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

Résumé : En Guadeloupe, la prévalence du diabète est deux fois plus élevée qu'en France hexagonale, avec une prédominance féminine. En dehors des facteurs environnementaux, la vitamine D et certains polymorphismes de gènes impliqués dans son métabolisme seraient associés à un risque de pathologies métaboliques. Les androgènes sont également associés aux anomalies du métabolisme glucidique, soit directement, soit via leur transporteur SHBG (Sex Hormone Binding Protein). Nous avons émis les hypothèses de recherche suivantes: 11 le statut en vitamine D et les polymorphismes des gènes impliqués dans son métabolisme pourraient être associés aux paramètres métaboliques chez des sujets Afro-Caribéens (AC). Ils expliqueraient l'importance des pathologies cardiométaboliques en Guadeloupe. 2/ la SHBG pourrait être associée aux anomalies du métabolisme glucidique, indépendamment des stéroïdes sexuels. Nos travaux sont présentés dans 4 études. Nous avons mis en évidence une prévalence élevée du déficit en vitamine D chez les sujets AC diabétiques de type 2. Nous avons trouvé une association significative entre le statut vitaminique D et le risque cardiométabolique chez ces sujets, mais aussi dans une population de sujets en hémodialyse chronique. Les polymorphismes des gènes impliqués dans le métabolisme de la vitamine D sont aussi associés à ce risque. Chez les sujets dysmétaboliques, une relation entre la SHBG, la graisse intra-hépatique, les hépatokines et les paramètres métaboliques a été mise en évidence, indépendamment des stéroïdes sexuels. En conclusion, la vitamine D et la SHBG pourraient être des marqueurs d'intérêt pour le dépistage des sujets à haut risque cardiométabolique.
In Guadeloupe, the prevalence of diabetes is two times higher than in Metropolitan France, with a female predominance. Apart from environmental factors, vitamin D and polymorphisms of genes involved in vitamin D metabolism would be associated with increased risk of metabolic diseases. Androgens are also associated with abnormal glucose metabolism, directly or through the Sex Hormone Binding Protein (SHBG). Our main hypotheses were: 11 Vitamin D status and polymorphisms of genes involved in its metabolism may be associated with metabolic pammeters in Afro-Caribbean (AC). They could explain the importance of cardiometabolic diseases in Guadeloupe. 2/ SHBG may be associated with abnormal glucose metabolism, independently of sex steroids. Our research is presente
http://www.theses.fr/2012AGUY0536/document

Résumé : Aux Antilles, la faible fréquence des coronaropathies pourrait être liée à des facteurs génétiques, ethniques et/ou une distribution spécifique des facteurs de risque cardio-vasculaire (FDRCV). Les propriétés l'ANP (Atrial Natriuretic Peptide) et l'influence de certains polymorphismes de son gène, fréquents dans les populations d'ascendance Africaine pourraient également être en cause. L'analyse des dossiers de 638 patients coronariens consécutifs a mis en évidence une forte prévalence de l'hypertension artérielle et du diabète dans cette population et révélé des différences significatives dans la prévalence des FDRCV entre Afro-Caribéens (AC), Caucasiens et descendants de migrants Indiens. L'analyse angiographique de 420 patients AC a révélé que le diabète était le FDRCV le plus fortement lié à la sévérité des lésions coronaires alors l'obésité apparaissait comme un facteur protecteur. La transfection in vitro, de cellules musculaires lisses artérielles par une construction adénovirale porteuse du gène de l'ANP a entrainé une inhibition de la prolifération et de la migration cellulaire de 31 % et 25% respectivement. In vivo, cet effet s'est traduit par une réduction de 25% de la formation néotimale et de 28% du rapport intima/média dans un modèle d'hyperplasie de carotide de rat. Dans étude transversale incluant 210 sujets diabétiques AC nous avons mis en évidence une association entre le polymorphisme rs5065 (22381>C) du gène de l'ANP et l'existence d'une coronaropatbie. Dans cette étude, l'odds ratio de la présence d'une coronaropathie chez les porteurs de l'allèle mineur de cette mutation (TC/CC) était de 0,50 (0,26- 0,96; P = 0,038).
In Guadeloupe and Martinique, the low frequency ofcoronary artery disease (CAD) could be related to genetic or ethniefactors and/or specifie distribution ofcardiovascular risk factors (CRFs). Atrial Natriuretic Peptide (ANP) properties and influence of sorne of ANP gene polymorphism that are frequent in populations of African descent could also be involved in CAD occurrence. We retrospectively studied 638 consecutive patients with documented CAO and found a high prevalence of hypertension and diabetes in this population. This study also demonstrated significant differences in the prevalence of CRFs between Afro-Caribbean (AC), Caucasians and Indians migrants. The angiographie analysis of420 patients revealed that in AC, diabetes emerged as the strongest CFR related to the severity ofcoronary lesions while obesity appeared as a protective factor. After transfection by an adenoviral construct carrying the ANP gene, vascular smooth muscle cell proliferation stimulated by 10% fetal calf serum was reduced by 31% and migration by 25%. In vivo, in rat carotid artery model ofvascular injury, neointima formation and intima/media ratio was reduced by 25% and 28% respectively. In a cross-sectional study inc1uding 210 AC diabetics we found an association between rs5065 (22381> C) polymorpbism and the presence of coronary artery disease suggesting that the minor allele could have a protective effect against CAD. The odds ratio for the presence ofCAD in carriers ofthe minor allele ofthis mutation (TC / CC) was 0.50 (0.26-0.96, P = 0.038).

http://www.theses.fr/2012AGUY0553/document

Éditeur(s) : EDP Sciences
Résumé : For centuries, several species of prawns and crabs have been raised from wild-caught juveniles in coastal brackish-water fish ponds in various countries of south east Asia. The Indonesian "tambaks" are well known examples of such traditional practices. In western countries, since the turn of the century, advances of marine biology and fast increase of marine fisheries enabled the development of large-scale production and release of larval stages of American and European lobsters in a fruitless attempt to restock natural populations. After the Second World War, the increasing demand for crustaceans in United States and Japan was satisfied by opening new prawn fisheries all over the world. A major breakthrough was achieved with the development of hatchery technologies for the penaeid prawn Penaeus japonicus (Hudinaga, 1942 in Japan) and the caridean prawn Macrobrachium rosenbergii (Ling, 1969 in Malaysia), which occurred during the first decades of the second half of this century. Together with the increasing market demand in developed countries for sea food, this led to a considerable interest of both public agencies and private investors in marine shrimp and prawn culture. In western countries, a large number of pioneering commercial ventures, often based on assumptions not scientifically founded, failed. Nevertheless, the aquaculture production of prawns mainly based on wild-caught juveniles increased in South-East Asia and Central America during the 1980s. This overall positive trend should not hide important failures which occurred at a local scale, such as the Taiwanese crisis of 1988 due principally to environmental degradation, resulting in severe disease problems and a near collapse of the farming activity. Following the early period of hatchery technology development, the major scientific achievements were related to food requirements and formulation of compound diets for larvae, juveniles and adults and to a better knowledge of diseases caused by bacteria and several viruses which have been identified from hatcheries and intensive farming ponds. Additional new technological advances have emerged from recent research in the fields of physiology (endocrinology) and genetics. By far, the major part of the world production of marine crustaceans relies on penaeid prawns and, to a lesser extent, on Macrobrachium species. However, some other species of marine crustaceans have potential for aquaculture. The economic aspects of marine crustacean aquaculture should be considered together with those of the fishing industry: market prices are rather similar, depending on the quality of the product. The balance between market demand and production is an important constraint which, in turn, establishes the success of prawn farming. Since the early 1980s, crustacean aquaculture has increased tremendously in both Asia and America: the world production for 1991 approximated 700,000 tons, with more than 600,000 tons from penaeid prawn culture.
Pendant des siècles, quelques espèces de crevettes et de crabes ont été élevées à partir d'individus juvéniles capturés dans le milieu naturel, dans des bassins à poissons d'eau saumâtre de différents pays d'Asie du Sud-Est. Les « tambaks » indonésiens sont des exemples bien connus de ces pratiques traditionnelles. Dans les pays occidentaux, depuis le début du siècle, les progrès réalisés en biologie marine et la croissance rapide des pêches maritimes ont permis le développement de la production à grande échelle de stades larvaires des homards européen et américain, dans une vaine tentative de reconstitution des stocks naturels. Après la Seconde Guerre mondiale, la demande croissante des Etats-Unis et du Japon a été satisfaite par l'ouverture de nouvelles pêcheries de crevettes dans l'océan mondial. Un progrès décisif a été réalisé avec la mise au point des techniques d'écloserie pour la crevette Pénaeidé Penaeus juponicus (Hudinaga, 1942 au Japon) et la crevette Caridé Macrobrachium rosenbergii (Ling, 1969 en Malaisie), qui sont apparues au cours des premières décennies de la seconde moitié de ce siècle. Parallèlement à la demande croissante du marché des pays développés pour les produits de la mer, ce résultat s'est traduit par un intérêt considérable porté à l'élevage des crevettes marines de la part des institutions de recherche et des investisseurs. Dans les pays occidentaux, un grand nombre de tentatives d'élevage commerciales, fondées sur des considérations non scientifiquement établies, ont échoué. Néanmoins, la production aquacole de crevettes reposant sur la capture d'animaux juvéniles dans la nature, s'est développée en Asie du Sud-Est et en Amérique Centrale au cours des années 1980. Cette tendance globalement positive ne doit pas dissimuler les faillites importantes qui se sont produites à l'échelle locale, comme la crise des élevages de Taiwan en 1988, causée principalement par une dégradation de l'environnement, entraînant l'apparition de problèmes pathologiques sévères et une disparition presque totale de l'activité d'élevage. Après la période pionnière du développement de la technologie d'écloserie, les principaux acquis scientifiques concernent les besoins alimentaires et la formulation d'aliments composés pour les larves, les jeunes et les adultes, et une meilleure connaissance des maladies bactériennes et virales qui interviennent dans les écloseries et les fermes d'élevage intensif. De nouveaux progrès techniques complémentaires ont vu le jour à la suite de recherches dans les domaines de la physiologie (endocrinologie) et de la génétique. De loin, la majeure partie de la production mondiale de Crustacés marins repose sur les crevettes Pénaeidés et, dans une moindre mesure, sur des espèces de Macrobrachium. Cependant, quelques autres espèces de Crustacés marins intéressent potentiellement l'aquaculture. Les aspects économiques de l'aquaculture de crustacés marins doivent être considérés avec ceux de l'industrie des pêches maritimes : les prix du marché sont à peu près les mêmes, et dépendent de la qualité du produit. Le rapport entre la demande du marché et la production est une contrainte importante qui à son tour, détermine les conditions du succès de l'élevage de crevettes. Depuis le début des années 1980, l'aquaculture de crustacés a augmenté considérablement en Asie et en Amérique : la production mondiale pour 1991 avoisine 700 000 tonnes, avec plus de 600 000 tonnes provenant des élevages de crevettes Pénaeidés.
Aquatic Living Resources (0990-7440) (EDP Sciences), 1993-10 , Vol. 6 , N. 4 , P. 319-329

Droits : IFREMER-Gauthier-Villars, 1993
http://archimer.ifremer.fr/doc/00190/30119/28587.pdf
DOI:10.1051/alr:1993033
http://archimer.ifremer.fr/doc/00190/30119/

Éditeur(s) : HAL CCSD Elsevier
Résumé : Field isolates of Toxoplasma gondii in Europe and North America have been grouped into three clonal lineages that display different virulence in mice. Whether the genetic structure of the parasite is related to clinical expression in humans has not yet been demonstrated. We developed an enzyme-linked immunosorbent assay which uses lineage-specific, polymorphic polypeptides derived from the dense granule antigens, GRA5 and GRA6. Our goal was to compare serotypical patterns observed in asymptomatic versus symptomatic (ocular disease and severe infection in human immunodeficiency virus (HIV)-positive patients) infections among patients from Europe and South America. Independent of the clinical presentation of the disease, serotypes differed according to geographical origin, with a homogeneous distribution of serotype II in Europe and of serotypes I and III in South America. We conclude that GRA5-GRA6 serotyping is an interesting tool to study serotype prevalence in populations but it is not an accurate marker of pathogenicity of Toxoplasma infection in humans.
ISSN: 1286-4579

hal-00306841
https://hal.archives-ouvertes.fr/hal-00306841
DOI : 10.1016/j.micinf.2008.04.001
PUBMED : 18539501

Éditeur(s) : Wiley-blackwell Publishing, Inc
Résumé : Aims: A description of bacterial pathogens in shrimp ponds is necessary to understand their pathogenesis. Vibrio nigripulchritudo was shown to contain saprophytic and pathogenic strains among New Caledonian isolates. We established a method to map the development of V. nigripulchritudo in pond sediments at three different genetic levels: the species level, then at the pathogenic cluster level and finally at the plasmid level, present only in all highly pathogenic isolates. Methods and Results: PCR methods were applied to shrimp pond sediments both before and after a mortality outbreak. Using crude samples, the species V. nigripulchritudo is not detected at first (0/42 samples at day 56 post stocking) but appears frequently in the sediments after the mortality event (30/42 at day 107). The distribution of strains from the pathogenic cluster of V. nigripulchritudo also follows this pattern. In contrast, the pSFn1 virulence-associated plasmid was detected in one sample at day 56 and none at day 107. An enrichment method was developed to lower the detection limits of our assays. After enrichment, the species V. nigripulchritudo was detected in all samples at both dates. The number of samples positive for pSFn1 was 42/42 samples at day 56 and 29/42 at day 107. Conclusions: These results show that the sediments contain V. nigripulchritudo, notably pathogenic strains. Surprisingly, the virulence-associated plasmid pSFn1 found in all V. nigripulchritudo isolated from moribund shrimp appears less frequently in sediments, possibly being useless or even detrimental to its recipient bacteria in this environment. Significance and Impact of the Study: This study confirms the presence of pathogenic V. nigripulchritudo strains in shrimp pond sediment before a mortality outbreak complying with a previous hypothesis that sediments could be the infecting reservoir. After the outbreak, both total V. nigripulchritudo and pathogenic strains populations have largely increased, possibly contributing to the recurrent mortality observed in this shrimp vibriosis.
Journal Of Applied Microbiology (1364-5072) (Wiley-blackwell Publishing, Inc), 2010-06 , Vol. 108 , N. 6 , P. 2003-2011

Droits : 2010 The Society for Applied Microbiology - Wiley-Blackwell
http://archimer.ifremer.fr/doc/00004/11484/8177.pdf
DOI:10.1111/j.1365-2672.2009.04601.x
http://archimer.ifremer.fr/doc/00004/11484/

Éditeur(s) : HAL CCSD
Résumé : International audience
Necroptosis is a regulated form of cell death involved in several disease models including in particular liver diseases. Receptor-interacting protein kinases, RIPK1 and RIPK3, are the main serine/threonine kinases driving this cell death pathway. We screened a noncommercial, kinase-focused chemical library which allowed us to identify Sibiriline as a new inhibitor of necroptosis induced by tumor necrosis factor (TNF) in Fas-associated protein with death domain (FADD)-deficient Jurkat cells. Moreover, Sib inhibits necroptotic cell death induced by various death ligands in human or mouse cells while not protecting from caspase-dependent apoptosis. By using competition binding assay and recombinant kinase assays, we demonstrated that Sib is a rather specific competitive RIPK1 inhibitor. Molecular docking analysis shows that Sib is trapped closed to human RIPK1 adenosine triphosphate-binding site in a relatively hydrophobic pocket locking RIPK1 in an inactive conformation. In agreement with its RIPK1 inhibitory property, Sib inhibits both TNF-induced RIPK1-dependent necroptosis and RIPK1-dependent apoptosis. Finally, Sib protects mice from concanavalin A-induced hepatitis. These results reveal the small-molecule Sib as a new RIPK1 inhibitor potentially of interest for the treatment of immune-dependent hepatitis. © 2017 Federation of European Biochemical Societies
ISSN: 1742464X

hal-01616420
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01616420
DOI : 10.1111/febs.14176
PUBMED : 28715128

Éditeur(s) : HAL CCSD Taylor & Francis
Résumé : International audience
The origin of replication complex subunit ORC1 is important for DNA replication. The gene is known to encode a meiotic transcript isoform (mORC1) with an extended 5′-untranslated region (5′-UTR), which was predicted to inhibit protein translation. However, the regulatory mechanism that controls the mORC1 transcript isoform is unknown and no molecular biological evidence for a role of mORC1 in negatively regulating Orc1 protein during gametogenesis is available. By interpreting RNA profiling data obtained with growing and sporulating diploid cells, mitotic haploid cells, and a starving diploid control strain, we determined that mORC1 is a middle meiotic transcript isoform. Regulatory motif predictions and genetic experiments reveal that the activator Ndt80 and its middle sporulation element (MSE) target motif are required for the full induction of mORC1 and the divergently transcribed meiotic SMA2 locus. Furthermore, we find that the MSE-binding negative regulator Sum1 represses both mORC1 and SMA2 during mitotic growth. Finally, we demonstrate that an MSE deletion strain, which cannot induce mORC1, contains abnormally high Orc1 levels during post-meiotic stages of gametogenesis. Our results reveal the regulatory mechanism that controls mORC1, highlighting a novel developmental stage-specific role for the MSE element in bi-directional mORC1/SMA2 gene activation, and correlating mORC1 induction with declining Orc1 protein levels. Because eukaryotic genes frequently encode multiple transcripts possessing 5′-UTRs of variable length, our results are likely relevant for gene expression during development and disease in higher eukaryotes. © 2016 Taylor & Francis Group, LLC.
ISSN: 1547-6286

hal-01367153
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01367153
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01367153/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01367153/file/Ndt80%20activates%20the%20meiotic%20ORC1%20transcript.pdf
PUBMEDCENTRAL : PMC5013992

Éditeur(s) : HAL CCSD
Résumé : International audience
Hemoglobin electrophoresis realised as a routine screening test on 1 500 gabonese individuals revealed the existence of a sickle cell abnormality n 24.40% cases (22.27% were AS heterozygotous and 2.1% were SS homozygotous). Bapounov and Fang ethnies appeared to be the most involved. The importance of such disturbance (I gabonese individual out of 4 is concerned) could justify the creation of Prenatal Counseling Centers mainly dealing with this genetic problem.
Bull Soc Pathol Exot Filiales

hal-00717071
https://hal.univ-antilles.fr/hal-00717071
PUBMED : 7460122

Éditeur(s) : HAL CCSD European Respiratory Society
Résumé : International audience
Telomerase reverse transcriptase (TERT) or telomerase RNA (TERC) gene mutation is a major monogenic cause of pulmonary fibrosis. Sequencing of TERT/TERC genes is proposed to patients with familial pulmonary fibrosis. Little is known about the possible predictors of this mutation and its impact on prognosis. We retrospectively analysed all the genetic diagnoses made between 2007-2014 in patients with pulmonary fibrosis. We evaluated the prevalence of TERT/TERC disease-Associated variant (DAV), factors associated with a DAV, and the impact of the DAV on survival. 237 patients with pulmonary fibrosis (153 with familial pulmonary fibrosis, 84 with telomere syndrome features without familial pulmonary fibrosis) were tested for TERT/TERC DAV. DAV was diagnosed in 40 patients (16.8%), including five with non-idiopathic interstitial pneumonia. Prevalence of TERT/TERC DAV did not significantly differ between patients with familial pulmonary fibrosis or with only telomere syndrome features (18.2% versus 16.4%). Young age, red blood cell macrocytosis, and low platelet count were associated with the presence of DAV; the probability of DAV was increased for patients 40-60 years. Transplant-free survival was lower with than without TERT/TERC DAV (4.2 versus 7.2 years; p=0.046). TERT/TERC DAV were associated with specific clinical and biological features and reduced transplantfree survival. ©ERS 2016.
ISSN: 0903-1936

hal-01467555
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01467555
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01467555/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01467555/file/Prevalence%20and%20characteristics%20of%20TERT.pdf
DOI : 10.1183/13993003.02115-2015

Éditeur(s) : HAL CCSD Wiley-Blackwell
Résumé :  
South American leaf blight caused by the ascomycete Microcyclus ulei is the most harmful disease of the rubber tree in Latin America and a potential threat to Asiatic and African natural rubber production. Until now, the variability of this fungus was assessed through observation of pathogenicity of isolates on a range of rubber tree clones with known resistance reactions. The present study describes the process used to design 11 microsatellite markers and evaluates their usefulness in detecting genetic polymorphism. Nine of these markers were polymorphic among six isolates from Brazil (with two to three alleles per locus) and five markers were polymorphic among four isolates from French Guiana (with two to four alleles per locus).
ISSN: 1471-8278

hal-01032087
https://hal.archives-ouvertes.fr/hal-01032087
DOI : 10.1111/j.1471-8286.2004.00589.x

Éditeur(s) : HAL CCSD
Résumé : International audience
In French Guiana, located on the northeastern coast of South America, bats of different species are very numerous. The infection of bats and their ticks with zoonotic bacteria, especially Rickettsia species, is so far unknown. In order to improve knowledge of these zoonotic pathogens in this French overseas department, the presence and diversity of tick-borne bacteria was investigated with molecular tools in bat ticks. In the beginning of 2013, 32 bats were caught in Saint-Jean-du-Maroni, an area close to the coast of French Guiana, and the ticks of these animals were collected. A total of 354 larvae of Argasidae soft ticks (Ornithodoros hasei) from 12 bats (Noctilio albiventris) were collected and 107 of them were analysed. DNA was extracted from the samples and quantitative real-time PCR was carried out to detect Rickettsia spp., Bartonella spp., Borrelia spp. and Coxiella burnetii. All tested samples were negative for Bartonella spp., Borrelia spp. and Coxiella burnetii. Rickettsia DNA was detected in 31 (28.9%) ticks. An almost entire (1118 base pairs long) sequence of the gltA gene was obtained after the amplification of some positive samples on conventional PCR and sequencing. A Bayesian tree was constructed using concatenated rrs, gltA, ompA, ompB, and gene D sequences. The study of characteristic sequences shows that this Rickettsia species is very close (98.3-99.8%) genetically to R. peacockii. Nevertheless, the comparative analysis of sequences obtained from gltA, ompA, ompB, rrs and gene D fragments demonstrated that this Rickettsia is different from the other members of the spotted fever group. The sequences of this new species were deposited in GenBank as Candidatus Rickettsia wissemanii. This is the first report showing the presence of nucleic acid of Rickettsia in Ornithodoros hasei ticks from South American bats. (C) 2016 Elsevier GmbH. All rights reserved.
TICKS AND TICK-BORNE DISEASES

hal-01459758
https://hal.archives-ouvertes.fr/hal-01459758
DOI : 10.1016/j.ttbdis.2016.09.004

Éditeur(s) : American society for microbiology
Résumé : Vibrio nigripulchritudo, the etiological agent of Litopenaeus stylirostris summer syndrome, is responsible for mass mortalities of shrimp in New Caledonia. Epidemiological studies led to the suggestion that this disease is caused by an emergent group of pathogenic strains. Genomic subtractive hybridization was carried out between two isolates exhibiting low and high virulence. Our subtraction library was constituted of 521 specific fragments; 55 of these were detected in all virulent isolates from our collection (n = 32), and 13 were detected only in the isolates demonstrating the highest pathogenicity (n = 19), suggesting that they could be used as genetic markers for high virulence capacity. Interestingly, 10 of these markers are carried by a replicon of 11.2 kbp that contains sequences highly similar to those of a plasmid detected in Vibrio shilonii, a coral pathogen. The detection of this plasmid was correlated with the highest pathogenicity status of the isolates from our collection. The origin and consequence of this plasmid acquisition are discussed.
Applied and environmental microbiology (depuis 1953) (0099-2240) (American society for microbiology), 2008-05 , Vol. 74 , N. 10 , P. 3038-3047

Droits : 2008 American Society for Microbiology
http://archimer.ifremer.fr/doc/2008/publication-4523.pdf
DOI:10.1128/AEM.02680-07
http://archimer.ifremer.fr/doc/00000/4523/

Éditeur(s) : HAL CCSD
Résumé : International audience
Introduction: Type 1 diabetes mellitus, a T cell-mediated autoimmune disease, is a complex process that results from the loss of tolerance to insulin and other beta-cell-specific antigens. Diabetes is associated with an increased risk of death from infectious disease. Hyperglycaemia, oxidative stress and inflammation have been identified as the main factor contributing to the development of diseases associated with diabetes mellitus. However, experimental evidence indicates individual susceptibility to develop complications of diabetes. Various genetic and environmental factors have been studied so far, but precise causation has yet to be established. Numerous studies in rodents and human subjects have been performed in order to elucidate the role of B and T cells, which determine the risk of development and progression of diabetes. Moreover, the therapy management of diabetes includes nutritional recommendations and exercise training. The effects of exercise training on glycemia, oxidative stress, inflammation and immune response are well known and favorable to limit the development of diabetes and its complications. More interestingly, ?-galacto-oligosaccharides (?-GOS) are prebiotics that selectively alter the composition of gut microbiota and exhibit strong antioxidant, anti- inflammatory and insulin-sensitive effects in vitro (Efstathiou and Fathi 2010) and in vivo (Boucher J et al. 2003). Thus, ? -GOS is a potential functional food for the treatment of diabetes. But, less is known about the effect of training and ? –GOS on immune response in diabetes. In this context, the aim of this work was to study the immune response in a streptozotocin-induced type 1 diabetes with two therapeutic means: training and ?-galacto-oligosaccharides (?-GOS) alone or combined. Methods: Forty-two male Wistar rats were divided into control placebo, streptozotocin-diabetic rat (STZ) groups supplemented or not with ?-GOS (20 mg/kg/day) for 8 weeks and/or following endurance training. The training program was individualized and consisted in a 1h/day, 5days/week running during 8 weeks on a motor-driven treadmill. At the end of the protocol, blood was obtained by venous puncture into heparin-containing tubes for further analyses (glucose, insulin, fructosamine and immune responses) Results: Relative to the control group, STZ rats exhibited hyperglycemia, insulin deficiency and a trend to higher plasma fructosamine levels, a marker of glycated proteins. They also exhibited a decrease in T and B cells and an increase in natural killers (NK). ?-GOS treatment reduced plasma fructosamine levels and increased B cells compared to STZ rats. Training induced a decrease in plasma glucose, T cells and an increase in B cells in STZ rats. The combined effect of ?-GOS and training didn’t potentiate the immune response on B and T cells but inhibited the effects of training on NK. Discussion: Our results suggest that training and ?-GOS alter positively plasma glucose and/or fructosamine and the immune response. But the effects of combined treatments only concern limited parameters. ? -GOS effects could be partly attributable to its immunomodulating activity. Keywords: ?-GOS, training, immune cells, diabetes. References Efstathiou, T. and D. Fathi. Sojasun Technologies. 2010 Boucher J et al. J Physiol Biochem. 59(3):169-73, 2003
18th Annual Congress of the European College of Sport Sciences, Barcelone, Spain, 26-29 juin.
Barcelone, Spain

hal-01159378
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01159378

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Estrogen receptors (ERs) α and β are distributed in most tissues of women and men. ERs are bound by estradiol (E2), a natural hormone, and mediate the pleiotropic and tissue-specific effects of E2, such as proliferation of breast epithelial cells or protection and differentiation of neuronal cells. Numerous environmental molecules, called endocrine disrupting compounds, also interact with ERs. Phytoestrogens belong to this large family and are considered potent therapeutic molecules that act through their selective estrogen receptor modulator (SERM) activity. Using breast cancer cell lines as a model of estrogen-dependent proliferation and a stably ER-expressing PC12 cell line as a model of neuronal differentiating cells, we studied the SERM activity of major dietary compounds, such as apigenin, liquiritigenin, daidzein, genistein, coumestrol, resveratrol and zearalenone. The ability of these compounds to induce ER-transactivation and breast cancer cell proliferation and enhance Nerve Growth Factor (NGF) -induced neuritogenesis was assessed. Surprisingly, although all compounds were able to activate the ER through an estrogen responsive element reporter gene, they showed differential activity toward proliferation or differentiation. Apigenin and resveratrol showed a partial or no proliferative effect on breast cancer cells but fully contributed to the neuritogenesis effect of NGF. However, daidzein and zearalenone showed full effects on cellular proliferation but did not induce cellular differentiation. In summary, our results suggest that the therapeutic potential of phytoestrogens can diverge depending on the molecule and the phenotype considered. Hence, apigenin and resveratrol might be used in the development of therapeutics for breast cancer and brain diseases.
ISSN: 0041-008X

hal-01558816
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01558816
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01558816/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01558816/file/Lecomte%20et%20al.%20-%20Assessment%20of%20the%20potential%20activity%20of%20major%20diet.pdf
DOI : 10.1016/j.taap.2017.04.005

Éditeur(s) : HAL CCSD American Physiological Society
Résumé : International audience
Excessive or persistent inflammation and hepatocyte death are the key triggers of liver diseases. The poly(ADP-ribose) polymerase (PARP) proteins induce cell death and inflammation. Chemical inhibition of PARP activity protects against liver injury during concanavalin A (ConA)-induced hepatitis. In this mice model, ConA activates immune cells, which promote inflammation and induce hepatocyte death, mediated by the activated invariant natural killer T (iNKT) lymphocyte population. We analyzed immune cell populations in the liver and several lymphoid organs, such as the spleen, thymus, and bone marrow in Parp2-deficient mice to better define the role of PARP proteins in liver immunity and inflammation at steady state and during ConA-induced hepatitis. We show that 1) the genetic inactivation of Parp2, but not Parp1, protected mice from ConA hepatitis without deregulating cytokine expression and leucocyte recruitment; 2) cellularity was lower in the thymus, but not in spleen, liver, or bone marrow of Parp2-/- mice; 3) spleen and liver iNKT lymphocytes, as well as thymic T and NKT lymphocytes were reduced in Parp2 knockout mice. In conclusion, our results suggest that the defect of T-lymphocyte maturation in Parp2 knockout mice leads to a systemic reduction of iNKT cells, reducing hepatocyte death during ConA-mediated liver damage, thus protecting the mice from hepatitis.NEW & NOTEWORTHY The genetic inactivation of Parp2, but not Parp1, protects mice from concanavalin A hepatitis. Immune cell populations are lower in the thymus, but not in the spleen, liver, or bone marrow of Parp2-deficient mice compared with wild-type mice. Spleen and liver invariant natural killer T (NKT) lymphocytes, as well as thymic T and NKT lymphocytes, are reduced in Parp2-deficient mice
ISSN: 0193-1857

hal-01630440
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01630440
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01630440/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01630440/file/102513_1_merged_1499199857-1.pdf
DOI : 10.1152/ajpgi.00436.2016

Éditeur(s) : HAL CCSD
Résumé : International audience
Semantic web standards, tools, ontologies and related technologies have considerably matured in the recent years. Nowadays, accessing a wide catalogue of biological, social, environmental, and ecological data sources helps stakeholders working on biodiversity to answer their complex questions. Will the real time access to web resources effectively support the definition of strategies to conserve and manage biodiversity? How might semantic web technologies help us to handle the complex and heterogeneous big data related to biodiversity? The workshop aims to identify the key challenges faced by the bioinformatics community, discuss potential solutions and identify the opportunities emerging from the trans-disciplinary interactions between Plant Science and Informatics experts. Therefore, we expect the bioinformatics experts to explain how they apply semantic web standards and tools to their scientific topic, from biology, agriculture, agro-ecology, genomics, environmental studies, to social sciences, citizen sciences. Research papers presenting various aspects of semantic web technologies applied to biodiversity data, ranging from position papers to implemented systems descriptions and their evaluation, will be selected. We are particularly interested in the use of the semantic technologies to design and develop systems that supports research on agricultural and wild biodiversity conservation and management for food security. Examples may include strategies for resilience to climate change pressures, sustainability of productive ecosystems, ecosystems services monitoring or territories management, rather than systems supporting only research on climate patterns or soil erosion.
http://hal-lirmm.ccsd.cnrs.fr/lirmm-00831757

lirmm-00831757
http://hal-lirmm.ccsd.cnrs.fr/lirmm-00831757
http://hal-lirmm.ccsd.cnrs.fr/lirmm-00831757/document

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 Elsevier
Résumé : International audience
BACKGROUND: Mutations in the telomerase complex (TERT and TR) are associated with pulmonary fibrosis and frequent hematologic manifestations. The aim of this study was to characterize the prognosis of lung transplantation in patients with TERT or TR mutations. METHODS: Patients with documented TERT or TR mutations who received a lung transplant between 2007 and 2013 in France were identified via an exhaustive search of the lung transplantation network, one expert genetic laboratory, and the clinical research network on rare pulmonary diseases. RESULTS: There were 9 patients (7 men) with TERT (n = 6) or TR (n = 3) mutations who received a single (n = 8) or a double (n = 1) lung transplant for pulmonary fibrosis. Median age was 50 years (range, 35-61 years) at diagnosis and 52 years (range, 37-62 years) at the time of lung transplantation. Thrombocytopenia was present in 7 patients before lung transplantation. After lung transplantation, 6 patients developed myelodysplasia and/or bone marrow failure, directly contributing to death in 4 cases. Anemia was observed in 9 patients, and neutropenia was observed in 3 patients. The median survival after lung transplantation was 214 days (range, 59-1,709 days). CONCLUSIONS: Patients with mutations of the telomerase complex are at high risk of severe hematologic complications after lung transplantation, in particular, bone marrow failure. Specific recommendations should be developed for appropriate guidance regarding hematologic risk assessment before transplantation and management of the post-transplantation immunosuppressive regimen.
ISSN: 1053-2498

hal-01146848
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01146848
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01146848/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01146848/file/Severe%20hematological%20complications%20after%20lung%20transplantation_accepted.pdf
DOI : 10.1016/j.healun.2014.11.010

Éditeur(s) : HAL CCSD
Résumé : ABSTRACT Infectious complications are a leading cause of morbidity and mortality in patients with sickle cell disease. Several mechanisms are supposed to contribute to this susceptibility. The exact reasons of the propensity of sickle cell patients to infection are not clear and are still matter of debate. Interferon gamma is a key cytokine involved namely in the defence against intracellular pathogens. We investigated a possible association of +874 T/A IFNγ polymorphism and infectious complications in sickle cell patients. Seventy-two sickle cell patients were typed for +874 T/A IFNγ polymorphism. Genotype frequencies were different between cases and controls. Indeed, T allele frequency was significantly higher in patients with infections than in patients without infections (χ² = 6.23 ; p = 0.013). Our results suggest that +874 T/A IFNγ polymorphism is associated with infectious complications in sickle cell patients. The T allele could be involved in infections in sickle cell patients.
https://hal.archives-ouvertes.fr/hal-00387081

hal-00387081
https://hal.archives-ouvertes.fr/hal-00387081
https://hal.archives-ouvertes.fr/hal-00387081/document
https://hal.archives-ouvertes.fr/hal-00387081/file/MO_Joannes_et_al._IFNG_polymorphism_and_sickle_cell_disease.pdf