Cognitive change and the APOE epsilon 4 allele

There is a marked variation in whether people retain sufficient cognitive function to maintain their quality of life and independence in old age, even among those without dementia, so it would be valuable to identify the determinants of normal age-related cognitive change. We have retested non-demented 80-year-olds who were participants in the Scottish Mental Survey of 1932, and find that the variation in their non-pathological cognitive change from age 11 to 80 is related to their apolipoprotein E (APOE) genotype. This effect of the APOE epsilon 4 allele on normal cognitive ageing may be mediated by a mechanism that is at least partly independent of its predisposing effect towards Alzheimer's disease.     

载脂蛋白E和SHCP66的基因单核苷酸多态性及其与长寿性状的相关研究

研究载脂蛋白E（Apolipoprotein E,APOE)和SHCP66（Src homology-domain cotaining protein,66ku)的基因在一个中国隔离人群中的单核苷酸多态性（single nucleotide polymorphism,SNP)，以及它们与长寿性状的相关性，应用多聚酶链式反应结合测序技术对2个基因的外显子区域进行小样本（40个随机个体）的单碱基多态位点（SNP）检测，并对其中apoe的2个侯选位点在大样本中进行基因分型，结果在apoe基因中发现3个SNP位点，其中一个在调控区内的位点是首次报道，shcp66发现3个SNP位点和一个缺失突变，均为首次报告.apoe的2个候选位点在隔离人群中的长寿个体及对照组中基因频率的卡方测验显示无显著差别（P＞5％），因此，在该长寿人群中，该基因的多态现象与长寿性状无显著的关联。     

Stochastic and genetic factors influence tissue-specific decline in ageing C. elegans

The nematode Caenorhabditis elegans is an important model for studying the genetics of ageing, with over 50 life-extension mutations known so far. However, little is known about the pathobiology of ageing in this species, limiting attempts to connect genotype with senescent phenotype. Using ultrastructural analysis and visualization of specific cell types with green fluorescent protein, we examined cell integrity in different tissues as the animal ages. We report remarkable preservation of the nervous system, even in advanced old age, in contrast to a gradual, progressive deterioration of muscle, resembling human sarcopenia. The age-1(hx546) mutation, which extends lifespan by 60-100%, delayed some, but not all, cellular biomarkers of ageing. Strikingly, we found strong evidence that stochastic as well as genetic factors are significant in C. elegans ageing, with extensive variability both among same-age animals and between cells of the same type within individuals.     

Audience drives male songbird response to partner's voice

According to the social intelligence hypothesis, social context represents an important force driving the selection of animal cognitive abilities such as the capacity to estimate the nature of the social relationships between other individuals. Despite this importance, the influence of this force has been assessed only in primates and never in other animals showing social interactions. In this way, avian communication generally takes place in a network of signallers and receivers, which represents an audience altering individual signalling behaviours. Indeed, vocal amplitude and repertoire are known to be socially regulated and the attitude towards the opposite sex may change depending on the audience. This 'audience effect' provides support for the reality of social awareness in some bird species. However no evidence has yet been found to suggest that birds are able to estimate the characteristics of the social relationships between group-mates. Here we show that the male of a gregarious songbird species--the zebra finch (Taeniopygia guttata)--pays attention to the mating status of conspecific pairs, and uses this information to control its behaviour towards its female partner.     

The ageing systemic milieu negatively regulates neurogenesis and cognitive function

In the central nervous system, ageing results in a precipitous decline in adult neural stem/progenitor cells and neurogenesis, with concomitant impairments in cognitive functions. Interestingly, such impairments can be ameliorated through systemic perturbations such as exercise. Here, using heterochronic parabiosis we show that blood-borne factors present in the systemic milieu can inhibit or promote adult neurogenesis in an age-dependent fashion in mice. Accordingly, exposing a young mouse to an old systemic environment or to plasma from old mice decreased synaptic plasticity, and impaired contextual fear conditioning and spatial learning and memory. We identify chemokines--including CCL11 (also known as eotaxin)--the plasma levels of which correlate with reduced neurogenesis in heterochronic parabionts and aged mice, and the levels of which are increased in the plasma and cerebrospinal fluid of healthy ageing humans. Lastly, increasing peripheral CCL11 chemokine levels in vivo in young mice decreased adult neurogenesis and impaired learning and memory. Together our data indicate that the decline in neurogenesis and cognitive impairments observed during ageing can be in part attributed to changes in blood-borne factors.     

The coming acceleration of global population ageing

The future paths of population ageing result from specific combinations of declining fertility and increasing life expectancies in different parts of the world. Here we measure the speed of population ageing by using conventional measures and new ones that take changes in longevity into account for the world as a whole and for 13 major regions. We report on future levels of indicators of ageing and the speed at which they change. We show how these depend on whether changes in life expectancy are taken into account. We also show that the speed of ageing is likely to increase over the coming decades and to decelerate in most regions by mid-century. All our measures indicate a continuous ageing of the world's population throughout the century. The median age of the world's population increases from 26.6 years in 2000 to 37.3 years in 2050 and then to 45.6 years in 2100, when it is not adjusted for longevity increase. When increases in life expectancy are taken into account, the adjusted median age rises from 26.6 in 2000 to 31.1 in 2050 and only to 32.9 in 2100, slightly less than what it was in the China region in 2005. There are large differences in the regional patterns of ageing. In North America, the median age adjusted for life expectancy change falls throughout almost the entire century, whereas the conventional median age increases significantly. Our assessment of trends in ageing is based on new probabilistic population forecasts. The probability that growth in the world's population will end during this century is 88%, somewhat higher than previously assessed. After mid-century, lower rates of population growth are likely to coincide with slower rates of ageing.     

杉木种子园遗传效益的估算

<正>杉木无性系种子园的面积3.0公顷,包括46个无性系,于1966年进行嫁接。实生苗种子园的面积0.6公顷,包括30个自由授粉的家系,于1967年栽植。 根据子代测定的结果,优良母树的后代,在相同立地条件和一致的经营管理下,在7年生时,材积生长比一般对照大“14—39％;种子园的后代则比对照大33—74％。然而,当半同胞子代在四个不同地点测定时,其树高生长比对照大6—22％。 7—13年生的杉木树高、胸径和材积的广义遗传力是按家系和单株估算的。单株树的树高和材积遗传力估值是0.2,而直径的遗传力估值为0.3。家系树高、胸径和材积遗传力估值是0.4。2—4年生时,全同胞家系树高狭义遗传力估值是0.3。 期望遗传效益是在各种不同选择强度下计算的(P_1=0.01;P_2=0.1,0.2和0.3;P_3=0.01,0.02和0.05)。对第一代无性系种子园在材积生产和其它生长性状方面的遗传效益进行预测。杉木各生长性状的遗传效益的估值如下:树高6.54一6.7.％,胸径19.12—19.68％,材积27.38—23.09％。然而,从第一代实生苗种子园在胸径生长方面预测的遗传效益值接近于20—26％。 第二代亲木的选择是在于代测定的材料中进行的。当假定把整个杉木育种方案的成木与期待增加的收益结合起来考虑时,其所得到的净收入值,证实了子代测定的实用价值。研究证明,每一公顷种子园的期待净收入元。     

基于遗传算法的特征子集选择方法

特征子集选择问题一直是人工智能领域研究的重要内容,特别是近几年来,特征子集选择算法研究已经成为机器学习和数据挖掘等领域的研究热点.本文提出了基于遗传算法的特征子集选择算法,实验证明该算法是简单、正确、有效的,并具有良好的收敛性和稳定性.     

2017—2019 年 CD ( SD)大鼠 240 个 SNP 位点遗传检测结果分析

摘要:目的 2017—2019 年北京维通利华实验动物技术有限公司(以下简称,维通利华) 连续三年参与美国 CharlesRiver Laboratories( CRL)对全球各地设施 CD( SD)大鼠生产群的遗传检测,以评估种群的遗传稳定性、杂交系数及各设施间种群的差异。 方法 从大鼠耳部样品中提取 DNA,使用荧光标记法检测 240 个单核苷酸多态性( SNP ) 基因位点,通过 GenA1Ex6. 5 软件统计分析得到位点多态性( P) 、观测杂合度( Ho ) 、期望杂合度( HE ) 、近交系数( F)和遗传分化系数( FST )等。 结果 位点多态性比例分别为 73. 6% ,76. 9% 和 74. 2% ,遗传具有多样性且保持稳定;杂交系数分别为-0. 02、-0. 06 和-0. 07,符合随机交配特性;遗传分化系数( FST ) 在 0. 05 上下波动。 结论 维通利华的 CD( SD)大鼠种群保持稳定的遗传多样性,符合随机交配方式繁殖,与 CRL 美国基础种群呈低至中等程度的遗传分化,定期的引种措施为保持种群的杂交性和稳定性发挥重要作用。     

Fine-scale recombination rate differences between sexes, populations and individuals

Meiotic recombinations contribute to genetic diversity by yielding new combinations of alleles. Recently, high-resolution recombination maps were inferred from high-density single-nucleotide polymorphism (SNP) data using linkage disequilibrium (LD) patterns that capture historical recombination events. The use of these maps has been demonstrated by the identification of recombination hotspots and associated motifs, and the discovery that the PRDM9 gene affects the proportion of recombinations occurring at hotspots. However, these maps provide no information about individual or sex differences. Moreover, locus-specific demographic factors like natural selection can bias LD-based estimates of recombination rate. Existing genetic maps based on family data avoid these shortcomings, but their resolution is limited by relatively few meioses and a low density of markers. Here we used genome-wide SNP data from 15,257 parent-offspring pairs to construct the first recombination maps based on directly observed recombinations with a resolution that is effective down to 10 kilobases (kb). Comparing male and female maps reveals that about 15% of hotspots in one sex are specific to that sex. Although male recombinations result in more shuffling of exons within genes, female recombinations generate more new combinations of nearby genes. We discover novel associations between recombination characteristics of individuals and variants in the PRDM9 gene and we identify new recombination hotspots. Comparisons of our maps with two LD-based maps inferred from data of HapMap populations of Utah residents with ancestry from northern and western Europe (CEU) and Yoruba in Ibadan, Nigeria (YRI) reveal population differences previously masked by noise and map differences at regions previously described as targets of natural selection.     

白桦天然次生林种群生态特征的研究

采用样地调查的方法,对太岳山七里峪白桦林种群进行了年龄结构分析、编制了静态生命表、绘制了存活曲线,并对该种群的四个函数（生存函数、积累死亡函数、死亡密度函数、危险率函数）进行数量分析,结果表明：①七里峪白桦种群龄级分布,不同环境下种群结构稍有差异：种群A、种群D为增长型种群,种群B、种群C、种群E趋向于稳定型．②白桦种群存活曲线接近于DeeveyⅡ型．③积累死亡率单调上升,生存率呈单调下降,上升或下降幅度前期大于后期,说明白桦种群在前期死亡率高,而种群后期则相对稳定．④在未来20年、40年、60年和80年中,白桦种群将呈现老龄级株数先增后减的趋势,种群稳定性长期维持较为困难．     

计量法学、计算法学到认知法学的演进

本文从技术发展和学科交叉的角度,论述了一般量化方法、计算智能和认知智能先后被应用于法学系统对法学理论与司法实践产生的重要推动作用,首次提出了认知法学的理论和概念,分析了认知法学的内容、研究意义与学科分支,并梳理了计量法学、计算法学与认知法学的发展脉络.自然科学的方法引入法律领域对减少法律系统中的主观性、为法律中的模糊表达提供客观参考具有积极意义,然而,法律信息语义模糊、法规冲突、司法解释具有开放性、司法裁判需要常识,各种隐性知识、过程知识、模糊知识等难以用计算机符号体系表达.认知智能重在提高智能系统对数据理解、知识表达、逻辑推理和自我学习能力,将更好地理解法学规则和分析法律行为.认知法学运用认知智能将提高智能系统对法学问题的理解和认知能力,增强智能裁判的可解释性,从计量法学、计算法学发展到认知法学是法学研究的必然趋势.作为认知社会科学的一部分,认知法学将完善和发展传统法学理论,促进英美法系和大陆法系的深度融合,并有望成为法学研究的新交叉学科分支.     

认知进化观:认知科学研究范式的新取向

认知科学在其发展过程中经历了几次研究范式的转换，认知进化观的兴起是认知科学各学科多层次整合的表现。在心理学领域，进化心理学采用功能分析的方法分析适应性行为下的心理机制和特征。在人工智能领域，采用进化计算和遗传算法探讨人工生命的适应性行为。在神经科学领域，是对神经网络的自组织机制和神经系统的可塑性进行考察。认知进化观的缺陷是自然主义的计算与进化，忽视了人的历史文化性。认知进化观作为一种新方法论，为智能研究带来了生机。     

Age-impaired impulse flow from nucleus basalis to cortex

Recent studies have renewed interest in the role of acetylcholine (ACh) in the cognitive changes associated with ageing and dementia. Deficits in cortical choline acetyltransferase (ChAT) in Alzheimer's disease have been consistently demonstrated, while other research has suggested a connection between deterioration of cortical ACh fibres and dementia. However, despite clear biochemical and anatomical evidence for a fall in ACh in dementia, results of therapeutic trials with cholinergic agonists, precursors and cholinesterase inhibitors have been inconsistent. Such findings suggest that cortical cholinergic disorders are not wholly a function of simple biochemical change; alterations of impulse flow along cholinergic fibres could well be as debilitating. An important extrinsic source of cortical ACh innervation derives from neurones diffusely located in rat basal forebrain, denoted the nucleus basalis (NB). We have now investigated the impulse conduction properties of cortically projecting, putatively cholinergic NB axons in adult and aged rats and have found that conduction latencies from NB to frontal cortex are significantly longer (by 51%) in aged animals. In addition, systematic analysis varying cortical stimulation depth revealed that these longer latencies are due entirely to decreased conduction velocities in the subcortical fibre projections. Indeed, intracortical velocities were virtually identical in the two groups. Our results indicate that ageing occasions a decrease in the temporal fidelity of impulse flow in the cholinergic input to the cortex from the NB, a previously overlooked but potentially important element in cognitive deficits that occur with age.     

Genetic linkage of Werner's syndrome to five markers on chromosome 8.

Werner's syndrome (WS) is a rare autosomal recessive disease in which the affected individuals display symptoms of premature ageing. The substantial phenotypic overlap between WS and normal ageing indicates that these two conditions may have pathogenetic mechanisms in common. The WS mutation has pleiotropic effects, and patients and their cells show many differences compared with normals. Despite extensive study of the clinical and biochemical features of this disorder, the primary genetic defect remains unknown. We have undertaken a genetic linkage study in an effort to identify the locus of the primary defect. Here we report close genetic linkage of the WS mutation to a group of markers on chromosome 8.     

Evidence for a genetic aetiology in reading disability of twins

Reading disability (dyslexia) is a major social, educational, and mental health problem. Although estimates of prevalence vary, up to 10-15% of school-age children have severe reading deficits in spite of average intelligence and adequate educational opportunity. That reading disability may have a constitutional basis has long been recognized, and results of twin and family studies suggest that one or more of its forms may be heritable; however, definitive evidence for a genetic aetiology has not been reported. Establishing a heritable basis for reading disability could suggest possible causes, give improved risk estimates, facilitate early diagnosis, and provide validity tests for ostensible subtypes. In this report, we apply a recently developed multiple regression analysis to data collected from a sample of 64 pairs of identical twins and 55 pairs of fraternal twins, in which at least one member of the pairs is reading disabled, and present evidence for a significant genetic aetiology.     

Methane bubbling from Siberian thaw lakes as a positive feedback to climate warming

Large uncertainties in the budget of atmospheric methane, an important greenhouse gas, limit the accuracy of climate change projections. Thaw lakes in North Siberia are known to emit methane, but the magnitude of these emissions remains uncertain because most methane is released through ebullition (bubbling), which is spatially and temporally variable. Here we report a new method of measuring ebullition and use it to quantify methane emissions from two thaw lakes in North Siberia. We show that ebullition accounts for 95 per cent of methane emissions from these lakes, and that methane flux from thaw lakes in our study region may be five times higher than previously estimated. Extrapolation of these fluxes indicates that thaw lakes in North Siberia emit 3.8 teragrams of methane per year, which increases present estimates of methane emissions from northern wetlands (< 6-40 teragrams per year; refs 1, 2, 4-6) by between 10 and 63 per cent. We find that thawing permafrost along lake margins accounts for most of the methane released from the lakes, and estimate that an expansion of thaw lakes between 1974 and 2000, which was concurrent with regional warming, increased methane emissions in our study region by 58 per cent. Furthermore, the Pleistocene age (35,260-42,900 years) of methane emitted from hotspots along thawing lake margins indicates that this positive feedback to climate warming has led to the release of old carbon stocks previously stored in permafrost.     

聚集数据线性模型参数聚集Liu估计的相对效率

 当线性模型中的变量间存在复共线性时,常用有偏估计代替无偏估计。其中广义岭估计是研究较多的一种有偏估计。很多实际问题只能观测到聚集数据。本文给出了聚集数据线性模型聚集Liu估计的定义,提出了聚集Liu估计相对于最小二乘估计的两种相对效率,并得到这两种相对效率的上界;给出了聚集Liu估计相对于Peter-Karsten估计的2种相对效率及其上界。本文提出的聚集Liu估计,既能保证估计参数的稳定性,又能保证估计参数的近似无偏性,从这个意义上说,该估计在某种程度上优于聚集广义岭估计。