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Les multi-thérapies actuelles permettent de maintenir l’infection au VIH-1 sous contrôle, mais malheureusement n’entraînent pas l’éradication du virus du fait de l’existence de réservoirs cellulaires, où le virus est intégré de façon latente. Les cellules microgliales, cibles privilégiées du VIH-1 dans le cerveau, sont les macrophages résidents du système nerveux central et ont été décrites comme un réservoir cellulaire avec une longue durée de vie. Ce genre de cellule, infectée de façon latente, apparaît comme un des principaux obstacles à l’éradication. Ainsi, la compréhension des mécanismes sous-jacents impliqués dans l’extinction de la transcription virale, semble une étape cruciale afin de parvenir à purger ces réservoirs. Notre laboratoire à déjà montré l’importance du répresseur transcriptionnel CTIP2 dans l’établissement et le maintien de la latence dans ces cellules. Dans le cadre de ma thèse je me suis intéressé à deux autres facteurs cellulaires, LSD1 et HIC1. Au cours de mes travaux, j’ai mis en évidence le rôle répresseur de ces protéines sur la transcription virale dans les microglies. LSD1 coopère avec CTIP2 pour promouvoir l’établissement de marques épigénétiques au niveau du promoteur viral pour induire la mise en place d’hétérochromatine. LSD1 est à l’origine du recrutement de CTIP2, mais aussi d’un autre complexe multiprotéique, COMPASS. A la différence de CTIP2 et LSD1, le suppresseur de tumeur HIC1 est un perturbateur du transactivateur viral TAT. HIC1 est préalablement modifié post-traductionnellement par la déacétylase SIRT1 et va ensuite contrecarrer l’activité de TAT afin d’empêcher la réactivation de la transcription du virus. Ainsi, tandis que LSD1 et CTIP2 favorise l’établissement de la latence, HIC1 permet quant à lui d’entretenir cet état du provirus dans les cellules microgliales. Les travaux présentés ici mettent en évidence deux nouveaux facteurs de la restriction de l’expression virale et permettent de définir de nouvelles cibles thérapeutiques potentielles pour les stratégies de purge des réservoirs. / Even though current multitherapies maintain HIV infection under control, they unfortunately do not achieve viral eradication due to the existence of latently infected cell reservoirs. Microglial cells are resident macrophages and the main HIV-1 target in brain. They have been described as a long-lived HIV-1 cell reservoir, and so appear as a one of the main obstacle to viral clearance. Thus, understanding of the mechanisms implicated in the establishment and maintaining of viral latency in these cells is a critical step on the way towards an HIV cure. Our team already demonstrated the implication of the cellular transcription factor CTIP2 in the establishment of HIV-1 silencing. In this work, I present two other cellular factors, LSD1 and HIC1 as new HIV-1 transcriptionnal expression inhibitors in microglial cells. LSD1 cooperates with CTIP2 to promote the establishment of epigenetic marks associated to heterochromatin structure at the viral promoter. LSD1 act as an anchoring plateform for CTIP2, and so the CTIP2-associated mutli-enzymatic chromatin remodeling complex, but also recruits the COMPASS methyltransferase complex. Unlike CTIP2 and LSD1, the tumor suppressor HIC1 disrupts the TAT-mediated transactivation cycle. HIC1 is beforehand modified post-translationnaly by the deacetylase SIRT1 and then counteracts TAT activity in order to limit viral transcription reactivation. Thus, while CTIP2 and LSD1 favour latency establishment, HIC1 maintains provirus silencing in microglial cells. All together, the results presented in this work introduce two new viral expression restriction factors and new potential therapeutic targets in reservoir purge strategies.

This diploma thesis makes use analytical methods of the Grounded theory to explore the theme "Reflection of relationship experiences by women in imprisonment". The goal of this thesis is qualitatively describing relationship experiences by women offenders of criminal activity and contribute to a deeper understanding of the psychosocial aspects of crime. Because the method of Grounded theory is chosen, which in a qualitative way makes it significant. Methods of data collection were chosen in the form of an interview and test method of the Thematic- apperceptive test. The research sample consists of five women, who are in the prison. Three levels of coding were used to analyze the interviews. The TAT analysis was followed by a qualitative method in the form of interpretation. The main topics covered include unsatisfied childhood relationships, rejection of guilt, the use of neutralizing techniques to maintain a positive self- image and passive role in life. Keywords Attachment, conscience, criminal behavior, criminal motivation, guilt, psychic development

Os vírus são eficazes na transferência de genes em células devido aos seus mecanismos especializados. No entanto, vírus como veículos de entrega de genes podem acarretar em problemas, particularmente quando proposto para reprogramar células somáticas em células-tronco pluripotentes induzidas (iPS) visando utilização terapêutica. No presente estudo, procurou-se desenvolver um sistema alternativo para entregar diretamente proteínas nucleares (Oct4, Sox2, KLF4, e c-Myc) fusionadas com o domínio de transdução de proteína TAT, para promover a reprogramação de fibroblastos embrionários de camundongos (MEF) ou células mesenquimais derivadas de tecido adiposo humano (hASC) em células iPS. Primeiramente o PTD TAT ou TAT- foi fundido a proteína verde fluorescente (GFP) como modelo para prova de princípio e padronização detalhada. Inesperadamente, TAT-GFP produzido e secretado pelas células NIH-3T3 produtora não foi capaz de ser detectado no meio de cultura por verificação quantitativa fluorimétrica, nem foi capaz de ser detectada em células-alvo, por citometria de fluxo, depois de co-cultura em transwells. Essa observação pode ser explicada por: (1) ineficiência desse tipo de célula em secretar proteínas e (2) falta de resistência à clivagem por endoproteases furinas. Para contornar esses fatores limitantes usou-se citometria de fluxo para avaliar as melhores condições para a transfecção por seis diferentes tipos de células (CHO, NIH-3T3, HT1080, HEK-293A, HEK-293t e COS-7) com TAT (modificada para ser resistente à furinas) fundido a GFP. Células 293t-TAT-GFP exibiram a maior eficiência de transfecção e também de secreção. O mesmo pôde ser observado para as seis linhagens celulares expressando fatores de transcrição nucleares TAT, determinados por ELISA. Em seguida, diferentes estratégias de entrega foram testadas. A primeira foi baseada na co-cultura de uma mistura de células produtoras com MEF ou hASC. No entanto, não foi possível observar a reprogramação devido à morte celular. A segunda foi baseada na concentração de meio condicionado de cultura de células por centrifugação usando colunas Amicon, trocando o meio a cada 24h, em quatro ciclos. No entanto, apesar da presença de algumas colônias após 20-30 dias, nenhuma colônia verdadeira iPS foi obtida. Na sequência, as células foram tratadas com cada proteína de forma independente, e as demais foram substituídas pelo retrovírus correspondente, trocando meio a cada 72h, em quatro ciclos. Essa estratégia, apesar de permitir verificar a função de cada proteína, também não resultou em reprogramação. Este achado pode ser explicado pela diferenciação celular induzida por BCS, que também é concentrado no processo. Assim, passou-se a adaptação de \"células produtoras\" em condições de cultura livre de soro, para enriquecer a produção dos fatores nucleares individuais, necessários para a reprogramação. A otimização sistematizada deste processo está sendo realizada em parceria com o IPT e deve resultar em quantidades de proteína de fusão suficientes para o teste final da hipótese proposta. Em conjunto, são apresentados os dados da geração de linhagens celulares expressando estavelmente os vários fatores de transcrição e estratégias para melhorar a eficiência necessária para a produção iPS. Esta nova estratégia garante uma produção eficiente de TAT fundida a fatores nucleares de reprogramação e sua eficácia para promover a reprogramação de células somáticas de maneira livre de vírus merece ser investigado futuramente / Viruses are effective at transferring genes into cells by its specialized mechanisms. However, viruses as gene delivery vehicles entail problems, particularly when proposed to reprogram somatic cells into induced pluripotent stem cells (iPS) for therapeutic uses. In the present study, we aimed to develop an alternative system for directly delivering nuclear proteins (Oct4, Sox2, Klf4, and c-Myc) fused with TAT protein transduction domain to promote reprogramming of mouse embryonic fibroblasts (MEF) or human adipose tissue derived mesenchymal cells (hASC) into iPS cells. First TAT- or TAT- PTD was fused to green fluorescent protein (GFP) as a proof of principle model and for detailed standardization. Unexpectedly, TAT-GFP produced and secreted by NIH-3T3 producer cells was not detected in the culture medium by quantitative fluorimetric verification, nor detected on target cells, by flow cytometry, after being co-cultured using transwells. This observation maybe explained by: (1) inefficiency of this cell type to be transfected and to secrete proteins and (2) lack of resistance to furin endoproteases cleavage on Golgi of TAT sequence. To circumvent these limiting factors we used flow cytometer to assess the best conditions for transfection in six different cell types (CHO, NIH-3T3, HT1080, HEK-293A, HEK-293t and COS-7) with TAT- (a modified PTD to be resistant to furin endoproteases) fused to GFP. 293t-TAT-GFP cells displayed the highest transfection efficiency and secretion levels. The same could be observed for the six cell lineages expressing TAT- nuclear transcription factors, determined by ELISA.Next, different delivery strategies were tested for TAT- nuclear transcription factor system. Co-culturing a mix of producer cells with MEF or hASC resulted in not reprogramming and this was associated with cell death. The second was based on the use of microconcentrated conditioned cell culture medium, changed every 24h, in four cycles. However, despite the presence of some emerging colonies after 20-30 days, no true iPS colonies were obtained. Then, cells were treated with each protein independently, and the others were replaced by the corresponding retrovirus, changing cell medium every 72h, in four cycles. We verified the reprogramming potential of each protein, but no true colonies were obtained.One possibility for this finding is that BCS is also concentrated by centrifugation and may induce cell differentiation. To circumvent these problems, we have started the adaptation of producer cells in a serum-free culture condition to enrich the production of the individual factors required for reprogramming. This optimization process is taking place in collaboration with the IPT and shall result in large amounts of the fusion protein to finally test the proposed hypothesis. Altogether, we presented the generation of several cell lines stably expressing the transcription factors and strategies to improve the efficiency required for iPS production. This novel strategy guarantees efficient production of TAT-fused reprogramming nuclear factors and its efficacy to promote somatic cells reprogramming in a virus-free manner deserves to be further investigated

No contexto da pesquisa e utilização prática das técnicas de autoexpressão, o Teste de Apercepção Temática (TAT) apresenta reconhecidas vantagens. Apesar de linhas de pesquisa bastante desenvolvidas internacionalmente, não existem estudos atuais sobre as propriedades deste instrumento no Brasil, levantando a necessidade de conhecer seus alcances e limites nesse contexto cultural. Desse modo, o desenvolvimento de normas que descrevam o desempenho típico de uma população não clínica se mostra um importante passo inicial rumo à retomada da pesquisa com o TAT e sua adoção por profissionais. Tendo em vista que a validação das técnicas de autoexpressão se refere aos sistemas de classificação e não aos instrumentos em si, o presente estudo adotou, dentre a miríade de sistemas de categorização das histórias do TAT descritos na literatura, o sistema proposto por Monique Morval, que foi desenvolvido para estudantes e profissionais com pouca experiência com o TAT, utilizando pressupostos da Personologia de Henry Murray, Psicologia Cognitiva e Psicologia do Ego, possibilitando leituras objetivas e qualitativas do material. Considerando o potencial de utilização desse sistema por parte dos psicólogos brasileiros - visto sua semelhança com o atual sistema aprovado para uso pelo Sistema de Avaliação dos Testes Psicológicos (SATEPSI) do Conselho Federal de Psicologia - foram feitos aprimoramentos no assim chamado sistema morvaliano, possibilitando sua adoção no estudo normativo proposto pelo presente projeto. Tais aprimoramentos consistiram na revisão e adição de categorias e subcategorias, a partir de trabalhos brasileiros e internacionais sobre o instrumento. Desta forma, o presente estudo teve por objetivo desenvolver normas para o TAT (Sistema Morvaliano) em adultos, a partir de uma amostra não clínica, aleatória e estratificada por critérios de idade, sexo, escolaridade e nível socioeconômico (NSE) da cidade de Ribeirão Preto (SP). Os participantes foram 100 adultos (25 a 44 anos de idade), selecionados através de visita a domicílios sorteados em bairros de diferentes NSE. Foram realizadas entrevistas de avaliação psicológica individuais, utilizando um roteiro de entrevista semiestruturada, o Teste de Inteligência Geral Não-Verbal (TIG-NV) e 20 cartões do TAT, pré-selecionados de acordo com as recomendações do manual original do instrumento. As histórias do TAT foram categorizadas no sistema morvaliano revisado e seus dados passaram por análises estatísticas e sínteses qualitativas em busca de diferenças de desempenho relacionadas ao sexo, escolaridade e NSE. Os resultados mostram poucas diferenças entre os grupos que justifiquem a elaboração de normas específicas; apesar disso, foi identificada uma tendência (ainda que pequena) de o nível de escolaridade e o NSE favorecerem um melhor desempenho nas variáveis relativas à organização formal das histórias. São discutidas as implicações dos dados obtidos em termos do perfil normativo de desempenho nas variáveis do sistema morvaliano, suas evidências preliminares de validade e futuras direções para estudos sobre o TAT nesse sistema. / Within the context of research and practice with self-expression techniques, the Thematic Apperception Test (TAT) presents several advantages widely acknowledged. However, in spite of well-developed research with this instrument being seen in other countries, no recent Brazilian studies have been carried out up to date. Such situation arise the need of efforts in order to show the properties of the TAT in the current Brazilian cultural context, so that its strengths and weaknesses can be known. In this sense, the development of norms on the typical performance of a non-clinic population is an important first step toward resuming the Brazilian studies on the TAT, at the same time such norms could be used by applied professionals. Considering that the validation of self-expression techniques is related to classification systems (and not the instruments themselves), the present project adopts - among the myriad of categorizing systems for TAT stories - the one proposed by Monique Morval, which was developed for students and professionals with no experience with the TAT. Such system adopts assumptions from Henry Murray\'s Personology, Cognitive Psychology and Ego Psychology, providing both objective and qualitative data on the stories. Due to resemblance of this system with the one currently approved for use by the Evaluation System of Psychological Tests (Sistema de Avaliação dos Testes Psicológicos, SATEPSI) of the Brazilian Federal Council of Psychological, there is a potential for the adoption of such system by Brazilian psychologists. In order to carry out the present project, the now called morvalian system was improved by revising and adding new categories and subcategories, which was based on both Brazilian and international studies regarding. The present project, thus, aimed to develop norms for the TAT (morvalian system) in adults from a randomized, non-clinical sample, which was stratified in terms of age, gender, schooling and socialeconomical levels. The study was carried out in the city of Ribeirão Preto (Brazilian state of São Paulo), with a n = 100 sample (25-44 years of age). Participants were invited to take part of the study during visits to randomly selected houses, located in regions of different socialeconomical levels. Participants were individually assessed, using a semi-structured interview script, a measure of intelligence (the TIG-NV - General Non-Verbal Intelligence Test) and 20 TAT cards, selected according to the original manual of this instrument. Data was compiled with the morvalian system\'s categories and went through both statistically and qualitative analyzes in search for performance differences related to gender, schooling and socialeconomical levels. The results showed few differences across the groups, which do not support for the elaboration of specific norms. However, results also showed a significant (although small) trend for better performance of groups with better schooling and socialeconomical levels on the variables related to stories\' formal organization. Such results are discussed in terms of their implication for describing the normative performance on the morvalian system, preliminary validity evidence and future directions for the TAT within this system.

Este Doutorado teve como objetivo o entendimento sobre a construção da conjugalidade homossexual feminina e masculina, a partir da eleição de casais longevos, com mais de vinte anos de relacionamento. A partir de coleta de dados por meio de entrevista semidirigida com o casal, acrescida da aplicação de pranchas previamente selecionadas do teste projetivo TAT (Teste de Apercepção Temática), individualmente, sob o método clínico-qualitativo, foram analisados quatro casais, dois masculinos e dois femininos, com e sem filhos vindos de relação heterossexual anterior, sob a perspectiva da psicanálise vincular. Os resultados apontaram para casamentos românticos, com vínculos protetivos e de afeto, porém com influências pós-modernas no que diz respeito ao fato de estarem juntos somente pelo desejo, com flexibilização das performances de gênero e democratização das relações. Os quatro casais demonstraram empenho na construção e manutenção do vínculo conjugal e harmonia no convívio, ressaltando a singularidade de cada um. Esses casais concretizaram suas relações amorosas em uma época não permissiva e patologizante da homossexualidade, fazendo uso do disfarce e da vida dupla como estratégia de sobrevivência, atitude presente ainda na vida de dois dos quatro pares. Essa característica em particular pode fazer com que casais gays necessitem de maiores espaços de fusionamento do que os heterossexuais, para que possam se fortalecer ante os desconfortos sociais pelos quais passam - principalmente os que têm filhos de uniões heterossexuais anteriores. Neste caso, além da própria separação, há também o confronto com a orientação sexual do ex-parceiro. Somente um casal de homens havia se casado legalmente, por temor aos bens conquistados frente aos filhos de um deles; o de mulheres com filho também havia legitimado a relação com União Estável e testamento. Os dois casais sem filhos não haviam providenciado nenhuma legitimação e nem estavam preocupados com isso. A herança heteronormativa que receberam foi adaptada aos seus estilos de vida, embora não tenha havido um espaço familiar e social a ser ocupado a homossexualidade e a homoconjugalidade, embora vistas, são ainda muitas vezes não-nomeadas ou reconhecidas. Não houve referências a traições, sendo que os filhos foram os deflagradores de crises em dois dos casais, ambas superadas. Os resultados alcançados confirmam a teoria psicanalítica vincular no sentido de enfatizar o conceito de alteridade, entre um e outro, como base para a compreensão desse tipo de conjugalidade / This Doctoral thesis aimed to understand the construction of female and male homosexual conjugality by selecting long-lived couples, with more than twenty years of relationship. Based on data collection through semi-structured interviews with the couples and the use of previously selected cards of the projective measure TAT (Thematic Apperception Test), under the clinical-qualitative method, four couples - two male and two female, with and without children from previous heterosexual relationships - were analyzed under the perspective of linkage psychoanalysis. Results point to romantic marriages, with protective and emotional bonds, but under post-modern influence based on the fact they are together only by their desire, with flexibility of the gender performances and democratization of the relations. The four couples demonstrated a commitment to building and sustaining the conjugal bond as well as coexisting in harmony, highlighting the individuality of each one. These couples materialized their love relationships at a nonpermissive and pathologizing time for homosexuality, using disguises and double lives as a strategy for survival, an attitude still present in the lives of two out of the four couples. This characteristic, in particular, may lead a gay couple to need bigger spaces of fusioning when compared to heterosexual couples, so that they can strengthen themselves in the face of the social discomfort which they go through particularly the ones who have kids from previous heterosexual relationships. In this case, in addition to the divorce itself, there is also the confrontation related to the sexual orientation of the ex-partner. Only one couple of men had legally married due to the fear of losing the assets acquired to the children of one of them; the couple of women with a child had also legitimated their relationship through common-law marriage and testament. Both couples without children hadnt sought any type of legal legitimacy nor were worried about it. The heteronormative heritage they received was adapted to their lifestyles, although there hadnt been a family and social place to be occupied homosexuality and homo-conjugality, while seen, are often not named nor recognized. There were no references to betrayals, although, among two of the couples, the children had been the triggers of already overcome crises. The findings confirm the linkage psychoanalysis theory, which emphasizes the concept of otherness, between one and another, as a basis to comprehend this type of conjugality

L'infection par le virus de l'immunodéficience humaine (VIH) est associée à la survenue de lymphomes B chez des patients infectés et l’incidence de certains lymphomes reste élevée même chez les individus infectés dont la fonction immunitaire est reconstituée sous traitement antirétroviral combiné. La contribution du VIH-1 à l'oncogenèse des cellules B reste donc énigmatique. Le VIH-1 induit un stress oxydant et des dommages à l'ADN (DA) dans les cellules infectées via de multiples mécanismes. Cependant il n'infecte pas les lymphocytes B. En revanche, la protéine virale Tat qui circule dans le sang des individus infectés est capable de pénétrer spontanément dans des cellules non infectables par VIH. Nous avons détecté des niveaux élevés d’espèces réactives de l’oxygène (ROS), principalement mitochondriales, et des DA dans les cellules B d'individus infectés par le VIH. Nous avons ainsi émis l'hypothèse que Tat pourrait induire des DA oxydants dans les cellules B et favoriser ainsi l'instabilité génétique et la transformation maligne de ces cellules.Dans des cellules B isolées à partir du sang périphérique de donneurs sains et incubées en présence de protéine Tat recombinante, un stress oxydant a été induit, la capacité antioxydante a diminué avec la diminution de taux du glutathion, le facteur de transcription NF-κB a été activé, et sont apparus des DA accompagnés d'aberrations chromosomiques. En outre, tous les effets induits par Tat dépendaient de son activité transcriptionnelle. Dans le but de mieux comprendre le(s) mécanisme(s) d’action de Tat chez les patients séropositifs, des extraits bruts de plantes endémiques du Liban ont été utilisés pour leur potentiel antioxydant. L’effet pro-oxydant de Tat a été contrecarré, le stress oxydant inhibé ainsi que les DA induits par la protéine virale. En conclusion, nous proposons que les dommages oxydants causés à l’ADN et les aberrations chromosomiques induites par Tat correspondent à de nouveaux facteurs oncogéniques favorisant le développement de lymphomes B chez les individus infectés par le VIH-1. / An infection with the Human immunodeficiency virus (HIV) is associated with Bcell lymphomas in infected patients. The incidence of some lymphomas remains elevated in HIVinfected individuals whose immune function has been reconstituted under combined antiretroviral therapy. Its contribution to B-cell oncogenesis cells remains enigmatic. HIV-1 is known to induce an oxidative stress and DNA damage (DD) in infected cells via multiple mechanisms. However, it does not infect B lymphocytes. This contrasts with the viral transactivator protein Tat which circulates in the blood of infected individuals and spontaneously penetrates even non infectable cells. We have detected high levels of reactive oxygen species (ROS), mainly from mitochondria, and DDs in Bcells of HIV-infected individuals. We have thus hypothesized that Tat could induce oxidative DD in B-cells thereby promoting genetic instability and malignant transformation in these cells.In B-cells isolated from peripheral blood of healthy donors and incubated in the presence of purified recombinant protein Tat, an oxidative stress has been induced, the antioxidant capacity was decreased due to diminished glutathione levels, the transcription factor NF-κB was activated, and DD and chromosomal aberrations induced. All the effects induced by Tat were shown to depend on its transcriptional activity. To better understand the mechanism(s) of action of this viral protein, crude extracts from endemic plants of Lebanon were tested for their antioxidant potential. The prooxidative effect of Tat was inhibited, as well as the DD and chromosoml aberrations induced by the viral protein. In conclusion, we propose that the oxidative DNA damage and chromosomal aberrations induced by the Tat protein correspond to novel oncogenic factors that favor the development of B-cell lymphomas in HIV-1 infected individuals.

L'adolescence, marquée par l'éclosion de la puberté et la résurgence des pulsions sexuelles et agressives, engage, un travail interne lié aux transformations psychiques et à l'émergence de la sexualité génitale. La puberté peut alors faire intrusion et trauma, blessant le sujet qui est plus ou moins prêt à supporter la contrainte au changement induit par le processus pubertaire. En référence au modèle théorique psychanalytique, nous nous intéressons dans cette étude à la manière dont les adolescents font face aux afflux d'excitations, tant externes qu'internes, selon un traitement psychique, par un travail de mentalisation et de symbolisation, ou bien comportemental ou somatique, par le langage du corps ou le recours à la sensorialité. En effet, quelles que soient les capacités d'élaboration mentale de l'adolescent, une vulnérabilité transitoire de l'appareil mental est attendue à cet âge de la vie. Notre travail se propose ainsi d'explorer le traitement de l'excitation à l'adolescence, mis en évidence par l'étude de la qualité de quatre mouvements psychiques : le narcissisme, le système pare-excitation, le recours au corps par la sensorialité et le langage du corps, ainsi que les processus de pensée à travers l'étude de la mentalisation et de la symbolisation. Notre objet de recherche questionne ainsi la qualité du traitement de l'excitation, à travers la mise en perspective de ces différentes dimensions conceptuelles, susceptible d'exposer une meilleure approche processuelle de l'adolescence. Partant de l'hypothèse principale selon laquelle le traitement de l'excitation est multifactoriel, l'objectif de cette étude est de dégager la manière dont l'articulation des différents concepts étudiés est à même de rendre compte, de manière plus sensible, du traitement de l'excitation à l'adolescence. La méthodologie projective a été choisie pour mettre à l'épreuve cette hypothèse à l'aide de grilles référées aux quatre dimensions précitées. Nous avons rencontré 17 adolescents tout-venants âgés de 14 à 18 ans auxquels nous avons proposé le Rorschach et le TAT. Dans une approche comparative, nous avons étudié le traitement de l'excitation auprès de deux groupes d'âge (14-16 ans et 16-18 ans). Les résultats mettent en avant des différences dans le traitement de l'excitation à l'adolescence entre les deux groupes d'âge, les plus jeunes ayant préférentiellement recours à l'inhibition, les plus âgés étant davantage en mesure de mentaliser et symboliser l'excitation. Conformément à notre hypothèse générale, l'analyse projective des quatre dimensions de notre travail permet une approche plus fine pour chaque adolescent des spécificités du traitement de l'excitation. / Adolescence, marked by the emergence of puberty and the resurgence of sexual and aggressive drives, engages an internal work linked to psychic transformations and to the emergence of genital sexuality. Puberty can therefore intrude and cause trauma, hurting the subject who is more or less ready to bear the constraint to change induced by the pubertal process. In reference to the theoretical psychoanalytic model, we are interested in the study of the way in which adolescents are confronted with the influx of excitations, both external and internal, through a psychic treatment, by a work of mentalisation and symbolisation, or behavioural, or somatic, by the language of the body or the use of sensoriality. Indeed, whatever the mental capacity of the adolescent, a transient vulnerability of the mental apparatus is expected at this age of life. Our work thus proposes to explore the treatment of excitation in adolescence, evidenced by the study of the quality of several psychic movements: narcissism, protective-shield system, sensoriality and body language, as well as the processes of thought through the study of mentalisation and symbolisation. Our research object thus questions the quality of the treatment of excitation, through the putting into perspective of these four conceptual dimensions, likely to expose a better process approach of adolescence. On the basis of the main hypothesis that the processing of the excitation is multifactorial, the objective of this study is to determine how the articulation of the different concepts studied is able to account more sensibly for the treatment of excitation in adolescence. The projective methodology was chosen to test this hypothesis using grids referred to the above four dimensions. We met 17 teenagers aged 14 to 18 years old who passed the Rorschach and TAT. In a comparative approach, we studied the treatment of excitation with two age groups (14-16 years and 16-18 years). The results highlight differences in the treatment of adolescent arousal between the two age groups, with the younger ones preferring inhibition, the older age groups being more able to mentalise and symbolize the excitation. According to our general hypothesis, the projective analysis of the four dimensions of our work allows a finer approach for each adolescent to the specificities of the treatment of excitation.

L'objet de ma recherche porte sur le désir d'enseigner qui interroge le choix d'un métier et la rencontre actuelle entre l'adulte et l'enfant, soit dans l'enseignement ordinaire soit pour les enseignants spécialisés qui choisissent de se confronter aux troubles graves des apprentissages et au handicap. Il s'agit d'explorer les origines du désir pris dans le discours spontané des enseignants appuyé sur des entretiens cliniques de recherche et dans un autre registre saisir la dynamique pulsionnelle, les choix identificatoires, les processus d'idéalisation et les mouvements fantasmatiques qui peuvent se déployer à travers l'utilisation des méthodes projectives. Pris dans la « métaphore vive » du mythe de Pygmalion déconstruit par Kaës (1973) à partir du fantasme de fustigation décrit par Freud en 1919, enseigner appelle un scénario fantasmatique mobile où les emplacements et les identifications entre l'enfant et l'adulte sont permutables, réversibles dans un retournement des positions actives et passives du sujet. Le désir d'enseigner s'inscrit dans une dimension narcissique patente actualisant le sentiment de continuité d'existence et la quête d'une image de soi idéale mais dans le même temps, se joue aussi la quête de la différence, ancrée dans l'infantile et le sexuel (Chabert, 2011) convoquant inévitablement la différence des sexes et la bisexualité psychique. Enfin, dans la réciprocité du désir d'apprendre et de savoir, enseigner à l'enfant, c'est aller à la rencontre de l'Inconnu posé par Rosolato (1978) comme une relation fondamentale entre le désir et l'idéal qui interroge l'inconnu en soi, le mystère de nos origines convoquant les fantasmes originaires rattachés aux questions de la naissance, de la mort et de la scène primitive. Le Rorschach et le TAT, ces autres objets énigmatiques qui font émerger des « arrêts » sur image et l'insistance de la répétition à certaines planches, mobilisent, dévoilent des enjeux fantasmatiques dans un écho singulier avec ce qui se joue dans la rencontre entre l'adulte et l'enfant à l'âge œdipien, celui de la latence et de l'adolescence. / This research focuses on the desire to teach that motivates the choices of a career and of the mutual encounter between the adult and the child, either in an ordinary school or a special educational setting for learning difficulty or severe disability needs. It aims at exploring the origins of the desire of teachers, on the one hand, through clinical research interviews, and on the other hand, by focusing on the underlying dynamics of drives, identifications and fantasies through projective testing. Caught up in the "rule of metaphor" of the Pygmalion myth, which was revisited by Kaës (1973) based on Freud's child beating fantasy concept (1919), teaching addresses mobile fantasized scenarios where identifications between the adult and the child are intertwined and reversible, turning around active and passive positions of the subject. The desire to teach is part of an evident narcissistic domain, restoring the sense of continuity of being and of an ideal self-image. However, the quest for differentiation, rooted in infantile psychosexuality (Chabert, 2011), is also played out, inevitably summoning gender differences and psychic bisexuality. Lastly, given the reciprocity between the desire to impart and to learn, teaching a child means encountering the Unknown which Rosolato (1978) defined as the fundamental relationship between the desire and the ideal; a relationship that questions the unknown in oneself, the mystery of one's origins and evoke primal fantasies which relate to questions of birth, death and primitive scenes. Enigmatic tools, such as the Rorschach and the TAT, produce fixated images and insistent repetitions on specific cards which summon fantasies echoing those at play in the encounter between the adult and the child of oedipal, latency or adolescent age.

L'immunité innée et l'immunité adaptative constituent les deux volets du système immunitaire. Contrairement à l'immunité adaptative qui utilise un vaste répertoire de récepteurs spécifiques obtenus par réarrangements géniques, l'immunité innée utilise un nombre réduit de récepteurs appelés " Pattern Recognition Receptors " ou PRR. Les PRR reconnaissent des motifs hautement conservés et exclusivement exprimés par les micro-organismes, et appelés " Pathogen-Associated Molecular Patterns " ou PAMP. Les PRR sont soit associés aux cellules (impliqués dans l'endocytose et/ou la signalisation), soit solubles (impliqués dans l'élimination des micro-organismes et du soi modifié). Les pentraxines courtes (SAP et CRP) et longues (PTX3) sont des PRR solubles impliqués dans la capture du non-soi et/ou du soi modifié et facilitent leur élimination par les phagocytes. La protéine Tat du VIH-1 est indispensable à la synthèse du génome viral. Sa forme soluble, sécrétée par les cellules infectées, régule de nombreuses fonctions cellulaires. Cependant, la nature des structures de fixation de Tat soluble aux cellules reste mal connue. Nous avons montré que Tat interagit sélectivement avec les pentraxines SAP, CRP et PTX3. Cependant, et de manière inattendue, nous avons observé que seule la protéine CRP augmente la transcription in vitro du VIH-1 induite par Tat en favorisant son accumulation nucléaire. Nous avons également observé une influence significative de Tat et des complexes Tat/pentraxines sur la différenciation de monocytes en cellules dendritiques (DC). L'ensemble de ces données met en évidence un nouveau mécanisme mis en jeu par le VIH pour exploiter le bras humoral de l'immunité innée et échapper au système immunitaire. Des données préliminaires suggèrent également un rôle potentiel de Tat dans l'acquisition d'un phénotype immunosuppresseur par les cellules dendritiques. En parallèle, dans le cadre d'un projet fédératif portant sur la régulation d'expression du FcγRIII (CD16), nous avons montré que les cytokines IL-1β, IL-6, IL-10 et IL-21 induisent non seulement l'augmentation d'expression de CD16 sur les monocytes/macrophages et son induction sur les DC, mais également son acquisition par la sous population monocytaire CD14+ CD16-. Ces données suggèrent donc un rôle de ces cytokines dans la modulation d'expression de CD16 par les cellules myéloïdes.