The SNRPN promoter is not required for genomic imprinting of the Prader-Willi/Angelman domain in mice.

In mice and humans, the locus encoding the gene for small nuclear ribonucleoprotein N (SNRPN/Snrpn), as well as other loci in the region are subject to genomic imprinting. The SNRPN promoter is embedded in a maternally methylated CpG island, is expressed only from the paternal chromosome and lies within an imprinting center that is required for switching to and/or maintenance of the paternal epigenotype. We show here that a 0.9-kb deletion of exon 1 of mouse Snrpn did not disrupt imprinting or elicit any obvious phenotype, although it did allow the detection of previously unknown upstream exons. In contrast, a larger, overlapping 4.8-kb deletion caused a partial or mosaic imprinting defect and perinatal lethality when paternally inherited.     

东亚赤道异常区电离层结构与扰动的CT成像

介绍东经 12 0°低纬电离层CT实验及CT重建结果 .提出一种改进的电离层CT算法 .该算法通过联合使用差分Doppler相位和差分Doppler频率数据 ,把相位积分常数估算融入重建过程之中 .CT重建结果发现 ,赤道异常峰电子密度等值线沿磁力线倾斜 ;峰位置逐日变化时 ,倾斜程度也随之改变 ,使峰电子密度等值线仍沿磁力线 ;峰朝赤道的运动通常伴随峰区展宽 .此外 ,对一次中等强度磁暴期间电离层响应的分析发现 ,在赤道异常峰区 ,磁暴急始之后 2 0min出现电子密度的深度耗空 ,这种耗空遍及从底到顶的整个F区 .结果表明 ,电离层CT技术在研究电离层赤道异常的动力过程、电离层行扰和不规则结构的时空演变以及暴时电离层响应等方面具有重要的应用价值与前景 .     

Two new susceptibility loci for Kawasaki disease identified through genome-wide association analysis

To find new candidate loci predisposing individuals to Kawasaki disease, an acute vasculitis that affects children, we conducted a genome-wide association study in 622 individuals with Kawasaki disease (cases) and 1,107 controls in a Han Chinese population residing in Taiwan, with replication in an independent Han Chinese sample of 261 cases and 550 controls. We report two new loci, one at BLK (encoding B-lymphoid tyrosine kinase) and one at CD40, that are associated with Kawasaki disease at genome-wide significance (P < 5 × 10(-8)). Our findings may lead to a better understanding of the role of immune activation and inflammation in Kawasaki disease pathogenesis.     

Meta-analysis identifies multiple loci associated with kidney function-related traits in east Asian populations

Chronic kidney disease (CKD), impairment of kidney function, is a serious public health problem, and the assessment of genetic factors influencing kidney function has substantial clinical relevance. Here, we report a meta-analysis of genome-wide association studies for kidney function-related traits, including 71,149 east Asian individuals from 18 studies in 11 population-, hospital- or family-based cohorts, conducted as part of the Asian Genetic Epidemiology Network (AGEN). Our meta-analysis identified 17 loci newly associated with kidney function-related traits, including the concentrations of blood urea nitrogen, uric acid and serum creatinine and estimated glomerular filtration rate based on serum creatinine levels (eGFRcrea) (P < 5.0 × 10(-8)). We further examined these loci with in silico replication in individuals of European ancestry from the KidneyGen, CKDGen and GUGC consortia, including a combined total of ～110,347 individuals. We identify pleiotropic associations among these loci with kidney function-related traits and risk of CKD. These findings provide new insights into the genetics of kidney function.     

Cloning of cDNA for the major DNA-binding protein of the erythroid lineage through expression in mammalian cells

Genes expressed in erythroid cells contain binding sites for a cell-specific factor believed to be an important regulator for this haematopoietic lineage. Using high-level transient expression in mammalian cells, we have identified complementary DNA encoding the murine protein. The factor, a new member of the zinc-finger family of DNA-binding proteins, is restricted to erythroid cells at the level of RNA expression and is closely homologous between mouse and man.     

Increased gamma-globin expression in a nondeletion HPFH mediated by an erythroid-specific DNA-binding factor

In man, a shift from gamma- to beta-globin gene expression in erythroblasts underlies a switch from fetal to adult haemoglobin during development. In hereditary persistence of fetal haemoglobin (HPFH), inappropriately high gamma-globin expression in adult life is associated with deletions in the beta-globin cluster or with single-base changes upstream of the gamma-globin genes. To account for enhanced gamma-gene expression in HPFH of the non-deletion type, we tested the nuclear proteins of human erythroleukaemia cells that bind gamma-promoter sequences in vitro by correlating specific mutations in their binding sites with promoter activity. An erythroid-specific factor (GF-1) binds as a single molecule to the -195 to -170 region and contacts two TATCT(AGATA) motifs, but not the conserved octamer (ATGCAAAT) that separates them. We observe that a single change (at -175, T----C) found in HPFH leads to increased promoter activity only in erythroid cells. This effect is mediated by GF-1, the human counterpart of the chicken erythroid factor Eryf 1. The form of HPFH we studied here is an inherited disorder which can be ascribed to the action of a cell-specific DNA-binding factor on a mutant promoter.     

Indian hedgehog is a major mediator of progesterone signaling in the mouse uterus

The hedgehog family of morphogens are regulators of cell proliferation, differentiation and cell-cell communication. These morphogens have been shown to have important roles in organogenesis, spermatogenesis, stem cell maintenance and oncogenesis. Indian hedgehog (encoded by Ihh) has been shown to be expressed in the uterine epithelium under the control of the steroid hormone, progesterone. Although in vivo and in vitro studies have shown that progesterone achieves its effects on uterine function through epithelial-stromal cross-talk, molecular mediator(s) for this cellular communication pathway have not been elucidated. Using new experimental approaches that ablate Ihh specifically in Pgr-positive uterine cells of the mouse, we demonstrate that Ihh is an essential mediator of Pgr action in the uterus, and expression of this factor is critical in mediating the communication between the uterine epithelium and stroma required for embryo implantation.     

甲烷氧化偶联金属氧化物催化剂组份分子设计程序

甲烷氧化偶联金属氧化物催化剂组份分子设计程序廖代伟，黄遵楠，林银钟，龚文华，万惠霖，张鸿斌，蔡启瑞（化学系　物理化学研究所　固体表面物理化学国家重点实验室）近几十年来所取得的显著成就提供了有可能在分子水平上进行催化剂分子设计的相当多的科学基础．国内外...     

Transformations and dynamic linear models

The dynamic linear model (DLM) with additive Gaussian errors provides a useful statistical tool that is easily implemented because of the simplicity of updating a normal model that has a natural conjugate prior. If the model is not linear or if it does not have additive Gaussian errors, then numerical methods are usually required to update the distributions of the unknown parameters. If the dimension of the parameter space is small, numerical methods are feasible. However, as the number of unknown parameters increases, the numerial methods rapidly grow in complexity and cost. This article addresses the situation where a state dependent transformation of the observations follows the DLM, but a priori the appropriate transformation is not known. The Box-Cox family, which is indexed by a single parameter, illustrates the methodology. A prior distribution is constructed over a grid of points for the transformation parameter. For each value of the grid the relevant parameter esitmates and forecasts are obtained for the transformed series. These quantities are then integrated by the current distribution of the transformation parameter. When a new observation becomes available, parallel Kalman filters are used to update the distributions of the unknown parameters and to compute the likelihood of the transformation parameter at each grid point. The distribution of the transformation parameter is then updated.