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.     

CD38 is critical for social behaviour by regulating oxytocin secretion

CD38, a transmembrane glycoprotein with ADP-ribosyl cyclase activity, catalyses the formation of Ca2+ signalling molecules, but its role in the neuroendocrine system is unknown. Here we show that adult CD38 knockout (CD38-/-) female and male mice show marked defects in maternal nurturing and social behaviour, respectively, with higher locomotor activity. Consistently, the plasma level of oxytocin (OT), but not vasopressin, was strongly decreased in CD38-/- mice. Replacement of OT by subcutaneous injection or lentiviral-vector-mediated delivery of human CD38 in the hypothalamus rescued social memory and maternal care in CD38-/- mice. Depolarization-induced OT secretion and Ca2+ elevation in oxytocinergic neurohypophysial axon terminals were disrupted in CD38-/- mice; this was mimicked by CD38 metabolite antagonists in CD38+/+ mice. These results reveal that CD38 has a key role in neuropeptide release, thereby critically regulating maternal and social behaviours, and may be an element in neurodevelopmental disorders.     

一类新型多氟氮超酸锂盐电解液的性质研究

合成了一类新型多氟氮超酸锂金属盐──二（多氟烷氧基）磺酰基氨化锂，ＬｉＮ（ＳＯ２ＯＲｆ）２（Ｒｆ＝－ＣＨ２ＣＦ３，－ＣＨ２ＣＦ２ＣＦ３，－ＣＨ３ＣＦ２ＣＦ２Ｈ，－ＣＨ（ＣＦ３）２），并用ＩＲ，１ＨＮＭＲ，１９ＦＮＭＲ对它们的结构进行了表征．以碳酸丙烯酯（ＰＣ）和乙二醇二甲醇（ＤＭＥ）为混合溶剂，研究了由这些锂盐组成的电解液的性质．结果显示，新型氟氮超酸锂盐的电化学性能十分优良，可以满足锂电池电解液的要求．讨论了引入不同的取代基所导致的对溶液导电性和阳极抗氧化性能的影响．     

宽带CDMA蜂窝系统中小区容量和覆盖半径的计算

在功率控制方程中加入干扰因子后,推导了中断概率,基站接收机灵敏度,移动台最大可允许的发射功率,信干比的期望值,路径抽耗与小区覆盖半径,小区容量的关系式,在2GHz频率,宽带,各种速率时,计算了基站接收信号的信干比,小区容量和小区的覆盖半径。     

Formation and branch migration of Holliday junctions mediated by eukaryotic recombinases

Holliday junctions (HJs) are key intermediates in homologous recombination and are especially important for the production of crossover recombinants. Bacterial RecA family proteins promote the formation and branch migration of HJs in vitro by catalysing a reciprocal DNA-strand exchange reaction between two duplex DNA molecules, one of which contains a single-stranded DNA region that is essential for initial nucleoprotein filament formation. This activity has been reported only for prokaryotic RecA family recombinases, although eukaryotic homologues are also essential for HJ production in vivo. Here we show that fission yeast (Rhp51) and human (hRad51) RecA homologues promote duplex-duplex DNA-strand exchange in vitro. As with RecA, a HJ is formed between the two duplex DNA molecules, and reciprocal strand exchange proceeds through branch migration of the HJ. In contrast to RecA, however, strand exchange mediated by eukaryotic recombinases proceeds in the 3'-->5' direction relative to the single-stranded DNA region of the substrate DNA. The opposite polarity of Rhp51 makes it especially suitable for the repair of DNA double-strand breaks, whose repair is initiated at the processed ends of breaks that have protruding 3' termini.     

Structure of the DNA deaminase domain of the HIV-1 restriction factor APOBEC3G

The human APOBEC3G (apolipoprotein B messenger-RNA-editing enzyme, catalytic polypeptide-like 3G) protein is a single-strand DNA deaminase that inhibits the replication of human immunodeficiency virus-1 (HIV-1), other retroviruses and retrotransposons. APOBEC3G anti-viral activity is circumvented by most retroelements, such as through degradation by HIV-1 Vif. APOBEC3G is a member of a family of polynucleotide cytosine deaminases, several of which also target distinct physiological substrates. For instance, APOBEC1 edits APOB mRNA and AID deaminates antibody gene DNA. Although structures of other family members exist, none of these proteins has elicited polynucleotide cytosine deaminase or anti-viral activity. Here we report a solution structure of the human APOBEC3G catalytic domain. Five alpha-helices, including two that form the zinc-coordinating active site, are arranged over a hydrophobic platform consisting of five beta-strands. NMR DNA titration experiments, computational modelling, phylogenetic conservation and Escherichia coli-based activity assays combine to suggest a DNA-binding model in which a brim of positively charged residues positions the target cytosine for catalysis. The structure of the APOBEC3G catalytic domain will help us to understand functions of other family members and interactions that occur with pathogenic proteins such as HIV-1 Vif.     

Plastid proteins crucial for symbiotic fungal and bacterial entry into plant roots

The roots of most higher plants form arbuscular mycorrhiza, an ancient, phosphate-acquiring symbiosis with fungi, whereas only four related plant orders are able to engage in the evolutionary younger nitrogen-fixing root-nodule symbiosis with bacteria. Plant symbioses with bacteria and fungi require a set of common signal transduction components that redirect root cell development. Here we present two highly homologous genes from Lotus japonicus, CASTOR and POLLUX, that are indispensable for microbial admission into plant cells and act upstream of intracellular calcium spiking, one of the earliest plant responses to symbiotic stimulation. Surprisingly, both twin proteins are localized in the plastids of root cells, indicating a previously unrecognized role of this ancient endosymbiont in controlling intracellular symbioses that evolved more recently.     

嵌入期权的激励相容型软件外包付款合同设计

扩展了文献[1]的经典模型, 建立起激励相容框架下软件外包付款合同设计的正式模型. 特别之处在于嵌入了一个"中期检查"的触发期权, 在模型中采用示性函数的方法简洁表示. 通过基准模型与嵌入触发期权的模型结果的比较, 证明了嵌入触发期权对外包的风险控制、促进承接商(vendor)提高努力程度均占有优势. 还发现嵌入期权对客户(client)与承接商的双重约束功能, 主要通过改变超支分担系数来约束客户行为. 利用中国对日本的软件外包承接商的调查研究数据, 证实了嵌入触发期权主要通 过促进承接商超支控制效率的提高而实现外包风险有效控制,也证实了双重约束功能及其他主要理论结果.     

Identification of nesfatin-1 as a satiety molecule in the hypothalamus

The brain hypothalamus contains certain secreted molecules that are important in regulating feeding behaviour. Here we show that nesfatin, corresponding to NEFA/nucleobindin2 (NUCB2), a secreted protein of unknown function, is expressed in the appetite-control hypothalamic nuclei in rats. Intracerebroventricular (i.c.v.) injection of NUCB2 reduces feeding. Rat cerebrospinal fluid contains nesfatin-1, an amino-terminal fragment derived from NUCB2, and its expression is decreased in the hypothalamic paraventricular nucleus under starved conditions. I.c.v. injection of nesfatin-1 decreases food intake in a dose-dependent manner, whereas injection of an antibody neutralizing nesfatin-1 stimulates appetite. In contrast, i.c.v. injection of other possible fragments processed from NUCB2 does not promote satiety, and conversion of NUCB2 to nesfatin-1 is necessary to induce feeding suppression. Chronic i.c.v. injection of nesfatin-1 reduces body weight, whereas rats gain body weight after chronic i.c.v. injection of antisense morpholino oligonucleotide against the gene encoding NUCB2. Nesfatin-1-induced anorexia occurs in Zucker rats with a leptin receptor mutation, and an anti-nesfatin-1 antibody does not block leptin-induced anorexia. In contrast, central injection of alpha-melanocyte-stimulating hormone elevates NUCB2 gene expression in the paraventricular nucleus, and satiety by nesfatin-1 is abolished by an antagonist of the melanocortin-3/4 receptor. We identify nesfatin-1 as a satiety molecule that is associated with melanocortin signalling in the hypothalamus.     

Statistical estimation of optimal portfolios for non‐Gaussian dependent returns of assets

This paper discusses the asymptotic efficiency of estimators for optimal portfolios when returns are vector‐valued non‐Gaussian stationary processes. We give the asymptotic distribution of portfolio estimators ? for non‐Gaussian dependent return processes. Next we address the problem of asymptotic efficiency for the class of estimators ?. First, it is shown that there are some cases when the asymptotic variance of ? under non‐Gaussianity can be smaller than that under Gaussianity. The result shows that non‐Gaussianity of the returns does not always affect the efficiency badly. Second, we give a necessary and sufficient condition for ? to be asymptotically efficient when the return process is Gaussian, which shows that ? is not asymptotically efficient generally. From this point of view we propose to use maximum likelihood type estimators for g, which are asymptotically efficient. Furthermore, we investigate the problem of predicting the one‐step‐ahead optimal portfolio return by the estimated portfolio based on ? and examine the mean squares prediction error. Copyright © 2008 John Wiley & Sons, Ltd.