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.     

中东

Thomson Reuters 发布的全球系列研究报告表明,以阿拉伯、伊朗、土耳其为主的中东国家的科学研究与西文国家相比落后许多.当然,也有部分中东的科学家或研究机构从事着世界一流的研究工作.事实上,论文数量及引文指标都清晰地表明,近10年中东地区的研究工作有了很大的进步,表现出了鼓舞人心的发展趋势.     

The type Ia supernova SNLS-03D3bb from a super-Chandrasekhar-mass white dwarf star

The accelerating expansion of the Universe, and the need for dark energy, were inferred from observations of type Ia supernovae. There is a consensus that type Ia supernovae are thermonuclear explosions that destroy carbon-oxygen white dwarf stars that have accreted matter from a companion star, although the nature of this companion remains uncertain. These supernovae are thought to be reliable distance indicators because they have a standard amount of fuel and a uniform trigger: they are predicted to explode when the mass of the white dwarf nears the Chandrasekhar mass of 1.4 solar masses (M(o)). Here we show that the high-redshift supernova SNLS-03D3bb has an exceptionally high luminosity and low kinetic energy that both imply a super-Chandrasekhar-mass progenitor. Super-Chandrasekhar-mass supernovae should occur preferentially in a young stellar population, so this may provide an explanation for the observed trend that overluminous type Ia supernovae occur only in 'young' environments. As this supernova does not obey the relations that allow type Ia supernovae to be calibrated as standard candles, and as no counterparts have been found at low redshift, future cosmology studies will have to consider possible contamination from such events.     

Effect of substrate pretreatment on renal organic ion transport in the adult rat.

The ability of renal cortical slices to accumulate PAH and NMN was not significantly affected by pretreatment of adult rats with large doses of PAH. Pretreatment of adult rats with THAM significantly increased PAH accumulation but had no effect on NMN. Inulin and PAH clearance and filtration fraction were significantly decreased by PAH pretreatment but unaffected by THAM pretreatment. The effects of pretreatment on transport are probably due to non-specific toxicity.     

Increased blood pressure in the SHR is not related to a deficit in renomedullary PGE2

Summary Synthesis of prostaglandin E₂ by renal medulla from SHR and WKY rats was compared during early postnatal development. Although arterial blood pressure was significantly higher in SHR as early as 6 weeks of age, no difference in renal medullary prostaglandin synthesis was observed.Supported in part by a grant from the michigan Heart Association and NIH grant AM-10913.     

Effect of medium pH onp-aminohippurate accumulation by slices of rat renal cortex

Zusammenfassung Nierenschnitte von verschiedenen Arten akkumulieren PAH mit zunehmendem pH-Wert des Mediums bei einem deutlichen Maximum zwischen pH 7.4 und pH 8.0

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Supported in part by USPHS grant No. AM-10913.

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USPHS predoctoral trainee (GM-01761).

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Predoctoral Fellow of the Canadian Food and Drug Directorate, Ottawa.