VE-PTP controls blood vessel development by balancing Tie-2 activity

Vascular endothelial protein tyrosine phosphatase (VE-PTP) is an endothelial-specific receptor-type tyrosine phosphatase that associates with Tie-2 and VE-cadherin. VE-PTP gene disruption leads to embryonic lethality, vascular remodeling defects, and enlargement of vascular structures in extraembryonic tissues. We show here that antibodies against the extracellular part of VE-PTP mimic the effects of VE-PTP gene disruption exemplified by vessel enlargement in allantois explants. These effects require the presence of the angiopoietin receptor Tie-2. Analyzing the mechanism we found that anti-VE-PTP antibodies trigger endocytosis and selectively affect Tie-2-associated, but not VE-cadherin-associated VE-PTP. Dissociation of VE-PTP triggers the activation of Tie-2, leading to enhanced endothelial cell proliferation and enlargement of vascular structures through activation of Erk1/2. Importantly, the antibody effect on vessel enlargement is also observed in newborn mice. We conclude that VE-PTP is required to balance Tie-2 activity and endothelial cell proliferation, thereby controlling blood vessel development and vessel size.

Agrin defines polarized distribution of orthogonal arrays of particles in astrocytes

Accumulating evidence indicates that agrin, a heparan sulphate proteoglycan of the extracellular matrix, plays a role in the organization and maintenance of the blood-brain barrier. This evidence is based on the differential effects of agrin isoforms on the expression and distribution of the water channel protein, aquaporin-4 (AQP4), on the swelling capacity of cultured astrocytes of neonatal mice and on freeze-fracture data revealing an agrin-dependent clustering of orthogonal arrays of particles (OAPs), the structural equivalent of AQP4. Here, we show that the OAP density in agrin-null mice is dramatically decreased in comparison with wild-types, by using quantitative freeze-fracture analysis of astrocytic membranes. In contrast, anti-AQP4 immunohistochemistry has revealed that the immunoreactivity of the superficial astrocytic endfeet of the agrin-null mouse is comparable with that in wild-type mice. Moreover, in vitro, wild-type and agrin-null astrocytes cultured from mouse embryos at embryonic day 19.5 differ neither in AQP4 immunoreactivity, nor in OAP density in freeze-fracture replicas. Analyses of brain tissue samples and cultured astrocytes by reverse transcription with the polymerase chain reaction have not demonstrated any difference in the level of AQP4 mRNA between wild-type astrocytes and astrocytes from agrin-null mice. Furthermore, we have been unable to detect any difference in the swelling capacity between wild-type and agrin-null astrocytes. These results clearly demonstrate, for the first time, that agrin plays a pivotal role for the clustering of OAPs in the endfoot membranes of astrocytes, whereas the mere presence of AQP4 is not sufficient for OAP clustering.

Myc regulates embryonic vascular permeability and remodeling

Previous work has shown that c-Myc is required for adequate vasculogenesis and angiogenesis. To further investigate the contribution of Myc to these processes, we conditionally expressed c-Myc in embryonic endothelial cells using a tetracycline-regulated system. Endothelial Myc overexpression resulted in severe defects in the embryonic vascular system. Myc-expressing embryos undergo widespread edema formation and multiple hemorrhagic lesions. They die between embryonic days 14.5 and 17.5. The changes in vascular permeability are not caused by deficiencies in vascular basement membrane composition or pericyte coverage. However, the overall turnover of endothelial cells is elevated as is revealed by increased levels of both proliferation and apoptosis. Whole-mount immunohistochemical analysis revealed alterations in the architecture of capillary networks. The dermal vasculature of Myc-expressing embryos is characterized by a reduction in vessel branching, which occurs despite upregulation of the proangiogenic factors vascular endothelial growth factor-A and angiopoietin-2. Thus, the net outcome of an excess of vascular endothelial growth factor-A and angiopoietin-2 in the face of an elevated cellular turnover appears to be a defect in vascular integrity.

Switching of vascular phenotypes within a murine breast cancer model induced by angiopoietin-2

Sustained growth of solid tumours can rely on both the formation of new and the co-option of existing blood vessels. Current models suggest that binding of angiopoietin-2 (Ang-2) to its endothelial Tie2 receptor prevents receptor phosphorylation, destabilizes blood vessels, and promotes vascular permeability. In contrast, binding of angiopoietin-1 (Ang-1) induces Tie2 receptor activation and supports the formation of mature blood vessels covered by pericytes. Despite the intense research to decipher the role of angiopoietins during physiological neovascularization and tumour angiogenesis, a mechanistic understanding of angiopoietin function on vascular integrity and remodelling is still incomplete. We therefore assessed the vascular morphology of two mouse mammary carcinoma xenotransplants (M6378 and M6363) which differ in their natural angiopoietin expression. M6378 displayed Ang-1 in tumour cells but no Ang-2 in tumour endothelial cells in vivo. In contrast, M6363 tumours expressed Ang-2 in the tumour vasculature, whereas no Ang-1 expression was present in tumour cells. We stably transfected M6378 mouse mammary carcinoma cells with human Ang-1 or Ang-2 and investigated the consequences on the host vasculature, including ultrastructural morphology. Interestingly, M6378/Ang-2 and M6363 tumours displayed a similar vascular morphology, with intratumoural haemorrhage and non-functional and abnormal blood vessels. Pericyte loss was prominent in these tumours and was accompanied by increased endothelial cell apoptosis. Thus, overexpression of Ang-2 converted the vascular phenotype of M6378 tumours into a phenotype similar to M6363 tumours. Our results support the hypothesis that Ang-1/Tie2 signalling is essential for vessel stabilization and endothelial cell/pericyte interaction, and suggest that Ang-2 is able to induce a switch of vascular phenotypes within tumours.

Empathie und Distanz. Zur Bedeutung der Übersetzung aktueller Literatur im interkulturellen Dialog

Bei vielen Germanisten, die an interkulturellen Fragen interessiert sind, nimmt seit jeher die Übersetzung - und hier auch die literarische Übersetzung - einen zentralen Platz ein in der Beschreibung ihrer relevanten Gegenstände. Daher setzt sich der Band zum Ziel, interkulturelle Probleme der Übersetzung, des Übersetzens, der Übersetzerausbildung, der translatorischen Theorie und Praxis insgesamt in ihrem ganzen Facettenreichtum zum Gegenstand der Diskussion zu machen und aus den unterschiedlichsten Perspektiven zu beleuchten. Dazu gehört z. B. nicht nur die Diskussion der Frage, was eigentlich ‘deutsch’ sei an der deutschsprachigen Literatur der Gegenwart, ob und vielleicht inwiefern sie wirke oder wirken könne als Indikator gesellschaftlicher Veränderungsprozesse, sondern auch eine kritische Erörterung des gegenwärtigen Stands und der sich abzeichnenden Probleme in der Ausbildung des Übersetzernachwuchses an den Universitäten und Hochschulen.

Lodz jenseits von "Fabriken, Wildwest und Provinz". Kulturwissenschaftliche Studien über die Deutschen in und aus den polnischen Gebieten

Die vor 100 Jahren von Polen, Juden und Deutschen bewohnte Textilmetropole Lodz wurde als «Eldorado des Ostens» angesehen. Lodz bot einerseits die Möglichkeit für Aufstieg und Wohlstand, barg andererseits aber auch die Gefahr der Proletarisierung und des sozialen Verfalls zahlreicher Familien. Die Stadt wurde und wird daher bis heute kaum mit Kultur assoziiert. Dennoch gab es auch hier ein vielfältiges kulturelles Leben. Der Band stellt mit den kulturellen Aktivitäten der neureichen Fabrikanten und gesellschaftlichen Aufsteiger sowie den volkstümlichen und heimatkundlichen Elementen der städtischen Kultur einige bisher kaum beachtete Aspekte in den Mittelpunkt. Dazu kommen Beiträge zur deutsch-jüdischen Literatur aus dem Getto Litzmannstadt sowie der deutschen Erinnerung an Lodz nach 1945. Ergänzt wird dies durch drei weitere Beiträge, die sich mit dem Zeitungswesen und der Heimatliteratur der Deutschen in Großpolen und Galizien beschäftigen. Dieser Tagungsband liefert zwölf Beiträge über die Deutschen in und aus den polnischen Gebieten und betrachtet neben dem Schwerpunkt Lodz auch Posen, Bromberg und Lemberg.