Éditeur(s) : HAL CCSD WB Saunders
Résumé : International audience
OBJECTIVE: We hypothesized that, in Human Immunodeficiency Virus and Hepatitis C Virus (HIV/HCV) co-infected patients who did not respond to peg-interferon and ribavirin, a maintenance therapy with peg-interferon could induce fibrosis regression. METHODS: This was a randomized study with two parallel groups. HIV/HCV co-infected patients received peg-interferon α-2a at 180 μg/week or remained on observation for 96 weeks. The primary endpoint was the percentage of patients who experienced a decrease of at least one point in their Metavir fibrosis score between initial and final liver biopsies. Secondary endpoints included plasma fibrosis markers at week 96, occurrence of HCV-related complications, and survival. RESULTS: A total of 52 patients were randomized (peg-interferon: 25; control: 27) including 18 with cirrhosis. The median (interquartile range) age was 44 (40-46) years, and 69% were male. A total of 64% had ALT levels >1.5 normal values, and the CD4 cell count was 391 (296-537) cells/mm(3); 67% of patients had HIV RNA <200 copies/mL at entry. The main endpoint was assessed in 41 patients. Response rates were 3/20 (15%) and 4/21 (19%) in the peg-interferon and control groups, respectively (p = 0.99). There was no significant difference between peg-interferon and control groups on plasma fibrosis markers at the final visit. Severe liver-related complications were observed in 2 and 5 patients in peg-interferon and control groups, respectively. Three deaths were observed, all in the control group. CONCLUSIONS: A maintenance therapy with peg-interferon α-2a over 96 weeks in HIV/HCV co-infected patients, who were non-responders to HCV treatment, did not change liver fibrosis. ClinicalTrials.gov Identifier: NCT00122616.
ISSN: 0163-4453

hal-00875067
https://hal.archives-ouvertes.fr/hal-00875067
DOI : 10.1016/j.jinf.2013.05.007
PUBMED : 23800784

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
Background: Myosin II (or Myosin Heavy Chain II, MHCII) is a family of molecular motors involved in the contractile activity of animal muscle cells but also in various other cellular processes in non-muscle cells. Previous phylogenetic analyses of bilaterian MHCII genes identified two main clades associated respectively with smooth/non-muscle cells (MHCIIa) and striated muscle cells (MHCIIb). Muscle cells are generally thought to have originated only once in ancient animal history, and decisive insights about their early evolution are expected to come from expression studies of Myosin II genes in the two non-bilaterian phyla that possess muscles, the Cnidaria and Ctenophora. Results: We have uncovered three MHCII paralogues in the ctenophore species Pleurobrachia pileus. Phylogenetic analyses indicate that the MHCIIa /MHCIIb duplication is more ancient than the divergence between extant metazoan lineages. The ctenophore MHCIIa gene (PpiMHCIIa) has an expression pattern akin to that of ``stem cell markers'' (Piwi, Vasa...) and is expressed in proliferating cells. We identified two MHCIIb genes that originated from a ctenophore-specific duplication. PpiMHCIIb1 represents the exclusively muscular form of myosin II in ctenophore, while PpiMHCIIb2 is expressed in non-muscle cells of various types. In parallel, our phalloidin staining and TEM observations highlight the structural complexity of ctenophore musculature and emphasize the experimental interest of the ctenophore tentacle root, in which myogenesis is spatially ordered and strikingly similar to striated muscle formation in vertebrates. Conclusion: MHCIIa expression in putative stem cells/proliferating cells probably represents an ancestral trait, while specific involvement of some MHCIIa genes in smooth muscle fibres is a uniquely derived feature of the vertebrates. That one ctenophore MHCIIb paralogue (PpiMHCIIb2) has retained MHCIIa-like expression features furthermore suggests that muscular expression of the other paralogue, PpiMHCIIb1, was the result of neofunctionalisation within the ctenophore lineage, making independent origin of ctenophore muscle cells a likely option.
ISSN: 1471-2148

hal-01544486
https://hal.archives-ouvertes.fr/hal-01544486
DOI : 10.1186/1471-2148-12-107

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The separation of the germ line from the soma is a classic concept in animal biology, and depending on species is thought to involve fate determination either by maternally localized germ plasm (''preformation'' or ``maternal inheritance'') or by inductive signaling (classically termed ``epigenesis'' or ``zygotic induction''). The latter mechanism is generally considered to operate in non-bilaterian organisms such as cnidarians and sponges, in which germ cell fate is determined at adult stages from multipotent stem cells. We have found in the hydrozoan cnidarian Clytia hemisphaerica that the multipotent ``interstitial'' cells (i-cells) in larvae and adult medusae, from which germ cells derive, express a set of conserved germ cell markers: Vasa, Nanos1, Piwi and PL10. In situ hybridization analyses unexpectedly revealed maternal mRNAs for all these genes highly concentrated in a germ plasm-like region at the egg animal pole and inherited by the i-cell lineage, strongly suggesting i-cell fate determination by inheritance of animal-localized factors. On the other hand, experimental tests showed that i-cells can form by epigenetic mechanisms in Clytia, since larvae derived from both animal and vegetal blastomeres separated during cleavage stages developed equivalent i-cell populations. Thus Clytia embryos appear to have maternal germ plasm inherited by i-cells but also the potential to form these cells by zygotic induction. Reassessment of available data indicates that maternally localized germ plasm molecular components were plausibly present in the common cnidarian/bilaterian ancestor, but that their role may not have been strictly deterministic.
ISSN: 0012-1606

hal-01544487
https://hal.archives-ouvertes.fr/hal-01544487
DOI : 10.1016/j.ydbio.2012.01.018

Éditeur(s) : HAL CCSD
Résumé : absent
ISSN: 0249-7395

hal-01210241
https://hal.archives-ouvertes.fr/hal-01210241
PRODINRA : 277457

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Signalling through the Wnt family of secreted proteins originated in a common metazoan ancestor and greatly influenced the evolution of animal body plans. In bilaterians, Wnt signalling plays multiple fundamental roles during embryonic development and in adult tissues, notably in axial patterning, neural development and stem cell regulation. Studies in various cnidarian species have particularly highlighted the evolutionarily conserved role of the Wnt/b-catenin pathway in specification and patterning of the primary embryonic axis. However in another key non-bilaterian phylum, Ctenophora, Wnts are not involved in early establishment of the body axis during embryogenesis. We analysed the expression in the adult of the ctenophore Pleurobrachia pileus of 11 orthologues of Wnt signalling genes including all ctenophore Wnt ligands and Fz receptors and several members of the intracellular b-catenin pathway machinery. All genes are strongly expressed around the mouth margin at the oral pole, evoking the Wnt oral centre of cnidarians. This observation is consistent with primary axis polarisation by the Wnts being a universal metazoan feature, secondarily lost in ctenophores during early development but retained in the adult. In addition, local expression of Wnt signalling genes was seen in various anatomical structures of the body including in the locomotory comb rows, where their complex deployment suggests control by the Wnts of local comb polarity. Other important contexts of Wnt involvement which probably evolved before the ctenophore/ cnidarian/bilaterian split include proliferating stem cells and progenitors irrespective of cell types, and developing as well as differentiated neuro-sensory structures.
ISSN: 1932-6203

hal-01544483
https://hal.archives-ouvertes.fr/hal-01544483
DOI : 10.1371/journal.pone.0084363

Éditeur(s) : HAL CCSD
Résumé : National audience
Il virus dell’epatite C (HCV), a trasmissione parenterale, è stato identificato nel 1989 come il virus responsabile delle epatiti «non A non B». L’infezione colpisce circa 170 milioni di persone nel mondo e 200 000 persone in Francia hanno una replicazione virale attiva. Nei paesi industrializzati, l’epidemia ha accompagnato lo sviluppo della trasfusione sanguigna e della tossicomania endovenosa. I test enzyme-linked immunosorbent assay che individuano gli anticorpi anti-HCV hanno permesso uno screening attendibile dell’infezione a partire dal 1992. La rilevazione dell’acido ribonucleico virale C permette la diagnosi dell’infezione cronica che fa seguito all’epatite acuta in circa l’80% dei casi. La gravità dell’infezione è legata allo sviluppo progressivo di una fibrosi epatica che conduce alla cirrosi dopo una mediana di evoluzione di 30-40 anni. La malattia è, così, responsabile di circa 350 000 decessi per anno nel mondo, legati, in parti uguali, all’insufficienza epatica e al carcinoma epatocellulare. Il trattamento ha compiuto enormi progressi in 20 anni e nuove molecole antivirali sono in corso di sviluppo clinico.
EMC - AKOS - Trattato di Medicina

hal-01154232
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01154232
DOI : 10.1016/S1634-7358(15)70635-2

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
The Caribbean bivalves Codakia orbicularis (Linnée, 1758) and C. orbiculata (Montagu, 1808) live in seagrass beds of Thalassia testudinum and harbor intracellular sulfuroxidizing gamma-proteobacteria. These bacterial symbionts fix CO2 via the Calvin Benson cycle and provide organic compounds to the bivalve. During experimentally induced starvation, no reduced sulfur compounds and no organic particle food are available; the symbionts could be considered as the sole nutrient source of the host bivalve. A previous study has shown that the intracellular bacterial population decreased considerably during starvation and that bacterial endosymbionts were not released by the bivalves. In this study, the activity of two lysosomal marker enzymes (acid phosphatase and arylsulfatase) was detected using cytochemical experiments coupled with energy-dispersive X-ray transmission electron microscopy during sulfide and organic particle starvation. The degradation of bacterial endosymbionts began after 2 weeks of starvation in C. orbiculata and after 3 weeks in C. orbicularis. Degradation processes seem to be continuous over several months and could be responsible for the disappearance of the bacterial endosymbionts within the gills during starvation. These data suggest that the host use symbionts as a nutrient source to survive a hunger crisis. The carbon transfer from the symbionts to the host could be flexible and could consist in transfer of organic matter, “milking,” under normal feeding conditions and digestion of the symbionts under starved conditions.
ISSN: 1059-910X

Droits : info:eu-repo/semantics/OpenAccess
hal-01206367
https://hal.univ-antilles.fr/hal-01206367
https://hal.univ-antilles.fr/hal-01206367/document
https://hal.univ-antilles.fr/hal-01206367/file/revised%20version%20to%20be%20submitted%20to%20the%20editor3oct.pdf
DOI : 10.1002/jemt.22458

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
BACKGROUND AND AIMS: Infection by hepatitis C virus is a worldwide health problem. An inadequate Th2 cytokine response promotes the fibrosis-cirrhosis fate. Immune-modulating molecules favoring a Th2 profile, such as HLA-G molecules of the HLA class Ib family, may play a role in chronic hepatitis. HLA-G contributes to the escape of tumors, and their involvement in viral infections has been increasingly described. The aim of this work was to study the expression of HLA-G in the liver, its cellular source and its regulation in cases of chronic C hepatitis. METHODS: HLA-G cells in blocks of liver derived from patients infected with HCV were labeled by immunohistochemistry and enumerated. Double immunofluorescence allowed the identification of the cellular source. HLA-G secretion by a human mast cell line was quantified by ELISA after various stimulations. After treatment with IFN-α real-time PCR was performed to determine the kinetics of cytokine expression profiles, followed by heat map clustering analysis. RESULTS: The number of HLA-G + cells was significantly associated with the area of fibrosis. For the first time, we identify the HLA-G+ cells as being mast cells. HLA-G secretion was significantly induced in human mast cells stimulated by IL-10 or interferons of class I. The transcriptome of the secretome of this cell line stimulated by IFN-α revealed that i) the HLA-G gene is upregulated late, ii) T lymphocytes and NK cells are recruited. CONCLUSIONS: These findings suggest an autocrine loop in the genesis of HCV liver fibrosis, based on mast cells expressing HLA-G.
ISSN: 0168-8278

hal-00874106
https://hal.archives-ouvertes.fr/hal-00874106
https://hal.archives-ouvertes.fr/hal-00874106/document
https://hal.archives-ouvertes.fr/hal-00874106/file/Amiot-Expression-HLA-G-revised.pdf
DOI : 10.1016/j.jhep.2013.09.006

Éditeur(s) : HAL CCSD
Résumé : National audience
El virus de la hepatitis C (VHC), que se transmite por vía parenteral, fue identificado en 1989 como el virus responsable de las hepatitis «no A no B». La infección afecta a alrededor de 170 millones de personas en el mundo. En Francia, por ejemplo, 200.000 personas tienen una replicación viral activa. En los países industrializados, la epidemia ha sido la consecuencia de la práctica de la transfusión sanguínea y de la toxicomanía intravenosa. El método ELISA (ensayo por inmunoabsorción ligado a enzimas), que identifica los anticuerpos anti-VHC, posibilita la detección fiable de la infección desde 1992. La detección del ácido ribonucleico viral C permite el diagnóstico de la infección crónica, consecutiva a la hepatitis aguda, en alrededor del 80% de los casos. La gravedad de la infección se debe al desarrollo progresivo de una fibrosis hepática que, tras una mediana de evolución de 30-40 años, conduce a la cirrosis. Así, la enfermedad es responsable de unos 350.000 fallecimientos por año a escala mundial, relacionados a partes iguales con la insuficiencia hepática y el carcinoma hepatocelular. El tratamiento ha progresado de forma considerable en 20 años y hay nuevas moléculas antivirales en fase de desarrollo clínico.
EMC - Tratado de Medicina

hal-01154228
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01154228
DOI : 10.1016/S1636-5410(15)70945-1

Éditeur(s) : HAL CCSD
Rencontres Biologie Physique RBPGO4
Berder, France

hal-00919259
https://hal.archives-ouvertes.fr/hal-00919259