MYH9 is a major-effect risk gene for focal segmental glomerulosclerosis

The increased burden of chronic kidney and end-stage kidney diseases (ESKD) in populations of African ancestry has been largely unexplained. To identify genetic variants predisposing to idiopathic and HIV-1-associated focal segmental glomerulosclerosis (FSGS), we carried out an admixture-mapping linkage-disequilibrium genome scan on 190 African American individuals with FSGS and 222 controls. We identified a chromosome 22 region with a genome-wide logarithm of the odds (lod) score of 9.2 and a peak lod of 12.4 centered on MYH9, a functional candidate gene expressed in kidney podocytes. Multiple MYH9 SNPs and haplotypes were recessively associated with FSGS, most strongly a haplotype spanning exons 14 through 23 (OR = 5.0, 95% CI = 3.5-7.1; P = 4 x 10(-23), n = 852). This association extended to hypertensive ESKD (OR = 2.2, 95% CI = 1.5-3.4; n = 433), but not type 2 diabetic ESKD (n = 476). Genetic variation at the MYH9 locus substantially explains the increased burden of FSGS and hypertensive ESKD among African Americans.     

深圳老城区局部雨污管网水质水量检测

为了给城市居民区雨污管网改造提供依据,通过在不同时段,特别是降雨时期对市区某段管网进行连续采样检测,研究了这种部分混流的分流制管网中,水质水量的变化特征.实验结果表明:在非雨期,由于错接,雨水管中仍有大量水排出,污水管中水量始终明显大于雨水管中水量,各项污染物指标包括溶解性有机碳(DOC)、总氮(TN)、 氨氮(NH3-N)和总磷(TP)的日峰值浓度均高于雨水管中浓度,且污水管中污染物浓度日变化量较雨水管中稳定.在降雨时,雨水管、污水管内各类污染物浓度变化不明显.     

Structural basis of HutP-mediated anti-termination and roles of the Mg2+ ion and L-histidine ligand

HutP regulates the expression of the hut structural genes of Bacillus subtilis by an anti-termination mechanism and requires two components, Mg2+ ions and L-histidine. HutP recognizes three UAG triplet units, separated by four non-conserved nucleotides on the terminator region. Here we report the 1.60-A resolution crystal structure of the quaternary complex (HutP-L-histidine-Mg2+-21-base single-stranded RNA). In the complex, the RNA adopts a novel triangular fold on the hexameric surface of HutP, without any base-pairing, and binds to the protein mostly by specific protein-base interactions. The structure explains how the HutP and RNA interactions are regulated critically by the l-histidine and Mg2+ ion through the structural rearrangement. To gain insights into these structural rearrangements, we solved two additional crystal structures (uncomplexed HutP and HutP-L-histidine-Mg2+) that revealed the intermediate structures of HutP (before forming an active structure) and the importance of the Mg2+ ion interactions in the complexes.     

文明戏(中国早期话剧)研究史的几个问题——以袁国兴和黄爱华近著为中心

近几年相继出版的袁国兴的《中国话剧的孕育与生成》和黄爱华的《中国早期话剧与日本》,是两部各有特色的文明戏研究专著,有体系的专门研究论著的出版,无疑标志着中国国内的文明戏研究达到了一个新的阶段。通过对文明戏研究现状和存在问题的考察,可知今后的文明戏研究方向应该是:一、加强戏剧史料的整理和研究,只有依靠正确的资料,才能期望文明戏研究有新的成果产生;二、加强中日学术交流,以解决中国学者对日本戏剧知识不足的问题;三、加强文明戏与中国传统戏曲以及早期电影的关系的研究,以更全面深入地认识和把握文明戏的特性。     

HAR1 mediates systemic regulation of symbiotic organ development

Symbiotic root nodules are beneficial to leguminous host plants; however, excessive nodulation damages the host because it interferes with the distribution of nutrients in the plant. To keep a steady balance, the nodulation programme is regulated systemically in leguminous hosts. Leguminous mutants that have lost this ability display a hypernodulating phenotype. Through the use of reciprocal and self-grafting studies using Lotus japonicus hypernodulating mutants, har1 (also known as sym78), we show that the shoot genotype is responsible for the negative regulation of nodule development. A map-based cloning strategy revealed that HAR1 encodes a protein with a relative molecular mass of 108,000, which contains 21 leucine-rich repeats, a single transmembrane domain and serine/threonine kinase domains. The har1 mutant phenotype was rescued by transfection of the HAR1 gene. In a comparison of Arabidopsis receptor-like kinases, HAR1 showed the highest level of similarity with CLAVATA1 (CLV1). CLV1 negatively regulates formation of the shoot and floral meristems through cell-cell communication involving the CLV3 peptide. Identification of hypernodulation genes thus indicates that genes in leguminous plants bearing a close resemblance to CLV1 regulate nodule development systemically, by means of organ-organ communication.     

Expression of bcl-2 gene increases in apoptosis of vascular endothelial cells induced by rattlesnake venom

Apoptosis of vascular endothelial cells (VEC) has been induced by deprivation of survival factors (aFGF and serum) and by rattlesnake venom. The expression of bcl-2 gene has been examined by Northern blotting in the two apoptosis inducing systems. Our results show that the expression of bcl-2 has not been detected in normal culture cells and in apoptotic cells induced by deprivation of survival factors. But in apoptotic cells induced by rattlesnake venom (10 g/mL), the expression of bcl-2 increases, and its mRNA exhibits two bands. The data first suggest that increasing expression and splitting of bcl-2 mRNA may play an important role in apoptosis of VEC induced by rattlesnake venom, and this finding is helpful to understanding the role of bcl-2 in regulation of apoptosis.     

Asymmetric Agglomerative Hierarchical Clustering Algorithms and Their Evaluations

This paper presents asymmetric agglomerative hierarchical clustering algorithms in an extensive view point. First, we develop a new updating formula for these algorithms, proposing a general framework to incorporate many algorithms. Next we propose measures to evaluate the fit of asymmetric clustering results to data. Then we demonstrate numerical examples with real data, using the new updating formula and the indices of fit. Discussing empirical findings, through the demonstrative examples, we show new insights into the asymmetric clustering.     

Histone H2AX-dependent GABA(A) receptor regulation of stem cell proliferation

Stem cell self-renewal implies proliferation under continued maintenance of multipotency. Small changes in numbers of stem cells may lead to large differences in differentiated cell numbers, resulting in significant physiological consequences. Proliferation is typically regulated in the G1 phase, which is associated with differentiation and cell cycle arrest. However, embryonic stem (ES) cells may lack a G1 checkpoint. Regulation of proliferation in the 'DNA damage' S/G2 cell cycle checkpoint pathway is known for its role in the maintenance of chromatin structural integrity. Here we show that autocrine/paracrine gamma-aminobutyric acid (GABA) signalling by means of GABA(A) receptors negatively controls ES cell and peripheral neural crest stem (NCS) cell proliferation, preimplantation embryonic growth and proliferation in the boundary-cap stem cell niche, resulting in an attenuation of neuronal progenies from this stem cell niche. Activation of GABA(A) receptors leads to hyperpolarization, increased cell volume and accumulation of stem cells in S phase, thereby causing a rapid decrease in cell proliferation. GABA(A) receptors signal through S-phase checkpoint kinases of the phosphatidylinositol-3-OH kinase-related kinase family and the histone variant H2AX. This signalling pathway critically regulates proliferation independently of differentiation, apoptosis and overt damage to DNA. These results indicate the presence of a fundamentally different mechanism of proliferation control in these stem cells, in comparison with most somatic cells, involving proteins in the DNA damage checkpoint pathway.