83 research outputs found

    La désambiguïsation lexicale d'une langue moins bien dotée, l'exemple de l'arabe

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    International audienceSense-annotated corpus are decisive resources for Word Sense Disambiguation (WSD). Most of the languages have none or too little to build robust systems. In this article, we present 12 sense-annotated corpra for the Arabic language automatically build from 12 corpus in English. We evaluate the quality of our WSD systems using a newly available Arabic evaluation corpus.Les corpus annotés en sens sont des ressources cruciales pour la tâche de désambiguïsation lexicale (Word Sense Disambiguation). La plupart des langues n'en possèdent pas ou trop peu pour pouvoir construire des systèmes robustes. Nous nous intéressons ici à la langue arabe et présentons 12 corpus annotés en sens, fabriqués automatiquement à partir de 12 corpus en langue anglaise. Nous évaluons la qualité de nos systèmes de désambiguïsation grâce à un corpus d'évaluation en arabe nouvellement disponible

    Regulation of DNA Methylation Patterns by CK2-Mediated Phosphorylation of Dnmt3a

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    DNA methylation is a central epigenetic modification that is established by de novo DNA methyltransferases. The mechanisms underlying the generation of genomic methylation patterns are still poorly understood. Using mass spectrometry and a phosphospecific Dnmt3a antibody, we demonstrate that CK2 phosphorylates endogenous Dnmt3a at two key residues located near its PWWP domain, thereby downregulating the ability of Dnmt3a to methylate DNA. Genome-wide DNA methylation analysis shows that CK2 primarily modulates CpG methylation of several repeats, most notably of Alu SINEs. This modulation can be directly attributed to CK2-mediated phosphorylation of Dnmt3a. We also find that CK2-mediated phosphorylation is required for localization of Dnmt3a to heterochromatin. By revealing phosphorylation as a mode of regulation of de novo DNA methyltransferase function and by uncovering a mechanism for the regulation of methylation at repetitive elements, our results shed light on the origin of DNA methylation patterns

    Human choriocarcinoma cell line JEG-3 produces and secretes active retinoids from retinol

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    DNA methyl transferases are differentially expressed in the human anterior eye segment

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    International audienceDNA methylation is an epigenetic mark involved in the control of genes expression. Abnormal epigenetic events have been reported in human pathologies but weakly documented in eye diseases. The purpose of this study was to establish DNMT mRNA and protein expression levels in the anterior eye segment tissues and their related (primary or immortalized) cell cultures as a first step towards future in vivo and in vitro methylomic studies

    Placental Implications of Peroxisome Proliferator-Activated Receptors in Gestation and Parturition

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    International audienceThe placenta is a transitory structure indispensable for the proper development of the embryo and fetus during mammalian gestation. Like other members of the nuclear receptor family, the peroxisome proliferator-activated receptors (PPARs) are known to be involved in the physiological and pathological events occurring during the placentation. This placental involvement has been recently reviewed focusing on the early stages of placental development (implantation and invasion, etc.), mouse PPARs knockout phenotypes, and cytotrophoblast physiology. In this review, we describe the placental involvement of PPARs (e.g., fat transport and metabolism, etc.) during the late stages of gestation and in the amniotic membranes, highlighting their roles in the inflammation process (e.g., chorioamnionitis), metabolic disorders (e.g., diabetes), and parturition

    Retinoids regulate human amniotic tissue-type plasminogen activator gene by a two-step mechanism

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    International audienceThe collagenolytic effects of the tissue-type plasminogen activator (t-PA) leading to extracellular matrix degradation are clearly involved in the physiopathology of human foetal membranes rupture. Nevertheless, the regulation of t-PA gene expression in extraembryonic developmental contexts remains unknown. The aim of our study is to propose the retinoic acids (RAs) as molecular regulators of t-PA expression in foetal membranes. RA induced t-PA mRNA and proteins in a time-dependent manner in amniotic membrane explants and Wistar Institute Susan Hayflick (WISH) cells. Furthermore, the use of cycloheximide revealed a two-step regulation of t-PA gene. Gene reporter assays confirmed that the RA-induced t-PA gene expression occurred through interactions of retinoid receptors (RARs and RXRs) with a DR5 response element located at -7 kb from the transcription site. Site-directed mutagenesis of this region of the t-PA promoter showed that SP1 factor was also retinoid-mediated induction, and immunoprecipitation assays revealed that SP1 and RAR/RXR interacted physically. Chromatin immunoprecipitation demonstrated that interactions between RARs, RXRs and t-PA promoter were time dependent: RAR-alpha/RXR-alpha bound DR5 motif before and up to 12 hrs of RA exposure, and RAR-beta/RXR-alpha bound DR5 response element after 12 hrs of RA treatment. Finally, experiments using shRNA and RAR-beta-specific antagonist revealed that reducing RAR-beta induction decreased t-PA induction. Altogether, our results established that the RA-mediated regulation of t-PA in human foetal membranes occurred through two steps, with a major role played by RAR-beta

    Placental expression of SCO-spondin during mouse and human development

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    International audienceDuring mammalian development, the placenta is a transitory but indispensable structure for a harmonious gestation involving several biological processes, such as adhesion, differentiation, apoptosis or cellular guidance. Nevertheless, the molecular pathways implicated during the placentation are still not totally understood. We previously described, the subcommissural organ (SCO)-spondin, a member of the 'thrombospondin' super-family, which is strongly expressed during mammalian central nervous system development. This extra-cellular matrix glycoprotein shows a unique arrangement of several conserved domains, including thrombospondin type 1 repeats, low-density lipoprotein receptor type A domains, two epidermal growth factor-like domains, and N- and C-terminal von Willebrand factor cysteine-rich domains. The presence of these domains strongly suggests the SCO-spondin involvement in cellular events occurring during placental development and physiology. In order to define this new role of SCO-spondin during development, we demonstrated its expression at relevant steps of gestation in human and mouse placenta, using RT-PCR, immunohistochemistry and Western-blot experiments. These data initiate further insights into the molecular and genetic functions of the neuronal gene SCO-spondin during trophoblastic and more globally during placental physiology and development

    Retinoic Acid Pathway Regulation of Vascular Endothelial Growth Factor in Ovine Amnion

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    International audienceVascular endothelial growth factor (VEGF) has been proposed as an important regulator of amniotic fluid absorption across the amnion into the fetal vasculature on the surface of the placenta. However, the activators of VEGF expression and action in the amnion have not been identified. Using the pregnant sheep model, we aimed to investigate the presence of the retinoic acid (RA) pathway in ovine amnion and to determine its effect on VEGF expression. Further, we explored relationships between RA receptors and VEGF and tested the hypothesis that RA modulates intramembranous absorption (IMA) through induction of amnion VEGF in sheep fetuses subjected to altered IMA rates. Our study showed that RA receptor isoforms were expressed in sheep amnion, and RA response elements (RAREs) were identified in ovine RARβ and VEGF gene promoters. In ovine amnion cells, RA treatment upregulated RARβ messenger RNA (mRNA) and increased VEGF transcript levels. In sheep fetuses, increases in IMA rate was associated with elevated VEGF mRNA levels in the amnion but not in the chorion. Further, RARβ mRNA was positively correlated with VEGF mRNA levels in the amnion and not chorion. We conclude that an RA pathway is present in ovine fetal membranes and that RA is capable of inducing VEGF. The finding of a positive relationship between amnion VEGF and RARβ during altered IMA rate suggests that the retinoid pathway may play a role through VEGF in regulating intramembranous transport across the amnion

    Effects of tracheal occlusion with retinoic acid administration on normal lung development

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    International audienceTracheal occlusion (TO) is an investigational therapy for severe congenital diaphragmatic hernia that decreases pulmonary hypoplasia, but sustained TO also induces deficient surfactant synthesis. Intramuscular maternal administration of retinoic acid (RA) in a surgical rabbit model of congenital diaphragmatic hernia showed a beneficial effect on lung maturation. We evaluated the potential of RA delivery into the trachea and studied the combined effects of TO and RA on normal lung development
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