Entendemos, conforme a perspectiva bakhtiniana, que nenhum fato ou fenômeno da natureza tem significado em si mesmo, mas que tal significado surge justamente por meio da língua. Sendo assim, a análise da língua auxilia a compreender os posicionamentos ideológicos que sustentam os discursos. Tendo isso em vista, pretendemos compreender como o gênero de divulgação científica, estreitamente relacionado com o gênero científico, funciona e quais são os mecanismos de que se utiliza para estruturar suas práticas discursivas. Para isso, analisamos um artigo científico e um artigo de divulgação científica acerca da experimentação científica em animais, utilizando como categorias de análise do artigo científico as noções de tema/significação e discurso de outrem/citação e como categorias de análise do artigo de divulgação científica as noções de discurso parafrástico. A fim de guiar nossa análise, propusemo-nos a responder as seguintes questões: a) quais são as condições sociais e históricas que originaram esse gênero?; b) quais as suas finalidades?; c) esse discurso é de cunho perifrástico ou parafrástico?; d) quem são os interlocutores levados em conta durante a construção dos seus enunciados?; e) qual a resposta que se espera desse auditório?; f) de que modo o tema dos artigos selecionados para análise é significado? Percebemos que as primeiras manifestações de divulgação científica ocorreram em um contexto em que as atividades relacionadas à ciência eram escassas, havia pouquíssimas instituições de ensino superior no país e a maioria da população era iletrada. Havia, dessa forma, a necessidade de: elaborar materiais sobre a ciência calcados em parâmetros culturais e linguísticos acessíveis às pessoas em geral; obter fundos e reconhecimento para a ciência; intervir na realidade de alienação do povo; e servir aos interesses econômicos de organizações como as editoras e a indústria farmacêutica. Entendemos que os discursos de divulgação científica são o resultado de um processo de parafraseamento de discursos científicos, funcionando discursivamente como um trabalho de reformulação e de pedagogização do discurso científico. Percebemos, também, nos discursos analisados, a perspectiva de que o emprego de animais é imprescindível ao progresso da ciência, de modo que toda e qualquer atividade contrária à realização de tal prática é vista como radical e prejudicial ao desenvolvimento científico. A partir disso, observamos que o discurso de divulgação científica referenda o status quo do modo de produção científico. / We understand, according to the bakhtinian perspective, that no fact or phenomenon of nature has meaning in itself, but the meaning just arises through language. Thus, the analysis of language helps to understand the ideological positions that support the discourses. In this sense, we aim to understand how the scientific divulgation genre, closely related to the scientific genre, works and what are the mechanisms that are used to structure its discursive practices. For this, we analyzed a scientific article and a scientific divulgation article about scientific experimentation on animals, using as categories of analysis of the scientific article the notions theme/meaning and others speech/quote and as categories of analysis of scientific divulgation article the notions of paraphrastic discourse. In order to guide our analysis, we have proposed ourselves to answer the following questions: a) what are the social and historical conditions that gave rise to this genre?; b) what are its purposes?; c) this speech is of periphrastic or paraphrastic nature?; d) who are the interlocutors considered during the construction of its statements ?; e) what response is expected from this audience ?; f) how the theme of the articles selected for analysis is meant? We realize that the first manifestations of scientific divulgation occurred in a context in which activities related to science were scarce, there were very few higher education institutions in the country and most of the population was illiterate. There was thus a need to: elaborate materials on science based on cultural and linguistic parameters accessible to people in general; obtain funding and recognition for science; intervene on the reality of alienation of people; serve the economic interests of organizations such as publishers and the pharmaceutical industry. We understand that the scientific divulgation discourses are the result of a paraphrasing process of scientific discourses, acting discursively as a work of redesign and pedagogization of scientific discourse. We realize, too, in the analyzed texts, the perspective that the use of animals is essential to the progress of science, so that any activity contrary to the realization of this practice is seen as radical and harmful to the scientific development. From this, we observed that the scientific divulgation discourse endorses the status quo of scientific production.

Este trabalho tem como objetivo descrever as principais doenças diagnosticadas em caprinos no Setor de Patologia Veterinária da Universidade Federal do Rio Grande do Sul no período de 2000 a 2016. No primeiro artigo foi realizado um estudo retrospectivo das causas de morte em caprinos diagnosticadas de 2000 a 2016. Do total de 322 caprinos necropsiados neste período, 290 (90%) obtiveram um diagnostico conclusivo. Dos casos conclusos, 167 (57,6%) corresponderam a enfermidades de origem infecciosa e toxi-infecciosas e 123 (42,4%) enquadrados em causas não infecciosas. Entre as doenças infecciosas foram contabilizados 54 casos de origem bacteriana, 60 casos com envolvimento parasitário, 14 casos de origem viral, além de 39 casos toxi-infecciosos. As doenças de caráter não infeccioso foram ainda agrupadas em doenças metabólicas (44 casos), intoxicações por plantas ou substâncias tóxicas (36), deficiências minerais e nutricionais (20), neoplasias e distúrbios no desenvolvimento (5). A hemoncose, eimeriose, pleuropneumonias e a enterotoxemia foram as doenças mais frequentemente diagnosticadas neste período. O segundo artigo descreve um surto de tuberculose em caprinos jovens. Onze de um total de 15 caprinos, de cinco a 15 dias de idade, foram positivos ao teste de tuberculina. Na necropsia, o parênquima pulmonar de todos os caprinos positivos apresentavam nódulos de 0,3 a 10 cm de diâmetro, coloração brancacenta a amarelada, ocasionalmente, também observados no fígado e baço Os linfonodos retrofaríngeos, mediastínicos e traqueobrônquicos apresentavam-se acentuadamente aumentados de tamanho e aspecto caseoso. Na avaliação histológica, a lesão era caracterizada por intensa necrose caseosa, com áreas de mineralização distrófica, associados a acentuado infiltrado inflamatório granulomatoso. A coloração de Ziehl-Neelsen e a marcação por imuno-histoquímica anti-complexo Micobacterium tuberculosis evidenciou discreta a moderada quantidade de bacilos álcool-ácido resistentes. O cultivo microbiológico e a análise molecular confirmaram o agente etiológico M. bovis. O terceiro artigo descreve dermatite e hepatopatia tóxica crônica natural e experimental em caprinos associadas ao consumo de farelo de arroz desengordurado. Caprinos jovens, de um a quatro meses de idade, apresentavam alopecia e formações crostosas na pele, apatia, emagrecimento, prurido discreto e, vinham a óbito em um período de 30-40 dias. À necropsia, o fígado apresentava irregularidades na superfície capsular, coloração alaranjada a avermelhada, além de rins com múltiplas áreas circulares brancacentas na superfície capsular. À análise microscópica, acentuada atrofia de hepatócitos em região periportal hepática e moderada degeneração hepatocelular microvacuolar. No estudo experimental comprovou-se a etiologia dos casos, através da manifestação de lesões de pele, hepática e renais similares ao dos casos naturais, entretanto em menor intensidade. / This work aims to describe the main diseases diagnosed in goats in the Sector of Veterinary Pathology of the Federal University of Rio Grande do Sul from 2000 to 2016. The first article describes the main causes of death in goats diagnosed between 2000 and 2016. A conclusive diagnosis was obtained in 290 (90%) cases from a total of 322 goats necropsied. Of these cases, 167 (57.6%) corresponded to infectious and toxi-infectious diseases, and 123 (42.4%) included non-infectious causes. Among the infectious diseases 54 cases were of bacterial origin, 60 cases were caused by parasite agents, 14 cases of viral origin, and 39 toxi-infectious cases. Non-infectious diseases were also grouped into metabolic diseases (44 cases), poisoning by plants or toxic substances (36), mineral and nutritional deficiencies (20), neoplasms and developmental disorders (5). Haemonchosis, eimeriosis, pleuropneumonia and enterotoxemia remain as one of the major control obstacles in goat farms. The second article describes an outbreak of tuberculosis in goat kids. Eleven of a total of 15 kids, from 5 to 15 days old, were positive to tuberculin. At necropsy, the pulmonary parenchyma of all positive goats had white to yellowish nodules of 0.3 to 10 cm in diameter, that were occasionally also observed in the liver and spleen The retropharyngeal, mediastinal and tracheobronchial lymph nodes were markedly enlarged and with a caseous aspect. Histologically, the lesion was characterized by an intense caseous necrosis, with areas of dystrophic mineralization, associated to a marked granulomatous inflammatory infiltrate. Ziehl-Neelsen histochemistry exam and immunohistochemical anti-Micobacterium tuberculosis complex evidenced mild to moderate amount of bacilli. Microbiological culture and molecular analysis confirmed M. bovis as the etiological agent. The third article describes a natural and an experimental toxic liver disease associated with the consumption of defatted rice bran in goats. These presented with alopecia and crusted formations on the skin, apathy, weight loss, mild pruritus, and death within a period of 30-40 days. At necropsy, the liver presented multifocal to coalescing orange to reddish irregular areas on the capsular surface, and the kidneys presented multiple white circular areas on the capsular surface. Microscopic analysis revealed a marked hepatocyte atrophy at the hepatic periportal region, and a moderate microvacuolar hepatocellular degeneration. In the experimental study, the etiology of the cases was demonstrated through the manifestation of lower intensity skin, liver and kidney lesions similar to those of the natural cases.

Submitted by PPGE PPGE (pgedu@ufba.br) on 2015-11-26T15:49:05Z No. of bitstreams: 1 Tese Ivan Maia de Mello.pdf: 2137353 bytes, checksum: c56787d91376923b4874548822cfecf1 (MD5) / Approved for entry into archive by Maria Auxiliadora da Silva Lopes (silopes@ufba.br) on 2015-12-18T13:53:49Z (GMT) No. of bitstreams: 1 Tese Ivan Maia de Mello.pdf: 2137353 bytes, checksum: c56787d91376923b4874548822cfecf1 (MD5) / Made available in DSpace on 2015-12-18T13:53:49Z (GMT). No. of bitstreams: 1 Tese Ivan Maia de Mello.pdf: 2137353 bytes, checksum: c56787d91376923b4874548822cfecf1 (MD5) / A tese aborda a questão da auto-educação a partir da perspectiva de Friedrich Nietzsche e outros pensadores, que o tomaram como referência para pensar filosoficamente possibilidades de uma aprendizagem voltada para fazer da vida uma obra de arte. A questão problematizada é como esta aprendizagem pode ocorrer de modo cada vez mais autônomo configurando uma arte de viver direcionada para a poetização da existência. A auto-educação é pensada como parte de uma autopoiesis, um processo de subjetivação mais abrangente quanto aos aspectos da existência em que a aprendizagem é experimentada no sentido proposto por Nietzsche para fazer da vida uma obra de arte, tornando-se poeta da própria existência e tomando o corpo como fio condutor desse processo. A perspectiva de Nietzsche é considerada juntamente com algumas outras que se apropriaram dela para formularem suas próprias concepções, tais como, principalmente: Oswald de Andrade, pela Antropofagia como visão de mundo voltada para a apropriação seletiva da alteridade subjetiva; Martin Heidegger, pela hermenêutica do acontecimento apropriativo na criação poética; Michel Foucault, pela genealogia dos processos de subjetivação, abrangendo desde a antiguidade greco-romana até a contemporaneidade, que o permitiu formular a questão da estética da existência; Gilles Deleuze e Felix Guattari, pela cartografia da autopoiesis como processo de subjetivação singularizante, modulado por paradigmas estéticos apropriados; e Dante Galeffi, pela proposta poemático-pedagógica de uma educação transdisciplinar para o fazer inventivo do ser-sendo, que configura a vita poemática. Essas e outras perspectivas foram usadas para elaborar a proposta de uma educação autopoiética do corpo criador que Nietzsche indicou como o ser próprio, e foi denominado nesta tese de corpoema. A educação autopoiética do corpoema é pensada ao longo da experimentação da autopoiesis em alguns campos da existência, nos quais se constitui a estética da existência corpoética: os campos de experimentação da habitação do espaço de vida, da dinâmica corporal dos impulsos, das relações de poder, das valorações afetivas, das linguagens de expressão e da compreensão dos sentidos do viver. Em cada um desses campos, são consideradas tendências vitais a serem apropriadas e dificuldades a serem superadas para a composição de um estilo singular na arte de viver corpoética, voltada para a poetização do corpo e incorporação da poesia. Assim, quanto à experiência da habitação, as tendências voltadas para o local e o global; quanto à corporeidade, as tendências dos impulsos eróticos e fraternos; quanto às relações de poder, as tendências para a emancipação e para a solidariedade; quanto à afetividade, as tendências para a dignidade ética e para a intensidade passional; quanto à expressividade, as tendências para a linguagem figurada e para o discurso conceitual; quanto à experiência da compreensão, as tendências para o aprofundamento e para a abrangência. A autopoiesis do corpoema é, portanto, apresentada transversalmente numa cartografia genealógica do processo de subjetivação constituído por essas experimentações, guiadas pelas perspectivas consideradas, no sentido de configurar um estilo corpoéticopara essa estética da existência autopoiética. / ABSTRACT The question of self-education is approached from the perspective of Friedrich Nietzsche and other authors, who took him as reference to think philosophically the possibilities of a learning whose objective is to make life a work of art. The problematized question is how this apprenticeship may occur in a more autonomous way configurating an art of living directed to the poeticization of existence. Self-education is thought as part of an autopoiesis, a widely process of subjectification that includes some aspects of existence in which the apprenticeship is experimented according to Nietzsche‟s proposal to make life a work of art, becoming the poet of one‟s own existence and considering the body as a conducting thread of this process. Nietzsche‟s perspective is considered together with some others which appropriated his ideas to formulate their own conceptions, like, mainly: Oswald de Andrade, for his Anthropophagic world vision turned to a selective appropriation of a subjective otherness; Martin Heidegger, for his hermeneutics of the appropriative happening in poetry creation; Michel Foucault, for his genealogy of subjectification processes, including since greco-roman antiquity until contemporaneity, which allowed him to formulate the question of the esthetics of existence; Gilles Deleuze and Felix Guattari, for their cartography of autopoiesis as a singularizing subjectification process, modulated by proper esthetical paradigms; and Dante Galeffi, for his poematic-pedagogical proposal of a transdisciplinary education for an inventive producing of being, which configurates the poematic vita. These and other perspectives were used to elaborate the proposal of an autopoietic education of the creator body that Nietzsche considered as the self, and is named in this thesis as corpoema. The autopoietic education of corpoemais thought along the experimentation of autopoiesisin some spheres of existence, in which the esthetics of existence of corpoemais constituted. They are the spheres of experimentation of: vital space occupation, body‟s dynamic of impulses, power relations, affective evaluations, languages of expression, and comprehension of living meanings. In each of these spheres, vital tendencies to be appropriated and difficulties to be overcomed are considered to compose a singular style of corpoema‟s art of living, turning to poeticization of the body and embodiment of poetry. Therefore, concerning the habitation experience, the tendencies for local and global; concerning the body experience, the tendencies for erotic and fraternal impulses; concerning the power relations, the tendencies for emancipation and solidarity; concerning affectivity, the tendencies for ethical dignity and for passional intensity; concerning expressivity, the tendencies for figurative languages and for conceptual discourse; concerning comprehension, the tendencies for deepening and for expanding. Corpoema‟s autopoiesis isthus presented transversally in a genealogical cartography of the subjectification process constituted by these experimentations, guided by the considered perspectives, in the way of seting the corpoema‟s style for this autopoietic esthetics of existence.

Orientadora: Prof. Dr. André Amaral Gonçalves Bianco / Dissertação (mestrado) - Universidade Federal do ABC, Programa De Pós-Graduação em Ensino, História, Filosofia das Ciências e Matemática, 2017. / De maneira geral, o ensino dos conteúdos curriculares da disciplina de Química tem sido focado na memorização de conceitos e procedimentos sem reflexão. Muitas críticas têm sido feitas a essa forma de ensino e são requeridas alternativas para mudar essa situação. Nesse contexto, as estratégias educacionais que vinculam a arte ao ensino de ciências apresentam destaque na pesquisa em Ensino por possibilitar a humanização da ciência nos currículos e a aproximação do campo das ciências humanas ¿ no qual se insere a arte ¿ ao das chamadas ciências naturais. O uso do teatro no ensino de ciências pode auxiliar o desenvolvimento e aperfeiçoamento de competências citadas nas Diretrizes Curriculares Nacionais do Ensino Médio (DCNEM). Capacidade de trabalhar em equipe, capacidade de abstração e disposição em aceitar críticas são exemplos de competências trabalhadas quando os estudantes se inserem na prática do teatro. Neste trabalho, elaboramos, aplicamos e analisamos uma estratégia de ensino de Química para alunos do 1º ano do Ensino Médio de uma escola da rede privada de ensino do município de Diadema. Utilizamos o teatro para a promoção de um espaço de discussão de ideias, no qual o aprender aconteceu de modo interativo, investigativo e dinâmico, baseado no estudo e discussão de experimentos investigativos, que buscavam despertar a curiosidade dos alunos para a compreensão dos fenômenos observados, de modo a promover o protagonismo dos alunos. Para isso, utilizamos a ideia de Ensino Ativo como referência à nossa proposta. Por meio de questionários, entrevistas e observações da aplicação da metodologia, foi possível verificar contribuições do ensino ativo associado ao teatro e à experimentação para o aprendizado dos alunos, bem como indícios do aumento do interesse dos alunos pela disciplina de Química. Foi possível observar também a importância do protagonismo do aluno no papel de ensino/aprendizagem, já que os alunos que apenas assistiram a uma apresentação de teatro não apresentaram resultados significativos, diferente daqueles que participaram de nossa metodologia. Dessa forma, verificamos as contribuições de nossa proposta para o ensino de Química. / In general, the teaching of the curricular contents of the discipline of Chemistry had been focused on memorizing concepts and procedures without consideration. Many objections have been made about this way of teaching. By this context, educational strategies, which bond art and science teaching, highlight teaching research enabling the humanization of science in educational problem becoming closer to human science field ¿ in which art is insert ¿ into what is known as natural sciences. The usage of theater in science teaching can collaborate with growing and improvement of the developing skills mentioned in Diretrizes Curriculares Nacionais do Ensino Médio (DCNEM). Ability to work as a team, abstraction ability and condition to accept criticism are examples of developing skills when students enable themselves into theater proceeding. In this work we elaborated, applied and analyzed Chemistry educational strategy aiming private first year high school students from Diadema city. The theater was used as a place to raise discussion across the act of learning and it happened in an interactive, analytical and productive way, based on study and discussion of investigative experiments which target was to stimulate students¿ curiosity towards the comprehension of observed phenomena, in order to promote the students¿ acting. To achieve this objective, we used the Active Teaching as reference to our proposal. Through questionnaires, interviews and methodology applications observed, it was possible to verify Active Teaching contributions associated with theater and attempting on students¿ learning, as well as students' interests increased on Chemistry subject. It was possible to observe the importance of the student¿s acting in the teaching/learning performance, since part of the students just watched to one presentation did not show significative results, different from those who participated of this methodology. Therefore, we verified the contributions of our purposes to Chemistry teaching.

Le soudage est un procédé clef dans l'industrie nucléaire. L'utilisation de ce procédé d'assemblage est nécessaire pour assurer la continuité physique et chimique indispensable à la sûreté des composants des centrales. Pour la société AREVA, un axe de développement important consiste à augmenter la productivité tout en garantissant une qualité optimale.L'approche expérimentale présentée dans ce travail a pour double objectif de proposer un dispositif de contrôle des températures des zones de métal liquide et de caractériser leur comportement dynamique, dans le cas du soudage MAG. Une méthode de mesure de température, en pyrométrie bichromatique, a été développée pour la mesure textit{in-situ} des champs de température des zones liquides. Les premiers essais réalisés en configuration industrielle permettent d'envisager l'utilisation de ce type de méthode pour le contrôle temps réel d'opérations de soudage. La méthode de pyrométrie bichromatique, couplée à l'observation et à l'étude des déformations des gouttelettes au cours de leur transfert, permet également d'évaluer l'influence de la température sur la tension superficielle, en interaction avec le plasma d'arc. Le rôle majeur de la tension superficielle dans le comportement dynamique des phases liquides apparaît clairement dans les résultats obtenus. Les outils d'investigation et d'analyse développés ont été utilisés pour étudier un procédé de soudage par court-circuit contrôlé (CMT). Il est ainsi possible d'analyser la rupture du pont liquide, mais aussi le comportement du dépôt de métal liquide, qui peut entraîner des défauts de forme, et la dynamique des transferts de masse pour identifier l'apparition des défauts opératoires. / Welding is a key process in nuclear industry. The use of this assembly process is needed to ensure chemical and physical continuity required for installations safety. For the firm AREVA, one of the major axis of development is improving the productivity of nuclear components with the guaranty of optimum quality.Experimental approach presented in the present work has the double objectives of proposing a monitoring device for temperature fields of liquid metal and characterising its dynamic behaviour in GMAW. A two colour measurement method has been developed for textit{in-situ} surface temperature measurement of liquid zones. First tests realised in an industrial configuration allow to consider this method as a possible real-time control device for welding. This two colour pyrometer, coupled to the observation and the study of droplets deformations during their transfer, allows to study the influence of temperature on surface tension, with the interaction of arc plasma. Main role of surface tension on liquid phase behaviour is clearly exposed in the obtained results. The developed investigating and analysis tools have been used to study a GMAW controlled short arc process. So, it is possible to analyse liquid bridge rupture, but also liquid metal deposition behaviour, which can induce shape defects, and mass transfer dynamic to identify the apparition of operative defects.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Studies show that the experimental activities based on problem solving improve student performance on the nature of scientific knowledge. In this context, this study evaluated the impact of experimental activities based on scientific method and previous conceptions in the early years of learning concepts and phenomena associated with the fermentation process. The activities were carried out through an experimental course of 20hs, with students of 1st and 2nd year of the Elementary Education of Municipal School Deacon João Luiz Pozzobon in Santa Maria-RS. The research involved 20 students aged 6 and 7 years, overseen by monitors (students and post graduate teachers) who played the role of instigating students to use reasoning and creativity for creating hypotheses and design experiments. Overall, the course emphasized the process of doing science by middle of questioning and search for answers for assembling simple experiments. The evaluation of the results was performed by comparing the interviews responses performed before the course (pretest) and after the course (post-test), post-tests being applied at the end of the experimental course, 6 and 12 months later. The obtained data set show that the activities have facilitated acquisition and construction of new concepts and caused changes in pre-conceptions of the students on the subject, which can be considered more scientifically correct. In addition, we observed that the issue worked through experimental activities was assimilated and memorized by the students in the short and long term. We assume that manipulation, observation and experimentation associated motivation are factors that bring cognitive benefits and facilitate the process of writing and scientific literacy in this school stage. / Estudos mostram que as atividades experimentais baseadas na resolução de problemas melhoram o desempenho dos alunos sobre a natureza do conhecimento científico. Neste contexto, este estudo avaliou o impacto de atividades experimentais baseadas no método científico e nas pré-concepções dos anos iniciais sobre a aprendizagem de conceitos e fenômenos associados ao processo de Fermentação. As atividades foram realizadas através de um curso experimental de 20hs, com estudantes do 1º e 2º ano do Ensino Fundamental da Escola Municipal Diácono João Luiz Pozzobon na cidade de Santa Maria-RS. A pesquisa envolveu 20 estudantes com idades entre 6 e 7 anos, supervisionados por monitores (alunos e professores de pós-graduação) que desempenharam o papel de instigar os alunos a utilizar o raciocínio e a criatividade para a criação de hipóteses e elaboração dos experimentos. De forma geral, o curso enfatizou o processo de fazer ciência por meio de questionamentos e busca de respostas pela montagem de experimentos simples. A avaliação dos resultados foi efetuada pela comparação de respostas de entrevistas realizadas antes do curso (pré-teste) e depois do curso (pós-teste), sendo os pós-testes aplicados no final do curso experimental, 6 e 12 meses depois. O conjunto de dados obtidos mostram que as atividades desenvolvidas facilitaram a aquisição e construção de novos conceitos e causaram mudanças nas concepções prévias dos alunos sobre o tema, as quais podem ser consideradas como cientificamente mais corretas. Além disso, foi possível observar que o tema trabalhado por meio de atividades experimentais foi assimilado e memorizado pelos estudantes a curto e a longo-prazo. Assumimos que a manipulação, a observação e a motivação associados a experimentação são fatores que trazem benefícios cognitivos e facilitam o processo de alfabetização escrita e científica nesta fase escolar.

Bile acid metabolism is integrally involved in cholesterol homeostasis in mammals because it is the major means by which cholesterol is eliminated from the body. We have undertaken an effort to study the molecular mechanisms underlying the regulation of bile acid metabolism by isolating and characterizing the cDNA and gene for an enzyme that hydroxylates lithocholic acid (LCA) at position 6β, lithocholic acid 6β-hydroxylase; the first bile acid-induced gene reported. LCA is a very hydrophobic, toxic bile acid formed from chenodeoxycholic acid in the gut lumen upon reduction of the 7α-hydroxy group by microbial enzymes. The proper elimination of LCA is essential for maintenance of the bile acid pool and for prevention of cholestasis which results from LCA precipitating in the cannaculi of the liver when its concentration is high. The LCA 6β-hydroxylase cDNA was isolated by differential hybridization of hamster liver libraries prepared from animals fed either a cholic acid enriched diet or a cholestipol-rich chow and was named CYP3A10 based on its homology with other cytochrome P450s (P450) in family 3A. We found that CYP3A10 was essentially expressed only in males. A statistical analysis of RNA from young males fed with cholic acid and normal chow showed that the cholic acid induction was about 50% at the RNA level. We determined the biological nature of the protein encoded by CYP3A10 by expression of the cDNA in COS cells. Microsomes prepared from transfected cells were assayed with LCA as a substrate and found to hydroxylate LCA predominantly at position 6β. We examined whether CYP3A10 could hydroxylate other steroid compounds by assays with testosterone, progesterone and androstenedione and found that, although 6β-hydroxylase (as well as others) activity was observed with all three, LCA was the preferred substrate based on kinetic analysis. A developmental time course of CYP3A10 expression in males showed little expression before puberty, a striking induction of expression at puberty and a fourfold induction thereafter through adulthood. We then examined the male-specific expression of CYP3A10 in hamster liver. We disrupted the pattern of GH secretion in male hamsters by hypophysectomy, neonatal glutamate treatment and by continuous infusion of GH via osmotic minipumps (to mimic the female pattern of GH secretion) and found no significant effect on CYP3A10 expression. Conversely, in females, hypophysectomy and neonatal glutamate treatment significantly induced CYP3A10 expression 5- to 10-fold. Additionally, when females treated neonatally with glutamate were injected twice daily with GH as adults (to mimic the male pattern of GH secretion), the levels of CYP3A10 expression were not significantly different from those of normal males. These results led us to conclude that the pattern of GH secretion in males does not control the male-specific expression of CYP3A10 but that in females expression can be induced by altering the tonic secretion of GH. No significant effect on CYP3A10 expression was observed by castration of adult males, indicating that circulating androgens were not required for expression. We found that gonadal hormones (e.g. estrogen and progesterone) do not have a suppressive effect on CYP3A10 expression in females since ovariectomy did not induce expression. Many genes are "imprinted" neonatally by exposure to a given effector for developmental-, tissue- or sexually regulated expression. We investigated whether neonatal androgen exposure was required for male-specific expression of CYP3A10 by castrating hamsters neonatally and determining the level of CYP3A10 expression in adulthood. Our results indicate that androgens are required neonatally for CYP3A10 expression since no expression was observed in neonatally castrated hamsters. We were unable to induce expression in neonatally castrated hamsters by either GH or testosterone injections. These results suggest several notable points 1) that CYP3A10 expression is programmed neonatally by androgen exposure; 2) that androgens exert their effect directly on the liver and not via the hypothalamus; 3) that neither testosterone nor GH can restore CYP3A10 expression when males have not been exposed to androgens neonatally; and 4) that in experimental conditions, females can be induced to express CYP3A10, which indicates that there are two modes for regulating expression: by "imprinting" in males and by GH and testosterone in females. We are now studying the molecular mechanisms involved in the bile acid-mediated induction and the male-specific expression of CYP3A10. We have cloned approximately 8 kb of 5' flanking DNA from a hamster genomic library and sequenced about 1 kb of proximal DNA. Primer extension and S1 digestion analyses indicate that the mRNA for CYP3A10 has multiple transcription initiation sites clustered about 90 bp from the initiator methionine codon. We have also prepared CYP3A10 promoter/lacZ chimeric constructs to begin delineating the cis-acting elements controlling CYP3A10 expression and regulation. We used H2.35 cells as recipients because they are a mouse hepatocyte cell line that has been transformed with a temperature sensitive SV40. These cells can be grown at the permissive temperature and can be induced to behave like liver cells, the differentiated condition, by switching to a nonpermissive temperature. We have found that the construct with 1 kb of proximal CYP3A10 5' flanking DNA was able to express the reporter gene at higher levels under differentiated conditions, which were consistent with higher expression of an albumin promoter/lacZconstruct, upon switching the cells to the more liver phenotype. The system characterized and described here is ideally suited for dissecting the molecular details governing bile acid-mediated regulation and sexually dimorphic expression of liver genes. Very little is known about both these very important biological phenomena. Much could be learned about transcriptional regulation of liver genes by investigating the cis-elements and trans-acting factors mediating regulation of CYP3A10 expression.

During embryonic development of the nematode Caenorhabditis elegans, cell fates are specified by asymmetric segregation of cell fate determinants and via cell-cell signaling events. Specification of the eight-cell stage blastomere E, the endoderm progenitor cell, requires both cell signaling and asymmetric cell division. At the four-cell stage, a polarity-inducing signal from the P2 cell is required for the EMS cell to divide asymmetrically to produce an anterior daughter MS, and posterior daughter E. In the absence of signal, the EMS cell divides symmetrically to produce two daughters that adopt the MS fate. This thesis describes the identification and analyses of seven genes required to tranduce this polarity-inducing signal and specify endoderm formation. The mom-1, mom-2, mom-5, apr-1, and wrm-1 genes are homologous to components of the Wnt/Wingless signal transduction pathway, and the mom-4, and lit-1 genes are related to components of the mitogen-activated protein kinase pathway. Biochemical analysis of these signaling molecules reveal a novel convergence of these pathways at the level of the LIT-1 and WRM-1 proteins, which appear to function as a kinase complex and are required for the downregulation of POP-1. Together these genes constitute components of a complex genetic pathway required for specification of the E cell fate.

The immunological mechanisms involved in virus-induced hepatitis were examined by measuring the cytotoxic capabilities and the morphological and antigenic phenotypes of leukocytes isolated from the livers of virus-infected mice. Large granular lymphocytes (LGL) of both natural killer (NK) cell and cytotoxic T lymphocyte (CTL) phenoytpes [phenotypes] accumulated in livers of mice infected with lymphocytic choriomeningitis virus (LCMV) of either the nonhepatotropic Armstrong strain (LCMV-ARM) or the hepatotropic WE strain (LCMV-WE). NK cell activity and LGL number increased 3- to 4-fold between days 1 and 5 postinfection (p.i.). These LGL were characterized as NK cells on the basis of cell surface antigens, kinetics of appearance, target cell range, and morphology. By day 7 p.i., virus-specific, H-2-restricted, Thy-1+, Lyt-2+CTL activity was present in the liver, and its appearance correlated with a second wave of LGL accumulation. Total CTL activity, leukocyte numbers, and CTL/LGL numbers were at least 5-fold higher in the livers of LCMV-WE-infected mice than in the livers of LCMV-ARM-infected mice. Mice infected with the cytopathic viruses, mouse hepatitis virus and murine cytomegalovirus, experienced greater increases in NK/LGL by day 3 p.i. than did mice either infected with LCMV or injected with poly I:C. The early and late accumulations of LGL in the virus-infected liver were associated with the appearance of two waves of LGL with blast cell morphology expressing the phenotypes of NK cells and CTL, respectively. Thus, the organ-associated accumulation, blastogenesis, and in situ proliferation of cytotoxic LGL provide a means for the localization and site-specific augmentation of a host's cell-mediated antiviral defenses. The mechanism of inhibition of virus synthesis in vivo by immune splenocytes containing virus-specific CTL was examined in mice dually infected with two different viruses and then adoptively immunized with spleen cells immune to one of the two viruses. Only the titer of the virus to which the splenocytes were immune was reduced in titer, and no nonspecific antiviral effect was seen on the titer of the 'bystander' heterologous virus. These data are consistent with an in vivo mechanism of CTL-mediated antiviral resistance involving direct cytotoxicity rather than release and dissemination of antigen-nonspecific antiviral factors, such as interferon, following recognition of appropriate viral antigen.

Este estudo aborda a formação em psicologia em contexto de intervenção num projeto de extensão acadêmica. O contexto de pesquisa envolve experiências com um programa de trabalho educativo que atende jovens que cumprem medidas socioeducativa e/ou protetiva e equipes que operam essa política pública, conforme o Estatuto da Criança e do Adolescente. Esta demanda da comunidade, enunciada na universidade através da extensão acadêmica, diz de uma produção social contemporânea brasileira que força um encontro entre a vida destes jovens e os modos de formar-praticar psicologia neste contexto. A problematização do processo de formação em psicologia nessas práticas é construída com os conceitos de experimentação, enunciação coletiva e subjetivação, no diálogo com Gilles Deleuze, Félix Guattari e Michel Foucault. Ao criar um regime de visibilidade "do não saber o que fazer" que acompanha a formação e a produção de conhecimento, como paradoxo que inventa outros modos de formar-praticar psicologia, se dá também a interlocução com Jacques Rancière e sua obra "O mestre ignorante". Com a indagação filosófica e sob a orientação da pesquisa-intervenção, foi utilizada uma ferramenta metodológica construída na experiência do grupo de trabalho da psicologia (professora, bolsistas e estagiários) nessas atividades de extensão, com o uso de uma modalidade de escrita em ambiente à distância, através de listas de discussão. A relevância deste processo vincula-se diretamente a uma proposta pedagógica e metodológica própria ao contexto e objetivo do uso deste tipo de ferramenta numa experiência de formação em ensino superior orientada pelo Laboratório de Linguagem, Interação e Cognição (LELIC) da Faculdade de Educação da UFRGS. Esse modo de escrever, denominado de diário coletivo, tem como pragmática a enunciação coletiva de matérias de expressão que emergem no agenciamento de uma psicologia que inventa sua prática na relação com as micropolíticas juvenis. Com essa matéria de expressão foram produzidas cartografias de práticas institucionais e práticas de si de uma formação em psicologia orientada pelo princípio ético-estético-político. Ao cartografar o "não saber o que fazer" no processo de formar psicólogos encontra-se a potencia de um paradoxo que força o pensamento e inventa uma psicologia que forma e se forma na composição de cartografias de um língua menor da psicologia. Assim, é construído um diálogo com formulações teórico-metodológicas da psicologia brasileira que afirmam possibilidades de intervenção nas zonas de interferência da esquizo-análise. / This study approaches higher education in psychology in the context of an intervention in a higher academic extension project. The research context involves experiences with an educative work program that supports young people in fulfilling socioeducational and/or protective measures and the work groups that operates in this public policy, as praised by ECA (Child and Adolescent Statute). This community need, enunciated at the university through the academic extension program, describes a Brazilian social contemporary production that forces a meeting between the life of these young people and the ways to become and practice psychology at this field. The problematization of higher education psychology process in these practices is constructed with the concepts of experimentation, collective enunciation collective and subjectivation, in the dialogue with Gilles Deleuze, Félix Guatarri and Michel Foucault. In creating a visibility regime of "not knowing what to do", that follows the formation and production of knowledge, as a paradox that invents other ways of become and practice psychology, it gives also a interlocution with Jaques Rancière and his work "The ignorant Master". Within the philosophical question and under the intervention research orientation, it was used a methodological tool built upon the experience of the work group in psychology course (teachers, fellowship and internship students) on these extension activities, with the use of a written modality in distant environment, trough discussion lists. The relevance of this process is directly associated to a pedagogical and methodological proposal, specific to the context and aim of using this type of tool in an experience of higher education, oriented by Cognition, Interaction and Language Laboratory (CILL) of Education School of Federal University of Rio Grande do Sul. This way of writing, named collective diary, has as its pragmatic a collective enunciation of expressive materials that emerges in the assemblage of a psychology that invents its practices in the relation with youth micropolitics. With this expression material, institutional and self practice cartographies were produced, of a academic education in psychology orientated by the politic-aesthetic-ethic principle. In the act of cartograph the "not knowing what to do" in the process of academic education in psychology it finds the power of a paradox that forces the thinking and invents a psychology that educates and educates itself in the cartography composition of minor language in psychology. Thus, a dialogue is constructed with theoric-methodological formulations of Brazilian psychology that states possibilities of intervention in the interferences zones of schizoanalyses.