A single positively selected West Nile viral mutation confers increased virogenesis in American crows

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.     

A genome-wide association study for celiac disease identifies risk variants in the region harboring IL2 and IL21

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.     

Loss of ACTN3 gene function alters mouse muscle metabolism and shows evidence of positive selection in humans

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.     

On the self-association potential of transmembrane tight junction proteins

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.     

条斑紫菜与坛紫菜挥发性风味的电子鼻分析

【目的】利用电子鼻技术区分条斑紫菜(Pyropia yezoensis)与坛紫菜(Pyropia haitanensis)的原藻及其制品。【方法】应用18个金属氧化型气体传感器并通过风味雷达图和主成分分析法对2种紫菜的挥发性风味进行轮廓性分析。【结果】两种方法分析原藻及其制品均显示条斑紫菜和坛紫菜的气味轮廓与敏感物质类型存在差异;相比紫菜原藻,各制品间的气味轮廓较为一致。【结论】电子鼻技术可以区分条斑紫菜与坛紫菜挥发性风味,原藻及其制品均有明显差异。加工过程使得产品挥发性风味趋于统一。     

探讨带参数微分方程边值问题的解法

主要讨论带参数微分方程边值问题的逼近值及渐近值解法,并且利用基础解系、边值函数等概念,解决了带参数的微分方程中参数充分小的范围内解的变化趋势.     

钎焊后自然时效对3003/6xxx/3003复合铝合金性能和组织的影响

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。     

含未知输入非线性系统的扩展平方根容积卡尔曼滤波算法

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。