14-3-3sigma controls mitotic translation to facilitate cytokinesis

14-3-3 proteins are crucial in a wide variety of cellular responses including cell cycle progression, DNA damage checkpoints and apoptosis. One particular 14-3-3 isoform, sigma, is a p53-responsive gene, the function of which is frequently lost in human tumours, including breast and prostate cancers as a result of either hypermethylation of the 14-3-3sigma promoter or induction of an oestrogen-responsive ubiquitin ligase that specifically targets 14-3-3sigma for proteasomal degradation. Loss of 14-3-3sigma protein occurs not only within the tumours themselves but also in the surrounding pre-dysplastic tissue (so-called field cancerization), indicating that 14-3-3sigma might have an important tumour suppressor function that becomes lost early in the process of tumour evolution. The molecular basis for the tumour suppressor function of 14-3-3sigma is unknown. Here we report a previously unknown function for 14-3-3sigma as a regulator of mitotic translation through its direct mitosis-specific binding to a variety of translation/initiation factors, including eukaryotic initiation factor 4B in a stoichiometric manner. Cells lacking 14-3-3sigma, in marked contrast to normal cells, cannot suppress cap-dependent translation and do not stimulate cap-independent translation during and immediately after mitosis. This defective switch in the mechanism of translation results in reduced mitotic-specific expression of the endogenous internal ribosomal entry site (IRES)-dependent form of the cyclin-dependent kinase Cdk11 (p58 PITSLRE), leading to impaired cytokinesis, loss of Polo-like kinase-1 at the midbody, and the accumulation of binucleate cells. The aberrant mitotic phenotype of 14-3-3sigma-depleted cells can be rescued by forced expression of p58 PITSLRE or by extinguishing cap-dependent translation and increasing cap-independent translation during mitosis by using rapamycin. Our findings show how aberrant mitotic translation in the absence of 14-3-3sigma impairs mitotic exit to generate binucleate cells and provides a potential explanation of how 14-3-3sigma-deficient cells may progress on the path to aneuploidy and tumorigenesis.     

沙能杂种山羊的生长发育研究

本研究对英国沙能山羊的杂种,进行了长达十数年的系列研究,不仅测定了一、二、三代杂种羊从初生到成年8个主要阶段的生长发育特点,而且将处于同等饲养条件下的父、母系品种作为对照,进行了同样测定,从而揭示了各代杂种羊的生长发育规律和体重体尺等性状的遗传特点。     

Sequence of reovirus haemagglutinin predicts a coiled-coil structure

The use of modern techniques has led to new insights into the molecular mechanisms of viral pathogenesis. Although the infectious process is quite complex, it is clear that one critical stage, the interaction of viral attachment proteins with cell-surface receptors, often has a major role in determining the pattern of infection. The mammalian reoviruses have served as useful models for understanding the molecular basis of viral pathogenesis. The mammalian reovirus haemagglutinin (sigma 1 protein), which is an outer capsid protein, has been shown to be a major factor in determining virus-host cell interactions. To further our understanding of the structure and function of the haemagglutinin, we have cloned a complementary DNA copy of the reovirus type 3 S1 double-stranded RNA gene which encodes the virus haemagglutinin and have sequenced the DNA complementary to the S1 gene. Analysis of the predicted amino-acid sequence of the virus haemagglutinin has allowed us to determine that the amino-terminal portion contains an alpha-helical coiled-coil structure and that the carboxy-terminal portion contains the receptor-interacting domains. Using this information, we propose here a model of how the reovirus haemagglutinin is attached to the virus particle.     

Rebasing the annual mid-year population estimates for England and Wales

The ONS produces mid-year population estimates annually, which are based on updating from the most recent census. Therefore, whenever results become available from a census, a new base is created for the population estimates. This has implications for historic series, which need to be revised to be consistent with both the past and the most recent census. This article describes the methodology that will be used for this rebasing of the mid-year population estimates following the availability of results from the 2001 Census. Census results also provide a unique opportunity to assess the accuracy of the population estimates that are based on the previous census and this article also describes the approach that will be taken to the assessment of accuracy.     

2013十大太空故事

正美国《天文学》杂志评选出2013年十大太空故事(发刊时"嫦娥三号"尚未发射),我们不会忘记在这一年出现了两颗明亮的彗星以及百年一遇的流星爆炸——对于空间科学而言,2013年无疑是一个丰收年2013年大部分的天文头条都涉及到了宇宙中最极端的天体和事件,例如黑洞、高能宇宙线以及宇宙的开端。不过,行星科学也不甘示弱。近期,美国《天文学》杂志评选出2013年十大太空故事。     

Models as Points of View: The Case of System Dynamics

We propose an analysis of the notion of model as crucially related to the notion of point of view. A model in this sense would always suggest a certain way of looking at a real system, a certain way of thinking about it and a certain way of acting upon it. We focus on System Dynamics as a paradigmatic case with respect to many of the features and problems we can find in the field of modelling and simulation. We analyse in detail some of those features. All of them would be present in many other cases of construction and use of models. Furthermore, they would support the thesis that a model can be fruitfully understood as offering a point of view capable of improving our own points of view over a certain system. The point of view offered by the model could include both non-conceptual and conceptual contents, it would have a complex structure and behaviour, and it would have direct consequences on the decisions made by the subjects adopting that point of view.     

Regulation of cap-dependent translation by eIF4E inhibitory proteins

Eukaryotic messenger RNAs contain a modified guanosine, termed a cap, at their 5' ends. Translation of mRNAs requires the binding of an initiation factor, eIF4E, to the cap structure. Here, we describe a family of proteins that through a shared sequence regulate cap-dependent translation. The biological importance of this translational regulation is immense, and affects such processes as cell growth, development, oncogenic transformation and perhaps even axon pathfinding and memory consolidation.