Autophagic failure promotes the exocytosis and intercellular transfer of α-synuclein

The accumulation of abnormal protein aggregates is a major characteristic of many neurodegenerative disorders, including Parkinson''s disease (PD). The intracytoplasmic deposition of α-synuclein aggregates and Lewy bodies, often found in PD and other α-synucleinopathies, is thought to be linked to inefficient cellular clearance mechanisms, such as the proteasome and autophagy/lysosome pathways. The accumulation of α-synuclein aggregates in neuronal cytoplasm causes numerous autonomous changes in neurons. However, it can also affect the neighboring cells through transcellular transmission of the aggregates. Indeed, a progressive spreading of Lewy pathology among brain regions has been hypothesized from autopsy studies. We tested whether inhibition of the autophagy/lysosome pathway in α-synuclein-expressing cells would increase the secretion of α-synuclein, subsequently affecting the α-synuclein deposition in and viability of neighboring cells. Our results demonstrated that autophagic inhibition, via both pharmacological and genetic methods, led to increased exocytosis of α-synuclein. In a mixed culture of α-synuclein-expressing donor cells with recipient cells, autophagic inhibition resulted in elevated transcellular α-synuclein transmission. This increase in protein transmission coincided with elevated apoptotic cell death in the recipient cells. These results suggest that the inefficient clearance of α-synuclein aggregates, which can be caused by reduced autophagic activity, leads to elevated α-synuclein exocytosis, thereby promoting α-synuclein deposition and cell death in neighboring neurons. This finding provides a potential link between autophagic dysfunction and the progressive spread of Lewy pathology.     

聚多巴胺功能化的四氧化三钴纳米复合材料的制备及电催化性能

通过简单的自聚合反应在四氧化三钴表面包覆聚多巴胺膜,联合使用纳米铂和辣根过氧化物酶用于电催化还原过氧化氢。结果表明,聚多巴胺的使用增强后续纳米铂的负载量和辣根过氧化物酶的生物活性;四氧化三钴、纳米铂和辣根过氧化物酶的多重信号放大作用,大大增强了该复合材料的催化活性,提高了过氧化氢传感器的灵敏度。优化实验条件下,传感器对过氧化氢的检测范围为0.1~700 μmol·L^-1,检测限为0.08 μmol·L^-1。     

宽离子能量检测范围垂直引入反射式飞行时间质谱仪的研制

本实验室研制了国内首台宽离子能量检测范围飞行时间质谱仪。仪器采用紧凑式电子轰击源设计,配合离子透镜系统有效的调制离子流,飞行时间质量分析器采用了离子垂直引入式,双场加速和双场反射以及大尺寸MCP检测装置设计。仪器单离子信号半峰宽约2 ns,仪器分辨率优于1600FWHM,检测实际样品质量范围为1~127 amu(仪器理论质量检测上限优于800 amu),可检测离子能量范围优于2个数量级(3~140 eV)。若该TOF质量分析器与短瞬高压脉冲放电离子源耦合联用,可广泛应用于高能离子束的快速检测,如真空阴极放电对制备薄膜、离子注入材料的表征,导电材料的离子电荷态分布以及离子扩散速度的测定等。     

Graphene Oxide Protected Nucleic Acid Probes for Bioanalysis and Biomedicine

Recently, the binding ability of DNA on GO and resulting nuclease resistance have attracted increasing attention, leading to new applications both in vivo and in vitro. In vivo, nucleic acids absorbed on GO can be effectively protected from enzymatic degradation and biological interference in complicated samples, making it useful for targeted delivery, gene regulation, intracellular detection and imaging with high uptake efficiencies, high intracellular stability, and very low toxicity. In vitro, the adsorption of ssDNA on GO surface and desorption of dsDNA or well‐folded ssDNA from GO surface result in the protection and deprotection of DNA from nucleic digestion, respectively, which has led to target‐triggered cyclic enzymatic amplification methods (CEAM) for amplified detection of analytes with sensitivity 2–3 orders of magnitude higher than that of 1:1 binding strategies. This Concept article explores some of the latest developments in this field.     

径向电场对纳米管中水分子通量的影响

水分子在纳米通道中的运动对于生命活动、纳米器件的设计等都有着重要的意义. 现在已经证实, 在(6,6)的碳纳米管中, 水分子会以单分子水链的形式协同通过碳纳米管. 但是如何控制水分子的流量仍然是一个困难的课题. 本文研究了在径向电场作用下, 碳纳米管中水分子通量的变化趋势和碳纳米管的开关行为.发现在碳纳米管两端存在200 MPa的压力差时, 电场强度从1 V·nm^-1增加到3 V·nm^-1, 水分子通量线性减小. 当径向电场强度增加到3 V·nm^-1时, 碳纳米管处于关闭状态, 水分子无法通过碳纳米管. 进一步, 我们发现水偶极与碳纳米管管轴夹角的平均值的概率分布和翻转频率都与水分子在纳米管中的个数有很大关系.     

航空通信网络中复杂干扰过滤技术研究

航空通信环境中存在复杂的干扰信号,对正常的通信信号造成强烈的干扰。利用传统算法进行干扰信号过滤,无法避免由于干扰信号过于复杂导致过滤不充分的缺陷。提出一种基于加权残差优化算法的航空通信网络中复杂干扰过滤方法。对原始信号进行降频处理,能够消除峰值干扰信号,提高了信号的准确性。根据加权残差修正优化算法的相关原理,对通信信号进行残差优化处理,经过处理后的通信信号在受到干扰时会形成零陷,实现了对复杂干扰信号的过滤。实验结果表明,利用该算法进行航空通信网络中复杂干扰信号过滤,能够有效提高过滤的准确性,效果令人满意。     

基于LVDT的新型信号调理电路的设计研究

LVDT线性可变差动变压器,其输出信号为两个线圈的差动电压信号,能够实时的、高准确性的将机械位移信号转化成电信号。传统LVDT信号调理电路存在不易散热、检测修复困难、性价比低、适用范围窄等问题,本文设计了一种新型LVDT信号调理电路,该信号调理电路由驱动电路、整流归一化电路和滤波放大电路组成,测试结果能够匹配LVDT的输出信号特性,达到LVDT信号调理的各项指标要求,实验结果表明本设计具有一定的可行性。     

Bootstrapping and Askey–Wilson polynomials

The mixed moments for the Askey–Wilson polynomials are found using a bootstrapping method and connection coefficients. A similar bootstrapping idea on generating functions gives a new Askey–Wilson generating function. Modified generating functions of orthogonal polynomials are shown to generate polynomials satisfying recurrences of known degree greater than three. An important special case of this hierarchy is a polynomial which satisfies a four term recurrence, and its combinatorics is studied.     

Signal moments for the short‐time Fourier transform associated with Hardy–Sobolev derivatives

The short‐time Fourier transform has been shown to be a powerful tool for non‐stationary signals and time‐varying systems. This paper investigates the signal moments in the Hardy–Sobolev space that do not usually have classical derivatives. That is, signal moments become valid for non‐smooth signals if we replace the classical derivatives by the Hardy–Sobolev derivatives. Our work is based on the extension of Cohen's contributions to the local and global behaviors of the signal. The relationship of the moments and spreads of the signal in the time, frequency and short‐time Fourier domain are established in the Hardy–Sobolev space. Copyright © 2014 John Wiley & Sons, Ltd.     

Kinetics of radical‐molecule reactions in aqueous solution: A benchmark study of the performance of density functional methods

The performance of 18 density functional approximations has been tested for a very challenging task, the calculations of rate constants for radical‐molecule reactions in aqueous solution. Despite of the many difficulties involved in such an enterprise, six of them provide high quality results, and are recommended to that purpose. They are LC‐ωPBE, M06‐2X, BMK, B2PLYP, M05‐2X, and MN12SX, in that order. This trend was obtained using experimental data as reference. The other relevant aspects used in this benchmark are: (i) the SMD model for mimicking the solvent; (ii) the conventional transition state, the zero‐curvature tunneling correction, and the limit imposed by diffusion for the calculation of the rate constants. Even though changing any of these aspects might alter the trend in performance, at least, when using them, the aforementioned functionals can be successfully used to obtain high quality kinetic data for the kind of reactions investigated in this work. © 2014 Wiley Periodicals, Inc.