IGFBP-4 is an inhibitor of canonical Wnt signalling required for cardiogenesis

Insulin-like growth-factor-binding proteins (IGFBPs) bind to and modulate the actions of insulin-like growth factors (IGFs). Although some of the actions of IGFBPs have been reported to be independent of IGFs, the precise mechanisms of IGF-independent actions of IGFBPs are largely unknown. Here we report a previously unknown function for IGFBP-4 as a cardiogenic growth factor. IGFBP-4 enhanced cardiomyocyte differentiation in vitro, and knockdown of Igfbp4 attenuated cardiomyogenesis both in vitro and in vivo. The cardiogenic effect of IGFBP-4 was independent of its IGF-binding activity but was mediated by the inhibitory effect on canonical Wnt signalling. IGFBP-4 physically interacted with a Wnt receptor, Frizzled 8 (Frz8), and a Wnt co-receptor, low-density lipoprotein receptor-related protein 6 (LRP6), and inhibited the binding of Wnt3A to Frz8 and LRP6. Although IGF-independent, the cardiogenic effect of IGFBP-4 was attenuated by IGFs through IGFBP-4 sequestration. IGFBP-4 is therefore an inhibitor of the canonical Wnt signalling required for cardiogenesis and provides a molecular link between IGF signalling and Wnt signalling.     

Novel metabolite of nitrazepam in the rabbit urine

Summary Two novel metabolites appearing mainly as conjugated form in the urine of rabbits fed nitrazepam have been isolated as deconjugated form. From the data of elemental and spectral analysis, the structure was confirmed as 2-amino-3-hydroxy-5-nitrobenzophenone (M-I) and 2-benzoyl-4-nitro-2-hydroxyacetanilide (M-II).     

四川蝙蝠核型的进一步研究

报道了含中国特有种大足鼠耳蝠(Myotis ricketti)在内的、四川地区6种蝙蝠的核型.菊头蝠科2种,即大耳菊头蝠(Rhinolophus macrotis),核型为2n=62,FN=60;云南菊头蝠(R.yunanensis),核型较为特殊,2n=46,FN=58.蹄蝠科1种,即普氏蹄蝠(Hipposideros pratti),核型为2n=32,FN=60;蝙蝠科鼠耳蝠属3种,即中华鼠耳蝠(Myotis chinensis),核型为2n=44,FN=50;大足鼠耳蝠为2n=44,FN=52;西南鼠耳蝠(M.altarium)为2n=44,FN=50.其中云南菊头蝠的核型为中国第1次报道.     

Identification of loci associated with schizophrenia by genome-wide association and follow-up

We carried out a genome-wide association study of schizophrenia (479 cases, 2,937 controls) and tested loci with P < 10(-5) in up to 16,726 additional subjects. Of 12 loci followed up, 3 had strong independent support (P < 5 x 10(-4)), and the overall pattern of replication was unlikely to occur by chance (P = 9 x 10(-8)). Meta-analysis provided strongest evidence for association around ZNF804A (P = 1.61 x 10(-7)) and this strengthened when the affected phenotype included bipolar disorder (P = 9.96 x 10(-9)).     

Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus

We carried out a multistage genome-wide association study of type 2 diabetes mellitus in Japanese individuals, with a total of 1,612 cases and 1,424 controls and 100,000 SNPs. The most significant association was obtained with SNPs in KCNQ1, and dense mapping within the gene revealed that rs2237892 in intron 15 showed the lowest Pvalue (6.7 x 10(-13), odds ratio (OR) = 1.49). The association of KCNQ1 with type 2 diabetes was replicated in populations of Korean, Chinese and European ancestry as well as in two independent Japanese populations, and meta-analysis with a total of 19,930 individuals (9,569 cases and 10,361 controls) yielded a P value of 1.7 x 10(-42) (OR = 1.40; 95% CI = 1.34-1.47) for rs2237892. Among control subjects, the risk allele of this polymorphism was associated with impairment of insulin secretion according to the homeostasis model assessment of beta-cell function or the corrected insulin response. Our data thus implicate KCNQ1 as a diabetes susceptibility gene in groups of different ancestries.     

A sulfur–microporous carbon composite positive electrode for lithium/sulfur and silicon/sulfur rechargeble batteries

Sulfur is an advantageous material as a promising next-generation positive electrode material for high-energy lithium batteries due to a high theoretical capacity of 1672 m A h g 1although its discharge potential is somewhat modest:ca.2 V vs Li/Lit.However,a sulfur positive electrode has some crucial problems for practical use,which are mainly attributed to the dissolution of its intermediate products in charge–discharge processes.In order to resolve the dissolution problem of lithium polysulfide,we attempted to synthesize a sulfur–microporous activated carbon(AC) composite positive electrode.Moreover,we have systematically researched the battery performance of sulfur–microporous AC positive electrode with variations of electrolytes as well as negative electrodes,and found its promising positive electrode performance for a nextgeneration rechargeable battery.     

The mitochondrial bottleneck occurs without reduction of mtDNA content in female mouse germ cells

Observations of rapid shifts in mitochondrial DNA (mtDNA) variants between generations prompted the creation of the bottleneck theory. A prevalent hypothesis is that a massive reduction in mtDNA content during early oogenesis leads to the bottleneck. To test this, we estimated the mtDNA copy number in single germline cells and in single somatic cells of early embryos in mice. Primordial germ cells (PGCs) show consistent, moderate mtDNA copy numbers across developmental stages, whereas primary oocytes demonstrate substantial mtDNA expansion during early oocyte maturation. Some somatic cells possess a very low mtDNA copy number. We also demonstrated that PGCs have more than 100 mitochondria per cell. We conclude that the mitochondrial bottleneck is not due to a drastic decline in mtDNA copy number in early oogenesis but rather to a small effective number of segregation units for mtDNA in mouse germ cells. These results provide new information for mtDNA segregation models and for understanding the recurrence risks for mtDNA diseases.