Human metabolic phenotype diversity and its association with diet and blood pressure

Metabolic phenotypes are the products of interactions among a variety of factors-dietary, other lifestyle/environmental, gut microbial and genetic. We use a large-scale exploratory analytical approach to investigate metabolic phenotype variation across and within four human populations, based on 1H NMR spectroscopy. Metabolites discriminating across populations are then linked to data for individuals on blood pressure, a major risk factor for coronary heart disease and stroke (leading causes of mortality worldwide). We analyse spectra from two 24-hour urine specimens for each of 4,630 participants from the INTERMAP epidemiological study, involving 17 population samples aged 40-59 in China, Japan, UK and USA. We show that urinary metabolite excretion patterns for East Asian and western population samples, with contrasting diets, diet-related major risk factors, and coronary heart disease/stroke rates, are significantly differentiated (P < 10(-16)), as are Chinese/Japanese metabolic phenotypes, and subgroups with differences in dietary vegetable/animal protein and blood pressure. Among discriminatory metabolites, we quantify four and show association (P < 0.05 to P < 0.0001) of mean 24-hour urinary formate excretion with blood pressure in multiple regression analyses for individuals. Mean 24-hour urinary excretion of alanine (direct) and hippurate (inverse), reflecting diet and gut microbial activities, are also associated with blood pressure of individuals. Metabolic phenotyping applied to high-quality epidemiological data offers the potential to develop an area of aetiopathogenetic knowledge involving discovery of novel biomarkers related to cardiovascular disease risk.     

Hsp90 as a capacitor of phenotypic variation

Heat-shock protein 90 (Hsp90) chaperones the maturation of many regulatory proteins and, in the fruitfly Drosophila melanogaster, buffers genetic variation in morphogenetic pathways. Levels and patterns of genetic variation differ greatly between obligatorily outbreeding species such as fruitflies and self-fertilizing species such as the plant Arabidopsis thaliana. Also, plant development is more plastic, being coupled to environmental cues. Here we report that, in Arabidopsis accessions and recombinant inbred lines, reducing Hsp90 function produces an array of morphological phenotypes, which are dependent on underlying genetic variation. The strength and breadth of Hsp90's effects on the buffering and release of genetic variation suggests it may have an impact on evolutionary processes. We also show that Hsp90 influences morphogenetic responses to environmental cues and buffers normal development from destabilizing effects of stochastic processes. Manipulating Hsp90's buffering capacity offers a tool for harnessing cryptic genetic variation and for elucidating the interplay between genotypes, environments and stochastic events in the determination of phenotype.     

Condition-dependent signalling of genetic variation in stalk-eyed flies

Handicap models of sexual selection predict that male sexual ornaments have strong condition-dependent expression and this allows females to evaluate male genetic quality. A number of previous experiments have demonstrated heightened condition-dependence of sexual ornaments in response to environmental stress. Here we show that genetic variation underlies the response to environmental stress (variable food quality) of a sexual ornament (male eye span) in the stalk-eyed fly Cyrtodiopsis dalmanni. Some male genotypes develop large eye span under all conditions, whereas other genotypes progressively reduce eye span as conditions deteriorate. Several non-sexual traits (female eye span, male and female wing length) also show genetic variation in condition-dependent expression, but their genetic response is entirely explained by scaling with body size. In contrast, the male sexual ornament still reveals genetic variation in the response to environmental stress after accounting for differences in body size. These results strongly support the hypothesis that female mate choice yields genetic benefits for offspring.     

祁连山青海云杉林物种分布模型与变量相异指数

选择了边界函数法、最大熵算法以及基于规则集的遗传算法,选取坡向、海拔、多年平均温度和多年平均降水量4个环境变量,对祁连山国家自然保护区的青海云杉进行分布预测.提出一种新的物种分布模型性能评价方法,通过提取分布区上各变量的特征,比较现实分布区和潜在分布区上环境变量的差别,来评价模型在性能上的表现.该方法以计算环境变量的边界相异指数和总体相异指数实现.应用两种指数对各模型的性能评价表明:GARP模型获得4组MDIV的最小值,BF和Maxen分别获得3,2组最小MDIV,表明GARP模型性能的优越性;GARP,Maxent和BF模型的DIV分别为10.9965,15.1455和18.8747,同样表现出GARP模型优于其他两种模型的物种分布预测性能.青海云杉主要分布在研究区中部,包括肃南、民乐、山丹县存在大面积的适宜分布区.研究区南部天祝县的潜在分布区也大于现实分布范围.     

Predicting mutation outcome from early stochastic variation in genetic interaction partners

Many mutations, including those that cause disease, only have a detrimental effect in a subset of individuals. The reasons for this are usually unknown, but may include additional genetic variation and environmental risk factors. However, phenotypic discordance remains even in the absence of genetic variation, for example between monozygotic twins, and incomplete penetrance of mutations is frequent in isogenic model organisms in homogeneous environments. Here we propose a model for incomplete penetrance based on genetic interaction networks. Using Caenorhabditis elegans as a model system, we identify two compensation mechanisms that vary among individuals and influence mutation outcome. First, feedback induction of an ancestral gene duplicate differs across individuals, with high expression masking the effects of a mutation. This supports the hypothesis that redundancy is maintained in genomes to buffer stochastic developmental failure. Second, during normal embryonic development we find that there is substantial variation in the induction of molecular chaperones such as Hsp90 (DAF-21). Chaperones act as promiscuous buffers of genetic variation, and embryos with stronger induction of Hsp90 are less likely to be affected by an inherited mutation. Simultaneously quantifying the variation in these two independent responses allows the phenotypic outcome of a mutation to be more accurately predicted in individuals. Our model and methodology provide a framework for dissecting the causes of incomplete penetrance. Further, the results establish that inter-individual variation in both specific and more general buffering systems combine to determine the outcome inherited mutations in each individual.     

3种辐射保护剂对60Co-γ射线辐照小苍兰的保护效应

采用水杨酸（SA）、褪黑素(MT)、赤霉素(GA)3种辐射保护剂对⁶⁰Co-γ射线辐射处理后的小苍兰进行保护处理,以期减轻植物辐照后的损伤,降低辐照后种球的死亡率,增加其存活率和开花率,为花卉品种培育与改良提供行之有效的技术支持和数据参考。     

建筑用户在室行为预测新方法

准确预测建筑用户在室行为可显著提高建筑能耗模拟精度,并进一步帮助建筑设计及运行控制优化.当前进行在室行为预测时所采用的主要是基于隐马尔可夫链方法的数学模型,该模型考虑了在室行为的时间关联性,可平稳有效地预测在室行为.然而现有隐马尔科夫模型难以准确描述在室行为动态变化规律以及在室行为与可观测参数之间的关联,降低了模型预测精度.针对该问题,本文提出一种基于状态转移的时变隐马尔科夫模型.该模型采用时变状态转移概率矩阵量化不同时刻在室行为的动态变化特征及关联,同时该模型基于状态转移计算可观测参数的概率分布以定量描述在室行为对可观测参数的影响.本文采用比利时某办公室在室行为数据库进行了相关建模和验证,结果表明该模型可更有效地捕捉在室状态变化,从而提高了在室行为预测精度.     

地基基础刚度变化对高层建筑的影响

以高层建筑巨型框架结构为例,将高层建筑巨型框架结构与其基础等效连续化为一个半无限大弹性地基上的加劲薄壁筒组合体,并以此三维模型,用半解析法分析计算了该结构地基基础刚度变化对其上部结构的影响.计算结果表明,地基基础刚度变化对高层建筑结构的顶端侧移、层间侧移、上部结构的翘曲位移、地基和基础结构底部应力的影响都是非常显著的.     

Adaptive variation in environmental and genetic sex determination in a fish

Two general mechanisms of sex determination have been identified among gonochoristic vertebrates: environmental sex determination where offspring become male or female in response to an environmental factor(s) during development (for example, some fishes and reptiles); and genetic sex determination where sex is determined by genotype at conception (as in birds and mammals). How do these sex-determining systems evolve? Direct evidence is virtually non-existent because the sex-determining systems of most species appear to have little genetic variation. Here we provide the first evidence of adaptive variation in environmental and genetic sex determination within a species. We show that in a fish with temperature-dependent sex determination, populations at different latitudes compensate for differences in thermal environment and seasonality by adjusting the response of sex ratio to temperature, and by altering the level of environmental as opposed to genetic control. The adjustments observed are precisely those predicted by adaptive sex ratio theory.     

Temporal targeting of tumour cells and neovasculature with a nanoscale delivery system

In the continuing search for effective treatments for cancer, the emerging model is the combination of traditional chemotherapy with anti-angiogenesis agents that inhibit blood vessel growth. However, the implementation of this strategy has faced two major obstacles. First, the long-term shutdown of tumour blood vessels by the anti-angiogenesis agent can prevent the tumour from receiving a therapeutic concentration of the chemotherapy agent. Second, inhibiting blood supply drives the intra-tumoural accumulation of hypoxia-inducible factor-1alpha (HIF1-alpha); overexpression of HIF1-alpha is correlated with increased tumour invasiveness and resistance to chemotherapy. Here we report the disease-driven engineering of a drug delivery system, a 'nanocell', which overcomes these barriers unique to solid tumours. The nanocell comprises a nuclear nanoparticle within an extranuclear pegylated-lipid envelope, and is preferentially taken up by the tumour. The nanocell enables a temporal release of two drugs: the outer envelope first releases an anti-angiogenesis agent, causing a vascular shutdown; the inner nanoparticle, which is trapped inside the tumour, then releases a chemotherapy agent. This focal release within a tumour results in improved therapeutic index with reduced toxicity. The technology can be extended to additional agents, so as to target multiple signalling pathways or distinct tumour compartments, enabling the model of an 'integrative' approach in cancer therapy.     

基于孔结构模型的混凝土干缩变形理论分析

根据混凝土多孔材料的特性,基于孔结构模型的假设,依据毛细管张力理论,初步完成了混凝土早龄期干缩变形的理论分析,并综合考虑了水灰比、环境和养护等多方面因素的影响。同时,采用三维有限元和有限差分的方法,基于混凝土内部湿度场分布的计算,建立了相关的计算模型,并通过与其他学者的实验结果的对比分析,来验证该模型的正确性。     

动态联盟伙伴选择问题的混合计算方法

针对已有伙伴选择问题方法的不足,以最小化竞标花费,交通运费和拖期惩罚成本之和为目标,给出伙伴问题的0-1整数规划模型,并提出了求解问题的混合遗传算法.该算法用染色体的编码确定合作伙伴的组合,结合专家经验,通过模糊神经网络对人工给定的隶属函数和模糊规则进行修正,用所得到的结果改进合作伙伴的组合.实验结果表明,模糊神经网络的使用提高了模糊推理的准确性,进而也提高了混合算法的有效性,使其具有比普通遗传算法更好的寻优能力.     

计算机辅助产品配色设计系统的构造研究

当现有的配色理论直接应用在产品上时,色彩配置往往会受到产品特有的形态与属性影响,从而与目标意象发生偏差。为了降低产品配色的意象偏差,文章拟构建产品配色的问卷系统,基于配色理论设计问卷,配合神经网络和遗传算法模拟消费者的意象评价,提供符合产品形态的配色建议,并在此基础上提出了计算机辅助配色设计系统的框架和实现方法。     

广西马尾松三个优良种源的遗传多样性及生长性状变异分析

【目的】以25年生马尾松种源、地点、林分3水平子代试验林为研究材料,从表型、遗传变异两方面开展研究,以期为马尾松遗传育种策略的制定提供有价值参考。【方法】采用SSR分子标记进行遗传结构分析,使用Arlequin 3.5软件依据线性模型估算各层次变异的相对分量。以SAS分析软件依据线性模型对林分生长量数据进行统计分析,以4因素嵌套模型估算各层次变异的相对分量。【结果】遗传多样性分析结果表明,种源间及种源内无明显的遗传分化。分子方差分析结果表明,种源间的遗传变异仅占总变异的2.56%,种源内不同地点间的变异占1.66%,地点内个体间的遗传变异则占总变异的95.78%。生长表型数据分析结果同样显示胸径与材积性状在种源间、种源内地点间、同一地点的优良林分与普通林分间均无显著差异。【结论】分子方差分析与生长性状表型数据方差分析的结果均表明,广西马尾松的主要遗传变异存在于林分内个体间。因此在优良种源中开展优良单株选择可以获得更好的改良效果。该结论对于马尾松遗传育种策略的制定具有重要的参考价值。     

Arbuscular mycorrhizal fungi: hyphal fusion and multigenomic structure

Arbuscular mycorrhizal (AM) fungi (Glomeromycota) reproduce asexually, are multinucleate, and have high genetic variation within single cells. Pawlowska and Taylor find that genetic variation within AM fungal cells is not lost as a result of segregation, and they interpret this as evidence that the variation is present within each nucleus and that all nuclei within individual spores are genetically identical (that is, homokaryotic). Here we show that their empirical observations are also consistent with a distribution of genetic variation between nuclei within spores (that is, heterokaryotic), given that there is fusion of fungal hyphae. This analysis, together with complementary findings, suggests that AM fungi have an unusual genomic structure in which multiple, genetically diverse nuclei are maintained within cells through remixing by hyphal fusion.     

Adaptive interactive genetic algorithms with individual interval fitness

It is necessary to enhance the performance of interactive genetic algorithms in order to apply them to complicated optimization problems successfully. An adaptive interactive genetic algorithm with individual interval fitness is proposed in this paper in which an individual fitness is expressed by an interval. Through analyzing the fitness, information reflecting the distribution of an evolutionary population is picked up, namely, the difference of evaluating superior individuals and the difference of evaluating a population. Based on these, the adaptive probabilities of crossover and mutation operators of an individual are presented. The algorithm proposed in this paper is applied to a fashion evolutionary design system, and the results show that it can find many satisfactory solutions per generation. The achievement of the paper provides a new approach to enhance the performance of interactive genetic algorithms.     

Catecholamine receptor polymorphisms affect decision-making in C. elegans

Innate behaviours are flexible: they change rapidly in response to transient environmental conditions, and are modified slowly by changes in the genome. A classical flexible behaviour is the exploration-exploitation decision, which describes the time at which foraging animals choose to abandon a depleting food supply. We have used quantitative genetic analysis to examine the decision to leave a food patch in Caenorhabditis elegans. Here we show that patch-leaving is a multigenic trait regulated in part by naturally occurring non-coding polymorphisms in tyra-3 (tyramine receptor 3), which encodes a G-protein-coupled catecholamine receptor related to vertebrate adrenergic receptors. tyra-3 acts in sensory neurons that detect environmental cues, suggesting that the internal catecholamines detected by tyra-3 regulate responses to external conditions. These results indicate that genetic variation and environmental cues converge on common circuits to regulate behaviour, and suggest that catecholamines have an ancient role in regulating behavioural decisions.     

Adaptive interactive genetic algorithms with individual interval fitness

It is necessary to enhance the performance of interactive genetic algorithms in order to apply them to complicated optimization problems successfully. An adaptive interactive genetic algorithm with individual interval fitness is proposed in this paper in which an indi-vidual fitness is expressed by an interval. Through analyzing the fitness, information reflecting the distribution of an evolutionary population is picked up, namely, the difference of evaluating superior individuals and the difference of evaluating a population. Based on these, the adaptive probabilities of crossover and mutation operators of an individual are presented. The algorithm proposed in this paper is applied to a fashion evolutionary design system, and the results show that it can find many satisfactory solutions per generation. The achievement of the paper provides a new approach to enhance the t~erformance of interactive genetic algorithms.     

基于MHCⅡ类B基因的凹耳臭蛙(Odorrana tormota)种群遗传分化模式

利用II类MHC基因单基因座位Odto-A作为分子标记,对皖南山区凹耳臭蛙6个种群的遗传多样性和遗传分化进行研究.结果显示,皖南凹耳臭蛙总的基因多样性为0.812,核苷酸多样性为0.018.局域种群单倍型多样性变化范围为0.531-0.864,香溪种群单倍型多样性最高,最低的是漳河种群.与线粒体cyt b基因所揭示的单倍型多样性差别不大,但B基因的核苷酸多样性较之线粒体cyt b基因的高达一个数量级.暗示MHC基因丰富的核苷酸多态性可能与其病原体抗性多样性密切相关.分子变异分析结果显示,皖南山区凹耳臭蛙种群MHC II类B基因遗传变异主要来源于种群内,种群间发生了显著的遗传分化(Fst=0.05644,P=0.00391).成对种群间的遗传分化分析结果显示,直线距离最近的浮溪和香溪种群间也发生了显著的遗传分化,暗示这两个种群经历了不同的选择压力.受平衡选择的作用,MHC基因与基于中性分子标记所揭示的遗传格局不同,基于MHC基因的种群遗传分化与水系和直线地理距离均没有明显的相关性,而与种群所经历的选择压力密切相关.结果表明皖南凹耳臭蛙不同局域种群所经历的环境病原体的选择压力存在时空变异.