This thesis examines the role of both the local and international media during the May 2000 coup, to determine whether the coverage was fair and to suggest solutions for the future. It will first discuss and compare literature that has been written on the Fiji coups, focusing on literature on the media and the coups in particular. According to Fowler (1991) the role of a journalist is to collect facts, report them objectively and present them fairly and without bias in language which is designed to be unambiguous, undistorting and agreeable to readers. However, in most times this is not the case. A thematic content analysis will be done on news articles that appeared in The Fiji Times, The New Zealand Herald and The Australian to find common themes during the coverage of the crisis. A lot of criticism of the both the local and international media’s role during the May 2000 coup emerged after the crisis. Critics included editors and journalists of the local and international media and political and historical analysts who knew the ‘real reasons’ behind the coup and did not see this being reported. A summary of interviews with journalists and editors who covered the coup, both local and overseas, will give an insight into their thoughts and reactions during the coup. It will also determine whether the journalists suffered from the Stockholm syndrome. The Stockholm syndrome describes the behaviour of kidnap victims or people who associate a lot with the captors, and who over time become sympathetic to their captors. The name is derived from a 1973 hostage siege in Stockholm, Sweden when at the end of six days of captivity at a bank; several kidnap victims actually resisted rescue attempts, and afterwards refused to testify against their captors. During the Fiji coup, apart from Speights supporters, journalists were the only ones who spent a lot of time with the coup leader either at press conferences or staying at Parliament to get good stories. As a result, some journalists began to ‘sway’ towards Speight or began to experience the Stockholm syndrome which was reflected in their stories. The thesis concludes that a few journalists in Fiji did suffer from the Stockholm syndrome. It also concludes that a crisis manual is needed for media organisations in Fiji to avoid the same mistakes being repeated as in the last three coups. The overseas media on the other hand need to attach themselves to the local media to avoid parachute journalism and inaccurate reporting. Overseas media organisations need to assign special reporters to Pacific Island affairs to understand the culture and other complex issues which would help in reporting their issues fairly and accurately.

Democracies worldwide are facing a third wave of autocratization, in which a new model tactic has emerged to end democracies. During previous waves coup d’état have been the main reason why democracies breakdown. However, they do still occur during the third wave of autocratization, but previous research has focused on theoretically develop the reasons for why coups occur through focusing on the military and specific regions. In addition, various definitions exist regarding coup d’état, and as a result, its definition has become fragmented, which has had real-life implications. The Capitol Insurrection that occurred in the United States on January 6th, 2021, introduced an unprecedented attack on one of the world’s most prominent and noticeable democracies, intending to overturn the 2020 Presidential Election. The Capitol Insurrection has been defined as a domestic terrorist attack and, thus, not an attempted takeover. Therefore, this thesis aims to analyze the concept of coup d´état to develop the understanding of takeover attempts in democracies. In addition, it aspires to theoretically develop the concept of takeovers in democracies through applying a multiple-case design consisting of three cases that have been defined as coups and three cases that follow the new tactic used in the third wave of autocratization. The thesis summarizes the previous definitions and explanations regarding takeovers and applies that to analyze how and what characterized the six cases. In addition, the findings of the six cases are compared to the previous definitions to analyze what speaks for and against a broadened definition of a takeover. The analysis of this thesis finds and argues for that there is a need to redefine the model tactic during the third wave of autocratization to a type of takeover performed by the chief executive and political elites, in other words, performed by the government for government.

The concern that democracy in the largest country in Latin America could drive toward fascism has surfaced as a point of departure for the creation of forms of resistance among Brazilians in the diaspora. This thesis addresses this development by bringing to light the narratives of FIBRA, a transnational social movement created in 2016 to denounce the coup in Brazil. By combining militant, translocal and online ethnography, this thesis explores how FIBRA has constructed its narratives surrounding the erosion of democracy in Brazil. It looks at the experience of Brazilian migrants involved in campaigning against the impeachment of former president Dilma Rousseff, the imprisonment of former president Luiz Inácio Lula da Silva, the assassination of the activist Marielle Franco, and the victory of Jair Bolsonaro in the 2018 presidential election. Anthropological theories on social movement, democracy and narrative are revisited in order to investigate FIBRA’s role in shaping ideas and expectations towards democracy. This thesis also explores ways to bring the artistic practices in the field into the anthropological text. I use elements of Bertolt Brecht’s Epic Theater, Greek Tragedy and Carnival in my writing and employ these artistic languages as conceptual tools to develop a notion of democracy as a tragic carnivalesque hero. In the spirit of the Brazilian carnivalesque, this thesis celebrates the subversive dimension of the relation between the “playful”, the “political”, and the “academic”.

El proyecto de investigación "Análisis del discurso periodístico de la prensa peruana en el frustrado levantamiento militar del 13 de noviembre de 1992" tiene el propósito de realizar un análisis en el discurso, como su nombre lo indica, basado en una muestra de los medios nacionales. elegido de una manera completamente aleatoria, con el fin de determinar el tipo de cobertura de los eventos que describen el título. Cabe señalar que los hechos en el asunto de los acontecimientos en el régimen dictatorial de Alberto Fujimori (1992-2000), por lo tanto, como una indicación, también se pretende mostrar si existe alguna relación, desde la situación política, con respecto a los discursos. construido a partir de la prensa seleccionada. Por lo anterior, el trabajo presentado tiene dos capítulos. El primero es un acercamiento a los términos y concepciones que condicionan el discurso, los medios a los hechos, aquellos que han tenido la necesidad actual de profundizar en los derechos más correctos de estas concepciones para, así, comprender la influencia de éstas. mostrado. El segundo, finalmente, planificó, a través de los criterios de evaluación, determinar el tipo de discurso que tuvo lugar durante los eventos, el análisis de estos criterios por cada medio de la muestra. / The research project "Analysis of the journalistic discourse of the Peruvian press in the frustrated military uprising of November 13, 1992" has the purpose of carrying out an analysis in the speech, as its name indicates, based on a sample of the national media, chosen in a completely random manner, in order to determine the type of coverage of the events that describe the title. It should be noted that the facts in the matter of the events in the dictatorial regime of Alberto Fujimori (1992-2000) so, as an indication, it is also intended to show whether there is any relationship, from the political situation, regarding speeches constructed from the selected press. For the above, the work presented has two chapters. The first is an approach to the terms and conceptions that condition the discourse, the means to the facts, those that have had the present need to delve into the most correct rights of these conceptions to, thus, understand the influence of these In the coverage shown. The second, finally, planned, through the evaluation criteria, to determine the type of discourse that took place during the events, the analysis of these criteria by each medium of the sample. / Trabajo de investigación

ABSTRACT Retinoic acid (RA) is a positive regulator of P19 EC cell differentiation. Pre-B cell leukemia transcription factors (PBXs) act in conjunction with homeobox genes during cell differentiation. PBX mRNA and protein levels are increased rapidly in P19 cells during RA-induced differentiation. However, silencing of PBX expression in P19 cells (AS cells) results in a failure of these cells to differentiate upon RA treatment. Chicken Ovalbumin Upstream Promoter Transcription Factor I (COUP-TFI) and Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII) are orphan members of the steroid-thyroid hormone superfamily. The mRNA and protein levels of both COUP-TFI and COUP-TFII are low in proliferating wild type P19 EC cells. However, when wild type P19 cells are induced to differentiate upon RA treatment, COUP-TFI and COUP-TFII mRNA and protein levels are dramatically increased while the levels of pluripotency associated gene products are strikingly reduced. Conversely, COUP-TFI and COUP-TFII mRNA levels fail to be elevated upon RA treatment in PBX AS P19 EC cells. Therefore it was hypothesized that COUP-TFs may be downstream targets of PBX and required factors mediating the RA-dependent differentiation cascade in P19 cells. To determine the role of COUP-TFI during differentiation of P19 cells, PBX AS cells that inducibly express V5 tagged COUP-TFI using the Tet-Off® Advanced Inducible Gene Expression system were prepared. Using this system, we demonstrate that exogenous COUP-TFI expression, in a dose-dependent fashion, leads to growth inhibition, modest cell cycle disruption and early apoptosis. Furthermore, using this cell model which inherently is incapable of undergoing RA-mediated differentiation due to blockage of PBX induction, we demonstrate that a supraphysiological level of COUP-TFI expression can overcome the blockage of RA-dependent differentiation in PBX AS cells. However, AS cells expressing a physiological level of COUP-TFI differentiate to endodermal cells only upon treatment with RA. Additionally, gene expression studies indicate that the reductions of pluripotency maintenance genes observed in the COUP-TFI expressing cells are similar to that of wild type P19 cells (upon RA treatment) suggesting that COUP-TFI expression is a driving force towards loss of pluripotency. Moreover, gene expression studies indicate COUP-TFI is involved in the regulatory modulation of at least two RA response genes, CYP26A1 and HoxA1, indicating that COUP-TFI may have some effect on either maintaining or reducing these genes expression levels when COUP-TFI becomes expressed. COUP-TFII is expressed as two distinct variants, Variant 1(V1) and Variant 2 (V2). V1 is the variant that functions as a classical nuclear receptor by binding target DNA sequences and affecting gene transcription whereas V2 is a truncated form of V1 lacking the ability to bind DNA. We therefore hypothesized that V2 could serve as a dominant negative receptor by limiting the amount of functional V1 in the cell. Unexpectedly, we found using P19 cells that overexpress V2 that RA-mediated differentiation proceeded normally suggesting V2 does not function as a dominant negative repressor. Taken together, these studies demonstrate for the first time (i) that COUP-TFI functions as a physiologically relevant regulator during RA-mediated endodermal differentiation of P19 cells and (ii) COUP-TFII V2 is endogenously expressed in P19 cells; however its role during RA-mediated differentiation remains unclear. / Biochemistry

This paper is a study of the journalistic practices currently involved in reporting on Myanmar since the 2021 military coup. Research was undertaken to get an understanding of what methods and to what extent journalists continue to publish quality, balanced reports in a context where independent press faces severe repression by authorities. Through a series of in-depth interviews with individuals working in the Myanmar media field, a collection of experiences and voices were gathered to understand the current journalistic playing field. A textual analysis was performed on themes reported on by a select group of media outlets which are currently operating in exile. Research findings were applied to a loose theoretical framework that comes under the ‘communication for development’ umbrella. Specifically, theories on particular features of globalisation, media for development and humanitarian journalism were examined and applied to as great an extent as possible. This paper finds that journalists reporting on Myanmar offer valuable experience, strategies and lessons learned in reporting remotely, as well as insights into current and impending challenges they are required to surmount in order to continue to produce quality news in a highly polarised context.

On estime qu'environ 5 millions d'hommes américains souffrent de taux de testostérone réduits ou d'hypogonadisme. Chez les hommes, les cellules de Leydig sont les principales productrices de testostérone et d'insuline-like 3, deux hormones essentielles à la différenciation sexuelle masculine, aux fonctions reproductives et à la santé globale de l’homme. Les facteurs de transcription sont des protéines qui régulent la transcription des gènes en se liant à des séquences d'ADN spécifiques. Le facteur de transcription “chicken ovalbumin upstream promoter type 2” (COUP-TFII) est un facteur de transcription qui appartient à la superfamille des récepteurs nucléaires. Dans le testicule, COUP-TFII est exprimé dans les cellules se différenciant en cellules de Leydig adulte (ALCs) pleinement fonctionnelles et joue un rôle majeur dans leur différenciation et leur fonction. La synthèse des stéroïdes est réduite dans des cellules de Leydig appauvries en COUP-TFII, ce qui suggère que ce facteur joue un rôle important dans la stéroïdogenèse. Cependant, le mécanisme d'action de COUP-TFII dans les cellules de Leydig demeuraient largement méconnus. Dans cette thèse, une analyse des données de puces à ADN de cellules MA-10 Leydig appauvries en COUP-TFII a été effectuée afin d’identifier le rôle global de ce facteur dans les cellules de Leydig. Cette étude a permis d’identifier 262 gènes différentiellement exprimés, notamment Hsd3b1, Cyp11a1, Prlr, Pdgfra, Shp, Ear1, Amhr2, Fdx1, Inha et Gsta3. De plus, l’étude du promoteur proximal d’Amhr2 par des études de gène rapporteur a permis de démontrer que COUP-TFII est recruté au promoteur proximal d’Amhr2 et coopère avec SP1 et GATA4 afin de réguler son expression. Les résultats présentés dans cette thèse fournissent une meilleure compréhension du mécanisme d'action de COUP-TFII dans les cellules de Leydig, et des preuves supplémentaires renforçant l'importance du récepteur nucléaire COUP-TFII dans la stéroïdogenèse, l'homéostasie androgénique, la défense cellulaire et la différenciation des cellules de Leydig. / It is estimated that about 5 million American men have low testosterone levels, hypogonadism, and infertility problems. Leydig cells are the primary producers of testosterone and insulin-like 3 hormones in males, both essential for male sex differentiation, reproductive roles, and overall health. Transcription factors are proteins that bind to various DNA sequences to control DNA transcription. Chicken ovalbumin upstream promotertranscription factors II (COUP-TFII) belongs to the steroid/thyroid hormone nuclear receptor superfamily of transcription factors. COUP-TFII is expressed in the cells that give rise to fully functional steroidogenic Adult Leydig cells in the testis and plays an important role in their function and differentiation. Steroid synthesis is reduced in COUP-TFII-depleted Leydig cells, suggesting that this protein plays a vital role in steroidogenesis. However, the mechanisms of action of COUP-TFII in Leydig cells were largely unknown. The analysis of microarray data from COUP-TFII-depleted MA-10 Leydig cells identified 262 differentially expressed genes, including Hsd3b1, Cyp11a1, Prlr, Pdgfra, Shp, Ear1, Amhr2, Fdx1, Inha, and Gsta3. Anti-Müllerian hormone (AMH), which is expressed in Sertoli cells, is essential for the regression of the Müllerian ducts during male embryonic development. In Leydig cells, AMH signals through the anti-Müllerian hormone type II receptor (AMHR2). In male mammals, mutations affecting AMH or AMHR2 expression cause Persistent Müllerian Duct Syndrome (PMDS), characterized by infertility, inguinal hernias, cryptorchidism, and reduced serum testosterone levels. COUP-TFII was found to cooperate with specificity protein 1 (SP1) and GATA-binding factor 4 (GATA4) in the regulation of the Amhr2 promoter using reporter promoter assays. COUP-TFII and GATA4 were found to be recruited to the same region of the Amhr2 gene via chromatin immunoprecipitation assay (ChIP), further strengthening their cooperative roles in the regulation of this gene. Furthermore, COUP-TFII and GATA4 were found to associate in the Leydig cells molecularly. The results presented in this thesis provide a better understanding of the mechanism of COUP-TFII action in Leydig cells, and additional evidence strengthening the importance of COUP-TFII in steroidogenesis, androgen homeostasis, cellular defense, and differentiation.

Orientador: Rafael Salatini Almeida / Resumo: Onze anos de guerra (1963/1973-1974) deixaram marcas indeléveis nos povos africano das colônias portuguesas, em particular de Guiné-Bissau e de Cabo Verde, marcas de quinhentos anos de feroz dominação de colonialistas e imperialismo português, que deixaram como herança países fragmentados e politicamente instáveis, enfraquecidos por conflitos internos. Assim, a presente dissertação procura entender o processo de movimento emancipatória contra o império português para a independência de Guiné-Bissau e Cabo-Verde, e esclarecer algumas dúvidas obscurecidas e distorcidas sobre reais fracassos, limitações e avanços do Partido Africano da Independência da Guiné e Cabo Verde (PAIGC), após a conquista das independências que permitiram emancipação de movimento reajustador de 14 de novembro, e, consequentemente, o golpe de Estado de 1980. Entender elementos de fragilidade do sistema político de Guiné-Bissau, que permitiram a ruptura democrática de 14 de novembro de 1980, e, consequentemente, o golpe de Estado que depôs o primeiro presidente da república democraticamente eleito, bem como analisar o governo posterior do presidente João Bernardo Nino Vieira. Nesse sentido, a estratégia metodológica selecionada para aproximar-se do real foi o estudo documental e bibliográfico, isto é, a pesquisa em livros, teses, dissertações, e jornais etc., que apresentam características relevantes do ponto de vista teórico e empírico para o tema. A conclusão que chegamos alimentam a tese de que o fato d... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Eleven years of war (1963/1973-1974) left indelible marks on the African peoples of the Portuguese colonies, in particular Guinea-Bissau and Cape Verde, marks of five hundred years of ferocious domination of colonialists and Portuguese imperialism, that left as inheritance countries fragmented and politically unstable, weakened by internal conflicts. Thus, this dissertation seeks to understand the process of emancipatory movement against the Portuguese empire for the independence of Guinea-Bissau and Cape Verde, and to clarify some obscured and distorted doubts about the real failures, limitations and advances of the African Party of Guinean Independence and Cape Verde (PAIGC), after the conquest of independence that allowed the emancipation of the readjustment movement of November 14, and consequently the coup d’État of 1980. Understand elements of fragility of the political system of Guinea-Bissau, which allowed the democratic rupture of November 14, 1980, and, consequently, the coup d’État that deposed the first president of the democratically elected republic, as well as analyze the subsequent government of President João Bernardo Nino Vieira. In this sense, the methodological strategy selected to approximate the real was the documentary and bibliographic study, that is, the research in books, theses, dissertations, etc., which present relevant theoretical and empirical characteristics for the subject. Our conclusion is that the fact that the transition and consolidation ... (Complete abstract click electronic access below) / Mestre

Submitted by BERNARDO JOSÉ ANTONIO PARALTA (bernardo.paralta@gmail.com) on 2018-09-24T14:31:31Z No. of bitstreams: 1 Dissertação de mestradoBernardo.pdf: 1073036 bytes, checksum: c4cc55c5d8d5135382771d14af025401 (MD5) / Approved for entry into archive by Satie Tagara (satie@marilia.unesp.br) on 2018-09-24T16:55:31Z (GMT) No. of bitstreams: 1 paralta_bja_me_mar.pdf: 1073036 bytes, checksum: c4cc55c5d8d5135382771d14af025401 (MD5) / Made available in DSpace on 2018-09-24T16:55:31Z (GMT). No. of bitstreams: 1 paralta_bja_me_mar.pdf: 1073036 bytes, checksum: c4cc55c5d8d5135382771d14af025401 (MD5) Previous issue date: 2018-08-29 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Onze anos de guerra (1963/1973-1974) deixaram marcas indeléveis nos povos africano das colônias portuguesas, em particular de Guiné-Bissau e de Cabo Verde, marcas de quinhentos anos de feroz dominação de colonialistas e imperialismo português, que deixaram como herança países fragmentados e politicamente instáveis, enfraquecidos por conflitos internos. Assim, a presente dissertação procura entender o processo de movimento emancipatória contra o império português para a independência de Guiné-Bissau e Cabo-Verde, e esclarecer algumas dúvidas obscurecidas e distorcidas sobre reais fracassos, limitações e avanços do Partido Africano da Independência da Guiné e Cabo Verde (PAIGC), após a conquista das independências que permitiram emancipação de movimento reajustador de 14 de novembro, e, consequentemente, o golpe de Estado de 1980. Entender elementos de fragilidade do sistema político de Guiné-Bissau, que permitiram a ruptura democrática de 14 de novembro de 1980, e, consequentemente, o golpe de Estado que depôs o primeiro presidente da república democraticamente eleito, bem como analisar o governo posterior do presidente João Bernardo Nino Vieira. Nesse sentido, a estratégia metodológica selecionada para aproximar-se do real foi o estudo documental e bibliográfico, isto é, a pesquisa em livros, teses, dissertações, e jornais etc., que apresentam características relevantes do ponto de vista teórico e empírico para o tema. A conclusão que chegamos alimentam a tese de que o fato de a transição e consolidação da democrática em Guiné-Bissau terem partido de base de regime militar contribuiu para que houvesse poderosa contradições entre o regime, tanto da primeira como da segunda república, variável que por si só pode oferecer razões para tantos golpes de Estados, e o fracasso na consolidação da democracia em Guiné-Bissau. Acreditamos, contudo, que outros fatores não diretamente relacionado a essa variável ajudam igualmente a explicar as tentativas e os golpes dos anos posteriores. / Eleven years of war (1963/1973-1974) left indelible marks on the African peoples of the Portuguese colonies, in particular Guinea-Bissau and Cape Verde, marks of five hundred years of ferocious domination of colonialists and Portuguese imperialism, that left as inheritance countries fragmented and politically unstable, weakened by internal conflicts. Thus, this dissertation seeks to understand the process of emancipatory movement against the Portuguese empire for the independence of Guinea-Bissau and Cape Verde, and to clarify some obscured and distorted doubts about the real failures, limitations and advances of the African Party of Guinean Independence and Cape Verde (PAIGC), after the conquest of independence that allowed the emancipation of the readjustment movement of November 14, and consequently the coup d’État of 1980. Understand elements of fragility of the political system of Guinea-Bissau, which allowed the democratic rupture of November 14, 1980, and, consequently, the coup d’État that deposed the first president of the democratically elected republic, as well as analyze the subsequent government of President João Bernardo Nino Vieira. In this sense, the methodological strategy selected to approximate the real was the documentary and bibliographic study, that is, the research in books, theses, dissertations, etc., which present relevant theoretical and empirical characteristics for the subject. Our conclusion is that the fact that the transition and consolidation of democracy in Guinea-Bissau started from a military regime has contributed to the existence of powerful contradictions between the regime of both the first and second republics, it can only offer reasons for so many coups, and the failure to consolidate democracy in Guinea-Bissau. We believe, however, that other factors not directly related to this variable also help explain the attempts and the blows of later years.

Arteriosklerose führt zu schwerwiegenden klinischen Komplikationen bei Herz-Kreislauf-erkrankungen, welche die führenden Todesursachen in den westlichen Industrieländern sind. Die Arteriosklerose ist typischerweise eine Erkrankung arterieller Gefäße und betrifft nicht die venöse Gefäßwand. Bei der Entstehung von Arteriosklerose spielen die Endothelzellen als Barrierezellen und Regulatoren der Gefäßfunktion eine Schlüsselrolle. Ein wichtiger Schwerpunkt der Forschung ist die Differenzierung der Endothelzellen. Arterielle und venöse Endothelzellen weisen schon im frühen Embryonalstadium unterschiedliche Phänotypen auf. Ein besseres Verständnis der arterio-venösen Differenzierung wäre von großer Bedeutung für antiarteriosklerotische Therapien. Darüber hinaus könnte eine Reprogrammierung (z.B. von Vene in Arterie) entscheidend für neue Therapieansätze bei der Senkung der Restenoserate venöser Bypässe von Patienten mit koronarer Herzkrankheit und bei AV-Shunt-Operationen von dialysepflichtigen Patienten sein. In dieser Arbeit wurden differenzierte humane primäre arterielle und venöse Endothelzellen nach Genmodulation untersucht. Der Fokus der Genmodulation wurde auf das arterielle Markergen Hey2 und auf das venöse Markergen COUP-TFII gelegt. Das arterielle Markergen Hey2 ist ein Zielgen der Notch-Signalkaskade, während der molekulare Mechanismus der Rolle von COUP-TFII bei der venösen Differenzierung noch nicht bekannt ist. Daher wurde der Einfluss des arteriellen Markergens Hey2 und des venösen Markergens COUP-TFII auf die Notch-Signalkaskade untersucht, um ein besseres Verständnis über die molekularen Mechanismen der arterio-venösen Differenzierung zu gewinnen. Da humane primäre Endothelzellen mit kommerziell verfügbaren Transfektionsmitteln schwer transfizierbar sind, wurde zunächst ein lentivirales Vektorsystem etabliert. Hiermit wurde eine erfolgreiche und stabile Genexpression bzw. Genrepression in arteriellen und venösen Endothelzellen ermöglicht. Die Genmodulationen in arteriellen Endothelzellen, die durch die Expression des venösen Markergen COUP-TFII bzw. durch die Repression des arterellen Markergen Hey2 verursacht wurden, führten zu der neuen Erkenntnis, dass das venöse Markergen COUP-TFII in arteriellen Endothelzellen als ein Repressor des arteriellen Markergens Hey2 fungiert. Diese Repression wird durch eine direkte Bindung von COUP-TFII an den Hey2-Promotor vermittelt. Die COUP-TFII Expression bewirkte keine Veränderung in der Expression von Notch4, Dll4 und Nrp1. Dies könnte bedeuten, dass (i) COUP-TFII in arteriellen Endothelzellen kein Regulator von diesen Genen ist, (ii) Kooperationspartner von COUP-TFII fehlen, die in arteriellen Endothelzellen nicht vorhanden sind, oder (iii) der molekulare Mechanismus dieser Gene aufgrund seiner wichtigen Rolle nicht durch die Modifikation eines einzigen Gens beeinflussbar ist, da die Gene der Notch-Signalkaskade redundant kontrolliert werden. In venösen Endothelzellen wurden Genmodulationen durch Expression des arteriellen Markergens Hey2 bzw. durch die Repression des venösen Markergens COUP-TFII durchgeführt. Eine Expression des arteriellen Markergens Hey2 in venösen Endothelzellen konnte nicht die Expression der Gene der Notch-Signalkaskade aktivieren. Dies bedeutet, dass die Regulation dieser Gene durch einen übergeordneten molekularen Mechanismus gesichert ist. Interessanterweise konnte die Expression von Hey2 eine Reduktion der Hey1 Expression bewirken. Dies ist ein alternativer Effekt von Hey2 im Vergleich zu arteriellen Endothelzellen. Eine Repression des venösen Markergens COUP-TFII konnte die Expression der Gene Dll4, EphrinB2 und EphB4 induzieren. Vermutlich ist die Induktion der EphB4 Expression ein Kompensationsmechanismus auf die reduzierte COUP-TFII Expression. COUP-TFII sichert den venösen Phänotyp wahrscheinlich durch die Repression von EphrinB2 und Dll4, wobei die Reduktion von Dll4 vermutlich eine größere Bedeutung hat. Da Dll4 ein Ligand und Aktivator der Notch-Signalkaskade ist, ist seine Repression entscheidend für venöse Endothelzellen. Das arterielle Markergen Hey2 ist für die normale Embryogenese von großer Bedeutung, jedoch ist Hey2 als eines der Zielgene der Notch-Signalkaskade wahrscheinlich nicht in der Lage, molekulare Mechanismen, die zu unterschiedlichen endothelialen Phänotypen führen, zu aktivieren. Um arterielle Endothelzellen zu einem Reprogramming zu bewegen, wären wahrscheinlich Genmodulationen der Mitglieder der Notch-Signalkaskade, die upstream von Hey2 liegen, nötig. Hingegen ist die Rolle des venösen Markergens COUP-TFII in der Regulation der arterio-venösen Differenzierung von entscheidender Bedeutung. COUP-TFII spielt eine direkte Rolle in der Aufrechterhaltung der venösen Identität. Die Repression von COUP-TFII in venösen Endothelzellen bewirkt, dass sich die Expression des Gens Dll4, das die Notch-Signalkaskade aktiviert, in Richtung des arteriellen Expressionsniveaus bewegt. Für eine Reprogrammierung der venösen Endothelzellen in einen arteriellen Phänotyp ist das venöse Markergen COUP-TFII eines der Zielgene.