Synaptic dysfunction in Huntington’s disease: a new perspective

Huntington’s disease (HD) is caused by a polyglutamine expansion in the protein huntingtin and is characterized by intraneuronal inclusions and widespread neuronal death at the late stage of the disease. In research, most of the emphasis has been on understanding the cell death and its mechanisms. Until recently, it was believed that the vast majority, if not all, of the symptoms in HD are a direct consequence of neurodegeneration. However, increasing evidence shows that subtle alterations in synaptic function could underlie the early symptoms. It is of particular interest to understand the nature of this neuronal dysfunction. Normal huntingtin interacts with various cytoskeletal and synaptic vesicle proteins that are essential for exocytosis and endocytosis. Altered interactions of mutant huntingtin with its associated partners could contribute to abnormal synaptic transmission in HD. This review describes recent advances in understanding synaptic dysfunction in HD.Received 2 March 2005; received after revision 13 April 2005; accepted 19 April 2005     

2019年深空探测热点回眸

深空探测是空间科学探索与发现的重要方式之一。2019年全球在轨工作的深空探测任务有29个,皆为非载人航天任务,主要开展了月球、火星和小行星等的探测、深空太阳观测及日-地L1点空间天气监测和L2点空间天文观测。在纪念人类登月50周年之际,美国加快推动重返月球的阿尔忒弥斯计划,中国嫦娥四号任务着陆器和玉兔二号月球车对月球背面的就位探测和巡视勘察陆续产出一批国际关注的科学成果。美国新视野号任务飞掠柯伊伯带小天体"2014 MU69"的首个科学成果揭示了该"接触双星系统"的发展、地质与构成。日本隼鸟二号任务完成对"龙宫"小行星的两次采样探测、启程返回地球。除了"史诗级"的太阳探测帕克号任务,被"遗忘"在L1点的多个超期服役的空间天气监测科学任务如SOHO、WIND等表现依然稳定和出色。2020年,人类将迎来探测火星的新发射窗口,中国、美国和欧洲等即将实施的多个火星任务引人注目。     

2019年人工智能研发热点回眸

2019年,人工智能学科各分支取得了一系列进展,并在众多领域得到广泛应用。遴选5G通信网络、区块链技术、脑机接口技术、AI芯片、AI教育、人脸识别、军事智能化等作为代表,回顾了2019年人工智能领域的热点事件。     

整建制管理模式下救治新型冠状病毒肺炎患者的应用探讨

医疗队应用整建制接管病区的模式,通过明确分工、明晰职责,实施制度化、流程化管理,开展多学科团队协作和感控并重的多元化救治策略,对新型冠状病毒肺炎患者进行救治,发现整建制管理救治在规范化管理、增强医护团队协调合作、加强医院感染防控、提升患者救治水平等方面效果良好,对高效开展新型冠状病毒肺炎救治具有良好的适用性,值得推广。     

低氧诱导因子在疾病治疗中的新进展——2019年诺贝尔生理学或医学奖成果简析

 低氧诱导因子是一种异二聚体结构的DNA结合转录因子，它可以与特定的核辅因子结合，激活多种基因，在缺氧条件下优化氧的利用。美国癌症学家William G.Kaelin Jr、英国医学家Sir Peter J.Ratcliffe和美国医学家Gregg L.Semenza因发现了细胞如何感知和适应氧可用性，获得了2019年的诺贝尔生理学或医学奖，其中HIF发挥了重要的作用。介绍了HIF在肾性贫血、肿瘤、心血管疾病等治疗中的研究进展，探讨了其对人类健康的意义。     

Response to one point in Gingras’s review of Gravity’s shadow

Yves Gingras says of my book Gravity’s shadow that it is too long, the style is poor, and in its 870 pages there is nothing new that is not to be regretted. Gingras’s purity of vision would be a cause for congratulation were it not for the appalling implications of one of his claims. For the sake of the future of social science—indeed for the sake of the future of civilisation—it is impossible to leave unchallenged the idea that respondents, who don’t like to see their use of data questioned, are to be commended when they withhold those data from public scrutiny.     

Chromosome 13 dementias

The importance of cerebral amyloid deposition in the mechanism of neurodegeneration is still debatable. Classic arguments are usually centered on amyloid β(Aβ) and its role in the neuronal loss characteristic of Alzheimer’s disease, the most common form of human cerebral amyloidosis. Two non-Aβ cerebral amyloidoses, familial British and Danish dementias (FBD and FDD), share many aspects of Alzheimer’s disease, including the presence of neurofibrillary tangles, parenchymal preamyloid and amyloid deposits, cerebral amyloid angiopathy and a variety of amyloid-associated proteins and inflammatory components. Both early-onset conditions are linked to specific mutations at or near the stop codon of the chromosome 13 gene BRI2 that cause generation of longer-than-normal protein products. Furin-like processing of these longer precursors releases two de novo-created peptides, ABri and ADan, which deposit as amyloid fibrils in FBD and FDD, respectively. Due to the similar pathology generated by completely unrelated amyloid subunits, FBD and FDD, collectively referred to as chromosome 13 dementias, constitute alternative models for studying the role of amyloid deposition in the mechanism of neuronal cell death.Received 4 March 2005; received after revision 24 April 2005; accepted 26 April 2005     

Causality and forecasting in incomplete systems

In this paper we examine how causality inference and forecasting within a bivariate VAR, consisting of y(t) and x(t), are affected by the omission of a third variable, w(t), which causes (a) none, (b) one, and (c) both variables in the bivariate system. We also derive conditions under which causality inference and forecasting are invariant to the selection of a bivariate or a trivariate model. The most general condition for the invariance of both causality and forecasting to model selection is shown to require the omitted variable not to cause any of the variables in the bivariate system, although it allows the omitted variable to be caused by the other two. We also show that the conditions for one-way causality inference to be invariant to model selection are not sufficient to ensure that forecasting will also be invariant to the model selected. Finally, we present a numerical illustration of the potential losses, in terms of the variance of the forecast, as a function of the forecast horizon and for alternative parameter values—they can be rather large, as the omission of a variable can make the incomplete model unstable. © 1997 John Wiley & Sons, Ltd.     

生命的低氧适应——2019年度诺贝尔生理学或医学奖成果解析

氧的利用和调节是高等生命赖以生存的基本条件,威廉·凯林、彼得·拉特克利夫和格雷格·塞门扎3位科学家因发现细胞感知和适应氧气供应的相关机制而获得了2019年度诺贝尔生理学或医学奖。他们发现低氧诱导因子1(hypoxia-inducible factors 1,HIF-1)广泛存在于急、慢性缺氧细胞中,是细胞适应低氧的重要转录因子。HIF-1水平受氧气含量的调节。高氧条件下,HIF-1被修饰进而降解;低氧条件下,HIF-1不被降解,并通过转录调节引起促红细胞生成素等低氧相关基因的表达。本文通过介绍HIF-1的发现和基本分子机制,探讨其在临床中的应用价值。     

基于社会分工的流行病动力学建模与仿真研究

疫情预测是流行病防控体系中的重要一环,准确建立流行病演化动力学模型具有十分重要的意义。针对现有流行病建模方法中鲜有考虑群体中的社会分工问题,拟将整个群体划分为普通居民、社会服务人员和一线医务工作人员等三个子群,基于异质均匀混合理论,利用子群邻接矩阵表示个体间的接触关系,建立了流行病传播与演化的延时动力学模型。仿真结果表明,本文方法更符合实际情况,可为流行病动力学建模与仿真提供一种有效手段,对武汉疫情做了动力学建模与仿真分析。