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William Hancock-Cerutti Zheng Wu Peng Xu Narayana Yadavalli Marianna Leonzino Arun Kumar Tharkeshwar Shawn M. Ferguson Gerald S. Shadel Pietro De Camilli 《The Journal of cell biology》2022,221(7)
Mutations in VPS13C cause early-onset, autosomal recessive Parkinson’s disease (PD). We have established that VPS13C encodes a lipid transfer protein localized to contact sites between the ER and late endosomes/lysosomes. In the current study, we demonstrate that depleting VPS13C in HeLa cells causes an accumulation of lysosomes with an altered lipid profile, including an accumulation of di-22:6-BMP, a biomarker of the PD-associated leucine-rich repeat kinase 2 (LRRK2) G2019S mutation. In addition, the DNA-sensing cGAS-STING pathway, which was recently implicated in PD pathogenesis, is activated in these cells. This activation results from a combination of elevated mitochondrial DNA in the cytosol and a defect in the degradation of activated STING, a lysosome-dependent process. These results suggest a link between ER-lysosome lipid transfer and innate immune activation in a model human cell line and place VPS13C in pathways relevant to PD pathogenesis. 相似文献
74.
LRG‐1 promotes fat graft survival through the RAB31‐mediated inhibition of hypoxia‐induced apoptosis
Chiakang Ho Danning Zheng Jiaming Sun Dongsheng Wen Shan Wu Li Yu Ya Gao Yifan Zhang Qingfeng Li 《Journal of cellular and molecular medicine》2022,26(11):3153
Autologous adipose tissue is an ideal soft tissue filling material, and its biocompatibility is better than that of artificial tissue substitutes, foreign bodies and heterogeneous materials. Although autologous fat transplantation has many advantages, the low retention rate of adipose tissue limits its clinical application. Here, we identified a secretory glycoprotein, leucine‐rich‐alpha‐2‐glycoprotein 1 (LRG‐1), that could promote fat graft survival through RAB31‐mediated inhibition of hypoxia‐induced apoptosis. We showed that LRG‐1 injection significantly increased the maintenance of fat volume and weight compared with the control. In addition, higher fat integrity, more viable adipocytes and fewer apoptotic cells were observed in the LRG‐1‐treated groups. Furthermore, we discovered that LRG‐1 could reduce the ADSC apoptosis induced by hypoxic conditions. The mechanism underlying the LRG‐1‐mediated suppression of the ADSC apoptosis induced by hypoxia was mediated by the upregulation of RAB31 expression. Using LRG‐1 for fat grafts may prove to be clinically successful for increasing the retention rate of transplanted fat. 相似文献
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Tingting Zheng Lulu Liu Jiayi Liu Zhengxiang Zhang 《Journal of musculoskeletal & neuronal interactions》2022,22(2):296
There are few reports of rhabdomyolysis caused by anticoagulants, and it is extremely rare for it to be caused by dabigatran etexilate. An 86-year-old female experienced sudden muscle weakness and pain, a significant increase in Creatine kinase, and renal impairment after oral administration of dabigatran etexilate for 3 weeks. The enhanced thigh MRI showed abnormal signal in multiple thigh muscle groups, indicating that the lesions should be considered inflammatory diseases. In conclusion, the possibility of rhabdomyolysis should be ruled out when muscle weakness and myalgia occur at the beginning of dabigatran etexilate treatment. 相似文献
77.
系统地给出了中国实施增汇型CO2减排政策对宏观经济影响的模拟结果,所采用的模拟系统包括基于Pizer,Demeter,Zwaan工作发展的中国气候保护决策支持系统和中国经济可计算一般均衡(CGE)系统。研究结果表明,增汇型气候保护政策较其他单一的气候保护政策更有利于国家经济安全;虽然增汇型气候保护政策在短期内会对国家GDP产出造成影响,但从长远角度看,增汇型气候保护将带动经济的发展,是一项值得推广的减排政策。同时,发现中国实行每年增加4%的碳汇和实施4%能源替代以减少CO2排放控制率,辅助于0.2%的生产型CO2排放控制率,如果能够促进世界其它地区到2050年减排1990年的10%的CO,是一个合适的方案。 相似文献
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典型亚热带热分层水库秋季细菌群落垂直分布 总被引:6,自引:0,他引:6
水库在我国东南沿海地区是重要的饮用水水源地,对地区经济发展和社会稳定起到重要作用。选择亚热带地区典型的热分层水库——福建莆田东圳水库,于2011年秋季稳定分层期,以水体温度的垂直变化特征为依据进行分层采样。应用PCRDGGE和克隆测序的方法研究浮游细菌群落的垂直分布特征,利用多元统计分析揭示细菌群落与热分层水体理化指标之间的关系。结果显示:溶解氧、电导率、叶绿素a、总氮、氨氮及硝氮在上下层水体中的分布有显著差异,下层缺氧区细菌的ShannonWiener指数和DGGE条带数明显高于上层好氧区,表明东圳水库热分层水体中存在明显的物理、化学及生物分层现象。测序结果表明β-变形菌可能是东圳水库中占优势的细菌类群,统计结果提示溶解氧是显著影响细菌群落组成的环境因子。热分层水体的物理化学分层与水体细菌群落结构密切相关,提示水库生态学研究应对水体热分层给予重视。 相似文献
79.
应用酶标仪动力学方法监测棉蚜的抗药性 总被引:14,自引:0,他引:14
用酶标仪动力学测定法对3个抗性水平不同的棉蚜品系(R1、R2和R3)和1个敏感品系(S)的羧酸酯酶进行了研究,S、R1、R2和R3品系对α-乙酸萘酯(α-NA)的平均比活力分别为57.10、1171.69、1236.14和3293.00μmol·mgpro-1·min-1(分光光度计终点测定法)和38.24、85.27、198.14和762.25mOD·min-1·aphid-1(酶标仪动力学法)。终点测定法结果显示出不同品系间最大相差达60倍;酶标仪动力学测定法研究表明,4个棉蚜品系羧酸酶活性与其抗药性程度显著相关。通过对这两种方法的比较,酶动力学方法的测定结果更可靠。 相似文献
80.
Hongchao Lv Yongshuai Jiang Jin Li Mingming Zhang Zhenwei Shang Jiajia Zheng Xin Wu Panpan Liu Ruijie Zhang Huimin Yu 《Molecular biology reports》2014,41(3):1299-1310
The aim of this study was to assess the association of polymorphisms in the promoter region of the IL-10 gene with the risk of inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC). Fifteen studies (3,693 cases and 4,574 controls) were included in a meta-analysis of association between IL-10 ?1082G/A, ?819C/T and ?592C/A polymorphisms, and IBD, CD and UC using allele contrast and the recessive, dominant, and additive models. Hardy–Weinberg equilibrium was confirmed for each study. Heterogeneity and study quality were investigated using stratification analyses and sensitivity analyses. Polymorphism ?1082G/A showed significant association with CD, with odds ratios (ORs) for the GG + GA genotype and GG versus AA genotype of 1.278 (1.004–1.627) and 1.238 (1.027–1.492) in all subjects. Significant associations were found in the Caucasian subgroup using the allele contrast, dominant, and additive models. C-allele carriers of the ?819C/T polymorphism were at increased risk of IBD (OR 1.093, 95 % CI 1.004–1.190). Association with the ?819C/T polymorphism was also found in Caucasians with CD (C vs. T: OR 1.104, 95 % CI 1.010–1.206; CC + CT vs. TT: OR 1.328, 95 % CI 1.006–1.754; CC vs. TT: OR 1.339, 95 % CI 1.008–1.778), and with UC (CC vs. CT + TT: OR 1.188, 95 % CI 1.019–1.385). No significant association was found between the ?592C/A polymorphism and IBD, CD or UC. In conclusion, the meta-analysis demonstrated clear association between the IL-10 polymorphisms ?1082G/A and ?819C/T and the risk of IBD. 相似文献