Defective Mitochondrial Dynamics Is an Early Event in Skeletal Muscle of an Amyotrophic Lateral Sclerosis Mouse Model

Mitochondria are dynamic organelles that constantly undergo fusion and fission to maintain their normal functionality. Impairment of mitochondrial dynamics is implicated in various neurodegenerative disorders. Amyotrophic lateral sclerosis (ALS) is an adult-onset neuromuscular degenerative disorder characterized by motor neuron death and muscle atrophy. ALS onset and progression clearly involve motor neuron degeneration but accumulating evidence suggests primary muscle pathology may also be involved. Here, we examined mitochondrial dynamics in live skeletal muscle of an ALS mouse model (G93A) harboring a superoxide dismutase mutation (SOD1^G93A). Using confocal microscopy combined with overexpression of mitochondria-targeted photoactivatable fluorescent proteins, we discovered abnormal mitochondrial dynamics in skeletal muscle of young G93A mice before disease onset. We further demonstrated that similar abnormalities in mitochondrial dynamics were induced by overexpression of mutant SOD1^G93A in skeletal muscle of normal mice, indicating the SOD1 mutation drives ALS-like muscle pathology in the absence of motor neuron degeneration. Mutant SOD1^G93A forms aggregates inside muscle mitochondria and leads to fragmentation of the mitochondrial network as well as mitochondrial depolarization. Partial depolarization of mitochondrial membrane potential in normal muscle by carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) caused abnormalities in mitochondrial dynamics similar to that in the SOD1^G93A model muscle. A specific mitochondrial fission inhibitor (Mdivi-1) reversed the SOD1^G93A action on mitochondrial dynamics, indicating SOD1^G93A likely promotes mitochondrial fission process. Our results suggest that accumulation of mutant SOD1^G93A inside mitochondria, depolarization of mitochondrial membrane potential and abnormal mitochondrial dynamics are causally linked and cause intrinsic muscle pathology, which occurs early in the course of ALS and may actively promote ALS progression.     

不同方法治疗飞行人员慢性失眠症的疗效比较

目的:飞行人员中睡眠问题发生率高,影响白天工作效能,危及飞行安全,寻找安全有效治疗方法为保证飞行十分必要,本实验观察不同治疗方法在治疗飞行人员慢性失眠的临床疗效,为飞行人员慢性失眠的临床治疗提供一种安全有效的措施。方法:将我院自2007年至2013年收治的52例飞行人员中的慢性失眠患者,排除严重影响睡眠的器质性疾病,随机分为舒乐安定组、中药治疗组和耳针及生物反馈联合治疗组。分别在治疗前、治疗结束后第2天采用匹兹堡睡眠质量指数(PSQI)对患者的睡眠质量进行评价。结果:治疗结束后3组PSQI均较治疗前均有所改善,其中舒乐安定治疗组优于中成药及耳针及生物反馈联合治疗组,差别有统计学意义(P0.05),中成药物治疗组与耳针及生物反馈联合治疗组无明显统计学差异(P0.05)。但对于重度的睡眠障碍,单独采用舒眠胶囊或生物反馈治疗,治疗效果欠佳。结论:舒乐安定治疗失眠疗效确切,但由于其影响工作效能,危及飞行安全较少使用,中成药物、耳针及生物反馈治疗安全有效,病人易于接受,是较好的治疗飞行人员慢性失眠的方法。     

Epidemiology of Hepatitis E Virus in China: Results from the Third National Viral Hepatitis Prevalence Survey, 2005–2006

In China, hepatitis E virus (HEV) is prevalent and causes disease, but its epidemiological profile is not well understood. We used a commercial enzyme-linked immunosorbent assay to detect total antibodies to hepatitis E virus in 15,862 serum samples collected during the Third National Viral Hepatitis Prevalence Survey. The results were analyzed to calculate estimates of HEV seroprevalence and to examine the effects of some putative risk factors. The seroprevalence of HEV in the general Chinese population during the period from 2005 through 2006 was 23.46% (95% confidence interval [CI], 18.41%–28.50%). The farming population, the age group of 15–60 year olds, and those living in the Midwest or Mideast region and in Xinjiang province had the highest seroprevalence estimates. The prevalence of HEV is high in China. The seroprevalence rate of HEV shows an unbalanced distribution among areas with different geographic location and economic development levels. The characteristics of the distribution associated may be due to the route of HEV transmission (via contaminated water or animal reservoirs). Within the same region, the seroprevalence of HEV is generally increased with age.     

A Reconstruction Method Based on AL0FGD for Compressed Sensing in Border Monitoring WSN System

In this paper, to monitor the border in real-time with high efficiency and accuracy, we applied the compressed sensing (CS) technology on the border monitoring wireless sensor network (WSN) system and proposed a reconstruction method based on approximately l₀ norm and fast gradient descent (AL0FGD) for CS. In the frontend of the system, the measurement matrix was used to sense the border information in a compressed manner, and then the proposed reconstruction method was applied to recover the border information at the monitoring terminal. To evaluate the performance of the proposed method, the helicopter sound signal was used as an example in the experimental simulation, and three other typical reconstruction algorithms 1)split Bregman algorithm, 2)iterative shrinkage algorithm, and 3)smoothed approximate l₀ norm (SL0), were employed for comparison. The experimental results showed that the proposed method has a better performance in recovering the helicopter sound signal in most cases, which could be used as a basis for further study of the border monitoring WSN system.     

High Concentration of Gadolinium Ion Modifying Isolated Rice Mitochondrial Biogenesis

Mitochondria play an important role in plant growth and development, cooperating with the endoplasmic reticulum and nucleus. Gadolinium, one of the rare earth elements, is an inhibitor of stretch-activated calcium channels located on the endoplasmic reticulum and plasma membrane and has no effect on nuclear calcium variation in plant cells. We analyzed the effects of Gd³⁺ on mitochondria function by monitoring mitochondrial swelling, changes of membrane fluidity, and transmembrane potential collapse and by observing mitochondrial ultrastructure. We found that high concentration of Gd³⁺ induces rice mitochondrial dysfunction through mitochondrial permeability transition (MPT). The protection of DTT and EDTA demonstrate that Gd³⁺ blocks the inner membrane ion channel through thiol chelation.     

A New 2α,5α,10β,14β-tetraacetoxy-4(20),11-taxadiene (SIA) Derivative Overcomes Paclitaxel Resistance by Inhibiting MAPK Signaling and Increasing Paclitaxel Accumulation in Breast Cancer Cells

Tumor resistance due to multiple mechanisms seriously hinders the efficacy of chemotherapy drugs such as paclitaxel. The most widely studied P-glycoprotein inhibitors still have limited ability to reverse resistance in the clinic. In this study, NPB304, a novel Sinenxan A (SIA) derivative, was found to significantly sensitize resistant breast cancer cells to paclitaxel in vitro and in vivo. Treatment with NPB304 increased paclitaxel-induced apoptosis in a p53-dependent manner through PARP cleavage. Importantly, NPB304 enhanced the antitumor effect of paclitaxel in resistant breast tumor xenografts in nude mice without significantly affecting weight loss. NPB304 regulated cell resistance through inhibition of MAPK pathway components, including p-ERK and p-p38. Moreover, NPB304 increased paclitaxel accumulation by affecting P-gp function. In addition to increasing Rhodamine 123 accumulation, NPB304 promoted bidirectional permeability but decreased the efflux ratio of paclitaxel in a Caco-2 monolayer model, thereby increasing the intracellular concentration of paclitaxel. Similarly, NPB304 increased the concentration of paclitaxel in the resistant tumor tissue. Hence, NPB304 is a novel compound that promotes the sensitization of resistant cells to paclitaxel through multiple mechanisms and has the potential for use in combination therapies to treat resistant breast cancer.     

SENP3 senses oxidative stress to facilitate STING-dependent dendritic cell antitumor function

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