Genome-wide association study identifies susceptibility loci for open angle glaucoma at TMCO1 and CDKN2B-AS1

We report a genome-wide association study for open-angle glaucoma (OAG) blindness using a discovery cohort of 590 individuals with severe visual field loss (cases) and 3,956 controls. We identified associated loci at TMCO1 (rs4656461[G] odds ratio (OR) = 1.68, P = 6.1 × 10(-10)) and CDKN2B-AS1 (rs4977756[A] OR = 1.50, P = 4.7 × 10(-9)). We replicated these associations in an independent cohort of cases with advanced OAG (rs4656461 P = 0.010; rs4977756 P = 0.042) and two additional cohorts of less severe OAG (rs4656461 combined discovery and replication P = 6.00 × 10(-14), OR = 1.51, 95% CI 1.35-1.68; rs4977756 combined P = 1.35 × 10(-14), OR = 1.39, 95% CI 1.28-1.51). We show retinal expression of genes at both loci in human ocular tissues. We also show that CDKN2A and CDKN2B are upregulated in the retina of a rat model of glaucoma.     

腾冲嗜酸两性菌硫氧化还原酶分子结构中铁原子结合位点的新特征

前期研究表明, 铁原子对于嗜酸两性菌中硫氧化还原酶(SOR)的活性至关重要. 本研究表明, 2,2′-联吡啶、1,2-二羟基苯-3,5-二磺酸钠、8-羟基喹啉等特异性铁离子螯合剂强烈抑制腾冲嗜酸两性菌SOR酶活性, 进一步表明铁原子是SOR酶活必需. 对目前基因组数据库中的SOR基因或者SOR类似基因进行序列比对, 发现了一个潜在的铁原子结合模体(H⁸⁶-X₃- H⁹⁰-X_n-E¹¹⁴-X_n-E¹²⁹). 据此, 本研究采用定点突变技术, 将氨基酸残基H⁸⁶, H⁹⁰和E¹²⁹分别突变为苯丙氨酸或者丙氨酸, 圆二色光谱测定发现突变体(H⁸⁶F, H⁹⁰F和E¹²⁹A)的二级结构没有明显改变, 但是这3个突变体全部丧失了酶活性. 突变体蛋白中铁原子含量测定结果表明, 3个突变体全部或者部分丢失了铁原子, 而之前研究中获得的3个半胱氨酸突变体(完全丧失了酶活)铁原子含量没有变化. 根据本研究并结合前期实验结果可知, SOR分子中模体C³¹-X_n-C¹⁰¹-X₂-C¹⁰⁴是底物硫分子活化区域; 而模体H⁸⁶-X₃-H⁹⁰-X₂₃-E¹¹⁴-X_¹⁴-(E/D)¹²⁹是SOR分子中铁原子的结合区域, 与铁原子结合形成一个非卟啉铁中心, 是SOR的氧化还原中心; 这两个区域均是SOR酶活性的必需部分.     

修正表面张力系数的包膜气泡动力学模型

基于包膜造影剂气泡的实际应用, 在传统的三层模型基础上提出了一个修正的动力学模型来描绘包膜气泡的动力学行为. 通过衔接三层模型中包膜的两个边界条件, 得到一个两层模型并简化了方程的结构. 为了使动力平衡更加准确, 在建立边界条件时考虑了包膜质量, 并将包膜层厚度与气泡半径的关系具体化. 更为重要的是, 我们对绝大多数文献中的表面张力系数不变的假设进行了修正, 认为其随半径变化呈非线性变化, 且通过数值计算对表面张力系数修正带来的变化进行了讨论. 此外, 我们应用本文模型对实验得到的Optison及Sonozoid微气泡的动力学曲线进行了拟合, 并与其他经典模型的拟合结果进行了比较, 结论证明了本文模型具有很好的适用性.     

东方龙虱鞘翅:形态学及力学性能研究

研究了东方龙虱鞘翅的拓扑结构及其鞘翅生物材料的力学性能. SEM观测表明鞘翅横向截面和纵向截面结构相同, 是一种具 “桥墩” 状连接的空腔轻质结构, 由致密的黑色外表皮层和其下数十层几丁质纤维层平行、螺旋交织构成的内表皮层组成; 纳米压痕仪测得新鲜鞘翅外侧区域的硬度和弹性模量分别为0.31和6.13 GPa; 拉伸实验得到新鲜鞘翅横向和纵向的强度极限分别为169.2和194.5 MPa; 干燥鞘翅对应的强度极限为85.38和90.91 MPa, 新鲜鞘翅的强度是干燥鞘翅值的2倍; 结果表明甲虫鞘翅是一种力学性能呈现拓扑分布规律的轻质生物复合材料, 该研究为航空航天材料的轻质结构的设计提供了生物学的参考.     

耦合诱导的金纳米棒禁戒等离激元模式激发

用时域有限差分方法（finite-difference time-domain,FDTD）模拟了有不同局域等离激元共振频率和不同体积的外来金纳米颗粒以及外来介质纳米颗粒与金纳米棒的耦合,研究了正入射条件下与各种颗粒耦合对诱发金棒上纵向等离激元的禁戒模式的不同影响,发现外来颗粒上足够多的电荷积聚造成的电场对称性破缺是诱发禁戒模式的原因.这一发现对理解金属纳米颗粒的近场光学实验探测有重要意义.     

常规及偶应力轴对称有限元分片检验函数

我们提出的增强型分片检验可以用于检验一类非齐次阶微分方程的有限元的收敛性.由此,建立了常规轴对称问题和轴对称偶应力/应变梯度C1理论有限元增强型分片检验的检验函数,并得到重要结论：这类轴对称有限元的分片检验函数不含常剪应力项.     

Towards genetic genome projects: genomic library screening and gene-targeting vector construction in a single step.

We have developed technologies that simplify genomic library construction and screening, substantially reducing both the time and the cost associated with traditional library screening methods and facilitating the generation of gene-targeting constructs. By taking advantage of homologous recombination in Escherichia coli, we were able to use as little as 80 bp of total sequence homology to screen for a specific gene from a genomic library in plasmid or phage form. This method, called recombination cloning (REC), takes only a few days instead of the several weeks required for traditional plaque-lift methods. In addition, because every clone in the mouse genomic library we have constructed has a negative selection marker adjacent to the genomic insert, REC screening can generate gene-targeting vectors in one step, from library screening to finished construct. Conditional targeting constructs can be generated easily with minimal additional manipulation.     

Effect of biogenic amines on γ-amylase (acid α-glucosidase)

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