Loss of ACTN3 gene function alters mouse muscle metabolism and shows evidence of positive selection in humans

More than a billion humans worldwide are predicted to be completely deficient in the fast skeletal muscle fiber protein alpha-actinin-3 owing to homozygosity for a premature stop codon polymorphism, R577X, in the ACTN3 gene. The R577X polymorphism is associated with elite athlete status and human muscle performance, suggesting that alpha-actinin-3 deficiency influences the function of fast muscle fibers. Here we show that loss of alpha-actinin-3 expression in a knockout mouse model results in a shift in muscle metabolism toward the more efficient aerobic pathway and an increase in intrinsic endurance performance. In addition, we demonstrate that the genomic region surrounding the 577X null allele shows low levels of genetic variation and recombination in individuals of European and East Asian descent, consistent with strong, recent positive selection. We propose that the 577X allele has been positively selected in some human populations owing to its effect on skeletal muscle metabolism.     

浑沌：它能有多少规律

40年前A.爱因斯坦给M.玻恩的一封信中写道,“上帝不玩骰子。”爱因斯坦是始终反对量子论的概率解释的,他不倦地探索着与经典力学更为直接的类比,即考虑没有概率不定性的确定过程。如今,40年过去了,没有人会惊讶:甚至在一个经典哈密顿动力系统中也存在着(chas)在物理客体规则运动的领域内,在没有人预期会有的地方冒出     

二甲基甲酰胺中Sm（Ⅲ）电化学性质及其合金膜研究

通过循环伏安法研究二甲基甲酰胺中Sm（Ⅲ）在Pt上的电化学性质,表明Sm（Ⅲ）在Pt上的还原为不可逆反应,同时测得传递系数α=0.0289,扩散系数D0=1.288×10^-5cm^2·S^-1;通过塔菲尔曲线求得交换电流密度i0=1.596×10^-7A/cm^2;对Sm（Ⅲ）在Pt上离子成核机理研究表明,Sm（Ⅲ）在Pt电极上是按三维模式扩散控制下连续成核的;用恒电位法可以制得有金属光泽、附着力好、表面均匀致密的Sm-Ni-Co合金膜,与Ni-Co合金膜相比较结构性能有所提高.     

Hexon-chimaeric adenovirus serotype 5 vectors circumvent pre-existing anti-vector immunity

A common viral immune evasion strategy involves mutating viral surface proteins in order to evade host neutralizing antibodies. Such immune evasion tactics have not previously been intentionally applied to the development of novel viral gene delivery vectors that overcome the critical problem of anti-vector immunity. Recombinant, replication-incompetent adenovirus serotype 5 (rAd5) vector-based vaccines for human immunodeficiency virus type 1 and other pathogens have proved highly immunogenic in preclinical studies but will probably be limited by the high prevalence of pre-existing anti-Ad5 immunity in human populations, particularly in the developing world. Here we show that rAd5 vectors can be engineered to circumvent anti-Ad5 immunity. We constructed novel chimaeric rAd5 vectors in which the seven short hypervariable regions (HVRs) on the surface of the Ad5 hexon protein were replaced with the corresponding HVRs from the rare adenovirus serotype Ad48. These HVR-chimaeric rAd5 vectors were produced at high titres and were stable through serial passages in vitro. HVR-chimaeric rAd5 vectors expressing simian immunodeficiency virus Gag proved comparably immunogenic to parental rAd5 vectors in naive mice and rhesus monkeys. In the presence of high levels of pre-existing anti-Ad5 immunity, the immunogenicity of HVR-chimaeric rAd5 vectors was not detectably suppressed, whereas the immunogenicity of parental rAd5 vectors was abrogated. These data demonstrate that functionally relevant Ad5-specific neutralizing antibodies are focused on epitopes located within the hexon HVRs. Moreover, these studies show that recombinant viral vectors can be engineered to circumvent pre-existing anti-vector immunity by removing key neutralizing epitopes on the surface of viral capsid proteins. Such chimaeric viral vectors may have important practical implications for vaccination and gene therapy.     

Nickel solvent extraction from cold purification filter cakes of Angouran mine concentrate using LIX984N

Cold purification filter cakes generated in the hydrometallurgical processing of Angouran mine zinc concentrate commonly contain significant amounts of Zn, Cd, and Ni ions and thus are valuable resources for metal recovery. In this research, a nickel containing solution that was obtained from sulfuric acid leaching of the filter cake following cadmium and zinc removal was subjected to solvent extraction experiments using 10vol% LIX984N diluted in kerosene. Under optimum experimental conditions (pH 5.3, volume ratio of organic/aqueous (O:A) = 2:1, and contact time = 5 min), more than 97.1% of nickel was extracted. Nickel was stripped from the loaded organic by contacting with a 200 g/L sulfuric acid solution, from which 77.7% of nickel was recovered in a single contact at the optimum conditions (pH 1–1.5, O:A = 5:1, and contact time = 15 min).