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.     

Carboxy terminus of vasopressin required for activity but not binding

Vasopressin antagonists are valuable pharmacological tools for investigating physiological and behavioural functions of the nonapeptide arginine-vasopressin (AVP). The removal of glycinamide from the carboxy terminus of AVP drastically reduces its characteristic vasopressor and antidiuretic activities. In contrast to this we show here that removal of the carboxy-terminal glycinamide or the glycine at position 9 from several vasopressin antagonists makes little difference to their ability to block vasopressor and antidiuretic responses to AVP. These data demonstrate the critical structural requirements of the carboxy-terminal position for receptor activation, in contrast to the lack of such requirements for receptor binding. They also provide an avenue to a wide variety of antagonists substituted at the carboxy terminus (for example radiolabelled derivatives and affinity ligands) and suggest clues for the development of more potent and/or selective antagonists.     

文明戏(中国早期话剧)研究史的几个问题——以袁国兴和黄爱华近著为中心

近几年相继出版的袁国兴的《中国话剧的孕育与生成》和黄爱华的《中国早期话剧与日本》,是两部各有特色的文明戏研究专著,有体系的专门研究论著的出版,无疑标志着中国国内的文明戏研究达到了一个新的阶段。通过对文明戏研究现状和存在问题的考察,可知今后的文明戏研究方向应该是:一、加强戏剧史料的整理和研究,只有依靠正确的资料,才能期望文明戏研究有新的成果产生;二、加强中日学术交流,以解决中国学者对日本戏剧知识不足的问题;三、加强文明戏与中国传统戏曲以及早期电影的关系的研究,以更全面深入地认识和把握文明戏的特性。     

The structures of minor congeners of detoxin complex,the selective antagonist of blasticidin S1

Summary The structures of the minor congeners of detoxin complex, viz., detoxins E₁, C₁, C₂, C₃, B₁, B₃ and A₁ have been established on the basis of spectral and degradative evidence.Acknowledgment. This work was supported by a Grant-in-Aid for Special Project Research (510208) from the Ministry of Education, Science and Culture, Japan. We are grateful to Kaken Chemical Co. Ltd for the supply of the detoxin complex. This is Part V of studies of Detoxin Complex, the Selective Antagonists of Blasticidin S'. For Part IV, see Ogita et al.⁸.     

Karyotype of the Japanese salamander,Hynobius abei

Summary A primitive representative of the Caudata endemic to Japan,Hynobius abei Sato (Caudata: Hynobiidae) has 2n=56 chromosomes, with 9 large, 4 medium and 15 small-sized homologous pairs. The morphology of the large-sized chromosomes is similar to that of the knownHynobius species, but the presence of a pair of acrocentrics in the medium-sized group and 5 pairs of biarmed chromosomes in the small-sized group characterized the karyotype ofH. abei.We thank A. Itoi, S. Segawa, K. Ban, T. Hikida and O. Murakami for their assistance in collecting specimens.     

Phosphonate biosynthesis: isolation of the enzyme responsible for the formation of a carbon-phosphorus bond

The first isolation of a naturally occurring phosphonate in 1959 led rapidly to the discovery of a variety of metabolites containing a phosphorus-carbon bond. Phosphonates have been found in bacteria, fungi, and higher organisms such as the snail schistosome vector Biomphalaria. The biosynthetic path to the P-C bond has, however, remained undefined. Thus although it was shown twenty years ago that the isotope label from [14C]glucose or from [32P]phosphoenolpyruvate is incorporated into 2-aminoethylphosphonate by the protozoan Tetrahymena pyriformis, the presumed stoichiometric transformation of phosphoenolpyruvate to phosphonopyruvate has never been demonstrated. Low conversions of phosphoenolpyruvate into 2-aminoethylphosphonate and the trapping of phosphonopyruvate from phosphoenolpyruvate have been reported, but these reactions have not proved reproducible, and the existence of the critical enzyme, phosphoenolpyruvate phosphonomutase, has remained notional. We now report experiments that resolve this enigma, and describe the isolation and characterization of the pure mutase from T. pyriformis.