ATP-dependent assembly of double hexamers of SV40 T antigen at the viral origin of DNA replication

Simian virus 40 (SV40) replicates in nuclei of human and monkey cells. One viral protein, large tumour (T) antigen, is required for the initiation of DNA replication. The development of in vitro replication systems which retain this property has facilitated the identification of the cellular components required for replication. T antigen recognizes the pentanucleotide 5'-GAGGC-3' which is present in four copies within the 64 base-pairs (bp) of the core origin. In the presence of ATP it binds with increased affinity forming a distinctive, bilobed structure visible in electron micrographs. As a helicase, it unwinds SV40 DNA bidirectionally from the origin. We report here that in vitro and in the presence of ATP, T antigen assembles a double hexamer, centred on the core origin and extending beyond it by 12 bp in each direction. The assembly of this dodecamer initiates an untwisting of the duplex by 2-3 turns. In the absence of ATP, a tetrameric structure is the largest found at the core origin. In the absence of DNA, but in the presence of ATP or its non-hydrolysable analogues, T antigen assembles into hexamers. This suggests that ATP effects an allosteric change in the monomer. The change alters protein-protein interactions and allows the assembly of a double hexamer, which initiates replication at the core origin.     

Neurodegenerative disease: amyloid pores from pathogenic mutations

Alzheimer's and Parkinson's diseases are associated with the formation in the brain of amyloid fibrils from beta-amyloid and alpha-synuclein proteins, respectively. It is likely that oligomeric fibrillization intermediates (protofibrils), rather than the fibrils themselves, are pathogenic, but the mechanism by which they cause neuronal death remains a mystery. We show here that mutant amyloid proteins associated with familial Alzheimer's and Parkinson's diseases form morphologically indistinguishable annular protofibrils that resemble a class of pore-forming bacterial toxins, suggesting that inappropriate membrane permeabilization might be the cause of cell dysfunction and even cell death in amyloid diseases.     

Effects of submandibularectomy and castration on thymus and spleen weights in male mice

Cellular and Molecular Life Sciences - Submandibular-sublingualectomy of male mice did not result in thymic hyperplasia or potentiate the thymic hyperplasia which occurs after castration....     

Evaluating forecasts: a look at aggregate bias and accuracy measures

In this paper an investigation is made of the properties and use of two aggregate measures of forecast bias and accuracy. These are metrics used in business to calculate aggregate forecasting performance for a family (group) of products. We find that the aggregate measures are not particularly informative if some of the one‐step‐ahead forecasts are biased. This is likely to be the case in practice if frequently employed forecasting methods are used to generate a large number of individual forecasts. In the paper, examples are constructed to illustrate some potential problems in the use of the metrics. We propose a simple graphical display of forecast bias and accuracy to supplement the information yielded by the accuracy measures. This support includes relevant boxplots of measures of individual forecasting success. This tool is simple but helpful as the graphic display has the potential to indicate forecast deterioration that can be masked by one or both of the aggregate metrics. The procedures are illustrated with data representing sales of food items. Copyright © 2005 John Wiley & Sons, Ltd.     

蚕豆(Vicia faba)染色体形态结构的研究

关于蚕豆等植物染色体形态结构的工作已有所报道在研究植物染色体结构和探索G显带技术时需要大量的收缩程度较低的有丝分裂前期染色。有人提到放线菌素D可能阻碍染色体高度集缩,使前期增多,我们也曾报道过这一药物对植物染色体结构和显带的可能机制。在本文工作中我们进一步用放线菌素D处理、Giemsa染色的方法研究蚕豆染色体的     

A frame-shift mutation in the cystic fibrosis gene.

Cystic fibrosis (CF) is a common recessive lethal genetic disorder, affecting 1 in 1,600 Caucasians. The disease causes defective regulation of chloride-ion transport in exocrine cells. Although in all CF families the disease is linked to a locus on chromosome 7q31, there is clinical heterogeneity in the severity of the disease and the age at which it is diagnosed. CF is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. A three-nucleotide deletion (delta F508) causing the loss of a phenylalanine residue in the tenth exon of the CFTR gene has been found on 70% of CF chromosomes. We have now characterized a CF family in which neither parent of the affected individual carries the common mutation, and identified a two-nucleotide insertion in the CF allele of the mother. The mutation introduces a termination codon in exon 13 of the CFTR gene at residue 821, and is predicted to result in the production of a severely truncated nonfunctional protein.     

一种单片机控制的高性能数字定位系统

本文介绍一种由8031单片微计算机作为数字控制器的高性能数字定位系统,阐述了以PWM开关放大器为核心的硬件电路原理和基于双模控制设计思想的软件设计方法,实验结果表明该方案是可行的。     

东莞迈向现代城市的重要一步--生活垃圾的分类收集

根据东莞市生活垃圾的现状，分析了存在的问题，提出了相应的解决方法和对策，为东莞市推广生活垃圾分类收集、整治环境污染、创建卫生城市和实施城市建设可持续发展战略提供决策依据。