Mutations in the gene encoding filamin B disrupt vertebral segmentation, joint formation and skeletogenesis

The filamins are cytoplasmic proteins that regulate the structure and activity of the cytoskeleton by cross-linking actin into three-dimensional networks, linking the cell membrane to the cytoskeleton and serving as scaffolds on which intracellular signaling and protein trafficking pathways are organized (reviewed in refs. 1,2). We identified mutations in the gene encoding filamin B in four human skeletal disorders. We found homozygosity or compound heterozygosity with respect to stop-codon mutations in autosomal recessive spondylocarpotarsal syndrome (SCT, OMIM 272460) and missense mutations in individuals with autosomal dominant Larsen syndrome (OMIM 150250) and the perinatal lethal atelosteogenesis I and III phenotypes (AOI, OMIM 108720; AOIII, OMIM 108721). We found that filamin B is expressed in human growth plate chondrocytes and in the developing vertebral bodies in the mouse. These data indicate an unexpected role in vertebral segmentation, joint formation and endochondral ossification for this ubiquitously expressed cytoskeletal protein.     

A complementary transposon tool kit for Drosophila melanogaster using P and piggyBac

With the availability of complete genome sequence for Drosophila melanogaster, one of the next strategic goals for fly researchers is a complete gene knockout collection. The P-element transposon, the workhorse of D. melanogaster molecular genetics, has a pronounced nonrandom insertion spectrum. It has been estimated that 87% saturation of the approximately 13,500-gene complement of D. melanogaster might require generating and analyzing up to 150,000 insertions. We describe specific improvements to the lepidopteran transposon piggyBac and the P element that enabled us to tag and disrupt genes in D. melanogaster more efficiently. We generated over 29,000 inserts resulting in 53% gene saturation and a more diverse collection of phenotypically stronger insertional alleles. We found that piggyBac has distinct global and local gene-tagging behavior from that of P elements. Notably, piggyBac excisions from the germ line are nearly always precise, piggyBac does not share chromosomal hotspots associated with P and piggyBac is more effective at gene disruption because it lacks the P bias for insertion in 5' regulatory sequences.     

TRPV3 is a calcium-permeable temperature-sensitive cation channel

Transient receptor potential (TRP) proteins are cation-selective channels that function in processes as diverse as sensation and vasoregulation. Mammalian TRP channels that are gated by heat and capsaicin (>43 degrees C; TRPV1 (ref. 1)), noxious heat (>52 degrees C; TRPV2 (ref. 2)), and cooling (< 22 degrees C; TRPM8 (refs 3, 4)) have been cloned; however, little is known about the molecular determinants of temperature sensing in the range between approximately 22 degrees C and 40 degrees C. Here we have identified a member of the vanilloid channel family, human TRPV3 (hTRPV3) that is expressed in skin, tongue, dorsal root ganglion, trigeminal ganglion, spinal cord and brain. Increasing temperature from 22 degrees C to 40 degrees C in mammalian cells transfected with hTRPV3 elevated intracellular calcium by activating a nonselective cationic conductance. As in published recordings from sensory neurons, the current was steeply dependent on temperature, sensitized with repeated heating, and displayed a marked hysteresis on heating and cooling. On the basis of these properties, we propose that hTRPV3 is thermosensitive in the physiological range of temperatures between TRPM8 and TRPV1.     

Localized mutations in the gene encoding the cytoskeletal protein filamin A cause diverse malformations in humans

Remodeling of the cytoskeleton is central to the modulation of cell shape and migration. Filamin A, encoded by the gene FLNA, is a widely expressed protein that regulates re-organization of the actin cytoskeleton by interacting with integrins, transmembrane receptor complexes and second messengers. We identified localized mutations in FLNA that conserve the reading frame and lead to a broad range of congenital malformations, affecting craniofacial structures, skeleton, brain, viscera and urogenital tract, in four X-linked human disorders: otopalatodigital syndrome types 1 (OPD1; OMIM 311300) and 2 (OPD2; OMIM 304120), frontometaphyseal dysplasia (FMD; OMIM 305620) and Melnick-Needles syndrome (MNS; OMIM 309350). Several mutations are recurrent, and all are clustered into four regions of the gene: the actin-binding domain and rod domain repeats 3, 10 and 14/15. Our findings contrast with previous observations that loss of function of FLNA is embryonic lethal in males but manifests in females as a localized neuronal migration disorder, called periventricular nodular heterotopia (PVNH; refs. 3-6). The patterns of mutation, X-chromosome inactivation and phenotypic manifestations in the newly described mutations indicate that they have gain-of-function effects, implicating filamin A in signaling pathways that mediate organogenesis in multiple systems during embryonic development.     

急性运动对血清氧自由基代谢水平影响的实验研究

本实验旨在观察急性运动后血清中氧自由基代谢水平的变化情况,本实验采用自身对照的方法,24名受试者于实验前和实验后各进行一次血清中MDA、SOD以及GSH-px的水平测试.运动方式为:以75%VO2max蹬功率自行车,持续1h.结果表明:急性较大强度运动后机体中产生了大量氧自由基,同时体内抗氧化酶的活性也明显增加,自由基生成与清除的动态平衡并未遭到破坏.     

有氧健身操对单纯性肥胖大学生心功能影响的实验研究

目的 探讨有氧健身运动对单纯性肥胖大学生心功能的影响;方法 选取西安工业大学25名单纯性肥胖男大学生,以有氧健身运动为原则,以心功能指标为评价系统,在安静状态下,采用MCA-4B心功测试系统测试单纯性肥胖男大学生有氧健身锻炼前后部分心功能指标;结果 有氧健身锻炼前后,心功能主要指标锻炼前后存在显著性差异;结论 有氧健身操可以很好地改善单纯性肥胖大学生的心功能.     

基于Extend的大型露天矿卡车调度系统仿真

在分析大型露天矿卡车调度系统的基础上，以Extend为平台，对露天矿卡车调度系统进行了动态仿真设计，提出了大型露天矿卡车调度系统仿真建模的新方法，具体描述了仿真建模的思路和过程。同时，提出了评价露天矿卡车调度系统的三个重要的性能指标并将其应用于系统仿真，仿真结果验证了仿真系统的合理性、正确性。     

基于有向循环图的多学科设计优化模型调度方法

复杂产品的多学科设计优化过程中，往往会涉及到不同学科的专业分析模型以及各种商业软件应用的集成调度运行问题。在多学科设计优化过程中模型应用集成的基础上，结合设计模型的调度需求，研究了多学科模型的调度运行，并给出了基于有向循环图的通用模型调度解决方案，包括回路探测算法和模型调度算法。最后设计并实现了支持复杂产品多学科设计优化软件框架——iDesign的调度引擎，并以一个设计模型的调度为例，验证了方法的正确性和可行性。     

轧制变形量对7A55铝合金淬火敏感性的影响

为了研究轧制变形量与淬火敏感性的关系,测量了变形量为70%,80%和90%的7A55铝合金轧制板材在不同淬火条件下的拉伸力学性能。结果表明,热处理T6态下合金的强度、延伸率随着淬火速率的增加而提高;合金的淬火敏感性随着轧制变形量的增加而增大;固溶发生再结晶的过程中,与基体共格的Al3Zr粒子被大角度晶界扫过转变为非共格粒子;在缓慢淬火过程中,粗大平衡相η（MgZn2）以非共格的Al3Zr粒子作为形核位置析出,显著减弱时效强化效果,造成淬火敏感性现象;再结晶程度随着轧制变形而增大,是导致淬火敏感性提高的主要原因。     

福州市居民用电情况及其与气温关系分析

分析了福州市居民用电情况和负荷曲线的特点,对最高负荷与各气象因素进行相关分析,着重分析了居民日负荷与气温的关系并计算了单位温升效应.分析表明,居民负荷的晚高峰对全网负荷晚高峰有较大的影响;气温对居民负荷的影响较直接和明显,夏季居民最大负荷与气温之间呈三次关系模型;单位温升效应约为3%-4%.