Genetic contributions to stability and change in intelligence from childhood to old age

Understanding the determinants of healthy mental ageing is a priority for society today. So far, we know that intelligence differences show high stability from childhood to old age and there are estimates of the genetic contribution to intelligence at different ages. However, attempts to discover whether genetic causes contribute to differences in cognitive ageing have been relatively uninformative. Here we provide an estimate of the genetic and environmental contributions to stability and change in intelligence across most of the human lifetime. We used genome-wide single nucleotide polymorphism (SNP) data from 1,940 unrelated individuals whose intelligence was measured in childhood (age 11 years) and again in old age (age 65, 70 or 79 years). We use a statistical method that allows genetic (co)variance to be estimated from SNP data on unrelated individuals. We estimate that causal genetic variants in linkage disequilibrium with common SNPs account for 0.24 of the variation in cognitive ability change from childhood to old age. Using bivariate analysis, we estimate a genetic correlation between intelligence at age 11 years and in old age of 0.62. These estimates, derived from rarely available data on lifetime cognitive measures, warrant the search for genetic causes of cognitive stability and change.     

Apolipoprotein E controls cerebrovascular integrity via cyclophilin A

Human apolipoprotein E has three isoforms: APOE2, APOE3 and APOE4. APOE4 is a major genetic risk factor for Alzheimer's disease and is associated with Down's syndrome dementia and poor neurological outcome after traumatic brain injury and haemorrhage. Neurovascular dysfunction is present in normal APOE4 carriers and individuals with APOE4-associated disorders. In mice, lack of Apoe leads to blood-brain barrier (BBB) breakdown, whereas APOE4 increases BBB susceptibility to injury. How APOE genotype affects brain microcirculation remains elusive. Using different APOE transgenic mice, including mice with ablation and/or inhibition of cyclophilin A (CypA), here we show that expression of APOE4 and lack of murine Apoe, but not APOE2 and APOE3, leads to BBB breakdown by activating a proinflammatory CypA-nuclear factor-κB-matrix-metalloproteinase-9 pathway in pericytes. This, in turn, leads to neuronal uptake of multiple blood-derived neurotoxic proteins, and microvascular and cerebral blood flow reductions. We show that the vascular defects in Apoe-deficient and APOE4-expressing mice precede neuronal dysfunction and can initiate neurodegenerative changes. Astrocyte-secreted APOE3, but not APOE4, suppressed the CypA-nuclear factor-κB-matrix-metalloproteinase-9 pathway in pericytes through a lipoprotein receptor. Our data suggest that CypA is a key target for treating APOE4-mediated neurovascular injury and the resulting neuronal dysfunction and degeneration.     

从认知心理学对知识的分类看数学变式教学

从认知心理学对于知识分类的角度分析了变式教学在不同的数学知识教学中所起到的作用.变式教学在陈述性知识的教学中促进了学生图式的形成,在程序性知识的教学中则促进了学生自动化技能的形成、增加活动途径的多样性和活动过程的层次性以及学生的元认知能力的培养.     

极紫外多层膜反射率的模拟计算与分析

使用matlab软件编程计算了钼/硅多层膜的反射率随膜层数、波长及入射角等的变化.结果显示,在极紫外波段,存在中心波长为13.3 nm和17.2 nm两个峰值反射波长,反射率分别达到73.1％和53.7％;两中心波长的最佳镀膜层数分别为80和60;两中心波长在入射角小于8°的近正入射情形均存在一个反射率曲线平坦段.     

Neuronal basis of age-related working memory decline

Many of the cognitive deficits of normal ageing (forgetfulness, distractibility, inflexibility and impaired executive functions) involve prefrontal cortex (PFC) dysfunction. The PFC guides behaviour and thought using working memory, which are essential functions in the information age. Many PFC neurons hold information in working memory through excitatory networks that can maintain persistent neuronal firing in the absence of external stimulation. This fragile process is highly dependent on the neurochemical environment. For example, elevated cyclic-AMP signalling reduces persistent firing by opening HCN and KCNQ potassium channels. It is not known if molecular changes associated with normal ageing alter the physiological properties of PFC neurons during working memory, as there have been no in vivo recordings, to our knowledge, from PFC neurons of aged monkeys. Here we characterize the first recordings of this kind, revealing a marked loss of PFC persistent firing with advancing age that can be rescued by restoring an optimal neurochemical environment. Recordings showed an age-related decline in the firing rate of DELAY neurons, whereas the firing of CUE neurons remained unchanged with age. The memory-related firing of aged DELAY neurons was partially restored to more youthful levels by inhibiting cAMP signalling, or by blocking HCN or KCNQ channels. These findings reveal the cellular basis of age-related cognitive decline in dorsolateral PFC, and demonstrate that physiological integrity can be rescued by addressing the molecular needs of PFC circuits.     

福建华安马尾松生长早晚期相关及早期选择

<正>本研究证明马尾松不同林分个体的高生长变异随年龄的增长而增大,而径生长变异在达到某一高峰后有所下降。生长变异增长率和相关系数增长率均在9年或10年时最高。初步确认10年生是该地区马尾松天然林早期选择的“最佳年龄”,并可用10年生时的树高、胸径平方分别对30年时的材积进行早期预估。人工林早期选择的“最佳年龄”比天然林提早一年。     

地下水位变化与地震活动关系初探

主要探讨降雨对地下水位的影响及地下水位变化与地震之间的关系,提出一种基于回归的思想从地下水位观测数据中消除降雨影响的方法。该方法加工后数据能更好地体现地震的影响。同时引入局部变化速率的概念来描述地下水位的变化趋势,然后讨论它和地震之间的关系。     

基于免疫网络理论的永磁同步电机控制

摘 要：PID控制器有着广泛的应用,其参数也有多种智能调整方法。本文分析了免疫系统的免疫网络理论,提出了一种用免疫网络理论调整PI控制器的策略,并用于永磁同步电机的直接转矩控制的调速系统,以克服电阻变化引起磁链控制器输出不准确,影响控制精度的问题。该策略计算简单,在永磁同步电机定子电阻变化较大情况下,仍具有高控制精度。仿真结果验证了这一免疫网络理论控制策略的有效性,并与一般PI控制和采用遗传算法的PI控制的效果进行了比较。     

Failure of neuronal homeostasis results in common neuropsychiatric phenotypes

Failure of normal brain development leads to mental retardation or autism in about 3% of children. Many genes integral to pathways by which synaptic modification and the remodelling of neuronal networks mediate cognitive and social development have been identified, usually through loss of function. Evidence is accumulating, however, that either loss or gain of molecular functions can be deleterious to the nervous system. Copy-number variation, regulation of gene expression by non-coding RNAs and epigenetic changes are all mechanisms by which altered gene dosage can cause the failure of neuronal homeostasis.     

说服教育中对无效认知方式的干预

认知方式指引着个体的行为,改变认知方式即改变个体的行为,即改变个体的人格.改变的方法是引导对象进行反向观察,反向思考和反向行为.     

“自我调节学习”在高校足球教学中的实验研究

运用教学实验法,以大学一年级男生作为研究对象,在高校足球课中进行＂自我调节学习＂的教学实验研究.研究表明,该理论教学效果明显优于常规教学,不仅能够弥补学生的个体差异,培养学生的发展性认知能力,还有助于开发学生的学习潜力.     

A mutation in APP protects against Alzheimer's disease and age-related cognitive decline

The prevalence of dementia in the Western world in people over the age of 60 has been estimated to be greater than 5%, about two-thirds of which are due to Alzheimer's disease. The age-specific prevalence of Alzheimer's disease nearly doubles every 5 years after age 65, leading to a prevalence of greater than 25% in those over the age of 90 (ref. 3). Here, to search for low-frequency variants in the amyloid-β precursor protein (APP) gene with a significant effect on the risk of Alzheimer's disease, we studied coding variants in APP in a set of whole-genome sequence data from 1,795 Icelanders. We found a coding mutation (A673T) in the APP gene that protects against Alzheimer's disease and cognitive decline in the elderly without Alzheimer's disease. This substitution is adjacent to the aspartyl protease β-site in APP, and results in an approximately 40% reduction in the formation of amyloidogenic peptides in vitro. The strong protective effect of the A673T substitution against Alzheimer's disease provides proof of principle for the hypothesis that reducing the β-cleavage of APP may protect against the disease. Furthermore, as the A673T allele also protects against cognitive decline in the elderly without Alzheimer's disease, the two may be mediated through the same or similar mechanisms.     

Dual effects of spatial updating in both real and virtual environments

When people move around in their environment, spatial updating, which is an automatic cognitive process, is essential to ensuring people can keep track of their relations between them and the surrounding objects, and to "recalculating" the relative position and orientation of those objects with regard to the current position of the persons. Despite the facilitating effect of spatial updating to people’s mental representation in most circumstances as demonstrated in most of the existing literature, the effect sometimes can be adversarial. For instance, some research suggested that even though people were asked to ignore their locomotion, it is difficult to suppress updating of the spatial representation during movement. The current two studies were conducted to systematically investigate the dual effects of spatial updating in both real and virtual environments. We used a typical spatial updating paradigm to explore the effects of scene familiarity (familiar vs. novel) and person’s locomotion (stationary vs. moving) on change detection accuracy (target object moved or not). The results indicated a facilitating effect of spatial updating in the novel scene condition, but an adversarial effect in the familiar scene condition-the dual effects, in both real and virtual environments.     

吐温-80和脂质体对厚朴酚荧光光谱的影响

分析厚朴酚在吐温-80胶束和脂质体溶液中荧光光谱的变化,发现：1）浓度为2mmol·L^-1的吐温-80胶束对厚朴酚有荧光增敏作用,厚朴酚存在于吐温-80的疏水核中,其荧光光谱发生了明显的红移;2）在4mg·mL^-1的脂质体溶液中,厚朴酚的荧光光谱变得复杂,谱图信息反映厚朴酚同时存在于水相和双脂层膜相中,且在二者之间存在分配平衡,通过测定λ365、λ397处的荧光光谱随厚朴酚浓度的变化,得到了厚朴酚在脂质体膜相和水相中的分配平衡关系;3）脂质体溶液中加入吐温-80,厚朴酚在双脂层膜相中的分布增加,其荧光光谱发生了红移．     

船体梁静水弯矩的统计分析

由装载状态决定的船体梁静水弯矩为－随机变量，其统计特征可利用随机模拟原理予以探讨，即按随机取样方法组成多种装载方案，用综合静力程序计算出相应的弯矩和吃水，再由计算结果确定其统计特征值．分析表明，此弯矩随装载的变化近似于正态分布律，并具有与船体中剖面模数或钢材屈服极限同样显著的变异系数。     

药理研究中常用学习记忆障碍动物模型的行为学分析

目的本研究对老年、基底前脑损伤、东莨菪碱注射和双侧颈总动脉结扎大鼠四种药理研究中常用的学习记忆障碍动物模型的行为学表现进行了分析。方法采用水迷宫及旷场分析法对上述四种动物模型组及正常青年对照和假手术组进行了研究,数据采用多因素方差分析法处理。结果发现老年动物学习记忆能力减弱,对新环境的紧张程度增强,但空间认知能力及兴奋性无明显改变;基底前脑损伤动物的学习记忆及空间认知能力明显下降,但兴奋性及情绪反应正常;东莨菪碱动物模型不但学习记忆及空间认知能力明显下降,而且兴奋性异常增强;双侧颈总动脉结扎动物的学习记忆及空间认知能力明显下降,但兴奋性及情绪反应正常。结论从行为学角度将上述四种动物模型进行了比较,为药理学研究应用这些模型提供了背景资料。     

谷氨酸AMPA受体拮抗剂CNQX对大鼠颠倒学习的影响

研究利用旋转T迷宫装置,通过食物强化,分别训练大鼠视觉辨别学习和颠倒学习任务;每次训练前均向动物腹腔注射20μg/kg的谷氨酸AMPA受体拮抗剂CNQX,以考察其对大鼠学习能力的影响.结果发现,CNQX并不影响正常学习,但对于颠倒学习,CNQX注射组的学习次数较控制组显著增加,说明CNQX可以对大鼠的认知灵活性造成损害.     

Cryptic genetic variation promotes rapid evolutionary adaptation in an RNA enzyme

Cryptic variation is caused by the robustness of phenotypes to mutations. Cryptic variation has no effect on phenotypes in a given genetic or environmental background, but it can have effects after mutations or environmental change. Because evolutionary adaptation by natural selection requires phenotypic variation, phenotypically revealed cryptic genetic variation may facilitate evolutionary adaptation. This is possible if the cryptic variation happens to be pre-adapted, or "exapted", to a new environment, and is thus advantageous once revealed. However, this facilitating role for cryptic variation has not been proven, partly because most pertinent work focuses on complex phenotypes of whole organisms whose genetic basis is incompletely understood. Here we show that populations of RNA enzymes with accumulated cryptic variation adapt more rapidly to a new substrate than a population without cryptic variation. A detailed analysis of our evolving RNA populations in genotype space shows that cryptic variation allows a population to explore new genotypes that become adaptive only in a new environment. Our observations show that cryptic variation contains new genotypes pre-adapted to a changed environment. Our results highlight the positive role that robustness and epistasis can have in adaptive evolution.     

影响实验小鼠肠道菌群的多因素比较研究

目的比较研究影响实验小鼠肠道菌群的六种主要因素,为动物实验的设计和实验结果的解释提供参考,为肠道微生态菌群结构的干预与调控提供借鉴。方法采用珠磨法和酚-氯仿-异戊醇法提取肠道内容物中细菌基因组DNA,然后用16S rDNA V3区通用引物进行PCR扩增,扩增产物经DGGE电泳后用电泳条带数字化软件Quantity One和统计学软件SPSS对影响肠道菌群的六种因素(年龄、品种、饲养环境、饲料、个体差异和性别差异)进行比较研究。结果 Dice相关系数和主成分分析显示,年龄因素在早期(7和14日龄)对肠道菌群影响较大,到28日龄后,菌群结构趋向稳定,饲料和饲养环境成为主要的影响因素。品种和个体差异对肠道菌群也存在较大的影响,但性别差异影响相对较小,存在一定的随机性。结论以上六种因素均能在一定程度上影响肠道菌群,但其影响程度存在差异,在动物实验设计和实验结果解释时应充分考虑避免或利用这些影响因素。     

弱智儿童常见食物的概念联系类型

采用自由分类法，以实龄相同的智力正常儿童为参照，考察低、中、高年级弱智儿童常见食物的概念联系类型。结果表明，弱智儿童的概念水平随着年龄增长而提高，概念联系类型由以SF联系为主向以分类学关系为主转交，概念发展趋势与正常儿童相同，但在时间和水平上却大大落后于智力正常儿童。教育与环境在弱智儿童的概念发展中起重要作用。