Deformed epidermal autoregulatory factor 1 (DEAF1) encodes a transcription factor essential in early embryonic and neuronal development. In humans, mutations in the DNA binding domain of DEAF1 cause intellectual disability together with clinical characteristics collectively termed DEAF1-associated neurodevelopmental disorders (DAND). The objective of this study is to 1) assess the pathogenicity of newly identified variants using established functional assays, and 2) confirm and map the interaction domain of DEAF1 with HDAC1 and evaluate the importance of DEAF1-HDAC1 interaction on DEAF1-mediated transcriptional repression. Exome sequencing analysis identified six de novo DEAF1 mutations (p.D200Y, p.S201R, p.K250E, p.D251N, p.K253E, and p.F297S). Promoter activity experiments indicate DEAF1 transcriptional repression activity was altered by p.K250E, p.K253E, and p.F297S. Transcriptional activation activity was altered by p.K250E, p.K253E, p.F297S, and p.D251N. Combined with clinical phenotype of the patients, this work establishes the pathogenicity of new DEAF1 variants. Previous studies identified a potential protein interaction between DEAF1 and several proteins of the nucleosome remodeling and deacetylating (NuRD) complex including Histone Deacetylase 1 (HDAC1), Retinoblastoma Binding Protein 4 (RBBP4), Methyl CpG Binding Domain Protein 3 (MBD3). GST pull-down and co-immunoprecipitation (CoIP) assays confirmed and mapped the interaction with HDAC1 between amino acids 113 – 176 of DEAF1. To determine whether DEAF1-mediated repression requires HDAC1 activity, HEK293t wild type or CRISPR/Cas9-mediated DEAF1 knockout cells were treated with the HDAC inhibitor Trichostatin A (TSA). Interestingly, this study demonstrates that the requirement of HDAC1 activity on DEAF1-mediated transcriptional repression activity is target gene specific and expands our understanding of DEAF1 mediated transcriptional repression.

Submitted in part fulfilment of the requirements for the Degree in Community Psychology in the Department of Psychology, University of Zululand, 2003. / "To penetrate the mysteries, to bless with good conscience, to be great yet empty, to return to stillness and be forgiven, to do good deeds and help people reach the other shore — these are the great benefits of our path of cultivation. To calm people in stormy times, to help them understand the nature of things, to maintain purity, to nourish all things, to respect all life, and to answer the needs of those whose beliefs come from the heart — The sun rises, the darkness is banished; and we are witness to true wonder" (The Religion of Light, 1005). Research in the area of clerical paedophilia in the Catholic Church initially focused on managing the problem at the level of treatment intervention, with treatment centres run by religious orders in the UK and USA. Protocols have been developed worldwide to deal with reports or complaints against Catholic clergy who have allegedly interfered sexually with a child. Yet consideration and evaluation of this intervention clearly highlights the 'after the fact' nature of intervention. Leaders of the Catholic Church are certainly aware of the need for the prevention of mental ill-health, and the promotion of mental health in their ranks. However, it is the negative and vast publicity given to child molestation, and the immediate damage inflicted on the Catholic Church, that has resulted in a 'mop-up operation' rather than an exploration of causes and interventions aimed at prevention and the promotion of a healthy lifestyle. Recently, however, psychologists and philosophers, who have been called on to evaluate the problem in the USA, the UK, Southern Africa, and Australia, have been asking questions such as: Why does this happen in the Catholic Church? Or, more to the point, what needs to be done about it? My guiding hypothesis for the research was: Do Catholic priests constitute a high-risk category for mental ill-health? As regards the second question — what is to be done? — I propose the establishment of a Community Health Centre for Catholic clergy. My research addresses both questions. As regards the first question, the evidence — gathered through interviews and workshops over a period of eight years — points to the conclusion that paedophilia is not purely a problem of intra-psychic factors but also a symptom of the closed and isolated nature of the Catholic institution, whose structures both attract and give life to, otherwise possibly latent pathology. In addition, many priests — young and old — feel unheard and misunderstood, and perceive themselves to have been inadequately trained and poorly supported and managed. It is possible that, combining both intra-psychic repression and institutional suppression, the potential for a disaster such as the crisis the Catholic Church faces today, is created. The community of Catholic priests is perhaps not conceptualized, nor cared for, as a community of male human beings. It is precisely a working model of this community care for Catholic priests, that is being explored in this thesis. This thesis presents a working model - or a work in progress — where any assessment is related to healing and therapeutic intervention, in intentionality and orientation.

No description available.

The presence of state capture and political disadvantages incite the emergence of social movements, which hope to induce a removal of political disadvantages. In Bosnia and Herzegovina (BiH) protests and social movements have been initiated for several reasons, often to lay attention on the government's dysfunction. Nationalism has been shown to potentially be destructive in those ways it is used to silence the opposition and this essay has identified how nationalism has been a tool for politicians to repress social movements in BiH. By using the paper's theoretical framework, a discursive analysis of politicians’ repressive statements towards three different types of social movements has been done. The three types of social movements included in the analysis are the LGBT movement in BiH, the student movements in Jajce and Travnik and the ‘Justice for David’ movement in Banja Luka. The results have shown that repression mostly occurs through emphasizing the threat of the movement in different ways as well as invoking nationalism. Nationalism is also frequently present through the classification of a “we” and “them”. Future research would benefit from explaining why specific aspects of nationalistic discourse are more common than others in politicians' repressive statements.

Estrogens exert numerous actions throughout the human body, targeting healthy tissue while also enhancing the proliferative capacity of breast cancers. Estrogen signaling is mediated by the estrogen receptor (ER), which binds DNA and ultimately affects the expression of adjacent genes. Current understanding of ER-mediated transcriptional regulation is mostly limited to genes whose transcript levels increase following estrogen exposure, though recent studies demonstrate that direct down-regulation of estrogen-responsive genes is also a significant feature of ER action. We hypothesized that differences in cis-regulatory DNA was a factor in determining target gene expression and performed computational and experimental studies to test this hypothesis. From our in silico analyses, we show that the binding motifs for certain transcription factors are enriched in cis-regulatory sequences adjacent to repressed target genes compared to induced target genes, including the motif for RUNX1. In silico analyses were tested experimentally using dual luciferase reporter assays, which indicate that several ER binding sites are estrogen responsive. Mutagenesis of transcription factor motifs (for ER and RUNX1) reduced the response of reporter gene. Further experiments demonstrated that co-recruitment of ER and RUNX1 is necessary for repression of gene expression at some target genes. These findings highlight a novel interaction between ER and RUNX1 and their role in transcriptional repression in breast cancer.

The Red Scare of 1919-1920 has been presented as a wave of anti-Radical hysteria that swept post WWI America; a hysteria to which the state reluctantly capitulated to by arresting Radicals and deporting those alien Radicals they deemed most threatening. This presentation, however, is ludicrous when the motivations of the state and its conservative allies are examined. The truth of the matter was that almost all of the people targeted by the Red Scare represented no significant threat to the institutions of the United States and were merely targeted for holding Leftwing ideas, or being connected to a group that did. This work examines how the Red Scare deportations were used as a performance to gain power and funding for the Bureau of Investigation and how the Bureau sought to use this performance to set itself up as the premier anti-Radical agency in the United States. While the topic of the Red Scare of 1919-1920 has been thoroughly covered, most works on the subject attempt to cover the whole affair or even address it as part of a larger study of political repression in the United States. In these accounts these authors do not see the Red Scare as a performance, which culminated in the Soviet Ark deportations, put on by the BI in order to fulfill its goal of expanding its own importance. This work addresses the events leading up to climactic sailing of the Soviet Ark, as political theater put on by the BI and its allies in order to impress policy makers and other conservative interest groups. Since the Soviet Ark deportations were the climax of the Red Scare performance, this work addresses the event as a theatrical production and follows a three act dramatic structure. It begins by exploring the cast of characters, both individuals and organizations, in the BI’s performance. This is followed by an analysis of the rising action of the BI, and other reactionary iii groups in the evolution of their grand performance. Finally the deportations serve as the climax of the Red Scare in this performance that the BI and its allies would use to justify an expansion of their influence. Through the use of government records, biographies, and first hand accounts, this work explores the Soviet Ark deportations as the high point of the first Red Scare, the point in which the BI and its allies took their quest for expanded power the furthest before having to change course. The grand performance that the Bureau of Investigation put on is looked at, not as a response to placate others – something the BI was merely swept up in – but as a performance that they designed to meet the specific needs of their campaign to grow their agency, a performance for which they were willing to draft those that represented no real threat despite the consequences to those individuals.

This essay explores the feminist message in Kate Chopin’s short story “The Story of an Hour” and Charlotte Perkins Gilman’s “An Extinct Angel” and “The Yellow Wallpaper”. The relationship between space and gender will be examined in connection with theoretical conceptions of female consciousness. The study makes use of feminist theory and is particularly inspired by Virginia Woolf’s conception of the gender-space relationship, along with later feminist critics’ works on gender consciousness. It is argued that the authors, through these short stories, describe the contemporary female experience and propose the claiming of space as the solution to end female repression. The study ultimately shows that these stories convey the authors’ appeal for the awakening of the feminist consciousness - an appeal to kill ‘the angel in the house’.

This dissertation consists of three papers exploring how critical historical moments can produce different electoral patterns in Latin American countries. Through the comprehension of times in which new institutions emerge (or are reformed), the articles investigate how factors can move voters beyond what the discipline has acknowledged as the typical patterns of voting behavior. Specifically, the papers look at elements such as biased information exposure during the expansion of the voting franchise, changes in technological and procedural rules of elections, and long-term exposure to autocratic government repression on the eve of the re-birth of democratic institutions. The first paper studies the 1958 Chilean presidential election to assess the impact of pro-partisan informational channels on aggregate voting patterns by using information retrieved from national election archives and an original dataset for radio stations across the territory. The analysis exploits as-if random variation in signal reception using a linear regression model to estimate the effect of exposure to pro-partisan radio signal strength on electoral results. Results show that exposure to partisan radio substantially increases electoral support for the ideologically closest candidates, providing persuasive evidence regarding the relevance of informational control. The second article explores the effect of the different periods of Pinochet’s repression machinery on the 1988 plebiscite results by using a two-part methodological strategy, achieved through collecting ecological data of repression cases, pre-existing security infrastructure, aggregate electoral outcomes, and survey responses. The first strategy employs a two-stage least square model to observe the possible influence of repression’s geographical variation on electoral outcomes. The second approach looks at a multilevel logistic regression with survey observations to assess the possible influence of different levels of repression on individual self-reported vote choice. Results show a null relationship between the variables of interest, but it is not possible to reject the idea that repression doomed Pinochet’s regime because its effect could be mediated by television and campaign ads. Lastly, the third paper investigates how the introduction of new voting technologies can decrease the rate of residual votes by limiting the capacity of political and bureaucratic agents to intervene during the vote-counting moment. Based on district-level data for elections in Peru and Paraguay, the analysis of this research uses a comparative framework taking advantage of the conditions under which the implementation of electronic voting happened by using a group-time difference-in-difference model. The quantitative exploration is complemented by in-depth interviews conducted in both countries. Results show that the implementation of electronic voting is associated with a decrease in the rate of residual votes that can be attributed to the user—error reduction and the limitation of political activists’ capacities to influence the rate of null votes. The findings of the different articles can serve as an important addition to the broader literature on comparative politics and political behavior in Latin America. Moreover, they highlight the relevance of observing how unique conditions and novel institutional settings might be essential to revisit crucial historical moments and comprehensively understand factors that shape political dynamics.

Authoritarian states have an extended reach on their populations residing outside of the country borders due to globalization and digitalization. This is part of the explanation of the increase of transnational repression globally. The aim of this paper is to investigate how authoritarian regime type affects the incidence of transnational repression. A bivariate hypothesis test is conducted using large scale quantitative methods and mediation analysis in order to conduct the study and investigate how the effect of regime type on transnational repression is mediated by domestic repression. Personalist regimes are expected to repress more domestically than for example single party regimes and therefore engage more in transnational repression. The results are inconclusive for the different measures of personalist rule. It is also suggested from the results that the effect of regime type on transnational repression is partially mediated by the level of domestic repression in the country.

No description available.