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21.
A calcium sensor in the sodium channel modulates cardiac excitability. 总被引:11,自引:0,他引:11
Hanno L Tan Sabina Kupershmidt Rong Zhang Svetlana Stepanovic Dan M Roden Arthur A M Wilde Mark E Anderson Jeffrey R Balser 《Nature》2002,415(6870):442-447
Sodium channels are principal molecular determinants responsible for myocardial conduction and maintenance of the cardiac rhythm. Calcium ions (Ca2+) have a fundamental role in the coupling of cardiac myocyte excitation and contraction, yet mechanisms whereby intracellular Ca2+ may directly modulate Na channel function have yet to be identified. Here we show that calmodulin (CaM), a ubiquitous Ca2+-sensing protein, binds to the carboxy-terminal 'IQ' domain of the human cardiac Na channel (hH1) in a Ca2+-dependent manner. This binding interaction significantly enhances slow inactivation-a channel-gating process linked to life-threatening idiopathic ventricular arrhythmias. Mutations targeted to the IQ domain disrupted CaM binding and eliminated Ca2+/CaM-dependent slow inactivation, whereas the gating effects of Ca2+/CaM were restored by intracellular application of a peptide modelled after the IQ domain. A naturally occurring mutation (A1924T) in the IQ domain altered hH1 function in a manner characteristic of the Brugada arrhythmia syndrome, but at the same time inhibited slow inactivation induced by Ca2+/CaM, yielding a clinically benign (arrhythmia free) phenotype. 相似文献
22.
We discuss a generalization of the standard notion of probability space and show that the emerging framework, to be called operational probability theory, can be considered as underlying quantal theories. The proposed framework makes special reference to the convex structure of states and to a family of observables which is wider than the familiar set of random variables: it appears as an alternative to the known algebraic approach to quantum probability. 相似文献
23.
Fibulin-5/DANCE is essential for elastogenesis in vivo. 总被引:19,自引:0,他引:19
Tomoyuki Nakamura Pilar Ruiz Lozano Yasuhiro Ikeda Yoshitaka Iwanaga Aleksander Hinek Susumu Minamisawa Ching-Feng Cheng Kazuhiro Kobuke Nancy Dalton Yoshikazu Takada Kei Tashiro John Ross Jr Tasuku Honjo Kenneth R Chien 《Nature》2002,415(6868):171-175
The elastic fibre system has a principal role in the structure and function of various types of organs that require elasticity, such as large arteries, lung and skin. Although elastic fibres are known to be composed of microfibril proteins (for example, fibrillins and latent transforming growth factor (TGF)-beta-binding proteins) and polymerized elastin, the mechanism of their assembly and development is not well understood. Here we report that fibulin-5 (also known as DANCE), a recently discovered integrin ligand, is an essential determinant of elastic fibre organization. fibulin-5-/- mice generated by gene targeting exhibit a severely disorganized elastic fibre system throughout the body. fibulin-5-/- mice survive to adulthood, but have a tortuous aorta with loss of compliance, severe emphysema, and loose skin (cutis laxa). These tissues contain fragmented elastin without an increase of elastase activity, indicating defective development of elastic fibres. Fibulin-5 interacts directly with elastic fibres in vitro, and serves as a ligand for cell surface integrins alphavbeta3, alphavbeta5 and alpha9beta1 through its amino-terminal domain. Thus, fibulin-5 may provide anchorage of elastic fibres to cells, thereby acting to stabilize and organize elastic fibres in the skin, lung and vasculature. 相似文献
24.
A. E. Yassen H. A. Hassan L. S. Kawashti 《Cellular and molecular life sciences : CMLS》1994,50(11-12):1111-1114
A detailed karyotypic analysis of two Egyptian species of bats,Taphozous perforatus andTaphozous nudiventris, was made on the basis of conventional data and G-band patterns. No detectable karyotypic difference was found between the two species (2n=42, F.N. 64). By comparison of G-band patterns, some differences between the two species were seen in the corresponding autosomal pairs. These results are reported for the first time in Egypt. 相似文献
25.
26.
Aeromonas caviae isolated from stools of diarrheic formula-fed infants and environmental sources produce acetic acid when grown in glucose broth, which is bactericidal (suicide phenomenon). A. caviae grows anaerobically in a minimal medium or under permissive conditions such as the intestinal tract of formula-fed infants. These isolates adhered to HEp-2 cells and produced a cytotoxic and a cytotonic enterotoxin which underscore their enteropathogenicity. 相似文献
27.
M E MacDonald A Novelletto C Lin D Tagle G Barnes G Bates S Taylor B Allitto M Altherr R Myers 《Nature genetics》1992,1(2):99-103
Analysis of 78 Huntington's disease (HD) chromosomes with multi-allele markers revealed 26 different haplotypes, suggesting a variety of independent HD mutations. The most frequent haplotype, accounting for about one third of disease chromosomes, suggests that the disease gene is between D4S182 and D4S180. However, the paucity of an expected class of chromosomes that can be related to this major haplotype by assuming single crossovers may reflect the operation of other mechanisms in creating haplotype diversity. Some of these mechanisms sustain alternative scenarios that do not require a multiple mutational origin for HD and/or its positioning between D4S182 and D4S180. 相似文献
28.
Structure of the detoxification catalyst mercuric ion reductase from Bacillus sp. strain RC607 总被引:10,自引:0,他引:10
Several hundred million tons of toxic mercurials are dispersed in the biosphere. Microbes can detoxify organo-mercurials and mercury salts through sequential action of two enzymes, organomercury lyase and mercuric ion reductase (MerA). The latter, a homodimer with homology to the FAD-dependent disulphide oxidoreductases, catalyses the reaction NADPH + Hg(II)----NADP+ + H+ + Hg(0), one of the very rare enzymic reactions with metal substrates. Human glutathione reductase serves as a reference molecule for FAD-dependent disulphide reductases and between its primary structure and that of MerA from Tn501 (Pseudomonas), Tn21 (Shigella), p1258 (Staphylococcus) and Bacillus, 25-30% of the residues have been conserved. All MerAs have a C-terminal extension about 15 residues long but have very varied N termini. Although the enzyme from Streptomyces lividans has no addition, from Pseudomonas aeruginosa Tn501 and Bacillus sp. strain RC607 it has one and two copies respectively of a domain of 80-85 residues, highly homologous to MerP, the periplasmic component of proteins encoded by the mer operon. These domains can be proteolytically cleaved off without changing the catalytic efficiency. We report here the crystal structure of MerA from the Gram-positive bacterium Bacillus sp. strain RC607. Analysis of its complexes with nicotinamide dinucleotide substrates and the inhibitor Cd(II) reveals how limited structural changes enable an enzyme to accept as substrate what used to be a dangerous inhibitor. Knowledge of the mode of mercury ligation is a prerequisite for understanding this unique detoxification mechanism. 相似文献
29.
LANE RE 《Advancement of science》1948,5(18):96-118
30.
陶娥 《长春师范学院学报》2007,(3)
由于民间文学的社会功能是多方面的,东北地区的民间文学在东北旅游文化中能起到传播知识、净化灵魂、陶冶情操、娱乐休闲等教益作用。 相似文献