Common variants at 12q15 and 12q24 are associated with infant head circumference

To identify genetic variants associated with head circumference in infancy, we performed a meta-analysis of seven genome-wide association studies (GWAS) (N = 10,768 individuals of European ancestry enrolled in pregnancy and/or birth cohorts) and followed up three lead signals in six replication studies (combined N = 19,089). rs7980687 on chromosome 12q24 (P = 8.1 × 10(-9)) and rs1042725 on chromosome 12q15 (P = 2.8 × 10(-10)) were robustly associated with head circumference in infancy. Although these loci have previously been associated with adult height, their effects on infant head circumference were largely independent of height (P = 3.8 × 10(-7) for rs7980687 and P = 1.3 × 10(-7) for rs1042725 after adjustment for infant height). A third signal, rs11655470 on chromosome 17q21, showed suggestive evidence of association with head circumference (P = 3.9 × 10(-6)). SNPs correlated to the 17q21 signal have shown genome-wide association with adult intracranial volume, Parkinson's disease and other neurodegenerative diseases, indicating that a common genetic variant in this region might link early brain growth with neurological disease in later life.     

Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways

Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control.     

Regulation of pyruvate metabolism and human disease

Pyruvate is a keystone molecule critical for numerous aspects of eukaryotic and human metabolism. Pyruvate is the end-product of glycolysis, is derived from additional sources in the cellular cytoplasm, and is ultimately destined for transport into mitochondria as a master fuel input undergirding citric acid cycle carbon flux. In mitochondria, pyruvate drives ATP production by oxidative phosphorylation and multiple biosynthetic pathways intersecting the citric acid cycle. Mitochondrial pyruvate metabolism is regulated by many enzymes, including the recently discovered mitochondria pyruvate carrier, pyruvate dehydrogenase, and pyruvate carboxylase, to modulate overall pyruvate carbon flux. Mutations in any of the genes encoding for proteins regulating pyruvate metabolism may lead to disease. Numerous cases have been described. Aberrant pyruvate metabolism plays an especially prominent role in cancer, heart failure, and neurodegeneration. Because most major diseases involve aberrant metabolism, understanding and exploiting pyruvate carbon flux may yield novel treatments that enhance human health.     

Mitochondrial point mutations do not limit the natural lifespan of mice

Whether mitochondrial mutations cause mammalian aging, or are merely correlated with it, is an area of intense debate. Here, we use a new, highly sensitive assay to redefine the relationship between mitochondrial mutations and age. We measured the in vivo rate of change of the mitochondrial genome at a single-base pair level in mice, and we demonstrate that the mutation frequency in mouse mitochondria is more than ten times lower than previously reported. Although we observed an 11-fold increase in mitochondrial point mutations with age, we report that a mitochondrial mutator mouse was able to sustain a 500-fold higher mutation burden than normal mice, without any obvious features of rapidly accelerated aging. Thus, our results strongly indicate that mitochondrial mutations do not limit the lifespan of wild-type mice.     

科学的不当评价

现代的科学社会是一个“审计社会”,广泛采用影响因子和被引频次对期刊和科学家进行评价,但
是这种评价方式却有助于科学不道德行为的滋生。该文总结了科学行为扭曲的6种情况,探讨了它们的形成
原因,最后尝试提出了解决问题的办法。     

Vaccination against ovine cysticercosis using a defined recombinant antigen

Cysticercosis caused by larval tapeworms is a major public health problem and a cause of substantial economic losses in the farm-animal industries. Taenia ovis in sheep is a particularly important example. Immunity to reinfection with the larvae has a central role in regulating natural transmission of the parasites, and vaccination with antigens from the early larval oncosphere stage can induce complete protection against infection. As it is impractical to obtain enough oncospheres for a commercial vaccine against these tapeworms, an alternative approach is to use recombinant DNA methods to generate a cheap and plentiful supply of antigens. We report here the expression in Escherichia coli of complementary DNA encoding T. ovis antigens as fusion proteins with the Schistosoma japonicum glutathione S-transferase. Vaccination of sheep with these fusion proteins gave significant, although not complete, immunity against challenge infection with T. ovis eggs. Commercial development of a vaccine is being pursued.     

Comment on “On linking climate to Chinese dynastic change: Spatial and temporal variations of monsoonal rain”

An article by Zhang et al. questions the interpretation of our oxygen isotope record from Wanxiang Cave and the sediment titanium record from Lake Huguang Maar, and the possible linkage between climate change and Chinese culture. In response, we explain that their approach lacks logical rigor and their major argument is broadly consistent with, rather than contradictory to our original conclusions. We also note that climate-culture relationships similar to those that we observe in China have been observed for other cultures around the world.     

广西崇左江州木榄山智人洞古人类遗址及其地质时代

关于现代智人起源的争论一直是国际古人类学研究的前沿与热点. 最近, 在广西崇左木榄山智人洞发现了具有现代人解剖特征初始状态的人类下颌骨化石及大量与之共生的哺乳动物化石. 木榄山智人洞哺乳动物群以江南象与初现的亚洲象及巨獏等组合为其特征, 截然不同于华南早更新世的巨猿动物群和中更新世的大熊猫-剑齿象动物群, 是典型亚洲象动物群的早期代表. 依动物群性质、地层对比及铀系年代测定木榄山化石智人和伴生的哺乳动物群的时代为距今约11万年的晚更新世早期. 该动物群主要由热带-亚热带型动物组成, 但木榄山动物群中森林型动物种类单调, 草地类型的动物相当多, 这表明当时的气候可能比以前干燥. 木榄山智人的发现对研究现代人起源及其环境背景具有非常重要的意义.