Genome-wide survey of protein kinases required for cell cycle progression

Cycles of protein phosphorylation are fundamental in regulating the progression of the eukaryotic cell through its division cycle. Here we test the complement of Drosophila protein kinases (kinome) for cell cycle functions after gene silencing by RNA-mediated interference. We observed cell cycle dysfunction upon downregulation of 80 out of 228 protein kinases, including most kinases that are known to regulate the division cycle. We find new enzymes with cell cycle functions; some of these have family members already known to phosphorylate microtubules, actin or their associated proteins. Additionally, depletion of several signalling kinases leads to specific mitotic aberrations, suggesting novel roles for familiar enzymes. The survey reveals the inter-digitation of systems that monitor cellular physiology, cell size, cellular stress and signalling processes with the basic cell cycle regulatory machinery.     

Chromosome nondisjunction yields tetraploid rather than aneuploid cells in human cell lines

Although mutations in cell cycle regulators or spindle proteins can perturb chromosome segregation, the causes and consequences of spontaneous mitotic chromosome nondisjunction in human cells are not well understood. It has been assumed that nondisjunction of a chromosome during mitosis will yield two aneuploid daughter cells. Here we show that chromosome nondisjunction is tightly coupled to regulation of cytokinesis in human cell lines, such that nondisjunction results in the formation of tetraploid rather than aneuploid cells. We observed that spontaneously arising binucleated cells exhibited chromosome mis-segregation rates up to 166-fold higher than the overall mitotic population. Long-term imaging experiments indicated that most binucleated cells arose through a bipolar mitosis followed by regression of the cleavage furrow hours later. Nondisjunction occurred with high frequency in cells that became binucleated by furrow regression, but not in cells that completed cytokinesis to form two mononucleated cells. Our findings indicate that nondisjunction does not directly yield aneuploid cells, but rather tetraploid cells that may subsequently become aneuploid through further division. The coupling of spontaneous segregation errors to furrow regression provides a potential explanation for the prevalence of hyperdiploid chromosome number and centrosome amplification observed in many cancers.     

The entomological inoculation rate and Plasmodium falciparum infection in African children

Malaria is an important cause of global morbidity and mortality. The fact that some people are bitten more often than others has a large effect on the relationship between risk factors and prevalence of vector-borne diseases. Here we develop a mathematical framework that allows us to estimate the heterogeneity of infection rates from the relationship between rates of infectious bites and community prevalence. We apply this framework to a large, published data set that combines malaria measurements from more than 90 communities. We find strong evidence that heterogeneous biting or heterogeneous susceptibility to infection are important and pervasive factors determining the prevalence of infection: 20% of people receive 80% of all infections. We also find that individual infections last about six months on average, per infectious bite, and children who clear infections are not immune to new infections. The results have important implications for public health interventions: the success of malaria control will depend heavily on whether efforts are targeted at those who are most at risk of infection.     

Stem cell division is regulated by the microRNA pathway

One of the key characteristics of stem cells is their capacity to divide for long periods of time in an environment where most of the cells are quiescent. Therefore, a critical question in stem cell biology is how stem cells escape cell division stop signals. Here, we report the necessity of the microRNA (miRNA) pathway for proper control of germline stem cell (GSC) division in Drosophila melanogaster. Analysis of GSCs mutant for dicer-1 (dcr-1), the double-stranded RNaseIII essential for miRNA biogenesis, revealed a marked reduction in the rate of germline cyst production. These dcr-1 mutant GSCs exhibit normal identity but are defective in cell cycle control. On the basis of cell cycle markers and genetic interactions, we conclude that dcr-1 mutant GSCs are delayed in the G1 to S transition, which is dependent on the cyclin-dependent kinase inhibitor Dacapo, suggesting that miRNAs are required for stem cells to bypass the normal G1/S checkpoint. Hence, the miRNA pathway might be part of a mechanism that makes stem cells insensitive to environmental signals that normally stop the cell cycle at the G1/S transition.     

刘易斯·沃尔特·阿尔瓦莱兹

我们时代最具创造力的科学家之一刘易斯·沃尔特·阿尔瓦莱兹于1988年9月1日去世了,终年77岁,一年前他曾为了部分切除良性脑瘤以及随后医治食道癌而动过手术。阿尔瓦莱兹分别具有三方面成功的记录——科学家,发明家以及在航空飞行方面的专家.他因发展并利用氢气泡室,从而发现了一系列粒子而获得了1968年度的诺贝尔物理学奖。在航空飞行方面,他因发明了首次在英国战争中运用的地面雷达盲着陆系统而获得了1946年的考利尔飞行奖。1978年,他因其灵敏的物理仪器,卓越的飞行雷达系统,以及精巧的光学仪器在两个有成就的公司中实现商品化而就职于著名的发明家协会。叙述阿尔瓦莱兹所获得的奖章荣誉,仅仅反映了这位经历丰富的科学狂人的一个简略轮廓。众所周知,作为第三代加利福尼亚人、有着物理学家血统的刘易斯是在明尼苏达州的罗彻斯特成长的。作为一名芝加哥大学的毕业生,刘易斯迷恋于光学的生涯开始了,光学也是他第一篇论文的课题,内容是利用在客厅灯条