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.     

Three-dimensional structural dynamics of myosin V by single-molecule fluorescence polarization

The structural change that generates force and motion in actomyosin motility has been proposed to be tilting of the myosin light chain domain, which serves as a lever arm. Several experimental approaches have provided support for the lever arm hypothesis; however, the extent and timing of tilting motions are not well defined in the motor protein complex of functioning actomyosin. Here we report three-dimensional measurements of the structural dynamics of the light chain domain of brain myosin V using a single-molecule fluorescence polarization technique that determines the orientation of individual protein domains with 20-40-ms time resolution. Single fluorescent calmodulin light chains tilted back and forth between two well-defined angles as the myosin molecule processively translocated along actin. The results provide evidence for lever arm rotation of the calmodulin-binding domain in myosin V, and support a 'hand-over-hand' mechanism for the translocation of double-headed myosin V molecules along actin filaments. The technique is applicable to the study of real-time structural changes in other biological systems.     

面向飞机PHM的大数据分析与人工智能应用

针对新一代电子产品密集型的飞机,其系统结构和失效机理复杂、失效模式多样,传统的方法难以对其进行有效健康管理的现状,因此提出了基于海量数据挖掘的飞机PHM研究。首先从系统结构、服役环境、数据来源与存储方式等角度分析了新一代飞机对海量数据挖掘的应用需求;其次论述了基于海量数据挖掘的关键技术,包括数据的预处理、集成管理、聚类、分类、关联、预测等;最后提出了一种基于私有云的飞机PHM海量数据挖掘平台,详细阐述了该平台的总体框架和软硬件结构,该平台为飞机PHM提供了验证平台,对促进飞机PHM的集成与工程化实现具有重大的军事应用意义。     

Drosophila Spire is an actin nucleation factor

The actin cytoskeleton is essential for many cellular functions including shape determination, intracellular transport and locomotion. Previous work has identified two factors--the Arp2/3 complex and the formin family of proteins--that nucleate new actin filaments via different mechanisms. Here we show that the Drosophila protein Spire represents a third class of actin nucleation factor. In vitro, Spire nucleates new filaments at a rate that is similar to that of the formin family of proteins but slower than in the activated Arp2/3 complex, and it remains associated with the slow-growing pointed end of the new filament. Spire contains a cluster of four WASP homology 2 (WH2) domains, each of which binds an actin monomer. Maximal nucleation activity requires all four WH2 domains along with an additional actin-binding motif, conserved among Spire proteins. Spire itself is conserved among metazoans and, together with the formin Cappuccino, is required for axis specification in oocytes and embryos, suggesting that multiple actin nucleation factors collaborate to construct essential cytoskeletal structures.     

Permeability of arthrodial membrane to water: A first measurement using in vivo techniques

Summary Despite differences in surface morphology and fine structure, the permeabilities of untreated scorpion sternite and pleural cuticle to water are similar (0.69 versus 0.79 g·cm^–2·h^–1·mm Hg^–1). Hexane applied to pleural membrane increased its permeability 9-fold, but neither hexane nor chloroform: methanol had much effect on sternite permeability. When sternite cuticle was treated with 1.0 N KOH followed by chloroform: methanol, permeability increased about three times over control values. In contrast, cockroach pronotum, which is 17 times more permeable than scorpion sternite, exhibited a marked increase in permeability when treated with just hexane. In both the scorpion pleuron and cockroach pronotum, disruption of the lipid barrier caused by rubbing is partially responsible for the higher permeabilities observed following solvent treatment.     

态度决定人生

态度是决定一个人的观点和人生经历的关键因素。我们的观点和经历反过来又会影响我们对人生的态度。态度是我们每时每刻自由做出的选择。人生经历中的种种因素都会影响到我们的人生观和世界观。探讨了人生态度是如何影响生活质量的。