兴奋性-抑制性的平衡突触、回路、系统

兴奋性和抑制性的理想平衡是大脑正常功能和可塑性的根基，而当前对神经元的研究中，很大程度上忽视了细胞同时涉及到兴奋-抑制两方面平衡网络系统这一事实。我们对于兴奋性突触传递和修饰有着比较深入的理解，而对于抑制性中间神经元和它们对应的可塑性的探索则大大落后。本书以一种兴奋．抑制均衡的整合方式对神经元的有关功能进行了阐述，侧重于大脑各区域各种水平上这种平衡的建立、保持、修饰过程，同时结合神经学研究中多项最新方法、技术，为读者展示了分子水平、细胞水平直到系统水平上神经科学的多项研究热点。     

一套用于秀丽隐杆线虫多感觉信息整合机制研究的行为学系统（英文）

动物通过感知不同的感觉信息来介导自己的行为.神经系统如何进行多感觉信息整合仍然是神经科学领域一个悬而未决的问题.本文对秀丽隐杆线虫如何整合温度和盐刺激这两种对其生存至关重要的刺激进行研究.我们设计了一套行为学系统,可以在正交方向同时产生稳定的线性温度和盐浓度梯度.通过将本文中的行为学系统与一套追踪系统和钙成像系统结合,我们对秀丽隐杆线虫趋向行为的行为策略以及参与这一行为的两个主要感觉神经元AFD和ASER的功能进行分析.我们的工作开启了一个全新的视野,在精巧的神经系统结构中进行多感觉信息整合的研究.     

基于PLS/ANN-RP-HPLC的甲基苯甲醛同分异构体的同时测定

将偏最小二乘法(PLS)和人工神经网络(ANN)技术与反相高效液相色谱法(RPHPLC)相结合,应用于邻、间、对三种甲基苯甲醛同分异构体的同时测定。通过确定主成分数、神经元个数、训练次数和目标误差,建立了预测模型,并比较了两种方法的预测能力。实验结果表明,所建立的同时测定甲基苯甲醛三种同分异构体的方法不仅可以正确识别三种同分异构体,而且成功预测了各组分的质量浓度,PLS-RP-HPLC和ANN-RP-HPLC两种方法精密度试验的相对标准偏差(RSD)分别≤1.20%、≤0.70%,而用于合成样品测定的加标回收率范围在97.54%~116.77%之间,其相对偏差≤±15.4%.表明这两种方法均可用于甲基苯甲醛三种同分异构体混合物中各组分的同时测定,并且ANN的预测能力相对较强。     

基于DSP的信号与系统仿真实验平台的设计

提出了一种基于DSP的信号与系统仿真实验平台实现方案．这一实验平台采用了将软件和硬件有机结合来进行仿真的方法,当用户在计算机界面上进行实验操作时,实验结果波形可以在实际的示波器上显示出来．仿真实验平台的软件方面主要是编写了一个在主机上运行的用户界面,用以将仿真实验的内容完整地展示给用户,并允许用户进行实验操作．硬件方面则使用一块以DSP系统为核心的实验板与主机通信,主要功能是将用户进行的实验操作进行计算,并将结果通过仿真,在示波器上显示出来．从而使使用者获得较为真实的实验感受,对信号处理有一个更深层次的认识．     

二硝基苯肼法测定电解混合液中苯甲醛的含量

本文作者用腙生成法分析了甲苯电解氧化生成苯甲醛过程的混合液里苯甲醛的含量．探讨了沉淀剂用量、酸度及混合液中其他共存物的影响．实验结果表明，该方法具有分析数据稳定、结果可靠、精密度较高、易于操作和重现性好等特点，回收率达到９６％～１０４％，可以作为电解过程生成的苯甲醛含量分析的一种实用方法．     

微波辐射下硫酸铜催化合成苯甲醛乙二醇缩醛

用无水硫酸铜作催化剂,在微波辐射下催化合成苯甲醛乙二醇缩醛.系统考察微波辐射功率、微波辐射时间、原料配比、催化剂用量、带水剂用量对产率的影响.实验结果表明：当微波输出功率为600 W,辐射时间为12 min,苯甲醛用量为0.075 mol,乙二醇用量为0.112 5 mol,无水硫酸铜用量为1.2 g,带水剂环己烷用量为12 mL时,产率可达77.9%.     

中华卵索线虫雌雄成虫可溶性总蛋白的初步比较

采用聚丙烯酰胺凝胶电泳技术对中华卵索线虫成虫可溶性总蛋白进行了比较和分析，初步的实验结果表明，雌性成虫特异表达3种以上蛋白质，分子量分别为78．33KD、72．39KD、24．58KD、15．99KD；雄性成虫则特异表达分子量为26．39KD的蛋白质．雌雄成虫总蛋白存在着差异，这为进一步研究中华卵索线虫的性别分化机制提供了基础数据．     

一种线性神经元PI控制器模型

在对常规PI控制器模型分析的基础上，结合线性神经元自学习能力和适应能力强的优点，提出了一种线性神经元PI控制器模型．该模型结构简单，在一定程度上实现了比例系数和积分比例系数的自整定功能，能够在简单系统中取得较好的效果，具有工程实践应用价值．以单级三冲量锅炉汽包水位控制系统为例，分析了线性神经元PI控制器的控制效果及特点，仿真实验表明应用该控制器的系统具有优良的控制品质．     

一种更精确的现实性动态神经网络模型

神经元的功能主要由突触后膜、胞体膜和始段膜三种膜结构的不同活动特性决定的．根据这三种膜结构的电生理性质及其形态结构提出了一个比较精确的现实性动态神经网络模型．计算机仿真结果表明这个模型在具有比较简明的形式及较小的计算量的同时，能较全面地反映神经元的活动特性．通过与其他模型的比较，对神经元各部分的结构与其功能的关系有进一步的认识．     

制药工程专业药物化学实验与有机化学实验教学存在问题与课程整合探讨

阐述了制药工程专业在有机化学实验和药物化学实验两门课程课程体系设置与教学中存在的问题，对于两门课程的整合进行了探讨。     

Dissecting a circuit for olfactory behaviour in Caenorhabditis elegans

Although many properties of the nervous system are shared among animals and systems, it is not known whether different neuronal circuits use common strategies to guide behaviour. Here we characterize information processing by Caenorhabditis elegans olfactory neurons (AWC) and interneurons (AIB and AIY) that control food- and odour-evoked behaviours. Using calcium imaging and mutations that affect specific neuronal connections, we show that AWC neurons are activated by odour removal and activate the AIB interneurons through AMPA-type glutamate receptors. The level of calcium in AIB interneurons is elevated for several minutes after odour removal, a neuronal correlate to the prolonged behavioural response to odour withdrawal. The AWC neuron inhibits AIY interneurons through glutamate-gated chloride channels; odour presentation relieves this inhibition and results in activation of AIY interneurons. The opposite regulation of AIY and AIB interneurons generates a coordinated behavioural response. Information processing by this circuit resembles information flow from vertebrate photoreceptors to 'OFF' bipolar and 'ON' bipolar neurons, indicating a conserved or convergent strategy for sensory information processing.     

Mitochondrial endonuclease G is important for apoptosis in C. elegans.

Programmed cell death (apoptosis) is a tightly regulated process of cell disassembly in which dying cells and their nuclei shrink and fragment and the chromosomal DNA is degraded into internucleosomal repeats. Here we report the characterization of the cps-6 gene, which appears to function downstream of, or in parallel to, the cell-death protease CED-3 of Caenorhabditis elegans in the DNA degradation process during apoptosis. cps-6 encodes a homologue of human mitochondrial endonuclease G, and its protein product similarly localizes to mitochondria in C. elegans. Reduction of cps-6 activity caused by a genetic mutation or RNA-mediated interference (RNAi) affects normal DNA degradation, as revealed by increased staining in a TUNEL assay, and results in delayed appearance of cell corpses during development in C. elegans. This observation provides in vivo evidence that the DNA degradation process is important for proper progression of apoptosis. CPS-6 is the first mitochondrial protein identified to be involved in programmed cell death in C. elegans, underscoring the conserved and important role of mitochondria in the execution of apoptosis.     

Genome-wide RNAi analysis of Caenorhabditis elegans fat regulatory genes

Regulation of body fat storage involves signalling between centres that regulate feeding in the brain and sites of fat storage and use in the body. Here we describe an assay for analysing fat storage and mobilization in living Caenorhabditis elegans. By using RNA-mediated interference (RNAi) to disrupt the expression of each of the 16,757 worm genes, we have systematically screened the C. elegans genome for genes necessary for normal fat storage. We identify 305 gene inactivations that cause reduced body fat and 112 gene inactivations that cause increased fat storage. Analysis of the fat-reducing gene inactivations in insulin, serotonin and tubby signalling mutants of C. elegans, which have increased body fat, identifies a core set of fat regulatory genes as well as pathway-specific fat regulators. Many of the newly identified worm fat regulatory genes have mammalian homologues, some of which are known to function in fat regulation. Other C. elegans fat regulatory genes that are conserved across animal phylogeny, but have not previously been implicated in fat storage, may point to ancient and universal features of fat storage regulation, and identify targets for treating obesity and its associated diseases.     

DRP-1-mediated mitochondrial fragmentation during EGL-1-induced cell death in C. elegans

Genetic analyses in Caenorhabditis elegans have been instrumental in the elucidation of the central cell-death machinery, which is conserved from C. elegans to mammals. One possible difference that has emerged is the role of mitochondria. By releasing cytochrome c, mitochondria are involved in the activation of caspases in mammals. However, there has previously been no evidence that mitochondria are involved in caspase activation in C. elegans. Here we show that mitochondria fragment in cells that normally undergo programmed cell death during C. elegans development. Mitochondrial fragmentation is induced by the BH3-only protein EGL-1 and can be blocked by mutations in the bcl-2-like gene ced-9, indicating that members of the Bcl-2 family might function in the regulation of mitochondrial fragmentation in apoptotic cells. Mitochondrial fragmentation is independent of CED-4/Apaf-1 and CED-3/caspase, indicating that it occurs before or simultaneously with their activation. Furthermore, DRP-1/dynamin-related protein, a key component of the mitochondrial fission machinery, is required and sufficient to induce mitochondrial fragmentation and programmed cell death during C. elegans development. These results assign an important role to mitochondria in the cell-death pathway in C. elegans.     

Chemical structure and biological activity of the Caenorhabditis elegans dauer-inducing pheromone

Pheromones are cell type-specific signals used for communication between individuals of the same species. When faced with overcrowding or starvation, Caenorhabditis elegans secrete the pheromone daumone, which facilitates communication between individuals for adaptation to adverse environmental stimuli. Daumone signals C. elegans to enter the dauer stage, an enduring and non-ageing stage of the nematode life cycle with distinctive adaptive features and extended life. Because daumone is a key regulator of chemosensory processes in development and ageing, the chemical identification of daumone is important for elucidating features of the daumone-mediated signalling pathway. Here we report the isolation of natural daumone from C. elegans by large-scale purification, as well as the total chemical synthesis of daumone. We present the stereospecific chemical structure of purified daumone, a fatty acid derivative. We demonstrate that both natural and chemically synthesized daumones equally induce dauer larva formation in C. elegans (N2 strain) and certain dauer mutants, and also result in competition between food and daumone. These results should help to elucidate the daumone-mediated signalling pathway, which might in turn influence ageing and obesity research and the development of antinematodal drugs.     

水溶性人参皂苷对秀丽隐杆线虫生物学功能的影响

 以秀丽隐杆线虫作模式生物, 研究水溶性人参皂苷成分对线虫的寿命、 产卵和运动等生命活动的影响. 结果表明: 质量浓度为200 μg/mL的人参皂苷可使线虫寿命延长, 减缓衰老; 质量浓度为500 μg/mL的人参皂苷则对线虫具有一定的毒性作用.     

Lethargus is a Caenorhabditis elegans sleep-like state

There are fundamental similarities between sleep in mammals and quiescence in the arthropod Drosophila melanogaster, suggesting that sleep-like states are evolutionarily ancient. The nematode Caenorhabditis elegans also has a quiescent behavioural state during a period called lethargus, which occurs before each of the four moults. Like sleep, lethargus maintains a constant temporal relationship with the expression of the C. elegans Period homologue LIN-42 (ref. 5). Here we show that quiescence associated with lethargus has the additional sleep-like properties of reversibility, reduced responsiveness and homeostasis. We identify the cGMP-dependent protein kinase (PKG) gene egl-4 as a regulator of sleep-like behaviour, and show that egl-4 functions in sensory neurons to promote the C. elegans sleep-like state. Conserved effects on sleep-like behaviour of homologous genes in C. elegans and Drosophila suggest a common genetic regulation of sleep-like states in arthropods and nematodes. Our results indicate that C. elegans is a suitable model system for the study of sleep regulation. The association of this C. elegans sleep-like state with developmental changes that occur with larval moults suggests that sleep may have evolved to allow for developmental changes.     

A C. elegans stretch receptor neuron revealed by a mechanosensitive TRP channel homologue

The nematode Caenorhabditis elegans is commonly used as a genetic model organism for dissecting integration of the sensory and motor systems. Despite extensive genetic and behavioural analyses that have led to the identification of many genes and neural circuits involved in regulating C. elegans locomotion behaviour, it remains unclear whether and how somatosensory feedback modulates motor output during locomotion. In particular, no stretch receptors have been identified in C. elegans, raising the issue of whether stretch-receptor-mediated proprioception is used by C. elegans to regulate its locomotion behaviour. Here we have characterized TRP-4, the C. elegans homologue of the mechanosensitive TRPN channel. We show that trp-4 mutant worms bend their body abnormally, exhibiting a body posture distinct from that of wild-type worms during locomotion, suggesting that TRP-4 is involved in stretch-receptor-mediated proprioception. We show that TRP-4 acts in a single neuron, DVA, to mediate its function in proprioception, and that the activity of DVA can be stimulated by body stretch. DVA both positively and negatively modulates locomotion, providing a unique mechanism whereby a single neuron can fine-tune motor activity. Thus, DVA represents a stretch receptor neuron that regulates sensory-motor integration during C. elegans locomotion.     

A genetic link between co-suppression and RNA interference in C. elegans

Originally discovered in plants, the phenomenon of co-suppression by transgenic DNA has since been observed in many organisms from fungi to animals: introduction of transgenic copies of a gene results in reduced expression of the transgene as well as the endogenous gene. The effect depends on sequence identity between transgene and endogenous gene. Some cases of co-suppression resemble RNA interference (the experimental silencing of genes by the introduction of double-stranded RNA), as RNA seems to be both an important initiator and a target in these processes. Here we show that co-suppression in Caenorhabditis elegans is also probably mediated by RNA molecules. Both RNA interference and co-suppression have been implicated in the silencing of transposons. We now report that mutants of C. elegans that are defective in transposon silencing and RNA interference (mut-2, mut-7, mut-8 and mut-9) are in addition resistant to co-suppression. This indicates that RNA interference and co-suppression in C. elegans may be mediated at least in part by the same molecular machinery, possibly through RNA-guided degradation of messenger RNA molecules.     

余甘子对秀丽隐杆线虫的抗衰老作用

以模式生物秀丽隐杆线虫(简称线虫)为模型,考察质量浓度分别为1.0,2.0,4.0mg/mL的余甘子提取物对线虫的抗氧化作用.实验结果表明:1.0 mg/mL的余甘子提取物能显著提高线虫产卵量,且对线虫的运动能力无显著影响,即在实验的质量浓度范围内,余甘子提取物具有低毒性;1.0mg/mL的余甘子提取物能显著延长线虫的寿命,并具有抗氧化压力作用;1.0mg/mL的余甘子提取物可显著提高线虫体内过氧化物酶活性,从而达到抗氧化的保护作用.