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排序方式: 共有79条查询结果,搜索用时 31 毫秒
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Serini G Valdembri D Zanivan S Morterra G Burkhardt C Caccavari F Zammataro L Primo L Tamagnone L Logan M Tessier-Lavigne M Taniguchi M Püschel AW Bussolino F 《Nature》2003,424(6947):391-397
The motility and morphogenesis of endothelial cells is controlled by spatio-temporally regulated activation of integrin adhesion receptors, and integrin activation is stimulated by major determinants of vascular remodelling. In order for endothelial cells to be responsive to changes in activator gradients, the adhesiveness of these cells to the extracellular matrix must be dynamic, and negative regulators of integrins could be required. Here we show that during vascular development and experimental angiogenesis, endothelial cells generate autocrine chemorepulsive signals of class 3 semaphorins (SEMA3 proteins) that localize at nascent adhesive sites in spreading endothelial cells. Disrupting endogenous SEMA3 function in endothelial cells stimulates integrin-mediated adhesion and migration to extracellular matrices, whereas exogenous SEMA3 proteins antagonize integrin activation. Misexpression of dominant negative SEMA3 receptors in chick embryo endothelial cells locks integrins in an active conformation, and severely impairs vascular remodelling. Sema3a null mice show vascular defects as well. Thus during angiogenesis endothelial SEMA3 proteins endow the vascular system with the plasticity required for its reshaping by controlling integrin function. 相似文献
13.
Gretarsdottir S Thorleifsson G Reynisdottir ST Manolescu A Jonsdottir S Jonsdottir T Gudmundsdottir T Bjarnadottir SM Einarsson OB Gudjonsdottir HM Hawkins M Gudmundsson G Gudmundsdottir H Andrason H Gudmundsdottir AS Sigurdardottir M Chou TT Nahmias J Goss S Sveinbjörnsdottir S Valdimarsson EM Jakobsson F Agnarsson U Gudnason V Thorgeirsson G Fingerle J Gurney M Gudbjartsson D Frigge ML Kong A Stefansson K Gulcher JR 《Nature genetics》2003,35(2):131-138
We previously mapped susceptibility to stroke to chromosome 5q12. Here we finely mapped this locus and tested it for association with stroke. We found the strongest association in the gene encoding phosphodiesterase 4D (PDE4D), especially for carotid and cardiogenic stroke, the forms of stroke related to atherosclerosis. Notably, we found that haplotypes can be classified into three distinct groups: wild-type, at-risk and protective. We also observed a substantial disregulation of multiple PDE4D isoforms in affected individuals. We propose that PDE4D is involved in the pathogenesis of stroke, possibly through atherosclerosis, which is the primary pathological process underlying ischemic stroke. 相似文献
14.
Reversals of the Earth's magnetic field reflect changes in the geodynamo--flow within the outer core--that generates the field. Constraining core processes or mantle properties that induce or modulate reversals requires knowing the timing and morphology of field changes that precede and accompany these reversals. But the short duration of transitional field states and fragmentary nature of even the best palaeomagnetic records make it difficult to provide a timeline for the reversal process. 40Ar/39Ar dating of lavas on Tahiti, long thought to record the primary part of the most recent 'Matuyama-Brunhes' reversal, gives an age of 795 +/- 7 kyr, indistinguishable from that of lavas in Chile and La Palma that record a transition in the Earth's magnetic field, but older than the accepted age for the reversal. Only the 'transitional' lavas on Maui and one from La Palma (dated at 776 +/- 2 kyr), agree with the astronomical age for the reversal. Here we propose that the older lavas record the onset of a geodynamo process, which only on occasion would result in polarity change. This initial instability, associated with the first of two decreases in field intensity, began approximately 18 kyr before the actual polarity switch. These data support the claim that complete reversals require a significant period for magnetic flux to escape from the solid inner core and sufficiently weaken its stabilizing effect. 相似文献
15.
A recessive contiguous gene deletion causing infantile hyperinsulinism, enteropathy and deafness identifies the Usher type 1C gene 总被引:18,自引:0,他引:18
Bitner-Glindzicz M Lindley KJ Rutland P Blaydon D Smith VV Milla PJ Hussain K Furth-Lavi J Cosgrove KE Shepherd RM Barnes PD O'Brien RE Farndon PA Sowden J Liu XZ Scanlan MJ Malcolm S Dunne MJ Aynsley-Green A Glaser B 《Nature genetics》2000,26(1):56-60
Usher syndrome type 1 describes the association of profound, congenital sensorineural deafness, vestibular hypofunction and childhood onset retinitis pigmentosa. It is an autosomal recessive condition and is subdivided on the basis of linkage analysis into types 1A through 1E. Usher type 1C maps to the region containing the genes ABCC8 and KCNJ11 (encoding components of ATP-sensitive K + (KATP) channels), which may be mutated in patients with hyperinsulinism. We identified three individuals from two consanguineous families with severe hyperinsulinism, profound congenital sensorineural deafness, enteropathy and renal tubular dysfunction. The molecular basis of the disorder is a homozygous 122-kb deletion of 11p14-15, which includes part of ABCC8 and overlaps with the locus for Usher syndrome type 1C and DFNB18. The centromeric boundary of this deletion includes part of a gene shown to be mutated in families with type 1C Usher syndrome, and is hence assigned the name USH1C. The pattern of expression of the USH1C protein is consistent with the clinical features exhibited by individuals with the contiguous gene deletion and with isolated Usher type 1C. 相似文献
16.
Allosteric transitions of glutamate dehydrogenase 总被引:5,自引:0,他引:5
17.
Two types of supernova are thought to produce the overwhelming majority of neutron stars in the Universe. The first type, iron-core-collapse supernovae, occurs when a high-mass star develops a degenerate iron core that exceeds the Chandrasekhar limit. The second type, electron-capture supernovae, is associated with the collapse of a lower-mass oxygen-neon-magnesium core as it loses pressure support owing to the sudden capture of electrons by neon and/or magnesium nuclei. It has hitherto been impossible to identify the two distinct families of neutron stars produced in these formation channels. Here we report that a large, well-known class of neutron-star-hosting X-ray pulsars is actually composed of two distinct subpopulations with different characteristic spin periods, orbital periods and orbital eccentricities. This class, the Be/X-ray binaries, contains neutron stars that accrete material from a more massive companion star. The two subpopulations are most probably associated with the two distinct types of neutron-star-forming supernova, with electron-capture supernovae preferentially producing systems with short spin periods, short orbital periods and low eccentricities. Intriguingly, the split between the two subpopulations is clearest in the distribution of the logarithm of spin period, a result that had not been predicted and which still remains to be explained. 相似文献
18.
Ancestral lysozymes reconstructed, neutrality tested, and thermostability linked to hydrocarbon packing 总被引:11,自引:0,他引:11
The controversy surrounding the idea that neutral mutations dominate protein evolution is attributable in part to the inadequacy of the tools available to evolutionary investigators. With a few exceptions, most investigations into the force driving protein evolution have relied on indirect criteria for distinguishing neutral and non-neutral variants. To investigate a particular pathway of molecular evolution, we have reconstructed by site-directed mutagenesis likely ancestral variants of the lysozymes of modern game birds (order Galliformes), tested their activity and thermostability and determined their three-dimensional structure. We focused on amino acids at three positions that are occupied in all known game birds either by the triplet Thr 40, Ile 55, Ser 91, or by the triplet Ser 40, Val 55, Thr 91. We have synthesized proteins representing intermediates along the possible three-step evolutionary pathways between these triplets. Although all of these are active and stable, none of these intermediates is found in known lysozymes. A comparison of the structures and thermostabilities of the variants reveals a linear correlation between the side-chain volume of the triplet and the thermostability of the protein. Each pathway connecting the two extant triplet sequences includes a variant with a thermostability outside the range of the extant proteins. This observation is consistent with a non-neutral evolutionary pathway. The existence of variants that are more stable than the extant proteins suggests that selection for maximum thermostability may not have been an important factor in the evolution of this enzyme. 相似文献
19.
Ultrastructural analysis of toxin binding and entry into mammalian cells 总被引:10,自引:0,他引:10
G L Nicolson 《Nature》1974,251(5476):628-630
20.