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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Bases moléculaires et structurales de l’interaction entre deux calréticulines de parasite et la protéine humaine C1q / Deciphering the molecular and structural mechanism of the interaction between two parasite calreticulins and the human protein C1q

Moreau, Christophe 01 October 2015 (has links)
Au cours de cette thèse, nous avons étudié plus particulièrement deux calréticulines de parasite et leur interaction avec la protéine C1q humaine, dans un contexte de détournement du système immunitaire. En effet, une stratégie de mimétisme moléculaire avec des cellules apoptotiques a été proposée pour l'exposition de calréticuline à la surface de la forme infectieuse du parasite Trypanosoma cruzi, agent vecteur de la maladie de Chagas. Dans le cas du parasite Entamoeba histolytica, agent vecteur de l'amibiase, l'interaction de C1q avec la calréticuline exposée à la surface de l'amibe est utilisée pour mieux phagocyter les cellules de l'hôte.La calréticuline est une protéine principalement localisée dans le réticulum endoplasmique où elle joue le rôle de protéine chaperonne en favorisant le repliement des protéines monoglucosylées. Une des fonctions extracellulaires de la calréticuline humaine est de favoriser l'élimination des cellules apoptotiques par les macrophages. Pour cela, la calréticuline est exposée à la surface des deux types cellulaires, à la surface desquelles elle est reconnue par C1q.Nous avons résolu la structure de fragments des deux CRTs de parasite. Des interactions de type chaperonne et un aperçu de la flexibilité du domaine P ont été observés dans l'empilement cristallin et approfondis par analyse de diffusion des rayons X aux petits angles. Ces fragments générés pour l'analyse structurale nous ont permis en plus d'identifier une région clé dans l'interaction des calréticulines avec C1q. Du côté de C1q, deux mutations dans les régions globulaires de C1q (GRC1q), inhibent l'interaction avec la CRT et les IgM, suggérant un site partagé. Pour approfondir la caractérisation de l'interaction, des études du complexe par RMN ont débuté et nous avons développé une première forme recombinante monocaténaire de GRC1q, dont nous avons déterminé la structure. Nos recherches peuvent aider à développer des traitements contre ces parasites, aussi bien qu'à décrypter le rôle de la CRT des mammifères présente à la surface des macrophages et des cellules apoptotiques. / During this thesis, we were interested in two parasite calreticulin and their interaction with the human C1q protein in the context of the subversion of the immune system. Indeed, a molecular mimicry strategy with human apoptotic cells is suggested for the calreticulin exposure on the surface of the infectious form of the parasite Trypanosoma cruzi, which is responsible of Chagas' disease. In the case of the parasite Entamoeba histolytica, which is involved in amoebiasis, the interaction of C1q with the surface-exposed calreticulin is used to enhance phagocytosis of host cells.Calreticulin is mainly localised in the endoplasmic reticulum, where it acts as a chaperone protein to favour the folding of monoglycosylated proteins. Moreover one of the extracellular functions of human calreticulin is to enhance the clearance of apoptotic cells by macrophages. This function is mediated through C1q interaction with calreticulin exposed on the surface of both cells.We solved the structure of fragments of both parasite calreticulins. Chaperone-like interactions and an overview of the flexibility of the P domain were observed in the crystal packing and deepened using SAXS analyses. The fragments generated for X-ray crystallography studies allowed us to identify a key region of the interaction between C1q and the calreticulins. Two C1q mutations located in its globular regions (GRC1q) inhibit the interaction with calreticulin and IgM, suggesting a common binding area. To further characterise theses interactions, we started NMR experiments and we produced the first single-chain recombinant form of GRC1q, which allowed solving its structure at high-resolution. Our investigations could provide tools to develop therapies against these parasites, and to decipher the role of mammal CRT on the surface of macrophages and apoptotic cells.
2

As jornadas de junho de 2013 e as estratégias de ação da Mídia Ninja no campo do jornalismo

Mendonça, Marcela Prado 30 August 2016 (has links)
This research aims to understand how Mídia N.I.N.J.A. (Independent Narratives, Journalism and Action in Portuguese) emerged from political actor within the political field, to a media actor within the media field, and its movement within the journalism field during the Journeys of June 2013 in order to conquer the symbolic capital of visibility. The phenomenon known as "Journeys of June" provides the space of time for this research. In June 2013, the Mídia Ninja (MN) conquered space on the pages of mainstream newspapers in both Brazilian and international presses. In order to understand the object Mídia Ninja, we follow the conceptual construction of Pierre Bourdieu's field, in order to relate the different spheres of activity of this collective actor, analyzing the struggles for symbolic capital and its relationship with the traditional press in the field of journalism. We investigated the Ninja Media as a social movement that acts in social media, based on the authors Maria Gloria Gohn and Ilse Scherer-Warren, in order to understand the collective configuration as a new social movement and analyze its appropriation of new information technologies (ICT's) to the media cyberactivism and the concept of collective action repertoire of Charles Tilly. From the identification of the group's action repertoire, the MN was located in the field of journalism and had their actions related with the actions of traditional media, using the newspapers Folha de S. Paulo and O Estado de S. Paulo. This analysis allowed us to investigate the following hypotheses: 1) Mídia Ninja is a new social movement that has appropriated new information and communication technologies to achieve media visibility; (2) that Mídia Ninja's actions express a kind of symbolic fight for the symbolic capital of the media field that is visible, to the consequent conquest of power within the political field; (3) the actions of Mídia Ninja has generated a collective position within the field recognized by the own journalism agents' field , representatives of the traditional press and finally (4) the Mídia Ninja overthrew the journalism field during Journeys of June. / A presente pesquisa tem como objetivo compreender como a Mídia N.I.N.J.A. (Narrativas Independentes, Jornalismo e Ação) emergiu de ator político, dentro do campo da política, para ator de mídia, dentro do campo das mídias, e sua movimentação dentro do campo do jornalismo durante as Jornadas de Junho de 2013 para a conquista do capital simbólico da visibilidade. O fenômeno conhecido como “Jornadas de Junho” oferece o recorte temporal dessa pesquisa. Em junho de 2013, a Mídia Ninja (MN) ganhou as páginas dos jornais da imprensa tradicional no Brasil e no exterior. Para compreender o objeto Mídia Ninja, seguimos a construção conceitual de campo social de Pierre Bourdieu, com o objetivo de relacionar as diferentes esferas de atuação deste ator coletivo, analisando as lutas por capital simbólico e sua relação com a imprensa tradicional no campo do jornalismo. Investigamos a Mídia Ninja enquanto movimento social de atuação em rede e na rede com base nas autoras Maria da Glória Gohn e Ilse Scherer-Warren, a fim de compreender a configuração do coletivo como novo movimento social e analisar sua apropriação das novas tecnologias da informação e comunicação (TIC’s) para o ciberativismo midiático, bem como o conceito de repertório de ação coletiva de Charles Tilly. A partir da identificação do repertório de ação do grupo, localizamos a MN no campo do jornalismo e relacionamos suas ações com as atividades da imprensa tradicional, utilizando os jornais Folha de S. Paulo e O Estado de S. Paulo. Essa análise nos permitiu investigar as hipóteses de que: (1) a Mídia Ninja é um novo movimento social que se apropriou das novas tecnologias da informação e comunicação para alcançar visibilidade midiática; (2) as ações da Mídia Ninja expressam um tipo de luta simbólica pelo capital simbólico do campo da mídia que é a visibilidade para a consequente conquista de poder dentro do campo político; (3) as ações da Mídia Ninja geraram um posicionamento do coletivo dentro do campo reconhecido pelos próprios agentes do área jornalística, representantes da imprensa tradicional e, por fim, (4) a Mídia Ninja subverteu o campo do jornalismo durante as Jornadas de Junho.

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