Les récepteurs couplés aux protéines G (RCPG) constituent l'une des plus grandes familles de gènes du génome des mammifères. Ils sont impliqués dans la plupart des processus physiologiques et physiopathologiques ce qui en a fait des cibles thérapeutiques de choix. GPR158 est un récepteur orphelin, dont on ne connaît pas de ligand, de la classe C des RCPG. Il partage 20% d'identité de séquence entre son domaine transmembranaire (TM) et celui du récepteur GABAB mais son domaine N-terminal est dépourvu du domaine Venus Flytrap (VFT), le domaine de liaison du ligand caractéristique des RCPG de la classe C, ce qui suggère que cette protéine a développé un autre mode de liaison de son ligand endogène (s'il existe). GPR158 est exprimé majoritairement au niveau du cerveau. De manière intéressante, son expression a été aussi décrite, dans des cribles à plus ou moins grande échelle, comme étant associée ou modifiée dans différentes conditions pathologiques dont 50% sont des maladies cancéreuses.À ce jour, on ne connait ni la fonction physiologique, ni les voies de signalisation de GPR158. Dans un premier temps, notre objectif était de comprendre la fonctionnalité de GPR158 en cherchant une activité constitutive de ce récepteur ou en essayant de générer des mutants, des récepteurs tronqués ou des récepteurs chimériques constitutivement actifs. Jusqu'à présent, nous n'avons pas réussi à avoir un récepteur actif, malgré les résidus des boucles intracellulaires et des domaines TM importants pour le couplage aux protéines G et pour l'activation des autres RCPG, qui sont conservés dans GPR158. Ce qui suggère que ce récepteur pourrait ne pas avoir une signalisation en lui même, et il régulerait ainsi l'activité d'autres RCPG. Dans le cas inverse, GPR158 aurait un mode de signalisation très original qui reste à découvrir. Puis nous avons cherché à comprendre le rôle physiologique lié aux trois motifs VCPWE, que nous avons identifiés au niveau du domaine C-terminal (C-ter), très long, de ce récepteur. Ces motifs sont bien conservés chez les différentes espèces et joueraient ainsi des rôles fonctionnels importants. À ce sujet, nous avons montré que le troisième motif s'associe spécifiquement avec la sous-unité Gαo, probablement activée, des protéines G. Et nous avons également identifié, un site d'interaction d'un régulateur de l'activité des protéines G, RGS7, au niveau du domaine C-ter de GPR158, en amont des motifs. Vu que Gαo est le substrat de RGS7, nous suggérons que Gαo lierait en même temps le domaine RGS de la protéine RGS7, et ils formeraient ainsi avec GPR158 un complexe de régulation de l'activité du récepteur orphelin ainsi que d'autres RCPG présents dans le nano-environnement de GPR158. Enfin, afin de mieux comprendre la fonction et les possibles voies de signalisation de GPR158, une analyse protéomique des complexes multi-protéiques bâtis autour du domaine C-ter de GPR158, a été menée. Après purification du récepteur orphelin et des protéines associées par immunoprécipitation, l'identification par spectrométrie de masse des protéines présentes a permis d'identifier 6 nouveaux partenaires potentiels. Parmi eux, quatre protéines, p53, PPM1G, Sgt1 et SIRT1, sont des régulateurs du facteur de transcription suppresseur de tumeur p53, et deux protéines, SIRT1 et TRIM58, sont impliquées dans le processus de vieillissement cellulaire. Par conséquent, une implication dans la transcription, la régulation du cycle cellulaire, la réparation de l'ADN, la prolifération, l'apoptose, la tumorigenèse et le vieillissement, du récepteur orphelin GPR158 peut être envisagée. / G protein-coupled receptors (GPCR) are known to form the largest family of cell communication proteins, and to participate to all functions of the body, making them high potential therapeutic targets. However, lots of these proteins are still orphan receptors, for which no ligand, neither function have been described, although some could be of very high interest, like GPR158, a class C orphan GPCR. The seven transmembrane domain (7TM) of this orphan receptor was related to class C GPCR (GPR158 and GABAB share 20% sequence identity in the TM core region) but its N-terminal domain was not homologous to the typical Venus Flytrap (VFT) known to bind the ligands in most of class C receptors. Which suggests that GPR158 has developed different ligand binding mode. GPR158 is expressed mainly in the brain. Interestingly, the expression of this receptor has been found in many cells and tissues to be potentially regulated in pathological conditions, of which 50% are cancerous diseases. We thus intended to decipher its cellular function and partners, to understand its potential physiological and physiopathological roles. Initially, our goal was to determine the functionality of GPR158, and the possible signaling and cellular mechanisms it was involved in, by looking for some constitutive activity for this orphan GPCR, in the absensce of any ligand. Curiously, we could not detect any G protein coupling, like constitutive G protein stimulation by overexpression of wild type, mutated, truncated and chimeric receptors. This despite the residues of intracellular loops and TM domain, important for the G protein coupling and for the activation of other GPCR, which are conserved in GPR158. This suggests that GPR158 in itself might not have a signalization, and thus it would regulate the activity of other GPCR. Alternatively, GPR158 would have an original way of signaling to be discovered with more sophisticated techniques.Then, we tried to understand the role of three VCPWE specific motifs that we have identified at the long C-terminal (C-ter) domain of GPR158. These motifs are well conserved among different species and thus would play important functional roles. Therefore, we have shown that the third motif indeed binds G protein alpha o subunit, likely in active state. Interestingly, we have also shown that RGS7 that deactivated alpha o, interacts constitutively with the C-terminal domain of GPR158 upstream of VCPWE motifs. Thus, RGS7 would regulate the alpha subunit association with GPR158. Hence, GPR158 would act as a signaling regulatory platform, controlling G protein pathways by binding active alpha subunit and RGS7. This would be of great importance as a local signaling regulatory mechanism. Finally, to better understand the function and possible signaling pathways of GPR158, a proteomic analysis of multi-protein complexes built around the C-ter domain of GPR158, was conducted. After purification of the orphan receptor and its associated proteins by immunoprecipitation, the identification by mass spectrometry of GPR158 interacting proteins led to the identification of six potential new partners. Among them, four proteins, p53, PPM1G, SGT1 and SIRT1, are regulators of the p53 tumor suppressor protein widely known for its role as a transcription factor that regulates the expression of stress response genes, and two proteins, SIRT1 and TRIM58 are involved in cellular aging process. Therefore, GPR158 could be involved in transcription, cell cycle regulation, DNA repair, proliferation, apoptosis, tumorigenesis and cell aging.

Expansive soils are a worldwide problem especially in the regions where climate is arid or semi arid. These soils swell when they are exposed to water and shrink when they dry. Cyclic swelling and shrinkage of clays and associated movements of foundations may result in cracking of structures. Several methods are used to decrease or prevent the swelling potential of such soils like prewetting, surcharge loading, chemical stabilization etc. Among these, one of the most widely used method is using chemical admixtures (chemical stabilization). Cyclic wetting and drying affects the swell &ndash / shrink behaviour of expansive soils. In this research, the effect of cyclic swell &ndash / shrink on swell percentage of a chemically stabilized expansive soil is investigated. Class C Fly Ash is used as an additive for stabilization of an expansive soil that is prepared in the laboratory environment by mixing kaolinite and bentonite. Fly ash was added to expansive soil with a predetermined percentage changing between 0 to 20 percent. Hydrated lime with percentages changing between 0 to 5 percent and sand with 5 percent were also used instead of fly ash for comparison. Firstly, consistency limits, grain size distributions and swell percentages of mixtures were determined. Then to see the effect of cyclic swell &ndash / shrink on the swelling behavior of the mixtures, swell &ndash / shrink cycles applied to samples and swell percentages were determined. Swell percentage decreased as the proportion of the fly ash increased. Cyclic swell-shrink affected the swell percentage of fly ash stabilized samples positively.

The Greater than Class C (GTCC) Environmental Impact Statement (EIS) evaluated the potential impacts from the construction and operation of a new facility or facilities, or use of an existing facility, employing various disposal methods (geologic repository, intermediate depth borehole, enhanced near surface trench, and above grade vault) at six federal sites and generic commercial locations. For three of the locations being considered as possible locations, consulting tribes were brought in to comment on their perceptions on how GTCC low level radioactive waste would affect Native American resources (land, water, air, plants, animals, archaeology, etc.) short and long term. The consulting tribes produced essays that were incorporated into the EIS and these essays are in turn included in this collection. This essay was produced by the Consolidated Group of Tribes and Organizations (CGTO) for the Nevada Test Site. The CGTO is a pan-Indian organization representing 17 tribes from California, Nevada, Utah and Arizona.

The Greater than Class C (GTCC) Environmental Impact Statement (EIS) evaluated the potential impacts from the construction and operation of a new facility or facilities, or use of an existing facility, employing various disposal methods (geologic repository, intermediate depth borehole, enhanced near surface trench, and above grade vault) at six federal sites and generic commercial locations. For three of the locations being considered as possible locations, consulting tribes were brought in to comment on their perceptions on how GTCC low level radioactive waste would affect Native American resources (land, water, air, plants, animals, archaeology, etc.) short and long term. The consulting tribes produced essays that were incorporated into the EIS and these essays are in turn included in this collection. This essay was produced by members of the culturally affiliated tribes to Los Alamos National Lab.

La consommation excessive et chronique de sucre est un facteur de risque pour l'apparition de pathologies telles que le diabète de type II ou l'obésité. Une des solutions pour répondre à cet enjeu majeur de santé publique, tout en conservant le plaisir de la saveur sucrée, consiste en l'utilisation d'édulcorants en substitution du sucre. Actuellement, un certain nombre d'édulcorants sur le marché présentent arrière-goût amer ou sont sujets à débat quant à leurs effets sur la santé. Un des objectifs de ces travaux de thèse consiste à proposer de nouveaux édulcorants grâce à des approches rationnelles in silico. Un modèle statistique a été établi sur la base des structures chimiques et a permis d'identifier de nouveaux édulcorants d'origine naturelle. Ensuite, la reconstruction par homologie du récepteur à la saveur sucrée et l'étude des sites de liaison apportent des indices, à l'échelle atomique, qui permettront d'identifier ou même de concevoir de nouveaux édulcorants. L'étude dynamique d'un récepteur de la même famille (Récepteur Couplé aux Protéines G (RCPG) de classe C) a permis d'émettre une hypothèse sur le mécanisme d'activation, phénomène important pour la compréhension de la conversion du signal chimique en signal électrique. / Sugar overconsumption is a risk factor for pathologies such as type II diabetes or obesity. Sweeteners consumption is used to overcome this public health issue. Indeed, they have low caloric value but still preserve the pleasure of sweet taste. Currently, number of sweeteners are commercially available, but they present a bitter aftertaste or there is a debate about their safety. One aim of this work was to propose new intense sweeteners using computational modeling strategies. Through a statistical approach to predict the sweetness based on the chemical structure of already known sweeteners, new natural compounds have been identified. Furthermore, the structural study of the homology model of the sweet taste receptor provides some clues to design new sweeteners. The molecular dynamic study of a class C G-protein coupled receptor gives the first molecular hypothesis of the activation process.

A pesquisa analisa o consumo cultural (especialmente de rádio e televisão) de um grupo de empregadas domésticas que trabalham na cidade de São Paulo. Por meio de um mapeamento das preferências culturais dessas trabalhadoras organizadas nos perfis românticas, descoladas e evangélicas , discuto a importância dessas mídias no universo estudado. Paralelamente, a partir da análise de representações das empregadas domésticas na televisão, em especial, por meio da uma análise compartilhada da telenovela Cheias de Charme (Globo, 2012, 19h30), avalio as transformações ocorridas na imagem da empregada doméstica na ficção e na vida real , explorando a passagem de trabalhadora pobre para consumidora da classe C. Nesse contexto, temáticas como trabalho doméstico, gênero, classe, cor, consumo e mídias são relacionadas. / The research analyses the cultural consumption (particularly television and radio) of domestic workers in São Paulo (SP). Through mapping the cultural preferences of these women workers divided in three profiles, romantic, up to date and evangelic I raise reflections on the importance of these media among them. In parallel, through the analyses of domestic workers representations in television, in particular in the telenovela Cheias de Charme (Globo, 2012, 19h30), I discuss the transformations on the image of these workers in fiction and in real life exploring the passage from poor workers to class C consumers. In this context, issues such as domestic labor, gender, class, race, consumption and media are interrelated.

Made available in DSpace on 2016-04-25T20:21:20Z (GMT). No. of bitstreams: 1 Maria Teresa Garcia.pdf: 7418975 bytes, checksum: cfe0bbdbecf7a293192cbc3a393b0a7f (MD5) Previous issue date: 2015-03-11 / This thesis analyses the effects of the brazilian social class "C" growth in the television news broadcasts. The work observes how this class loomed in the first decade of this century and reflects the impact this social transformation had in the press. The case study that this thesis proposes is the one of the "Jornal Hoje", from Rede Globo. Editions of the TV news program from 2000 to 2014 were analysed, showing the transformations in the formatting and in the language of its contents. This work also focuses on how communication with the viewer can become more colloquial from the use of the portuguese language oral modality / Esta dissertação analisa os efeitos provocados pelo crescimento da Classe C brasileira na narrativa dos telejornais. O trabalho observa como a Classe C se agigantou na primeira década deste século e reflete que impacto essa transformação social provocou na imprensa. O estudo de caso proposto nesta dissertação é do JORNAL HOJE, da Rede Globo. São analisadas as edições do JH entre os anos de 2000 e 2014 e demonstradas as transformações na formatação e na linguagem do telejornal. Este trabalho enfoca também como a comunicação com o telespectador pode tornar-se mais coloquial, a partir do uso da modalidade oral da língua portuguesa

Made available in DSpace on 2016-04-26T14:55:11Z (GMT). No. of bitstreams: 1 Maria Teresa Garcia.pdf: 7418975 bytes, checksum: cfe0bbdbecf7a293192cbc3a393b0a7f (MD5) Previous issue date: 2015-03-11 / This thesis analyses the effects of the brazilian social class "C" growth in the television news broadcasts. The work observes how this class loomed in the first decade of this century and reflects the impact this social transformation had in the press. The case study that this thesis proposes is the one of the "Jornal Hoje", from Rede Globo. Editions of the TV news program from 2000 to 2014 were analysed, showing the transformations in the formatting and in the language of its contents. This work also focuses on how communication with the viewer can become more colloquial from the use of the portuguese language oral modality / Esta dissertação analisa os efeitos provocados pelo crescimento da Classe C brasileira na narrativa dos telejornais. O trabalho observa como a Classe C se agigantou na primeira década deste século e reflete que impacto essa transformação social provocou na imprensa. O estudo de caso proposto nesta dissertação é do JORNAL HOJE, da Rede Globo. São analisadas as edições do JH entre os anos de 2000 e 2014 e demonstradas as transformações na formatação e na linguagem do telejornal. Este trabalho enfoca também como a comunicação com o telespectador pode tornar-se mais coloquial, a partir do uso da modalidade oral da língua portuguesa

A presente pesquisa pretende estudar aspectos da midiatização do consumo e do sentido de classe social na telenovela com foco na representação do que vem sendo considerada a \"nova classe C\" ou \"nova classe média\" brasileira. Para tanto, analisou-se cenas das telenovelas Avenida Brasil (2012), de João Emanuel Carneiro, e Cheias de Charme (2012), de Filipe Miguez e Izabel de Oliveira. Ambas exibidas na Rede Globo, a primeira no horário das 21 horas e a segunda às 19 horas. As duas foram consideradas pela mídia como tramas que representam a \"nova classe C\", o que justifica a escolha. Inicialmente, o trabalho traz uma breve discussão teórica sobre o termo midiatização, sobre as concepções sociológicas de classe social e os estudos realizados sobre telenovela e classe. Pretende-se, assim, problematizar a expressão \"nova classe C\", de modo a entender sua natureza e validade sociológica, bem como levantar a forma como a telenovela costuma retratar as classes sociais, para, assim, rumar às análises com embasamento teórico. A metodologia de análise se fundamenta na concepção marxista de materialismo histórico e dialética, com a qual estão relacionadas as teorias do filósofo da linguagem Mikhail Bakhtin, a Análise do Discurso Francesa e a Análise do Discurso Crítica. Essas teorias tiveram alguns de seus elementos mesclados e utilizadas como protocolo metodológico. A partir do protocolo e dos levantamentos teóricos sobre classes sociais e telenovela, objetiva-se averiguar as nuanças da midiatização do consumo e do sentido de classe social na representação discursiva do que vem sendo chamada a \"nova classe C\" em cenas selecionadas de Avenida Brasil e Cheias de Charme. Com as análises das cenas que retratam situações que aludem ao consumo, obtivemos resultados que apontam para o fato de ambas as telenovelas, em diferentes graus, apresentarem em seus discursos características que condizem com o modo próprio da telenovela tratar as classes sociais, assim como elementos que se relacionam com uma visão social hegemônica, além de aspectos que estão conectados com a realidade comentada pelos sociólogos e que também indicam mudanças na forma usual das telenovelas retratarem as diferenças sociais. Ademais, de acordo com o conceito de midiatização e com o papel da telenovela no Brasil, acreditamos que essas representações contribuem para a formação de um conhecimento social do que seria a \"nova classe C\" brasileira. / This search aims to study aspects of the mediatization of consumption and the sense of social class in telenovela, with focus on what is dubbed \"the new class C\" or \"new middle class\" in Brazil. For that purpose, it was analyzed scenes of the telenovelas Avenida Brasil (2012), by João Emanuel Carneiro, and Cheias de Charme (2012), by Filipe Miguez and Izabel de Oliveira. Both were aired in Rede Globo, at 9pm. and 7pm., respectively. These two productions were considered by the media as representative of the \"new class C\", which justifies the choice. Initially, this work brings a brief theoretical discussion about the mediatization concept, about the sociologic concept of social class and the studies which cover telenovela and social class altogether. It is intended, therefore, to problematize the expression \"new class C\", in order to understand its origin and sociologic nature, as well as to look at the manner by which the telenovela usually portrays the social classes, so as to produce an analysis which has theoretical base. The methodology to analyze the matter is based on the Marxist conception of dialectic and in the historical materialism, which are related to the theories of the Russian language philosopher Mikhail Bakhtin, the French Discourse Analysis and Critical Discourse Analysis. These theories had some of their elements combined and used as methodological protocol. From methodological protocol and from the theoretical points about social classes and telenovelas, the objective is to investigate the nuances of the mediatization of consumption and the sense of social class in the discursive representations of the dubbed \"new class C\" in scenes picked from Avenida Brasil and Cheias de Charme. Based on the analysis of scenes that portray situations that allude to consumption, we obtained results which demonstrate that both telenovelas, yet in different degrees, reveal in their plots characteristics that connect with the particular view with which the telenovela approaches the social classes, as well as with elements that are related with the hegemonic social view, apart from aspects that are connected with the reality commented by sociologists and which indicates changes in the usual way that the telenovela portrays the social differences. Moreover, according to the concept of mediatization as well as to the role of telenovela in Brazil, we believe that those representations contribute to the making of a social knowledge of what the new Brazilian \"new class C\" would be.

Made available in DSpace on 2016-06-02T20:39:18Z (GMT). No. of bitstreams: 1 5204.pdf: 4069568 bytes, checksum: 75d233339e33ba4f8ff9ab69a948d8a3 (MD5) Previous issue date: 2013-03-11 / Universidade Federal de Minas Gerais / The present work focus on investigating processes of subjectivity in contemporary self-help speeches aiming the female audience, which when penetrating the network through a specific form of using digital media, they become practical mutual help. To achieve this goal, I established three main lines of research, which I will discuss through a ethnographic method: the website Bolsa de Mulher, with its discussion forums, advertisements and products sales and the group created by the users on Facebook, the lines among users within that platform, their life stories and experiences both with the internet and the self-help speech; finally, some books of this genre, most cited by my collaborators and some of the best selling in recent years, in Brazil. I discuss a theoretical framework that examines issues of subjectivity through the use of digital media as well as one that addresses a perspective of intersectionality of class differences, gender, sexuality, race, religion, all markers crossing such use. Last but not least, I problematize and bring into discussion the sociological debate around the so-called New Class C, public that composes this research and has specific characteristics regarding the use of digital media and the dynamics of mutual help, in Brazil. / Esta dissertação tem como tema central investigar processos de subjetivação em discursos de autoajuda contemporânea voltada para o público feminino, que quando penetram na rede, através de uma específica forma de uso das mídias digitais, se transformam em práticas de ajuda-mútua. Para alcançar este objetivo estabeleci três principais frentes de pesquisa as quais abordarei por meio de método etnográfico: o site Bolsa de Mulher, com seus fóruns de debate, propagandas e venda de produtos e o grupo criado pelas usuárias no Facebook; as falas das usuárias e usuários que integram essa plataforma, suas histórias de vida e experiências tanto com a internet, quanto com o próprio discurso da autoajuda; e, por fim, alguns livros do gênero, mais citados por minhas colaboradoras e alguns exemplares dos mais vendidos nos últimos anos, no Brasil. Discuto com um referencial teórico que analisa questões de subjetividade por meio do uso das mídias digitais, bem como aquele que aborda uma perspectiva de interseccionalidade das diferenças de classe, gênero, sexualidade, raça, religião, todos marcadores que atravessam tal uso. Por fim, mas não menos importante, problematizo e trago para o debate a discussão sociológica em torno da chamada Nova Classe C, público que compõe esta pesquisa e que apresenta características específicas no tocante ao uso das mídias digitais e as dinâmicas de ajuda-mútua, no Brasil.