Neuronal autophagy and neurodegenerative diseases

Autophagy is a dynamic cellular pathway involved in the turnover of proteins, protein complexes, and organelles through lysosomal degradation. The integrity of postmitotic neurons is heavily dependent on high basal autophagy compared to non-neuronal cells as misfolded proteins and damaged organelles cannot be diluted through cell division. Moreover, neurons contain the specialized structures for intercellular communication, such as axons, dendrites and synapses, which require the reciprocal transport of proteins, organelles and autophagosomes over significant distances from the soma. Defects in autophagy affect the intercellular communication and subsequently, contributing to neurodegeneration. The presence of abnormal autophagic activity is frequently observed in selective neuronal populations afflicted in common neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis. These observations have provoked controversy regarding whether the increase in autophagosomes observed in the degenerating neurons play a protective role or instead contribute to pathogenic neuronal cell death. It is still unknown what factors may determine whether active autophagy is beneficial or pathogenic during neurodegeneration. In this review, we consider both the normal and pathophysiological roles of neuronal autophagy and its potential therapeutic implications for common neurodegenerative diseases.     

多肽抑制剂抑制淀粉质多肽42构象转换的分子动力学模拟和结合自由能计算

应用分子动力学模拟和结合自由能计算方法研究了多肽抑制剂KLVFF、VVIA和LPFFD抑制淀粉质多肽42 (Aβ42)构象转换的分子机理. 结果表明, 三种多肽抑制剂均能够有效抑制Aβ42的二级结构由α-螺旋向β-折叠的构象转换. 另外, 多肽抑制剂降低了Aβ42分子内的疏水相互作用, 减少了多肽分子内远距离的接触, 有效抑制了Aβ42的疏水塌缩, 从而起到稳定其初始构象的作用. 这些抑制剂与Aβ42之间的疏水和静电相互作用(包括氢键)均有利于它们抑制Aβ42的构象转换. 此外, 抑制剂中的带电氨基酸残基可以增强其和Aβ42之间的静电相互作用(包括氢键), 并降低抑制剂之间的聚集, 从而大大增强对Aβ42构象转换的抑制能力. 但脯氨酸的引入会破坏多肽的线性结构, 从而大大降低其与Aβ42 之间的作用力. 上述分子模拟的结果揭示了多肽抑制剂KLVFF、VVIA和LPFFD抑制Aβ42构象转换的分子机理, 对于进一步合理设计Aβ的高效短肽抑制剂具有非常重要的理论指导意义.     

A new quantitative evaluation method of spiral drawing for patients with Parkinson’s disease based on a polar coordinate system with varying origin

Parkinson’s disease (PD) is a common disease of the central nervous system among the elderly, and its complex symptoms bring up challenges for the clinical diagnosis. In this paper, a new method based on a polar coordinate system with varying origin was proposed in order to quantitatively evaluate the performance in spiral drawing tasks for patients with Parkinson’s disease, since this method can assess the movement ability of spiral drawing before and after deep brain stimulation (DBS) among the patients. In this paper, three normal subjects and twelve PD patients participated in spiral drawing experiment. The hand movements of patients, before and after DBS, were recorded by a digitized tablet respectively in this experiment. And the variation of origin, radius, degree and other characteristics of hand movements were evaluated by introducing a set of parameters for feature extraction. The result showed that the proposed polar coordinate system embraced good performance in the quantitative evaluation of spiral drawing. Therefore, the proposed method overcame the limitation of data processes with fixed origin for diagnosis and evaluation, and by combining with extraction and analysis of characteristic parameters it had clinical significance in measuring the effectiveness of operation or treatment for the PD patients.     

CT小肠造影和消化内镜检查用于克罗恩病诊断的价值比较

目的探讨CT小肠造影检查和消化内镜对克罗恩病（CD）的诊断价值。方法选取24例CD患者,先行多层螺旋CT小肠造影（MSCT）检查,再行消化内镜检查,其中小肠MSCT检查24例,结肠镜检查22例,胶囊内镜检查2例。结果24例CD病患者小肠MSCT检查显示节段性肠壁增厚并异常强化,肠腔狭窄5例,木梳征5例,肠系膜淋巴结增生10例,腹腔脓肿1例,不完全肠梗阻2例。小肠MSCT检查中病变范围累积结肠22例,回肠24例,盲肠5例,直肠1例。小肠MSCT检查的敏感度、特异度、阳性预测值、阴性预测值分别为40％、77％、67％、67％,消化内镜为36％、61％、44％、53％。结论小肠MSCT检查是诊断小肠CD的一种有效的检查方法,并可判断病变的活动期,能较好的评估活动性CD,对指导临床治疗具有重要意义。     

PARK18基因多态性与中国汉族人帕金森病的相关性

目的研究PARK18基因多态性与中国汉族人群帕金森病(PD)的相关性,旨在探讨PD的发病机制,为PD的风险预测提供新的遗传标记.方法选取224例PD患者(PD组)及同期体检健康者309例(对照组),采用PCR、DNA测序等方法检测比较两组PARK18基因多态性位点,分析rs3129882与PD遗传易感性的相关性.结果两组对象rs3129882基因型频率和等位基因频率分布的差异均无统计学意义(均P>0.05).rs3129882多态性与PD发生风险的关联性在3种遗传模式下均无统计学意义(均P>0.05).结论本研究暂不支持中国汉族人群中PARKl8区域rs3129882位点单核苷酸多态性与PD的发生有显著关联性.     

Modeling plant disease with biological control of insect pests

Abstract

Introduction: This article discusses the problem of plant diseases that pose major threat to agriculture in several parts of the World. Herein, our focus is on viruses that are transmitted from one plant to another by insect vectors. We consider predators that prey on insect population leading to reduction in infection transmission of plant diseases. Methods: We formulate and analyze a deterministic model for plant disease by incorporating predators as biological control agents. Existence of equilibria and the stability of the model are discussed in-detail. Basic reproduction number R₀ of the proposed model is also computed and this helps in determining the impact of different key parameters on the transmission dynamics of disease. Additionally, the proposed model is extended to stochastic model and simulation results of both deterministic and stochastic models are compared and analyzed. Results: Our results of stochastic model show the less number of infected plants and insects compared to corresponding results for deterministic model. Also, our results analyze the impact of different key parameters on the equilibrium levels of infected plants and identify the key parameters. Discussion: Presented results are used to conclude and demonstrate that the biological control is effective in reducing the infection transmission of plant disease and there is a need to use plant-insect-specific predators to get desirable results.     

一种双正交心音小波的构造方法

为了提高小波分析在心音信号处理中的性能, 在分析小波构造理论的基础上, 构造了一种专门用于心音信号处理的小波基. 首先提出一种构造滤波器长度为偶数的紧支撑双正交小波的一般方法; 然后根据心音信号的特点, 讨论心音小波的构造原则和一种基于心音 小波族的心音信号合成模型, 并且在此基础上构造出心音小 波. 为了突出使用心音小波处理心音信号的先进性和实用性, 对心音小波进行了比较全面的理论和数值仿真分析. 实验结果表明, 相比常用的db, bior系列小波, 运用心音小波对心音信号进行处理, 能够获得更好的去噪效果、 更精确的心音分类信息以及更小的重构误差率, 为心音特征提取和身份识别的深入研究提供了一种新方法, 在表征心音个体特征的细节方面具有积极的意义. 本文根据应用对象设计专用小波的方法也为工程应用中小波基的选择提供了一种新途径. 关键词： 双正交小波 心音小波 构造方法 心音合成模型     

Pork Heart Tissue‐Based Chemiluminescence Biosensor for Pyruvic Acid

Abstract

A novel chemiluminescence (CL) animal tissue‐based sensor for pyruvic acid is presented in this paper. Pork heart tissue was chopped into small pieces and packed into a mini‐glass column as the recognition element. When pyruvic acid passed through the column, hydrogen peroxide was produced under the catalytic oxidation of oxygen by pyruvic acid oxidase present in the pork heart tissue. This produced hydrogen peroxide could react with luminol in alkaline solution to produce chemiluminescence in the presence of potassium hexacyanoferrate(III). The developed sensor system promises simplicity, fastness, stability, and sensitivity. Under the optimum conditions, CL intensities are proportional to the concentration of pyruvic acid in the range of 0.02–12 µmol/L, with a detection limit of 0.004 µmol/L (3σ). RSD is 2.3% for 0.5 µmol/L pyruvic acid (n=11). The sensor could be stable for 150 min by more than 100 times determination. The proposed method has been applied successfully to the analysis of pyruvic acid in biological samples. The results obtained by the proposed method are consistent with those obtained by spectrophotometry.     

An ESR Method for Determination of Serum Lipase Activity

Abstract

An ESR method for determination of serum lipase is described in principle and demonstrated in practice. A lipid soluble nitroxide is dissolved in an olive oil emulsion. When the intensity of the ESR signal of the nitroxide in the aqueous phase is monitored as a function of time after an aliquot of lipase is added a linear plot of peak height as a function of enzyme concentration is obtained.