Cells of the stratified adult corneal epithelium undergo centripetal migration throughout adult life from the edge of the cornea to the centre. To date nothing is known about the mechanism underpinning the oriented cellular migration. Failure to replenish apoptotic cells lost by desquamation from the superficial layer of the corneal epithelium leads to severe pathological conditions that may result in blindness. In this study we investigated the role of planar cell polarity (PCP) core proteins as the guidance cue for centripetal migration in the cornea. Cre-mediated conditional deletion of floxed alleles of the core PCP gene Vangl2 in the corneal epithelium and lens of adult mice was achieved. The effect of this deletion was studied by microscopic and immunohistological observation of the cornea compared to littermate controls, showing defects consistent with disrupted apical-basal polarity in mutant mice. Planar behaviour of the corneal epithelial cells was assayed by breeding the mutant alleles (Le-CreTg/-; Vangl2flox/flox) and the Looptail mouse (Vangl2Lp/+) onto an X-linked LacZ reporter transgene (XLacZ) background, demonstrating the importance of PCP core components for normal cell migration. In vitro directional migration studies were performed on Vangl2 and Frizzled6 knock-down human corneal epithelial cells following the application of direct current electric fields (DC-EFs), resulting in the reduction of directional migratory response to the DC-EF. This study showed for the first time roles for the planar cell polarity (PCP) signalling in orchestrating and coordinating cellular cues that drive oriented migration in the unwounded adult corneal epithelium. It is likely that mutations in PCP genes could lead to ocular surface abnormalities in humans.

Immigration into Europe has always been at the center of EU’s agenda. With the candidacy of Turkey for entry into the EU, the issue of immigration is being discussed with a new intensity. That is why this paper aims to understand the dynamics that will govern Turkish migration into EU after membership and to provide a sound basis for its complicated nature. In order to do that, different theories of migration have been categorized at different levels of approaches and analyzed to understand the reasons for migration. To ground these theories in the reality of migration, the statistics on countries that joined the EU in 2004 and 2007 have been used. After identifying the reasons why citizens of these new member states migrate, prospective Turkish migration has been analyzed accordingly. It has been found out that the reasons for Turkish migration will be mostly the same as those for new member states’ citizens. As a result of this, it has been concluded that the prospective Turkish migration will be extremely diverse and complicated and that the directions of migration will not only be from Turkey to Europe but also from Europe to Turkey.

Immigration into Europe has always been at the center of agenda of the EU. With the candidacy of Turkey, the issue of immigration is being discussed at an accelerating rate. That is why this paper aims to understand the dynamics behind the prospective Turkish migration into EU after membership and to provide a sound basis for its complicated nature. In order to do that, different theories of migration have been categorized at different levels of approaches and analyzed to understand the reasons for migration. To set the relationship between theory and reality of migration, the statistics on countries that joined the EU in 2004 and 2007 have been used. After identifying the reasons why citizens of these new member states migrate, the prospective Turkish migration has been analyzed accordingly. It has been found out that the reasons for Turkish migration will be mostly the same as those for new member states’ citizens. As a result of this, it has been concluded that the prospective Turkish migration will be so diverse and complicated and that the direction of migration will not only be from Turkey to Europe but also from Europe to Turkey.

La migration cellulaire est une étape clé intervenant à un stade précoce de la dissémination des cellules cancéreuses dans l’organisme, et est donc responsable de la formation des métastases qui tuent environ nonante pourcent des patients atteints de cancer. De plus, ces cellules migrantes résistent à l’apoptose grâce à l’activation constitutive de voies de signalisation anti-apoptotiques, et développent donc une résistance vis-à-vis des traitements anti-cancéreux actuels qui sont généralement pro-apoptotiques. Nous avons pris pour cible ce processus de migration cellulaire dans l’espoir d’identifier des agents anti-migratoires qui permettraient de lutter contre la formation des métastases et de restaurer chez les cellules migrantes une certaine sensibilité aux traitements pro-apoptotiques. Dans la première partie de notre travail, nous avons analysé les effets anti-angiogéniques et anti-migratoires des agents anti-tubuline. Nous avons confirmé que le Taxol® présentait une action anti-angiogénique à des concentrations non-cytotoxiques. Nous avons ensuite démontré que d’autres agents anti-tubuline exerçaient la même action que le Taxol®, et que cette action leur était spécifique. Nous avons montré que certains de ces agents étaient également capables de réduire la migration de lignées cellulaires tumorales, toujours à des concentrations non-cytotoxiques, et que cette action pouvait s’exercer via une affectation du cytosquelette d’actine. Dans la deuxième partie du présent travail, nous avons démontré l’importance de la mise au point d’une approche pharmacologique originale permettant l’identification de composés à action anti-migratoire puisque l’outil utilisé par le U.S. National Cancer Institute pour le criblage de nouvelles molécules anti-cancéreuses ne permet pas de discerner l’activité anti-migratoire des molécules testées. Enfin dans la troisième partie de ce travail, après avoir souligné la raison du choix de l’actine comme cible pour inhiber la migration cellulaire, nous avons développé une stratégie pharmacologique in vitro originale de découverte de composés anti-actine à activité anti-migratoire. Grâce à une approche divisée en plusieurs étapes, à savoir un essai de cytotoxicité, une étude de la dynamique de la polymérisation d’actine en tubes ou sur cellules entières, et des essais de migration bidimensionnelle sur cellules individuelles ou sur population cellulaire, nous avons montré d’une part que des molécules connues pour affecter le cytosquelette actinique étaient capables d’affecter la migration cellulaire, et d’autre part que la méthodologie que nous avons développée permettait bien l’identification de composés affectant l’actine et capables de réduire la migration de cellules tumorales. En conclusion, cette stratégie in vitro pourrait être utilisée dans l’identification de nouvelles molécules à activité anti-migratoire pour lutter contre le cancer.

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In this dissertation I explore the relationship between women, the state, and religious institutions in western Austria--the most conservative part of the country. The fall of the Iron Curtain triggered widespread fears of massive migration flows from Eastern Europe, and created strong sentiments against migrants, especially those from the East and South and led to a rise in ethnocentrism and xenophobia. Turks, who comprise the largest migrant population, are especially vulnerable to the resulting discriminatory practices and attitudes.The questions I posed focused on how Turkish women who have arrived since the economic boom of the 1980s, their children born in Austria, and women of pre-WWII Austrian ancestry deal with the challenges integration brings. Further, I examine the effect patriarchal, elitist discourse has on both Austrian and Turkish migrant women's self-perception, sociopolitical status and their worldviews.

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