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61.
Loss of GLIS2 causes nephronophthisis in humans and mice by increased apoptosis and fibrosis 总被引:4,自引:0,他引:4
62.
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
63.
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
64.
65.
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
66.
针对工程实际应用中存在的未知输入会导致经典的非线性滤波器状态估计精度下降甚至滤波发散的问题,提出了一种基于最小方差无偏估计(minimum variance unbiased estimation, MVUE)准则的扩展平方根容积卡尔曼滤波(extended square-root cubature Kalman filter, ESRCKF)算法。首先,结合上一时刻未知输入估计值对状态一步预测值进行修正,得到含未知输入条件下的状态预测值。其次,设计新息并采用加权最小二乘(weighted least squares, WLS)法获取当前时刻未知输入的无偏估计。最后,通过最小化协方差矩阵的迹,同时采用拉格朗日乘子法和舒尔补引理得到系统状态的最小方差无偏估计。仿真结果表明,相比于现有的非线性滤波算法,ESRCKF算法提高了在处理含未知输入非线性系统时的状态估计精度,并能同时实现系统状态和未知输入的最优估计,验证了该算法的有效性。 相似文献
67.
以新鲜槐花为原料,辅以麦芽糖醇、柠檬酸、鸡蛋清和黄果槲寄生果实多糖等食品添加剂开发低糖槐花蜜饯。通过单因素试验,对鸡蛋清、麦芽糖醇、蜂蜜和黄果槲寄生果实多糖添加量进行筛选,采用响应面结合模糊数学感官评价法优化配方,对其重金属和微生物指标和抗氧化性进行了检验。结果表明,蜜饯最优化参数为鸡蛋清添加量为15%,麦芽糖醇添加量为30%,蜂蜜添加量为10%,黄果槲寄生果实多糖添加量为0.35%,柠檬酸量添加为0.18%、氯化钙添加量和D-异抗坏血酸钠添加量分别为0.01%为0.05%,得到了质地良好的槐花蜜饯产品,颜色均一微黄色,组织状态良好,薄厚均匀、口感细腻、咀嚼性好,槐花风味突出,气味协调。重金属含量低于国家标准限量(< 0.05 mg/kg),未检出沙门氏菌和金黄色葡萄球菌,大肠杆菌和霉菌数量等卫生指标符合国家标准。蜜饯具有较强的总抗氧化能力(FRAP)和较好的清除 1,1-二苯基-2-三硝基苯肼(DPPH)的作用。研究结果表明,研制的低糖槐花蜜饯感官指标好,其质量符合国家标准,具有很好的营养价值和抗氧化功能。 相似文献
68.
以6xxx系铝合金为芯材,3003铝合金为两侧皮材,经熔炼、铸造、复合、热轧、冷轧及成品退火制备了厚度为1.5 mm的3层复合铝合金。在600 ℃下模拟钎焊,经空冷后进行1、5、10、15、20、25、30 d的自然时效。结果显示:复合铝合金的强度、维氏硬度在自然时效初期快速增加,20 d后上升缓慢,30 d时抗拉强度、屈服强度、芯材维氏硬度达到最大,分别为242.3 MPa、122.9 MPa、84.0;芯材晶粒尺寸钎焊后较钎焊前略微长大,经不同自然时效时间的芯材晶粒平均尺寸大小相当,表明自然时效不改变芯材晶粒的大小;钎焊后以及经自然时效之后芯材中标识出的第二相为不规则的AlFeSiMnCu相。 相似文献
69.
The very low fertility experienced in several European countries in recent decades in the presence of higher intended family sizes has renewed interest in fertility intentions data. While the overall level of childbearing in Britain over the past few decades has remained relatively stable and high in comparison with many other European countries, we have seen sizeable increases in the age at which childbearing starts. This study uses data from the 1991 to 2007 General Household Surveys to examine trends in family intentions data in an attempt to arrive at a better understanding of these recent fertility developments. First, time trends in intended family size are compared with trends in observed fertility. Next, aggregate changes in intentions regarding the level and timing of fertility across the life course for cohorts are investigated together with the extent to which these aggregate intentions are matched by the subsequent childbearing of cohorts. Finally, both change across the life course and uncertainty in family intentions are examined. We conclude by discussing what these findings might tell us about contemporary reproductive decision making. 相似文献
70.