Oxidant stress evoked by pacemaking in dopaminergic neurons is attenuated by DJ-1

Parkinson's disease is a pervasive, ageing-related neurodegenerative disease the cardinal motor symptoms of which reflect the loss of a small group of neurons, the dopaminergic neurons in the substantia nigra pars compacta (SNc). Mitochondrial oxidant stress is widely viewed as being responsible for this loss, but why these particular neurons should be stressed is a mystery. Here we show, using transgenic mice that expressed a redox-sensitive variant of green fluorescent protein targeted to the mitochondrial matrix, that the engagement of plasma membrane L-type calcium channels during normal autonomous pacemaking created an oxidant stress that was specific to vulnerable SNc dopaminergic neurons. The oxidant stress engaged defences that induced transient, mild mitochondrial depolarization or uncoupling. The mild uncoupling was not affected by deletion of cyclophilin D, which is a component of the permeability transition pore, but was attenuated by genipin and purine nucleotides, which are antagonists of cloned uncoupling proteins. Knocking out DJ-1 (also known as PARK7 in humans and Park7 in mice), which is a gene associated with an early-onset form of Parkinson's disease, downregulated the expression of two uncoupling proteins (UCP4 (SLC25A27) and UCP5 (SLC25A14)), compromised calcium-induced uncoupling and increased oxidation of matrix proteins specifically in SNc dopaminergic neurons. Because drugs approved for human use can antagonize calcium entry through L-type channels, these results point to a novel neuroprotective strategy for both idiopathic and familial forms of Parkinson's disease.     

Rhodopsin inactivation is a modulated process in Limulus photoreceptors.

Many G-protein-coupled receptors are only transiently active because an inactivation process stops the receptor from activating G protein molecules. Although this inactivation has been investigated in vitro, the real kinetics of the process can only be obtained from intact cells. Here we describe a method for measuring the inactivation of rhodopsin in intact photoreceptors and the application of this method to the ultraviolet rhodopsin of Limulus median eye. The results show that the inactivation process is very rapid (less than 150 ms) and occurs well before the peak of the receptor potential. We have also investigated whether the inactivation process can itself be modulated. Our results show that light-adaptation accelerates inactivation by about 10-fold, providing evidence that G-protein-mediated transduction can be modulated at this first stage.     

大学生L1水平、L2水平与L2阅读能力的相关性

运用定量和定性研究相结合的方法,考察了中国大学新生母语水平、二语水平及其二语阅读能力之间的关系.多元回归分析表明：中国大学新生的汉语水平与英语水平之间似乎没有关联;被试的英语水平对其英语阅读能力有较强的预测力,但其母语水平与英语阅读能力之间的相关程度不显著.     

Hax1-mediated processing of HtrA2 by Parl allows survival of lymphocytes and neurons

Cytokines affect a variety of cellular functions, including regulation of cell numbers by suppression of programmed cell death. Suppression of apoptosis requires receptor signalling through the activation of Janus kinases and the subsequent regulation of members of the B-cell lymphoma 2 (Bcl-2) family. Here we demonstrate that a Bcl-2-family-related protein, Hax1, is required to suppress apoptosis in lymphocytes and neurons. Suppression requires the interaction of Hax1 with the mitochondrial proteases Parl (presenilin-associated, rhomboid-like) and HtrA2 (high-temperature-regulated A2, also known as Omi). These interactions allow Hax1 to present HtrA2 to Parl, and thereby facilitates the processing of HtrA2 to the active protease localized in the mitochondrial intermembrane space. In mouse lymphocytes, the presence of processed HtrA2 prevents the accumulation of mitochondrial-outer-membrane-associated activated Bax, an event that initiates apoptosis. Together, the results identify a previously unknown sequence of interactions involving a Bcl-2-family-related protein and mitochondrial proteases in the ability to resist the induction of apoptosis when cytokines are limiting.     

母语和第二语言阅读的文化差异与认知体系

母语阅读与第二语言或外语的阅读之间尽管有许多共同的基本要素，但阅读过程却差异很大，令人感兴趣的问题为是否存在着两个平行发挥作用的认知过程，或着是否存在着对两种语言的处理都适应的策略，本文将着力探讨母语与第二语言的阅读的异同之处，尤其是在文化方面的差异，如语言文化内容或背景知识认知体系，形式上的（或字面的）认知体系，语言学（或语言）认知体系等。     

母语语音向英语语音负迁移的案例假设与证明

对比分析假设理论对母语在外语学习中的作用提出了正迁移和负迁移的说法。通过对英语教师以及大学生进行调查之后,得出了与提出的假设部分相符的结论。即母语为粤语的英语学习者,大部分人在发摩擦音／v／时,或多或少会有一定的困难;具体地说,当／v／在元音之前时,大部分人出现母语负迁移的现象,而当／v／在元音之后或音节的结尾时,负迁移的现象没有发现。     

Glucose sensing by POMC neurons regulates glucose homeostasis and is impaired in obesity

A subset of neurons in the brain, known as 'glucose-excited' neurons, depolarize and increase their firing rate in response to increases in extracellular glucose. Similar to insulin secretion by pancreatic beta-cells, glucose excitation of neurons is driven by ATP-mediated closure of ATP-sensitive potassium (K(ATP)) channels. Although beta-cell-like glucose sensing in neurons is well established, its physiological relevance and contribution to disease states such as type 2 diabetes remain unknown. To address these issues, we disrupted glucose sensing in glucose-excited pro-opiomelanocortin (POMC) neurons via transgenic expression of a mutant Kir6.2 subunit (encoded by the Kcnj11 gene) that prevents ATP-mediated closure of K(ATP) channels. Here we show that this genetic manipulation impaired the whole-body response to a systemic glucose load, demonstrating a role for glucose sensing by POMC neurons in the overall physiological control of blood glucose. We also found that glucose sensing by POMC neurons became defective in obese mice on a high-fat diet, suggesting that loss of glucose sensing by neurons has a role in the development of type 2 diabetes. The mechanism for obesity-induced loss of glucose sensing in POMC neurons involves uncoupling protein 2 (UCP2), a mitochondrial protein that impairs glucose-stimulated ATP production. UCP2 negatively regulates glucose sensing in POMC neurons. We found that genetic deletion of Ucp2 prevents obesity-induced loss of glucose sensing, and that acute pharmacological inhibition of UCP2 reverses loss of glucose sensing. We conclude that obesity-induced, UCP2-mediated loss of glucose sensing in glucose-excited neurons might have a pathogenic role in the development of type 2 diabetes.     

Social feeding in Caenorhabditis elegans is induced by neurons that detect aversive stimuli

Natural Caenorhabditis elegans isolates exhibit either social or solitary feeding on bacteria. We show here that social feeding is induced by nociceptive neurons that detect adverse or stressful conditions. Ablation of the nociceptive neurons ASH and ADL transforms social animals into solitary feeders. Social feeding is probably due to the sensation of noxious chemicals by ASH and ADL neurons; it requires the genes ocr-2 and osm-9, which encode TRP-related transduction channels, and odr-4 and odr-8, which are required to localize sensory chemoreceptors to cilia. Other sensory neurons may suppress social feeding, as social feeding in ocr-2 and odr-4 mutants is restored by mutations in osm-3, a gene required for the development of 26 ciliated sensory neurons. Our data suggest a model for regulation of social feeding by opposing sensory inputs: aversive inputs to nociceptive neurons promote social feeding, whereas antagonistic inputs from neurons that express osm-3 inhibit aggregation.     

Connectivity of chemosensory neurons is controlled by the gene poxn in Drosophila.

The function of the nervous system depends on the formation of a net of appropriate connections, but little is known of the genetic program underlying this process. In Drosophila two genes that specify different types of sense organs have been identified: cut (ct), which specifies the formation of external sense organs as opposed to chordotonal organs, and pox-neuro (poxn), which specifies the formation of poly-innervated (chemosensory) organs as opposed to mono-innervated (mechanosensory) organs. Whether these genes are also involved in specifying the connectivity of the corresponding neurons is not known. The larval sense organs are unsuitable for analysis of the axonal pathway and connections and so we have investigated the effect of poxn on the adult. Here we show that overexpression of poxn induces the morphological transformation of mechanosensory into chemosensory bristles on the legs and that the neurons innervating the morphologically transformed bristles follow pathways and establish connections that are appropriate for chemosensory bristles.     

Differential inhibition of neurone-neurone, neurone-astrocyte and astrocyte-astrocyte adhesion by L1, L2 and N-CAM antibodies

The cell adhesion molecules L1, N-CAM and Ng-CAM have been implicated in cell-cell interactions among developing neural cells. L1 and N-CAM are structurally and functionally distinct molecular entities and act synergistically in mediating Ca2+-independent adhesion between re-aggregating early postnatal cerebellar cells. N-CAM has been reported to be neurone-specific in the chicken and to mediate fasciculation of neurites and of nerve-muscle interactions. L1, which in the central nervous system has been found only on post-mitotic neurones, mediates migration of granule cell neurones in the mouse cerebellar cortex. In view of the molecules' distinct effects on cell interactions, we wondered whether different neural cell types are involved in the actions of each molecule. Here we report that L1 antigen promotes neurone-neurone adhesion. N-CAM, which is expressed on both neurones and glia, mediates neurone-neurone, neurone-astrocyte and astrocyte-astrocyte adhesion. The L2 carbohydrate epitope shared between the two adhesion molecules seems to be involved in neurone-astrocyte and astrocyte-astrocyte adhesion and acts in a more than additive manner in N-CAM-mediated neurone-neurone adhesion.     

宝钢冷轧3级控制系统L3_L2_L1间通讯实现

探讨了宝钢冷轧一般连续处理生产线过程控制计算机系统Level2的操作系统为WINDOWS时各级控制系统间的通讯方式,主要包括以TCP/IP Socket电文方式来完成生产控制系统Level3与过程控制系统Level2系统之间通讯;使用MICROSOFT公司.NET框架推出的信道技术实现过程控制系统内部通讯以及采用OPC开放控制协议实现过程控制系统Level2与基础自动化系统Level1之间通讯,最后给出了宝钢冷轧过程控制系统L2的一种典型架构。     

Time to collision is signalled by neurons in the nucleus rotundus of pigeons.

Throughout the animal kingdom, the sight of a rapidly approaching object usually signals danger and elicits an escape response. Gibson suggested that the symmetrical expansion of an object's image (looming) is the critical variable determining that the object is on a collision course with the observer. Similarly, large expanding flow-fields like those produced by locomotion may precipitate manoeuvres such as turning or landing. From such observations it has been shown that the optic flow parameter, tau, which specifies time to contact with the approaching object best fits the behavioural data. We describe a subpopulation of neurons in the nucleus rotundus of the pigeon brain that respond selectively to objects moving on a collision course towards the bird.     

Differential modulation of three separate K-conductances in hippocampal CA1 neurons by serotonin

The hippocampus receives a dense serotonin-containing innervation from the divisions of the raphe nucleus. Serotonin applied to hippocampal neurons to mimic the action of endogenous transmitter often produces complex and variable responses (see for example ref. 3). Using voltage-clamp methods and new ligands that are selective for subtypes of serotonin receptors, we have been able to clarify the mechanism of serotonin action on CA1 cells in rat hippocampal slices. We describe three distinct actions of serotonin (or 5-HT) on identified K-conductances in these cells. First, it activates a Ca-independent K-current which is responsible for neuronal hyperpolarization and is inhibitory. Second, it simultaneously suppresses the slow Ca-dependent K-conductance that is largely responsible for the accommodation of cell firing in CA1 neurons: this produces a paradoxical increase in neuronal discharge in response to a depolarizing input. Third, serotonin produces a more slowly developing and long-lasting suppression of an intrinsic voltage-dependent K-conductance, Im (ref. 9), leading to neuronal depolarization and excitation. The hyperpolarizing response is mediated by class 1A serotonin receptors, whereas the other responses are not. Modulation of these different conductances by endogenously released serotonin could therefore change the probability or the duration (or both) of neuronal firing in the mammalian brain in different ways to give inhibitory, excitatory or mixed effects.     

核图与L(2,1)标号

图的L(2,1)-标号λ(G)来自于通讯频道分配问题.定义了一个图的核图并研究了它们的性质,最后给出了关于λ(G)的两个重要定理的简短证明.     

基于简单L_(1/2)稀疏正则化的高光谱混合像元分解

高光谱图像解混方法中基于稀疏性的混合像元分解方法成为近来研究的热点,其中稀疏正则化高光谱混合像元分解方法(SUnSAL)得到了较好的解混效果。尽管如此,但正则化解的稀疏性和稳健性并不好。基于正则子比正则子更易于求解,同时比正则子具有更好的稀疏性和稳健性,本文引入用正则子来代替正则子。同时,采用了一种简单有效的稀疏正则化的求解方法,将正则化非凸优化问题转化为一系列迭代重复加权正则化问题,并利用变量分裂和增广拉格朗日算法(ADMM)对加权正则化问题进行求解。实验数据表明,此方法不但实现简单,而且可以获得更好的混合像元分解精度。     

Odorant receptor gene choice is reset by nuclear transfer from mouse olfactory sensory neurons

Of the approximately 1,000 odorant receptor (OR) genes in the mouse genome, an olfactory sensory neuron (OSN) is thought to express one gene, from one allele. This is reminiscent of immunoglobulin and T-cell receptor genes, which undergo DNA rearrangements in lymphocytes. Here, we test the hypothesis that OR gene choice is controlled by DNA rearrangements in OSNs. Using permanent genetic marking, we show that the choice by an OSN to express an allele of the OR gene M71 is irreversible. Using M71-expressing OSNs as donors for nuclear transfer, we generate blastocysts, embryonic stem (ntES) cell lines and clonal mice. DNA analysis of these cell lines, whose genome is clonally derived from an M71-expressing OSN, does not reveal DNA rearrangements or sequence alterations at the M71 locus. OSNs that differentiate from ntES cells after injection into blastocysts are not restricted to expression of M71 but can express other OR genes. Thus, M71 gene choice is irreversible but is reset upon nuclear transfer, and is not accompanied by genomic alterations.