Expression of polyglutamine-expanded Huntingtin activates the SEK1-JNK pathway and induces apoptosis in a hippocampal neuronal cell line

Huntington's disease is one of a growing number of hereditary neurodegenerative disorders caused by expansion of a polyglutamine stretch at the NH2 terminus of huntingtin. To explore whether polyglutamine-expanded huntingtin induces neuronal toxicity, I examined the expression of the full-length of huntingtin with 16, 48, or 89 polyglutamine repeats in a rat hippocampal neuronal cell (HN33). Expression of mutated huntingtin with 48 or 89 polyglutamine repeats stimulated c-Jun amino-terminal kinases (JNKs) activity and induced apoptotic cell death in HN33 cells while expression of normal huntingtin with 16 polyglutamine repeats had no toxic effect. The JNK activation precedes apoptotic cell death and co-expression of a dominant negative mutant form of stress-signaling kinase (SEK1) nearly completely blocked activation of JNKs and neuronal apoptosis mediated by mutated huntingtin. Taken together, my studies demonstrate that expression of polyglutamine-expanded huntingtin induces neuronal apoptosis via activation of the SEK1-JNK pathway.     

Trends and variations in neonatal length of in-hospital stay in Canada

The objectives of this study were to evaluate the possible mechanisms involved in prolongation of bleeding time in pre-eclamptic patients receiving a magnesium sulfate infusion to prevent convulsions. Eighteen pre-eclamptic patients near term or at term (4 cases 33 to 35 weeks; the remainder > 36 weeks) were studied. Fifteen of them received magnesium sulfate infusion; 3 did not and served as controls. Bleeding time (modified Ivy method with Surgicutt), platelet count, platelet aggregation pattern, as well as serum arachidonic acid metabolites [thromboxane B2 (TxB2) and 6-Keto-prostaglandin F1 alpha (6-Keto-PGF1 alpha)] werde done on admission to the labor floor (before magnesium infusion) and repeated at discontinuation of the infusion, 12-24 hours postpartum; the controls received the second test 24 hours postpartum. Thirteen of 15 patients receiving magnesium sulfate had an increase in bleeding time from an average of 6 minutes 31 seconds to 11 minutes 56 seconds, an 82% rise (p < 0.004). In 2 there was a decrease. Among the 3 controls the averages were 6 minutes 38 seconds and 6 minutes 3 seconds. The total magnesium given ranged from 52.5 to 145 grams. Platelet counts averaged 251,000/mm3 (range 145,000-519,000). Platelet aggregation pattern done in 11 patients and was normal and unchanged after magnesium in 10 of the patients with increased bleeding time and one control. TxB2 and 6-Keto-PGF1 alpha levels did not change significantly either after magnesium administration (688 and 135 pgm/ml, to 654 and 117) or in controls (695 and 230 pgm/ml, to 445 and 225). Likewise, the ratio of these 2 substances did not change in either group (6.3 to 6.6, and 4.2 to 2.2). There was no correlation between duration of infusion or total magnesium given and directions of small changes observed. This study confirms a prior preliminary observation that magnesium sulfate infusion, as currently used to prevent eclamptic convulsions, induces a significant prolongation of bleeding time. This effect is mediated neither by changes in platelets count or aggregation pattern, nor by changing the level or ratios of serum arachidonic acid metabolites (TxB2 and 6-Keto-PGF1 alpha). Further studies are needed to clarify the mechanism of this clinically important observation of increased bleeding following magnesium sulfate infusion.     

Early patterning of prelimbic cortical axons to the striatal patch compartment in the neonatal mouse

The striatum receives excitatory input from virtually the entire cerebral cortex. In the adult, this input is segregated into two functionally distinct compartments of the striatum, the patch (striosome) and matrix regions. This study determined whether the patterning of corticostriatal afferents from the prelimbic cortex to the striatal patch compartment develops during the early period of collateral formation or instead at the time of peak synaptogenesis. Initial formation of corticostriatal axon collaterals was observed by embryonic day (E) 19. Quantification of corticostriatal collaterals revealed a significant increase in the number and complexity of collateral branches at postnatal day 6 as compared to E19. Concomitant with the increase in collateral branching, a heterogeneous pattern of collateralization consisting of parallel rows of corticostriatal collaterals was observed in the medial striatum. In addition to the rows, clusters of corticostriatal axons occurred more laterally. These clusters colocalized with patches of dense tyrosine hydroxylase-positive fibers, a marker for the striatal patch compartment in the neonatal mouse. Together, these data indicate that corticostriatal patterning occurs during the period of early axon collateralization resulting in a segregation of corticostriatal axon collaterals from the prelimbic cortex to the striatal patch compartment.     

Suppressive effect of corticosteroids on the gene expression of interleukin-5 and eosinophil activation in asthmatics

Although cortico steroids are effective anti-inflammatory agents in ameliorating asthma symptoms and bronchial hperreactivity, their mechanism of action is unknown. Interleukin (IL)-5 is known to play a key role in regulating eosinophil proliferation and activation. Therefore, we examined the changes of IL-5 mRNA expressions in PBMC semi-quantitatively with RT-PCR as well as serum ECP levels and MCH-PC20 values in asthmatics before and after being treated with corticosteroids. The results revealed that there were significant decrease in the level of IL-5 mRNA and serum ECP concentration after therapy (P < 0.05) and there was remarkable improvement in the values of MCH-PC20 and FEV1% (P < 0.05). It was also found that the changes of serum ECP levels or MCH-PC20 values were accompanied by a reduction in IL-5 mRNA expression (r = 0.5426 or 0.4857, P < 0.05). These results suggested that the therapeutic effects of corticosteroids in asthma may result from modulation of IL-5 gene expression with consequent inhibition of eosinophil activation.     

A multi-agent decision support system for stock trading

A distributed problem solving system can be characterized as a group of individual cooperating agents running to solve common problems. As dynamic application domains continue to grow in scale and complexity, it becomes more difficult to control the purposeful behavior of agents, especially when unexpected events may occur. This article presents an information and knowledge exchange framework to support distributed problem solving. From the application viewpoint the article concentrates on the stock trading domain; however, many presented solutions can be extended to other dynamic domains. It addresses two important issues: how individual agents should be interconnected so that their resources are efficiently used and their goals accomplished effectively; and how information and knowledge transfer should take place among the agents to allow them to respond successfully to user requests and unexpected external situations. The article introduces an architecture, the MASST system architecture, which supports dynamic information and knowledge exchange among the cooperating agents. The architecture uses a dynamic blackboard as an interagent communication paradigm to facilitate factual data, business rule, and command exchange between cooperating MASST agents. The critical components of the MASST architecture have been implemented and tested in the stock trading domain, and have proven to be a viable solution for distributed problem solving based on cooperating agents     

R22替代制冷剂的生产控制评价

本文详细介绍了R2 2替代制冷剂的生产过程控制和整机可靠性评价 ,并介绍了一些具体做法。     

8096/8098单片机集成开发系统

本集成开发环境集编辑、编译、调试和运行于一体,模拟了MCS-96系列单片机的指令系统,并给教学、实验、应用、科研和单片机的开发提供了强有力的手段。     

8Li次级束的产生

在北京串列加速器次级束流线上通过2 H(7Li,8Li) 1H逆运动学反应产生了用于核天体物理研究的8Li次级束。准直后的次级束纯度达到 80 %以上 ,对于 44MeV的7Li强度约为 3 0s- 1·pnA- 1,可以用来进行逆几何转移反应的实验测量。     

NO emission characteristics in counterflow diffusion flame of blended fuel of H2/CO2/Ar

Flame structure and NO emission characteristics in counterflow diffusion flame of blended fuel of H₂/CO₂/Ar have been numerically simulated with detailed chemistry. The combination of H₂, CO₂ and Ar as fuel is selected to clearly display the contribution of hydrocarbon products to flame structure and NO emission characteristics due to the breakdown of CO₂. A radiative heat loss term is involved to correctly describe the flame dynamics especially at low strain rates. The detailed chemistry adopts the reaction mechanism of GRI 2.11, which consists of 49 species and 279 elementary reactions. All mechanisms including thermal, NO₂, N₂O and Fenimore are taken into account to separately evaluate the effects of CO₂ addition on NO emission characteristics. The increase of added CO₂ quantity causes flame temperature to fall since at high strain rates a diluent effect is prevailing and at low strain rates the breakdown of CO₂ produces relatively populous hydrocarbon products and thus the existence of hydrocarbon products inhibits chain branching. It is also found that the contribution of NO production by N₂O and NO₂ mechanisms are negligible and that thermal mechanism is concentrated on only the reaction zone. As strain rate and CO₂ quantity increase, NO production is remarkably augmented. Copyright © 2002 John Wiley & Sons, Ltd.     

浅析2020年前美军事战略重点的转变--从装备发展看美国军事战略重点可能的变化

美国21世纪前期的军事战略重点将是争夺外空优势，夺取制天权和制信息权。分析了美国夺取外空优势的原因，及其为夺取外空优势在国家政策、航天发展和技术准备等方面采取的措施。