Éditeur(s) : HAL CCSD
Résumé : Indigenous territories comprise extensive areas of tropical forest and hold significant social and conservation value. Today, they are subject to various constraints and opportunities, and face many territorial transformations. These transformations are complex and multifaceted. They involve the adoption of new production and consumption modes, the modification of forms of social organisation and identity and territorial claims. However, the links between these on-going processes are still poorly understood, and make difficult to appreciate the adaptation dynamics of indigenous common natural resources management. This thesis is particularly concerned with the territorial dynamics of the Wayãpi and Teko indigenous people of the municipality of Camopi in French Guiana. It integrates methods that include land use analysis using remotely sensed data, socio-economic and agricultural systems analysis at the household scale, and empirical analysis on the influence of identity claims, kinship networks, and conservation policies. It shows that despite the residential settlement around local towns, the growth of cash income from wage labour and welfare, associated with strong kinship networks, allows the revival of mobility and the diversification of indigenous territorialities. Environmental policies implemented on the territory involve processes of identity and territorial claims and motivate the construction of a collective project of endogenous local development. A comparative approach with the situation of the wayãpi people living in Brazil and evolving in a completely different institutional, socio-economic and environmental context shows similar dynamics. Indigenous peoples of these two sites adopt "multi-local" land use systems, allowing them to extend their territory occupation and taking part of a broader dynamic of territorial and identity affirmation. They articulate forest and local town environments. This multi-local land use system can be interpreted as a new form of environmental governance, which overcomes the access difficulties to natural resources around local towns and ensures their sovereignty over the territory.
Les territoires amérindiens couvrent de vastes étendues de forêts tropicales et possèdent une forte valeur sociale et environnementale. Soumis à des contraintes et opportunités variées, ils sont de nos jours le siège de nombreuses transformations territoriales. Ces transformations sont complexes et multiformes. Elles impliquent l'adoption de nouveaux modes de production et de consommation, le réajustement des formes d'organisation sociale et des dynamiques de réaffirmation identitaire et territoriale. Or les liens entre tous ces processus sont encore mal compris, et rendent délicate la compréhension des dynamiques d'adaptation des systèmes amérindiens de gestion des ressources communes. Cette thèse s'intéresse particulièrement aux dynamiques territoriales des Amérindiens wayãpi et teko de la commune de Camopi en Guyane française. Elle intègre des données sur l'occupation du sol obtenues par télédétection, des données socio-économiques et productives à l'échelle des ménages et des données qualitatives sur les processus identitaires, les réseaux de parenté, les politiques de conservation et la gouvernance du territoire. Elle montre que malgré la sédentarisation de l'habitat autour des bourgs locaux, la croissance des revenus monétaires issus des emplois salariés et des aides sociales, combinée avec le maintien de réseaux de parenté et d'entraide, permet une redynamisation des systèmes de mobilité et une diversification des territorialités amérindiennes. De plus, les politiques environnementales mises en place sur le territoire impliquent des processus de territorialisation et de revendications identitaires et motivent la construction collective d'un projet de développement local endogène. Une approche comparative avec la situation des Amérindiens wayãpi vivant au Brésil et évoluant dans un contexte socio-économique, institutionnel et environnemental bien différent montre des dynamiques similaires. Les Amérindiens de ces deux pays adoptent des systèmes d'exploitation du territoire multi-locaux, leur permettant d'étendre leur occupation du territoire et s'inscrivant dans une dynamique de réaffirmation identitaire et territoriale. Ils articulent ainsi les espaces de la forêt et des bourgs. Cette forme d'exploitation multi-locale du territoire peut être interprétée comme une nouvelle forme de gouvernance environnementale, qui leur permet de contourner les difficultés d'accès aux ressources naturelles autour des bourgs et d'affirmer leur souveraineté sur le territoire.
https://tel.archives-ouvertes.fr/tel-00831619

tel-00831619
https://tel.archives-ouvertes.fr/tel-00831619
https://tel.archives-ouvertes.fr/tel-00831619/document
https://tel.archives-ouvertes.fr/tel-00831619/file/These_TRITSCH_mai2013_vf.pdf

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The strikingly complex structural organization of the mammalian testis in vivo creates particular difficulties for studies of its organization, function and regulation. These difficulties are particularly pronounced for investigations of the molecular communication networks within the seminiferous tubules that govern spermatogenesis. The use of classical molecular and cell biology approaches to unravel this complexity has proved problematic, due to difficulties in maintaining differentiated germ cells in vitro, in particular. The lack of a suitable testing ground has led to a greater reliance on high-quality proteomic and genomic analyses as a prelude to the in vitro antx1d in vivo testing of hypotheses. In this study, we highlight the options currently available for research, as used in our laboratory, in which proteomic and integrative genomic strategies are applied to the study of spermatogenesis in mammals. We will comment on results providing insight into the molecular mechanisms underlying normal and pathological spermatogenesis and new perspectives for the treatment of male infertility in humans. Finally, we will discuss the relevance of our strategies and the unexpected potential and perspectives they offer to teams involved in the study of male reproduction, within the framework of the Human Proteome Project. SIGNIFICANCE: Integrative genomics is becoming a powerful strategy for discovering the biological significance hidden in proteomic datasets. This work introduces some of the integrative genomic concepts and works used by our team to gain new insight into mammalian spermatogenesis, a remarkably sophisticated process. We demonstrate the relevance of these integrative approaches to understand the cellular cross talks established between the somatic Sertoli cells and the germ cell lineage, within the seminiferous epithelium. Our work also contributes to new knowledge on the pathophysiology of testicular function, with promising clinical applications. This article is part of a Special Issue entitled: 20years of Proteomics in memory of Viatliano Pallini. Guest Editors: Luca Bini, Juan J. Calvete, Natacha Turck, Denis Hochstrasser and Jean-Charles Sanchez.
ISSN: 1874-3919

hal-01063931
https://hal.archives-ouvertes.fr/hal-01063931
DOI : 10.1016/j.jprot.2014.04.013
PUBMED : 24751586

Résumé : La vie d'un organisme, comme celle d'un être vivant, comprend des périodes bien caractérisées. Nous pouvons considérer qu'au 31 décembre 1977 la première de ces périodes s'est achevée, celle de ia mise en place, celle de la réunion des équipes et des moyens indispensables, celle de la définition des principaux thèmes d'action, du lancement des programmes de travail. Nous sommes entrés en 1978 dans une période où notre souci primordial est de coordonner le plus efficacement possible les efforts de tous ceux qui contribuent à faire de l'océan une source de développement et de croissance du pays. Nous devons avoir dans cette perspective le souci, et presque l'obsession, de nous assurer de la valorisation concrète, au bénéfice de notre économie, des résultats acquis dans les laboratoires et les stations pilotes. A cet égard, le CNEXO doit animer et organiser l'effort commun autour d'idées nouvelles. [OCR NON CONTRÔLE]

Droits : info:eu-repo/semantics/openAccess
http://archimer.ifremer.fr/doc/1978/rapport-4822.PDF
http://archimer.ifremer.fr/doc/00000/4822/

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The quasi-equilibrium approximation is acceptable when molecular interactions are fast enough compared to circuit dynamics, but is no longer allowed when cellular activities are governed by rare events. A typical example is the lactose operon (lac), one of the most famous paradigms of transcription regulation, for which several theories still coexist to describe its behaviors. The lac system is generally analyzed by using equilibrium constants, contradicting single-event hypotheses long suggested by Novick and Weiner (1957). Enzyme induction as an all-or-none phenomenon. Proc. Natl. Acad. Sci. USA 43, 553-566) and recently refined in the study of (Choi et al., 2008. A stochastic single-molecule event triggers phenotype switching of a bacterial cell. Science 322, 442-446). In the present report, a lac repressor (LacI)-mediated DNA immunoprecipitation experiment reveals that the natural LacI-lac DNA complex built in vivo is extremely tight and long-lived compared to the time scale of lac expression dynamics, which could functionally disconnect the abortive expression bursts and forbid using the standard modes of lac bistability. As alternatives, purely kinetic mechanisms are examined for their capacity to restrict induction through: (i) widely scattered derepression related to the arrival time variance of a predominantly backward asymmetric random walk and (ii) an induction threshold arising in a single window of derepression without recourse to nonlinear multimeric binding and Hill functions. Considering the complete disengagement of the lac repressor from the lac promoter as the probabilistic consequence of a transient stepwise mechanism, is sufficient to explain the sigmoidal lac responses as functions of time and of inducer concentration. This sigmoidal shape can be misleadingly interpreted as a phenomenon of equilibrium cooperativity classically used to explain bistability, but which has been reported to be weak in this system.
ISSN: 0022-5193

inserm-00818506
http://www.hal.inserm.fr/inserm-00818506
http://www.hal.inserm.fr/inserm-00818506/document
http://www.hal.inserm.fr/inserm-00818506/file/LacI-TeX.pdf
ARXIV : 1312.5566

Éditeur(s) : HAL CCSD
Résumé : Mon document "Titres et travaux" contient 5 articles au format éditeur.
Mes premiers travaux de recherche, me permettant de soutenir une thèse de doctorat en décembre 1999, ont été effectués au sein du laboratoire du professeur Bernard GRANDCHAMP (unité 409 de l'INSERM) sous la direction du docteur Marie-Christine LECOMTE. Mon travail s'est intégré dans l'étude fonctionnelle et structurale de certains domaines des spectrines érythroïdes et non érythroïdes, principalement le site de tétramérisation et le domaine SH3. Concernant la tétramérisation de la spectrine érythroïde j'ai identifié les régions minimales nécessaires et suffisantes pour former le tétramère puis j'ai mis en évidence une relation entre certaines mutations de la spectrine associées à des anomalies membranaires du globule rouge et la sévérité du défaut de formation du tétramère. J'ai ensuite identifié plusieurs ligands du domaine SH3 de la spectrine non érythroïde. L'un d'entre eux m'a permis de définir une régulation de la protéolyse ciblée de cette spectrine faisant intervenir un mécanisme de phosphorylation/déphosphorylation. Ma formation initiale fut donc celle d'un biochimiste que j'ai étendue peu à peu vers la biologie moléculaire et la biologie cellulaire.
Puis, souhaitant acquérir les connaissances nécessaires au développement de modèles murins, j'ai décidé d'effectuer mon stage post-doctoral à l'Institut COCHIN (unité 567 de l'INSERM) dans une équipe co-dirigée par le docteur Sophie VAULONT et le professeur Axel KAHN. Je me suis ainsi familiarisé avec la souris comme « outil » de recherche (gestion d'un élevage, établissement de nouvelles lignées, génotypage, phénotypage). Je travaillais initialement sur le métabolisme du glucose mais j'ai complètement réorienté ma thématique de recherche au bout d'un an pour finalement identifier et caractériser une hormone, l'hepcidine, contrôlant l'homéostasie du fer.
J'ai été nommé chargé de recherche de grade 2 dans l'unité 409 de l'INSERM en octobre 2002 pour y développer une souche de souris exprimant une spectrine non érythroïde résistante à des mécanismes de protéolyse ciblée. Il s'agit donc toujours d'appréhender certaines fonctions des spectrines mais dans un contexte in vivo. En janvier 2005 j'ai intégré l'unité 665 de l'INSERM dirigée par Yves COLIN afin de poursuivre ce projet. Aujourd'hui, je suis chargé de recherche de grade 1.
Le chapitre scientifique de ce mémoire est divisé en deux parties distinctes : la première traite de mon travail sur la spectrine tandis que la seconde porte sur l'hepcidine. Chaque partie est composée d'une introduction au sujet suivie d'un résumé des travaux que j'ai effectués et/ou dirigés.
https://tel.archives-ouvertes.fr/tel-00285035

Droits : info:eu-repo/semantics/OpenAccess
tel-00285035
https://tel.archives-ouvertes.fr/tel-00285035
https://tel.archives-ouvertes.fr/tel-00285035/document
https://tel.archives-ouvertes.fr/tel-00285035/file/HDR_Titre_et_travaux_-_Gael_Nicolas.pdf

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Endocrine disrupting chemicals and especially oestrogen receptor (ER) agonists have been extensively studied over the years due to their potential effects on sexual development and reproduction in vertebrates, notably fish. As ER agonists can exist as complex mixtures in the aquatic environment, evaluating the impact of combined exposure on oestrogenic effects has become increasingly important. Use of predictive models such as concentration addition (CA) and independent action (IA) has allowed assessment of combined estrogenic effects of complex multi-compound mixtures of ER agonists in various fish in vitro and in vivo experimental models. The present work makes use of a transgenic zebrafish strain, tg(cyp19a1b-GFP), which expresses the green fluorescent protein (GFP) under the control of the cyp19a1b (brain aromatase or aromatase B) gene to determine the oestrogenic potency of ER agonists alone or in mixtures. In these studies, tg(cyp19a1b-GFP) zebrafish embryos were exposed for four days (from one to five days post fertilization) to five different oestrogenic chemicals; 17α-ethinylestradiol (EE2), 17β-estradiol (E2), estrone (E1), bisphenol A (BPA) and 4-tert-octylphenol (OP), and three mixtures of up to four of these compounds. The mixture of BPA, OP and E2 was also tested with primary cultures of rainbow trout hepatocytes by analysing the ER-mediated induction of the oestrogenic biomarker vitellogenin in order to compare the performance of the two methods for assessing oestrogenic effects of complex mixtures. The three tested mixtures were predominantly acting in an additive manner on the expression of GFP. Additivity was indicated by the overlap of the 95% confidence interval of the concentration response curves for the observed data with the CA and IA prediction models, and model deviation ratios within a factor of two for a majority of the mixture concentrations. However, minor deviations determined as more than additive effects for the mixture of EE2, E1 and E2 and less than additive effects for the mixture of BPA, OP, EE2 and E1 were observed at the higher mixture concentrations tested. The successful prediction of additivity by CA and IA in tg(cyp19a1b-GFP) zebrafish embryos and deviations at high mixture concentrations seemed to correspond well to results obtained in the rainbow trout hepatocyte assay. The present results clearly show the usefulness of combining predictive modelling and use of in vitro bioassays for rapid screening of oestrogenic effects of complex mixtures and environmental samples.
ISSN: 0166-445X

hal-00877351
https://hal.archives-ouvertes.fr/hal-00877351
DOI : 10.1016/j.aquatox.2013.05.001
PUBMED : 23721851

Éditeur(s) : Inter-research
Résumé : Vibriosis is a major disease problem in shrimp aquaculture. 'Syndrome 93' is a seasonal juvenile vibriosis caused by Vibrio penaeicida which affects Litopenaeus stylirostris in grow-out ponds in New Caledonia. This study assessed the toxic activities of extracellular products (ECPs) from V: penaeicida, V. alginolyticus and V, nigripulchritudo using in vivo injections in healthy juvenile L. stylirostris (= Penaeus stylirostris) and in vitro assays on shrimp primary cell cultures and the fish cell line epithelioma papulosum cyprini (EPC). Toxic effects of ECPs were demonstrated for all pathogenic Vibrio strains tested both in vivo and in vitro, but for shrimp only; no effect was observed on the fish cell line. ECP toxicity for New Caledonian V. penaeicida was found only after cultivation at low temperature (20 degrees C) and not at higher temperature (30 degrees C). This points to the fact that 'Syndrome 93' episodes are triggered by temperature drops. The assays used here demonstrate the usefulness of primary shrimp cell cultures to study virulence mechanisms of shrimp pathogenic bacteria.
Diseases Of Aquatic Organisms (0177-5103) (Inter-research), 2000-03 , Vol. 40 , N. 2 , P. 101-107

Droits : info:eu-repo/semantics/openAccess
http://archimer.ifremer.fr/doc/00000/10543/7600.pdf
DOI:10.3354/dao040101
http://archimer.ifremer.fr/doc/00000/10543/

Éditeur(s) : HAL CCSD Oxford University Press (OUP): Policy B1 - Oxford Open Option B Oxford University Press (OUP)
Résumé : International audience
BACKGROUNDA very large proportion of the literature on the endocrine disruptors categorized as anti-androgens deals with phthalates, which are produced in large amounts for use as plastic emollients and additives. In this review, we bring together and analyse work on the effects of phthalates in animals and humans at different stages of their development to assess whether or not their possible anti-androgenic properties represent a significant threat to human health.METHODSThe database PubMed was systematically searched for all English language articles until July 2013 in each subject area discussed.RESULTSWe provide an up-to-date exhaustive, comparative and critical assessment of both in vivo and in vitro studies undertaken to explore the effects of phthalates on the human testis from fetal life to adulthood. These results are compared and discussed in the light of the key data reported in the literature for mice and rats.CONCLUSIONSThe current literature highlights the fact that (i) there is a huge difference between the number of studies performed in animals and in humans, with many fewer for humans; (ii) there are differences in the way rats, mice, primates and humans respond to phthalates, for reasons that need to be further explored; (iii) more work is required to clarify the contradictions, in the few existing human epidemiological studies at all stages of development, which may be partly explained by varying methods of exposure assessment; (iv) in accordance with recent findings in rodents, it cannot be excluded that transgenerational effects of phthalates and/or epigenetic changes exist in humans; (v) a number of methodological limitations need to be solved for the in vitro and xenografting models using human fetal testis to fulfil their 'missing link' role between epidemiological studies in humans and rodent models; and (vi) epidemiological and in vitro studies generally converge sufficiently to conclude that phthalate anti-androgenicity is plausible in adult men.
ISSN: 1355-4786

inserm-00869540
http://www.hal.inserm.fr/inserm-00869540
DOI : 10.1093/humupd/dmt050
PUBMED : 24077978

Éditeur(s) : HAL CCSD
Résumé : International audience
Migration of chemicals from packaging materials to foods may lead to human exposure. Polyfluoroalkyl substances (PFAS) can be used in technical mixtures (TMs) for use in food packaging of paper and board, and PFAS have been detected in human serum and umbilical cord blood. The specific structures of the PFAS in TMs are often unknown, but polyfluorinated alkyl phosphate esters (PAPs) have been characterized in TMs, food packaging, and in food. PAPs can be metabolized into fluorotelomer alcohols (FTOHs) and perfluoroalkyl carboxylic acids (PFCAs). Some PFAS have endocrine activities, highlighting the need to investigate these effects. Herein, we studied the endocrine activity of less characterized PFAS, including short-chain PFCAs and FTOHs, PAPs, and TMs of unknown chemical composition. Long-chain PFCAs were also included. We applied seven assays covering effects on estrogen, glucocorticoid, androgen, and peroxisome proliferator-activated receptor (PPAR) activity, as well as steroidogenesis in vitro and ex vivo. In general, PAPs, FTOHs, TMs, and long-chain PFCAs showed estrogenic activity through receptor activation and/or increasing 17β-estradiol levels. Furthermore, short- and long-chain PFCAs activated PPARα and PPARγ. Collectively, this means that (i) PAPs, FTOHs, and PFCAs exhibit endocrine activity through distinct and sometimes different mechanisms, (ii) two out of three tested TMs exhibited estrogenic activity, and (iii) short-chain FTOHs showed estrogenic activity and short-chain PFCAs generally activate both PPARα and PPARγ with similar potency and efficacy as long-chain PFCAs. In conclusion, several new and divergent toxicological targets were identified for different groups of PFAS. © 2016 American Society of Andrology and European Academy of Andrology
Andrology

hal-01367144
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01367144
DOI : 10.1111/andr.12190
PUBMED : 27152447

Éditeur(s) : HAL CCSD Oxford University Press (OUP): Policy C - Option B
Résumé : International audience
We report the characterization of a DNA primase/ polymerase protein (PolpTN2) encoded by the pTN2 plasmid from Thermococcus nautilus. Sequence analysis revealed that this protein corresponds to a fusion between an N-terminal domain homologous to the small catalytic subunit PriS of heterodimeric archaeal and eukaryotic primases (AEP) and a C-terminal domain related to their large regulatory subunit PriL. This unique domain configuration is not found in other virus-and plasmid-encoded primases in which PriS-like domains are typically fused to different types of helicases. PolpTN2 exhibited primase, polymerase and nucleotidyl transferase activities and specifically incorporates dNTPs, to the exclusion of rNTPs. PolpTN2 could efficiently prime DNA synthesis by the T. nautilus PolB DNA polymerase, suggesting that it is used in vivo as a primase for pTN2 plasmid replication. The N-terminal PriS-like domain of PolpTN2 exhibited all activities of the full-length enzyme but was much less efficient in priming cellular DNA polymerases. Surprisingly, the N-terminal domain possesses reverse transcriptase activity. We speculate that this activity could reflect an ancestral function of AEP proteins in the transition from the RNA to the DNA world.
ISSN: 0305-1048

Droits : http://creativecommons.org/licenses/by/
hal-01332620
http://hal.upmc.fr/hal-01332620
http://hal.upmc.fr/hal-01332620/document
http://hal.upmc.fr/hal-01332620/file/Nucl.%20Acids%20Res.-2014-Gill-3707-19.pdf
DOI : 10.1093/nar/gkt1385

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
Résumé : The recent accumulation of genomic sequence data has shown that gene evolution is not strictly tree-Like. Many evolutionary processes, like exon shuffling, gene fusion or nonhomologous recombination remodel genes by creating composite structures that are made from parts with different evolutionary histories. The development of sequence similarity networks provides an analytical framework to study the impact of these processes on molecular evolution, by structuring the resemblance relationships between sequences and by formalizing, in terms of graph theory, the detection of composite genes (intransitive triplets) and gene families (clique minimal separators). The size of current data sets, typically several million sequences, has also required the development of new tools and methods: sequence comparison parallelization, large networks visualization with Louvain communities and large cycles identification. When applied to eukaryotic and viral genome data sets, these methods have shown that composite genes are found throughout cellular organisms and mobile genetic elements. Proportionally, composite genes are more numerous in eukaryotic genomes; in absolute number, they are more numerous in viruses. In the latter, composite genes functional distribution is biased (enrichment of genes families that are essential for the perpetuation of the viral cycle), and the various parts of composite genes sometimes even originate from the genetic material of different viral classes. More generally, the extent of combinatorial processes, by unravelling other evolutionary bonds than homology bonds in the strictest sense, legitimates a pluralistic study of similarity relationships between sequences.
L’accumulation récente de données de séquences génomiques a montré que l’évolution des gènes n’est pas strictement arborescente. De nombreux processus évolutifs, comme l’exon shuffling, la fusion de gènes ou la recombinaison illégitime remodèlent les gènes, créant des structures composites, formées de parties dont les histoires évolutives sont différentes. Le développement de réseaux de similarité de séquences fournit un cadre analytique permettant d’étudier l’impact de ces processus sur l’évolution moléculaire, en structurant les relations de ressemblance entre séquences et en formalisant en termes de graphes la détection de gènes (triplets intransitifs) et de familles de gènes (cliques minimales séparatrices) composites. La taille des jeux de données actuels, de l’ordre de plusieurs millions de séquences, a également requis le développement de nouveaux outils et méthodes : parallélisation des comparaisons de séquences, visualisation de très grands réseaux par simplification en communautés de Louvain et identification de grands cycles. Appliquées à des jeux de données de génomes eucaryotes et viraux, ces méthodes ont démontré la présence de gènes composites dans tout le vivant et les éléments génétiques mobiles. En proportion, les gènes composites sont plus nombreux dans les génomes eucaryotes ; en nombre absolu, ils sont plus nombreux à être portés par des virus. Chez ces derniers, la distribution fonctionnelle des gènes composites est biaisée (enrichissement dans les familles essentielles pour la perpétuation du cycle viral), et les éléments des gènes composites trouvent même parfois leurs origines dans le matériel génétique de classes virales différentes. Plus généralement, l’étendue des processus combinatoires, en révélant des liens évolutionnaires autres que les liens d’homologie au sens fort, justifie une étude pluraliste des relations de similarité entre séquences.
https://tel.archives-ouvertes.fr/tel-01127379

NNT : 2014PA066358
tel-01127379
https://tel.archives-ouvertes.fr/tel-01127379
https://tel.archives-ouvertes.fr/tel-01127379/document
https://tel.archives-ouvertes.fr/tel-01127379/file/2014PA066358.pdf

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Mantle cell lymphoma (MCL) is a hematologic neoplasm characterised by the t(11;14)(q13;q32) translocation leading to aberrant cyclin D1 expression. The cell functions of cyclin D1 depend on its partners and/or subcellular distribution, resulting in different oncogenic properties. We observed the accumulation of cyclin D1 in the cytoplasm of a subset of MCL cell lines and primary cells. In primary cells, this cytoplasmic distribution was correlated with a more frequent blastoid phenotype. We performed immunoprecipitation assays and mass spectrometry on enriched cytosolic fractions from two cell lines. The cyclin D1 interactome was found to include several factors involved in adhesion, migration and invasion. We found that the accumulation of cyclin D1 in the cytoplasm was associated with higher levels of migration and invasiveness. We also showed that MCL cells with high cytoplasmic levels of cyclin D1 engrafted more rapidly into the bone marrow, spleen, and brain in immunodeficient mice. Both migration and invasion processes, both in vivo and in vitro, were counteracted by the exportin 1 inhibitor KPT-330, which retains cyclin D1 in the nucleus. Our data reveal a role of cytoplasmic cyclin D1 in the control of MCL cell migration and invasion, and as a true operator of MCL pathogenesis.
ISSN: 2045-2322

hal-01635754
https://hal.archives-ouvertes.fr/hal-01635754
DOI : 10.1038/s41598-017-14222-1
PUBMED : 29066743

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : International audience
Background. An association with cancer is described in 17–32% of cases of dermatomyositis (DM) and in 5–16% of cases of anti-synthetase syndrome (ASS). The literature contains very few studies involving Afro-Caribbean patients with DM or ASS. The aim of our retrospective study was to determine the prevalence of cancer in a series of patients with DM or ASS at the University Hospital of Pointe-à-Pitre between 1st January 2000 and 31st December 2012. The secondary objective was to review the clinical and laboratory features as well as the course of DM/ASS in these patients.Patients and methods. The inclusion criteria were as follows: Afro-Caribbean origin; age >15 years; patient living in Guadeloupe; screening for malignancy.Results. Twenty-two patients were included (15 DM, 7 ASS). Only one case of cancer was diagnosed in the entire study population at a mean follow-up of 6±4 years (prevalence: 6.7%, CI95% [1.7–31.9]). Of the 15 patients presenting DM (sex ratio F/M: 4, mean age: 45±14 years), 6 (40%) had associated connective tissue disease.Conclusion. Our study suggests a weak association between DM and cancer in Afro-Caribbean patients. These results may be explained by the features of the disease seen in these patients (female gender, young age at onset, associated connective tissue disease) and the low prevalence in the Caribbean region of cancers typically associated with DM.
Introduction. Dix-sept à 32 % des cas de dermatomyosite (DM) et 5 à 16 % des cas de syndrome des anti-synthétases (SAS) sont associés à un cancer. Les séries de patients afro-caribéens atteints de DM ou de SAS sont exceptionnellement rapportées dans la littérature. Le but de notre étude rétrospective était d’estimer la prévalence des cancers dans une série de patients guadeloupéens atteints de DM ou de SAS. L’objectif secondaire était de préciser les caractéristiques cliniques, biologiques et évolutives de la maladie chez ces patients.Patients et méthode. Les critères d’inclusion étaient les suivants : patient afro-caribéen ; âge >15ans ; patient vivant en Guadeloupe ; réalisation d’un bilan d’extension à la recherche d’une néoplasie.Résultats. Vingt-deux patients ont été inclus (15 atteints de DM, 7 de SAS). Un seul cancer a été diagnostiqué, avec une durée moyenne de suivi de 6±4ans sur l’ensemble de la série (prévalence de 6,7 % ; IC 95 % [1,7 ; 31,9]). Parmi les 15 patients atteints de DM (sex-ratio H/F=1/4 ; âge moyen : 45±14ans), 6 (40 %) avaient une connectivite associée.Conclusion. Notre étude suggère une faible association entre DM et cancer chez les patients afro-caribéens. Ces résultats s’expliquent principalement par les caractéristiques de la maladie chez ces patients (sexe féminin, jeune âge, connectivite associée) et la faible prévalence, aux Antilles, des cancers classiquement associés aux DM.
ISSN: 0151-9638

inserm-01110999
http://www.hal.inserm.fr/inserm-01110999
http://www.hal.inserm.fr/inserm-01110999/document
http://www.hal.inserm.fr/inserm-01110999/file/2014%2C%20Tersiguel%20-%20Epid%C3%A9miologie%20de%20la%20dermatomyosite%20et%20du%20syndrome%20des%20anti-synth%C3%A9tases%20en%20population%20afro-carib%C3%A9enne.pdf
PUBMED : 25288059

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
The mucosal events of HIV transmission have been extensively studied, but the role of infected cells present in the genital and rectal secretions, and in the semen, in particular, remains a matter of debate. As a prerequisite to a thorough in vivo investigation of the early transmission events through infected cells, we characterized in detail by multi-parameter flow cytometry the changes in macaque seminal leukocytes during SIVmac251 infection, focusing on T cells, macrophages and dendritic cells. Using immunocytofluorescence targeting SIV proteins and real-time quantitative PCR targeting SIV DNA, we investigated the nature of the infected cells on sorted semen leukocytes from macaques at different stages of infection. Finally, we cocultured semen CD4(+) T cells and macrophages with a cell line permissive to SIV infection to assess their infectivity in vitro. We found that primary infection induced strong local inflammation, which was associated with an increase in the number of leukocytes in semen, both factors having the potential to favor cell-associated virus transmission. Semen CD4(+) T cells and macrophages were productively infected at all stages of infection and were infectious in vitro. Lymphocytes had a mucosal phenotype and expressed activation (CD69 & HLA-DR) and migration (CCR5, CXCR4, LFA-1) markers. CD69 expression was increased in semen T cells by SIV infection, at all stages of infection. Macrophages predominated at all stages and expressed CD4, CCR5, MAC-1 and LFA-1. Altogether, we demonstrated that semen contains the two major SIV-target cells (CD4+ T cells and macrophages). Both cell types can be productively infected at all stages of SIV infection and are endowed with markers that may facilitate transmission of infection during sexual exposure.
ISSN: 1553-7366

hal-00955292
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00955292
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00955292/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00955292/file/Semen_CD4_T-accepted.pdf
PUBMED : 24348253

Éditeur(s) : HAL CCSD
Résumé : National audience
La sédimentation en baie du Mont Saint Michel se caractérise par la mixité des apports, presque exclusivement d’origine marine, carbonatés et silicoclastiques. La question du comblement de cet environnement hypertidal et de l’évolution de son trait de côte, représenté dans le fond de baie (sud et ouest) par des barrières coquillières, se pose à l’horizon des décennies à venir. Comment ce comblement va t-il être affecté par le changement climatique global marqué entre autres par l’accélération de la remontée du niveau marin et par des modifications potentielles de faunes (habitats, espèces..etc) auxquelles peut également contribuer le développement d’activités humaines comme la conchyliculture ?Les travaux présentés ici (projet Sédibaie, DDTM35 / Région Basse Normandie) ont pour objectif de quantifier le taux de sédimentation dans le fond de baie du Mont-Saint-Michel depuis les derniers siècles, et cela afin d’appréhender les tendances à venir. Pour ce faire des carottages courts (moy. 75 cm) ont été réalisés selon 5 radiales côte-large réparties de St Benoit des Ondes (près de Cancale) à La Chapelle Ste Anne (à l’Ouest du Mt St Michel). Les carottes ont fait l’objet d’analyses variées (faciès, granulométrie, teneur en carbonate, XRF, Scopix, datations 14C...). Un échantillonnage de surface a également été réalisé afin de caractériser les assemblages faunistiques actuels (malacofaune, microfaune, vivant, mort). Parallèlement, des travaux spécifiques sont menés sur les barrières coquillières (stratigraphie THR, évolution contenu faunistique, processus d’édification..). Les enregistrements étudiés sur les carottes couvrent la sédimentation du dernier millénaire au moins. Ils mettent en évidence le passage entre un environnement de dépôt dominé par l’action des marées, à un environnement de plus haute énergie, sans doute dominé par l’action des houles (tempêtes ?). Ce changement majeur, visible sur quasiment toutes les carottes à une profondeur variant entre 30 et 50 cm, s’opère peu après 1000 ans cal. BP. (à confirmer). Il est attribué à un changement climatique d’échelle au moins régionale (Atlantique nord). La complexite de l’enregistrement sédimentaire au-dessus du passage tidal/houle met en évidence une variabilité de faciès sédimentaires à haute fréquence, probablement liée à une fluctuation du climat de houle (NAO, Petit Age Glaciaire), ainsi que dans la partie supérieure à des changements d’apports bioclastiques relatifs au développement des installations conchylicoles.
25e Réunion des Sciences de la Terre
Caen, France

hal-01413154
https://hal.archives-ouvertes.fr/hal-01413154

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
Fucoxanthin is a carotenoid present in brown micro-and macro algae, that induces apoptosis or autophagy in cancer cells grown in vitro. In vivo studies confirmed its interest as a natural anticancer compound, as it exerts antitumoral, antimetastatic and antiangiogenic activities in animal models. Studies focused on the pharmacology of fucoxanthin in cancer cells and tumors have revealed that it affects a wide panel of cellular, molecular and tissular processes, suggesting that its biological activity may be related in part to a nonspecific integration in cell membranes, and possible interaction with lipid rafts. Thus, preliminary data confirming this interaction of fucoxanthin with lipid rafts were obtained in mast cells and hepatoma WIF-B9 cells. We here discuss this hypothesis, in view of the critical function of lipid rafts in cancer cell survival, invasivity and communication with the tumoral microenvironment.
ISSN: 2141-2294

hal-01391001
https://hal.archives-ouvertes.fr/hal-01391001
https://hal.archives-ouvertes.fr/hal-01391001/document
https://hal.archives-ouvertes.fr/hal-01391001/file/could-fucoxanthin-interaction-with-lipid-rafts-mediate-its-cytotoxicity-incancer-cells-.pdf
DOI : 10.4172/jomr.1000144

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
BACKGROUND: Hepatocellular carcinoma (HCC) is a particularly severe disease characterized by a high rate of recurrence and death even after surgical resection. Molecular characterization of HCC helps refine prognosis and may facilitate the development of improved therapy. Phosphatidylinositol 4-kinases have recently been identified as cellular factors associated with cancer. Also, phosphatidylinositol 4-kinase type IIIα (PI4KA) is necessary for the propagation of the hepatitis C virus, a major etiological factor for HCC. METHODS: Reverse transcription, quantitative real-time PCR was used to assay PI4KA mRNA. The expression levels were investigated both in a collection of molecularly and clinically characterized hepatic tissues from 344 patients with diverse liver diseases and in human hepatocyte cell lines whose proliferative and differentiation status was controlled by specific culture conditions. Analytical microarray data for 60 HCC and six normal liver tissue samples were exploited to study correlations between PI4KA mRNA levels and cell proliferation markers in vivo. Postoperative disease-specific survival and time to recurrence in a set of 214 patients with HCC were studied by univariate and multivariate analyses. RESULTS: PI4KA mRNA was more abundant in HCC than normal healthy tissues. This upregulation correlated significantly with both poor differentiation and the active proliferation rate in HCC. These associations were confirmed with in vitro models. Moreover, patients with HCC who had been treated by surgical resection and had higher PI4KA mRNA concentrations in their tumor tissue exhibited a higher risk of tumor recurrence (median time: 20 months versus 49 months, P = 0.0012) and shorter disease-specific survival (first quartile time: 16 months versus 48 months, P = 0.0004). Finally, the abundance of PI4KA mRNA proved to be an independent prognostic marker of survival for cases of HCC (hazard ratio = 2.36, P = 0.0064). CONCLUSIONS: PI4KA mRNA could be used as a new molecular marker to improve established prognostic models for HCC. These findings also indicate possible new lines of research for the development of innovative therapeutic approaches targeting PI4KA.
ISSN: 1471-2407

inserm-00934294
http://www.hal.inserm.fr/inserm-00934294
http://www.hal.inserm.fr/inserm-00934294/document
http://www.hal.inserm.fr/inserm-00934294/file/1471-2407-14-7.pdf
DOI : 10.1186/1471-2407-14-7

Éditeur(s) : HAL CCSD
Résumé :   Diplôme : DEA
il s'agit d'un type de produit dont les métadonnées ne correspondent pas aux métadonnées attendues dans les autres types de produit : DISSERTATION
En forêt tropicale humide les espèces arborées ont des stratégies différentes d'acquisition de l'azote : les espèces fixatrices utilisent l'azote atmosphérique N2 de l'air. Il existe des espèces à préférence à ammonium (NH+) ou à nitrate (NO3-), mais aussi des espèces ubiquistes se nourrissant des deux sources d'azote du sol. L'objectif de ce travail était de déterminer si ces stratégies différentes étaient intrinsèques à l'espèce ou si elles étaient conditionnées par le milieu du fait des compétitions intra et/ou interspécifiques. Nous avons étudié la nutrition azotée d'une vingtaine d'espèces d'arbres juvéniles élevés en pot sur sol de forêt en conditions semi-contrôlées (20% d'éclairement). Deux méthodes ont été utilisées : la mesure de l'activité nitrate réductase in vivo après induction par pulvérisation de nitrate sur les feuilles et la signature isotopique naturelle δ15N. Les résultats obtenus ont montré que la majorité des plantes en serre sembleraient capable d'utiliser l'une ou l'autre des deux sources avec une forte plasticité vis-à-vis de l'azote. Quelques espèces cependant n'utiliseraient que l'ammonium comme source d'azote malgré le milieu limitant, bien qu'ayant une activité nitrate reductase potentielle, traduisant une capacité non exploitée à assimiler le nitrate, les plantes fixatrices, elles, sembleraient avoir accès aux deux sources d'azote du sol. En utilisant des traits d'héliophile peu de liens ont été observés avec le tempérament des espèces vis-à-vis de la lumière. Des mesures complémentaires sous différents éclairements (5, 10 et 30%) seraient nécessaires pour conclure sur ce sujet. Les différences de nutrition observées dans le milieu naturel seraient dues aux conditions du milieu même si indirectement il se pourrait que la plante ait le pouvoir d'influencer le choix de la source en inhibant la nitrification au niveau rhizosphérique par le biais d'exsudats racinaires.
https://hal.archives-ouvertes.fr/hal-01189235

hal-01189235
https://hal.archives-ouvertes.fr/hal-01189235
PRODINRA : 17890