Regulated expression and neural functions of human natural killer-1 (HNK-1) carbohydrate

Human natural killer-1 (HNK-1) carbohydrate, comprising a unique trisaccharide HSO₃-3GlcAβ1-3Galβ1-4GlcNAc, shows well-regulated expression and unique functions in the nervous system. Recent studies have revealed sophisticated and complicated expression mechanisms for HNK-1 glycan. Activities of biosynthetic enzymes are controlled through the formation of enzyme-complexes and regulation of subcellular localization. Functional aspects of HNK-1 carbohydrate were examined by overexpression, knockdown, and knockout studies of these enzymes. HNK-1 is involved in several neural functions such as synaptic plasticity, learning and memory, and the underlying molecular mechanisms have been illustrated upon identification of the target carrier glycoproteins of HNK-1 such as the glutamate receptor subunit GluA2 or tenascin-R. In this review, we describe recent findings about HNK-1 carbohydrate that provide further insights into the mechanism of its expression and function in the nervous system.     

一种新的决策支持系统开发方法——层次模型法

层次模型法是我国研究的新的决策支持系统开发方法。文章介绍了层次模型法的研究背景和研究思想。层次模型也包括应用层、任务层、功能层和物理层。文章详细介绍了其独有的任务层和功能层的实现方法。最后，文章说明了基于层次模型法的某公司年度生产经营决策支持系统的设计和开发思路。层次模范法作为通用决策支持系统生成器，具有一定的理论价值和实践价值。     

Regulation of primary cilia formation and left-right patterning in zebrafish by a noncanonical Wnt signaling mediator, duboraya

Primary cilia are microtubule-based organelles that project from the surface of nearly every animal cell. Although important functions of primary cilia in morphogenesis and tissue homeostasis have been identified, the mechanisms that control the formation of primary cilia are not understood. Here we characterize a zebrafish gene, termed duboraya (dub), that is essential for ciliogenesis. Knockdown of dub in zebrafish embryos results in both defects in primary cilia formation in Kupffer's vesicle and randomization of left-right organ asymmetries. We show that, at the molecular level, the function of dub in ciliogenesis is regulated by phosphorylation, which in turn depends on Frizzled-2-mediated noncanonical Wnt signaling. We also provide evidence that, at the cellular level, dub function is essential for actin organization in the cells lining Kupffer's vesicle. Taken together, our findings identify a molecular factor that links noncanonical Wnt signaling with the control of left-right axis specification, and provide an entry point for analyzing the mechanisms that regulate primary cilia formation.     

任务管理系统的研究

对我们研究的决策支持系统(actDSS)而言，一个任务不仅由许多集成的模型组成，而且还包括各种算法，进行输入输出的图形模型，以及表示数据关系的数据模型，所有这些部分的集合就是一个任务。任务管理系统(TMS)必须考虑到任务构造和运行的各个方面。     

Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase.

Leptin is a hormone secreted by adipocytes that plays a pivotal role in regulating food intake, energy expenditure and neuroendocrine function. Leptin stimulates the oxidation of fatty acids and the uptake of glucose, and prevents the accumulation of lipids in nonadipose tissues, which can lead to functional impairments known as "lipotoxicity". The signalling pathways that mediate the metabolic effects of leptin remain undefined. The 5'-AMP-activated protein kinase (AMPK) potently stimulates fatty-acid oxidation in muscle by inhibiting the activity of acetyl coenzyme A carboxylase (ACC). AMPK is a heterotrimeric enzyme that is conserved from yeast to humans and functions as a 'fuel gauge' to monitor the status of cellular energy. Here we show that leptin selectively stimulates phosphorylation and activation of the alpha2 catalytic subunit of AMPK (alpha2 AMPK) in skeletal muscle, thus establishing a previously unknown signalling pathway for leptin. Early activation of AMPK occurs by leptin acting directly on muscle, whereas later activation depends on leptin functioning through the hypothalamic-sympathetic nervous system axis. In parallel with its activation of AMPK, leptin suppresses the activity of ACC, thereby stimulating the oxidation of fatty acids in muscle. Blocking AMPK activation inhibits the phosphorylation of ACC stimulated by leptin. Our data identify AMPK as a principal mediator of the effects of leptin on fatty-acid metabolism in muscle.     

A FORMAL SYSTEMS APPROACH TO SOLVER DESIGN—HILL CLIMBING METHOD WITH PUSH DOWN STACK

This paper presents a formal approach to design of a solver of an intelligent managementinformation system and its implementation. The approach implies set theoretic modeling based on thegeneral systems concepts and implementation in the extProlog. There are research efforts which attack(optimization)problems using the set theory and logics.Furthermore, they use logic programming languages for their implementation. Although their methodslook quite similar to the approach of this paper, there are clear differences between them. This paper isinterested in exploration of the solving system rather than algorithms. The paper first presents a design and implementation procedure of a solver. Then, classificationof problems is discussed. The least structured class of the classification is the target of this paper. Adata mining system is an example of the class. Formal theories are derived for the design procedure assuming the least structured case. A solvingstrategy,which is called a hill climbing method with a     

SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populations

We conducted a genome-wide association study using 207,097 SNP markers in Japanese individuals with type 2 diabetes and unrelated controls, and identified KCNQ1 (potassium voltage-gated channel, KQT-like subfamily, member 1) to be a strong candidate for conferring susceptibility to type 2 diabetes. We detected consistent association of a SNP in KCNQ1 (rs2283228) with the disease in several independent case-control studies (additive model P = 3.1 x 10(-12); OR = 1.26, 95% CI = 1.18-1.34). Several other SNPs in the same linkage disequilibrium (LD) block were strongly associated with type 2 diabetes (additive model: rs2237895, P = 7.3 x 10(-9); OR = 1.32, 95% CI = 1.20-1.45, rs2237897, P = 6.8 x 10(-13); OR = 1.41, 95% CI = 1.29-1.55). The association of these SNPs with type 2 diabetes was replicated in samples from Singaporean (additive model: rs2237895, P = 8.5 x 10(-3); OR = 1.14, rs2237897, P = 2.4 x 10(-4); OR = 1.22) and Danish populations (additive model: rs2237895, P = 3.7 x 10(-11); OR = 1.24, rs2237897, P = 1.2 x 10(-4); OR = 1.36).     

Collapse ratios of buildings due to the 1995 Kobe earthquake and interference between S-wave and the second surface wave at basin edge

The distribution characteristics of collapse ratios of buildings in Kobe city due to the 1995 M7.2 Hyogo-ken Nanbu, Japan (Kobe) earthquake and the interferenres due to SH or P-SV and the second surface waves propagating in heterogeneous medium are discussed in this paper by using numerical simulation technique of wave equation. The staggered grid real value fast Fourier transform differentiation (SGRFFTD) is used in the pseudospectral method of ground motion simulations because of its speed, high stability and accuracy. The results show that the maximum amplitude of simulated acceleration waveforms on the ground coincides well with the complicated distributions of collapse ratios of buildings. The peak collapse ratio of buildings away from the earthquake fault also coincides well with the peak ground acceleration. The spatial interference process is analyzed by using the snap shots of seismic wave propagation. The peak ground acceleration is probably caused by the interferences due to the second surfare wave transmitting from the bedrock to sedimentary basin and the upward body wave. Analyses of the interference process show that seismic velocity structure and geologic structure strongly influence the distribution of the maximum amplitude of acceleration waveforms. Interferences occurring near the basin boundary are probably the cause of the peak collapse ratio of buildings away from the fault. Therefore it is necessary to analyze wave propagations and interference process using numerical simulation strategy for studies on the seismic disasters.     

AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus

Obesity is an epidemic in Western society, and causes rapidly accelerating rates of type 2 diabetes and cardiovascular disease. The evolutionarily conserved serine/threonine kinase, AMP-activated protein kinase (AMPK), functions as a 'fuel gauge' to monitor cellular energy status. We investigated the potential role of AMPK in the hypothalamus in the regulation of food intake. Here we report that AMPK activity is inhibited in arcuate and paraventricular hypothalamus (PVH) by the anorexigenic hormone leptin, and in multiple hypothalamic regions by insulin, high glucose and refeeding. A melanocortin receptor agonist, a potent anorexigen, decreases AMPK activity in PVH, whereas agouti-related protein, an orexigen, increases AMPK activity. Melanocortin receptor signalling is required for leptin and refeeding effects on AMPK in PVH. Dominant negative AMPK expression in the hypothalamus is sufficient to reduce food intake and body weight, whereas constitutively active AMPK increases both. Alterations of hypothalamic AMPK activity augment changes in arcuate neuropeptide expression induced by fasting and feeding. Furthermore, inhibition of hypothalamic AMPK is necessary for leptin's effects on food intake and body weight, as constitutively active AMPK blocks these effects. Thus, hypothalamic AMPK plays a critical role in hormonal and nutrient-derived anorexigenic and orexigenic signals and in energy balance.     

Retinoic acid signalling links left-right asymmetric patterning and bilaterally symmetric somitogenesis in the zebrafish embryo

During embryogenesis, cells are spatially patterned as a result of highly coordinated and stereotyped morphogenetic events. In the vertebrate embryo, information on laterality is conveyed to the node, and subsequently to the lateral plate mesoderm, by a complex cascade of epigenetic and genetic events, eventually leading to a left-right asymmetric body plan. At the same time, the paraxial mesoderm is patterned along the anterior-posterior axis in metameric units, or somites, in a bilaterally symmetric fashion. Here we characterize a cascade of laterality information in the zebrafish embryo and show that blocking the early steps of this cascade (before it reaches the lateral plate mesoderm) results in random left-right asymmetric somitogenesis. We also uncover a mechanism mediated by retinoic acid signalling that is crucial in buffering the influence of the flow of laterality information on the left-right progression of somite formation, and thus in ensuring bilaterally symmetric somitogenesis.