Éditeur(s) : HAL CCSD Ecole nationale du génie rural
Résumé :  
Le modelé forestier guyanais se présente comme une vaste surface basse développée dans le manteau d'altération et constituée de croupes et de plateaux aux formes très diverses. De cet ensemble émergent, sur des surfaces réduites, des reliefs de commandement, inselbergs et chaînons, aux altitudes modestes mais avec des dénivellations locales fortes. La diversité des modèles guyanais est principalement influencée par le substrat géologique, directement à travers sa capacité à avoir produit au cours du temps une cuirasse, matériau induré résistant à l'érosion. Les modelés forestiers guyanais et africains ont une très forte unité géologique. Par contre, des histoires climatiques différentes depuis le Crétacé ont conduit pour le modelé guyanais à un morcellement extrême des interfluves et à un moindre rôle du cuirassement des sols.
ISSN: 0035-2829

hal-01032096
https://hal.archives-ouvertes.fr/hal-01032096

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
The increased expression of the Disintegrin and Metalloprotease ADAM12 has been associated with human cancers, however its role remain unclear. We have previously reported that ADAM12 expression is induced by the transforming growth factor, TGF-β and promotes TGF-β-dependent signaling through interaction with the type II receptor of TGF-β. Here we explore the implication of ADAM12 in TGF-β-mediated epithelial to mesenchymal transition (EMT), a key process in cancer progression. We show that ADAM12 expression is correlated with EMT markers in human breast cancer cell lines and biopsies. Using a non-malignant breast epithelial cell line (MCF10A), we demonstrate that TGF-β-induced EMT increases expression of the membrane-anchored ADAM12L long form. Importantly, ADAM12L overexpression in MCF10A is sufficient to induce loss of cell-cell contact, reorganization of actin cytoskeleton, up-regulation of EMT markers and chemoresistance. These effects are independent of the proteolytic activity but require the cytoplasmic tail and are specific of ADAM12L since overexpression of ADAM12S failed to induce similar changes. We further demonstrate that ADAM12L-dependent EMT is associated with increased phosphorylation of Smad3, Akt and ERK proteins. Conversely, inhibition of TGF-β receptors or ERK activities reverses ADAM12L-induced mesenchymal phenotype. Together our data demonstrate that ADAM12L is associated with EMT and contributes to TGF-β-dependent EMT by favoring both Smad-dependent and Smad-independent pathways
ISSN: 1932-6203

hal-01207281
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01207281
DOI : 10.1371/journal.pone.0139179
PUBMED : 26407179

Éditeur(s) : HAL CCSD SAGE Publications (UK and US)
Résumé : International audience
Enamel and enameloid, the highly mineralized tooth-covering tissues in living vertebrates, are different in their matrix composition. Enamel, a unique product of ameloblasts, principally contains enamel matrix proteins (EMPs), while enameloid possesses collagen fibrils and probably receives contributions from both odontoblasts and ameloblasts. Here we focused on type I collagen (COL1A1) and amelogenin (AMEL) gene expression during enameloid and enamel formation throughout ontogeny in the caudate amphibian, Pleurodeles waltl. In this model, pre-metamorphic teeth possess enameloid and enamel, while post-metamorphic teeth possess enamel only. In first-generation teeth, qPCR and in situ hybridization (ISH) on sections revealed that ameloblasts weakly expressed AMEL during late-stage enameloid formation, while expression strongly increased during enamel deposition. Using ISH, we identified COL1A1 transcripts in ameloblasts and odontoblasts during enameloid formation. COL1A1 expression in ameloblasts gradually decreased and was no longer detected after metamorphosis. The transition from enameloid-rich to enamel-rich teeth could be related to a switch in ameloblast activity from COL1A1 to AMEL synthesis. P. waltl therefore appears to be an appropriate animal model for the study of the processes involved during enameloid-to-enamel transition, especially because similar events probably occurred in various lineages during vertebrate evolution.
ISSN: 0022-0345

hal-01545475
https://hal.archives-ouvertes.fr/hal-01545475
DOI : 10.1177/0022034514526236

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
The extracellular signal-regulated kinase (ERK)1/2 mitogen-activated protein (MAP) kinase pathway has been involved in the positive and negative regulation of cell proliferation. Upon mitogen stimulation, ERK1/ERK2 activation is necessary for G1- to S-phase progression whereas when hyperactived, this pathway could elicit cell cycle arrest. The mechanisms involved are not fully elucidated but a kinase-independent function of ERK1/2 has been evidenced in the MAPK-induced growth arrest. Here, we show that p70S6K, a central regulator of protein biosynthesis, is essential for the cell cycle arrest induced by overactivation of ERK1/2. Indeed, whereas MEK1 silencing inhibits cell cycle progression, we demonstrate that active mutant form of MEK1 or MEK2 triggers a G1 phase arrest by stimulating an activation of p70S6K by ERK1/2 kinases. Silencing of ERK1/2 activity by shRNA efficiently suppresses p70S6K phosphorylation on Thr421/Ser424 and S6 phosphorylation on Ser240/244 as well as p21 expression, but these effects can be partially reversed by the expression of kinase-dead mutant form of ERK1 or ERK2. In addition, we demonstrate that the kinase p70S6K modulates neither the p21 gene transcription nor the stability of the protein but enhances the translation of the p21 mRNA. In conclusion, our data emphasizes the importance of the translational regulation of p21 by the MEK1/2-ERK1/2-p70S6K pathway to negatively control the cell cycle progression. J. Cell. Physiol. 229: 903-915, 2014. © 2013 Wiley Periodicals, Inc.
ISSN: 0021-9541

hal-01061238
https://hal.archives-ouvertes.fr/hal-01061238
https://hal.archives-ouvertes.fr/hal-01061238/document
https://hal.archives-ouvertes.fr/hal-01061238/file/MEK12_OveractivationArticle_GUEGAN_JCP_2014.pdf
DOI : 10.1002/jcp.24521

Éditeur(s) : HAL CCSD Wiley
Résumé : Tank bromeliads form a conspicuous, yet neglected freshwater habitat in Neotropical forests. Recent studies driven by interests in medical entomology, fundamental aspects of bromeliad ecology and experimental research on food webs have, however, prompted increasing interest in bromeliad aquatic ecosystems. As yet, there is nothing in the literature about the life histories and environmental drivers of invertebrate population dynamics in tank bromeliads. Based on fortnightly samples taken over oneyear, size frequency plots and individual dry masses allowed us to establish the life cycles and growth rates of the dominant aquatic invertebrates in a common bromeliad species of French Guiana. Linear mixed-effect models and Mantel tests were used to predict changes in density, biomass, and growth rates in relation to temperature, rainfall, humidity and detrital resources. Annual variations in invertebrate densities and biomasses could be described according to three types of distribution: unimodal, bimodal or almost constant. Despite seasonal variations, precipitation, temperature, relative humidity and detritus concentration accounted significantly for changes in density and biomass, but we found no significant responses in growth rates of most invertebrate species. Species rather displayed non-seasonal life cycles with overlapping cohorts throughout the year. There was also a trend for delayed abundance peaks among congeneric species sharing similar functional traits, suggesting temporal partitioning of available resources. Beyond novel knowledge, quantitative information on life histories is important to predict food-web dynamics under the influence of external forcing and self-organisation. Our results suggest that changes in species distribution that will affect population dynamics through biotic interactions in space and/or time could have greater effects on food webs and ecosystem functioning than changes in environmental factors per se.
ISSN: 0046-5070

hal-01607779
https://hal.archives-ouvertes.fr/hal-01607779
DOI : 10.1111/fwb.12862
PRODINRA : 407311

Éditeur(s) : HAL CCSD Microbiology Society
Résumé : International audience
An actinobacterial strain, designated ViU22(T), was isolated from a natural uranium-rich soil and was studied using a polyphasic approach. Cells formed orange-pigmented colonies, were rod-shaped, Gram-positive (non-staining method), non-motile and non-spore-forming. This organism grew in 0-4.5 % (w/v) NaCl and at 15-37 °C, with optimal growth occurring in 0.5 % (w/v) NaCl and at 30 °C. Comparative 16S rRNA gene sequence analysis revealed that the strain ViU22(T) belonged to the genus Microbacterium. It exhibited highest 16S rRNA gene sequence similarity with the type strains of Microbacterium testaceum (98.14 %) and Microbacterium binotii (98.02 %). The DNA-DNA relatedness of strains ViU22(T) with the most closely related type strains Microbacterium testaceum and Microbacterium binotii DSM 19164(T) was 20.10 % (± 0.70) and 28.05 % (± 0.35), respectively. Strain ViU22(T) possessed a type B2β peptidoglycan with partial substitution of glutamic acid by 3-hydroxy glutamic acid. The major menaquinones were MK-11 and MK-12. Major polar lipids detected in the strain ViU22(T) were diphosphatidylglycerol, phosphatidylglycerol, an unknown phospholipid and unknown glycolipids. The predominant fatty acids were anteiso-C15 : 0, anteiso-C17 : 0 and iso-C16 : 0, a pattern reported for other Microbacterium species. The major cell-wall sugars were galactose, xylose and mannose and the DNA G+C content was 71 mol%. Together, the DNA-DNA hybridization results and the differentiating phenotypic characteristics, showed that strain ViU22(T) should be classified as the type strain of a novel species within the genus Microbacterium, for which the name Microbacterium lemovicicum sp. nov. is proposed. The type strain is ViU22(T) ( = ATCC BAA-2396(T) = CCUG 62198(T) = DSM 25044(T)).
ISSN: 1466-5026

hal-01561095
https://hal-amu.archives-ouvertes.fr/hal-01561095
PUBMED : 23264499
DOI : 10.1099/ijs.0.048454-0

Éditeur(s) : HAL CCSD
Résumé : National audience
Objectifs La recherche d’anticorps anti-aspergillaires est une analyse essentielle au diagnostic des formes chroniques d’aspergilloses. De nombreuses techniques sont disponibles, commerciales ou non, regroupées par la nomenclature française en méthodes de dépistage et de confirmation. La SFMM a mené en janvier–février 2015 une étude de type « avis d’expert » sur les performances de ces techniques et leur stratégie de mise en œuvre. Méthodes Quarante experts ont été sollicités pour répondre à un questionnaire en ligne comprenant 37 questions. Les réponses, obligatoires pour tous les items, devaient être cotées de 1 à 9 selon l’accord total (9) ou le désaccord total (1) de l’expert. L’analyse a été faite sur la valeur de la cote médiane et les coefficients de variation (écart-type/moyenne) pour juger de la variabilité des réponses. Résultats Trente-six questionnaires ont été complétés. Les CV des réponses allaient de 10 % à 75 %, seuls 38 % d’entre eux étant supérieurs à 50 %. La distinction entre méthode de dépistage et méthode de confirmation est globalement jugée comme pertinente (médiane = 7) mais un positionnement clair des techniques en dépistage ou confirmation n’est obtenu avec un CV inférieur à 30 % que pour l’Elisa en dépistage et l’immunoélectrophorèse et le western blot en confirmation. La pratique d’une technique de confirmation est essentiellement recommandée en cas de positivité de la méthode de dépistage (médiane = 9 ; CV = 14 %), en fonction du contexte clinique (8 ; 31 %) ou lors d’un suivi (8 ; 33 %). En cas de discordance entre méthode de dépistage et de confirmation, les experts recommandent une interprétation directe des résultats en donnant priorité aux résultats de la méthode de confirmation (en fonction du dossier du patient) (8 ; 28 %). Conclusion Cette enquête montre l’absence de consensus sur la stratégie de détection des anticorps anti-aspergillaires et doit inciter les mycologues français à harmoniser au mieux leurs pratiques, afin de répondre à la demande des cliniciens
Congrès de la SFMM
Talence-Bordeaux, France

hal-01198639
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01198639
DOI : 10.1016/j.mycmed.2015.06.012

Éditeur(s) : HAL CCSD American Geophysical Union (AGU)
Résumé : Structural, metamorphic, and geochronologic work shows that the Ampelos/Dilek nappe of the Cycladic blueschist unit in the eastern Aegean constitutes a wedge of high-pressure rocks extruded during early stages of orogeny. The extrusion wedge formed during the incipient collision of the Anatolian microcontinent with Eurasia when subduction and deep underthrusting ceased and the Ampelos/Dilek nappe was thrust southward over the greenschist-facies Menderes nappes along its lower tectonic contact, the Cycladic-Menderes thrust, effectively cutting out a ∼30- to 40-km-thick section of crust. The upper contact of the Ampelos/Dilek extrusion wedge is the top-to-the-NE Selçuk normal shear zone, along which the Ampelos/Dilek nappe was exhumed by ∼30–40 km. Detailed Rb-Sr and 40Ar/39Ar dating of mylonites demonstrates that both shear zones operated between 42 and 32 Ma. There is no evidence for episodic motion during the ∼10 Myr life span of the shear zones, suggesting that both shear zones operated in a steady, nonepisodic fashion. Our data provide supporting evidence that simultaneous thrust-type and normal sense shearing can accomplish the early exhumation of deep-seated rocks
ISSN: 0278-7407

hal-00405013
https://hal.archives-ouvertes.fr/hal-00405013
DOI : 10.1029/2005TC001872

Éditeur(s) : HAL CCSD
Résumé :  
Les Aracées forment une famille de plantes dont on connaît actuellement quelque 150 genres et 3300 espèces réparties sur toute la surface du globe, principalement dans les zones tropicales et équatoriales de l'Asie et de l'Amérique du Sud. Au-delà d'une immense diversité de formes, de modes de vies et d'habitats, les Aracées ont en commun - à quelques exceptions près - d'être entomophiles. Pour attirer et retenir les insectes qui les pollinisent, elles ont développé des inflorescences très particulières.
Insectes

hal-01032101
https://hal.archives-ouvertes.fr/hal-01032101

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
Questions: Several studies have described aggregated spatial patterns in tropical tree species. This study investigates aggregate dynamics of Vouacapoua americana (Aublet), a climax species whose spatial pattern is not simply related to light and soil conditions or to its short seed dispersal range. Location: Two rain forest sites: Nouragues and Paracou, in the Guiana Shield. Methods: We described the spatial pattern of tree locations and spatial autocorrelation of tree diameters, using statistics derived from Ripley's K. We particularly used methods to define analysis subplots according to local density or local mean diameter. We investigated relationships between spatial distributions of adults and saplings. Results: At both sites, populations of Vouacapoua demonstrated several nested levels of aggregation. Tree diameters were spatially autocorrelated, revealing the existence of clusters with similar diameters. In the largest aggregates, tree diameters declined from the centre to the edge. Regeneration was aggregated and occurred mainly at cluster edges and around rare isolated trees, and sapling densities and basal area of adults were negatively correlated. We show that long-distance dispersal events are rare. Conclusions: Environmental factors and seed dispersal only explain part of the observed spatial patterns. We provide two main hypotheses about Vouacapoua population dynamics. First, the lack of regeneration in aggregate centres results in the ageing of existing aggregates. We suggest that this lack of recruitment close to mature trees is due to a Janzen-Connell effect. However, aggregates can continue to grow along colonization fronts. Second, long-distance dispersal events allow the formation of new clusters and play a crucial role in the colonization process. We investigate aggregate dynamics of Vouacapoua americana (Aublet) whose spatial pattern is not simply related to environmental conditions or to its seed dispersal. Regeneration does not occur in centers of aggregate of adults. We suggest that rare long-distance dispersal events and density-dependence predation of seeds and seedlings play a crucial role in formation of new clusters and structuration of larger aggregates.
ISSN: 1100-9233

hal-01502642
https://hal-agroparistech.archives-ouvertes.fr/hal-01502642
DOI : 10.1111/jvs.12080

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
: In non-mammalian vertebrates, serotonin (5-HT)-producing neurons exist in the paraventricular organ (PVO), a diencephalic structure containing cerebrospinal fluid (CSF)-contacting neurons exhibiting 5-HT or dopamine (DA) immunoreactivity. Because the brain of the adult teleost is known for its neurogenic activity supported, for a large part, by radial glial progenitors, this study addresses the origin of newborn 5-HT neurons in the hypothalamus of adult zebrafish. In this species, the PVO exhibits numerous radial glial cells (RGCs) whose somata are located at a certain distance from the ventricle. To study relationships between RGCs and 5-HT CSF-contacting neurons, we performed 5-HT immunohistochemistry in transgenic tg(cyp19a1b-GFP) zebrafish in which RGCs are labelled with GFP under the control of the cyp19a1b promoter. We show that the somata of the 5-HT neurons are located closer to the ventricle than those of RGCs. RGCs extend towards the ventricle cytoplasmic processes that form a continuous barrier along the ventricular surface. In turn, 5-HT neurons contact the CSF via processes that cross this barrier through small pores. Further experiments using proliferating cell nuclear antigen or 5-bromo-2'-deoxyuridine indicate that RGCs proliferate and give birth to 5-HT neurons migrating centripetally instead of centrifugally as in other brain regions. Furthermore, treatment of adult zebrafish with tryptophan hydroxylase inhibitor causes a significant decrease in the number of proliferating cells in the PVO, but not in the mediobasal hypothalamus. These data point to the PVO as an intriguing region in which 5-HT appears to promote genesis of 5-HT neurons that accumulate along the brain ventricles and contact the CSF.
ISSN: 0953-816X

inserm-00866212
http://www.hal.inserm.fr/inserm-00866212
DOI : 10.1111/ejn.12348
PUBMED : 23981075

Éditeur(s) : HAL CCSD
Résumé : Communication between tumoral cells and the microenvironnement plays an essential role in the developpement of tumors. In that context, the new family of metalloproteases, the ADAM proteins, are major regulators of the tumoral progression by acting on the bioavaibility of importants mediators of cellular communication as cytokines and growth factors. Among this family, ADAM12 is the most associated with cancer. It has been shown to mediate signaling pathways by a process independant of its metalloproteasis activity, in particular for TGFβ signaling. This study show for the first time a role for the membrane form of ADAM12 in the induction of epithelial to mesenchymal transition (EMT), a essential process involved in tumor invasion, whom TGFβ is a main inducer. This effect is mediated by the activation of TGFβ signaling pathways, SMAD3, AKT and ERK and require the cytoplasmic tail of ADAM12L but not its catalytic activity. Activation of these pathways could involve a relocalisation of ADAM12L in special signaling platform in lipid rafts. Moreover, we have shown that ADAM12L interact with ZO-1 and ZO-2, two proteins of tight junctions, and could facilitate their desassembling during EMT. This work underscore for the first time a new function of ADAM12L in EMT, by a mecanism invovlving a modulation of signals regulating this process. A better understanding of the dynamic of these molecular mecanisms could allow the developpement of new targeted therapies to fight against tumoral progression.
Les échanges entre les cellules tumorales et le microenvironnement jouent un rôle essentiel dans le développement des tumeurs. Dans ce contexte, la nouvelle famille de métalloprotéases, les protéines ADAM, constituent aujourd’hui des régulateurs majeurs de la progression tumorale en agissant sur la biodisponibilité des médiateurs de la communication cellulaire que sont les cytokines, chimiokines et facteurs de croissance. Au sein de cette famille, ADAM12 est la plus associée au cancer. Elle possède la particularité de jouer un rôle dans la signalisation cellulaire, de façon indépendante de son activité métalloprotéase, notamment dans les voies de signalisation du TGFβ. Notre étude montre pour la première fois un rôle pour la forme membranaire d'ADAM12 dans l'induction de la transition épithélio-mésenchymateuse (EMT), un processus essentiel à l'invasion tumorale dont le TGFβ est un inducteur majeur. Cet effet est médié par l'activation des voies de signalisation du TGFβ, impliquant les protéines SMAD3, AKT et ERK et requiert le domaine cytoplasmique d'ADAM12L mais pas son domaine catalytique. L'activation de ces voies de signalisation pourrait impliquer une relocalisation d'ADAM12L au sein de plates-formes de signalisation dans les radeaux lipidiques. Par ailleurs, nous avons montré qu'ADAM12L interagit avec les protéines ZO-1 et ZO-2, des protéines des jonctions serrées, et pourrait favoriser leur désassemblage au cours de l'EMT. Nos travaux ont permis de mettre en évidence une nouvelle fonction pour ADAM12L dans l'EMT, par un mécanisme impliquant une modulation des signaux régulant ce processus. Une meilleure compréhension de la dynamique de ces mécanismes moléculaires pourrait permettre de développer de nouvelles thérapies ciblées pour lutter contre la progression tumorale.
https://tel.archives-ouvertes.fr/tel-01267577

Droits : info:eu-repo/semantics/OpenAccess
NNT : 2015REN1S063
tel-01267577
https://tel.archives-ouvertes.fr/tel-01267577
https://tel.archives-ouvertes.fr/tel-01267577/document
https://tel.archives-ouvertes.fr/tel-01267577/file/RUFF_Michael.pdf

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
We sought transversotrematid trematodes from French Polynesian fishes by examining 304 individual scaled fishes of 53 species from seven families known to harbour the family elsewhere. A single species was found at two locations in the Tuamotus Archipelago on two species of Chaetodontidae (Chaetodon auriga and Chaetodon ephippium) and one species of Lutjanidae (Lutjanus gibbus). The species closely resembles Transversotrema borboleta Hunter & Cribb, 2012 from chaetodontids and lutjanids of the northern Great Barrier Reef (GBR) but differs from it consistently in 8 base positions of ITS2 rDNA. This level of variation exceeds that between some clearly morphologically distinct pairs of species of Transversotrema and the form from French Polynesia is thus interpreted as a distinct, though cryptic, species and named Transversotrema polynesiae n. sp. The new species forms part of a complex of species, here characterised as the T. borboleta complex, associated with chaetodontids and lutjanids in the tropical Indo-West Pacific. Most of the putative species within this complex are yet to be described. Comparison of identical numbers of matched samples of fishes from French Polynesia, Heron Island (southern GBR) and Lizard Island (northern GBR) revealed 1, 4 and 10 species of Transversotrema respectively suggesting that the French Polynesian fauna is depauperate for this family. In addition to those species apparently missing from suitable hosts in French Polynesia, several species from further west infect fishes (especially Nemipteridae) that are themselves absent from French Polynesia. This dramatic east–west decline in richness contrasts strongly with what is known for monogeneans, which appear to maintain their richness over the same scale, and is more precipitate than is known for other groups of trematodes. The decline might be explained in part by the absence of the as yet unknown first intermediate hosts in French Polynesia. However, we predict that it is explained by other life cycle traits. We hypothesise that the characters of large short-lived cercariae, short-lived miracidia, the absence in the life-cycle of second intermediate hosts that are capable of transporting the species, and definitive and first intermediate hosts that have limited vagility combine to give marine Transversotrematidae limited dispersal capacity and a propensity for localised speciation.
ISSN: 1383-5769

hal-01333467
https://hal-univ-perp.archives-ouvertes.fr/hal-01333467
DOI : 10.1016/j.parint.2013.11.009

Éditeur(s) : HAL CCSD National Academy of Sciences
Résumé : International audience
We applied single-molecule photobleaching to investigate the stoichiometry of human Orai1 and Orai3 channels tagged with eGFP and expressed in mammalian cells. Orai1 was detected predominantly as dimers under resting conditions and as tetramers when coexpressed with C-STIM1 to activate Ca(2+) influx. Orai1 was also found to be tetrameric when coexpressed with STIM1 and evaluated following fixation. We show that fixation rapidly causes release of Ca(2+), redistribution of STIM1 to the plasma membrane, and STIM1/Orai1 puncta formation, and may cause the channel to be in the activated state. Consistent with this possibility, Orai1 was found predominantly as a dimer when coexpressed with STIM1 in living cells under resting conditions. We further show that Orai3, like Orai1, is dimeric under resting conditions and is predominantly tetrameric when activated by C-STIM1. Interestingly, a dimeric Orai3 stoichiometry was found both before and during application of 2-aminoethyldiphenyl borate (2-APB) to activate a nonselective cation conductance in its STIM1-independent mode. We conclude that the human Orai1 and Orai3 channels undergo a dimer-to-tetramer transition to form a Ca(2+)-selective pore during store-operated activation and that Orai3 forms a dimeric nonselective cation pore upon activation by 2-APB.
ISSN: 0027-8424

hal-00873833
https://hal.archives-ouvertes.fr/hal-00873833
DOI : 10.1073/pnas.1114814108
PUBMED : 21987805

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 Public Library of Science
Résumé : International audience
Beggiatoaceae, giant sulphur-oxidizing bacteria, are well known to occur in cold and temperatewaters, as well as hydrothermal vents, where they form dense mats on the floor.However, they have never been described in tropical marine mangroves. Here, we describetwo new species of benthic Beggiatoaceae colonizing a marine mangrove adjacent to mangroveroots. We combined phylogenetic and lipid analysis with electron microscopy in orderto describe these organisms. Furthermore, oxygen and sulphide measurements in and exsitu were performed in a mesocosm to characterize their environment. Based on this, two new species, Candidatus Maribeggiatoa sp. and Candidatus Isobeggiatoa sp. inhabiting tropical marine mangroves in Guadeloupe were identified. The species identified as CandidatusMaribeggiatoa group suggests that this genus could harbour a third cluster with organisms ranging from 60 to 120 μm in diameter. This is also the first description of an Isobeggiatoa species outside of Arctic and temperate waters. The multiphasic approach also gives information about the environment and indications for the metabolism of these bacteria. Our study shows the widespread occurrence of members of Beggiatoaceae family and provides new insight in their potential role in shallow-water marine sulphide-rich environments such as mangroves.
ISSN: 1932-6203

hal-01205641
https://hal.univ-antilles.fr/hal-01205641
https://hal.univ-antilles.fr/hal-01205641/document
https://hal.univ-antilles.fr/hal-01205641/file/Beggiatoa%20Plosone2015.pdf
DOI : 10.1371/journal.pone.0117832

Éditeur(s) : HAL CCSD Elsevier
Résumé : Remerciements :- Dr. Jacques Delabie- Andrea Yockey-Dejean- Geoff Brown- Jean-Pierre Andrieu
Background: Most ant venoms consist predominantly of small linear peptides, although some contain disulfide linked peptides as minor components. However, in striking contrast to other ant species, some Anochetus venoms are composed primarily of disulfide-rich peptides. In this study, we investigated the venom of the ant Anochetus emarginatus with the aim of exploring these novel disulfide-rich peptides.Methods: The venom peptidome was initially investigated using a combination of reversed-phase HPLC and mass spectrometry, then the amino acid sequences of the major peptides were determined using a combination of Edman degradation and de novo MS/MS sequencing. We focused on one of these peptides, U-1-PONTX-Ae1a (Ae1a), because of its novel sequence, which we predicted would form a novel 3D fold. Ae1a was chemically synthesized using Fmoc chemistry and its 3D structure was elucidated using NMR spectroscopy. The peptide was then tested for insecticidal activity and its effect on a range of human ion channels.Results: Seven peptides named poneritoxins (PONTXs) were isolated and sequenced. The three-dimensional structure of synthetic Ae1a revealed a novel, compact scaffold in which a C-terminal beta-hairpin is connected to the N-terminal region via two disulfide bonds. Synthetic Ae1a reversibly paralyzed blowflies and inhibited human L-type voltage-gated calcium channels (Ca(v)1).Conclusions: Poneritoxins from Anochetus emarginatus venom are a novel class of toxins that are structurally unique among animal venoms.General significance: This study demonstrates that Anochetus ant venoms are a rich source of novel ion channel modulating peptides, some of which might be useful leads for the development of biopesticides.
ISSN: 0304-4165

hal-01511987
https://hal.archives-ouvertes.fr/hal-01511987
https://hal.archives-ouvertes.fr/hal-01511987/document
https://hal.archives-ouvertes.fr/hal-01511987/file/2016_Touchard_Biochimica_Biophysica_%7B4B3BE6A3-AE83-4C6E-B678-BBFB5CC84AF7%7D.pdf
DOI : 10.1016/j.bbagen.2016.07.027

Éditeur(s) : HAL CCSD Institute of Electrical and Electronics Engineers Inc.
Résumé : International audience
An important issue in epilepsy research is to understand the structural and functional modifications leading to chronic epilepsy, characterized by spontaneous recurrent seizures, after initial brain insult. To address this issue, we recorded and analyzed electroencephalography (EEG) and quantitative magnetic resonance imaging (MRI) data during epileptogenesis in the in vivo mouse model of Medial Temporal Lobe Epilepsy (MTLE, kainate). Besides, this model of epilepsy is a particular form of drug-resistant epilepsy. The results indicate that high-field (4.7T) MRI parameters (T2-weighted; T2-quantitative) allow to detect the gradual neuro-anatomical changes that occur during epileptogenesis while electrophysiological parameters (number and duration of Hippocampal Paroxysmal Discharges) allow to assess the dysfunctional changes through the quantification of epileptiform activity. We found a strong correlation between EEG-based markers (invasive recording) and MRI-based parameters (non-invasive) periodically computed over the 'latent period' that spans over two weeks, on average. These results indicated that both structural and functional changes occur in the considered epilepsy model and are considered as biomarkers of the installation of epilepsy. Additionally, such structural and functional changes can also be observed in human temporal lobe epilepsy. Interestingly, MRI imaging parameters could be used to track early (day-7) structural changes (gliosis, cell loss) in the lesioned brain and to quantify the evolution of epileptogenesis after traumatic brain injury. © 2016 IEEE.
38th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBC 2016
Unknown, Unknown or Invalid Region

hal-01467552
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01467552
DOI : 10.1109/EMBC.2016.7591605

Éditeur(s) : HAL CCSD American Association for Cancer Research
Résumé : International audience
Triple-negative breast cancers (TNBC) lacking estrogen and progesterone receptors and HER2 amplification have a relatively high risk of metastatic dissemination, but the mechanistic basis for this risk is not understood. Here we report that serum levels of CD95L are higher in TNBC patients compared to other breast cancer patients. Metalloprotease-mediated cleavage of CD95L expressed by endothelial cells surrounding tumors generates a gradient that promotes cell motility, due to formation of an unconventional CD95-containing receptosome termed the motility-inducing signaling complex. Formation of this complex was instrumental for Nox3-driven ROS generation. Mechanistic investigations revealed a Yes-Orai1-EGFR-PI3K pathway that triggered migration of TNBC cells exposed to CD95L. Our findings establish a pro-metastatic function for metalloprotease-cleaved CD95L in triple-negative breast cancers, revisiting its role in carcinogenesis.
ISSN: 0008-5472

hal-00873634
https://hal.archives-ouvertes.fr/hal-00873634
PUBMED : 24072745
DOI : 10.1158/0008-5472.CAN-13-1794

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : International audience
Adult lymphatic filariae (Wuchereria bancrofti, Brugia malayi) can cause blocking of lymphatics producing obliterating endolymphitis lesions. The subsequent extravasation of lymph (or chyle when the obstruction is canal) is at the origin of the formation of lymphedema or elephantiasis, in which the main histological finding is great hypertrophy of collagen elements. This theory involving filaria only is not the full picture, and bacterial infection, mainly by streptococci, is an important factor. The association of filaria with microbes is particularly dangerous because the presence of the latter, or its toxins, causes death of local microfilariae and even adult worms, which are known to be more harmful dead than alive. The progression of the disease, especially in cases with lymphedema, which mainly affects the limbs and the genital organs, depends on three factors: the species of filaria, the degree of transmission, and the receptivity of the patient to the parasite. Large differences are found according to the region involved, and in the same endemic zone, according to the individuals affected. However, they almost always occur progressively in areas where there have been recurrent attacks of acute lymphangitis.
ISSN: 0398-0499

hal-00715440
https://hal.univ-antilles.fr/hal-00715440
PUBMED : 7007545