Cornelia de Lange syndrome is caused by mutations in NIPBL, the human homolog of Drosophila melanogaster Nipped-B

Cornelia de Lange syndrome (CdLS; OMIM 122470) is a dominantly inherited multisystem developmental disorder characterized by growth and cognitive retardation; abnormalities of the upper limbs; gastroesophageal dysfunction; cardiac, ophthalmologic and genitourinary anomalies; hirsutism; and characteristic facial features. Genital anomalies, pyloric stenosis, congenital diaphragmatic hernias, cardiac septal defects, hearing loss and autistic and self-injurious tendencies also frequently occur. Prevalence is estimated to be as high as 1 in 10,000 (ref. 4). We carried out genome-wide linkage exclusion analysis in 12 families with CdLS and identified four candidate regions, of which chromosome 5p13.1 gave the highest multipoint lod score of 2.7. This information, together with the previous identification of a child with CdLS with a de novo t(5;13)(p13.1;q12.1) translocation, allowed delineation of a 1.1-Mb critical region on chromosome 5 for the gene mutated in CdLS. We identified mutations in one gene in this region, which we named NIPBL, in four sporadic and two familial cases of CdLS. We characterized the genomic structure of NIPBL and found that it is widely expressed in fetal and adult tissues. The fly homolog of NIPBL, Nipped-B, facilitates enhancer-promoter communication and regulates Notch signaling and other developmental pathways in Drosophila melanogaster.     

深圳福田红树林区浮游藻类时空分布的研究

在2005年11月（秋）、2006年1月（冬）、2006年4月（春）,分别对深圳福田红树林保护区5个水质监测站的浮游藻类进行采样研究.共鉴定到浮游藻类5门27属52种（含1变种和9未知种）,密度在1.2×10^6～8.8×10^6个/L之间,平均密度为4.9×10^6个/L.硅藻门种类最多,有17属35种（含未知7种）,占总种类数的67.3%,而且密度最大,高达8.7×10^6个/L;最少为隐藻门的种类,尚未发现甲藻门的种类.耐污染特征的种类如极微小环藻（Cyclotella caspia）、颤藻（Oscillatoriaspp.）和小球藻（Chlorella vulgaris）是藻类群落的主要成分.各站分布的藻类群落组成季节差异明显,而种类数和密度并没有明显的季节变化.各站的优势种和优势类群存在时空差异.评价各站水质,反映出该红树林区水体处在中营养至富营养化状态.     

Vaspin inhibits kallikrein 7 by serpin mechanism

The molecular target of the adipokine vaspin (visceral adipose tissue-derived serpin; serpinA12) and its mode of action are unknown. Here, we provide the vaspin crystal structure and identify human kallikrein 7 (hK7) as a first protease target of vaspin inhibited by classical serpin mechanism with high specificity in vitro. We detect vaspin–hK7 complexes in human plasma and find co-expression of both proteins in murine pancreatic β-cells. We further demonstrate that hK7 cleaves human insulin in the A- and B-chain. Vaspin treatment of isolated pancreatic islets leads to increased insulin concentration in the media upon glucose stimulation without influencing insulin secretion. By application of vaspin and generated inactive mutants, we find the significantly improved glucose tolerance in C57BL/6NTac and db/db mice treated with recombinant vaspin fully dependent on the vaspin serpin activity and not related to vaspin-mediated changes in insulin sensitivity as determined by euglycemic-hyperinsulinemic clamp studies. Improved glucose metabolism could be mediated by increased insulin plasma concentrations 150 min after a glucose challenge in db/db mice, supporting the hypothesis that vaspin may inhibit insulin degradation by hK7 in the circulation. In conclusion, we demonstrate the inhibitory serpin nature and the first protease target of the adipose tissue-derived serpin vaspin, and our findings suggest hK7 inhibition by vaspin as an underlying physiological mechanism for its compensatory actions on obesity-induced insulin resistance.     

双酚A对微小小环藻的毒性效应

以微小小环藻(Cyclotella caspia)为测试藻种,研究了不同浓度的双酚A对微小小环藻的急性毒性效应。在双酚A(4,6,8,10,12 mg/L)作用下,藻细胞生长受到不同程度的抑制;藻细胞叶绿素a含量随着双酚A浓度的增加呈下降趋势;藻细胞SOD活性随着双酚A浓度和作用时间的变化基本呈现为从诱导到抑制的动态过程;4~6 mg/L双酚A对藻细胞形态影响不大,8~12 mg/L双酚A可导致藻细胞不易分裂,细胞体积增大,细胞内含物增多,细胞器受到不同程度的破坏。     

Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways

To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 × 10(-8)). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-κB signaling and mitochondrial dysfunction as biological processes related to timing of menopause.