A Novel LRRK2 Variant p.G2294R in the WD40 Domain Identified in Familial Parkinson’s Disease Affects LRRK2 Protein Levels

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.     

MicroRNAs,Parkinson’s Disease,and Diabetes Mellitus

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.     

Dual effect synergistically triggered Ce:(Y,Tb)3(Al,Mn)5O12 transparent ceramics enabling a high color-rendering index and excellent thermal stability for white LEDs

Ce:Y₃Al₅O₁₂ transparent ceramics (TCs) with appropriate emission light proportion and high thermal stability are significant to construct white light emitting diode devices with excellent chromaticity parameters. In this work, strategies of controlling crystal-field splitting around Ce³⁺ ion and doping orange-red emitting ion, were adopted to fabricate Ce:(Y,Tb)₃(Al,Mn)₅O₁₂ TCs via vacuum sintering technique. Notably, 85.4 % of the room-temperature luminescence intensity of the TC was retained at 150 °C, and the color rendering index was as high as 79.8. Furthermore, a 12 nm red shift and a 16.2 % increase of full width at half maximum were achieved owing to the synergistic effects of Tb³⁺ and Mn²⁺ ions. By combining TCs with a 460 nm blue chip, a warm white light with a low correlated color temperature of 4155 K was acquired. Meanwhile, the action mechanism of Tb³⁺ ion and the energy transfer between Ce³⁺ and Mn²⁺ ions were verified in prepared TCs.     

儿童用品TBT通报数据可视化预警研究

探索采用数据可视化技术分析儿童用品TBT通报数据,以可视化图形图像呈现通报热点并揭示趋势信息,提出对策与建议,助力为儿童用品产业升级、TBT预警数据分析和信息传播工作提供新思路,提高中小企业的国外市场准入机会。     

Multi-discharge EDM coring of single crystal SiC ingot by electrostatic induction feeding method

A new technique of EDM coring of single crystal silicon carbide (SiC) ingot was proposed in this paper. Currently single crystal SiC devices are still of high cost due to the high cost of bulk crystal SiC material and the difficulty in the fabrication process of SiC. In the manufacturing process of SiC ingot/wafer, localized cracks or defects occasionally occur due to thermal or mechanical causes resulted from fabrication processes which may waste the whole piece of material. To save the part of ingot without defects and maximize the material utilization, the authors proposed EDM coring method to cut out a no defect ingot from a larger diameter ingot which has localized defects. A special experimental setup was developed for EDM coring of SiC ingot in this study and its feasibility and machining performance were investigated. Meanwhile, in order to improve the machining rate, a novel multi-discharge EDM coring method by electrostatic induction feeding was established, which can realize multiple discharges in single pulse duration. Experimental results make it clear that EDM coring of SiC ingot can be carried out stably using the developed experimental setup. Taking advantage of the newly developed multi-discharge EDM method, both the machining speed and surface integrity can be improved.