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101.
Samuel CS Hewitson TD Unemori EN Tang ML 《Cellular and molecular life sciences : CMLS》2007,64(12):1539-1557
The peptide hormone relaxin is emerging as a multi-functional factor in a broad range of target tissues including several
non-reproductive organs, in addition to its historical role as a hormone of pregnancy. This review discusses the evidence
that collectively demonstrates the many diverse and vital roles of relaxin: the homeostatic role of endogenous relaxin in
mammalian pregnancy and ageing; its gender-related effects; the therapeutic effects of relaxin in the treatment of fibrosis,
inflammation, cardioprotection, vasodilation and wound healing (angiogenesis) amongst other pathophysiological conditions,
and its potential mechanism of action. Furthermore, translational issues using experimental models (to humans) and its use
in various clinical trials, are described, each with important lessons for the design of future trials involving relaxin.
The diverse physiological and pathological roles for relaxin have led to the search for its significance in humans and highlight
its potential as a drug of the future.
Received 12 December 2006; received after revision 12 February 2007; accepted 15 March 2007 相似文献
102.
Loss of GLIS2 causes nephronophthisis in humans and mice by increased apoptosis and fibrosis 总被引:4,自引:0,他引:4
103.
A single positively selected West Nile viral mutation confers increased virogenesis in American crows 总被引:1,自引:0,他引:1
Brault AC Huang CY Langevin SA Kinney RM Bowen RA Ramey WN Panella NA Holmes EC Powers AM Miller BR 《Nature genetics》2007,39(9):1162-1166
West Nile virus (WNV), first recognized in North America in 1999, has been responsible for the largest arboviral epiornitic and epidemic of human encephalitis in recorded history. Despite the well-described epidemiological patterns of WNV in North America, the basis for the emergence of WNV-associated avian pathology, particularly in the American crow (AMCR) sentinel species, and the large scale of the North American epidemic and epiornitic is uncertain. We report here that the introduction of a T249P amino acid substitution in the NS3 helicase (found in North American WNV) in a low-virulence strain was sufficient to generate a phenotype highly virulent to AMCRs. Furthermore, comparative sequence analyses of full-length WNV genomes demonstrated that the same site (NS3-249) was subject to adaptive evolution. These phenotypic and evolutionary results provide compelling evidence for the positive selection of a mutation encoding increased viremia potential and virulence in the AMCR sentinel bird species. 相似文献
104.
A genome-wide association study for celiac disease identifies risk variants in the region harboring IL2 and IL21 总被引:14,自引:0,他引:14
van Heel DA Franke L Hunt KA Gwilliam R Zhernakova A Inouye M Wapenaar MC Barnardo MC Bethel G Holmes GK Feighery C Jewell D Kelleher D Kumar P Travis S Walters JR Sanders DS Howdle P Swift J Playford RJ McLaren WM Mearin ML Mulder CJ McManus R McGinnis R Cardon LR Deloukas P Wijmenga C 《Nature genetics》2007,39(7):827-829
We tested 310,605 SNPs for association in 778 individuals with celiac disease and 1,422 controls. Outside the HLA region, the most significant finding (rs13119723; P = 2.0 x 10(-7)) was in the KIAA1109-TENR-IL2-IL21 linkage disequilibrium block. We independently confirmed association in two further collections (strongest association at rs6822844, 24 kb 5' of IL21; meta-analysis P = 1.3 x 10(-14), odds ratio = 0.63), suggesting that genetic variation in this region predisposes to celiac disease. 相似文献
105.
106.
MacArthur DG Seto JT Raftery JM Quinlan KG Huttley GA Hook JW Lemckert FA Kee AJ Edwards MR Berman Y Hardeman EC Gunning PW Easteal S Yang N North KN 《Nature genetics》2007,39(10):1261-1265
More than a billion humans worldwide are predicted to be completely deficient in the fast skeletal muscle fiber protein alpha-actinin-3 owing to homozygosity for a premature stop codon polymorphism, R577X, in the ACTN3 gene. The R577X polymorphism is associated with elite athlete status and human muscle performance, suggesting that alpha-actinin-3 deficiency influences the function of fast muscle fibers. Here we show that loss of alpha-actinin-3 expression in a knockout mouse model results in a shift in muscle metabolism toward the more efficient aerobic pathway and an increase in intrinsic endurance performance. In addition, we demonstrate that the genomic region surrounding the 577X null allele shows low levels of genetic variation and recombination in individuals of European and East Asian descent, consistent with strong, recent positive selection. We propose that the 577X allele has been positively selected in some human populations owing to its effect on skeletal muscle metabolism. 相似文献
107.
Gout AM;ADPKD Gene Variant Consortium Ravine D Harris PC Rossetti S Peters D Breuning M Henske EP Koizumi A Inoue S Shimizu Y Thongnoppakhun W Yenchitsomanus PT Deltas C Sandford R Torra R Turco AE Jeffery S Fontes M Somlo S Furu LM Smulders YM Mercier B Ferec C Burtey S Pei Y Kalaydjieva L Bogdanova N McCluskey M Geon LJ Wouters CH Reiterova J Stekrová J San Millan JL Aguiari G Del Senno L 《Nature genetics》2007,39(4):427-428
108.
Blasig IE Winkler L Lassowski B Mueller SL Zuleger N Krause E Krause G Gast K Kolbe M Piontek J 《Cellular and molecular life sciences : CMLS》2006,63(4):505-514
Tight junctions seal intercellular clefts via membrane-related strands, hence, maintaining important organ functions. We investigated
the self-association of strand-forming transmembrane tight junction proteins. The regulatory tight junction protein occludin
was differently tagged and cotransfected in eucaryotic cells. These occludins colocalized within the plasma membrane of the
same cell, coprecipitated and exhibited fluorescence resonance energy transfer. Differently tagged strand-forming claudin-5
also colocalized in the plasma membrane of the same cell and showed fluorescence resonance energy transfer. This demonstrates
self-association in intact cells both of occludin and claudin-5 in one plasma membrane. In search of dimerizing regions of
occludin, dimerization of its cytosolic C-terminal coiledcoil domain was identified. In claudin-5, the second extracellular
loop was detected as a dimer. Since the transmembrane junctional adhesion molecule also is known to dimerize, the assumption
that homodimerization of transmembrane tight junction proteins may serve as a common structural feature in tight junction
assembly is supported.
Received 6 October 2005; received after revision 14 December 2005; accepted 27 December 2005
†These authors contributed equally to this work. 相似文献
109.
Masroor Ahmad Bhat Rayees A. Zargar Anchit Modi Manju Aror N.K. Gaur 《自然科学进展(英文版)》2016,26(6):579-583
Silver ions substituted samarium strontium manganite (Sm0.55Sr0.30Ag0.15MnO3) pervoskite was synthesized by using respective oxides in stoichiometric ratio through solid state reaction. The as-prepared sample was characterized by various analytical techniques to confirm its formation and understand the effect of monovalent silver ions in pervoskite lattice. X-ray diffraction pattern confirms the single phase formation while grain morphology in SEM image indicates good connectivity among the grains. The enhancement in metal to insulator transition temperature shows quenched disorder and magnetoresistance phenomena. The magnetoresistance (MR) and temperature coefficient of resistance (TCR) emerge from grain growth factor and homogeneity induced by Ag+ ions in the lattice. The reduction in hysteresis loss resulted from antiferromagnetic - ferromagnetic (TN) and ferromagnetic - paramagnetic (Tc) transitions reveals the removal of disorder in perovskite lattice by Ag+ ions substitution. This increases the magnetic moment across distinct ions on the applying magnetic field. The rise in MR% (~99%) with silver doping emerging from smooth spin tunneling of the grains across the boundary and suppression of the disordered magnetic fluctuations with increase in magnetic field has been reported. The present compound exhibits the first order nature of magnetism and observed first time the highest value of TCR ~ 95%. 相似文献
110.
假高粱(Sorghum halepense(L.)Pers.)是世界十大恶性杂草之一.黑高粱(S.almum Parodi)和高粱(S.bicolor(L.)Moench)是假高粱的两种近缘种,其中黑高粱有入侵性,高粱则为栽培植物,不表现出入侵性.为了解影响植物入侵能力的生物学因素,比较了高粱属3种植物根尖分生组织细胞的染色体、细胞核、细胞大小和细胞有丝分裂指数.结果表明,高粱染色体平均投影面积最大,其次是黑高粱,假高粱的最小;就细胞和细胞核大小而言,都是高粱最大、其次是黑高粱和假高粱;在25~35℃的温度范围内,高粱根尖分生区细胞的有丝分裂速率最低,假高粱的最高.3种植物的种子(颖果)以高粱最大,黑高粱和假高粱的显著小,幼苗相对生长速率以高粱最小,假高粱的最高.3种植物的细胞分裂速率与其染色体、细胞核、细胞和种子大小存在显著相关,表明入侵性植物往往具有较小的分生组织细胞、细胞核和种子,但是有相对高的细胞分裂速率和幼苗相对干重.因此,根尖分生组织细胞学指标在高粱属植物入侵能力评估上有潜在应用价值. 相似文献