Essential role for the peroxiredoxin Prdx1 in erythrocyte antioxidant defence and tumour suppression

Reactive oxygen species are involved in many cellular metabolic and signalling processes and are thought to have a role in disease, particularly in carcinogenesis and ageing. We have generated mice with targeted inactivation of Prdx1, a member of the peroxiredoxin family of antioxidant enzymes. Here we show that mice lacking Prdx1 are viable and fertile but have a shortened lifespan owing to the development beginning at about 9 months of severe haemolytic anaemia and several malignant cancers, both of which are also observed at increased frequency in heterozygotes. The haemolytic anaemia is characterized by an increase in erythrocyte reactive oxygen species, leading to protein oxidation, haemoglobin instability, Heinz body formation and decreased erythrocyte lifespan. The malignancies include lymphomas, sarcomas and carcinomas, and are frequently associated with loss of Prdx1 expression in heterozygotes, which suggests that this protein functions as a tumour suppressor. Prdx1-deficient fibroblasts show decreased proliferation and increased sensitivity to oxidative DNA damage, whereas Prdx1-null mice have abnormalities in numbers, phenotype and function of natural killer cells. Our results implicate Prdx1 as an important defence against oxidants in ageing mice.     

Extracting multiple layers from data having graph structures

Much data such as geometric image data and drawings have graph structures.Such data are called graph structured data. In order to manage efficiently such graph structured data, we need to analyze and abstract graph structures of such data. The purpose of this paper is to find knowledge representations which indicate plural abstractions of graph structured data. Firstly, we introduce a term graph as a graph pattern having structural variables, and a substitution over term graphs which is graph we also define a multiple layer for S as a pair (D,O) of a set D of term graphs and a list of substitutions. Secondly, for a graph G and a set S of graphs, we present effective algorithms for extracting minimal multiple layers of G and S which give us stratifying abstractions of G and S, respectively. Finally, we report experimental results obtained by applying our algorithms to both artificial data and drawings of power plants which are real world data.     

Common variants at 11q12, 10q26 and 3p11.2 are associated with prostate cancer susceptibility in Japanese

We have previously reported multiple loci associated with prostate cancer susceptibility in a Japanese population using a genome-wide association study (GWAS). To identify additional prostate cancer susceptibility loci, we genotyped nine SNPs that were nominally associated with prostate cancer (P < 1 × 10(-4)) in our previous GWAS in three independent studies of prostate cancer in Japanese men (2,557 individuals with prostate cancer (cases) and 3,003 controls). In a meta-analysis of our previous GWAS and the replication studies, which included a total of 7,141 prostate cancer cases and 11,804 controls from a single ancestry group, three new loci reached genome-wide significance on chromosomes 11q12 (rs1938781; P = 1.10 × 10(-10); FAM111A-FAM111B), 10q26 (rs2252004; P = 1.98 × 10(-8)) and 3p11.2 (rs2055109; P = 3.94 × 10(-8)). We also found suggestive evidence of association at a previously reported prostate cancer susceptibility locus at 2p11 (rs2028898; P = 1.08 × 10(-7)). The identification of three new susceptibility loci should provide additional insight into the pathogenesis of prostate cancer and emphasizes the importance of conducting GWAS in diverse populations.     

松材线虫的表被层蛋白

线虫表被层在寄主寄生者互作中起着多种关键作用。几种凝集素在不同虫龄的表被层中的结合能力测定证明,麦胚凝集素(WGA)仅结合到3龄繁殖幼虫及卵壳表面,但这种结合经常发生在毒性松材线虫分离物中,而不是低毒松材线虫分离物的表被层。卵壳表面WGA的结合最强。WGA经常结合到线虫表被层上。表被层蛋白提取物的分析显示其碳氢化合物及蛋白质谱随线虫发育和对松树寄主的入侵而变化。研究结果表明,松材线虫的表被层蛋白在松树寄主和线虫间的互作中起着重要作用。     

Identification of a ferrireductase required for efficient transferrin-dependent iron uptake in erythroid cells

The reduction of iron is an essential step in the transferrin (Tf) cycle, which is the dominant pathway for iron uptake by red blood cell precursors. A deficiency in iron acquisition by red blood cells leads to hypochromic, microcytic anemia. Using a positional cloning strategy, we identified a gene, six-transmembrane epithelial antigen of the prostate 3 (Steap3), responsible for the iron deficiency anemia in the mouse mutant nm1054. Steap3 is expressed highly in hematopoietic tissues, colocalizes with the Tf cycle endosome and facilitates Tf-bound iron uptake. Steap3 shares homology with F(420)H(2):NADP(+) oxidoreductases found in archaea and bacteria, as well as with the yeast FRE family of metalloreductases. Overexpression of Steap3 stimulates the reduction of iron, and mice lacking Steap3 are deficient in erythroid ferrireductase activity. Taken together, these findings indicate that Steap3 is an endosomal ferrireductase required for efficient Tf-dependent iron uptake in erythroid cells.