'Rejuvenation' protects neurons in mouse models of Parkinson's disease

Why dopamine-containing neurons of the brain's substantia nigra pars compacta die in Parkinson's disease has been an enduring mystery. Our studies suggest that the unusual reliance of these neurons on L-type Ca(v)1.3 Ca2+ channels to drive their maintained, rhythmic pacemaking renders them vulnerable to stressors thought to contribute to disease progression. The reliance on these channels increases with age, as juvenile dopamine-containing neurons in the substantia nigra pars compacta use pacemaking mechanisms common to neurons not affected in Parkinson's disease. These mechanisms remain latent in adulthood, and blocking Ca(v)1.3 Ca2+ channels in adult neurons induces a reversion to the juvenile form of pacemaking. Such blocking ('rejuvenation') protects these neurons in both in vitro and in vivo models of Parkinson's disease, pointing to a new strategy that could slow or stop the progression of the disease.     

Dopamine neurons derived from human ES cells efficiently engraft in animal models of Parkinson's disease

Human pluripotent stem cells (PSCs) are a promising source of cells for applications in regenerative medicine. Directed differentiation of PSCs into specialized cells such as spinal motoneurons or midbrain dopamine (DA) neurons has been achieved. However, the effective use of PSCs for cell therapy has lagged behind. Whereas mouse PSC-derived DA neurons have shown efficacy in models of Parkinson's disease, DA neurons from human PSCs generally show poor in vivo performance. There are also considerable safety concerns for PSCs related to their potential for teratoma formation or neural overgrowth. Here we present a novel floor-plate-based strategy for the derivation of human DA neurons that efficiently engraft in vivo, suggesting that past failures were due to incomplete specification rather than a specific vulnerability of the cells. Midbrain floor-plate precursors are derived from PSCs 11 days after exposure to small molecule activators of sonic hedgehog (SHH) and canonical WNT signalling. Engraftable midbrain DA neurons are obtained by day 25 and can be maintained in vitro for several months. Extensive molecular profiling, biochemical and electrophysiological data define developmental progression and confirm identity of PSC-derived midbrain DA neurons. In vivo survival and function is demonstrated in Parkinson's disease models using three host species. Long-term engraftment in 6-hydroxy-dopamine-lesioned mice and rats demonstrates robust survival of midbrain DA neurons derived from human embryonic stem (ES) cells, complete restoration of amphetamine-induced rotation behaviour and improvements in tests of forelimb use and akinesia. Finally, scalability is demonstrated by transplantation into parkinsonian monkeys. Excellent DA neuron survival, function and lack of neural overgrowth in the three animal models indicate promise for the development of cell-based therapies in Parkinson's disease.     

A Drosophila model of Parkinson's disease

Parkinson's disease is a common neurodegenerative syndrome characterized by loss of dopaminergic neurons in the substantia nigra, formation of filamentous intraneuronal inclusions (Lewy bodies) and an extrapyramidal movement disorder. Mutations in the alpha-synuclein gene are linked to familial Parkinson's disease and alpha-synuclein accumulates in Lewy bodies and Lewy neurites. Here we express normal and mutant forms of alpha-synuclein in Drosophila and produce adult-onset loss of dopaminergic neurons, filamentous intraneuronal inclusions containing alpha-synuclein and locomotor dysfunction. Our Drosophila model thus recapitulates the essential features of the human disorder, and makes possible a powerful genetic approach to Parkinson's disease.     

The corticomotoneurone connection is normal in Parkinson's disease

Voluntary movements in Parkinson's disease are initiated and executed slowly. It is assumed that the motor cortex and its output pathway are intact and that bradykinesia is due to abnormal motor commands delivered to a normal corticospinal system. We have tested this assumption using electrical stimulation of the motor cortex through the scalp in three patients with severe Parkinson's disease, studied during fluctuations from relatively normal mobility when receiving drugs (ON) to severe bradykinesia when not receiving drugs (OFF). Thresholds and latencies for motor cortex stimulation to excite thumb flexor muscles and the resulting fast mechanical responses were the same in both ON and OFF conditions, even though the patients were unable to execute fast thumb flexion movements voluntarily when OFF. We conclude that the excitability and conduction velocity of the corticospinal motor pathways are normal in Parkinson's disease.     

异步电机的交直轴模型及其仿真

介绍了三相异步电动机的直轴和交轴模型的建立方法，并利用MATLAB语言对两种模型进行仿真．仿真数据包括定子电流、电磁转矩以及转速．并针对仿真结果，比较两种模型的特点以及各自所适合应用的场合，所得结果对交流凋速系统的优化设计以及异步电机的故障状态下的数据获取具有参考价值。     

藏药复方珍珠丸对记忆获得障碍动物模型的智力影响

目的研究珍珠丸改善记忆获得障碍动物模型的智力影响. 方法采用腹腔注射东莨菪碱法制作记忆获得障碍动物模型, 检测珍珠丸对记忆获得障碍动物模型的逃避潜伏期、错误次数影响. 结果珍珠丸可以提高记忆获得障碍动物模型逃避潜伏期、降低其错误次数. 结论珍珠丸可以改善记忆获得障碍动物模型的智力.     

Overlap of internal models in motor cortex for mechanical loads during reaching

A hallmark of the human motor system is its ability to adapt motor patterns for different environmental conditions, such as when a skilled ice-hockey player accurately shoots a puck with or without protective equipment. Each object (stick, shoulder pad, elbow pad) imparts a distinct load upon the limb, and a key problem in motor neuroscience is to understand how the brain controls movement for different mechanical contexts. We addressed this issue by training non-human primates to make reaching movements with and without viscous loads applied to the shoulder and/or elbow joints, and then examined neural representations in primary motor cortex (MI) for each load condition. Even though the shoulder and elbow loads are mechanically independent, we found that some neurons responded to both of these single-joint loads. Furthermore, changes in activity of individual neurons during multi-joint loads could be predicted from their response to subordinate single-joint loads. These findings suggest that neural representations of different mechanical contexts in MI are organized in a highly structured manner that may provide a neural basis for how complex motor behaviour is learned from simpler motor tasks.     

Regenerative medicine and human models of human disease

Recent advances in stem-cell technology are now allowing the mechanisms of human disease to be studied in human cells. A new era for regenerative medicine is arising from such disease models, extending beyond early cell-based therapies and towards evaluating genetic variation in humans and identifying the molecular pathways that lead to disease, as well as targets for therapy.     

三星电子公司与华为技术公司专利布局的比较

比较分析国内外通信技术领域典型公司的专利布局,可以为我国通信产业的发展提供重要参考。在专利申请地域布局方面,三星电子公司专利在国外和国际的申请比例明显高于华为技术公司;从专利的热点技术领域布局看,三星电子公司专利的涵盖领域比华为技术公司更加多元化。加强专利的国外和国际保护、跟踪世界研发前沿热点领域,是我国通信产业发展的当务之急。     

Melanized dopaminergic neurons are differentially susceptible to degeneration in Parkinson's disease

In idiopathic Parkinson's disease massive cell death occurs in the dopamine-containing substantia nigra. A link between the vulnerability of nigral neurons and the prominent pigmentation of the substantia nigra, though long suspected, has not been proved. This possibility is supported by evidence that N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its metabolite MPP+, the latter of which causes destruction of nigral neurons, bind to neuromelanin. We have directly tested this hypothesis by a quantitative analysis of neuromelanin-pigmented neurons in control and parkinsonian midbrains. The findings demonstrate first that the dopamine-containing cell groups of the normal human midbrain differ markedly from each other in the percentage of neuromelanin-pigmented neurons they contain. Second, the estimated cell loss in these cell groups in Parkinson's disease is directly correlated (r = 0.97, P = 0.0057) with the percentage of neuromelanin-pigmented neurons normally present in them. Third, within each cell group in the Parkinson's brains, there is greater relative sparing of non-pigmented than of neuromelanin-pigmented neurons. This evidence suggests a selective vulnerability of the neuromelanin-pigmented subpopulation of dopamine-containing mesencephalic neurons in Parkinson's disease.     

MRS study on lentiform nucleus in idiopathic Parkinson‘s disease with unilateral symptoms

OBJECTIVE: To investigate changes in magnetic resonance spectroscopy (MRS) of lentiform nucleus during the early stage of Parkinson's disease. METHODS: Twenty-five patients with idiopathic Parkinson disease with unilateral symptoms (IPDUS) and 25 healthy volunteers were enrolled in this study. MRS of the lentiform nucleus in each patient was taken and then concentrations of N-acetylaspartate (NAA), Creatine (Cr) and Choline (Cho) were calculated. RESULTS: Compared to that in the control, NAA/ (Cho+Cr) was significantly lower in the lentiform nucleus contralateral to symptoms and even that in the ipsilateral side in IPDUS patients (all P<0.05); while there was no difference between the two sides in the healthy volunteer (P>0.05). The ratio of NAA/(Cho+Cr) ipsilateral to the sympatomatic side of the patient was also lower than that of the control (P<0.05). CONCLUSIONS: There might be some changes with MRS on the lentiform nucleus during the early stage of idiopathic Parkinson's disease with unilateral symptom. MRS may be one of the reliable methods for early or even sub-clinical diagnosis.     

一类STD模型的竞争熄灭与共存

研究了一种存在于异性活动人群中的,通过性活动进行传播的病菌所构成的系统.在这个系统中,女性被分成N-1个不同的群体,而根据传播能力的不同,病原体菌株被分成两类.对这种系统,讨论了其地方病平衡点以及边界平衡点的稳定性,得到了这些平衡点存在及稳定的充分必要条件.结果确认,在边界平衡点的稳定性和地方病平衡点的存在性之间存在强烈的联系,即地方病平衡点存在当且仅当地方病平衡点同时存在并且具有相同的稳定性.     

Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson's disease

Parkinson's disease is a widespread condition caused by the loss of midbrain neurons that synthesize the neurotransmitter dopamine. Cells derived from the fetal midbrain can modify the course of the disease, but they are an inadequate source of dopamine-synthesizing neurons because their ability to generate these neurons is unstable. In contrast, embryonic stem (ES) cells proliferate extensively and can generate dopamine neurons. If ES cells are to become the basis for cell therapies, we must develop methods of enriching for the cell of interest and demonstrate that these cells show functions that will assist in treating the disease. Here we show that a highly enriched population of midbrain neural stem cells can be derived from mouse ES cells. The dopamine neurons generated by these stem cells show electrophysiological and behavioural properties expected of neurons from the midbrain. Our results encourage the use of ES cells in cell-replacement therapy for Parkinson's disease.     

自发光材料在隧道安全救援中的应用试验研究

隧道侧壁涂刷反射率较高的材料有利于改善隧道内部照明环境,对隧道安全救援也有积极作用。本文利用自发光材料蓄能释光的功能,分析自发光材料的施工工艺,对7种光源条件下自发光材料的余辉亮度进行模型隧道试验测试,得到自然光照射下初始余辉亮度最大,光源停止照射10 min 后,自发光材料的余辉亮度衰减至初始亮度的10％。同时依托云南保腾高速公路鹿山隧道,现场开展了 LED 灯源条件下的余辉亮度实验,探讨了余辉持续时间与安全救援的关系,发现断电30 min 后墙面的视觉诱导作用仍较明显,能对突发事件中隧道内人员的紧急避险和安全救援起到积极作用,为今后进一步合理利用和开发自发光材料在隧道应急救援中的作用提供参考。     

基于ARM的救援信息采集传输系统设计

灾害的发生是不可避免的,为了快速有效地开展救援,准确获知灾难现场的情况就显得非常重要.设计了一种基于ARM嵌入式的救援信息采集传输系统方案.该方案以ARM9芯片为核心,配以视频、音频和生命信号等采集模块,可以采集灾难现场的多种信息,改变了以往的比较单一的功能,并且通过无线网络实时地将信息传回服务器,帮助救援人员及时掌握现场情况,有利于积极有效的救援.P     

船舶破舱危险状态及施救能力

建立船舶破舱瞬时进水速度的计算模型,通过程序计算得到船舶破舱浮态、稳性、强度与进水时间的函数关系．提出船舶破舱危险状态的概念,确定船舶危险状态所对应的进水速度,通过将此船舶破舱进水速度与船舶排水设备能力的比较确定船舶的施救能力．分析船舶的施救机理,确定船舶施救的可行性,提供相应的施救决策．该决策为船员迅速判断出船舶破损的安全状态并得到正确的施救方案提供理论依据。     

煤矿应急救援研究现状及建议

我国煤矿受水文地质条件等多种因素影响,煤矿事故多发且较为严重,而应急救援能有效控制和防止事故的发生,降低事故损失。本文对我国煤矿应急救援的研究以及存在的问题进行了分析,为提高煤矿应急救援能力提出建议。     

Generalization in vision and motor control

Learning is more than memory. It is not simply the building of a look-up table of labelled images, or a phone-directory-like list of motor acts and the corresponding sequences of muscle activation. Central to learning and intelligence is the ability to predict, that is, to generalize to new situations, beyond the memory of specific examples. The key to generalization, in turn, is the architecture of the system, more than the rules of synaptic plasticity. We propose a specific architecture for generalization for both the motor and the visual systems, and argue for a canonical microcircuit underlying visual and motor learning.     

北部湾最佳搜救合作机制的建立

为建立北部湾最佳搜救合作机制,采用SWOT、比较和系统分析方法,对合作层次进行分级,划分搜救合作区域和信息共享区,对海上险情进行分级.采用"轮值主席"的制度进行操作,指定不同阶段的缔约方,指定社会搜救资源,获得双方政府的授权.建议北部湾各方签订谅解备忘录并以此作为基本性法律框架,以提高北部湾最佳搜救合作机制的可行性.