Differential effects of the serotonin receptors on cultured rat cerebral cortical neurons

Effects of serotonin (5-HT) on cerebral cortical neurons were examined by patch clamp techniques. 5-HT produced a variety of responses such as outward (19/73 patches/neurons), slow inward (15/73 patches/neurons), fast inward (8/73 patches/neurons), and mixed currents (initially fast inward deflection followed by an outward response: 2/73 patches/neurons), with a latency of 12 sec, 15 sec, 0 sec, and 0 sec respectively, at a holding potential of −60 mV in whole-cell patches. The fast inward currents were again evoked by a selective 5-HT3 receptor agonist, 1-(m-chlorophenyl)-biguanide hydrochloride (CPBG). In the cell-attached patch clamp configuration, 5-HT inside the patch pipette elicited single channel currents with slope conductances of 42 pS and 132 pS (4/42 patches/neurons). CPBG inside the patch pipette evoked inward single channel currents with a lower slope conductance of 41 pS (3/23 patches/neurons). In contrast, application of 5-HT or a 5-HT₂ receptor agonist, α-methyl-5-hydroxytryptamine-maleate, outside the patch pipette induced outward single channel currents with a major slope conductance of 140 pS (8/30 patches/neurons) or 135 pS (6/20 patches/neurons), respectively. These results indicate that the outward and fast inward currents may be mediated respectively by the 5-HT₂ receptor, which is coupled to a G-protein, and by the 5-HT₃ receptor, which contains the non-selective cation channel, and that the mixed type may be caused by both the 5-HT₂ and 5-HT₃ receptors. Received 27 September 1996; received after revision 4 November 1996; accepted 7 November 1996     

机械合金化工艺对Fe-Ni合金显微结构的影响

对机械合金化制备的Fe-Ni粉体利用X射线衍射(XRD)进行分析，得到了不同Ni含量和不同球磨时间Fe-Ni纳米晶的XRD谱．实验表明，w(Ni)=10％和20％时，Ni溶入Fe晶格，分别在球磨20h和50h后形成单一的a(bcc)相；w(Ni)=50％时，其先后经历了γ(fcc)→←a(bcc)正逆转变，在球磨120h后最终形成单一γ(fcc)相．无论是a(bcc)相还是γ(fcc)相．它们的固溶度均比块体Fe-Ni合金显著提高．w(Ni)=35％时，则始终是两相共存．对试样的XRD谱采用3种不同的方法测定了Fe-Ni粉体的晶粒尺寸和显微畸变，发现经球磨20h后，不同Ni含量的粉体均呈纳米结构，并随球磨时间延长，Fe-Ni纳米晶的晶粒尺寸下降而显微畸变上升．     

Mutations in the gene encoding the basal body protein RPGRIP1L, a nephrocystin-4 interactor, cause Joubert syndrome

Protein-protein interaction analyses have uncovered a ciliary and basal body protein network that, when disrupted, can result in nephronophthisis (NPHP), Leber congenital amaurosis, Senior-L?ken syndrome (SLSN) or Joubert syndrome (JBTS). However, details of the molecular mechanisms underlying these disorders remain poorly understood. RPGRIP1-like protein (RPGRIP1L) is a homolog of RPGRIP1 (RPGR-interacting protein 1), a ciliary protein defective in Leber congenital amaurosis. We show that RPGRIP1L interacts with nephrocystin-4 and that mutations in the gene encoding nephrocystin-4 (NPHP4) that are known to cause SLSN disrupt this interaction. RPGRIP1L is ubiquitously expressed, and its protein product localizes to basal bodies. Therefore, we analyzed RPGRIP1L as a candidate gene for JBTS and identified loss-of-function mutations in three families with typical JBTS, including the characteristic mid-hindbrain malformation. This work identifies RPGRIP1L as a gene responsible for JBTS and establishes a central role for cilia and basal bodies in the pathophysiology of this disorder.     

基于多AGENT的机器人装配系统结构

采用Ａｇｅｎｔ的基本思想,对多Ａｇｅｎｔ系统分别从个体和群体的角度出发,构造系统结构。通过对系统行为方式的定义,将全局运行流程与局部运行流程相分离,将任务的执行和任务间的协调相分离,将任务的选择与自身及状态相结合,从而系统结构可以隔离高层的系统控制与低层的执行过程,使虚拟系统在结构上具有更大灵活性,可扩充性和可重用性。     

A multiple intelligent agent system for credit risk prediction via an optimization of localized generalization error with diversity

Company bankruptcies cost billions of dollars in losses to banks each year. Thus credit risk prediction is a critical part of a bank＇s loan approval decision process. Traditional financial models for credit risk prediction are no longer adequate for describing today＇s complex relationship between the financial health and potential bankruptcy of a company. In this work, a multiple classifier system （embedded in a multiple intelligent agent system） is proposed to predict the financial health of a company. In our model, each individual agent （classifier） makes a prediction on the likelihood of credit risk based on only partial information of the company. Each of the agents is an expert, but has limited knowledge （represented by features） about the company. The decisions of all agents are combined together to form a final credit risk prediction. Experiments show that our model out-performs other existing methods using the benchmarking Compustat American Corporations dataset.     

Protein kinase C and phospholipase D: intimate interactions in intracellular signaling

Diacylglycerol (DAG) was discovered as a potent lipid second messenger with protein kinase C (PKC) as its major cellular target more than 25 years ago. There is increasing evidence of significant complexity within lipid signaling, and the classical DAG-PKC model no longer stands alone but is part of a larger bioactive lipid universe involving glycerolipids and sphingolipids. Multiple layers of regulation exist among PKC- and DAG-metabolizing enzymes such as phosphatidylcholine (PC)-specific phospholipase D, and cross-talk exists between the glycerolipid and sphingolipid pathways, with PKC at the center. Currently, there is intense interest in the question of whether DAG derived from PC can function as a lipid second messenger and regulate PKC analogous to DAG derived from phosphatidylinositol-4,5-bisphosphate (PIP₂). To address these issues and incorporate DAG-PKC and other signaling pathways into an expanded view of cell biology, it will be necessary to go beyond the classical approaches and concepts.Received 29 November 2004; received after revision 18 January 2005; accepted 4 March 2005This work is dedicated to the memory of Dr. Yasutomi Nishizuka, the discoverer of protein kinase C, who was both a gentleman and a scientist.     

Cellular responses to mild heat stress

Since its discovery in 1962 by Ritossa, the heat shock response has been extensively studied by a number of investigators to understand the molecular mechanism underlying the cellular response to heat stress. The most well characterized heat shock response is induction of the heat shock proteins that function as molecular chaperones and exert cell cycle regulatory and anti-apoptotic activities. While most investigators have focused their studies on the toxic effects of heat stress in organisms such as severe heat stress-induced cell cycle arrest and apoptosis, the cellular response to fever-ranged mild heat stress has been rather underestimated. However, the cellular response to mild heat stress is likely to be more important in a physiological sense than that to severe heat stress because the body temperature of homeothermic animals increases by only 1–2°C during febrile diseases. Here we provide information that mild heat stress does have some beneficial role in organisms via positively regulating cell proliferation and differentiation, and immune response in mammalian cells.Received 14 May 2004; received after revision 2 August 2004; accepted 16 August 2004     

Phosphodiesterase: overview of protein structures, potential therapeutic applications and recent progress in drug development

Phosphodiesterases (PDEs) are essential regulators of cyclic nucleotide signaling with diverse physiological functions. Because of their great market potential and therapeutic importance, PDE inhibitors became recognized as important therapeutic agents in the treatment of various diseases. Currently, there are seven PDE inhibitors on the market, and the pharmacological and safety evaluations of many drug candidates are in progress. Three-dimensional (3D) structures of catalytic domains of PDE 1, -3, -4, -5 and -9 in the presence of their inhibitors are now available, and can be utilized for rational drug design. Recent advances in molecular pharmacology of PDE isoenzymes resulted in identification of new potential applications of PDE inhibitors in various therapeutic areas, including dementia, depression and schizophrenia. This review will describe the latest advances in PDE research on 3D structural studies, the potential of therapeutic applications and the development of drug candidates.Received 30 November 2004; received after revision 24 January 2005; accepted 5 February 2005