Profilin1 biology and its mutation,actin(g) in disease

Profilins were discovered in the 1970s and were extensively studied for their significant physiological roles. Profilin1 is the most prominent isoform and has drawn special attention due to its role in the cytoskeleton, cell signaling, and its link to conditions such as cancer and vascular hypertrophy. Recently, multiple mutations in the profilin1 gene were linked to amyotrophic lateral sclerosis (ALS). In this review, we will discuss the physiological and pathological roles of profilin1. We will further highlight the cytoskeletal function and dysfunction caused by profilin1 dysregulation. Finally, we will discuss the implications of mutant profilin1 in various diseases with an emphasis on its contribution to the pathogenesis of ALS.     

Na+ binding to meizothrombin desF1

Meizothrombin is the physiologically active intermediate generated by a single cleavage of prothrombin at R320 to separate the A and B chains. Recent evidence has suggested that meizothrombin, like thrombin, is a Na(+)-activated enzyme. In this study we present the first X-ray crystal structure of human meizothrombin desF1 solved in the presence of the active site inhibitor PPACK at 2.1 A resolution. The structure reveals a Na(+) binding site whose architecture is practically identical to that of human thrombin. Stopped-flow measurements of Na(+) binding to meizothrombin desF1 document a slow phase of fluorescence change with a k(obs) decreasing hyperbolically with increasing [Na(+)], consistent with the existence of three conformations in equilibrium, E*, E and E:Na(+), as for human thrombin. Evidence that meizothrombin exists in multiple conformations provides valuable new information for studies of the mechanism of prothrombin activation.     

Tribbles: novel regulators of cell function; evolutionary aspects

Identification of rate-limiting steps or components of intracellular second messenger systems holds promise to effectively interfere with these pathways under pathological conditions. The emerging literature on a recently identified family of signalling regulator proteins, called tribbles gives interesting clues for how these proteins seem to link several ‘independent’ signal processing systems together. Via their unique way of action, tribbles co-ordinate the activation and suppression of the various interacting signalling pathways and therefore appear to be key in determining cell fate while responding to environmental challenges. This review summarises our current understanding of tribbles function and also provides an evolutionary perspective on the various tribbles genes. Received 10 January 2006; received after revision 20 March 2006; accepted 5 April 2006     

Sperm viability in the reproductive tract of females in a population of Sceloporus mucronatus exhibiting asynchronous reproduction

Asynchronous reproduction is a common phenomenon in high-elevation populations of lizards from Central México. Sperm storage in the reproductive tract of females is the mechanism for making oocyte fertilization possible. Our study addresses questions related to functional oviductal sperm storage of females mating on different dates throughout the reproductive season. A population of Sceloporus mucronatus with copulation in the summer and ovulation in the fall was chosen for this experiment. Eleven females that copulated in the field during June and 13 females that copulated in captivity during August were maintained in the laboratory until parturition. The number of pregnant females and the litter sizes produced in each experimental group were indicative of the viability of the stored sperm. Sperm stored in the reproductive tract of females were able to fertilize eggs after 4 months. No significant differences were found in the number of pregnant females between the 2 experimental groups nor in the litter sizes that they produced. We found that the amount of time sperm were held in the female reproductive tract (ca. 3 months) had no effect on the capacity of sperm to fertilize eggs. Histological examination of 8 oviducts collected before the mating season eliminated the possibility of sperm storage from one year to the next. In this system, sperm retention could have evolved as a response mechanism to deal with the asynchrony between sexes in the reproductive cycles. However, we cannot rule out alternative hypotheses.     

Small G proteins are expressed ubiquitously in lymphoid cells and do not correspond to Bcl-2

The bcl-2 gene is consistently associated with t(14; 18) chromosomal translocations observed in a large fraction of human B-cell lymphomas. The t(14; 18) translocation results in deregulated expression of the bcl-2 gene and synthesis of inappropriately high levels of the Bcl-2 protein. Gene transfer studies suggest a role for Bcl-2 in cell survival, growth enhancement and oncogenic transformation. To test the suggestion that GTP-binding by Bcl-2 may mediate its biological effects we characterized the GTP-binding proteins in lymphoid cells expressing Bcl-2. Expression of several small GTP-binding proteins was found to be ubiquitous and did not vary with levels of Bcl-2. By using immunological, electrophoretic and cell-fractionation techniques, we separated Bcl-2 from G proteins of small relative molecular mass (Mr) and showed that it is incapable of binding GTP. Our results show that small Mr G proteins are widely expressed in lymphoid cells and that Bcl-2 is not a novel member of this GTP-binding protein family.     

二自由度自谐式机器人动力学的研究

本文对引用弹性元件的二自由度谐式机器人的动力学进行了分析,在该模型中引入了负反馈系统。按预期的机构运动规律和系统的稳定性要求,研究了反馈放大系数的合理选择,并对构件单独和同时运动的仿真图线进行了分析。     

Towards genetic genome projects: genomic library screening and gene-targeting vector construction in a single step.

We have developed technologies that simplify genomic library construction and screening, substantially reducing both the time and the cost associated with traditional library screening methods and facilitating the generation of gene-targeting constructs. By taking advantage of homologous recombination in Escherichia coli, we were able to use as little as 80 bp of total sequence homology to screen for a specific gene from a genomic library in plasmid or phage form. This method, called recombination cloning (REC), takes only a few days instead of the several weeks required for traditional plaque-lift methods. In addition, because every clone in the mouse genomic library we have constructed has a negative selection marker adjacent to the genomic insert, REC screening can generate gene-targeting vectors in one step, from library screening to finished construct. Conditional targeting constructs can be generated easily with minimal additional manipulation.     

硼钛复合纤维拉伸曲线分析

研究了硼钛复合纤维在拉伸过程中的行为，结果表明：复合纤维的变形是由纤维的弹性应变与基体的弹塑性应变复合迭加而成，并且在纤维与基体结合十分牢固，基体组元体积分数又较少的情况下，复合纤维表现为高强度，高弹性模量及低塑性，将试验结果同理论计算模型进行了比较，所得结果基本一致。