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41.
Roberts AE Araki T Swanson KD Montgomery KT Schiripo TA Joshi VA Li L Yassin Y Tamburino AM Neel BG Kucherlapati RS 《Nature genetics》2007,39(1):70-74
Noonan syndrome, the most common single-gene cause of congenital heart disease, is characterized by short stature, characteristic facies, learning problems and leukemia predisposition. Gain-of-function mutations in PTPN11, encoding the tyrosine phosphatase SHP2, cause approximately 50% of Noonan syndrome cases. SHP2 is required for RAS-ERK MAP kinase (MAPK) cascade activation, and Noonan syndrome mutants enhance ERK activation ex vivo and in mice. KRAS mutations account for <5% of cases of Noonan syndrome, but the gene(s) responsible for the remainder are unknown. We identified missense mutations in SOS1, which encodes an essential RAS guanine nucleotide-exchange factor (RAS-GEF), in approximately 20% of cases of Noonan syndrome without PTPN11 mutation. The prevalence of specific cardiac defects differs in SOS1 mutation-associated Noonan syndrome. Noonan syndrome-associated SOS1 mutations are hypermorphs encoding products that enhance RAS and ERK activation. Our results identify SOS1 mutants as a major cause of Noonan syndrome, representing the first example of activating GEF mutations associated with human disease and providing new insights into RAS-GEF regulation. 相似文献
42.
Paraneoplastic myasthenic syndrome IgG inhibits 45Ca2+ flux in a human small cell carcinoma line 总被引:1,自引:0,他引:1
Certain cancers exert unexplained remote effects on the nervous system. Small cell carcinoma (SCC) of the lung, a tumour capable of spike electrogenesis and which is of possible neural crest origin, is present in approximately 70% of patients with the Lambert-Eaton myasthenic syndrome (LEMS), a disorder characterized by fatigable muscle weakness. Patients with this syndrome have a defect in the (Ca2+-dependent) quantal release of acetylcholine from motor nerve terminals evoked by a nerve impulse or by high K+ (ref.5), and a decreased number of presynaptic active zone particles. The physiological and morphological features of the syndrome can be transferred to mice by the patients' IgG, consistent with an autoantibody interfering with the function of voltage-dependent Ca2+ channels. Here we demonstrate that K+-induced 45Ca2+ flux in a cultured human SCC line is significantly reduced by LEMS IgG, suggesting that in SCC-LEMS an autoantibody to tumour Ca2+-channel determinants is triggered; its cross-reaction with similar determinants at the motor nerve terminal could lead to the remote neurological syndrome. 相似文献
43.
The yeast Saccharomyces cerevisiae can synthesize, process and secrete higher eukaryotic proteins. We have investigated the expression of immunoglobulin chains in yeast and demonstrate here the synthesis, processing and secretion of light and heavy chains, the glycosylation of heavy chain, the intracellular localization of these foreign proteins by immunofluorescence, and the detection of functional antibodies in cells co-expressing both chains. This may provide the basis of a microbial fermentation process for the production of monoclonal antibodies. The co-expression of light and heavy chains in Escherichia coli has been reported but functional antibodies were not assembled in vivo. Furthermore, only low-level assembly of these chains was found in vitro. 相似文献
44.
45.
讨论强度为Yψ(t),其中Y为初始随机变量,ψ(t)是t的单调递减连续实函数,应力为强度函数λ(t)=exp(α+βt)(t≥0;α,β为任意实数)的复合非时齐Poisson过程模型结构可靠度,获得应力与强度在各种不同情况下的结构可靠度表达式。 相似文献
46.
47.
The inhibition of cyclic nucleotide phosphodiesterase from the nerve cord of Manduca sexta was studied using theophylline as a model compound. 11 putative neurotransmitters had no effect on enzyme activity. 相似文献
48.
宁艳阳 《科技情报开发与经济》2004,14(6):230-231
绩效目标是绩效考评必不可少的一个重要组成部分。基于激励理论对企业绩效目标的设置和实施进行了探讨,得到如下几点启示:一是制定有一定难度,但切实可行的目标是提高员工绩效的关键;二是确定员工期望结果、建立反馈机制、将报酬和绩效联系起来、阐明职责和自我管理是实现目标和提高员工绩效的可靠保证。 相似文献
49.
太原市二氧化硫污染状况及评价 总被引:1,自引:0,他引:1
通过对太原市不同季节、不同监测位点大气二氧化硫(SO2)浓度的监测,分析了太原市SO2污染状况,指出在太原市对SO2排放企业的治理和管理工作势在必行。 相似文献
50.
Development and differentiation of the intestinal epithelium 总被引:12,自引:0,他引:12
de Santa Barbara P van den Brink GR Roberts DJ 《Cellular and molecular life sciences : CMLS》2003,60(7):1322-1332
The gastrointestinal tract develops from a simple tube to a complex organ with patterns of
differentiation along four axes of asymmetry. The organ is composed of all three germ layers
signaling to each other during development to form the adult structure. The gut epithelium
is a constitutively developing tissue, constantly differentiating from a stem cell in a progenitor
pool throughout the life of the organism. Signals from the adjacent mesoderm and between epithelial
cells are required for normal orderly development/differentiation, homeostasis, and apoptosis.
Embryonically important patterning factors are used during adult stages for these processes.
Such critical pathways as the hedgehog, bone morphogenetic protein, Notch, Sox, and Wnt systems
are used both in embryologic and adult times of gut development. We focus on and review the roles
of these factors in gut epithelial cell development and differentiation.Received 18 October 2002; received after revision 18 December 2002; accepted 18 December 2002 相似文献