K252a: A new blocker of the cell-cycle at G1 phase in a human hepatoma cell line

The administration of 200 nM K252a to HuH7 suppressed the proliferation of the cells almost completely. The uptake of [³H]thymidine was inhibited, and flow cytometry revealed only one peak at 2C on day 3 after treatment with 100 nM K252a. The expression of proto-oncogene c-myc was not reduced. Despite the blockage at G1, both the size of the cells and the amount of cell protein had increased by 4 times by day 3 after treatment with K252a, while the cells secreted albumin and -fetoprotein into the medium as usual. These results show that K252a can increase the cell size of HuH7 without losing its function by blocking the cell cycle at G1 phase.     

Formation and branch migration of Holliday junctions mediated by eukaryotic recombinases

Holliday junctions (HJs) are key intermediates in homologous recombination and are especially important for the production of crossover recombinants. Bacterial RecA family proteins promote the formation and branch migration of HJs in vitro by catalysing a reciprocal DNA-strand exchange reaction between two duplex DNA molecules, one of which contains a single-stranded DNA region that is essential for initial nucleoprotein filament formation. This activity has been reported only for prokaryotic RecA family recombinases, although eukaryotic homologues are also essential for HJ production in vivo. Here we show that fission yeast (Rhp51) and human (hRad51) RecA homologues promote duplex-duplex DNA-strand exchange in vitro. As with RecA, a HJ is formed between the two duplex DNA molecules, and reciprocal strand exchange proceeds through branch migration of the HJ. In contrast to RecA, however, strand exchange mediated by eukaryotic recombinases proceeds in the 3'-->5' direction relative to the single-stranded DNA region of the substrate DNA. The opposite polarity of Rhp51 makes it especially suitable for the repair of DNA double-strand breaks, whose repair is initiated at the processed ends of breaks that have protruding 3' termini.     

Frequent pathway mutations of splicing machinery in myelodysplasia

Myelodysplastic syndromes and related disorders (myelodysplasia) are a heterogeneous group of myeloid neoplasms showing deregulated blood cell production with evidence of myeloid dysplasia and a predisposition to acute myeloid leukaemia, whose pathogenesis is only incompletely understood. Here we report whole-exome sequencing of 29 myelodysplasia specimens, which unexpectedly revealed novel pathway mutations involving multiple components of the RNA splicing machinery, including U2AF35, ZRSR2, SRSF2 and SF3B1. In a large series analysis, these splicing pathway mutations were frequent (～45 to ～85%) in, and highly specific to, myeloid neoplasms showing features of myelodysplasia. Conspicuously, most of the mutations, which occurred in a mutually exclusive manner, affected genes involved in the 3'-splice site recognition during pre-mRNA processing, inducing abnormal RNA splicing and compromised haematopoiesis. Our results provide the first evidence indicating that genetic alterations of the major splicing components could be involved in human pathogenesis, also implicating a novel therapeutic possibility for myelodysplasia.     

Spatio-temporal images of growth-factor-induced activation of Ras and Rap1.

G proteins of the Ras family function as molecular switches in many signalling cascades; however, little is known about where they become activated in living cells. Here we use FRET (fluorescent resonance energy transfer)-based sensors to report on the spatio-temporal images of growth-factor-induced activation of Ras and Rap1. Epidermal growth factor activated Ras at the peripheral plasma membrane and Rap1 at the intracellular perinuclear region of COS-1 cells. In PC12 cells, nerve growth factor-induced activation of Ras was initiated at the plasma membrane and transmitted to the whole cell body. After three hours, high Ras activity was observed at the extending neurites. By using the FRAP (fluorescence recovery after photobleaching) technique, we found that Ras at the neurites turned over rapidly; therefore, the sustained Ras activity at neurites was due to high GTP/GDP exchange rate and/or low GTPase activity, but not to the retention of the active Ras. These observations may resolve long-standing questions as to how Ras and Rap1 induce different cellular responses and how the signals for differentiation and survival are distinguished by neuronal cells.     

几种绣线菊叶片表皮形态的扫描电镜研究

用扫描电镜对几种绣线菊叶片的表皮结构进行了比较观察，结果表明，所观察的几种绣线菊叶片上表皮均呈波纹网状结构，而下表皮存在着较显著的差别，其细胞的形状，大小和排列方式不甚相同，此外气孔的大小，形态及密度亦存在差异。     

Some Thoughts on Multimethodology

This paper poses questions to which I have only tentative answers. It considers the limitations that practice places on any theoretical statements about how methodologies might be mixed, merged, or compared. It draws attention to less ambitious ways of improving the processes that we individually use and to aspects of process which I judge to be of central importance.     

Linkage of high-density lipoprotein-cholesterol concentrations to a locus on chromosome 9p in Mexican Americans.

High-density lipoproteins (HDLs) are anti-atherogenic lipoproteins that have a major role in transporting cholesterol from peripheral tissues to the liver, where it is removed. Epidemiologic studies have shown that low levels of high-density lipoprotein-cholesterol (HDL-C) are associated with an increased incidence of coronary heart disease and an increased mortality rate, indicating a protective role of high concentrations of HDL-C against atherogenesis and the development of coronary heart disease. HDL-C level is influenced by several genetic and nongenetic factors. Nongenetic factors include smoking, which has been shown to decrease the HDL-C level. Exercise and alcohol have been shown to increase HDL-C levels. Decreased HDL-C is often associated with other coronary heart disease risk factors such as obesity, hyperinsulinemia and insulin resistance, hypertriglyceridemia and hypertension. Although several genes have been identified for rare forms of dyslipidemia, the genes accounting for major variation in HDL-C levels have yet to be identified. Using a multipoint variance components linkage approach, we found strong evidence of linkage (lod score=3.4; P=0.00004) of a quantitative trait locus (QTL) for HDL-C level to a genetic location between markers D9S925 and D9S741 on chromosome 9p in Mexican Americans. A replication study in an independent set of Mexican American families confirmed the existence of a QTL on chromosome 9p.     

A Systems Approach for Engaging Groups in Global Complexity: Capacity Building Through an Online Course

Sustainability is not simply about changing practices but more centrally about agreeing to change practices together. To achieve such an end, groups need to improve processes for making complex decisions together. An online course was designed and tested linking students in the United States and in Australia. Students engaged in a re-enactment of deliberations based on Hasan Ozbekhan’s “Predicament of Mankind,” which was constructed originally under assignment from the founders of the Club of Rome in 1970. This re-enactment included contemporary research for examples of a set of 49 continuous critical problems of mankind, asynchronous clarification of these problems using a wiki, pair-wise construction of a systems view of problems assessed to be of highest priority by the class, narrative analysis of the structure, and creative suggestions for resolving the systems problem based on resources available today. This report comments on the strengths and challenges identified in an initial application of an approach for building collaborative and systems thinking skills through an online course in a general education curriculum. Findings are particularly meaningful for contemporary policy makers as well as online educators.     

交流信号真有效值数字测量方法

提出了一种新的交流信号真有效值数字测量方法.交流信号被逐个周波地采样,而不必满足采样频率必须等于交流信号频率的整数倍或有理分数倍这一条件.通过程序先找出信号基频、采样点与过零点间的时段长,然后算出各周波的真有效值.分析表明在周波内测量点数为128时测量误差约为1×10-6,且随测量点数的增大而进一步减小.该方法提供了一种新的真有效值测量手段,具有测量过程简化、响应时间减少、可输出每个周波的真有效值等优点.