An elaborate pathway required for Ras-mediated epigenetic silencing

The conversion of a normal cell to a cancer cell occurs in several steps and typically involves the activation of oncogenes and the inactivation of tumour suppressor and pro-apoptotic genes. In many instances, inactivation of genes critical for cancer development occurs by epigenetic silencing, often involving hypermethylation of CpG-rich promoter regions. It remains to be determined whether silencing occurs by random acquisition of epigenetic marks that confer a selective growth advantage or through a specific pathway initiated by an oncogene. Here we perform a genome-wide RNA interference (RNAi) screen in K-ras-transformed NIH 3T3 cells and identify 28 genes required for Ras-mediated epigenetic silencing of the pro-apoptotic Fas gene. At least nine of these RESEs (Ras epigenetic silencing effectors), including the DNA methyltransferase DNMT1, are directly associated with specific regions of the Fas promoter in K-ras-transformed NIH 3T3 cells but not in untransformed NIH 3T3 cells. RNAi-mediated knockdown of any of the 28 RESEs results in failure to recruit DNMT1 to the Fas promoter, loss of Fas promoter hypermethylation, and derepression of Fas expression. Analysis of five other epigenetically repressed genes indicates that Ras directs the silencing of multiple unrelated genes through a largely common pathway. Last, we show that nine RESEs are required for anchorage-independent growth and tumorigenicity of K-ras-transformed NIH 3T3 cells; these nine genes have not previously been implicated in transformation by Ras. Our results show that Ras-mediated epigenetic silencing occurs through a specific, complex, pathway involving components that are required for maintenance of a fully transformed phenotype.     

Reversing EphB2 depletion rescues cognitive functions in Alzheimer model

Amyloid-β oligomers may cause cognitive deficits in Alzheimer's disease by impairing neuronal NMDA-type glutamate receptors, whose function is regulated by the receptor tyrosine kinase EphB2. Here we show that amyloid-β oligomers bind to the fibronectin repeats domain of EphB2 and trigger EphB2 degradation in the proteasome. To determine the pathogenic importance of EphB2 depletions in Alzheimer's disease and related models, we used lentiviral constructs to reduce or increase neuronal expression of EphB2 in memory centres of the mouse brain. In nontransgenic mice, knockdown of EphB2 mediated by short hairpin RNA reduced NMDA receptor currents and impaired long-term potentiation in the dentate gyrus, which are important for memory formation. Increasing EphB2 expression in the dentate gyrus of human amyloid precursor protein transgenic mice reversed deficits in NMDA receptor-dependent long-term potentiation and memory impairments. Thus, depletion of EphB2 is critical in amyloid-β-induced neuronal dysfunction. Increasing EphB2 levels or function could be beneficial in Alzheimer's disease.     

认知诊断框架下的语言认知测验的实证分析与研究

采用认知诊断理论和技术,对初中生的中文阅读能力进行认知诊断测验分析。结果显示:通过推导得到的项目属性的定义和属性层级关系与专家的界定之间有一定的差异,这个差异会影响到对被试的属性掌握模式分类;通过推导得到项目属性定义和属性层关系的方法对于测验的分析和编制可以提供很好的参考作用,可以与专家界定的方法互为补充。     

The social brain: Insights from cognitive neuroscience

Cognitive neuroscience has provided powerful tools that now permit the investigation of human social cognition and behavior with unprecedented accuracy. This review summarizes some of the features of the human brain that differentiate it from the brains of other animals, some of the methods used in cognitive neuroscience, and concludes with an example of research from the author’s own lab that implicates the amygdala in emotion recognition, social judgment, and autism.     

脑认知功能与外科脑功能保护

 神经外科的手术模式是随着人类对脑结构和脑功能认识的深入、对脑保护要求的不断提高而进步发展的。目前,对脑功能的认识已从大脑神经功能延伸到认知功能,对认知功能的保护成为未来微创神经外科脑功能保护的新要求。以术中神经导航为连接手段,结合已知的脑认知功能定位,保护已知的脑认知功能,验证和探索未知的脑认知功能是未来神经外科脑功能保护的重要方向。     

Early brain growth in Homo erectus and implications for cognitive ability

Humans differ from other primates in their significantly lengthened growth period. The persistence of a fetal pattern of brain growth after birth is another important feature of human development. Here we present the results of an analysis of the 1.8-million-year-old Mojokerto child (Perning 1, Java), the only well preserved skull of a Homo erectus infant, by computed tomography. Comparison with a large series of extant humans and chimpanzees indicates that this individual was about 1 yr (0-1.5 yr) old at death and had an endocranial capacity at 72-84% of an average adult H. erectus. This pattern of relative brain growth resembles that of living apes, but differs from that seen in extant humans. It implies that major differences in the development of cognitive capabilities existed between H. erectus and anatomically modern humans.     

Spontaneous epigenetic variation in the Arabidopsis thaliana methylome

Heritable epigenetic polymorphisms, such as differential cytosine methylation, can underlie phenotypic variation. Moreover, wild strains of the plant Arabidopsis thaliana differ in many epialleles, and these can influence the expression of nearby genes. However, to understand their role in evolution, it is imperative to ascertain the emergence rate and stability of epialleles, including those that are not due to structural variation. We have compared genome-wide DNA methylation among 10 A. thaliana lines, derived 30 generations ago from a common ancestor. Epimutations at individual positions were easily detected, and close to 30,000 cytosines in each strain were differentially methylated. In contrast, larger regions of contiguous methylation were much more stable, and the frequency of changes was in the same low range as that of DNA mutations. Like individual positions, the same regions were often affected by differential methylation in independent lines, with evidence for recurrent cycles of forward and reverse mutations. Transposable elements and short interfering RNAs have been causally linked to DNA methylation. In agreement, differentially methylated sites were farther from transposable elements and showed less association with short interfering RNA expression than invariant positions. The biased distribution and frequent reversion of epimutations have important implications for the potential contribution of sequence-independent epialleles to plant evolution.     

政府在"人肉搜索"中的行政职能分析

"人肉搜索"是一种特殊的信息共享方式,其产生的社会根源涉及互联网、焦点社会问题和网民等多种社会因素,它是一把双刃剑,具有维护社会正义和异化为"网络暴政"的双重社会功能.文章认为"人肉搜索"需要规范和引导,因此,行政机关应该行使好自己的行政职能,对"人内搜索"加以规范和管制,促使"人肉搜索"走上更加规范化、合理化的轨道,在实现社会正义、舆论监督、防治腐败等方面发挥积极的作用,成为社会的"道德法庭"、人民反腐败的有力武器.     

姜黄素对老年鼠脑内氧化性平衡和星形胶质细胞的影响

以SD大鼠为动物模型,采用Western blotting、酶活性测定、免疫荧光和高效液相色谱-质谱(LC-MS)方法考察姜黄素处理12周后正常衰老大鼠皮层和海马的氧化性平衡和星形胶质细胞形态功能的变化.结果显示,姜黄素降低了老年鼠脑内氧化产物MDA和8-OHdG的含量,提升了γ-谷氨酰胺半胱氨酸合成酶(GCS)的活性并且促进GSH的产生,提示姜黄素可显著改善伴随正常衰老过程的脑内氧化性平衡;同时姜黄素可以抑制胶质纤维酸性蛋白(GFAP)的过度表达,提升GS活性,增加GDNF水平和D-丝氨酸含量,表明其抑制星形胶质细胞过度活化的同时也改善了星形胶质细胞的功能.     

一种优化的认知无线电网络分簇协作频谱感知算法

目前对于认知无线电分簇协作频谱感知算法的研究,大都认为每个簇均等地参与协作.没有考虑簇所经历的不同衰落对判决结果的影响.为有效解决这一问题,提出一种优化的认知无线电网络分簇协作频谱感知算法.该算法采用能量节省的分簇感知机制,充分考虑路径损耗与衰落对检测性能的影响.在满足虚警率和检测率的前提下,此方案不仅算法实现简单,而且在分簇结果上可以显著提高系统的稳定性,因此在信道环境复杂的情况下能有效提高频谱感知效率.     

关于B - 预不变凸函数的一个等价条件

在η(x,y)满足条件C,f(x)满足条件D的情况下,给出了B-预不变凸函数的一个等价条件,通过上述等价条件将Rn上的实值函数转化为[0,1]上的实值函数,简化了问题.     

美国认知教练研究综述与启示

知教练作为一种视导模式由柯斯塔和甘斯顿开创,在世界范围内尤其是在美国的中小学教师专业发展中得到的广泛的应用并取得了不错的效果。然而,该模式却没有引起我国学者和教师的重视。因此,对认知教练的理论与实践进行了概述,无疑对教师专业与教学的发展具有重要的指导意义。     

An analysis of the spatial and temporal changes in Chinese terrestrial ecosystem service functions

Since Westman(1977) and Ehrlich(1982) put forward the concepts of "the service of nature" and "ecosystem service functions",respectively,methods for conducting value accounting for them,and their practical application have become the subjects of intense study.Based on an overview of available research findings,we discuss three scientific hypotheses.First,the terrestrial ecosystem offers both positive and negative service functions.Second,changes in terrestrial ecosystem service functions lie not only in the number of ecosystem types and the coverage area of each type,but also in their quality.Third,the value of terrestrial ecosystem service functions should be assessed both in terms of the value stocked and the value added.We collected land use data from China during the period 1999-2008,and Normalized Difference Vegetation Index data based on remote sensing images from the Global Inventory Modeling and Mapping Studies for the same period.We then calculated and analyzed spatial and temporal changes in China’s terrestrial ecosystem service values over the 10-year period.Considering temporal change,the total value(stocked) of China’s terrestrial ecosystem service functions decreased from 6.82 trillion Yuan RMB in 1999 to 6.57 trillion Yuan RMB in 2008.During that period,the positive value decreased by 240.17 billion Yuan RMB and the negative value increased by 8.85 billion Yuan RMB.The decrease in total value lies mainly in the humidity control,soil formation,and waste recycling functions.The total value(added) of China’s terrestrial ecosystem service functions increased by 4.31 billion Yuan RMB in 2000,but decreased by 0.13 billion Yuan RMB in 2008(based on the constant price of China in 1999).The value(added) was a negative figure.From the perspective of spatial change,we can see that the supply of China’s terrestrial ecosystem service functions fell slightly over the past 10 years,mainly in Northeast and Southern China.As a result of human activities on ecosystems,the loss of ecosystem service functions’ value was relatively prominent in Shanxi and Gansu provinces,compared with an increase in value in Shaanxi Province.Terrestrial ecosystem service functions’ value per unit area was relatively high in mid-and East China,showing a prominent spatial change over the 10-year period,but low in Western China.Some conclusions are drawn after an in-depth analysis of the factors causing the spatial and temporal changes in China’s terrestrial ecosystem service functions,in the hope that our suggestions will be helpful for the management of China’s terrestrial ecosystems.     

认知无线网络中一种基于博弈的自适应功率控制算法

为了实现认知无线电中频谱分配公平性以及满足需要省电的情况,提出了一种基于博弈论的自适应功率控制算法,并证明了纳什均衡发射功率的存在性与唯一性。该算法不仅通过博弈论效用函数表达功率控制过程,解决了远近不公平现象和解决省电难题,而且通过设定信干噪比的最大与最小阀值,可以将不满足阀值的信干噪比值通过自适应加权公式,将其调整到阀值范围内,以满足省电需要。通过仿真分析可知,与其他算法比较,该算法不仅解决了认知无线电的远近不公平性现象,还可以通过减少发射功率,有效地解决了省电问题,而且当信干噪比在设定的阀值外时,通过自适应调整,使之在阀值范围内,减少了功率的浪费。     

Chromatin dynamics during epigenetic reprogramming in the mouse germ line

A unique feature of the germ cell lineage is the generation of totipotency. A critical event in this context is DNA demethylation and the erasure of parental imprints in mouse primordial germ cells (PGCs) on embryonic day 11.5 (E11.5) after they enter into the developing gonads. Little is yet known about the mechanism involved, except that it is apparently an active process. We have examined the associated changes in the chromatin to gain further insights into this reprogramming event. Here we show that the chromatin changes occur in two steps. The first changes in nascent PGCs at E8.5 establish a distinctive chromatin signature that is reminiscent of pluripotency. Next, when PGCs are residing in the gonads, major changes occur in nuclear architecture accompanied by an extensive erasure of several histone modifications and exchange of histone variants. Furthermore, the histone chaperones HIRA and NAP-1 (NAP111), which are implicated in histone exchange, accumulate in PGC nuclei undergoing reprogramming. We therefore suggest that the mechanism of histone replacement is critical for these chromatin rearrangements to occur. The marked chromatin changes are intimately linked with genome-wide DNA demethylation. On the basis of the timing of the observed events, we propose that if DNA demethylation entails a DNA repair-based mechanism, the evident histone replacement would represent a repair-induced response event rather than being a prerequisite.