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Graupera M Guillermet-Guibert J Foukas LC Phng LK Cain RJ Salpekar A Pearce W Meek S Millan J Cutillas PR Smith AJ Ridley AJ Ruhrberg C Gerhardt H Vanhaesebroeck B 《Nature》2008,453(7195):662-666
Phosphoinositide 3-kinases (PI3Ks) signal downstream of multiple cell-surface receptor types. Class IA PI3K isoforms couple to tyrosine kinases and consist of a p110 catalytic subunit (p110alpha, p110beta or p110delta), constitutively bound to one of five distinct p85 regulatory subunits. PI3Ks have been implicated in angiogenesis, but little is known about potential selectivity among the PI3K isoforms and their mechanism of action in endothelial cells during angiogenesis in vivo. Here we show that only p110alpha activity is essential for vascular development. Ubiquitous or endothelial cell-specific inactivation of p110alpha led to embryonic lethality at mid-gestation because of severe defects in angiogenic sprouting and vascular remodelling. p110alpha exerts this critical endothelial cell-autonomous function by regulating endothelial cell migration through the small GTPase RhoA. p110alpha activity is particularly high in endothelial cells and preferentially induced by tyrosine kinase ligands (such as vascular endothelial growth factor (VEGF)-A). In contrast, p110beta in endothelial cells signals downstream of G-protein-coupled receptor (GPCR) ligands such as SDF-1alpha, whereas p110delta is expressed at low level and contributes only minimally to PI3K activity in endothelial cells. These results provide the first in vivo evidence for p110-isoform selectivity in endothelial PI3K signalling during angiogenesis. 相似文献
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RIDLEY A J 《科学通报(英文版)》2010,55(9):857-864
A substorm event has been simulated for the first time by using SWMF (Space Weather Modeling Framework) developed by the University of Michigan. The model results have been validated using Geotail and Cluster satellite observations. The substorm onset occurs at 22:08 UT on September 28, 2004, as identified from FUV WIC observations on the NASA IMAGE spacecraft. SWMF can couple effectively the magnetosphere, inner magnetosphere and ionosphere processes and is driven by the solar wind and IMF (Interplanetary Magnetic Field) parameters, which are measured by ACE satellite and time delayed to the upstream boundary of the model. It shows that (1) SWMF can predict well the large-scale variations of the magnetospheric magnetic field and ionospheric currents during the substorm event; and (2) the accuracy of the time delay of the solar wind from ACE to the outer boundary of the model has great effects on the model results. Finally, the substorm trigger mechanism has been discussed and the way of improvement of the model has been pointed out. 相似文献
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Lava erupts into cold sea water on the ocean floor at mid-ocean ridges (at depths of 2,500 m and greater), and the resulting flows make up the upper part of the global oceanic crust. Interactions between heated sea water and molten basaltic lava could exert significant control on the dynamics of lava flows and on their chemistry. But it has been thought that heating sea water at pressures of several hundred bars cannot produce significant amounts of vapour and that a thick crust of chilled glass on the exterior of lava flows minimizes the interaction of lava with sea water. Here we present evidence to the contrary, and show that bubbles of vaporized sea water often rise through the base of lava flows and collect beneath the chilled upper crust. These bubbles of steam at magmatic temperatures may interact both chemically and physically with flowing lava, which could influence our understanding of deep-sea volcanic processes and oceanic crustal construction more generally. We infer that vapour formation plays an important role in creating the collapse features that characterize much of the upper oceanic crust and may accordingly contribute to the measured low seismic velocities in this layer. 相似文献