Identification and synthesis of an efficient multivalent E. coli heat labile toxin inhibitor __ A dynamic combinatorial chemistry approach

A polymer based dynamic combinatorial library (DCL) was generated through condensation between aldehyde functionalized linear poly(glycidol) (APG) and galactose containing acylhydrazide derivatives. Pentameric E. coli heat labile enterotoxin B subunit (LTB) was subsequently applied to the DCL as external stimulus, resulting in amplification of a specific acylhydrazone side chain that was further used for the synthesis of a multivalent LTB inhibitor. In the in vitro biological evaluation, this inhibitor exhibited strong inhibition properties as well as low cytotoxicity.     

Aging in the rat hippocampus is associated with widespread reductions in the number of glutamate decarboxylase-67 positive interneurons but not interneuron degeneration

Increased excitability of principal excitatory neurons is one of the hallmarks of aging in the hippocampus, signifying a diminution in the number and/or function of inhibitory interneurons with aging. To elucidate this, we performed comprehensive GABA-ergic interneuron cell counts in all layers of the dentate gyrus and the CA1 and CA3 subfields, using serial sections from adult, middle-aged and aged Fischer 344 rats. Sections were immunostained for glutamate decarboxylase-67 (GAD-67, a synthesizing enzyme of GABA) and GAD-67 immunopositive interneurons were counted using an unbiased cell counting method, the optical fractionator. Substantial declines in the absolute number of GAD-67 immunopositive interneurons were found in all hippocampal layers/subfields of middle-aged and aged animals, in comparison with the adult animals. However, the counts were comparable between the middle-aged and aged groups for all regions. Interestingly, determination of the absolute number of interneurons using neuron-specific nuclear antigen (NeuN) expression in the strata oriens and radiatum of CA1 and CA3 subfields revealed an analogous number of interneurons across the three age groups. Furthermore, the ratio of GAD-67 immunopositive and NeuN positive interneurons decreased from adult age to middle age but remained relatively static between middle age and old age. Collectively, the results underscore that aging in the hippocampus is associated with wide-ranging decreases in the number of GAD-67 immunopositive interneurons and most of the age-related changes in GAD-67 immunopositive interneuron numbers transpire by middle age. Additionally, this study provides novel evidence that age-related reductions in hippocampal GAD-67 immunopositive interneuron numbers are due to loss of GAD-67 expression in interneurons rather than interneuron degeneration.     

土地利用变化的时空分异特征及驱动机制——以北京市海淀区、延庆县为例

研究土地利用变化的时空分异规律和机制对认识人类活动在全球变化中的作用机制具有重要意义.选择北京市海淀区、延庆县作为研究区,利用1992、2002年的遥感影像数据,采用转移矩阵法和多元线性回归法,分析了1992～2002年海淀区、延庆县土地利用变化的时空分异特征及其驱动机制.研究表明:①1992到2002年间,海淀区、延庆县土地利用变化的差异主要表现在:海淀区建设用地扩展速度明显高于延庆县,且内部改造强烈;延庆县农业用地面积减少程度明显低于海淀区,且有明显的内部结构调整;海淀区原有建设用地开始转变为林地. ②1992到2002年间,海淀区土地利用变化主要外在驱动力包括人口增长、第二产业(高新技术)、第三产业(房地产)的发展及北京市总体规划政策;最主要内在因素为前期土地利用方式;延庆县土地利用变化的主要外在驱动力包括非农业人口的增长、第三产业(旅游业)的发展、农业结构调整及生态建设;最主要内在因素为地形因素. ③海淀区土地利用变化是政策主导,延庆县土地利用变化是经济发展主导.     

Calystegines in Calystegia sepium do not inhibit fungal growth and invertase activity but interact with plant invertase

Abstract: Calystegines are alkaloidal glycosidase inhibitors. They accumulate predominantly in young and meristemic parts of Calystegia sepium (Convolvulaceae). C. sepium, bindweed, infests meadows and cereal fields and is difficult to control chemically. Fungal pathogens against C. sepium are established as mycoherbicides. Stagonospora convolvuli LA39 attacks C. sepium and does not affect crop plants, but young plants of C. sepium are less susceptible to the fungus. The interaction of Stagonospora convolvuli with calystegines was investigated. Further, endophytic fungi of several classes were isolated from wild-grown Calystegia sepium leaves, and selected strains were tested for interaction with calystegines. Fungal growth on agar containing calystegines was not affected considerably. Plants in climate chambers were infected with an endophyte, Phomopsis, and with the fungal pathogen, Stagonospora convolvuli. Calystegine levels were measured in infected and non-infected plant tissues. Accumulation depended on developmental stage of the plant tissue and was not influenced by infection. Acid invertase was measured from fungal mycelia and from infected and non-infected plant tissues. Fungal acid invertase activity was not inhibited by 10 mM calystegine B₂, while invertase from C. sepium leaves was inhibited. It is concluded that calystegines do not inhibit fungal development and sucrose consumption under the conditions of the present investigation, but may act by redirection of plant carbohydrate metabolism.     

False belief reasoning in the brain: An ERP study

Understanding others mind and interpersonal interaction are the cognitive basis of successful social interactions. People's mental states and behaviors rely on their holding beliefs for self and others. To investigate the neural substrates of false belief reasoning, the 32 channels event-related potentials (ERP) of 14 normal adults were measured while they understood false-belief and true belief used de-ceptive appearance task. After onset of the false-belief or true-belief questions, N100, P200 and late negative component (LNC) were elicited at centro-frontal sites. Compared with true belief, false belief reasoning elicited significant declined LNC in the time window from 400 to 800 ms. The source analysis of difference wave (False minus True) showed a dipole located in the middle cingulated cortex. These findings show that false belief reasoning probably included inhibitive process.     

Structure and function of ferredoxin-NADP+-oxidoreductase

The redox-enzyme ferredoxin-NADP-oxidoreductase has been shown to be activated by light and inactivated in the dark. This review will summarize recent data concerning the biochemical characterization of the enzyme compared to its in-vivo activation. Further-more the mechanism of this activation process is discussed as a conformational change caused by the light-driven proton gradient.Abbreviations cyt cytochrome - fd ferredoxin - FNR1 large form of ferredoxin-NADP-oxidoreductase - FNRox oxidized FNR - FNRred reduced FNR - FNRs small form of FNR - FNRsq FNR-semiquinone     

The other kind of biological NMR—Studies of enzyme-substrate interactions

NMR spectroscopy has proved to be a valuable tool in the study of the interactions between enzymes and their substrates. The kinds of structural and dynamic information which can be obtained are illustrated by studies of three enzymes involved in drug metabolism. Cytochromes P₄₅₀ play a crucial role in metabolism of a wide range of exogenous chemicals. NMR has been used to measure distances from the haem iron of the cytochrome to protons of the bound substrate, leading to detailed structural models for the enzyme-substrate complexes. The other two enzymes, chloramphenicol acetyltransferase and β-lactamase, are responsible for bacterial resistance to specific antibiotics. In chloramphenicol acetyltransferase, NMR has been used to determine the conformation of coenzyme A bound to the enzyme, while in the case of β-lactamase the pK of a specific lysine residue at the active site has been determined, providing valuable information on the catalytic mechanism. Special issue dedicated to Dr. Herman Bachelard.     

Blackboard Mechanism Based Ant Colony Theory for Dynamic Deployment of Mobile Sensor Networks

A novel bionic swarm intelligence algorithm, called ant colony algorithm based on a blackboard mechanism, is proposed to solve the autonomy and dynamic deployment of mobiles sensor networks effectively. A blackboard mechanism is introduced into the system for making pheromone and completing the algorithm. Every node, which can be looked as an ant, makes one information zone in its memory for communicating with other nodes and leaves pheromone, which is created by ant itself in naalre. Then ant colony theory is used to find the optimization scheme for path planning and deployment of mobile Wireless Sensor Network （WSN）. We test the algorithm in a dynamic and unconfigurable environment. The results indicate that the algorithm can reduce the power consumption by 13% averagely, enhance the efficiency of path planning and deployment of mobile WSN by 15% averagely.     

Tn5转座突变技术在革兰氏阴性细菌分子遗传研究中的应用

随着广宿主载体系统的发展,Tn5及其衍生载体已经广泛应用于革兰氏阴性细菌的分子遗传学研究。主要综述了Tn5转座突变技术在生防细菌生防机理研究、细菌必需基因的鉴定、病原细菌毒力相关基因研究、代谢调控基因研究和菌株的遗传改良方面的应用研究进展。     

The potato tuber,maize endosperm and a chimeric maize-potato ADP-glucose pyrophosphorylase exhibit fundamental differences in Pi inhibition

ADP-glucose pyrophosphorylase (AGPase) is highly regulated by allosteric effectors acting both positively and negatively. Enzymes from various sources differ, however, in the mechanism of allosteric regulation. Here, we determined how the effector, inorganic phosphate (Pi), functions in the presence and absence of saturating amounts of the activator, 3-phosphoglyceric acid (3-PGA). This regulation was examined in the maize endosperm enzyme, the oxidized and reduced forms of the potato tuber enzyme as well as a small subunit chimeric AGPase (MP), which contains both maize endosperm and potato tuber sequences paired with a wild-type maize large subunit. These data, combined with our previous kinetic studies of these enzymes led to a model of Pi inhibition for the various enzymes. The Pi inhibition data suggest that while the maize enzyme contains a single effector site that binds both 3-PGA and Pi, the other enzymes exhibit more complex behavior and most likely have at least two separate interacting binding sites for Pi. The possible physiological implications of the differences in Pi inhibition distinguishing the maize endosperm and potato tuber AGPases are discussed.