The main question this bachelor thesis aims to answer is how the public service program Tg1’s news broadcasts may look. The following questions were used to discuss thetendencies of the result: How can the distribution of the news categories appear in Tg1’sbroadcasts? Can the main news be considered as impartial and objective in its linguisticand pictorial representation? To answer the aforementioned question I chose to do a combined study, using aquantitative content analysis and a qualitative content analysis. To lead my research, I focused on two requirements underlined by public servicebroadcasters, namely, objectivity and impartiality, and diversity. The outcome shows thatthe diversity in Tg1’s broadcast is disproportionate and that the pictorial representation isnot impartial and objective without the linguistic part. Then, additionally to mytheoretical choice, the public service role in a democracy, a discussion about the resultand its consequences has been set up.

MeCP2 est une protéine multifonctionnelle agissant à de nombreux niveaux de contrôle des programmes génétiques. Un mauvais dosage de MeCP2 cause un groupe de maladies neurologiques dont le point commun est une déficience intellectuelle sévère. Des mutations ou une délétion de MECP2 causent le syndrome de Rett chez les filles, alors que sa surexpression cause chez les garçons le syndrome de duplication de MECP2. Plusieurs modèles murins de Mecp2-pathies ont été générés qui permettent d’expliciter les mécanismes qui sous-tendent l’apparition des symptômes dans ces différentes maladies. Dans notre laboratoire, deux modèles murins sont utilisés: le modèle Mecp2tm1Bird qui présente une déficience en Mecp2 et le modèle Mecp2Tg1 présentant une surexpression de Mecp2. Ce travail de thèse a permis de caractériser l’évolution postnatale des déficits moteurs et physiologique affectant la souris Mecp2Tg1. Nos résultats montrent que la surexpression de Mecp2 conduit à l’apparition de problèmes moteurs, et des convulsions chez la souris. En parallèle, nous avons étudié les déficits neuronaux affectants la voie GABAergique et glutamatergique chez la souris déficiente en Mecp2. Nous avons montré que la déficience en Mecp2 cause une dérégulation de la transmission synaptique dépendante du ‘territoire’ et de l’âge de la maladie. Ces dérégulations sous-tendent vraisemblablement des différences neurophysiologiques importantes entre les régions du cerveau qu’il nous reste encore à découvrir. Par ailleurs, nous avons constaté que la stimulation pharmacologique du système GABAergique par la Tiagabine, permet d’augmenter la survie des animaux Mecp2-déficients. / MeCP2 is a multifunctional protein acting on many levels of control of genetic programs. Thus, an abnormal dosage of MeCP2 protein causes a group of neurological disorders with a common feature of severe intellectual disability. Mutations or deletions in MECP2 gene cause Rett Syndrome in females, whereas in boys its overexpression causes the MECP2-duplication Syndrome. Several mouse models of MECP2-pathologies were generated. The use of these models is crucial for understanding the mechanisms underlying the onset of symptoms related to the pathology. In our laboratory, two mouse models are under study: The Mecp2tm1Bird model with an Mecp2 deficiency and the transgenic Mecp2Tg1 model with a double expression of Mecp2. My thesis work enabled the characterization of the postnatal physiological and motor deficits affecting Mecp2Tg1 mice. My work led to a better understanding of the gene dosage effect. Our results showed that overexpression of Mecp2 in mice, led to the occurrence of motor problems, and seizures. In parallel, we studied the neural deficits affecting the GABA and the glutamate pathway in several structures of the Mecp2 deficient brain (Mecp2tm1bird). We showed that Mecp2-deficiency causes deregulation of the synaptic transmission, which is dependent on the area, and the age of the study. These deregulations underlie significant neurophysiological differences between the different regions of the brain that we still have to uncover. Furthermore, we found that pharmacological stimulation of the GABA system with Tiagabine, a molecule capable of acting on GABA transporters to prevent its uptake, increases the survival of Mecp2-deficients animals.

RNR Polymerase I (RNA Pol I) is a “factory” that orchestrate the transcription of ribosomal rRNA for constructing ribosomes as a primary workshop for protein translation to sustain cell growth. Misregulation of RNA Pol I can cause uncontrolled cell proliferation, which leads to the development of cancer. Yeast (Saccharomyces cerevisiae) is a valuable model system to study RNA Pol I. Recently, the X-ray crystal structure of the yeast homologue of RNA Pol I was elucidated, offering the structural basis to selectively target this transcriptional machinery. The approach to selective RNA Pol I targeting was to disrupt the interaction between a specific transcription factor, RRN3 that bind distinct regions of RNA Pol I. For this purpose, a recombined plasmid was designed to carry human rDNA plus its promoter as target together with a selection marker gene. Therefore, this plasmid could not only introduce the target gene into the yeast (host), but also facilitate the passage of this target gene into a stable yeast strain. In this project, one uracil deficient yeast strain of YBR140C was transformed with the recombined yeast integrative plasmid of pHmrDNA-YIPlac211-TG1. This is a recombined plasmid containing not only the human rDNA but also the URA3 gene as a selection marker. PCR amplification of the human ribosomal DNA was indicative of successful integration of the human ribosomal DNA into the genome of the two yeast strains. Virtual screening using a library of 700 FDA-approved compounds was docked into the RRN3-RNA Pol I complex to identify small molecule disruptors of the RRN3-RNA Pol I as a selective strategy. Using growth assays, gel electrophoresis and transcriptional assays, we identified cerivastatin sodium as a lead virtual hit. The result implicates cerivastatin sodium as a selective RNA Pol I inhibitor worthy of further development with potential as targeted anticancer therapeutic.