P2Y<Subscript>2</Subscript> receptor modulates shear stress-induced cell alignment and actin stress fibers in human umbilical vein endothelial cells

Endothelial cells release ATP in response to fluid shear stress, which activates purinergic (P2) receptor-mediated signaling molecules including endothelial nitric oxide (eNOS), a regulator of vascular tone. While P2 receptor-mediated signaling in the vasculature is well studied, the role of P2Y₂ receptors in shear stress-associated endothelial cell alignment, cytoskeletal alterations, and wound repair remains ill defined. To address these aspects, human umbilical vein endothelial cell (HUVEC) monolayers were cultured on gelatin-coated dishes and subjected to a shear stress of 1 Pa. HUVECs exposed to either P2Y₂ receptor antagonists or siRNA showed impaired fluid shear stress-induced cell alignment, and actin stress fiber formation as early as 6 h. Similarly, when compared to cells expressing the P2Y₂ Arg-Gly-Asp (RGD) wild-type receptors, HUVECs transiently expressing the P2Y₂ Arg-Gly-Glu (RGE) mutant receptors showed reduced cell alignment and actin stress fiber formation in response to shear stress as well as to P2Y₂ receptor agonists in static cultures. Additionally, we observed reduced shear stress-induced phosphorylation of focal adhesion kinase (Y397), and cofilin-1 (S3) with receptor knockdown as well as in cells expressing the P2Y₂ RGE mutant receptors. Consistent with the role of P2Y₂ receptors in vasodilation, receptor knockdown and overexpression of P2Y₂ RGE mutant receptors reduced shear stress-induced phosphorylation of AKT (S473), and eNOS (S1177). Furthermore, in a scratched wound assay, shear stress-induced cell migration was reduced by both pharmacological inhibition and receptor knockdown. Together, our results suggest a novel role for P2Y₂ receptor in shear stress-induced cytoskeletal alterations in HUVECs.     

Effect of splenectomy on the growth of adenovirus 12 tumors in hamsters

Zusammenfassung Die Empfänglichkeit splenektomierter Hamster für Transplantate von Adenovirus-12-Tumorzellen wurde verglichen mit jener von scheinsplenektomierten Kontrolltieren. Splenektomie vor der Inokulation mit Tumorzellen verringerte die Tumorinzidenz oder verzögerte das Tumorwachstum. Splenektomie zum Zeitpunkt des Erscheinens der Tumoren führte immer noch in einem Drittel der Tiere zu Remissionen.     

Strukturelle und funktionelle Veränderungen am menschlichen Ovar unter Einwirkung hormonaler Antikonzeptiva

Summary In two cases, a fresh corpus luteum was found during treatment with hormonal anticonceptiva (Lyndiol 2.5^®). The decreased excretion of all oestrogen fractions can be explained by the lack of proliferation of the theca interna. The striking proliferation of the follicle epithelium after the completed ovulation is as yet an unexplained phenomenon. The possible endocrine actions of such steroid combinations upon the pituitary are discussed. Further investigations are in progress.     

High velocity dispersion in a rare grand-design spiral galaxy at redshift z = 2.18

Although grand-design spiral galaxies are relatively common in the local Universe, only one has been spectroscopically confirmed to lie at redshift z?>?2 (HDFX 28; z = 2.011); and it may prove to be a major merger that simply resembles a spiral in projection. The rarity of spirals has been explained as a result of disks being dynamically 'hot' at z?>?2 (refs 2-5), which may instead favour the formation of commonly observed clumpy structures. Alternatively, current instrumentation may simply not be sensitive enough to detect spiral structures comparable to those in the modern Universe. At z?相似文献