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.     

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.     

Human Plasma Metabolic Profiles of Coronary Heart Disease by Gas Chromatography-Mass Spectrometry with Monte Carlo Tree Approach

Metabolomics is a useful approach to explore systemic metabolic variation and to elucidate disease mechanisms. In this study, human plasma metabolic profiles of coronary heart disease (CHD) patients and healthy controls were obtained by gas chromatography-mass spectrometry (GC-MS). A relatively new pattern recognition method, the Monte Carlo tree (MCTree) approach, was used to explore metabolic differences between CHD patients and healthy controls. In this way, CHD patients with different severity of coronary atherosclerosis were classified by the corresponding metabolic profiles. Furthermore, important metabolites contributing to the classification were screened and identified by their mass spectra. Several potential biomarkers were discussed in some detail. The results demonstrated that the proposed method might be a useful tool for discovering metabolic abnormalities and potential biomarkers for diseases.     

A preliminary study of blood-oxygen-level-dependent MRI in patients with chronic kidney disease

Background

Blood-oxygen-level-dependent (BOLD) magnetic resonance imaging (MRI) can provide regional measurements of oxygen content using deoxyhemoglobin paramagnetic characteristics. The apparent relaxation rate or R2*(=1/T2*) can be determined from the slope of log (intensity) versus echo time and is directly proportional to the tissue content of deoxyhemoglobin. Thus, as the level of deoxyhemoglobin increases, T2* will decrease, leading to an increase in R2*. Chronic kidney disease (CKD) can affect oxygenation levels in renal parenchyma, which influences the clinical course of the disease. The goal of this study was to detect and assess renal oxygenation levels in CKD using BOLD MRI.

Methods

Fifteen healthy subjects and 11 patients with CKD underwent a renal scan using multigradient-recalled-echo sequence with eight echoes. R2* (1/s) of the renal cortex and medulla was measured on BOLD images. Of the 11 patients, nine had biopsy-proven chronic glomerulonephritis, and two had a similar diagnosis based on clinical symptoms and investigations.

Results

Mean medullary R2* (MR2*) and cortex R2* (CR2*) levels were significantly higher in patients (22 kidneys, MR2*=24.79±4.84 s⁻¹, CR2*=18.97±2.72 s⁻¹) than in controls (30 kidneys, MR2*=19.98±1.19 s⁻¹, CR2*=16.03±1.23 s⁻¹) (P<.01), and MR2* was increased more than CR2*. Medullary to cortical R2* ratios (MCR2*) of patients were significantly increased when compared with those of controls (P<.01). In the patient group, estimated glomerular filtration rate levels were greater than or equal to 60 ml/min/1.73 m² in six patients (12 kidneys), whose MR2* and CR2* were also significantly higher than those of controls (P<.01). Serum creatinine levels were normal in seven patients (14 kidneys), whose MR2*, CR2* and MCR2* were also higher than those of controls (P<.01).

Conclusions

BOLD MRI can be used to evaluate changes in renal oxygenation in CKD, suggesting that it has the potential to be an excellent noninvasive tool for the evaluation of renal function.