless, the importance of side effects and the emergence of resistant mutants require the development of new antivirals. In this context, our team has recently discovered that Type III phosphatidylinositol 4-kinases (PI4KIIIα and PI4KIIIβ) are essential for the propagation of the virus in a human hepatic cell line at the entry and replication steps. To further characterize these potential therapeutic targets, we investigate the implication of these kinases during the HCV entry, using primary human hepatocytes, a model closer to the in vivo conditions. Two lines of research were developed: Verification of the importance of the kinase activity of PI4KIIIs during HCV entry in primary human hepatocytes, through a chemical approach; Validation of the involvement of these kinases and their enzymatic activity during viral entry through a genetic approach based on RNA interference and phenotype rescue. In parallel, we studied the expression of PI4KIIIα in liver diseases. Our results suggest the involvement of PI4KIIIα in HCV entry; the involvement of PI4KIIIIβ needs to be confirmed. The analysis of PI4KIIIα expression in hepatocellular carcinoma led us to propose this kinase as a new molecular marker, which could improve the already established prognosis models and could lead to the development of new therapeutic approaches.
Le virus de l’hépatite C (VHC) est l’un des principaux facteurs étiologiques du carcinome hépatocellulaire. Le traitement des hépatites virales C a été récemment amélioré grâce à une trithérapie (interféron, ribavirine et anti-protéase virale). Néanmoins l’importance des effets secondaires et l’émergence de mutants résistants nécessitent de découvrir de nouveaux antiviraux. Dans ce contexte, notre équipe a récemment découvert que les phosphatidylinositol 4-kinases de type III (PI4KIIIα et PI4KIIIβ) étaient indispensables à la propagation du virus dans une lignée hépatique humaine, et ce, à 2 étapes de son cycle biologique : l’entrée et la réplication. L’objectif du présent travail était de poursuivre la validation de ces nouvelles cibles thérapeutiques potentielles, en approfondissant nos connaissances sur la dépendance du virus à l’égard de ces kinases au cours de son entrée. Pour cela, nous avons utilisé le modèle des hépatocytes humains primaires, système in vitro plus proche du contexte physiologique que les modèles utilisés jusqu’à présent et qui étaient basés sur l’exploitation de lignées. Deux axes ont été développés : Vérification de l’importance de l’activité kinase des PI4KIIIs au cours de l’entrée du VHC dans les hépatocytes humains primaires, à travers une approche chimique ; Validation de l’implication de ces kinases et de leur activité enzymatique au cours de l’entrée virale grâce à une approche génétique basée sur l’ARN interférence et la restauration de phénotype. En parallèle, nous avons étudié l’expression de PI4KIIIα au cours de pathologies hépatiques. Nos résultats suggèrent une implication de PI4KIIIα au cours de l’entrée du VHC dans les hépatocytes humains primaires, mais restent à confirmer quant à l’implication de PI4KIIIβ. Par ailleurs, l’analyse de l’expression de PI4KIIIα dans le carcinome hépatocellulaire (CHC) conduit à proposer cette kinase comme un nouveau marqueur moléculaire, qui pourrait améliorer les modèles de pronostic déjà établis et pourrait conduire au développement de nouvelles approches thérapeutiques pour les patients atteints d’un CHC, quelque soit l’étiologie.
https://tel.archives-ouvertes.fr/tel-00950335

Droits : info:eu-repo/semantics/OpenAccess
NNT : 2013REN1B006
tel-00950335
https://tel.archives-ouvertes.fr/tel-00950335
https://tel.archives-ouvertes.fr/tel-00950335/document
https://tel.archives-ouvertes.fr/tel-00950335/file/ILBOUDOAdeodat.pdf

Éditeur(s) : HAL CCSD American Society for Microbiology
Résumé : International audience
The bivalve Codakia orbicularis, hosting sulfur-oxidizing gill endosymbionts, was starved (in artificial seawater filtered through a 0.22- m-pore-size membrane) for a long-term experiment (4 months). The effects of starvation were observed using transmission electron microscopy, fluorescence in situ hybridization and catalyzed reporter deposition (CARD-FISH), and flow cytometry to monitor the anatomical and physiological modifications in the gill organization of the host and in the symbiotic population housed in bacteriocytes. The abundance of the symbiotic population decreased through starvation, with a loss of one-third of the bacterial population each month, as shown by CARD-FISH. At the same time, flow cytometry revealed significant changes in the physiology of symbiotic cells, with a decrease in cell size and modifications to the nucleic acid content, while most of the symbionts maintained a high respiratory activity (measured using the 5-cyano-2,3-ditolyl tetrazolium chloride method). Progressively, the number of symbiont subpopulations was reduced, and the subsequent multigenomic state, characteristic of this symbiont in freshly collected clams, turned into one and five equivalent genome copies for the two remaining subpopulations after 3 months. Concomitant structural modifications appeared in the gill organization. Lysosymes became visible in the bacteriocytes, while large symbionts disappeared, and bacteriocytes were gradually replaced by granule cells throughout the entire lateral zone. Those data suggested that host survival under these starvation conditions was linked to symbiont digestion as the main nutritional source.
ISSN: 0099-2240

hal-00750419
https://hal.univ-antilles.fr/hal-00750419
DOI : 10.1128/AEM.02659-08

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
BACKGROUND: African Americans with head and neck squamous cell carcinoma (HNSCC) have a lower survival rate than whites. This study investigated the functional importance of ancestry-informative single-nucleotide polymorphisms (SNPs) in HNSCC and also examined the effect of functionally important genetic elements on racial disparities in HNSCC survival. METHODS: Ancestry-informative SNPs, RNA sequencing, methylation, and copy number variation data for 316 oral cavity and laryngeal cancer patients were analyzed across 178 DNA repair genes. The results of expression quantitative trait locus (eQTL) analyses were also replicated with a Gene Expression Omnibus (GEO) data set. The effects of eQTLs on overall survival (OS) and disease-free survival (DFS) were evaluated. RESULTS: Five ancestry-related SNPs were identified as cis-eQTLs in the DNA polymerase beta (POLB) gene (false discovery rate [FDR]<0.01). The homozygous/heterozygous genotypes containing the African allele showed higher POLB expression than the homozygous white allele genotype (P<.001). A replication study using a GEO data set validated all 5 eQTLs and also showed a statistically significant difference in POLB expression based on genetic ancestry (P=.002). An association was observed between these eQTLs and OS (P<.037; FDR<0.0363) as well as DFS (P=.018 to.0629; FDR<0.079) for oral cavity and laryngeal cancer patients treated with platinum-based chemotherapy and/or radiotherapy. Genotypes containing the African allele were associated with poor OS/DFS in comparison with homozygous genotypes harboring the white allele. CONCLUSIONS: Analyses show that ancestry-related alleles could act as eQTLs in HNSCC and support the association of ancestry-related genetic factors with survival disparities in patients diagnosed with oral cavity and laryngeal cancer. (C) 2016 American Cancer Society.
ISSN: 0008-543X

hal-01519253
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01519253
DOI : 10.1002/cncr.30457
PUBMED : 27906459

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
Motility and invasiveness events require specific intracellular signaling cascade activations. In cancer liver cells, one of these mechanisms could involve the MAPK MEK/ERK cascade activation which has been shown over expressed and activated in hepatocellular carcinoma. To study whether the MEK/ERK cascade is involved in the motility of HCC, we examined the effect of MEK inhibitor and ERK2 silencing using monolayer wound-healing assays and fluoroblock invasion systems. Evidence was provided that the MAPK cascade is a key transduction pathway which controls HCC cells motility and invasiveness. We could disconnect proliferation to motility using mitomycin C and we established that RNAi-mediated inhibition of ERK2 led to strongly reduced cell motility. To improve our understanding, we analysed the regulation and the role of urokinase receptor (uPAR) in this process. We provided evidence that uPAR was under a MEK/ERK dependent mechanism and blocking uPAR activity using specific antagonist or inhibiting its expression by RNA interference which resulted in complete inhibition of motility. Moreover, we found in MAPK inhibited cultures and in uPAR silencing cells that p70S6K phosphorylation on residue Thr-389 was significantly reduced, whereas Ser-421/Thr-424 phosphorylation did not change. We highlighted that the FRAP/mTOR pathway did not affect motility and Thr-389 phosphorylation. Furthermore, we demonstrated that p70S6K inhibition by RNA interference completely inhibited hepatocarcinoma cell motility. Therefore, targeting uPAR and/or MEK/ERK/S6K by RNA interference could be a major therapeutic strategy for the future treatment of invasive hepatocarcinoma cells.
ISSN: 0021-9541

hal-00697044
https://hal.archives-ouvertes.fr/hal-00697044
DOI : 10.1002/jcp.21049
PUBMED : 17427199

Éditeur(s) : HAL CCSD
Résumé : International audience
A long standing debate in biochemistry is to determine whether the conformational changes observed during biomolecular interactions proceed through conformational selection (of preexisting isoforms) or induced fit (ligand-induced 3D reshaping). The latter mechanism had been invoked in certain circumstances, for example to explain the non-Michaelian activity of monomeric enzymes like glucokinase. But the relative importance of induced fit has been recently depreciated in favor of conformational selection, assumed to be always sufficient, predominant in general and in particular for glucokinase. The relative contributions of conformational selection and induced fit are reconsidered here in and out of equilibrium, in the light of earlier concepts such as the cyclic equilibrium rule and the turning wheel of Wyman, using single molecule state probability, one-way fluxes and net fluxes. The conditions for a switch from conformational selection to induced fit at a given ligand concentration are explicitly determined. Out of equilibrium, the inspection of the enzyme states circuit shows that conformational selection alone would give a Michaelian reaction rate but not the established nonlinear behaviour of glucokinase. Moreover, when induced fit and conformational selection coexist and allow kinetic cooperativity, the net flux emerging in the linkage cycle necessarily corresponds to the induced fit path. © 2016 Elsevier B.V. and Société Française de Biochimie et Biologie Molé
Biochimie

hal-01367150
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01367150
DOI : 10.1016/j.biochi.2016.06.012

Éditeur(s) : HAL CCSD Elsevier
Résumé : Understanding the pattern in spatial distribution of soil microbial processes is critical to understand the environmental factors that regulate them as well as to scale up these processes to ecosystem. Soil samples from a I ha tropical rainforest plot (Paracou, French Guiana) were analyzed according a nested sampling approach using different separation distances ranging from 0.4 to 40 m. The variability of substrate induced respiration (SIR) and of denitrification enzyme activity (DEA) was characterized in relation to various soil properties (total C and N contents, NIRS related index of soil organic matter quality, SOMQ and index of tree influence potential, IP). The variability of SIR and DEA was higher than that of environmental properties. The patterns of accumulated variance as a function of distance varied among the soil properties. The variability of SIR and DEA mainly occurred at small (1 m) scale (and at the 10-40 m-scales for SIR), probably reflecting the quality of litter input that results of the influence of local assemblage of different tree species, though changes in the soil N and C contents. Indeed, total soil C and N contents explained the microbial properties at every scale. Coefficients of codispersion showed that neither SOMQ nor IP did correlate with SIR and DEA, and confirmed that total C and N contents explained microbial properties in a scale dependent and complex manner. Such spatial dependency underlines the importance of soil heterogeneity in this tropical forest with implications for sampling strategies when studying the microbial processes and their response to disturbances. (C) 2012 Elsevier B.V. All rights reserved.
ISSN: 0016-7061

hal-01032409
https://hal.archives-ouvertes.fr/hal-01032409
DOI : 10.1016/j.geoderma.2012.12.009

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Monocytes/macrophages (MΦ), considered as plastic cells, can differentiate into either a pro-inflammatory (M1) subtype, also known as a classically activated subtype, or an anti-inflammatory alternatively activated subtype (M2) according to their microenvironment. Phenotypic markers of mouse polarized MΦ have been extensively studied, whereas their human counterparts remain less characterized. The main goal of this study was therefore to carefully characterize phenotypic and genomic markers of primary human MΦ generated from M-CSF-treated blood monocytes and polarized towards M1 or M2 subtype upon the action of lipopolysaccharide and interferon-γ (for M1) or interleukin (IL)-4 (for M2). Membrane expression of the markers CD80 and CD200R was found to be specific of human M1 and M2 polarized MΦ, respectively, whereas, by contrast, mannose receptor (CD206) expression did not discriminate between M1 and M2. mRNA expression analysis further identified six markers of M1 polarization (IL-12p35, CXCL10, CXCL11, CCL5, CCR7 and IDO1), five markers of M2 polarization (TGF-β, CCL14, CCL22, SR-B1 and PPARγ) and transcription factors involved in MΦ polarization. Ability of human M-CSF-generated MΦ to polarize toward M1 or M2 subtype was also associated with enhanced secretion of TNFα, IL-1β, IL-12p40, CXCL10 and IL-10 (for M1) or CCL22 (for M2). Moreover, the comparison of the expression of M1 markers in M-CSF- and GM-CSF-MΦ polarized towards M1 subtype has revealed similarities. In conclusion, we demonstrated that human M-CSF MΦ can polarize toward a M1 type after IFNγ/LPS stimulation. Moreover, the M1 and M2 markers of human polarized MΦ identified in the present study may be useful to better identify human MΦ subtypes, particularly at the tissue level, in order to better understand their respective roles in the development of pathologies.
ISSN: 0008-8749

inserm-00823273
http://www.hal.inserm.fr/inserm-00823273
DOI : 10.1016/j.cellimm.2013.01.010
PUBMED : 23454681

Éditeur(s) : HAL CCSD
Résumé : International audience
Spermatogenesis is a highly sophisticated process involved in the transmission of genetic heritage. It includes halving ploidy, repackaging of the chromatin for transport, and the equipment of developing spermatids and eventually spermatozoa with the advanced apparatus (e.g., tightly packed mitochondrial sheat in the mid piece, elongating of the tail, reduction of cytoplasmic volume) to elicit motility once they reach the epididymis. Mammalian spermatogenesis is divided into three phases. In the first the primitive germ cells or spermatogonia undergo a series of mitotic divisions. In the second the spermatocytes undergo two consecutive divisions in meiosis to produce haploid spermatids. In the third the spermatids differentiate into spermatozoa in a process called spermiogenesis. Paracrine, autocrine, juxtacrine, and endocrine pathways all contribute to the regulation of the process. The array of structural elements and chemical factors modulating somatic and germ cell activity is such that the network linking the various cellular activities during spermatogenesis is unimaginably complex. Over the past two decades, advances in genomics have greatly improved our knowledge of spermatogenesis, by identifying numerous genes essential for the development of functional male gametes. Large-scale analyses of testicular function have deepened our insight into normal and pathological spermatogenesis. Progress in genome sequencing and microarray technology have been exploited for genome-wide expression studies, leading to the identification of hundreds of genes differentially expressed within the testis. However, although proteomics has now come of age, the proteomics-based investigation of spermatogenesis remains in its infancy. Here, we review the state-of-the-art of large-scale proteomic analyses of spermatogenesis, from germ cell development during sex determination to spermatogenesis in the adult. Indeed, a few laboratories have undertaken differential protein profiling expression studies and/or systematic analyses of testicular proteomes in entire organs or isolated cells from various species. We consider the pros and cons of proteomics for studying the testicular germ cell gene expression program. Finally, we address the use of protein datasets, through integrative genomics (i.e., combining genomics, transcriptomics, and proteomics), bioinformatics, and modelling.
Systems Biology in Reproductive Medicine

hal-00877749
https://hal.archives-ouvertes.fr/hal-00877749
DOI : 10.3109/19396368.2012.691943
PUBMED : 22788530

Éditeur(s) : HAL CCSD Éditions de la Maison des sciences de l'homme
Résumé : International audience
For over a century, the complementary nature of fishing and farming activities in the floodplain of the Rufiji River (Tanzania) has formed the basis of the economy in its villages. Starting in the 1970s, the fishery evolved from a seasonal activity practiced on foot during flooding and using traditional traps to year-round dugout canoe operated lake fisheries using nets.The paper analyses the drivers of this change. After having rejected the simplistic technocratic hypothesis that technical innovation equals progress, the paper examines the relevance of the productivity of the different fishing techniques in the light of the evolution of the role of fisheries in the village economy. During the change-over period, the national and international economy deprives the villages of their main habitual sources of cash income. In the absence of any alternative, fisheries imposed themselves as the unique source of cash income, a function they can only fulfil if practiced year-round and this can only be achieved using canoes and nets. However, the perception of the causes of these changes in the villages is differentiated. For those who initiated the change-over, and who are now of an advanced age, the main driver of the transition to nets was the empowerment of the youth versus the elders. Such an interpretation resonates well with the economic determinants. However, it requires considering the modernisation process as a contextualised multi-sided expression of market globalisation.
Depuis plus d’un siècle, l’économie des villages de la plaine inondable du Rufiji (Tanzanie) est fondée sur la complémentarité des activités agricoles et des activités halieutiques. À partir de la fin des années 1970, les pêches traditionnelles à la nasse, pratiquées à pied saisonnièrement lors de la crue annuelle, sont supplantées par les pêches embarquées (pirogues monoxyles) au filet dans les lacs, pratiquées elles toute l’année. L’article s’interroge sur les déterminants de cette substitution.Après avoir rejeté l’hypothèse techniciste vulgaire qui voudrait que l’innovation technique soit synonyme de progrès, la pertinence du critère de productivité des différentes techniques de pêche est examinée à la lumière de l’évolution de la place des activités halieutiques dans l’économie villageoise. Il apparaît qu’à partir de cette époque, l’évolution économique nationale et internationale prive les villageois de leurs principales ressources monétaires habituelles. En l’absence de toute alternative, la pêche s’impose alors comme unique source de revenu monétaire, une fonction qu’elle ne peut remplir qu’à condition d’être pratiquée tout au long de l’année, ce que seules les techniques au filet permettent. Cependant, les représentations villageoises des causes de la généralisation de la pêche au filet sont différentes. Pour ceux d’entre eux, aujourd’hui très âgés, qui furent les pionniers de cette innovation, c’est le souci d’émancipation des cadets vis-à-vis des aînés qui aurait été le moteur de l’adoption de techniques de pêche au filet. Ce point de vue entre en résonance avec les déterminations économiques à condition de considérer le processus de modernisation comme manifestation multiforme contextualisée de la mondialisation marchande.
ISSN: 0248-6016

hal-01344410
https://hal.univ-antilles.fr/hal-01344410
https://hal.univ-antilles.fr/hal-01344410/document
https://hal.univ-antilles.fr/hal-01344410/file/Pauletal2015Version_Def.pdf

Éditeur(s) : HAL CCSD IOS Press
Résumé : International audience
Sickle cell anemia (SCA) is an inherited red blood cells (RBC) disorder characterized by significantly decreased RBC deformability. The present study aimed to assess whether modulation of RBC Nitric Oxide Synthase (RBC-NOS) activation could affect RBC deformability in SCA.Blood of twenty-five SCA patients was treated for 1 hour at 37°C with Phosphate Buffered Saline (PBS) or PBS containing 1% of Dimethylsulfoxyde as control, L-arginine or N(5)-(1-Iminoethyl)-L-ornithine (L-NIO) to directly stimulate or inhibit RBC-NOS, insulin or wortmannin to indirectly stimulate or inhibit RBC-NOS through their effects on the PI3 Kinase/Akt pathway, and sodium nitroprusside (SNP) and 2-(4-Carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) as NO donor and NO scavenger, respectively. RBC deformability was measured by ektacytometry at 3 Pa.RBC deformability significantly increased after insulin treatment and significantly decreased after L-NIO and wortmannin incubation. The other conditions did not affect deformability. Significantly increased nitrotyrosine levels, a marker of enhanced free radical generation, were detected by immunohistochemistry in SNP and insulin treated samples.These data suggest that RBC deformability of SCA can be modulated by RBC-NOS activity but also that oxidative stress may impair effectiveness of RBC-NOS produced NO.
ISSN: 1386-0291

hal-01669738
https://hal.univ-antilles.fr/hal-01669738
DOI : 10.3233/CH-162042

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
In intrauterine pregnancies of uncertain viability with a gestational sac without a yolk sac (with a mean of three orthogonal transvaginal ultrasound measurements <25 mm), the suspected pregnancy loss should only be confirmed after a follow-up scan at least 14 days later shows no embryo with cardiac activity (Grade C). In intrauterine pregnancies of uncertain viability with an embryo <7 mm on transvaginal ultrasound, the suspected pregnancy loss should only be confirmed after a follow-up scan at least 7 days later (Grade C). In pregnancies of unknown location after transvaginal ultrasound (i.e. not visible in the uterus), a threshold of at least 3510 IU/l for the serum human chorionic gonadotrophin assay is recommended; above that level, a viable intrauterine pregnancy can be ruled out (Grade C). Postponing conception after an early miscarriage in women who want a new pregnancy is not recommended (Grade A). A work-up for women with recurrent pregnancy loss should include the following: diabetes (Grade A), antiphospholipid syndrome (Grade A), hypothyroidism with anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-Tg) antibodies (Grade A), vitamin deficiencies (B9, B12) (Grade C), hyperhomocysteinaemia (Grade C), hyperprolactinaemia (Grade B), diminished ovarian reserve (Grade C), and a uterine malformation or an acquired uterine abnormality amenable to surgical treatment (Grade C). The treatment options recommended for women with a missed early miscarriage are vacuum aspiration (Grade A) or misoprostol (Grade B); and the treatment options recommended for women with an incomplete early miscarriage are vacuum aspiration (Grade A) or expectant management (Grade A). In the absence of both chorioamnionitis and rupture of the membranes, women with a threatened late miscarriage and an open cervix, with or without protrusion of the amniotic sac into the vagina, should receive McDonald cerclage, tocolysis with indomethacin, and antibiotics (Grade C). Among women with a threatened late miscarriage and an isolated undilated shortened cervix (<25 mm on ultrasound), cerclage is only indicated for those with a history of either late miscarriage or preterm delivery (Grade A). Among women with a threatened late miscarriage, an isolated undilated shortened cervix (<25 mm on ultrasound) and no uterine contractions, daily treatment with vaginal progesterone up to 34 weeks of gestation is recommended (Grade A). Hysteroscopic section of the septum is recommended for women with a uterine septum and a history of late miscarriage (Grade C). Correction of acquired abnormalities of the uterine cavity (e.g. polyps, myomas, synechiae) is recommended after three early or late miscarriages (Grade C). Prophylactic cerclage is recommended for women with a history of three late miscarriages or preterm deliveries (Grade B). Low-dose aspirin and low-molecular-weight heparin at a preventive dose are recommended for women with obstetric antiphospholipid syndrome (Grade A). Glycaemic levels should be controlled before conception in women with diabetes (Grade A)
ISSN: 0301-2115

hal-01295639
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01295639
DOI : 10.1016/j.ejogrb.2016.02.015
PUBMED : 27039249

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : International audience
Late Jurassic coral reefs are present in the Western High Atlas of Morocco along the eastern paleomargin of the young Atlantic Ocean. The Izwarn section shows two reef units made of scleractinian corals and microbialites, included in a progradational shallowing-upward succession. Changes in reefal composition and structure observed in a ca. 50 cm-thick interval at the base of the reef unit 1 are interpreted to represent the first well-documented ecological succession in Late Jurassic reefs. Bioclastic deposits, sparse and poorly diversified corals (five genera) preserved in life position, and finally a more diversified coral assemblage (11 genera) building a reef framework with stromatolitic crusts reflect pioneer, colonization and diversification stages, respectively. A specific depth window, where light was reduced but sufficient for a catch-up growth mode and below the erosive action of waves, probably at the lower slope of a fore-reef area, has made possible the development and the record of this ecological succession. With a more diversified coral assemblage (16 genera), the reef unit 2 reflects shallower and well-agitated waters of a fore-reef area. Overlaying this second reef unit, the upper part of the section reveals back-reef deposits made of reworked reef elements, whereas a putative reef crest area is not recorded.
ISSN: 0016-6995

hal-00795549
https://hal.archives-ouvertes.fr/hal-00795549
DOI : 10.1016/j.geobios.2012.05.002

Éditeur(s) : HAL CCSD
Résumé : National audience
Since the 1950s, Friedman's curves served as reference to guide obstetrical practice around the world. However, recent studies have suggested guidelines based on Freidman's results were too stringent and induce inappropriate and excessive interventionism. The committee aimed to redefine the structure and the normal duration of the labor, as well as the criterion to be fulfilled to consider a labor as abnormal. Several recommendations have been produced based on a systematic literature review. Labor dystocia should not be diagnosed during the latency phase. The beginning of the active phase of the 1st stage of labor has been established between 5 and 6 cm of cervical dilatation, which is later than previously suggested. Rate of cervical dilatation is considered as abnormal below 1 cm per 4 hour during the first part of the active phase, and blow 1 cm per 2 hour above 7 cm of dilatation. A maximum duration for the 2nd stage of labor cannot be defined in the French context, based on the literature. However, exceeding 3 hours, the risk-benefit balance becomes less beneficial. These new guidelines would help to reduce the use of oxytocin and caesarian delivery for labor dystocia. © 2016 Elsevier Masson SAS
Revue Sage - Femme

hal-01467546
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01467546
PUBMED : 28483643
DOI : 10.1016/j.sagf.2016.10.006