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371.
A novel cyclin encoded by a bcl1-linked candidate oncogene   总被引:145,自引:0,他引:145  
We have previously identified a candidate oncogene (PRAD1 or D11S287E) on chromosome 11q13 which is clonally rearranged with the parathyroid hormone locus in a subset of benign parathyroid tumours. We now report that a cloned human placental PRAD1 complementary DNA encodes a protein of 295 amino acids with sequence similarities to the cyclins. Cyclins can form a complex with and activate p34cdc2 protein kinase, thereby regulating progress through the cell cycle. PRAD 1 messenger RNA levels vary dramatically across the cell cycle in HeLa cells. Addition of the PRAD1 protein to interphase clam embryo lysates containing inactive p34cdc2 kinase and lacking endogenous cyclins allows it to be isolated using beads bearing p13suc1, a yeast protein that binds cdc2 and related kinases with high affinity and coprecipitates kinase-associated proteins. Addition of PRAD1 also induces phosphorylation of histone H1, a preferred substrate of cdc2. These data suggest that PRAD1 encodes a novel cyclin whose overexpression may play an important part in the development of various tumours with abnormalities in 11q13.  相似文献   
372.
Importance of a novel GABAA receptor subunit for benzodiazepine pharmacology   总被引:48,自引:0,他引:48  
Neurotransmission effected by GABA (gamma-aminobutyric acid) is predominantly mediated by a gated chloride channel intrinsic to the GABAA receptor. This heterooligomeric receptor exists in most inhibitory synapses in the vertebrate central nervous system (CNS) and can be regulated by clinically important compounds such as benzodiazepines and barbiturates. The primary structures of GABAA receptor alpha- and beta-subunits have been deduced from cloned complementary DNAs. Co-expression of these subunits in heterologous systems generates receptors which display much of the pharmacology of their neural counterparts, including potentiation by barbiturates. Conspicuously, however, they lack binding sites for, and consistent electrophysiological responses to, benzodiazepines. We now report the isolation of a cloned cDNA encoding a new GABAA receptor subunit, termed gamma 2, which shares approximately 40% sequence identity with alpha- and beta-subunits and whose messenger RNA is prominently localized in neuronal subpopulations throughout the CNS. Importantly, coexpression of the gamma 2 subunit with alpha 1 and beta 1 subunits produces GABAA receptors displaying high-affinity binding for central benzodiazepine receptor ligands.  相似文献   
373.
Tolerance to self-antigens has been shown to develop during ontogeny as a result of the clonal deletion of self-reactive T cells. Tolerance, or better 'nonresponsiveness', to specific antigens can also be induced in adult animals but the mechanism(s) involved are not well understood. Most murine T-helper cells that express the V beta 6 T-cell receptor gene segment are specific for Mls-1a antigens. We have therefore been able to use an anti-V beta 6 monoclonal antibody to follow the fate of Mls-1a specific T cells in adult Mls-1b mice made specifically unresponsive to Mls-1a. We show that the induced unresponsiveness is not due to clonal deletion, but rather to clonal anergy. The anergic V beta 6 T-helper cells express IL-2 receptors and undergo limited blastogenesis in vitro upon stimulation, but do not produce IL-2, in marked contrast to V beta 6 cells from naive mice. Our data appear to represent an in vivo correlate for the induction of anergy that has been observed in T-cell lines in vitro.  相似文献   
374.
The Caenorhabditis elegans gene unc-22 encodes a very large muscle protein, called twitchin, which consists of a protein kinase domain and several copies of two short motifs. The sequence of twitchin has unexpected similarities to the sequences of proteins of the immunoglobulin superfamily, cell adhesion molecules and vertebrate muscle proteins, including myosin light-chain kinase. These homologies, together with results from earlier genetic and molecular analyses, indicate that twitchin is involved in a novel mechanism of myosin regulation.  相似文献   
375.
R D Nicholls  J H Knoll  M G Butler  S Karam  M Lalande 《Nature》1989,342(6247):281-285
Prader-Willi syndrome (PWS) is the most common form of dysmorphic genetic obesity associated with mental retardation. About 60% of cases have a cytological deletion of chromosome 15q11q13 (refs 2, 3). These deletions occur de novo exclusively on the paternal chromosome. By contrast, Angelman syndrome (AS) is a very different clinical disorder and is also associated with deletions of region 15q11q13 (refs 6-8), indistinguishable from those in PWS except that they occur de novo on the maternal chromosome. The parental origin of the affected chromosomes 15 in these disorders could, therefore, be a contributory factor in determining their clinical phenotypes. We have now used cloned DNA markers specific for the 15q11q13 subregion to determine the parental origin of chromosome 15 in PWS individuals not having cytogenetic deletions; these individuals account for almost all of the remaining 40% of PWS cases. Probands in two families displayed maternal uniparental disomy for chromosome 15q11q13. This is the first demonstration that maternal heterodisomy--the presence of two different chromosome 15s derived from the mother--can be associated with a human genetic disease. The absence of a paternal contribution of genes in region 15q11q13, as found in PWS deletion cases, rather than a mutation in a specific gene(s) in this region may result in expression of the clinical phenotype. Thus, we conclude that a gene or genes in region 15q11q13 must be inherited from each parent for normal human development.  相似文献   
376.
给出一种表达加权有向图的数据结构,它使得对此有向图进行“插入”操作后,只需进行O(n2)时间的维护工作,就可使得每对结点间的最短路径迅速地得到修整。  相似文献   
377.
介绍了稻谷壳的物理化学特性及热重试验结果,与煤燃烧特性进行对比,阐述了稻谷壳燃烧过程中,挥发分与焦炭分阶段燃烧的概念;并通过燃烧试验提出了独特的以纯稻谷壳流态化燃烧方式为主的组合燃烧方式,为纯稻谷壳流态化燃烧锅炉设计和运行提供了理论依据。  相似文献   
378.
研究一类线性多变量系统的鲁棒极点配置问题,提出了一种基于极点配置和目标函数优化的鲁棒极点配置方法。基本思想是,利用极点配置的参数化表示结果,以系统输出的L∞范数作为极点配置寻优的准则函数,通过解优化问题的途径确定极点配置问题中的自由参数。  相似文献   
379.
运用气相k-ε模型和颗粒相代数方程模型对正交射流煤粉燃烧器气固两相流场进行了数值模拟,获得了该燃烧器内的气、固两相速度分布,颗粒质量流分布,并与实验值进行了对比,两者定性符合,同时,探讨了颗粒直径对颗粒混合的影响,得到了一些很有价值的结论。  相似文献   
380.
研究了永磁同步电动机(PMSM)伺服系统的一种新型数字电流环方案,该方案采用了规则采样法生成PWM波的比例型电流调节器,提出用前馈补偿和变电流环增益技术才能提高电流调节性能,给出了数字仿真和实验结果。  相似文献   
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