FIN DE SIÈCLE LITERATURE, FIN DE LANGUE LITERATURE? LINGUISTIC IMAGINARIES AROUND 1900 IN REMY DE GOURMONT’S ESSAYS

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Altérité slave et imaginaire de la langue.

La langue joue un rôle décisif dans les questionnements sur l’identité : on tend en effet (tel est le postulat du concept « d’identité linguistique ») à enraciner l’identité dans la langue, cette dernière étant abusivement conçue comme un objet homogène et appropriable. L’intrication de la langue et de la culture présente des racines et des prolongements nationaux, voire nationalistes, et on sait quel rôle capital elle a joué dans le cadre de l’éveil des nationalités en Europe centrale et ori..

Etude des mécanismes moléculaires de la Dystrophie Myotonique de Type 1 à l'aide de cellules souches embryonnaires humaines porteuses de la mutation causale

Les cellules souches embryonnaires humaines (hESC) représentent un nouvel outilbiologique au potentiel prometteur pour l amélioration de la compréhension des mécanismes moléculaires et cellulaires impliqués dans le développement de maladies monogéniques. Cette application est dans un premier temps devenue possible grâce à l utilisation de lignées de cellules souches embryonnaires humaines porteuses de mutation causale de pathologie, obtenues au cours d un diagnostique pré-implantatoire. Mon travail de thèse s est inscrit dans la validation de ce nouveau concept en utilisant des lignées de cellules souches embryonnaires humaines porteuses de la mutation causale de la Dystrophie Myotonique de type 1 (DM1). Ces cellules, ainsi que leurs progenies neurales et mésenchymateuses représentent un modèle pertinent pour l étude des conséquences physiopathologiques de la mutation DM1 dans la mesure où elles reproduisent certaines caractéristiques moléculaires connues de la pathologie. Mon projet a eu pour objectif de caractériser d un point de vue moléculaire et physiopathologique deux nouvelles altérations géniques identifiées par transcriptome différentiel entre les cellules contrôles et DM1. Ainsi, ce travail nous a permis d identifier un nouveau marqueur, le facteur de transcription ZNF37A, dont l expression est diminuée en association avec la mutation DM1 et qui serait impliqué dans les défauts myogéniques caractérisant cette pathologie. Parallèlement nous avons identifié un nouveau défaut d épissage alternatif d un gène impliqué dans la guidance axonale, l EphA5 qui pourrait être impliqué dans les défauts cognitifs des patients DM1.Abstract not availableEVRY-Bib. électronique (912289901) / SudocSudocFranceF

On-line PLE-LC sample preparation for the measurement of dioxins and WHO-PCBs in food and feed

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Du jeu des identités à la transformation de réalités partagées : un programme d’ateliers d’expression théâtrale pour adolescents immigrants et réfugiés

La migration à l’adolescence est particulièrement délicate à cause du fardeau conjugué que représente à ce stade de la vie l’intégration des multiples pertes associées à la migration et l’adaptation au statut de jeune adulte. Le programme d’ateliers d’expression théâtrale vise à faciliter l’adaptation des adolescents immigrants et réfugiés à leur nouvel environnement à partir d’un travail créatif autour des enjeux identitaires liés à la migration et à un statut de minorité. Ces ateliers conjuguent une approche inspirée du théâtre playback qui permet une mise en scène du vécu personnel et le théâtre forum de Boal qui met l’accent sur la transformation collective de l’expérience. Les résultats d’une évaluation qualitative des ateliers d’expression théâtrale suggèrent que ceux-ci constituent un lieu d’expression ou les participants se sentent en sécurité et soutenus par l’équipe ainsi que par le caractère rituel du jeu théâtral. Les ateliers permettent de représenter la multiplicité des valeurs et des références internes et externes de l’adolescent et de les renégocier sans dichotomiser le « eux » et le « nous », en s’adressant aux questions de justice sociale qui se posent à la collectivité. Ils favorisent aussi l’élaboration des transitions de l’adolescence en permettant l’évocation des pertes de la migration et le passage vers une identité hybride.Migration during adolescence represents a challenge for the youth who need to simultaneously work through the multiple losses associated with the migratory journey and adapt to a young adult status. The drama workshop program described here was designed to facilitate the adjustment of newly arrived immigrant teens. The aim of the program is to make it easier for adolescents to adjust to their new environment through creative group work around identity issues. The program also seeks to improve intergroup relations in multiethnic schools. The workshops are inspired both from playback theater and from Boal’s form theater which emphasizes the collective transformation of the singular experience. The qualitative assessment of the program effects on the adolescents suggests that the workshops constitute a safe space of expression, in which the team and the ritual nature of the play hold the participants. The workshops facilitate the representation of the multiplicity of values in the adolescent world and invite them to reconsider the way in which they interact, with their environment, without splitting between “us” and “them,” but rather creating solidarities around issues of social justice. The workshops also address the life transformation associated both with adolescence and migration and help the elaboration of the losses linked to the migratory journey and the construction of a hybrid identity.La migración en la adolescencia es particularmente delicada a causa de la carga conjunta que representa en esta etapa de la vida la integración de las múltiples pérdidas asociadas a la migración y la adaptación a un estatus de joven adulto. El programa de talleres de expresión teatral busca facilitar la adaptación de los adolescentes inmigrantes y refugiados a su nuevo entorno, a partir de un trabajo creativo relacionado con las cuestiones de identidad ligadas a la migración y a un estatus de minoría. Estos talleres conjugan un enfoque inspirado del teatro playback, que permite una puesta en escena de una experiencia personal, y el teatro forum de Boal, que pone el acento en la transformación colectiva de la experiencia. Los resultados de una evaluación cualitativa de los talleres de expresión teatral sugieren que éstos constituyen un lugar de expresión en el que los participantes se sienten seguros y apoyados por el equipo, así como por el carácter ritual de la representación teatral. Los talleres permiten representar la multiplicidad de los valores y referencias internas y externas del adolescente, y renegociarlos sin crear una dicotomía entre el “ellos” y “nosotros” al tratar cuestiones de justicia social que se plantean a la colectividad. Favorecen también la elaboración de las transiciones de la adolescencia al permitir la evocación de las pérdidas de la migración y el paso hacia una identidad híbrida.A imigração na adolescência é especialmente delicada, por causa do fardo conjugado que representa, neste ponto da vida, a integração das múltiplas perdas associadas à imigração e à adaptação ao estatuto de jovem adulto. O programa de ateliês de expressão teatral visa facilitar a adaptação dos adolescentes imigrantes e refugiados ao seu novo ambiente, a partir de um trabalho criativo a respeito das preocupações identitárias relacionadas à imigração e a um estatuto de minoria. Estes ateliês conjugam uma abordagem inspirada no teatro playback, que permite uma representação da vivência pessoal, e no teatro fórum de Boal, que ressalta a transformação coletiva da experiência. Os resultados de uma avaliação qualitativa dos ateliês de expressão teatral sugerem que estes continuam sendo um lugar de expressão onde os participantes sentem-se em segurança e apoiados pela equipe e pelo caráter ritual da representação teatral. Os ateliês permitem representar a multiplicidade dos valores e das referências internas e externas do adolescente e renegociá-los sem dicotomizar o “eles” e o “nós”, falando sobre questões de justiça social que são colocadas à coletividade. Os ateliês favorecem também a elaboração das transições da adolescência permitindo a evocação das perdas da imigração e a passagem para uma identidade híbrida

Levels and trends of PCDD/Fs and cPCBs in the Belgian food-stuffs one year after the "Dioxin Crisis

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A defective Krab-domain zinc-finger transcription factor contributes to altered myogenesis in myotonic dystrophy type 1

Myotonic dystrophy type 1 (DM1) is an RNA-mediated disorder caused by a non-coding CTG repeat expansion that, in particular, provokes functional alteration of CUG-binding proteins. As a consequence, several genes with misregulated alternative splicing have been linked to clinical symptoms. In our search for additional molecular mechanisms that would trigger functional defects in DM1, we took advantage of mutant gene-carrying human embryonic stem cell lines to identify differentially expressed genes. Among the different genes found to be misregulated by DM1 mutation, one strongly downregulated gene encodes a transcription factor, ZNF37A. In this paper, we show that this defect in expression, which derives from a loss of RNA stability, is controlled by the RNA-binding protein, CUGBP1, and is associated with impaired myogenesis—a functional defect reminiscent of that observed in DM1. Loss of the ZNF37A protein results in changes in the expression of the subunit α1 of the receptor for the interleukin 13. This suggests that the pathological molecular mechanisms linking ZNF37A and myogenesis may involve the signaling pathway that is known to promote myoblast recruitment during development and regeneratio

Single-cell transcriptomics reveals shared immunosuppressive landscapes of mouse and human neuroblastoma

BACKGROUND High-risk neuroblastoma is a pediatric cancer with still a dismal prognosis, despite multimodal and intensive therapies. Tumor microenvironment represents a key component of the tumor ecosystem the complexity of which has to be accurately understood to define selective targeting opportunities, including immune-based therapies. METHODS We combined various approaches including single-cell transcriptomics to dissect the tumor microenvironment of both a transgenic mouse neuroblastoma model and a cohort of 10 biopsies from neuroblastoma patients, either at diagnosis or at relapse. Features of related cells were validated by multicolor flow cytometry and functional assays. RESULTS We show that the immune microenvironment of MYCN-driven mouse neuroblastoma is characterized by a low content of T cells, several phenotypes of macrophages and a population of cells expressing signatures of myeloid-derived suppressor cells (MDSCs) that are molecularly distinct from the various macrophage subsets. We document two cancer-associated fibroblasts (CAFs) subsets, one of which corresponding to CAF-S1, known to have immunosuppressive functions. Our data unravel a complex content in myeloid cells in patient tumors and further document a striking correspondence of the microenvironment populations between both mouse and human tumors. We show that mouse intratumor T cells exhibit increased expression of inhibitory receptors at the protein level. Consistently, T cells from patients are characterized by features of exhaustion, expressing inhibitory receptors and showing low expression of effector cytokines. We further functionally demonstrate that MDSCs isolated from mouse neuroblastoma have immunosuppressive properties, impairing the proliferation of T lymphocytes. CONCLUSIONS Our study demonstrates that neuroblastoma tumors have an immunocompromised microenvironment characterized by dysfunctional T cells and accumulation of immunosuppressive cells. Our work provides a new and precious data resource to better understand the neuroblastoma ecosystem and suggest novel therapeutic strategies, targeting both tumor cells and components of the microenvironment

Reversible transitions between noradrenergic and mesenchymal tumor identities define cell plasticity in neuroblastoma

Noradrenergic and mesenchymal identities have been characterized in neuroblastoma cell lines according to their epigenetic landscapes and core regulatory circuitries. However, their relationship and relative contribution in patient tumors remain poorly defined. We now document spontaneous and reversible plasticity between the two identities, associated with epigenetic reprogramming, in several neuroblastoma models. Interestingly, xenografts with cells from each identity eventually harbor a noradrenergic phenotype suggesting that the microenvironment provides a powerful pressure towards this phenotype. Accordingly, such a noradrenergic cell identity is systematically observed in single-cell RNA-seq of 18 tumor biopsies and 15 PDX models. Yet, a subpopulation of these noradrenergic tumor cells presents with mesenchymal features that are shared with plasticity models, indicating that the plasticity described in these models has relevance in neuroblastoma patients. This work therefore emphasizes that intrinsic plasticity properties of neuroblastoma cells are dependent upon external cues of the environment to drive cell identity