Les troubles schizophréniques (SCZ) ont une forte héritabilité, de l’ordre de 80%, mais, une très faible part du risque génétique a été identifiée. La plupart des études ont considéré l’implication de polymorphismes fréquents, chacun ayant un effet relativement faible individuellement, alors que les études de variants du nombre de copies (CNVs) ainsi que les études d’anomalies chromosomiques ont pointé l’implication possible de variants rares et de novo à une forte pénétrance. Dans une première partie, nous présentons une synthèse sur les facteurs génétiques dans la SCZ, puis une revue des arguments en faveur de l’implication d’anomalies du système glutamatergique dans la SCZ, domaine sur lequel s’est centré notre travail. Notre travail s’inscrit dans un projet plus vaste, Synapse to Disease (S2D) ayant pour objectif de séquencer 1000 gènes synaptiques dans des cohortes de patients atteints de schizophrénie ou de troubles du spectre autistique. Nous avons exploré en particulier le système glutamatergique et les récepteurs NMDA. Dans un premier article, nous montrons une association d’une mutation troncante de novo de la kinésine 17, impliquée dans le transport de la sous-unité GRIN2B des récepteurs NMDA. Dans un second article, nous explorons les mutations rares et de novo dans les sous-unités des récepteurs NMDA et montrons l’association de mutation de novo dans GRIN2A et GRIN2B avec des cas de SCZ et d’autisme. Nos résultats renforcent l’idée qu’une part des cas de schizophrénie pourrait être due à l’implication de mutations rare à effet majeur, hypothèse alternative mais non exclusive à l’hypothèse d’interactions entre variants génétiques fréquents à effet mineur. / Schizophrenic disorders (SCZ) have high heritability (around 80%), but only a small part has been characterized. Most studies have focussed on common polymorphisms, each having small individual effect, whereas copy number variant and chromosomal abnormalities studies have pointed to the possible involvement of rare and de novo mutations with high penetrance. In the first part of this manuscript, we will present a synthesis on genetic factors of SCZ and then a review of the arguments supporting an involvement of glutamatergic system abnormalities in SCZ, which is the focus of our research. Our work is part of a global project, Synapse to Disease (S2D), that aimed to sequence 1000 synaptic genes in cohort of patients affected with schizophrenia or autism spectrum disorders. We focussed in particular on the glutamatergic system and NMDA receptors. In a first publication we show an association between SCZ and a de novo truncating mutation of kinesin 17, wich has been implicated in the transport of the GRIN2B subunit of NMDA receptors. In a second publication we explore rare and de novo mutations in NMDA receptor subunits. We show an association between de novo mutations in GRIN2A and GRIN2B with cases of SCZ and autism. Our results strengthen the idea that a portion of schizophrenia cases could be related to rare mutations having a high penetrance, an alternative but not contradictory explanation to the hypothesis for an interaction between common variants having a small effect.

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

[pt] A presente pesquisa de mestrado tem como objetivo refletir o que se chama novo homem, termo utilizado para descrever os homens ocidentais do século XXI, tendo em vista a relação existente entre o design de moda e a noção de masculinidade no Brasil e os corpos dóceis que são fabricados a partir da mesma. Para tal, investigou-se a natureza do novo homem, o discurso que o mercado se utiliza para caracterizá-lo e como ele é comunicado na mídia. / [en] The present Master Degrees research aims to reflect what is called the New Man, a term used to describe the 21st century Western man, based on the relationship between fashion design and the notion of masculinity in Brazil and Michel Foucault s notion of docile bodies which are constructed from the same. To this end, we investigated the nature of the New Man, the discourse used by the market to characterize him and how it is communicated in the media.

[pt] O objetivo desta dissertação é analisar o processo de construção de um conceito de democracia adequado aos propósitos da ordem política instaurada no Brasil com o advento do Estado Novo, regime ao qual o país esteve submetido de 1937 a 1945. Os intelectuais convidados pelo governo de Getúlio Vargas a colaborar em Cultura Política, revista mensal que circulou entre 1941 e 1945, desempenharam importante papel nesse processo. A dissertação tem como eixo a análise de uma seleção de artigos publicados em Cultura Política por alguns desses intelectuais e é conduzida com base nos procedimentos sugeridos pela história dos conceitos (Begriffsgeschichte), conforme desenvolvida pelo historiador alemão Reinhart Koselleck. Este trabalho pretende ser somar-se aos estudos existentes sobre o tema, no sentido de aprofundar a compreensão dos argumentos mobilizados na re-significação do conceito. / [en] The objective of this dissertation is to analyse the process of construction of a concept of democracy designed to suit the purposes of the political order established in Brazil with the institution of the Estado Novo, regime which governed the country from 1937 to 1945. The intellectuals invited by the Getulio Vargas government to collaborate in Cultura Política, a monthly publication which circulated between 1941 and 1945, played an important part in that process. The dissertation is primarily focused on the analysis of a selection of articles published in Cultura Política by some of those intellectuals, and is conducted in accordance with the procedures proposed by the history of concepts (Begriffsgeschichte) as developed by the german historian Reinhart Koselleck. The paper is aimed as a contribution to the existing studies on the subject in the sense of providing a further understanding of the arguments mobilized in the resignification of the concept.

[pt] Este trabalho, Bem na foto - a invenção do Brasil na fotografia de Jean Manzon, tem como foco principal a articulação das imagens produzidas pelo fotógrafo francês Jean Manzon no Brasil nos anos de 1940 com o contexto ideológico do período. Para isso, leva-se em conta a expressiva experiência de Manzon na imprensa européia da década de 1930, momento em que a fotografia se desvincula de uma função meramente ilustrativa do mundo para assumir autonomia como linguagem, tornando-se construtora da realidade. Nessa trajetória, ganha relevância o contexto do Estado Novo, em particular a relação do regime com a imprensa, a partir da atuação do Departamento de Imprensa e Propaganda (DIP). Depois disso, esta investigação centra-se na contribuição de Jean Manzon para a revista ilustrada O Cruzeiro, entre 1943 e 1951. A partir de uma série de imagens, Manzon se apresenta como agente da consolidação de uma identidade nacional, operando uma síntese do Brasil, como tradução da convergência das diferentes idéias de Brasil existentes na época. / [en] This essay, Photogenic - the invention of Brazil on Jean Manzon s photography, has as its main focus the articulation of the images performated by the french photographer Jean Manzon, in the 1940 s, and the ideological project of the period. In this context we take into consideration Manzon s experience in the european press in the 1930 s, moment when the photography interrupts its function of only illustrating the world, turning into a constructor of reality. In this path, the political context of the so called Estado Novo acquires relevance, in particular with its association with the press, by means, most of all, through the Departamento de Imprensa e Propaganda (DIP). Afterwards, this investigation focuses on Jean Manzon s contribution for the illustrated magazine O Cruzeiro between 1943 and 1951. From a series of images, Manzon emerges as an agent of the national identity consolidation, producing a synthesis of Brazil, as a translation of the multiple existing ideas at that time.

Human acidic fibroblast growth factor (FGF-1) is a member of the £]-trefoil superfamily and exhibits a characteristic three-fold tertiary structure symmetry. However, evidence of this symmetry is not readily apparent at the level of the primary structure. This suggests that while selective pressures may exist to retain (or converge upon) a symmetric tertiary structure, other selective pressures have resulted in divergence of the primary structure during evolution. Using intra-chain and homologue sequence comparisons for 19 members of this family of proteins, we have designed mutants of FGF-1 that constrain a subset of core-packing residues to three-fold symmetry at the level of the primary structure. The consequences of these mutations upon structure, stability, folding and unfolding kinetics have been evaluated using a combination of x-ray crystallography, differential scanning calorimetry, isothermal equilibrium denaturation and stopped flow protein refolding/unfolding kinetics. An alternative core packing group has been introduced into FGF-1. The alternative core is very similar from the wild type (WT) core with regard to structure, stability, folding and unfolding kinetics. The remaining asymmetry within the protein core is related to asymmetry in the tertiary structure. The removal of tertiary structure asymmetry greatly increases protein stability and results in a conversion from three-state to a two-state folding pathway. The tertiary structure asymmetry is intimately linked to functional regions of the protein. Surprisingly, upon deletion of the functional insertions, the mutant protein is approximately 80 times more potent than the wild type form as determined by functional bioassays. The results show that the ƒÒ-trefoil superfold is compatible with a three-fold symmetric constraint upon the core region, as might be the case if the superfold arose as a result of gene duplication/fusion events. Furthermore, this new protein arrangement can form the basis of a structural "building block" that can greatly simplify the de novo design of ƒÒ-trefoil proteins by utilizing symmetric structural complementarity. This study implies that a symmetric architecture of the £]-trefoil fold is kinetically and thermodynamically ¡§fit¡¨. / Dissertation / PhD

Esta investigação é dedicada ao tema da alimentação e procura abordá-lo em perspectiva cultural. Detida principalmente na dinâmica dos contatos culturais que resultaram do processo de colonização da América pelas nações ibéricas, a pesquisa tem como foco, principalmente, fontes e outros registros de caráter \"etnográfico\", tais como cartas e crônicas escritas no decorrer do século XVI que, de algum modo, registraram a \"cultura alimentar\" nativa dos povos americanos. Tendo em vista a possibilidade de considerar a alimentação como importante elemento na constituição do sistema de vida nos mais diversos grupos sociais - principalmente no âmbito das práticas cotidianas e dos valores culturais -, o que se procura apresentar nesta dissertação é o modo como os elementos simbólicos ligados aos alimentos emergem como instrumento mediador na construção de igualdades e diferenças culturais que, em última instância, permitem ao europeu presente no Novo Mundo, incorporar, intelectualmente, sua experiência no continente americano. / Considering that food can be a constituint element in the life system of several different social groups mainly in what concerns every day life and cultural values. We try here to deal with the way symbolic issues mediate cultural differences and similarities. We try to show that these constructions eventually allow the Europeans to intellectualy incorporate their New World experiences.

Neste trabalho, é apresentada a revisão taxonômica dos Pyrgotidae pertencentes à fauna do Novo Mundo, atualmente composta por 66 nomes válidos de espécies distribuídas em 15 gêneros. A revisão taxonômica resultou na descrição de dois novos gêneros e de duas novas espécies e na sinonímia de quatro gêneros e 18 espécies e uma espécie foi revalidada. De acordo com esses resultados a fauna de Pyrgotidae do Novo Mundo possui 51 espécies válidas dispostas em 12 gêneros. Análises filogenéticas foram processadas com o intuito de testar o monofiletismo dos gêneros e estabelecer o relacionamento entre suas espécies, além de testar o desempenho dos caracteres contínuos na filogenia de Pyrgotidae. Com este propósito foram levantados 54 caracteres morfológicos dos adultos, sendo 14 contínuos e 40 discretos. Os caracteres contínuos e discretos foram analisados separadamente e em evidência total. As análises em que se utilizaram apenas caracteres discretos e as que utilizaram os caracteres em evidência total, resultaram em topologias muito semelhantes entre si, divergindo apenas nas posições entre três terminais. Na topologia obtida em evidência total, o suporte dos ramos aumentou na maioria dos ramos o que demonstra que os caracteres contínuos são filogeneticamente informativos para serem utilizados em Pyrgotidae. / This work presents a taxonomic revision of New World Pyrgotidae, currently composed of 66 valid species names distributed in 15 genera. The taxonomic revision resulted in the description of two new genera and two species, synonymy of four genera and 18 species and revalidation of 1 species. According to these results, the Pyrgotidae of the New World contains 51 valid species arranged in 12 genera. Phylogenetic analyses were conducted to test the monophyly of the genera, establish the relationships among their species, and test the performance of continuous characters in the phylogeny of Pyrgotidae. Fifty-four morphological characters of adults were coded and divided as: 14 continuous and 40 discrete. Continuous and discrete characters were analyzed separately and under total evidence. The analyses using only discrete characters and in total evidence each resulted in one tree, which were very similar, diverging only in the positions of three terminals. In the tree obtained using total evidence, the branch support increased in more branches, which demonstrates that continuous characters are phylogenetically informative for use in analyses of the Pyrgotidae.

Thesis advisor: Clare O'Connor / Telomeres are repeated sequences at the ends of chromosomes, which promote chromosome stability by preventing the loss of necessary nucleotides from the DNA with successive rounds of replication. Telomeres are elongated by the enzyme telomerase, which has both a protein component and an RNA component. In the yeast Saccharomyces cerevisiae, the TLC1 gene encodes the RNA component of the enzyme. Telomerase RNA interacts with several proteins to perform its function, including the Ku protein, which binds to the end of the DNA and helps to recruit telomerase to the chromosome thereby facilitating the lengthening of chromosome ends. Ku interacts with telomerase RNA at the site of a 48-nucleotide stem-loop on the RNA's structure. Previous experiments have shown that yeast strains engineered to carry two copies of the TLCI gene exhibit higher levels of telomerase RNA than those that have only one copy of the gene. Also, a yeast strain carrying a copy of the mutant tlc1Δ48 gene, which contains a deletion of the 48-nucleotide stem-loop, contains lower levels of telomerase RNA than a strain with the wild type TLC1 gene. This series of experiments is investigating whether the copy number of the telomerase RNA gene affects the elongation of telomeres in S. cerevisiae. In order to determine this effect, the de novo telomere addition of four strains was examined, as were the native telomere lengths of these strains. The assay indicated that the efficiency of telomere elongation was unchanged by increasing the copy number of the wild type gene but was increased upon increasing the copy number of the mutant gene. Analysis of the native telomere lengths showed that increasing the copy number of either the wild type or the mutant gene allowed the cells to maintain their telomeres at a longer length. / Thesis (BS) — Boston College, 2008. / Submitted to: Boston College. College of Arts and Sciences. / Discipline: Biology. / Discipline: College Honors Program.

A presente dissertação tem como objeto central de estudo o conceito de Desenvolvimento mediante a compreensão das estruturas historicamente estabelecidas pelo fruto do Produto Social. Para entender tal conceito, faz-se necessário percorrer o caminho das discussões com a tarefa de desvelar como as aspirações individuais interferem no coletivo e como o resultado coletivo interfere na particularidade dos indivíduos. O texto traz uma discussão sobre os caminhos do Desenvolvimento (crescimento e bem-estar), da importância do Ambiente Institucional na trajetória do desenvolvimento e apresenta um estudo de caso aplicado à gestão de bancos de fomento, em especial, o Novo Banco de Desenvolvimento do BRICS. Apesar das expectativas positivas e do cenário promissor de crescimento dos BRICS, a incerteza sempre rodeou o ambiente institucional de tais países pelo modo de relacionamento político-social causado pela ambiguidade de governantes e empresários e da inércia social perante os fatos. Neste contexto, o Novo Banco de Desenvolvimento foi criado para estreitar as relações intragrupo e ampliar os esforços para superar os obstáculos do desenvolvimento via ambiente institucional. / This dissertation has as main object of study the concept of development by understanding of historically existent structures as a result of Social Product. To understand the concept, it is necessary to pursue the course of discussions with the task of revealing how individual aspirations interfere with collective and how the collective result interferes with individual particularities. The text provides a discussion on the course of development (growth and well-being), the importance of institutional environment in the course of development and a case study of development banks, in particular, the New Development Bank of BRICS. Despite positive expectations and the favorable scenario for the growth of the BRICS countries, the uncertainty has always surrounded the BRICS countries by the mode of social-political relationship caused by the ambiguity of politicians, businessmen and the social inertia facing the facts. In this context, the New Development Bank was created to strengthen intragroup relations and expand efforts to overcome obstacles to development across institutional environment.