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Leucine-rich repeat kinase 2 (LRRK2) is a major causative gene of late-onset familial Parkinson’s disease (PD). The suppression of kinase activity is believed to confer neuroprotection, as most pathogenic variants of LRRK2 associated with PD exhibit increased kinase activity. We herein report a novel LRRK2 variant—p.G2294R—located in the WD40 domain, detected through targeted gene-panel screening in a patient with familial PD. The proband showed late-onset Parkinsonism with dysautonomia and a good response to levodopa, without cognitive decline or psychosis. Cultured cell experiments revealed that p.G2294R is highly destabilized at the protein level. The LRRK2 p.G2294R protein expression was upregulated in the patient’s peripheral blood lymphocytes. However, macrophages differentiated from the same peripheral blood showed decreased LRRK2 protein levels. Moreover, our experiment indicated reduced phagocytic activity in the pathogenic yeasts and α-synuclein fibrils. This PD case presents an example wherein the decrease in LRRK2 activity did not act in a neuroprotective manner. Further investigations are needed in order to elucidate the relationship between LRRK2 expression in the central nervous system and the pathogenesis caused by altered LRRK2 activity.  相似文献   
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A novel TiO2 thin film was prepared on the ceramic hollow fiber by the sol-gel method using poly(vinylpyrrolidone) (PVP) and polyvinyl alcohol (PVA) as additives. SEM images verified the formation of TiO2 layer with various thickness using different composition of titania sols. The effect of the PVP and PVA contents on the TiO2 sol properties, the separation and the antifouling performance of the ultrafiltration membranes were investigated thoroughly. When the contents of PVP and PVA were 1.0 wt% and 0.8 wt%, respectively, the resultant membrane showed a thickness of 0.55 μm with a pure water flux of 255 L m?2 h?1. In addition, the adherent foulant bovine serum albumin was applied to evaluate the antifouling performance. During the three fouling-recovery cycles, the flux recovery ratio and the flux decay ratio maintained about 99% and 30%. The BSA flux and rejection were still 169 L m?2 h?1 and 96.9% after the cycles, indicating a superior antifouling property.  相似文献   
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Parkinson’s disease (PD) is a neurodegenerative disorder that affects 1% of the population over the age of 60. Diabetes Mellitus (DM) is a metabolic disorder that affects approximately 25% of adults over the age of 60. Recent studies showed that DM increases the risk of developing PD. The link between DM and PD has been discussed in the literature in relation to different mechanisms including mitochondrial dysfunction, oxidative stress, and protein aggregation. In this paper, we review the common microRNA (miRNA) biomarkers of both diseases. miRNAs play an important role in cell differentiation, development, the regulation of the cell cycle, and apoptosis. They are also involved in the pathology of many diseases. miRNAs can mediate the insulin pathway and glucose absorption. miRNAs can also regulate PD-related genes. Therefore, exploring the common miRNA biomarkers of both PD and DM can shed a light on how these two diseases are correlated, and targeting miRNAs is a potential therapeutic opportunity for both diseases.  相似文献   
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One specific class of non-linear evolution equations, known as the Tzitzéica-type equations, has received great attention from a group of researchers involved in non-linear science. In this article, new exact solutions of the Tzitzéica-type equations arising in non-linear optics, including the Tzitzéica, Dodd–Bullough–Mikhailov and Tzitzéica–Dodd–Bullough equations, are obtained using the expa function method. The integration technique actually suggests a useful and reliable method to extract new exact solutions of a wide range of non-linear evolution equations.  相似文献   
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The n-type thermoelectric Bi1.9Lu0.1Te3 was prepared by microwave-solvothermal method and spark plasma sintering. The magnetic field and temperature dependences of transverse magnetoresistance measured within temperature 2–200 K interval allow finding the peculiarities characteristic for strongly disordered and inhomogeneous semiconductors. The first peculiarity is due to appearance of linear-in-magnetic field contribution to the total magnetoresistance reflected in a crossover from quadratic magnetoresistance at low magnetic fields to linear magnetoresistance at high magnetic fields. The linear magnetoresistance can result from the Hall resistance picked up from macroscopically distorted current paths due to local variations in stoichiometry of the compound studied. The second peculiarity is that both linear magnetoresistance magnitude and crossover field are functions of carrier mobility which is in agreement with the Parish and Littlewood model developed for disordered and inhomogeneous semiconductors. An increase in the mobility due to a decrease in temperature is accompanied by an increase in the magnetoresistance magnitude and a decrease in the crossover field. Finally, the third peculiarity is related to the remarkable deviation of the total magnetoresistance measured at various temperatures from the Kohler's rule. Presence of strong inhomogeneity and disorder in the Bi1.9Lu0.1Te3 structure concluded from the magnetoresistance peculiarities can be responsible for the remarkable reduction in the total thermal conductivity of this compound.  相似文献   
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为探讨喷油方式对齿面温度的影响,以斜齿轮为研究对象,通过CFD仿真和试验研究不同喷油方式对斜齿轮齿面温度的影响。针对斜齿轮喷油润滑过程的特点,分析其齿面摩擦生热量,简化轮齿喷油润滑计算模型,并基于CFX进行齿面对流换热仿真研究,得到了不同喷油方式下的齿面温度;基于功率开放式斜齿轮试验平台,对不同喷油方式下的齿面温度进行了试验测量,与仿真计算结果进行对比分析。结果表明:在高速重载斜齿轮传动系统中,啮出侧喷油润滑的方式比啮入侧喷油润滑方式的冷却降温效果要好。  相似文献   
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