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Retinoid X receptors (RXRα, β, and γ) are essential members of the nuclear receptor (NR) superfamily of ligand-dependent transcriptional regulators that bind DNA response elements and control the ...expression of large gene networks. As obligate heterodimerization partners of many NRs, RXRs are involved in a variety of pathophysiological processes. However, despite this central role in NR signaling, there is still no consensus regarding the precise biological functions of RXRs and the putative role of the endogenous ligands (rexinoids) previously proposed for these receptors. Based on available crystal structures, we introduced a series of amino acid substitutions into the ligand-binding pocket of all three RXR subtypes in order to alter their binding properties. Subsequent characterization using a battery of cell-based and in vitro assays led to the identification of a double mutation abolishing the binding of any ligand while keeping the other receptor functions intact and a triple mutation that selectively impairs interaction with natural rexinoids but not with some synthetic ligands. We also report crystal structures that help understand the specific ligand-binding capabilities of both variants. These RXR variants, either fully disabled for ligand binding or retaining the property of being activated by synthetic compounds, represent unique tools that could be used in future studies to probe the presence of active endogenous rexinoids in tissues/organs and to investigate their role in vivo. Last, we provide data suggesting a possible involvement of fatty acids in the weak interaction of RXRs with corepressors.
In an effort to define the varied expression of three vasoactive markers in the clinical models of normal placenta/ normal invasion (n = 11), preeclampsia/restricted trophoblast invasion (n = 15), ...and placenta accreta/exaggerated invasion (n = 6), we performed semiquantitative immunohistochemistry for kallikrein, bradykinin B2 receptor, and endothelial nitric oxide synthase (eNOS). In the floating villi, the syncytiotrophoblast expressed more kallikrein in placenta accreta (p < 0.05), than in normal and preeclamptic placentas, while the bradykinin B2 receptor and eNOS were similarly expressed in all groups; in the fetal endothelium, the bradykinin B2 receptor was enhanced in placenta accreta (p < 0.005), but kallikrein and eNOS were similarly expressed in the other two groups. In the extravillous trophoblast, both kallikrein and eNOS expression were higher in placenta accreta (p < 0.001), while the bradykinin B2 receptor signal was only enhanced in preeclampsia (p < 0.05). The presence and localization of kallikrein, the bradykinin B2 receptor, and eNOS in the fetomaternal interface in the three study conditions supports a local role for interrelated vasodilatory/antiaggregating systems. This first report of the variations observed in kallikrein and eNOS in a condition of exaggerated trophoblast invasion supports the participation of vasodilatation in trophoblast migration.
Difficile à lire, connu de réputation pour ses objections aux Méditations de Descartes, sa réhabilitation d’Épicure et des atomes, voire le caractère ambigu de ses relations avec les “libertins”, ...Pierre Gassendi est un personnage un peu flou dans notre galerie de portraits imaginaire. Il fut cependant un auteur important, lu, connu, approuvé ou critiqué dans toute l’Europe, surtout par les savants qui voulaient fonder efficacement leur physique moderne sans renier pour autant les acquis des anciens. Les études réunies ici ont cherché comme la trace et le reflet de l’œuvre de Gassendi dans les écrits d’autres auteurs qui ont vécu de son temps et jusqu’à la fin des Lumières – non seulement en France –, mais aussi en Angleterre (comme Walter Charleton, John Locke, David Hume ou Robert Boyle), en Hollande (professeurs d’Université), en Allemagne (Leibniz), en Pologne (Sociniens et “libertins”), en Italie du Nord (comme le jésuite milanais Thommaso Ceva), en Italie du Sud (comme le fondateur de l’Accademia degli Investiganti Tommaso Cornelio ou Giambattista Vico), en Espagne enfin (comme le médecin Martínez). Aujourd’hui encore Gassendi fait des adeptes parmi ceux que séduisent les chemins non battus de l’effort gratuit et de l’érudition austère, ceux que ravit absolument une certaine esthétique baroque de l’esprit pur.
Le doublage Albera, François; Angelini, Claire; Barnier, Martin ...
Décadrages,
2013
Journal Article
Open access
Les articles de ce dossier examinent la question du doublage et du sous-titrage de cinéma dans une perspective historique (censure, technologie sonore, discours sur le cinéma) et théorique (rapport ...entre le corps et la voix), à travers des exemples issus de plusieurs pays (France, Espagne, Québec, Suisse) et périodes, des débuts du parlant aux jeux vidéo actuels. Les enjeux de la traduction sont pensés en des termes sociopolitiques, et la postsynchronisation des voix est plus largement appréhendée comme une pratique de détournement et de réappropriation.
Phospholipid methylase and cyclic nucleotide phosphodiesterase activities were studied in human B lymphoïd hemopathies (51 patients: acute lymphoblastic leukemia, B lymphoma, chronic lymphocytic ...leukemia, hairy cell leukemia) and compared with activities in lymphoblastïd and Burkitt lymphoma cell lines and with normal B lymphocytes: methylase activity proved to be lower in ALL and high grade lymphoma and inversely related to the percent of cells in S phase state; the A/G ratio of phosphodiesterases was low in ALL and CLL and high in hairy cell leukemia and it was related to the percent of cells in S phase state.
