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排序方式: 共有287条查询结果,搜索用时 46 毫秒
101.
Gudbjartsson DF Arnar DO Helgadottir A Gretarsdottir S Holm H Sigurdsson A Jonasdottir A Baker A Thorleifsson G Kristjansson K Palsson A Blondal T Sulem P Backman VM Hardarson GA Palsdottir E Helgason A Sigurjonsdottir R Sverrisson JT Kostulas K Ng MC Baum L So WY Wong KS Chan JC Furie KL Greenberg SM Sale M Kelly P MacRae CA Smith EE Rosand J Hillert J Ma RC Ellinor PT Thorgeirsson G Gulcher JR Kong A Thorsteinsdottir U Stefansson K 《Nature》2007,448(7151):353-357
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in humans and is characterized by chaotic electrical activity of the atria. It affects one in ten individuals over the age of 80 years, causes significant morbidity and is an independent predictor of mortality. Recent studies have provided evidence of a genetic contribution to AF. Mutations in potassium-channel genes have been associated with familial AF but account for only a small fraction of all cases of AF. We have performed a genome-wide association scan, followed by replication studies in three populations of European descent and a Chinese population from Hong Kong and find a strong association between two sequence variants on chromosome 4q25 and AF. Here we show that about 35% of individuals of European descent have at least one of the variants and that the risk of AF increases by 1.72 and 1.39 per copy. The association with the stronger variant is replicated in the Chinese population, where it is carried by 75% of individuals and the risk of AF is increased by 1.42 per copy. A stronger association was observed in individuals with typical atrial flutter. Both variants are adjacent to PITX2, which is known to have a critical function in left-right asymmetry of the heart. 相似文献
102.
Corneo B Wendland RL Deriano L Cui X Klein IA Wong SY Arnal S Holub AJ Weller GR Pancake BA Shah S Brandt VL Meek K Roth DB 《Nature》2007,449(7161):483-486
Mammalian cells repair DNA double-strand breaks (DSBs) through either homologous recombination or non-homologous end joining (NHEJ). V(D)J recombination, a cut-and-paste mechanism for generating diversity in antigen receptors, relies on NHEJ for repairing DSBs introduced by the Rag1-Rag2 protein complex. Animals lacking any of the seven known NHEJ factors are therefore immunodeficient. Nevertheless, DSB repair is not eliminated entirely in these animals: evidence of a third mechanism, 'alternative NHEJ', appears in the form of extremely rare V(D)J junctions and a higher rate of chromosomal translocations. The paucity of these V(D)J events has suggested that alternative NHEJ contributes little to a cell's overall repair capacity, being operative only (and inefficiently) when classical NHEJ fails. Here we find that removing certain portions of murine Rag proteins reveals robust alternative NHEJ activity in NHEJ-deficient cells and some alternative joining activity even in wild-type cells. We propose a two-tier model in which the Rag proteins collaborate with NHEJ factors to preserve genomic integrity during V(D)J recombination. 相似文献
103.
不同饰面材料高强混凝土柱的耐火性能 总被引:1,自引:0,他引:1
通过对8根装饰有不同饰面材料的高强混凝土柱式构件进行ISO834标准升温条件下的明火试验,考察了饰面材料对构件表面混凝土爆裂的影响,分析了不同饰面材料高强混凝土构件的内部温度场,并与试验结果进行了对比.研究结果表明:饰面材料的引入虽然延缓了构件表面混凝土的起爆时刻,却加重了其爆裂程度;双层防火板可较好地抑制构件表面混凝土的高温爆裂;将饰面材料折算为等效混凝土的做法,总体上可较好地反映饰面材料对构件截面温度场的影响. 相似文献
104.
P Wei WW Wong JS Park EE Corcoran SG Peisajovich JJ Onuffer A Weiss WA Lim 《Nature》2012,488(7411):384-388
Bacterial pathogens have evolved specific effector proteins that, by interfacing with host kinase signalling pathways, provide a mechanism to evade immune responses during infection. Although these effectors contribute to pathogen virulence, we realized that they might also serve as valuable synthetic biology reagents for engineering cellular behaviour. Here we exploit two effector proteins, the Shigella flexneri OspF protein and Yersinia pestis YopH protein, to rewire kinase-mediated responses systematically both in yeast and mammalian immune cells. Bacterial effector proteins can be directed to inhibit specific mitogen-activated protein kinase pathways selectively in yeast by artificially targeting them to pathway-specific complexes. Moreover, we show that unique properties of the effectors generate new pathway behaviours: OspF, which irreversibly inactivates mitogen-activated protein kinases, was used to construct a synthetic feedback circuit that shows novel frequency-dependent input filtering. Finally, we show that effectors can be used in T cells, either as feedback modulators to tune the T-cell response amplitude precisely, or as an inducible pause switch that can temporarily disable T-cell activation. These studies demonstrate how pathogens could provide a rich toolkit of parts to engineer cells for therapeutic or biotechnological applications. 相似文献
105.
Xiaofeng Xia Shaoxiong Wang Jianbang Luo Ricky N. S. Wong Senfang Sui 《科学通报(英文版)》1999,44(20):1892-1892
Tianhuafen is a kind of traditional Chinese medicine for abortion, which has long been used in China. The basic protein trichosanthin (TCS) is responsible for such activity. As a ribosome inactivating protein (RIP), trichosanthin removes A4304 in the 28s rRNA via the N-glycosidase activity and inactivates the ribosome. However, it remains unclear how TCS can enter the cytoplasm. In the experiment, monolayers at air/water interface have been used to study the interaction between TCS and phospholipid membrane. The results show that TCS can penetrate negatively charged phospholipid monolayer under acid condition, and its membrane penetrating ability is obviously pH-dependent. A hypothesis of TCS penetrating biological membrane under acid condition is proposed based on the obtained result. 相似文献
106.
Directional guidance of neuronal migration in the olfactory system by the protein Slit. 总被引:34,自引:0,他引:34
Although cell migration is crucial for neural development, molecular mechanisms guiding neuronal migration have remained unclear. Here we report that the secreted protein Slit repels neuronal precursors migrating from the anterior subventricular zone in the telencephalon to the olfactory bulb. Our results provide a direct demonstration of a molecular cue whose concentration gradient guides the direction of migrating neurons. They also support a common guidance mechanism for axon projection and neuronal migration and suggest that Slit may provide a molecular tool with potential therapeutic applications in controlling and directing cell migration. 相似文献
107.
王永初 《华侨大学学报(自然科学版)》1987,(2):176-180
极值调节器是DDZ-Ⅲ型或DDZ-Ⅱ型系列仪表的一个新单元,可用于生产过程的静态最佳控制,如燃烧效率控制、蒸发器最佳液位控制,由于本调节器是由模拟线路构成,所以在模拟信号的保持,传送以及梯度方向的判断遇到某些困难,本文介绍这些问题及其解决办法。这台仪表的精度为±0.5%。 相似文献
108.
L. Yin C. M. Chung R. Huo H. Liu C. Zhou W. Xu H. Zhu J. Zhang Q. Shi H. Y. C. Wong J. Chen Y. Lu Y. Bi C. Zhao Y. Du M. Ma Y. Cai W. Y. Chen K. L. Fok L. L. Tsang K. Li Y. Ni Y. W. Chung Z. Zhou J. Sha H. C. Chan 《Cellular and molecular life sciences : CMLS》2009,66(5):900-908
The acrosome reaction has long been thought to be induced by the zona pellucida. Here we report the identification and function
of a novel human sperm glycosylphosphatidylinositol (GPI)-anchored membrane protein, NYD-SP8. The release of the protein during
sperm-egg interaction and its binding to the cumulus, the first layer of egg investment, elicits cross-talk between the gametes
and produces calcium dependant release of progesterone, which lead to the acrosome reaction. An in vivo mouse model of NYD-SP8 immunization is also established showing a reduced fertility rate. Thus, contrary to accepted dogma,
our study demonstrates for the first time that, prior to reaching the zona pellucida, sperm may release a surface protein
that acts on the cumulus cells leading to the acrosome reaction, which may be important for determining the outcome of fertilization.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
Received 11 August 2008; received after revision 18 December 2008; accepted 22 December 2008 相似文献
109.
This paper presents a network equilibrium formulation for modeling commuters' travel choices in a bimodal transport system with park-and-ride (P&R) trips while the total demand is elastic to the congestion level of the network. A super-network approach is adopted in the proposed model. It is assumed that commuters' trips are categorized into two types, auto mode only and a combined mode with both auto and transit modes. The former is referred to as the pure mode trip and the latter as the P&R mode trip. The proposed model simultaneously considers the commuter's choice of the pure mode versus the P&R mode, the choice of parking location for the pure mode, the choice of transfer point for the P&R mode, as well as the route choice for each mode. The demand elasticity of transport system, the capacity constraints of transport facilities, and the congestion interaction throughout the super-network are also explicitly incorporated into the proposed model. The results of the numerical experiment show the following key findings: (i) traditional parking/P&R models may overestimate or underestimate travel demand distribution over network; (ii) parking/P&R, transit scheduling, and carpooling schemes bring significant impacts on commuters' travel behavior and network performance; and (iii) different transport policies may be to some extent mutually substituted . 相似文献
110.
合成了通式为(C15H15N2O3)xRE(NO3)y(H2O)z(当RE=La~Pr时,x=3,y=6,z=0;RE=Nd时,x=2,y=5,z=1;RE=Sm~Lu,Y时,x=2,y=5,z=0)的一系列15种标题配合物.通过元素分析,IR,UV,1HNMR,TG-DTA,摩尔电导和X射线粉末衍射分析等对配合物的性质进行了表征.认为可能生成包含一分子水的11配位钕配合物的原因在于抗衡阳离子的空间效应,使其与络阴离子间的vanderWaals力增强的结果 相似文献