Um território, uma substância e três Políticas Públicas atuando sobre uma mesma população. O trabalho tem como objetivo oferecer uma análise das Políticas Públicas para usuários de Crack instaladas no território da \"Cracolândia\" paulista, localizado no Bairro da Luz (São Paulo-SP). A criação do Programa Crack É Possível Vencer em 2010, articulada à emergência de discursos que especulavam sobre uma possível epidemia e crescente interesse dos meios de comunicação sobre a população usuária, abriu a possibilidade de criação de espaços institucionais para que o Estado intervisse sobre os usuários de crack. Dentro desse contexto, e articuladas a esse Programa do Governo Federal, surgem duas Políticas Públicas: Programa Recomeço de gestão Estadual e Programa De Braços Abertos de gestão Municipal. As ações dessas duas políticas durante os anos 2014 e 2015 constituem o foco do recorte empírico do presente trabalho. O esforço de pesquisa foi no sentido de investigar como as novas Políticas Públicas que se propunham a operar no campo da Saúde Pública e do cuidado iriam se materializar no território, como o discurso institucional iria se traduzir enquanto práticas. Em especial, interessava observar se as novas ações iriam inibir o movimento histórico de higienização do território e expulsão dos usuários. Visando contemplar na pesquisa ponto de vistas, experiências e discursos que não se limitassem ao relato institucional, foram utilizadas três fontes de dados: pesquisas realizadas na região, reportagens e documentos lançados pela mídia e pesquisa de campo. Foi realizada uma leitura e descrição detalhada de três etnografias feitas na região, com o objetivo de comparar as intervenções passadas com o contexto atual; através da análise de duas personagens midiáticas, que surgiram nos meios de comunicação em 2015, traçou-se a imagem do usuário de crack que é veiculada socialmente. E através de observação participante no território, foram descritos os eventos acontecidos durante o período de tempo delimitado, distribuídos em três eixos: Saúde, Repressão e Resistência. À partir desse itinerário de pesquisa, foi elaborada uma discussão que pontua as diferenças entre o discurso e a prática. Dentre as considerações finais, destaca-se a diferença dos modelos de tratamentos propostos pelas Políticas Públicas internação e Redução de Danos e a forma como essa disputa se materializa no cuidado aos usuários de crack. Embora tenha ocorrido um crescimento de ofertas de saúde, também ocorreu um aumento progressivo no número de agentes de segurança e equipamentos de vigilância na Cracolândia, instaurando aquilo que é chamado de Confinamento dos usuários, composto de práticas de limpeza das ruas, retirada de bens dos usuários e filmagem dos usuários. Uma estratégia de gentrificação foi detectada e descrita, ação cujo protagonista é uma empresa de seguros que, no período delimitado, se mostrou excessivamente atuante no território, mobilizando as ações estatais. E por fim, também foram descritas as ações de resistência dos usuários frente à criação das Políticas Públicas e das outras formas de intervenção estatal, ações tais como a construção das favelinhas e a atuação dos profissionais e militantes da região. Espera-se que esse trabalho contribua para uma maior compreensão da Cracolândia paulista e forneça subsídios para que melhores Políticas Públicas sejam criadas no território. / One territory, one substance and three Public Policies acting on the same population. The work has as its goal to offer an analysis of the Pubic Policies for crack users installed in the São Paulos Cracôlandia territory, located in the Luz neighborhood ( São Paulo - SP). The creation of the program Crack é Possível Vencer, articulated on the emergence of speeches which speculated about a possible epidemic and growing interest on media about the users population, opened the possibility to the creation of institutional spaces to the State to intervene on crack users. Within this context, and within this context, and articulated to this program of the Federal Government, there are two Public Policies: Programa Recomeço of State management - and Programa De Braços Abertos- of Municipal management. The actions of these two policies during the years 2014 and 2015 are the focus of the empirical object of this work. The effort of the researching was in the sense of investigate with Public Policies which proposed to operate on the field of Public Health and care - they would materialize in the territory, as the institutional discourse would translate as practical. In particular, it was interesting to observe if the new actions would inhibit the historical movement of cleaning the territory and expulsion of members. Seeking to include in the research point of views, experiences and discourses that are not confined to institutional account, it was used three data sources: surveys conducted in the region, reports and documents released by the media and field research in the region, reports and documents released by the media and field research. It was done a reading and detailed description of three ethnographies done in the region, with the intend of comparing the past interventions with the current one; through the analysis of two characters that appeared in the media in 2015, it was drew up the crack user image that is conveyed socially. In addition, through the observation done in the territory, it was described the events that happened during a delimitated time, it was distributed I three areas: Health, Repression and Resistance. From this research itinerary was drawn up a discussion that punctuates the differences between theory and practice. Among the final considerations, there is the difference of treatment models proposed by Public Policies - hospitalization and Harm Reduction - and how this dispute materializes in the caring of crack users. Although there was an increasing in health offers, there was also a progressive increase in the numbers of security agents and surveillance gear in Cracolândia, establishing what is called users Confinement, through cleaning practices, removal of the users goods and recording of the users. One strategy of gentrification was detected and described, action which the protagonist is an insurance company which, in the delimitated period, showed overly active in the territory, mobilizing state actions. And at least, were also described the resisting actions of the users facing the creation of Public Policies and the other forms of state intervention, actions as the creation of little slums and the work of professionals and militants of the region. It is expected this work helps to a better comprehension of the São Paulos Cracolândia and provides subsidies for better public policies that are created on the territory.

Le régime de la responsabilité pénale du dirigeant décontenance par l’originalité des mécanismes juridiquespermettant sa mise en oeuvre. Cette responsabilité révèle des insuffisances tant au niveau de l’incriminationque de la répression. Alors que la première est affectée par de graves déficiences conceptuelles etfonctionnelles, la deuxième se démarque par une prééminence doublement perceptible. Cette dernière semanifeste, d’une part, par l’élargissement sans cesse croissant de la sphère de la répression, ainsi que par lamultiplication des acteurs potentiellement responsables. L’excès répressif s’illustre, d’autre part, par la placeréduite réservée à l’impunité. Il apparaît, en effet, que le dirigeant ne peut que très exceptionnellementinvoquer utilement les causes objectives et subjectives d’irresponsabilité de droit commun, ces dernièresétant généralement, soit inadaptées, soit dotées d’un impact limité à son égard. La restriction de l’impunitésemble par ailleurs corroborée par la quasi-imprescriptibilité de certaines infractions le visant. Cette politiquecriminelle fondamentalement axée sur la répression se révèle inefficace, voire contre-productive. Aussi, uneanalyse critique de la responsabilité pénale du dirigeant permet-elle d’en relever les insuffisances et d’ensouligner les contradictions. Elle conduit à s’interroger sur l’opportunité de la répression en droit pénal desaffaires et à redéfinir sur des bases plus cohérentes les critères devant gouverner le recours à la sanctionpénale à l’égard du dirigeant. Une telle redéfinition permet d’opérer un redéploiement de la répression versdes alternatives civiles à finalité répressive ou régulatrice / The criminal liability system of the leader disconcerts by the originality of the legal mechanisms allowing itsimplementation. That responsibility reveals insufficiencies as well on the level of the incrimination as ofrepression. Whereas first is affected by serious conceptual and functional deficiencies, the second isdissociated by a doubly perceptible preeminence. The latter appears, on the one hand, by wideningunceasingly crescent of the sphere of repression, like by the multiplication of the potentially responsibleactors. Repressive excess is illustrated, in addition, by the reduced place booked with impunity. It appears,indeed, which the leader can only very exceptionally call upon usefully the objective and subjective causesof irresponsibility of common right, these last being generally, either misfit, or equipped with an impactlimited in its connection. The restriction of impunity in addition seems corroborated by the quasiimprescriptibilityof certain infringements aiming it. This criminal policy basically centered on repressionappears ineffective, even against-productive. Also, a critical analysis of the criminal responsibility of theleader makes it possible it to raise the insufficiencies of them and to underline contradictions of them. Itresults wondering about the appropriateness of repression in criminal law of the business and in redefiningon more coherent bases the criteria having to control the recourse to the penal sanction with regard to theleader. Such a redefinition makes it possible to operate a redeployment of repression towards civilalternatives to repressive or regulating purpose.

Descreve e analisa os dados sobre repressão a livros considerados subversivos entre abril de 1964 a março de 1979, no Brasil. Os dados estudados são os autos de busca e apreensão cumpridos pela polícia política e exército para confiscar obras durante a Ditadura Militar e que fizeram parte de processos judiciais que chegaram ao Superior Tribunal Militar. Cerca de 707 processos foram resgatados e reunidos pelo Projeto Brasil Nunca Mais durante a Ditadura e estão disponíveis integralmente na internet desde 2013. A pesquisa abrange todos os resultados da busca de autos de apreensão de livros confiscados contra suspeitos. Ao todo foram encontrados 323 autos de busca e apreensão em 145 processos jurídicos, representando 20% (vinte por cento) da totalidade. A pesquisa tem dois momentos. O primeiro é uma análise descritiva dos dados presentes nos autos, em que é possível saber quantos livros foram apreendidos por ano, por organizações, pelo perfil dos atingidos e por quem executou as ordens. Os autos foram analisados como um conjunto desmembrado dos processos. O segundo é a análise do auto de busca e apreensão como parte do processo jurídico. A escolha do processo analisado foi feita porque os livros apreendidos constaram como prova para condenação do réu. As constatações finais da pesquisa foram três. A primeira é que ao se analisar os dados dos autos percebeu-se que eles revelam uma fotografia da ditadura militar, sendo possível fazer uma correlação da repressão sofrida pelas diferentes organizações de resistência e o confisco dos livros. A segunda constatação é que os agentes repressivos buscavam especificamente livros que pudessem incriminar os suspeitos, sendo instruídos para identificar quais livros poderiam ser tidos como subversivos. Por fim, a terceira observação é que os livros apreendidos tinham peso relativo dentro de cada processo. Às vezes figurando apenas como anexo e em outros casos sendo usados como prova para condenação do réu. Além das contribuições apresentadas acima, a pesquisa lista os títulos dos livros apreendidos para servir de consulta e referência para próximas pesquisas sobre o tema. / It describes and analyzes data on repression of books considered subversive between April 1964 and March 1979 in Brazil. The data studied are the seizure cases carried out by the political police and the army to confiscate books during the Military Dictatorship and which were part of legal proceedings that reached the Superior Military Tribunal. Almost 707 cases have been rescued and assembled by the Brazil Never Again Project during the dictatorship and is available on the internet since 2013. The search covers all the results for the warrants against suspects in which books were confiscated. In all, 323 search and seizure cases were found in 145 legal proceedings, representing twenty percent (20%) of the totality. The research has two moments. The first is a descriptive analysis of the data present in the records, in which it is possible to know how many books were seized per year, by organizations, by the profile of those affected and by those who executed the orders. The records were analyzed as a set dismembered of the processes. The second is the analysis of the search and seizure self as part of the legal process. The choice of the process analyzed was made because the books seized were evidence for the defendant\'s conviction. The final findings of the survey were three. The first is that when analyzing the data of the records it was noticed that they reveal a photograph of the military dictatorship, being possible to make a correlation of the repression suffered by the different organizations of resistance and the confiscation of the books. The second finding is that repressive agents specifically searched for books that could incriminate suspects and were instructed to identify which books might be considered subversive. Finally, the third observation is that the seized books had relative weight within each process. Sometimes appearing only as an attachment and in other cases being used as evidence for the conviction of the defendant. In addition to the contributions presented above, the research presents the list of the books seized to serve as a reference for future research on the subject.

Chez les eucaryotes, le génome est organisé en chromatine, une structure nucléoprotéique essentielle pour la régulation de l’expression génique ainsi que pour le maintien de la stabilité du génome. Les ciliés sont d’excellents organismes modèles pour étudier les mécanismes généraux qui maintiennent l’intégrité du génomes eucaryote. Chez Paramecium tetraurelia, la différentiation du génome somatique à partir du génome germinal est caractérisée par des événements massifs et reproductibles d’élimination d’ADN. D’une part, des éléments répétés (transposons,régions minisatellites), de plusieurs kilobases de long, sont imprécisément éliminés.D’autre part, 45000 séquences courtes et uniques, appelées IES, sont précisément éliminées au nucléotide près. Une classe de petits ARN, appelé scnRNAs, est impliquée dans la régulation epigénétique de l’élimination d’ADN, mais comment les scnRNA contrôlent l’élimination d’ADN reste mystérieux. Nous avons testé l’hypothèse selon laquelle une organisation particulière de la chromatine, en particulier des modifications post-traductionelles des histones associées à des formes répressives de la chromatine, est impliquée dans le processus d’élimination d’ADN. Nous avons montré que la triméthylation de l’histone H3 sur la lysine 9 et la lysine 27 (H3K9me3 et H3K27me3)apparaît transitoirement dans le noyau somatique en développement au moment où se produisent les événements d’élimination d’ADN. Nous avons identifié la protéine de type Polycomb, Ezl1, et montré qu’elle est une histone methyltransferase qui présente une dualité de substrat et catalyse à la fois la mise en place de K9me3 et K27me3 sur l’histone H3. Nous avons montré que la déposition de H3K9me3 et H3K27me3 dans le noyau en développement requiert les scnRNAs. Des analyses de séquençage haut débit ont montré que Ezl1 est requise pour l’élimination des longues séquences répétées germinales, suggérant que les scnRNA guident la déposition des marques d’histones au niveau de ces séquences. Au contraire des régions répétées du génome, les IES montrent une sensibilité différente aux scnRNAs et à Ezl1, suggérant que plusieurs voies partiellement chevauchantes sont impliquées dans leur élimination. Notre étude montre que des caractéristiques intrinsèques des séquences d’ADN, telles que leur taille, peut contribuer à la définition des séquences germinales à éliminer. De manière intéressante, nous avons aussi montré que Ezl1 est requise pour la répression transcriptionnelle des éléments transposables. Nous suggérons que les voies H3K9me3et H3K27me3 coopèrent et contribuent à préserver le génome somatique de Paramecium des parasites génomiques. / Eukaryotic genomes are organized into chromatin, a complex nucleoprotein structureessential for the regulation of gene expression and for maintaining genome stability.Ciliates provide excellent model organisms with which to gain better understandinginto the regulation of genome stability in eukaryotes. In the ciliate Parameciumtetraurelia, differentiation of the somatic genome from the germline genome ischaracterized by massive and reproducible programmed DNA elimination events. Longregions of several kilobases in length, containing repeated sequences and transposableelements are imprecisely eliminated, whereas 45,000 short, dispersed, single-copyInternal Eliminated Sequences (IESs) are precisely excised at the nucleotide level. Aspecific class of small RNAs, called scnRNAs, is involved in the epigenetic regulation ofDNA deletion. How scnRNAs may guide DNA elimination in Paramecium remains tobe discovered. Here, we investigated whether chromatin structure, in particular histonepost-translational modifications known to be associated with repressive chromatin,might control DNA elimination. We showed that trimethylated lysine 9 and 27 onhistone H3 (H3K9me3 and H3K27me3) appear in the developing somaticmacronucleus when DNA elimination occurs. We identified the Polycomb-groupprotein, Ezl1, and showed that it is a dual histone methyltransferase that catalyzes bothH3K9me3 and H3K27me3 in vitro and in vivo. Genome-wide analyses show thatscnRNA-mediated H3K9me3 and H3K27me3 deposition is necessary for theelimination of long, repeated germline DNA. Conversely, single copy IESs displaydifferential sensitivity to depletion of scnRNAs and Ezl1, unveiling the existence ofpartially overlapping pathways in programmed DNA elimination. Our study revealsthat cis-acting determinants, such as DNA length, also contribute to the definition ofgermline sequences to delete. We further showed that Ezl1 is required fortranscriptional repression of transposable elements. We suggest that H3K9me3 andH3K27me3 pathways cooperate and contribute to safeguard the Paramecium somaticgenome against intragenomic parasites.

Le dix-huitième siècle est une période propice à l’essor du débat sur la prostitution à Londres.Parce que la politique répressive des autorités se révèle défaillante dans son combat en la matière, un grand débat se fait jour dès le milieu du siècle, dans l’espoir de trouver des recours plus adaptés à l’ampleur du phénomène. Cette thèse est consacrée à l’analyse chronologique de ce débat qui adopte, au fil de son évolution, une dynamique complexe. Créé à Londres en 1758, le Magdalen Hospital devient la première maison de charité pour prostituées repenties en Angleterre. Il est la concrétisation d’une vigoureuse croisade humanitaire menée par des réformateurs philanthropes, afin de porter secours aux nombreuses filles publiques de la ville. Soutenue par le discours sentimental, une politique de »victimisation » à l’égard de la prostituée est mise en place, avec des répercussions majeures sur son image : celle-ci a subi le « crime » de séduction, et c’est par nécessité économique,non par choix, qu’elle se prostitue. À partir des années 1780, on constate néanmoins un tournant sensible dans le débat. Le discours philanthropique semble s’essouffler et présage le retour d’une pensée plus radicale : celle qui rappelle le crime de la prostitution. Dans un contexte social agité, ce commerce est devenu un « mal national » auquel il faut s’attaquer avec plus de fermeté. Par-dessus tout, ce sont deux discours habituellement opposés, celui delà charité et celui de la répression, qui, au tournant du siècle, collaborent peu à peu afin de combattre le « fléau ». / The eighteenth century witnessed an intensifying debate on prostitution in London. Asrepressive state policies became a less effective counter to the burgeoning sex trade, agrowing debate starting in the middle of the century sought a more coherent response. Thisthesis offers a chronological analysis of the debate, which took on a complex dynamic overthe course of its development. Founded in London in 1758, the Magdalen Hospital becamethe first charity house in England for repentant prostitutes. It represented the concretization ofa vigorous humanitarian crusade spurred on by philanthropist reformers hoping to help thecity’s many « streetwalkers ». A new policy, rooted in sentimentalist discourse, whichmaintained the « victimization » of the prostitute, had major repercussions on her image: theprostitute was seen to have been subjected to the crime of « seduction », and it was financialnecessity, not choice, which had led her to prostitution. The 1780s, however, brought about anoticeable shift in the debate. As the philanthropic discourse ran out of steam, it presaged thereturn of a more radical line of thought, which evoked the « crime » of prostitution. At a timeof social turbulence, prostitution increasingly became seen as a « national evil », which neededto be attacked with greater firmness. Above all, it was these two normally opposed lines ofthought – that of charity and that of repression – which, at the turn of the century, tentativelyworked together to put an end to the « scourge » of prostitution.

Why do women protest? Why do women protest “as women”? Why do some women participate in protests but not others? In the wake of the Women’s March of 2017, perhaps the largest single day protest event in history, these questions are particularly timely and deserve scholarly attention. One important but understudied and undertheorized motivation for women’s protests is state sanctioned violence, particularly repression. This dissertation explicitly theorizes about how state perpetration of violence, particularly state use of repression, both motivates and shapes women’s protests on a global scale. In this dissertation, I argue that one key motivation for women’s protest is repression by the state, and I theorize that women will protest more frequently when the state uses repression. Repression negatively impacts members of the population, particularly relatives, friends, and communities of those targeted by the state, and this motivates those people to protest. However, I argue that the type of repression, and more specifically how gendered the state practices repression, matters. The more that gender plays a role in determining who states target with repression, the more gender matters in the societal response to repression. In particular, I examine the use of forced disappearances. Based on historical and contemporary accounts, I show that forced disappearance largely targets males, and thus motivates women’s protests but has no effect on protests by other groups. When the state makes use of forced disappearances, some women are motivated to protest due to their connections to victims of repression. Furthermore, opportunities to protest in these circumstances are more available to women than to men, due to their relatively lower likelihood of being targeted, as well as women’s distinctive positions in society and their ability to organize themselves as women. Not only do women have additional space relative to men to protest when the state is repressive, but individual women recognize that their gender can serve as a resource in such contexts. Thus, individual women are more likely to participate in protests themselves when the state uses repression, closing the gender gap in protest participation between men and women. I test my theory of women’s protest using two unique approaches. First, utilizing unique new data on women’s protests that is globally comprehensive for all countries from 1990-2009, I show that women’s protests are more frequent when the state is repressive, and that forced disappearances in particular motivate women’s protests, specifically, but do not have an observable effect on general protests. Second, I utilize regionally comprehensive data on citizens in Latin America from 2006 and 2008 to show that women are more likely to participate in protests when the state uses forced disappearances, but that men are not more likely to participate in protests in repressive contexts.

This thesis discusses the growing body of work on transnational social movement theory. Transnational social movement theory is an attempt to adapt social movement theory to the changing nature of international relations. To further this theory, I test the hypothesis that "a transnational social movement has caused drug law reforms at the local and state level". To test this hypothesis I undertake a case study of one local and one national drug law reform. The drug laws in the state of New South Wales, Australia were reformed in 1999 to allow heroin addicts to use a medical center to inject their drug. The second case study is of Bolivia's national coca laws where the government allows a small amount of coca to be grown for legal traditional consumption. I conclude that a transnational social movement has had little impact on these law reforms but perhaps in the future such a movement will begin to have a greater impact on local and national drug laws around the world. To become more effective, I suggest that the transnational movement should establish a set of goals, strengthen networks among activists, develop insurgent consciousness, develop an innovative repertoire of contention, and it needs to take advantage of the political opportunity structure when it opens.

Nesta dissertação são apresentadas duas contribuições originais de Silvia Bleichmar em relação a Laplanche: recalque originário e signos de percepção. Partindo das observações de Laplanche sobre a ideia freudiana que considera o inconsciente fundado pelo recalque originário, Silvia Bleichmar ampliou o conceito, produzindo importantes contribuições em comparação ao pensamento freudiano e laplancheano. A autora articulou o recalque originário com os destinos pulsionais anteriores ao recalque, tornando-o um conceito metapsicológico passível de ser observado clinicamente, sobretudo na clínica de crianças. O recalque originário, em Silvia Bleichmar, longe de ser um processo mítico em algum momento, aproxima-se da ideia freudiana de recalque propriamente dito. Para Bleichmar, tal como em Freud, o recalque originário extrai sua força inicial de contrainvestimentos. No entanto, a autora entende que estes contrainvestimentos seriam originados no outro, pela interdição ao autoerotismo infantil. Outra importante contribuição da autora para a psicanálise foi sua conceituação sobre signos de percepção, tradução para a expressão alemã Wahrnehmungszeichen (Wz), usada por Freud em seu modelo de aparelho psíquico apresentado na Carta 52 a Fliess. Laplanche questiona se o termo Zeichen deveria ser entendido como signos ou indícios, fazendo sua escolha pela palavra signos. Para este autor, os signos de percepção se equivalem às mensagens enigmáticas, portanto, seriam portadores de mensagens. Silvia Bleichmar entende que Zeichen seriam indícios, pegadas, marcas, vestígios, huellas (em espanhol), dando ênfase ao caráter indiciário dos signos de percepção. A autora partiu da concepção de Charles S. Peirce sobre signos indiciários para articular sua própria concepção de signos de percepção. Para a autora, estes seriam as primeiras inscrições pulsionais que podem permanecer no psiquismo como arcaico se não transcritas ou as inscrições advindas de traumatismos severos, a qualquer momento, que ficam igualmente sem possibilidade de transcrição no psiquismo. Assim, o arcaico seria formado pelos signos de percepção que permanecem sem transcrições enquanto o originário seria o conteúdo do inconsciente originariamente recalcado / Two original Silvia Bleichmars contributions to Laplanche are presented in this essay: the primal repression and the perceptual signs. Stemming from Laplanches observations on the Freudian conception that considers the unconscious founded by the primal repression, Silvia Bleichmar expanded the concept, producing important contributions in comparison to the Freudian and the Laplanchean lines of thought. The author connected the primal repression to the Freudian destinies of the drive (instinct) existing prior to repression, which made it a metapsychological concept subject to clinical observation, most of all in the work with children. In Silvia Bleichmars thinking, far from being a mythical process at some point, the primal repression is close to the Freudian idea of repression itself. To Bleichmar, as well as to Freud, the primal repression extracts its initial strength from anticathexes. Nevertheless, the author believes that these anticathexes stem from the other through the interdiction of child auto-erotism. Another important contribution of the author to psychoanalysis was her conceptualization of perceptual signs, which is a translation of the German expression Wahrnehmungszeichen (Wz), used by Freud in his model of psychic apparatus presented in the Letter 52 to Fliess. Laplanche questions if the term Zeichen should be understood as signs or indexes, preferring the word signs. For him, the perceptual signs are equivalent to the enigmatic messages, therefore they would be message carriers. Silvia Bleichmar believes that Zeichen are indexes, footprints, marks, vestiges, huellas (in Spanish), emphasizing the indexing character of the perceptual signs. Therefore, deriving from Charles S. Peirces conception of indexing signs, the author built her own conception of perceptual signs. For her, these would be the first drive inscriptions that may remain in the psyche as archaic if not transcript, as well as the inscriptions stemming from severe trauma, at any point, which equally remain without transcription in the psyche. Hence, the archaic would be composed by the perceptual signs that remain without transcriptions whereas the primal would be the content of the primally repressed unconscious

<p>In this study, adenovirus E1A has been used to target and analyse the transcriptional function of the cellular C-terminal Binding Protein (CtBP).</p><p>Transcription is a complex biochemical process that represents a major regulatory step in gene expression. Formation of condensed chromatin by histone deacetylation and inhibition of efficient assembly of the transcription machinery are hallmarks of transcriptional repression. During a virus infection, an extensive modulation of the host cell gene expression in favour of viral gene expression can be observed. For example, the transcription regulatory E1A protein from adenovirus has been proven to be a valuable research-tool in characterising cellular proteins controlling eukaryotic gene expression.</p><p>Expression of a CtBP-binding peptide, encoded by the second exon of E1A, de-repressed transcription from a broad range of promoters, suggesting that CtBP functioned as a repressor of transcription. Artificial promoter recruitment of CtBP, by using different Gal4-fusion proteins, confirmed that CtBP functioned as a repressor. Repression of transcription by Gal4E1A-recruited CtBP was efficiently prevented by a CtBP binding competent E1A peptide, indicating that E1A relieved CtBP mediated repression by displacing CtBP from the promoter. Furthermore, Gal4CtBP repressed both basal and activated transcription in a distance dependent manner, suggesting that CtBP might repress transcription by interfering with the assembly of the basal transcription machinery. Interestingly, CtBP was found to interact with histone deacetylase-1 (HDAC-1) both <i>in vivo</i> and <i>in vitro</i> and endogenous CtBP could also recruit histone deacetylase activity. This might indicate that histone deacetylation was involved in CtBP mediated repression. However, Gal4CtBP mediated repression was insensitive to inhibition of histone deacetylase activity, suggesting an alternative function of HDAC-binding in CtBP mediated repression.</p><p>In conclusion, this work demonstrates that CtBP can act as a general repressor of activated and basal transcription. Furthermore, although CtBP was shown to recruit histone deacetylase activity the relevance of this binding remains unclear.</p>

<p>Krüppel-related zinc finger proteins constitute the largest single class of transcription factors within the human genome. Members of this protein family have the ability to either activate or repress transcription depending on the presence of specific activator or repressor domains within the protein. Approximately one third of the Krüppel-related zinc finger proteins contain an evolutionarily well-conserved repressor domain termed the KRAB domain. This domain acts as a potent repressor of transcription by interacting with the co-repressor protein, TIF1β. TIF1β then, in turn, recruits HP1 proteins, HDACs and probably other proteins involved in gene silencing. In order to identify novel KRAB-containing zinc finger proteins, one mouse monocytic cDNA library and two testis cDNA libraries were screened for novel members of this multigene family. Six novel KRAB-ZNF cDNAs, four mouse and two human, were isolated. The corresponding proteins were all shown to contain N-terminally located KRAB domains as well as varying numbers of C-terminally located zinc finger motifs. An extensive comparative sequence analysis of the KRAB domains of these proteins together with KRAB domains from a large number of previously identified KRAB-ZNF proteins resulted in a clear subdivision into three different subfamilies, A+B, A+b and A. Later, we also isolated a fourth KRAB box, which is present downstream of the KRAB A box in a few proteins of the KRAB A family. This module was named KRAB C. Potential functional differences between these different subfamilies were investigated. In line with previous observations, the KRAB A box was shown to repress transcription, an activity which was enhanced by the presence of the KRAB B box. However, addition of neither the KRAB b box nor the KRAB C box had any effect on repression. Moreover, all KRAB A motifs had the ability to bind TIF1β, and this binding was increased both by the presence of the KRAB B box and by the KRAB C box. The KRAB b box, however, did not seem to contribute to TIF1β-binding. One of the novel human cDNAs, HKr19, was found to be a member of the large ZNF91 family of KRAB zinc finger genes. Interestingly, the expression of HKr19 and a number of other closely related genes were restricted to lymphoid cells, indicating that these genes may be involved in regulating lineage commitment. The effect of HKr19 on cell viability was investigated by transfection into human embryonic kidney cells (HEK 293). The results indicated that HKr19, or its zinc finger domain in isolation, were toxic to these cells when expressed at high levels. The MZF6D protein, on the other hand, showed a testis-specific expression. <i>In situ</i> hybridization analysis located this expression to meiotic germ cells, suggesting a role for this protein in spermatogenesis. Further, the evolutionary perspectives of this large gene family were addressed, and its enormous expansion throughout evolution probably includes numerous duplication events. The results from two extensive sequence analyses give clues to how the repetitive nature of the ZNF motif has given rise to both internal duplications of single motifs as well as duplications of entire genes resulting in gene clusters.</p>