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Das Polycomb group Protein PCGF6 ist ein neuer und essentieller Faktor der iPS Reprogrammierung und kann in Kombination mit Oct4, Klf4 und c-Myc den Transkriptionsfaktor Sox2 ersetzen / The Polycomb group protein PCGF6 is a new and essential factor for iPS reprogramming that can replace the transcription factor Sox2 in combination with Oct4, Klf4 and c-MycZdzieblo, Daniela January 2014 (has links) (PDF)
Embryonale Stammzellen (ESCs) sind durch zwei charakteristische Eigenschaften definiert. Neben einer kontinuierlichen Selbsterneuerungskapazität weisen ESCs die Fähigkeit auf, in alle Zelltypen der drei Keimblätter differenzieren zu können. Diese Eigenschaften werden unter anderem durch ein Netzwerk wichtiger Pluripotenzfaktoren als auch durch epigenetische Mechanismen reguliert, welche die Transkription von Pluripotenz- und Differenzierungsgenen kontrollieren.
In murinen ESCs sind an der Repression von Differenzierungsgenen auch Polycomb group (PcG) Proteine beteiligt. Diese Proteine bauen zwei Chromatin-modifizierende Komplexe auf, die als Polycomb repressive complex 1 bzw. 2 (PRC1 bzw. PRC2) bezeichnet werden. Nach dem klassischen Modell der Polycombfunktion, katalysieren PRC1 und PRC2 gemeinsam zwei charakteristische Histonmodifikationen, die zur Repression PRC-spezifischer Zielgene beitragen. Zahlreiche Studien in den letzten Jahren belegen, dass der Proteinaufbau der PRC1 Komplexe stark variieren kann, wobei die Familie der Polycomb group RING finger (Pcgf) Proteine eine wichtige Rolle spielt. In diesem Zusammenhang definieren einzelne Pcgf Paraloge (Pcgf1 – 6) verschiedene PRC1 Varianten (PRC1.1 – 1.6), die Komplex-spezifische Bindestellen im Genom aufweisen. Diese Erkenntnisse lassen auf unterschiedliche Mechanismen der PRC1 Varianten und Pcgf Paralog-spezifische Funktionen schließen, die zum jetzigen Zeitpunkt nur wenig erforscht sind.
Für manche Pcgf Paraloge sind wichtige Rollen in verschiedenen Stammzelltypen und während der iPS Reprogrammierung bekannt. Pcgf1 (Nspc1), Pcgf2 (Mel18) und Pcgf4 (Bmi1) zeigen eine Funktion in verschiedenen adulten Stammzellen. Pcgf4 spielt darüber hinaus eine wichtige Rolle in der murinen iPS Reprogrammierung. Für Pcgf6 (Mblr) wird eine Pluripotenz-assoziierte Funktion angenommen, denn Pcgf6 ist das einzige Pcgf Paralog, das eine erhöhte Expression in murinen ESCs aufweist, die jedoch im Verlauf der ESC-Differenzierung absinkt. Außerdem zeigen murine Pcgf6 KD ESCs eine verminderte Expression der Pluripotenzgene Oct4, Sox2 und Nanog, eine De-Repression mesodermaler und Testes-spezifischer Gene als auch eine erhöhte Tendenz zur hämatopoetischen Differenzierung. Wie genau Pcgf6 an der Regulation dieser Prozesse in murinen ESCs beteiligt ist, ist nicht bekannt.
In der hier vorliegenden Dissertation wurde die Funktion von Pcgf6 in der murinen iPS Reprogrammierung untersucht. Da bereits für Pcgf4 eine Rolle in der Reprogrammierung somatischer Zellen gezeigt wurde und Pcgf6 eine erhöhte Expression in ESCs aufweist, wurde auch für Pcgf6 eine Funktion in der iPS Reprogrammierung angenommen. Zunächst konnte in dieser Arbeit gezeigt werden, dass Pcgf6 während der iPS Reprogrammierung verstärkt exprimiert wird und in iPS Zellen eine ESC-ähnliche Expression aufweist. Darüber hinaus konnte Pcgf6 in Kombination mit Oct4, Klf4 und c-Myc spezifisch den Transkriptionsfaktor Sox2 in der iPS Reprogrammierung ersetzen. Zudem wurden für OPKM-induzierte iPS Zellen charakteristische Eigenschaften pluripotenter Zellen nachgewiesen. Außerdem konnte eine Rolle von Pcgf6 als Enhancer-Faktor für die iPS Reprogrammierung ausgeschlossen werden, da die Überexpression von Pcgf6 zusammen mit den OSKM Faktoren keine additiven Effekte auf die Reprogrammierungseffizienz erzielte. Im Gegensatz dazu führte der Knockdown (KD) von Pcgf6 in embryonalen Mausfibroblasten (MEFs) zu verminderten Effizienzen nach OSKM Reprogrammierung. Darüber hinaus handelte es sich bei der Mehrheit der AP+ Kolonien, die unter Pcgf6 KD Konditionen entstanden, um partiell-reprogrammierte iPS Zellen.
Zusammengefasst zeigen die Ergebnisse der hier vorliegenden Arbeit, dass Pcgf6 ein neuer und essentieller Faktor der iPS Reprogrammierung ist, der in Kombination mit Oct4, Klf4 und c-Myc spezifisch den Transkriptionsfaktor Sox2 ersetzen kann. / Embryonic stem cells (ESCs) are characterized by their ability for continuous self-renewal maintaining the undifferentiated cell state and their capacity to generate all differentiated cell types of the three germ layers. Regulators of these characteristics include a protein interaction network of pluripotency-specific factors and epigenetic mechanisms that together control the transcription of pluripotency- and differentiation-associated genes.
Among the interaction partners of the pluripotency-specific protein network in murine ESCs are Polycomb group (PcG) proteins. These proteins assemble in two complexes termed Polycomb group repressive complex 1 and 2 (PRC1 and PRC2). In the classical model, PRC1 and PRC2 act hierarchically together in catalyzing two characteristic histone modifications thereby contributing to the repression of PRC-specific target genes like differentiation-associated genes in ESCs. Recently, it has been shown that there are numerous PRC1 variants that differ in their protein composition. In this context, the family of Polycomb group RING finger (Pcgf) proteins (Pcgf1 – 6) defines distinct PRC1 variants (PRC1.1 – 1.6) that exhibit complex-specific genomic binding sites. Together, this indicates diverse mechanisms of PRC1 variants and Pcgf Paralog-specific functions that are not well understood.
Pcgf Paralogs are known to play essential roles in various stem cell types and during iPS reprogramming. Pcgf1 (Nspc1), Pcgf2 (Mel18) and Pcgf4 (Bmi1) function in diverse adult stem cells. Further, Pcgf4 plays a role in murine iPS Reprogramming. For Pcgf6 (Mblr), a pluripotency-associated function is assumed. Pcgf6 is the only Pcgf paralog with an elevated expression in murine ESCs and when ESCs differentiate Pcgf6 expression decreases. In addition, following Pcgf6 KD in ESCs the expression of Oct4, Sox2 and Nanog declines while mesodermal and testes-specific genes become de-repressed. Furthermore, Pcgf6 KD ESCs are more prone for hematopoietic lineage differentiation. The precise mechanisms by which Pcgf6 controls these processes in murine ESCs are not known.
In this work, I investigated the function of Pcgf6 in murine iPS reprogramming. I assumed a role for Pcgf6 in iPS reprogramming because it is highly expressed in ESCs and it was recently shown that Pcgf4 plays a role in the reprogramming of somatic cells. The data of my work show that Pcgf6 expression is increased in iPS reprogramming and that Pcgf6 exhibits an ESC-like gene expression pattern in iPS cells. Furthermore, Pcgf6 was able to replace the transcription factor Sox2 in combination with Oct4, Klf4 and c-Myc. In addition, OPKM-induced iPS cells showed pluripotency-specific characteristics. The overexpression of Pcgf6 together with the OSKM factors did not result in significantly increased reprogramming efficiencies indicating that Pcgf6 does not function as an enhancer-factor. However, Pcgf6 knockdown (KD) in mouse embryonic fibroblasts (MEFs) resulted in decreased efficiencies after iPS reprogramming. Additionally, the majority of AP+ colonies formed after OSKM reprogramming of Pcgf6 KD MEFs represented partially reprogrammed iPS cells, as they did not exhibit ESC-like morphologies and reduced expression levels of Oct4, Sox2 and Nanog.
Together, the data of my work show that Pcgf6 is a new and essential factor in iPS reprogramming that can specifically replace the transcription factor Sox2 in combination with Oct4, Klf4 and c-Myc.
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Dödens vara eller icke-vara i individens vardag : Om individuella och kulturella uppfattningar om människans förgänglighetSavkic, Aleksandar January 2007 (has links)
<p>Though death and mortality is an inevitable part of our lives it seems like both the society with its culture and the individual in some way repress death. This study was set to explore how and why the individual holds back thoughts on his/her own death and in which way society affect the individual’s repression of death-thoughts. Using a hermeneutic approach I have interviewed five informants about death and thoughts about death in everyday life. Also for the analysis of the empirical material a hermeneutic approach was used, and the works of Bauman, Giddens, Heidegger, Fromm and May served as a theoretical starting point. The findings reveal that society influences the individual’s thoughts about death and that the individual’s fear of death comes out of the fear of one owns body being in some sort of suffering just pre death. The institutionalization of sick persons and dead bodies is part of the medical culture and can explain the fact that the individual sees the bodily death as more frightening than human mortality itself. Even the way persons want to be remembered by survivors is part of the evidence of our society’s and culture’s objectification of the human body and death.</p>
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Dödens vara eller icke-vara i individens vardag : Om individuella och kulturella uppfattningar om människans förgänglighetSavkic, Aleksandar January 2007 (has links)
Though death and mortality is an inevitable part of our lives it seems like both the society with its culture and the individual in some way repress death. This study was set to explore how and why the individual holds back thoughts on his/her own death and in which way society affect the individual’s repression of death-thoughts. Using a hermeneutic approach I have interviewed five informants about death and thoughts about death in everyday life. Also for the analysis of the empirical material a hermeneutic approach was used, and the works of Bauman, Giddens, Heidegger, Fromm and May served as a theoretical starting point. The findings reveal that society influences the individual’s thoughts about death and that the individual’s fear of death comes out of the fear of one owns body being in some sort of suffering just pre death. The institutionalization of sick persons and dead bodies is part of the medical culture and can explain the fact that the individual sees the bodily death as more frightening than human mortality itself. Even the way persons want to be remembered by survivors is part of the evidence of our society’s and culture’s objectification of the human body and death.
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Repression in the young and elderly : impression management or self-deception?Ashley, Aaron L. January 2000 (has links)
The construct of repression has received a resurgence of experimental attention in the past 20 years, due in large part to the development of the typology method of classification (Weinberger, Schwartz, and Davidson, 1979). According to the typology method, individuals are classified as repressors if they self-report low anxiety and high social desirability. Since the typology method of classification does not differentiate between the two factors comprising social desirability (impression management and self-deception), it is important to determine which component is actually characterizing repressors, or whether it is a combination of the two. The present study examined two questions; (1) are repressors engaging in self-deception, impression management, or both and (2) does the construct of repression change as a function of age? Results suggest that in a college age population self-deception characterized the repressor memory; in an elderly population present negative mood state was the only variable predicting repressive memory. / Department of Psychological Science
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Transcriptional Repression of the Plasminogen Activator Inhibitor Type 2 GeneOgbourne, Steven Unknown Date (has links)
Plasminogen activator inhibitor type 2 (PAI-2) is a serine protease inhibitor traditionally regarded as a regulator of fibrinolysis and extracellular matrix degradation. More recently, PAI-2 has been implicated in diverse processes such as keratinocyte differentiation, cell death and viral pathogenesis. Although PAI-2s limited pattern of expression in vivo generates significant interest in this molecule, little is known about the underlying mechanisms controlling its cell specific regulation. In this thesis, the function that the previously identified PAI-2 gene silencer (Antalis et al., 1996) plays in the regulation of PAI-2 gene expression was investigated. The PAI-2 upstream silencer element 1 (PAUSE-1) is located approximately 1800bp upstream of the PAI-2 transcription initiation site. By employing electrophoretic mobility shift assays and transient transfection assays with mutant PAUSE-1 sequences, the sequence that defines PAUSE-1 was identified as TCT N3 AGA N3 T4. This element was shown to bind a number of protein complexes of similar electrophoretic mobility from various cultured cell lines. Transient transfection assays with the cervical adenocarcinoma, HeLa S3 and the macrophage-like, U937 cell lines, showed that PAUSE-1 repressed transcription by approximately 2.5 fold when cloned into the SV40 promoter or the minimal PAI-2 promoter. Ultraviolet (UV)-crosslinking analyses determined that the PAUSE-1 binding protein (BP) was approximately 67kDa. Examination of several similar DNA promoter sequences, such as the human IFNb and insulin promoters, suggested that PAUSE-1 might be an example of a universal silencer with the consensus sequence TCT Nx AGA, where x=4. The PAUSE-1 sequence shows significant homology to the binding sequence of the transcriptional regulators Ski, Smad3 and Smad4. EMSAs incorporating anti-Ski, -Smad3 and -Smad4 antibodies suggested that each are members of the PAUSE-1 BP complex in HeLa S3 cells. The PAUSE-1 BP complex has been purified by employing DNA affinity chromatography using streptavidin labelled magnetic beads. Approximately nine PAUSE-1 associated proteins from HeLa S3 extracts were visualised. Amino-terminal protein sequencing identified the first eight amino acids of the PAUSE-1 BP as EIQQRAAQ. The PAUSE-1 BP fails to show significant sequence similarity to any known protein and therefore potentially represents a novel DNA binding protein.
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Charakterisierung und Nachweis des E8Ê2C Repressorproteins des humanen "high-risk" Papillomvirus Typ 31 (HPV31)Zobel, Thomas, January 2005 (has links)
Tübingen, Univ., Diss., 2005.
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Understanding state repression in the light of gender equality : Exploring under which conditions states use violent repression toward violent and nonviolent dissentLarsson, Jenny January 2018 (has links)
States respond to dissent with repressive means to stay in power. However, there are observed variations in how violently this repressive behavior actually is. Drawing on theories using gender inequality as one of the main, but often dismissed, determinants of violence and armed conflict, the thesis hypothesizes that attitudes to gender equality can help explain the variations in state repression. The theoretical argument is grounded in how gender norms characterized by militarized masculinities shape conflict norms since it is related to how ‘others’ in general are treated in society. By employing regression analysis, and testing the relationship between gender equality, operationalized through the Women’s Political Empowerment Index, and state repression in relation to a maximalist campaign, I found statistical support for the hypothesis that at higher levels of gender equality, repression is less likely to be extreme. The results also suggest that previous repressive behavior matters and that the severity of repression depends on the primary method of resistance within the campaign as well. The thesis thus further reinforces the importance of incorporating gender equality when attempting to explain collective violence.
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When Activism Is Terrorism: Special Interest Politics and State Repression of the Animal Rights MovementShirley, Wesley, Shirley, Wesley January 2012 (has links)
The radical animal rights movement has been labeled a terrorist movement by federal law enforcement and elected officials, and there have been laws passed making direct action in the name of animal rights a federal offense of domestic terrorism. This dissertation explores the ways in which terrorism has been socially and politically constructed to marginalize the animal rights movement, to the benefit of powerful and well connected interests. I do this by comparing the radical animal rights and extreme anti-abortion movements, especially in the ways each gets labeled by federal law enforcement. The animal rights movement is more likely to be referred to as a terrorist movement, even though the extreme anti-abortion movement has been responsible for the murders and assaults of health clinic workers and doctors. This in spite of the fact that no one has been physically harmed by the animal rights movement. I examine the ways in which the pharmaceutical and bio-medical industries have been able to get laws passed, at both the state and federal levels, criminalizing animal rights activism. I also explore the various ways animal rights activists have faced political repression based on their political beliefs, as well as the response of animal rights activists and civil liberties lawyers to this form of state repression.
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Poder sobre a vida: Herbert Marcuse e a biopolítica / Power over life: Herbert Marcuse and biopoliticsSilvio Ricardo Gomes Carneiro 12 September 2014 (has links)
A pesquisa apresenta a teoria marcuseana do poder como perspectiva crítica no debate contemporâneo acerca do conceito foucaultiano de biopolítica. À primeira vista, tal relação parece controversa, ao reconhecer que Foucault desenvolve seu conceito paralelamente à crítica contra Marcuse. Ora, o conceito foucaultiano de biopolítica descreve jogos de poder como administração dos corpos e também como um modo de cálculo da vida da população. Tal concepção contraria diretamente a hipótese marcuseana do poder repressivo, um modelo crítico que tem em vista uma camada verdadeira e subjacente de poder, recalcada nas formações sociais e subjetivas estabelecidas. Com esse quadro, como reunir os dois autores na crítica do poder, assumindo a biopolítica como premissa da teoria do poder? De fato, a aproximação seria impossível ao partir da aposta marcuseana em uma civilização nãorepressiva, presente em Eros e Civilização. Contudo, com a análise do avanço da racionalidade instrumental no pós-Guerra em O Homem Unidimensional, Marcuse avalia a possibilidade de um poder não-repressiva. Afinal, na nova ordem social não se apresenta mais um controle repressivo dos corpos, mas sim uma excitação da vida e dos corpos em movimento. Seria este um sinal de concordância entre os autores? E ainda, dada esta nova correspondência, é possível aproveitar a crítica foucaultiana à biopolítica para redimensionar não apenas as reflexões de Marcuse sobre o poder, como também as passagens contemporâneas entre a teoria crítica e a genealogia do poder? / This research presents Marcuses theory of power as an essential perspective for the contemporary debate on the Foucaultian concept of biopolitics. This would seem a rather controversial choice at a first glance, as, admittedly, the development of Foucaults concept occurred alongside that of his critique of Marcuse. Indeed, Foucaults conception of biopolitics describes games of power that include the administration of the bodies and the calculated management of the life of a given population a notion entirely adverse to Marcuses repressive hypothesis of power, a critical model that assumes a real, subjacent layer of power that is repressed in established social and subjective formations. Given these differences, as well as an adoption of biopolitics as a fundamental premise for a theory of power, how are the two authors to be brought together for a critique of power? Such an approximation would certainly be impossible in light of Marcuses arguments, in Eros and Civilization, for the possibility of a non-repressive civilization. Still, through the analysis of the advancement of instrumental rationality in the postwar period conducted in One- Dimensional Man, Marcuse will revise his former perspective on non-repressive power; after all, the new social order no longer features a repressive control of bodies, but rather an excitation of life, and of bodies to motion. Could that be understood as a sign of agreement between the authors? Furthermore, given this new correspondence, would it be possible to employ Foucaults critique to add dimensions not only to Marcuses reflections on power, but to contemporary mediations between critical theory and the genealogy of power?
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Resistência e repressão no oeste paranaense : o caso da VAR--Palmares em Nova Aurora em 1970 / Resistance and repression in west paranaense: the case of Var-Palmares in Aurora in 1970Campos, Marcos Adriani Ferrari de 04 September 2014 (has links)
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Previous issue date: 2014-09-04 / This research aims to establish some reflections on the resistance to dictatorship and repression in western Paraná, in Nova Aurora from a study on the Var Palmares, more particularly herein, a "territorial command" formed in 1969, by people linked to the regional revolutionary group of Rio Grande do Sul and local peasants. Developed its activities in the area where work was done for the regimentation of guerrilla training, aiming at the strengthening of leftist groups against dictatorship. This command leaders were also teachers, associating strength with work and social policy through the magisterium at full awareness. All of this group were arrested and tortured in May 1970 on charges of terrorist execute banking expropriations and participation in kidnappings / A presente pesquisa tem por objetivo estabelecer algumas reflexões sobre a resistência à ditadura e a repressão no Oeste Paranaense, no município de Nova Aurora a partir de um estudo sobre a Var-Palmares, mais particularmente aqui, um comando territorial formado em 1969, por pessoas ligadas ao grupo revolucionário regional do Rio Grande do Sul e camponeses locais. Desenvolveram suas atividades na região onde foi feito um trabalho de arregimentação para o treinamento de guerrilha, visando o fortalecimento dos grupos de esquerda contra a ditadura. Os líderes deste comando também eram professores, associando a resistência com o trabalho de conscientização social e política através do magistério em pleno regime. Todos daquele grupo foram presos e torturados em maio de 1970, acusados de terroristas, realizarem expropriações bancárias e participação em sequestros
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