排序方式: 共有41条查询结果,搜索用时 9 毫秒
1.
Loss-of-function mutations in TGFB2 cause a syndromic presentation of thoracic aortic aneurysm 总被引:2,自引:0,他引:2
ME Lindsay D Schepers NA Bolar JJ Doyle E Gallo J Fert-Bober MJ Kempers EK Fishman Y Chen L Myers D Bjeda G Oswald AF Elias HP Levy BM Anderlid MH Yang EM Bongers J Timmermans AC Braverman N Canham GR Mortier HG Brunner PH Byers J Van Eyk L Van Laer HC Dietz BL Loeys 《Nature genetics》2012,44(8):922-927
Loeys-Dietz syndrome (LDS) associates with a tissue signature for high transforming growth factor (TGF)-β signaling but is often caused by heterozygous mutations in genes encoding positive effectors of TGF-β signaling, including either subunit of the TGF-β receptor or SMAD3, thereby engendering controversy regarding the mechanism of disease. Here, we report heterozygous mutations or deletions in the gene encoding the TGF-β2 ligand for a phenotype within the LDS spectrum and show upregulation of TGF-β signaling in aortic tissue from affected individuals. Furthermore, haploinsufficient Tgfb2(+/-) mice have aortic root aneurysm and biochemical evidence of increased canonical and noncanonical TGF-β signaling. Mice that harbor both a mutant Marfan syndrome (MFS) allele (Fbn1(C1039G/+)) and Tgfb2 haploinsufficiency show increased TGF-β signaling and phenotypic worsening in association with normalization of TGF-β2 expression and high expression of TGF-β1. Taken together, these data support the hypothesis that compensatory autocrine and/or paracrine events contribute to the pathogenesis of TGF-β-mediated vasculopathies. 相似文献
2.
RK Koenekoop H Wang J Majewski X Wang I Lopez H Ren Y Chen Y Li GA Fishman M Genead J Schwartzentruber N Solanki EI Traboulsi J Cheng CV Logan M McKibbin BE Hayward DA Parry CA Johnson M Nageeb;Finding of Rare Disease Genes 《Nature genetics》2012,44(9):1035-1039
Leber congenital amaurosis (LCA) is a blinding retinal disease that presents within the first year after birth. Using exome sequencing, we identified mutations in the nicotinamide adenine dinucleotide (NAD) synthase gene NMNAT1 encoding nicotinamide mononucleotide adenylyltransferase 1 in eight families with LCA, including the family in which LCA was originally linked to the LCA9 locus. Notably, all individuals with NMNAT1 mutations also have macular colobomas, which are severe degenerative entities of the central retina (fovea) devoid of tissue and photoreceptors. Functional assays of the proteins encoded by the mutant alleles identified in our study showed that the mutations reduce the enzymatic activity of NMNAT1 in NAD biosynthesis and affect protein folding. Of note, recent characterization of the slow Wallerian degeneration (Wld(s)) mouse model, in which prolonged axonal survival after injury is observed, identified NMNAT1 as a neuroprotective protein when ectopically expressed. Our findings identify a new disease mechanism underlying LCA and provide the first link between endogenous NMNAT1 dysfunction and a human nervous system disorder. 相似文献
3.
Gridlock signalling pathway fashions the first embryonic artery. 总被引:27,自引:0,他引:27
Arteries and veins are morphologically, functionally and molecularly very different, but how this distinction is established during vasculogenesis is unknown. Here we show, by lineage tracking in zebrafish embryos, that angioblast precursors for the trunk artery and vein are spatially mixed in the lateral posterior mesoderm. Progeny of each angioblast, however, are restricted to one of the vessels. This arterial-venous decision is guided by gridlock (grl), an artery-restricted gene that is expressed in the lateral posterior mesoderm. Graded reduction of grl expression, by mutation or morpholino antisense, progressively ablates regions of the artery, and expands contiguous regions of the vein, preceded by an increase in expression of the venous marker EphB4 receptor (ephb4) and diminution of expression of the arterial marker ephrin-B2 (efnb2). grl is downstream of notch, and interference with notch signalling, by blocking Su(H), similarly reduces the artery and increases the vein. Thus, a notch-grl pathway controls assembly of the first embryonic artery, apparently by adjudicating an arterial versus venous cell fate decision. 相似文献
4.
5.
H M Fishman 《Nature》1969,224(5224):1116-1118
6.
7.
8.
Zusammenfassung Die optische Rotationsdispersion sowie das Infrarotund Ultraviolett-Absorptionsspektrum von mehreren-Bromderivaten der 16-Keto- und 17-Ketosteroide wurde gemessen. Die Schlussfolgerungen aus Rotationsdispersion und Infrarotanalyse stimmen gut überein, es scheint jedoch, dass die Verschiebungen im Ultraviolett zur Bestimmung der Orientierung eines Halogenatoms in-Bromocyclopentanonen nicht in allen Fällen gebraucht werden können.
Paper XXXV in the seriesOptical Rotatory Dispersion Studies by C. D. For the preceding article seeN. L. Allinger, R. B. Hermann, andC. Djerassi, J. org. Chem., in press. 相似文献
Paper XXXV in the seriesOptical Rotatory Dispersion Studies by C. D. For the preceding article seeN. L. Allinger, R. B. Hermann, andC. Djerassi, J. org. Chem., in press. 相似文献
9.
以半胱氨酸为配体合成一种新型亚金配合物NH4Au(Cys)2,对该配合物进行元素分析、红外光谱、紫外光谱、热失重分析和导电性测量等理化性质研究;以该亚金配合物为金源开展相关的电镀金工艺探索,并通过四因素三水平的正交试验获得其最佳条件参数;采用扫描电子显微镜(SEM)和X线衍射(XRD)对镀金层的表面质量进行探讨。研究结果表明:该目标产物的分子式为NH4Au(Cys)2·2H2O,该配合物中以半胱氨酸的巯基和金配位为成健特征,在170℃以下热稳定性较好,该亚金配合物是一个典型的离子化合物。在电流密度为200~300 A/m2,p H为10.5~12.0,温度为35~45℃,金质量浓度为15~25 g/L的电镀工艺条件下,得到粒度为0.5~1.0μm的单质金,且主要沿着(111)面进行生长。 相似文献
10.
随机纳米碳管网络及其渗流性质 总被引:1,自引:0,他引:1
数值模拟了实验上构造纳米碳管网络的溶液沉积方法.与一般的随机网络模型不同,将碳管的长度计算在内,而且考虑了不同的空间相交位形.数值模拟发现网络的度分布为高斯分布,平均集聚系数约为0.11.当网络中碳管平均面密度取值在σ0=179 200根/cm2附近时,网络系综达到渗流.在临界点附近,网络的连通概率p、两极之间电导G、... 相似文献