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Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells 总被引:27,自引:0,他引:27
Nauli SM Alenghat FJ Luo Y Williams E Vassilev P Li X Elia AE Lu W Brown EM Quinn SJ Ingber DE Zhou J 《Nature genetics》2003,33(2):129-137
Several proteins implicated in the pathogenesis of polycystic kidney disease (PKD) localize to cilia. Furthermore, cilia are malformed in mice with PKD with mutations in TgN737Rpw (encoding polaris). It is not known, however, whether ciliary dysfunction occurs or is relevant to cyst formation in PKD. Here, we show that polycystin-1 (PC1) and polycystin-2 (PC2), proteins respectively encoded by Pkd1 and Pkd2, mouse orthologs of genes mutated in human autosomal dominant PKD, co-distribute in the primary cilia of kidney epithelium. Cells isolated from transgenic mice that lack functional PC1 formed cilia but did not increase Ca(2+) influx in response to physiological fluid flow. Blocking antibodies directed against PC2 similarly abolished the flow response in wild-type cells as did inhibitors of the ryanodine receptor, whereas inhibitors of G-proteins, phospholipase C and InsP(3) receptors had no effect. These data suggest that PC1 and PC2 contribute to fluid-flow sensation by the primary cilium in renal epithelium and that they both function in the same mechanotransduction pathway. Loss or dysfunction of PC1 or PC2 may therefore lead to PKD owing to the inability of cells to sense mechanical cues that normally regulate tissue morphogenesis. 相似文献
165.
Lappe-Siefke C Goebbels S Gravel M Nicksch E Lee J Braun PE Griffiths IR Nave KA 《Nature genetics》2003,33(3):366-374
Myelination of axons by oligodendrocytes enables rapid impulse propagation in the central nervous system. But long-term interactions between axons and their myelin sheaths are poorly understood. Here we show that Cnp1, which encodes 2',3'-cyclic nucleotide phosphodiesterase in oligodendrocytes, is essential for axonal survival but not for myelin assembly. In the absence of glial cyclic nucleotide phosphodiesterase, mice developed axonal swellings and neurodegeneration throughout the brain, leading to hydrocephalus and premature death. But, in contrast to previously studied myelin mutants, the ultrastructure, periodicity and physical stability of myelin were not altered in these mice. Genetically, the chief function of glia in supporting axonal integrity can thus be completely uncoupled from its function in maintaining compact myelin. Oligodendrocyte dysfunction, such as that in multiple sclerosis lesions, may suffice to cause secondary axonal loss. 相似文献
166.
Cancer cells frequently have disease-specific chromosome rearrangements. It is poorly understood why translocations between chromosomes recur at specific breakpoints in the genome. Here we provide evidence that higher-order spatial genome organization is a contributing factor in the formation of recurrent translocations. We show that MYC, BCL and immunoglobulin loci, which are recurrently translocated in various B-cell lymphomas, are preferentially positioned in close spatial proximity relative to each other in normal B cells. Loci in spatial proximity are non-randomly positioned towards the nuclear interior in normal B cells. This locus proximity is the consequence of higher-order genome structure rather than a property of individual genes. Our results suggest that the formation of specific translocations in human lymphomas, and perhaps other tissues, is determined in part by higher-order spatial organization of the genome. 相似文献
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The unique properties of water in the supercooled (metastable) state are not fully understood. In particular, the effects of solutes and mechanical pressure on the kinetics of the liquid-to-solid phase transition of supercooled water and aqueous solutions to ice have remained unresolved. Here we show from experimental data that the homogeneous nucleation of ice from supercooled aqueous solutions is independent of the nature of the solute, but depends only on the water activity of the solution--that is, the ratio between the water vapour pressures of the solution and of pure water under the same conditions. In addition, we show that the presence of solutes and the application of pressure have a very similar effect on ice nucleation. We present a thermodynamic theory for homogeneous ice nucleation, which expresses the nucleation rate coefficient as a function of water activity and pressure. Recent observations from clouds containing ice are in good agreement with our theory and our results should help to overcome one of the main weaknesses of numerical models of the atmosphere, the formulation of cloud processes. 相似文献
169.
数字地形是指将地球表面的形态以数字的形式进行表达,它通过对地面坐标和高程的数字描述来实现。景观数据的可视化在这里主要指地球表面的一些自然要素,如植被、气候、水等要素在计算机环境下的2维和3维描述。 相似文献
170.
机动车排放模型的应用及其适用性比较 总被引:2,自引:0,他引:2
运用模型估算城市机动车排放因子及排放总量,是机动车污染控制研究的一个重要方向。目前,在模型使用方面,国内主要借用MOBILE等国外较为成熟的模型,这在我国排放因子计算方面缺乏数据积累、基础研究薄弱情况下不失为一种选择。然而,这些模型一般根据不同的需要开发,在数据积累等方面具有较强的地域性,难免会与国内实际情况不符。国内现有研究更多集中于对利用模型得到的排放因子进行分析,对模型适用性的研究鲜有涉及。本文从MOBILE、IVE、EMFAC、CMEM、COPERT模型在国内应用的实际情况出发,从模型类型,地域性,数据库的完整性、模型的可移植性和参数可获性这几个方面,比较了这几个有代表性的机动车排放模型在国内的适用程度,指出了在不同地区情况和不同阶段,模型不同的适用范围。 相似文献