Predicting Statistical Properties of Open Reading Frames in Bacterial Genomes

An analytical model based on the statistical properties of Open Reading Frames (ORFs) of eubacterial genomes such as codon composition and sequence length of all reading frames was developed. This new model predicts the average length, maximum length as well as the length distribution of the ORFs of 70 species with GC contents varying between 21% and 74%. Furthermore, the number of annotated genes is predicted with high accordance. However, the ORF length distribution in the five alternative reading frames shows interesting deviations from the predicted distribution. In particular, long ORFs appear more often than expected statistically. The unexpected depletion of stop codons in these alternative open reading frames cannot completely be explained by a biased codon usage in the +1 frame. While it is unknown if the stop codon depletion has a biological function, it could be due to a protein coding capacity of alternative ORFs exerting a selection pressure which prevents the fixation of stop codon mutations. The comparison of the analytical model with bacterial genomes, therefore, leads to a hypothesis suggesting novel gene candidates which can now be investigated in subsequent wet lab experiments.     

Statistical Mechanical Approach for Predicting the Transition to Non-B DNA Structures in Supercoiled DNA

Abstract

Supercoiling causes global twist of DNA structure and the supercoiled state has wide influence on conformational transition. A statistical mechanical approach was made for prediction of the transition probability to non-B DNA structures under torsional stress. A conditional partition function was defined as the sum over all possible states of the DNA sequence with basepair 1 and basepair n being in B-form helix and a recurrence formula was developed which expressed the partition function for basepair n with those for less number of pairs. This new definition permits a quick enumeration of every configuration of secondary structures. Energetic parameters of all conformations concerned, involving B-form, interior loop, cruciform and Z-form, were included in the equation. The probability of transition to each non-B conformation could be derived from these conditional partition functions. For treatment of effects of superhelicity, supercoiling energy was considered, and a twist of each conformation was determined to minimize the supercoiling energy. As the twist itself affects the transition probability, the whole scheme of equations was solved by renormalization technique. The present method permits a simultaneous treatment of serveral types of conformations under a common torsional stress.

A set of energetic parameters of DNA secondary structures has been chosen for calculation. Some DNA sequences were submitted to the calculation, and all the sequences that we submitted gave stable convergence. Some of them have been investigated the critical supercoil density for the transition to non-B DNA structures. Even though the reliability of the set of parameters was not enough, the prediction of secondary structure transition showed good agreement with reported observation. Hence, the present algorithm can estimate the probability of local conformational change of DNA under a given supercoil density, and also be employed to predict some specific sequences in which conformational change is sensitive to superhelicity.     

真核蛋白质的亚细胞位点预测研究进展

研究真核蛋白质的亚细胞位点是了解真核蛋白质功能,深入研究蛋白质相关信号通路内在机制的基础。同时,可以为了解 疾病发病机制及为新药研发提供帮助。因此,研究真核蛋白质的亚细胞位点意义十分重大。随着基因组测序的完成,真核蛋白质 序列信息增长迅速,为真核蛋白质亚细胞位点的研究提出了更多的挑战。传统的实验法难以满足蛋白质信息量迅速增长的需求。 而采用生物信息学手段处理大规模数据的计算预测方法,可在较短时间内获得大量真核蛋白质亚细胞位点信息,弥补了实验法 的不足。因此,运用计算预测法预测真核蛋白质的亚细胞位点成为生物信息学领域的研究热点之一。本文主要从提取真核蛋白质 的特征信息、计算预测方法及预测效果的评价三个方面,介绍近年来真核蛋白质亚细胞位点预测的研究进展。     

蛋白质组研究的技术体系及其进展

随着后基因组时代的到来,蛋白质组研究越来越受到国内外科学工作者的密切关注, 我国国家自然科学基金委员会已把蛋白质组研究列为重大科研项目.概述了蛋白质组研究中的基本技术,包括双向凝胶电泳的样品制备和分离、蛋白质的检测、凝胶图像分析、蛋白质的鉴定以及蛋白质数据库构建等,并就蛋白质鉴定的常用方法如氨基酸组成分析方法、蛋白质末端序列分析、肽质量指纹谱作了详细阐述.直观地列出了蛋白质组研究的技术体系流程图,着重介绍了蛋白质组研究的最新技术及其进展.     

作物杂种优势遗传基础的研究进展

杂种优势是指两个遗传基础有差异的亲本杂交生成的杂合子在生长势和生物量等方面优于两个亲本的现象。虽然杂种优势在农业生产中已经得到很好的利用,但对于其形成的遗传机理仍没有统一的解释。目前,解释杂种优势遗传基础的模型主要有显性、超显性和上位性。分子数量遗传学的发展加快了杂种优势的研究。该文主要综述了近期在数量性状位点(QTL)水平的杂种优势遗传基础的研究进展,对作物杂种优势的QTL定位进行了回顾和展望。     

语音处理的神经电生理学基础研究进展

解码大脑在语音处理过程中涉及的信息加工层级结构、皮质响应机制及功能连接模式,是神经语言学领域的研究重点.以语音信息加工时序为依据,可将该认知过程划分为:初级声学信号时频编码(spectrotemporal analysis of primary acoustic signals)、音素处理(phonemic processing)以及词汇-语义加工(lexical-semantic processing) 3个处理阶段.目前,研究者已对各阶段的神经机制进行了广泛且深入的研究,但不同模型理论/假说难以整合互补,有必要进行梳理与总结.本文将以大脑处理语音信息的3个阶段为主线,以电生理学方法为侧重范式,对各阶段下的皮质映射、神经振荡模式以及事件相关响应机制等神经基础研究现状进行总结评述,以期为进一步了解语音信号如何在人脑中进行处理和表达等相关研究提供一定的参考.     

果实风味的代谢基础及其调控机制研究进展

果实风味是重要农艺性状,基因组、代谢组、转录组等多组学联用技术的发展和应用,已相对系统地揭示了风味物质基础。这些物质代谢具有明显的器官、发育以及环境特异性调控的特点,其代谢机制的阐述是果品调控的重要研究热点问题。乙烯是植物生长发育过程中重要的信号分子,对果实风味物质的合成和代谢具有独特的调节作用。在近年来国内外果实风味物质研究的基础上,本文总结了果实风味的代谢基础、调控机制、风味物质对乙烯信号的响应以及生物信息学在果实风味研究中的应用。最后,对该方向未来的发展提出展望,以期为果实风味营养的提高和调控提供理论参考。     

Taking the Mumbo Out of the Jumbo: Progress Towards a Robust Basis for Ecological Scaling

Ecosystems - The challenges of the Anthropocene have forced ecologists into the public space, to contend with issues manifest at scales of tens of kilometers and more, unfolding over decades to...     

Basis for vaccine recommendations

Once a new vaccine has been granted its licensing, a public health expertise is needed in order to support the decision regarding its possible inclusion within the national immunisation schedule. This analysis, based on an assessment of the benefits/risks balance and costs/effectiveness ratio, is a multidisciplinary exercise. Largely based on epidemiological and immunological expertises, it also requires bio-mathematical and economical inputs, if the long term consequences of the vaccination are to be taken into account. Indeed, the main drivers of the decision are the burden of the disease, the characteristics of the vaccine in term of effectiveness and safety, the cost of the vaccination, the feasibility of the adjunction of the vaccine in the schedule, the social demand for this vaccination and the positive or negative indirect effects of a large vaccination on the epidemiology of the disease, in addition to the direct protective effect for vaccinated individuals. New vaccines are generally characterised by a more limited epidemiological impact than older vaccines, in a context of growing requirements from our society regarding drugs, and especially vaccines, safety. Both the real and perceived benefits/risks balances for the more recent vaccines appear questionable. The possibility of detrimental epidemiological consequences of either insufficient vaccination coverage or serotype (or serogroup) replacement is another factor that makes the decision regarding vaccination strategies increasingly complex.     

木质纤维生产燃料乙醇工艺的研究进展

利用丰富而廉价的木质纤维原料代替粮食生产燃料乙醇,对经济和社会的可持续发展有着重要的意义。以木质纤维为原料发酵生产燃料乙醇可分为4种工艺:分步糖水解化发酵法、同步糖化发酵法、同步糖化共发酵法和直接微生物转化法。介绍了以上4种工艺的研究进展,并对今后进一步研究提出了建议。     

Optimization and Technological Development Strategies of an Antimicrobial Extract from Achyrocline alata Assisted by Statistical Design

Achyrocline alata, known as Jateí-ka-há, is traditionally used to treat several health problems, including inflammations and infections. This study aimed to optimize an active extract against Streptococcus mutans, the main bacteria that causes caries. The extract was developed using an accelerated solvent extraction and chemometric calculations. Factorial design and response surface methodologies were used to determine the most important variables, such as active compound selectivity. The standardized extraction recovered 99% of the four main compounds, gnaphaliin, helipyrone, obtusifolin and lepidissipyrone, which represent 44% of the extract. The optimized extract of A. alata has a MIC of 62.5 μg/mL against S. mutans and could be used in mouth care products.     

Drivers of Inequality in Millennium Development Goal Progress: A Statistical Analysis

Background

Many low- and middle-income countries are not on track to reach the public health targets set out in the Millennium Development Goals (MDGs). We evaluated whether differential progress towards health MDGs was associated with economic development, public health funding (both overall and as percentage of available domestic funds), or health system infrastructure. We also examined the impact of joint epidemics of HIV/AIDS and noncommunicable diseases (NCDs), which may limit the ability of households to address child mortality and increase risks of infectious diseases.

Methods and Findings

We calculated each country''s distance from its MDG goals for HIV/AIDS, tuberculosis, and infant and child mortality targets for the year 2005 using the United Nations MDG database for 227 countries from 1990 to the present. We studied the association of economic development (gross domestic product [GDP] per capita in purchasing-power-parity), the relative priority placed on health (health spending as a percentage of GDP), real health spending (health system expenditures in purchasing-power-parity), HIV/AIDS burden (prevalence rates among ages 15–49 y), and NCD burden (age-standardised chronic disease mortality rates), with measures of distance from attainment of health MDGs. To avoid spurious correlations that may exist simply because countries with high disease burdens would be expected to have low MDG progress, and to adjust for potential confounding arising from differences in countries'' initial disease burdens, we analysed the variations in rates of change in MDG progress versus expected rates for each country. While economic development, health priority, health spending, and health infrastructure did not explain more than one-fifth of the differences in progress to health MDGs among countries, burdens of HIV and NCDs explained more than half of between-country inequalities in child mortality progress (R ²-infant mortality  = 0.57, R ²-under 5 mortality  = 0.54). HIV/AIDS and NCD burdens were also the strongest correlates of unequal progress towards tuberculosis goals (R ² = 0.57), with NCDs having an effect independent of HIV/AIDS, consistent with micro-level studies of the influence of tobacco and diabetes on tuberculosis risks. Even after correcting for health system variables, initial child mortality, and tuberculosis diseases, we found that lower burdens of HIV/AIDS and NCDs were associated with much greater progress towards attainment of child mortality and tuberculosis MDGs than were gains in GDP. An estimated 1% lower HIV prevalence or 10% lower mortality rate from NCDs would have a similar impact on progress towards the tuberculosis MDG as an 80% or greater rise in GDP, corresponding to at least a decade of economic growth in low-income countries.

Conclusions

Unequal progress in health MDGs in low-income countries appears significantly related to burdens of HIV and NCDs in a population, after correcting for potentially confounding socioeconomic, disease burden, political, and health system variables. The common separation between NCDs, child mortality, and infectious syndromes among development programs may obscure interrelationships of illness affecting those living in poor households—whether economic (e.g., as money spent on tobacco is lost from child health expenditures) or biological (e.g., as diabetes or HIV enhance the risk of tuberculosis). Please see later in the article for the Editors'' Summary     

Statistical tests for clonality

Cancer investigators frequently conduct studies to examine tumor samples from pairs of apparently independent primary tumors with a view to determine whether they share a "clonal" origin. The genetic fingerprints of the tumors are compared using a panel of markers, often representing loss of heterozygosity (LOH) at distinct genetic loci. In this article we evaluate candidate significance tests for this purpose. The relevant information is derived from the observed correlation of the tumors with respect to the occurrence of LOH at individual loci, a phenomenon that can be evaluated using Fisher's exact test. Information is also available from the extent to which losses at the same locus occur on the same parental allele. Data from these combined sources of information can be evaluated using a simple adaptation of Fisher's exact test. The test statistic is the total number of loci at which concordant mutations occur on the same parental allele, with higher values providing more evidence in favor of a clonal origin for the two tumors. The test is shown to have high power for detecting clonality for plausible models of the alternative (clonal) hypothesis, and for reasonable numbers of informative loci, preferably located on distinct chromosomal arms. The method is illustrated using studies to identify clonality in contralateral breast cancer. Interpretation of the results of these tests requires caution due to simplifying assumptions regarding the possible variability in mutation probabilities between loci, and possible imbalances in the mutation probabilities between parental alleles. Nonetheless, we conclude that the method represents a simple, powerful strategy for distinguishing independent tumors from those of clonal origin.     

Statistical Genetics of an Annual Plant, Impatiens Capensis. I. Genetic Basis of Quantitative Variation

Analysis of quantitative genetics in natural populations has been hindered by computational and methodological problems in statistical analysis. We developed and validated a jackknife procedure to test for existence of broad sense heritabilities and dominance or maternal effects influencing quantitative characters in Impatiens capensis. Early life cycle characters showed evidence of dominance and/or maternal effects, while later characters exhibited predominantly environmental variation. Monte Carlo simulations demonstrate that these jackknife tests of variance components are extremely robust to heterogeneous error variances. Statistical methods from human genetics provide evidence for either a major locus influencing germination date, or genes that affect phenotypic variability per se. We urge explicit consideration of statistical behavior of estimation and testing procedures for proper biological interpretation of statistical results.     

Basis functions for object-centered representations

In an object-centered representation, the position of the subparts of an object are encoded with respect to a set of axes and an origin centered on the object. Several physiological and neuropsychological results support the existence of such representations in humans and monkeys. An explicit representation would involve neurons with invariant response properties in object-centered coordinates. We consider an alternative scheme using basis functions in which the cells have retinotopic receptive fields modulated by the orientation of the object and task-related signals. We show that this alternative is consistent with single-cell data, is computationally efficient, and accounts for object-centered hemineglect, a syndrome observed in humans after fronto-parietal lesions.