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Arterial thrombosis is considered to arise from the interaction of tissue factor (TF) in the vascular wall with platelets and coagulation factors in circulating blood. According to this paradigm, coagulation is initiated after a vessel is damaged and blood is exposed to vessel-wall TF. We have examined thrombus formation on pig arterial media (which contains no stainable TF) and on collagen-coated glass slides (which are devoid of TF) exposed to flowing native human blood. In both systems the thrombi that formed during a 5-min perfusion stained intensely for TF, much of which was not associated with cells. Antibodies against TF caused ≈ 70% reduction in the amount of thrombus formed on the pig arterial media and also reduced thrombi on the collagen-coated glass slides. TF deposited on the slides was active, as there was abundant fibrin in the thrombi. Factor VIIai, a potent inhibitor of TF, essentially abolished fibrin production and markedly reduced the mass of the thrombi. Immunoelectron microscopy revealed TF-positive membrane vesicles that we frequently observed in large clusters near the surface of platelets. TF, measured by factor Xaformation, was extracted from whole blood and plasma of healthy subjects. By using immunostaining, TF-containing neutrophils and monocytes were identified in peripheral blood; our data raise the possibility that leukocytes are the main source of blood TF. We suggest that blood-borne TF is inherently thrombogenic and may be involved in thrombus propagation at the site of vascular injury.

The use of human pluripotent stem cells for in vitro disease modelling and clinical applications requires protocols that convert these cells into relevant adult cell types. Here, we report the rapid and efficient differentiation of human pluripotent stem cells into vascular endothelial and smooth muscle cells. We found that GSK3 inhibition and BMP4 treatment rapidly committed pluripotent cells to a mesodermal fate and subsequent exposure to VEGF-A or PDGF-BB resulted in the differentiation of either endothelial or vascular smooth muscle cells, respectively. Both protocols produced mature cells with efficiencies exceeding 80% within six days. On purification to 99% via surface markers, endothelial cells maintained their identity, as assessed by marker gene expression, and showed relevant in vitro and in vivo functionality. Global transcriptional and metabolomic analyses confirmed that the cells closely resembled their in vivo counterparts. Our results suggest that these cells could be used to faithfully model human disease. Cowan and colleagues report a method to generate mature endothelial or vascular smooth muscle cells from human pluripotent stem cells with high efficiency and purity.

Zusammenfassung Der Fetozid hat sich als therapeutisches Angebot der ersten Wahl im Fall eines gewünschten späten Schwangerschaftsabbruchs weitestgehend etabliert. Dennoch stellt sich die Frage nach Alternativen für Frauen und Paare, die möglicherweise diese invasive, das Kind im Mutterleib tötende Vorgehensweise nur schlecht verarbeiten könnten. Diese Alternative steht im Sinne der palliativen Geburt zu Verfügung. Das Angebot der palliativen Geburt besteht auch dann, wenn Eltern vor der extrauterinen Lebensfähigkeit des Kindes mit einer lebenslimitierenden Diagnose konfrontiert werden. Die palliative Geburt stellt zu jedem Zeitpunkt eine Alternative zum Schwangerschaftsabbruch dar, unabhängig davon, ob dieser Abbruch durch Einleitung der Geburt vor Erreichen der Lebensfähigkeit des Fetus oder durch Fetozid bei gegebener Lebensfähigkeit erfolgen soll.

We show that any two left-invariant metrics on \\(S^3\\cong\\operatorname{SU}(2)\\) which are isospectral for the associated classical Dirac operator \\(D\\) must be isometric. In the case of left-invariant metrics of positive scalar curvature, we compute and use the smallest eigenvalue of \\(D^2\\). We show analogous results for left-invariant metrics on \\(\\operatorname{SO}(3)=S^3/\\{\\pm1\\}\\) for each of its two spin structures.