Thesis (Ph. D.)--University of Washington, 2000. / Vita. Includes bibliographical references (leaves 100-103).

Thesis (Ph. D.)--University of California, San Diego and San Diego State University, 1997. / Vita. Includes bibliographical references (leaves 99-129).

Lysine acetyltransferases (KATs) and lysine deacetylases (KDACs) are known to cooperate with the glucocorticoid receptor (GR) to regulate transcription. The current model of GR-mediated transcription classifies KATs as coactivators as they acetylate histones to form an open chromatin conformation and casts KDACs as corepressors that deacetylate histones and condense chromatin. Our recent studies have challenged this long-standing model. In the current study, we show that KDACs act as versatile coregulators, facilitating both the onset and maintenance of GC-induced transcriptional activation and repression. Through siRNA depletion studies, we define KDAC1 as the predominant Class I KDAC for efficient transactivation of a majority of the GR-target genes tested. KDACs 1 and 2 co-operate with each other to activate and repress a few target genes, however KDAC2 alone is not sufficient for activation or repression of the genes, thus questioning the functional redundancy of KDACs 1 and 2. Additionally, we found that there is a unique population of KDAC2 that does not associate with KDAC1 in our cell line. Through a series of siRNA depletion studies, steroid receptor coactivator proteins (SRCs) were shown to be dispensable for GC-induced gene activation and SRC2 was not required for Dex-induced transcriptional repression. We performed ChIP assays to address the mechanism by which Class I KDACs facilitate transactivation and transrepression. At GC-activated genes we found that KDACs are constitutively present at the gene enhancers and that KDAC inhibition does not affect the binding of GR or SRC proteins to chromatin. However, KDACs do influence the histone methylation status of H3K4 at GREs of activated genes and TSSs of repressed genes. To explain the change in the methylation status of this marker, we depleted LSD1, the specific demethylase for mono- and demethylation of H3K4, and found that LSD1 action is required for GC-mediated transrepression. However it is unlikely that KDAC inhibition impairs GR transactivation through effects on LSD1. Glucocorticoid signaling regulates multiple vital biological processes. Glucocorticoids play a major role in regulating carbohydrate, protein and lipid metabolism. They increase hepatic gluconeogenesis to maintain blood glucose concentration in the fasting state. GCs also act as potent anti-inflammatory molecules, stimulate lung maturation in the developing fetus, and affect bone metabolism. Additionally, excess or deficiency of GCs can lead to a variety of psychological abnormalities, indicating their role in CNS functions. Our results indicate that pharmaceutical modulation of KDACs may impair proper glucocorticoid signaling and disrupt vital biological processes. Other steroid hormone receptors function similarly to GR in regulating gene expression and could also be impacted by KDAC inhibition, thus suggesting serious physiological implications in patients. Therefore, the possibility of endocrine modulation should be taken into account when using KDAC inhibitors in the clinic.

Orientador: Flavia Lombardi Lopes / Banca: Silvia Helena Venturoli Perri / Banca: José Fernando Garcia / Banca: Ricardo da Fonseca / Banca: José bento Sterman Ferraz / Resumo: O objetivo desse estudo foi identificar polimorfismos de nucleotídeo único (SNPs) potencialmente sujeitos a controle epigenético exercido por metilação do DNA via seus envolvimentos na criação, remoção ou deslocamento de sítios CpG (meSNPs) e a partir de tal identificação criar um banco de dados para meSNPs, bem como determinar a possível associação desses marcadores com ilhas CpG (CGIs) e com o perfil metilacional de tecidos submetidos ao ensaio de recuperação de ilhas CpG metiladas combinado com plataformas de sequenciamento de nova geração (MIRA-seq) em bovinos. Usando as variantes anotadas para os SNPs identificados no Run5 do projeto 1000 Bull Genomes e a sequência genômica bovina de referência UMD3.1.1, identificamos e anotamos 12.836.763 meSNPs de acordo com o padrão de variação criado por cada SNP em um sítio CpG. Também analisamos a distribuição genômica desses meSNPs, sendo a maioria deles localizados em regiões intergênicas (68,00%) e intrônicas (26,32%). Globalmente, os meSNPs representam 22,53% dos 56.969.697 SNPs descritos na base de dados e 12,35% deles estão localizados em CGIs. Comparando o número observado com o número esperado de meSNPs nas CGIs e nos tecidos submetidos ao MIRA-seq, verificamos um enriquecimento médio (P<0,01) para meSNPs de 2,47 vezes em CGIs relaxadas e 1,90 vezes em CGIs rigorosas. Nos tecidos, o enriquecimento foi de 1,52 vezes em longissimus dorsi e 2,09 vezes em intestino delgado. Dez meSNPs com metilação diferencial, sendo 1 em longi... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The aim of this study was to identify single nucleotide polymorphisms (SNPs) potentially subject to epigenetic control exerted by DNA methylation via their involvement in creating, removing or displacement CpG sites (meSNPs) and from this identification create a database for meSNPs, as well as to determine its possible association with CpG islands (CGIs) and the methylation profile of tissues submitted to the methylated-CpG island recovery assay combined with next generation sequencing platforms (MIRA-seq) in cattle. Using the variant annotations for SNPs identified in Run5 of the 1000 bull genomes project and the UMD3.1.1 bovine reference genome sequence assembly, we identified and classified 12,836,763 meSNPs according to the pattern of variation caused at the CpG site. We have also analyzed the genomic distribution of the meSNPs, with the majority being located in intergenic regions (68.00%) and then in introns (26.32%) and the remainder distributed among proximal promoters (3.93%), coding regions (1.27%), untranslated regions (UTRs) (0.29%), non-coding RNAs (0.11%) and splice regions (0.08%). Overall, meSNPs represent 22.53% of 56,969,697 SNPs described in the database of which 12.35% are located in CGIs. Comparing the observed number with the expected number of meSNPs in the CGIs and tissues submitted to the MIRAseq we found a mean enrichment (P<0.01) for meSNPs of 2.47 times in the relaxed CGIs and 1.90 times in the strict CGIs. In the tissues the enrichment was of 1.52... (Complete abstract click electronic access below) / Doutor

L’ARN hélicase UPF1 est un facteur clé du Nonsense-Mediated Decay (NMD), un mécanisme impliqué dans le contrôle de la qualité des ARNm et la régulation de l’expression des gènes. Malgré d’importantes fonctions chez les plantes, le NMD y est peu décrit. Cette thèse présente l’identification et l’étude des protéines interagissant avec UPF1 chez Arabidopsis. Nous avons identifié un nouveau réseau d’interaction protéine-protéine entre UPF1 et des répresseurs de traduction dans les P-bodies. Nous proposons un modèle dans lequel la répression traductionnelle exerce une action protectrice sur les cibles du NMD. Notre approche a également identifié de nouveaux composants des P-bodies, comme l’endonucléase UCN. Son étude détaillée a révélé un lien direct avec la machinerie de decapping ainsi que de possibles rôles dans la signalisation hormonale ou les mécanismes de défense, suggérant que la modulation de l’expression d’UCN pourrait influencer d’importantes caractéristiques agronomiques. Ce travail décrit des facteurs associés à UPF1 jusqu’alors inconnus, leur étude permettra de découvrir de nouveaux mécanismes impliqués dans l’équilibre entre la traduction, le stockage et la dégradation des ARNm chez les plantes. / The RNA helicase UPF1 is a key factor of Nonsense-Mediated Decay (NMD), a paneukaryotic mechanism involved in mRNA quality control and fine-tuning of gene expression. Despite important biological functions in plants, NMD is poorly described compared to other eukaryotes. This thesis presents the identification and study of UPF1 interacting proteins in Arabidopsis. Using approaches based on immunoaffinity and mass spectrometry, we identified a novel protein-protein interaction network between UPF1 and translation repressors in P-bodies. We propose a model in which translation repression exerts a protective action on NMD targets in plants. Our approach also identified novel P-body components, including the UCN endonuclease. A detailed study revealed its direct link with the decapping machinery and possible roles in hormone signaling and defense mechanisms, suggesting that the modulation of UCN expression could influence important agronomical traits. This work describes hitherto unknown UPF1 associated factors, their study will provide novel insights into the mechanisms involved in the balance between mRNA translation, storage and decay in plants.

387f. / Submitted by Suelen Reis (suziy.ellen@gmail.com) on 2013-04-22T16:15:04Z No. of bitstreams: 3 Tese Ileana Limonta3.pdf: 3908228 bytes, checksum: f95d8bba1c5ec0e4d8ef9961db5dc65d (MD5) Tese Ileana Limonta2.pdf: 5969335 bytes, checksum: 71ada33384664a2717a4be6bfe0c8137 (MD5) Tese Ileana Limonta1.pdf: 8530405 bytes, checksum: f35dc1d3ce53f4921cd5e8bfcb94ed7a (MD5) / Approved for entry into archive by Rodrigo Meirelles(rodrigomei@ufba.br) on 2013-05-24T11:39:35Z (GMT) No. of bitstreams: 3 Tese Ileana Limonta3.pdf: 3908228 bytes, checksum: f95d8bba1c5ec0e4d8ef9961db5dc65d (MD5) Tese Ileana Limonta2.pdf: 5969335 bytes, checksum: 71ada33384664a2717a4be6bfe0c8137 (MD5) Tese Ileana Limonta1.pdf: 8530405 bytes, checksum: f35dc1d3ce53f4921cd5e8bfcb94ed7a (MD5) / Made available in DSpace on 2013-05-24T11:39:35Z (GMT). No. of bitstreams: 3 Tese Ileana Limonta3.pdf: 3908228 bytes, checksum: f95d8bba1c5ec0e4d8ef9961db5dc65d (MD5) Tese Ileana Limonta2.pdf: 5969335 bytes, checksum: 71ada33384664a2717a4be6bfe0c8137 (MD5) Tese Ileana Limonta1.pdf: 8530405 bytes, checksum: f35dc1d3ce53f4921cd5e8bfcb94ed7a (MD5) Previous issue date: 2009 / Esta tese tem como enfoque o estudo comparativo da Santería cubana e dos Candomblés brasileiros de tradição iorubá. O objetivo foi estudar os perfis identitários destas expressões religiosas de matriz africana, como cultura de resistência ante uma cultura imposta durante séculos de colonialismo pelas elites do poder, no período histórico que vai de 1950 a 2000. Teve-se em vista os mecanismos de enfrentamento ou confrontação que estas religiosidades criaram como via de defesa e inserção social. Tentamos desvendar, na medida do possível e de forma comparativa, as relações políticas e a incidência sócio-cultural no entorno social em que atuaram estas expressões em Cuba e no Brasil, conhecendo de antemão a influência que tradicionalmente elas têm exercido na esfera da consciência individual dos iniciados em seus cultos religiosos. Temas como: africanidade, etnicidade, cultura, resistência, poder e repressão foram analisados em função da estrutura religiosa da Santería e do Candomblé, em contrate com a realidade social que enfrentaram nos países para onde foram transplantadas. Esta estrutura teve como núcleo principal a família religiosa em uma intrincada rede de sociabilidades, que encontrou e ainda encontra nos terreiros e nas casas-templo o ambiente propício para recriar os elementos culturais africanos que sustentam, como parte do continuum das tradições culturais herdadas dos africanos, que buscaram e encontraram um lugar na história e identidade nacional cubana e brasileira, como expressões religiosas de resistência em defesa da identidade cultural. / Salvador

The following abstract analyses female participation in drug trafficking in Alagoas considering the adaptations in the modus operandi of local drug dealers to dodge repression, gender differences in current social panorama, both in the workplace and in relationships, on top of police action in order to restrain female workforce in the State, which mostly takes place in the city outskirts. The current study demonstrates that Brazilian anti-drug policies favours the imprisonment of poor drug dealers while the ones who are more powerful economically and politically are left unpunished. It brings punishment and gender selection into action as well as individual criminal tendencies. Such processes allow police officers to choose whom Justice will target. The research also discusses social and economic aspects of female drug dealers in Alagoas, the male power to which such women are subjected to and their roles in drug trafficking. In order to perform such delicate task, experienced investigators on drug trafficking in state police force were interviewed to gather information about the peculiarities of their action in Alagoas. Furthermore, female inmates at Santa Luzia State Prision, in Maceió were interviewed as to unveil their reasons to participate in such illegal market, the relationships with male drug dealers and their imprisonment circumstances. / Fundação de Amparo a Pesquisa do Estado de Alagoas / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Esta dissertação analisa a participação das mulheres no tráfico de drogas em Alagoas, considerando as adaptações no modo de atuar das redes de traficantes locais para driblar a repressão, as diferenças de gênero na contemporaneidade, tanto no mercado de trabalho como nas relações afetivas, além da ação da polícia nas periferias com objetivo de coibir a mão de obra feminina no estado. O estudo demonstra que a política antidrogas brasileira favorece o aprisionamento de traficantes pobres, em detrimento dos traficantes de maior poder econômico e político, colocando em prática a seletividade punitiva, a seletividade de gênero e a sujeição criminal, processos que permitem aos policiais escolher quem será atingido pela Justiça Penal. A pesquisa discute ainda as condições socioeconômicas das mulheres traficantes de Alagoas, a dominação masculina a que estão submetidas nas redes criminosas locais e o protagonismo feminino no exercício das funções no tráfico de drogas. Para isso, foram realizadas entrevistas com agentes da segurança pública experientes em investigações sobre o tráfico, visando captar as particularidades de sua dinâmica em solo alagoano; e com mulheres presas recolhidas no Presídio Feminino Santa Luzia, em Maceió, para, através das suas histórias de vida, desvendar o que as levaram a ingressar no mercado ilícito, a relação que vivenciaram com outros traficantes, além das circunstâncias de suas prisões.

This thesis is concerned with the implications of the financial liberalisation of the Chinese economy for savings, investment, monetary policy and the exchange rate, in China. In the first part, the financial repression hypothesis is tested on savings and investment, with the result that there is some evidence to support the complementarity between money and physical capital in China since 1987, although this effect is shown to have become weaker over the sample period as liberalisation has taken place. The second issue is to investigate the consequences of interest rate liberalisation in China, using a dynamic stochastic general equilibrium (DSGE) model. There are two main findings. First, raising deposit rates serves to alter the division of production between consumption and investment and to improve the efficiency of the monetary policy transmission mechanism through interest rates. Second, the deregulation of deposit and loan rates leads to less volatility in inflation as interest rates are allowed to partly absorb shocks to the economy. Other monetary policies under financial repression in China are examined as well. The results based on the DSGE model suggest that the interest rate rule is more effective and powerful than the conventional money growth rule and the adjustment of the required reserve ratio helps little to contain inflation. In addition, the administrative window guidance on bank loans contributes to less volatility of inflation and stabilises the deregulation process of deposit and loan rates. The final part of the thesis examines the sources of the volatility in real exchange rate, which are shown to stem essentially from demand shocks, although up to a quarter of the volatility comes from relative supply disturbances, perhaps reflecting the importance of supply-side reform in China since the early 1990s.

La présente étude porte sur l’encadrement juridique et pas sur la mise en oeuvre, car nous souhaitons nous interroger sur l’existence d’une volonté des Etats de combattre à travers du droit positif le phénomène. Dans l’ensemble on constate qu’il existe un lien indissociable entre la prévention et la répression de la traite et la protection des droits fondamentaux des victimes. L'histoire du droit international relatif à la traite remonte à 1904, la date d’adoption du premier instrument juridique international sur la question. En 1926 a été élaboré la première Convention relative à l’esclavage. Suite à l’ampleur du phénomène, la Convention relative à la répression de la traite des êtres humains et à l’exploitation de la prostitution d’autrui de 1949 et la Convention supplémentaire relative à l’abolition de l’esclavage, de la traite des esclaves et des institutions et pratiques analogues à l’esclavage de 1956 ont été adoptées. Ces conventions, ne prenaient pas en compte tous les aspects du problème, étaient antérieures à la plupart des pratiques modernes relatives au trafic de personnes, et ne disposaient pas d’organe de contrôle au niveau international. Le Protocole additionnel de la Convention des Nations Unies contre la criminalité transnationale organisée visant à prévenir, réprimer et punir la traite des personnes, et en particulier des femmes et des enfants donne pour la première fois une définition conventionnelle la plus élaborée du phénomène. De son côté le Statut de Rome de la Cour pénale internationale institue un nouvel organe international pour la traite en citant la réduction en esclavage au nombre des crimes considérés comme étant des crimes contre l'humanité. A coté des conventions universelles plusieurs organisations internationales et régionales se penchent sur le phénomène. La Convention du Conseil de l'Europe sur la lutte contre la traite des êtres humains est l'instrument du Conseil la plus susceptible de contribuer de manière efficace à la lutte contre la traite des êtres humains. L’Union européenne a adoptés plusieurs résolutions spécifiques concernant la traite, au niveau du continent Américain, l’Organisation des États Américains a adopté plusieurs instruments concernant la traite, à l’échelle du continent africain, il y a des initiatives importantes qui se préoccupent directement du problème. Au niveau étatique les États membres disposent dans l’ensemble de dispositions pénales spécifiques permettant d'incriminer la traite en introduisant des sanctions effectives et dissuasives. En établissant des dispositions dans les différents codes, la Turquie prévoit une efficace répression en répriment toutes les formes de la traite. De son coté l’Ukraine pays d’origine de la traite doit non seulement sanctionner sévèrement les trafiquants, mais en même temps doit se conformer aux normes et exigences internationales. Avec le développement du phénomène une protection aux victimes est assurée, non seulement à travers les conventions à vocation universelle, mais aussi à travers diverses institutions régionales. Avec le Protocole de Palerme la communauté internationale a mis en place un cadre juridique international visant assurer une meilleure protection. De son côté dans le Statut de Rome de la Cour pénale internationale la protection et l’assistance proposées aux victimes sont applicables à toutes victimes de crime. Tandis que les deux conventions de Conseil de l’Europe, la Convention des droits de l’homme et la Convention sur la traite des êtres humains protègent efficacement les victimes, et les instruments adoptés au niveau de l’Union européenne contribuent à l’harmonisation des politiques de protection, les engagements pris par l’OSCE ne prévoient pas de dispositions contraignantes, de la manque de mécanisme de contrôle. / This study examines the legal framework of the trafficking in human beings, because we want to question the existence of a will of states to fight the phenomenon through positive law. Overall we find that there is an inextricable link between prevention and repression of trafficking and protection of victims' rights. The history of international law on the trafficking dates back to 1904, the date of adoption of the first international legal instrument on this issue. The first convention on slavery was developed in 1926. Following the magnitude, the Convention for the Suppression of the Traffic in Persons and of the Exploitation of the Prostitution of Others in 1949, Supplementary Convention on the Abolition of Slavery, the Slave Trade and Institutions and Practices Similar to Slavery of 1956 were adopted. These agreements, not taking into account all aspects of the problem predated the most modern practices relating to trafficking in persons, and did not have supervisory body at the international level. The Additional Protocol to the United Nations Convention Against Transnational Organized Crime to Prevent, Suppress and Punish Trafficking in Persons, especially Women and Children first gives the most elaborate definition of the phenomenon in the convention. For its part the Rome Statute of the International Criminal Court establishes a new international body for human trafficking, citing enslavement as a crime treated as crimes against humanity. Besides the universal conventions several international and regional organizations are looking at the phenomenon. The Convention of the Council of Europe, Convention on Action Against Trafficking in Human Beings is the instrument of the Council most likely to contribute effectively to the fight against trafficking in human beings. The European Union has adopted several resolutions concerning the specific processes; in America, the Organization of American States has adopted several instruments on trafficking; there are important initiatives that directly concern the problem in African continent. At the state level, the member States have in all specific criminal provisions to criminalize trafficking in human beings by introducing effective and dissuasive sanctions. In provisions in the various codes, Turkey provides an effective crackdown repress in all forms of trafficking. For its part the Ukraine country of origin of trafficking must not only severely punish traffickers, but at the same time must comply with international standards and requirements. With the development of the phenomenon, protection for victims is provided, not only through the conventions of international, but also through various regional institutions. With the Palermo Protocol the international community has established an international legal framework to ensure better protection. For his part in the Rome Statute of the International Criminal Court, protection and assistance shall apply to all victims of the crime. While both conventions Council of Europe Convention on Human Rights and the Convention on Trafficking in Human Beings effectively protect victims. While instruments adopted at the EU contribute to the harmonization of policies to protect, the commitment of the OSCE does not provide binding provisions because of the lack of control mechanism. Protection across America and Africa is rather ensured by the provisions concerning human rights, and the provisions regarding the protection of victims are very limited. At the state level the current trend of European states about protection and assistance to victims is a prerequisite for their cooperation with law enforcement authorities In all these countries, as well as Turkey and Ukraine, protection of victims is conditioned, but the last two do not have specific provisions for the protection of victims, contain provisions to protect witnesses and victims in general.

Made available in DSpace on 2014-06-11T19:26:35Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-02-20Bitstream added on 2014-06-13T20:54:49Z : No. of bitstreams: 1 thomaz_rc_me_assis.pdf: 278396 bytes, checksum: 7dfcf25806b5d320b44527744ab28136 (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Nas suas obras culturais Freud apresenta uma visão esclarecedora da complicada relação que se dá entre o indivíduo e a sociedade. Assim como ele, Wilhelm Reich e Herbert Marcuse teorizaram sobre este tema, priorizando o problema da falsa consciência e da ausência de liberdade na civilização. Para isto, se utilizaram do elo entre psicanálise e materialismo histórico. O que pretendemos em nossa pesquisa é analisar como os dois desenvolveram este referencial teórico e chegaram a um estudo sistematizado da sociedade a que pertenciam. Isto nos permitirá realizar nosso objetivo de estudar a possibilidade da utilização da psicanálise na investigação histórica e as reelaborações dos conceitos freudianos. A escolha de Reich e Marcuse se legitima numa pesquisa histórica pelo fato de que ambos exploraram o componente histórico das categorias psicanalíticas. / In his cultural works, Freud presents an interesting view of the complicated connection between the individual and society. Like him, Wilhelm Reich and Herbert Marcuse theorize about this subject, emphasizing the problem in relation to the false consciousness and the lack of freedom in civilization. Then they used the link between psychoanalysis and historical materialism. In this research I intend to examine how they used this theoretical point and have got a systematic study of their society. So this will help us to study the possibility of the use of psychoanalysis in historical research. The choice of Reich and Marcuse is legitimated by historical research because they explored the history component of psychoanalytic categories.