细胞外信号调节蛋白激酶-cAMP反应元件结合蛋白信号通路在应激所致抑郁行为障碍中的作用

Stress is the most important factor in the vulnerability to depression and other behavioral disorders, but the mechanisms that stress signals are transferred into depression are far from understanding. To date, the neurotransmitters, neurotrophins and signal pathway have been concerned in the topic focusing on the pathophysiology of depression, but there are still many puzzles. Increasing evidence has indicated that the alteration in neuronal plasticity is the “trace” of stress-induced damages. The extracellular signal-regulated protein kinase(ERK)-cyclic-AMP-responsive element（CRE）-binding protein(CREB)signal pathway is a powerful intracellular signal transduction pathway participating in neuronal plasticity which is involved in higher brain cognitive functions such as learning and memory. However, so far, little is known about the role of the ERK-CREB signal pathway in response to stress and emotional modulations. Thus the aim of the study was to systematically investigate the role of the ERK-CEB signal pathway in depressive-like behaviors induced by stress. Depression animal models, antidepressant agent treatment and disruption of signal pathway in specific brain regions were applied. In the present study, three experiment sessions were designed to make sure whether the ERK-CREB signal pathway was indeed one of pathophysiological mechanisms of depressive-like behaviors induced by stress. In experiment one, two different stress animal models were applied, chronic forced swim stress and chronic empty water bottle stress. After stress, all animals were tested behaviorally using open-field, elevated-plus maze and saccharine preference test, and brain samples were processed for determination of ERK, P-ERK, CREB and P-CREB using western blot. The relationships between the proteins of ERK, P-ERK, CREB and P-CREB in the brain and the behavioral variables were also analyzed. In experiment two, rats were treated with antidepressant agent fluoxetine once a day for 21 consecutive days, then the brain levels of ERK, P-ERK, CREB and P-CREB was determined, the depressive-like behaviors were also examined. In experiment three, mitogen activated extracellular-signal-regulated kinase kinase (MEK) inhibitor U0126 was administrated to inhabit the activation of ERK in the hippocampus and prefrontal cortex respectively, then behavioral measurements and protein detection were conducted. The main results of the study were as the following: (1) Chronic forced swim stress induced animals to suffer depression and disrupted the ERK-CREB signal pathway in hippocampus and prefrontal cortex. There were significant correlations between P-ERK2, P-CREB and multiple variables of depressive-like behaviors. (2) Chronic empty water bottle stress did not induce depressive-like behaviors. Such stress decreased the brain level of P-ERK2 in hippocampus and prefrontal cortex, but the level of P-CREB in the hippocampus was increased. (3) The antidepressant agent fluoxetine relieved depressive-like behaviors and increased the activities of the ERK-CREB signal pathway in stressed animals. (4) Animals treated with U0126 injection into hippocampus showed decreased activities of the ERK-CREB signal pathway in the hippocampus, and suffered depression comorbid with anxiety. (5) Animals treated with U0126 injection into prefrontal cortex showed decreased activities of the ERK-CREB signal pathway in the prefrontal cortex, and exhibited depressive-like behaviors. In conclusion, The ERK-CREB signal pathway in the hippocampus and prefrontal cortex was involved in stress responses and significantly correlated with depressive-like behaviors; The ERK-CREB signal pathway in the hippocampus and prefrontal cortex participated in the mechanism that fluoxetine reversed stress-induced behavioral disorders, and might be the target pathway of the therapeutic action of antidepressants; The disruption of the ERK-CREB signal pathway in the hippocampus or prefrontal cortex led to depressive-like behaviors in animals, suggesting that disruption of ERK-CREB pathway in the hippocampus or prefrontal cortex was involved in the pathophysiology of depression, and might be at least one of the mechanisms of depression induced by stress.

Xanthohumol, a novel anti-HIV-1 agent purified from Hops Humulus lupulus

Xanthohumol, prenylchacone flavonoid, is a natural product with multi-biofunctions purified from Hops Humulus lupulus. Its anti-HIV-1 activity was tested in the present study. Results showed that xanthohumol inhibited HIV-1 induced cytopathic effects, the production of viral p24 antigen and reverse transcriptase in C8166 lymphocytes at non-cytotoxic concentration. The EC50 values were 0.82, 1.28 and 0.50 mug/ml, respectively. The therapeutic index (TI) was about 10.8. Xanthohumol also inhibited HIV-1 replication in PBMC with EC50 value of 20.74 mug/ml. The activity of recombinant HIV-1 reverse transcriptase and the HIV-1 entry were not inhibited by xanthohumol. The results from this study suggested that xanthohumol is effective against HIV-1 and might serve as an interesting lead compound. It may represent a novel chemotherapeutic agent for HIV-1 infection. However, the mechanism of its anti-HIV-1 effect needs to be further clarified. (C) 2004 Elsevier B.V. All rights reserved.

Concentricolide, an anti-HIV agent from the ascomycete Daldinia concentrica

A novel benzofuran lactone, named concentricolide (=rel-(6R)-6-ethylbenzo[2.1-b:3,4-c']difuran-8(6H)-one; 1), was isolated along with four known compounds (friedelin, cytochalasin L-696.474, armillaramide, and russulamide) from the fruiting bodies of the

mobile agent system model based on servlet technology

A mobile agent system model based on the servlet technology is presented, the constitution and working process of the system are analyzed. The implementation of key parts of this model and the current development situation as well as the development trend of mobile agent technology are introduced. The mobile agent system model enhances its internal structure recognition and facilitates the system expansion and reformation. The remotely mobile agent control method by means of the protocol modification is presented.

一种基于Agent的自适应的分布式入侵检测系统

针对传统分布式入侵检测系统组件之间依赖程度大、系统不够健壮且入侵检测系统自身结构固定不能适应入侵的变化的问题,提出了一种基于Agent的自适应的分布式入侵检测系统(简称AAA-DIDS)·AAADIDS采用Agent概念重新构造系统的组件,改进了分布式入侵检测系统由于高层节点单一无冗余而产生的可靠性差的缺陷,从构造上克服了分布式入侵检测系统的脆弱性·同时,AAADIDS系统采用智能技术构建了自适应的入侵检测系统模型,增加了系统应对入侵行为变化的智能性·AAA-DIDS系统相对于传统的分布式入侵检测系统有效地提高了系统自身的可靠性和针对外界变化的适应能力·

一种用于软件过程建模的适应性Agent协商

大多软件过程模型是预定义的.在变化的应用环境中,需要由相应人员进行适应性调整.提出一种用于软件过程建模的适应性多边协商模型——AMNM-PA,其采用Agent封装软件过程中所涉及的个体,包含组织、团队、个人等,通过Agent间的协商动态、适应地建立针对给定软件项目的软件过程模型.AMNM-PA基于非静态有限阶段Markov决策过程,采用模型无关的Q学习算法选取协商策略,因此能够支持动态、非预知环境下的适应性协商,从而满足软件过程建模对环境的适应性需求.AMNM-PA已经实施于软件过程管理系统——SoftPM.

一种基于Agent的自适应软件过程模型

传统的软件过程模型大多是静态的、机械的、被动的,它们要求软件工程人员在描述软件过程时预期所有可能发生的情况,并且显式地定义这些问题的解决方案.当软件过程所处的环境发生变化时,软件过程无法自适应地对这些变更作出相应的调整.提出了一种基于Agent的自适应软件过程模型.在这种软件过程模型中,软件过程被描述为一组相互独立而对等的实体——软件过程Agent.这些软件过程Agent能够对软件过程环境的变化主动地、自治地作出反应,动态地确定和变更其行为以实现软件开发的目标.

基于Agent的智能交通体系及仿真

交通问题已成为全世界所共同关注的主要问题 ,如何运用现代的科技手段来缓解日益严峻的交通压力 ,是目前研究的重点。该文基于目前交通问题及交通系统发展的现状 ,结合计算机软件技术的最新成果———Agent技术 ,提出了基于Agent技术的智能交通控制的体系结构 ,论述了该结构的优点 ;并根据Agent的特点 ,介绍了运用Agent技术进行交通仿真的优势 ,探讨了具体采用Agent技术进行交通仿真的方法。

一种基于移动Agent的复合Web服务容错模型

现有的Web服务容错侧重于通过扩展Web服务标准来提供容错能力.由于Web服务标准体系本身不断发展变化,并且标准之间的兼容性问题依然存在,使得这些研究成果的可实施性较弱.文章提出一种基于移动Agent的复合Web服务容错模型--MAFTM模型,从系统层次而非标准层次来解决复合Web服务的容错问题.首先说明基于移动Agent的工作流与复合Web服务的关系.在此基础上,给出MAFTM模型,包括故障类型、复制机制、"exactly once"语义和一致性算法,并证明MAFTM模型的正确性.

智能交通仿真与车辆Agent决策策略的研究

文章介绍了Agent技术及特点,根据Agent的原理及其仿真的优势,着重叙述了Agent技术在交通仿真中的应用,详细探讨了基于Agent的智能仿真系统中车辆Agent的决策特点及模糊决策方法,同时,还分析了驾驶员因素对驾驶行为的影响。

a flexible negotiation model for an agent-based software process modelling

Our Agent-based Software Process Modelling (ASPM) approach describes a software process as a set of cooperative agents. Negotiation is the way in which the agents construct their cooperative relations, and thus the software process. Currently, most negotiation models use a fixed negotiation protocol and fixed strategies. In order to achieve the flexibility that the negotiation of the agents in ASPM requires, we propose a negotiation model NM-PA. NM-PA mainly includes a generic negotiation protocol and some rules, which possibly change in different negotiation processes. By changing the rules, the model can support multi-protocols and multi-decision-making strategies at a lower cost.