• 【胆碱能和去甲肾上腺素能系统参与慢性应激大鼠接受氧代雷莫林治疗后的行为恢复。】 复制标题 收藏 收藏
    DOI:10.1016/j.neuroscience.2006.08.041 复制DOI
    作者列表:Srikumar BN,Raju TR,Shankaranarayana Rao BS
    BACKGROUND & AIMS: :Chronic stress in rats has been shown to impair learning and memory, and precipitate several affective disorders like depression and anxiety. The mechanisms involved in these stress-induced disorders and the possible reversal are poorly understood, thus limiting the number of drugs available for their treatment. Our earlier studies suggest cholinergic dysfunction as the underlying cause in the behavioral deficits following stress. Muscarinic cholinergic agonist, oxotremorine is demonstrated to have a beneficial effect in reversing brain injury-induced behavioral dysfunction. In this study, we have evaluated the effect of oxotremorine treatment on chronic restraint stress-induced cognitive deficits. Rats were subjected to restraint stress (6 h/day) for 21 days followed by oxotremorine treatment for 10 days. Spatial learning and memory was assessed in a partially baited eight-arm radial maze task. Stressed rats exhibited impairment in performance, with decreased percentage of correct choices and an increase in the number of reference memory errors (RMEs). Oxotremorine treatment (0.1 or 0.2 mg/kg, i.p.) to stressed rats resulted in a significant increase in the percent correct choices and a decrease in the number of RMEs compared with stress as well as the stress+vehicle-treated groups. In the retention test, oxotremorine treated rats committed less RMEs compared with the stress group. Chronic restraint stress decreased acetylcholinesterase (AChE) activity in the hippocampus, frontal cortex and septum, which was reversed by both the doses of oxotremorine. Further, oxotremorine treatment also restored the norepinephrine levels in the hippocampus and frontal cortex. Thus, this study demonstrates the potential of cholinergic muscarinic agonists and the involvement of both cholinergic and noradrenergic systems in the reversal of stress-induced learning and memory deficits.
    背景与目标: 大鼠慢性应激已被证明会损害学习和记忆,并引发多种情绪障碍,如抑郁和焦虑。这些压力引起的疾病和可能的逆转涉及的机制了解甚少,因此限制了可用于治疗的药物数量。我们较早的研究表明,胆碱能功能障碍是压力后行为缺陷的根本原因。毒蕈碱胆碱能激动剂,oxotremorine被证明在逆转脑损伤引起的行为功能障碍方面具有有益作用。在这项研究中,我们评估了氧代雷莫林治疗对慢性束缚应激诱导的认知缺陷的影响。对大鼠进行束缚应激(6小时/天),持续21天,然后进行氧代莫瑞林治疗10天。在部分诱饵的八臂径向迷宫任务中评估了空间学习和记忆。应激大鼠表现出功能受损,正确选择的百分比降低,参考记忆错误(RME)数量增加。与应激组和应激载体治疗组相比,对应激大鼠进行氧代雷莫林治疗(0.1或0.2 mg / kg,腹膜内)导致正确选择的百分比显着增加,RME数量减少。在保留测试中,与应激组相比,用氧代苯甲酸治疗的大鼠的RME较少。慢性束缚应激会降低海马,额叶皮层和隔垫中的乙酰胆碱酯酶(AChE)活性,这两种剂量的奥索莫瑞宁均可逆转。此外,oxotremorine治疗还可以恢复海马和额叶皮层的去甲肾上腺素水平。因此,这项研究证明了胆碱能毒蕈碱激动剂的潜力以及胆碱能和去甲肾上腺素能系统在逆转应激诱导的学习和记忆缺陷中的作用。
  • 【储存时间和温度对两个自蚀刻系统性能的影响。】 复制标题 收藏 收藏
    DOI:10.1016/j.jdent.2006.08.004 复制DOI
    作者列表:Sadr A,Ghasemi A,Shimada Y,Tagami J
    BACKGROUND & AIMS: OBJECTIVES:To evaluate the micro-shear bond strength to enamel and dentin, pH and hardness of two self-etching adhesives over a period of 60 weeks storage at different temperatures. MATERIALS AND METHODS:Two self-etching systems, an all-in-one adhesive, Clearfil Tri-S Bond (TS) and a two-step adhesive, Clearfil SE Bond (SE) were used in this study (both by Kuraray Medical, Osaka, Japan). Their micro-shear bond strengths to enamel and dentin were measured. The materials were then stored at 4, 23 or 37 degrees C. Their bond strengths were measured again after 1, 4, 16 and 60 weeks and compared to the base line. The nano-indentation hardness of the polymerized bonding, pH of SE primer and TS were also measured at the baseline and after 60 weeks of storage at three different temperatures. Bond-strength and hardness data were analyzed using ANOVA and post hoc tests at the significance level of 0.05. RESULTS:Two-way ANOVA analysis showed that both storage conditions and material type had significant effects on bond strength to enamel or dentin but the interactions of these factors were not significant for any of the substrates. One-way ANOVA post hoc tests revealed that the bond strength of adhesives stored at 37 degrees C significantly decreased during the storage period; with the earliest significant decreases observed at 4 weeks for TS and at 16 weeks for SE. After 60 weeks of storage, the hardness obtained for SE bonding resin was not significantly different with that at the baseline for 4, 23 and 37 degrees C groups, but there was a significant decrease observed in hardness for TS stored at 37 degrees C, compared to that at the baseline. The pH of both self-etching materials decreased when they were stored at 37 degrees C. CONCLUSION:Storage time and temperature significantly affected the bond strength of both materials through the time dependent hydrolysis and other changes that are likely to occur in the water-containing self-etching agents at high temperatures.
    背景与目标: 目的:评估两种在不同温度下储存60周的自蚀刻胶粘剂对牙釉质和牙本质的微剪切粘合强度,pH值和硬度。
    材料与方法:这项研究使用了两个自蚀刻系统,即一体式粘合剂Clearfil Tri-S Bond(TS)和两步式粘合剂Clearfil SE Bond(SE)(均由Kuraray Medical,日本大阪)。测量了它们对牙釉质和牙本质的微剪切粘合强度。然后将材料存储在4、23或37摄氏度下。在1、4、16和60周后再次测量其粘合强度,并与基准线进行比较。还在基线和在三种不同温度下储存60周后,测量了聚合键的纳米压痕硬度,SE底漆和TS的pH。使用ANOVA和事后检验分析粘结强度和硬度数据,显着性水平为0.05。
    结果:双向方差分析表明,储存条件和材料类型对与牙釉质或牙本质的粘合强度均具有显着影响,但这些因素的相互作用对任何底物均不显着。单向方差分析事后测试表明,在37°C下储存的胶粘剂的粘合强度在储存期间显着降低;在TS的第4周和SE的第16周观察到最早的显着下降。储存60周后,SE粘合树脂的硬度与4、23和37摄氏度组的基线硬度没有显着差异,但是与在37摄氏度下储存的TS相比,硬度明显降低达到基线时的水平。两种自蚀刻材料的pH值均在37摄氏度下存储时降低。
    结论:储存时间和温度通过时间依赖性水解和在高温下水性自蚀刻剂中可能发生的其他变化,显着影响两种材料的粘合强度。
  • 【逆向工程细胞系统的贝叶斯方法:非线性高斯网络的仿真研究。】 复制标题 收藏 收藏
    DOI:10.1186/1471-2105-8-S5-S2 复制DOI
    作者列表:Ferrazzi F,Sebastiani P,Ramoni MF,Bellazzi R
    BACKGROUND & AIMS: BACKGROUND:Reverse engineering cellular networks is currently one of the most challenging problems in systems biology. Dynamic Bayesian networks (DBNs) seem to be particularly suitable for inferring relationships between cellular variables from the analysis of time series measurements of mRNA or protein concentrations. As evaluating inference results on a real dataset is controversial, the use of simulated data has been proposed. However, DBN approaches that use continuous variables, thus avoiding the information loss associated with discretization, have not yet been extensively assessed, and most of the proposed approaches have dealt with linear Gaussian models. RESULTS:We propose a generalization of dynamic Gaussian networks to accommodate nonlinear dependencies between variables. As a benchmark dataset to test the new approach, we used data from a mathematical model of cell cycle control in budding yeast that realistically reproduces the complexity of a cellular system. We evaluated the ability of the networks to describe the dynamics of cellular systems and their precision in reconstructing the true underlying causal relationships between variables. We also tested the robustness of the results by analyzing the effect of noise on the data, and the impact of a different sampling time. CONCLUSION:The results confirmed that DBNs with Gaussian models can be effectively exploited for a first level analysis of data from complex cellular systems. The inferred models are parsimonious and have a satisfying goodness of fit. Furthermore, the networks not only offer a phenomenological description of the dynamics of cellular systems, but are also able to suggest hypotheses concerning the causal interactions between variables. The proposed nonlinear generalization of Gaussian models yielded models characterized by a slightly lower goodness of fit than the linear model, but a better ability to recover the true underlying connections between variables.
    背景与目标: 背景技术:反向工程蜂窝网络目前是系统生物学中最具挑战性的问题之一。动态贝叶斯网络(DBN)似乎特别适用于通过对mRNA或蛋白质浓度的时间序列测量结果进行分析来推断细胞变量之间的关系。由于评估真实数据集上的推理结果存在争议,因此提出了使用模拟数据的建议。然而,尚未对使用连续变量,从而避免与离散化相关的信息丢失的DBN方法进行了广泛的评估,并且大多数提议的方法已经处理了线性高斯模型。
    结果:我们提出了动态高斯网络的一般化,以适应变量之间的非线性依赖性。作为测试新方法的基准数据集,我们使用了发芽酵母中细胞周期控制数学模型的数据,真实地再现了细胞系统的复杂性。我们评估了网络描述蜂窝系统动态的能力及其在重构变量之间真正的因果关系上的精度。我们还通过分析噪声对数据的影响以及不同采样时间的影响,测试了结果的鲁棒性。
    结论:结果证实具有高斯模型的DBN可以有效地用于复杂细胞系统数据的第一级分析。推断的模型是简约的,并且具有令人满意的拟合优度。此外,这些网络不仅提供了细胞系统动力学的现象学描述,而且还能够提出有关变量之间因果关系的假设。提出的高斯模型非线性泛化得出的模型的拟合优度比线性模型低,但具有恢复变量之间真正基础联系的能力。
  • 【化学遗传学:阐明具有小分子化合物的生物系统。】 复制标题 收藏 收藏
    DOI:10.1038/sj.jid.5700853 复制DOI
    作者列表:Kawasumi M,Nghiem P
    BACKGROUND & AIMS: :Chemical genetics employs diverse small-molecule compounds to elucidate biological processes in a manner analogous to the mutagenesis strategies at the core of classical genetics. Screening small-molecule libraries for compounds that induce a phenotype of interest represents the forward chemical genetic approach, whereas the reverse approach involves small molecules targeting a single protein. Here, we review key differences between the goals for small-molecule screening in industry versus academia, recent developments in high-throughput screening, and publicly available resources of compound collections, screening facilities, and databases. A particularly exciting outcome of a chemical genetic screen is the discovery of a previously unknown role for a protein in a pathway together with compounds that affect the function of that protein. In illustrative cases, such discoveries have led to progress toward therapeutic development and more commonly have increased the size of the small molecule "toolbox" available to the research community for the study of biological processes.
    背景与目标: 化学遗传学采用多种小分子化合物来阐明生物学过程,其方式类似于经典遗传学的核心诱变策略。在小分子文库中筛选诱导目标表型的化合物代表了正向化学遗传方法,而反向方法则涉及靶向单个蛋白质的小分子。在这里,我们回顾了工业界和学术界对小分子筛选的目标,高通量筛选的最新发展以及化合物集合,筛选设施和数据库的公开可用资源之间的主要区别。化学遗传筛选的一个特别令人兴奋的结果是,发现一种蛋白质在通路中的作用是未知的,而化合物会影响该蛋白质的功能。在说明性情况下,这样的发现导致了治疗发展的进步,并且更普遍地增加了可供研究团体用于生物学过程研究的小分子“工具箱”的大小。
  • 【主动灯丝系统中集体运动的出现和瞬态行为。】 复制标题 收藏 收藏
    DOI:10.1038/s41467-017-00035-3 复制DOI
    作者列表:Suzuki R,Bausch AR
    BACKGROUND & AIMS: :Most living systems, ranging from animal flocks, self-motile microorganisms to the cytoskeleton rely on self-organization processes to perform their own specific function. Despite its importance, the general understanding of how individual active constituents initiate the intriguing pattern formation phenomena on all these different length scales still remains elusive. Here, using a high density actomyosin motility assay system, we show that the observed collective motion arises from a seeding process driven by enhanced acute angle collisions. Once a critical size is reached, the clusters coarsen into high and low density phases each with fixed filament concentrations. The steady state is defined by a balance of collision induced randomization and alignment effects of the filaments by multi-filament collisions within ordered clusters.Self-organization is observed in cytoskeletal systems but emergence of order from disorder is poorly understood. Using a high density actomyosin system, the authors capture the transition from disorder to order, which is driven by enhanced alignment effects caused by increase in multi-filament collisions.
    背景与目标: :从动物群,自我活动性微生物到细胞骨架的大多数生命系统都依赖于自我组织过程来执行其自身的特定功能。尽管它很重要,但是对于各个活性成分如何在所有这些不同的长度尺度上引发有趣的图案形成现象的一般理解仍然是难以捉摸的。在这里,使用高密度放线菌素运动分析系统,我们显示观察到的集体运动是由增强的锐角碰撞驱动的播种过程产生的。一旦达到临界尺寸,簇就粗化为高密度相和低密度相,每个相都具有固定的灯丝浓度。稳态是由碰撞诱导的随机化和在有序簇内的多丝碰撞引起的长丝排列效应之间的平衡所定义的。在细胞骨架系统中观察到自组织,但对从无序出现的顺序了解甚少。使用高密度放线菌素系统,作者捕获了从无序到有序的过渡,这是由多丝碰撞增加引起的增强排列效果驱动的。
  • 6 Biological redox systems and oxidative stress. 复制标题 收藏 收藏

    【生物氧化还原系统和氧化应激。】 复制标题 收藏 收藏
    DOI:10.1007/s00018-007-7230-8 复制DOI
    作者列表:Sies H
    BACKGROUND & AIMS: :This account revolves around fascination and excitement with science. Early curiosity and fortunate opportunities can lead to a satisfying career. The privilege of performing basic research in biochemistry and molecular biology at a university coupled with teaching motivated students and working with dedicated co-workers makes for sustained thrust in the advance of knowledge. Research fields centered around cellular redox systems, oxidants and antioxidants, and the concept of oxidative stress. A noteworthy aspect is the global network of scientists joining in these endeavors worldwide.
    背景与目标: :这个科目围绕着对科学的迷恋和兴奋。早期的好奇心和幸运的机会可以带来令人满意的职业。在一所大学从事生物化学和分子生物学基础研究的特权,再加上积极进取的学生教学以及与敬业的同事一起工作的特权,为不断发展的知识提供了动力。研究领域围绕细胞氧化还原系统,氧化剂和抗氧化剂以及氧化应激的概念。一个值得注意的方面是参与全球这些努力的全球科学家网络。
  • 【碳源对生物电化学系统中脱氮性能的影响。】 复制标题 收藏 收藏
    DOI:10.1016/j.biortech.2012.11.004 复制DOI
    作者列表:Feng H,Huang B,Zou Y,Li N,Wang M,Yin J,Cong Y,Shen D
    BACKGROUND & AIMS: :In order to ascertain the effects of different carbon sources (methanol, glucose, starch and NaHCO(3)) on denitrification in BESs, the experiment was conducted in a constant current, 3.5 of chemical oxygen demand to nitrate ratio in a greenhouse. Among the four carbon sources investigated in BESs, NaHCO(3) showed the highest nitrite accumulation and the ratio of soluble microbial products to soluble chemical oxygen demand (SMP/SCOD) with a value of 3.68 ± 0.68 mg/L and 94%, respectively. And the addition of organic substrates could reduce SMP production and enhance the denitrification process. In the constant voltage experiment, it was observed that the organics could be used by microbes to generate electrons at the anode. And a maximal current value of 11.0 mA in the BESs fed with starch indicated that the complex carbon source was easier to be used by microorganisms to generate electricity than the simple carbon source.
    背景与目标: :为了确定不同碳源(甲醇,葡萄糖,淀粉和NaHCO(3))对BES中反硝化的影响,该实验在恒定电流下进行,该温室中化学需氧量与硝酸盐的比率为3.5。在BES中研究的四种碳源中,NaHCO(3)表现出最高的亚硝酸盐积累和可溶性微生物产物与可溶性化学需氧量(SMP / SCOD)的比率,分别为3.68±0.68 mg / L和94% 。并且添加有机底物可以减少SMP的产生并增强反硝化过程。在恒压实验中,观察到微生物可以将有机物用于在阳极产生电子。淀粉喂养的BES中的最大电流值为11.0 mA,这表明与简单碳源相比,微生物更容易使用复杂的碳源发电。
  • 【案例研究:机械网络模型在系统毒理学中的作用。】 复制标题 收藏 收藏
    DOI:10.1016/j.drudis.2013.07.023 复制DOI
    作者列表:Hoeng J,Talikka M,Martin F,Sewer A,Yang X,Iskandar A,Schlage WK,Peitsch MC
    BACKGROUND & AIMS: :Twenty first century systems toxicology approaches enable the discovery of biological pathways affected in response to active substances. Here, we briefly summarize current network approaches that facilitate the detailed mechanistic understanding of the impact of a given stimulus on a biological system. We also introduce our network-based method with two use cases and show how causal biological network models combined with computational methods provide quantitative mechanistic insights. Our approach provides a robust comparison of the transcriptional responses in different experimental systems and enables the identification of network-based biomarkers modulated in response to exposure. These advances can also be applied to pharmacology, where the understanding of disease mechanisms and adverse drug effects is imperative for the development of efficient and safe treatment options.
    背景与目标: :20世纪系统毒理学方法使人们能够发现响应活性物质而受到影响的生物途径。在这里,我们简要概述了当前的网络方法,这些方法有助于对给定刺激对生物系统的影响进行详细的机械理解。我们还将介绍基于网络的方法以及两个用例,并说明因果生物学网络模型与计算方法的结合如何提供定量的机理见解。我们的方法提供了不同实验系统中转录反应的可靠比较,并能够鉴定响应暴露而调制的基于网络的生物标记。这些进展也可以应用于药理学,在这种药理学中,对于疾病机理和药物不良作用的了解对于开发有效和安全的治疗方法至关重要。
  • 【脊髓镇痛的血清素能介导及其与去甲肾上腺素能系统的相互作用。】 复制标题 收藏 收藏
    DOI:10.1097/00000542-199009000-00017 复制DOI
    作者列表:Nakagawa I,Omote K,Kitahata LM,Collins JG,Murata K
    BACKGROUND & AIMS: :Serotonin was administered intrathecally onto cat spinal cords to evaluate the pharmacology by which it suppresses noxiously evoked activity of wide-dynamic-range (WDR) neurons in the spinal dorsal horn. Doses of 500, 1,000 and 2,000 micrograms serotonin produced significant suppression of the mean noxiously evoked activity of WDR neurons in the dorsal horn of the spinal cord (21, 44, and 69% at 30 min, respectively). The dose-dependent effects were partially reversed by the intravenous administration of the serotonin antagonist methysergide (1 or 2 mg). Intravenous administration of the alpha 2-adrenergic antagonist yohimbine (0.5 or 1.0 mg/kg) produced a significant antagonism of the effects of serotonin. In contrast to the effects of methysergide and yohimbine, intravenous administration of naloxone or the alpha 1-antagonist corynanthine had no effect upon the suppressive effects of serotonin. The combination of low-dose serotonin and low-dose clonidine produced a supraadditive effect (30% at 30 min). These data support the concept that noradrenergic systems, possibly through an alpha 2-adrenergic mechanism, are involved in the modulation of spinal WDR neurons by serotonin.
    背景与目标: :5-羟色胺通过鞘内注射到猫脊髓上,以评估其抑制脊髓背角宽动态范围(WDR)神经元的有害诱发活性的药理作用。剂量为500、1,000和2,000微克的血清素可显着抑制脊髓背角中WDR神经元的平均有害诱发活性(分别在30分钟时分别为21%,44%和69%)。通过静脉内注射5-羟色胺拮抗剂美塞麦肽(1或2毫克)可部分逆转剂量依赖性作用。静脉内注射α2-肾上腺素拮抗剂育亨宾(0.5或1.0 mg / kg)对5-羟色胺的作用产生明显的拮抗作用。与甲基异麦角胺和育亨宾的作用相反,纳洛酮或α1拮抗药七氢鸟嘌呤的静脉内给药对5-羟色胺的抑制作用没有影响。低剂量5-羟色胺和低剂量可乐定的组合产生了超加和作用(30分钟时为30%)。这些数据支持以下概念:去甲肾上腺素系统可能通过α2-肾上腺素机制参与了5-羟色胺对脊髓WDR神经元的调节。
  • 【复杂的竞争系统和竞争热力学。】 复制标题 收藏 收藏
    DOI:10.1098/rsta.2012.0244 复制DOI
    作者列表:Klimenko AY
    BACKGROUND & AIMS: :This publication reviews the framework of abstract competition, which is aimed at studying complex systems with competition in their generic form. Although the concept of abstract competition has been derived from a specific field--modelling of mixing in turbulent reacting flows--this concept is, generally, not attached to a specific phenomenon or application. Two classes of competition rules, transitive and intransitive, need to be distinguished. Transitive competitions are shown to be consistent (at least qualitatively) with thermodynamic principles, which allows for introduction of special competitive thermodynamics. Competitive systems can thus be characterized by thermodynamic quantities (such as competitive entropy and competitive potential), which determine that the predominant direction of evolution of the system is directed towards higher competitiveness. There is, however, an important difference: while conventional thermodynamics is constrained by its zeroth law and is fundamentally transitive, the transitivity of competitive thermodynamics depends on the transitivity of the competition rules. The analogy with conventional thermodynamics weakens as competitive systems become more intransitive, while strongly intransitive competitions can display types of behaviour associated with complexity: competitive cooperation and leaping cycles. Results of simulations demonstrating complex behaviour in abstract competitions are presented in the electronic supplementary material.
    背景与目标: :本出版物回顾了抽象竞争的框架,该框架旨在研究具有通用形式竞争的复杂系统。尽管抽象竞争的概念是从特定领域派生出来的-湍流反应流中的混合建模-但是,该概念通常不附属于特定现象或应用。需要区分两类竞争规则,即传递规则和不传递规则。传递竞争被证明与热力学原理一致(至少在定性上),这允许引入特殊的竞争热力学。竞争系统因此可以通过热力学量(例如竞争熵和竞争潜力)来表征,这确定了系统演化的主要方向是朝着更高的竞争力发展。但是,有一个重要的区别:常规热力学受其零定律约束并从根本上具有传递性,而竞争热力学的传递性取决于竞争规则的传递性。随着竞争系统变得更加不可传递,与传统热力学的类比减弱了,而强烈的不可传递竞争则可能显示出与复杂性相关的行为类型:竞争合作和跨越式循环。在电子补充材料中提供了证明抽象比赛中复杂行为的模拟结果。
  • 【内源性大麻素系统的药理作用:与其他神经递质系统的功能和结构相互作用及其在行为成瘾中的影响。】 复制标题 收藏 收藏
    DOI:10.1111/j.1369-1600.2008.00105.x 复制DOI
    作者列表:López-Moreno JA,González-Cuevas G,Moreno G,Navarro M
    BACKGROUND & AIMS: :Addiction is a chronic, recurring and complex disorder. It is characterized by anomalous behaviors that are linked to permanent or long-lasting neurobiological alterations. Furthermore, the endocannabinoid system has a crucial role in mediating neurotransmitter release as one of the main neuromodulators of the mammalian central nervous system. The purpose of the present review is to instruct readers about the functional and structural interactions between the endocannabinoid system and the main neurotransmitter systems of the central nervous system in the context of drug addiction. With this aim, we have systematically reviewed the main findings of most of the existing literature that explores cross-talk in the five brain areas that are most traditionally implicated in addiction: amygdala, prefrontal cortex, nucleus accumbens, hippocampus and ventral tegmental area (VTA). The neurotransmission systems influenced by the pharmacology of the endocannabinoid system in these brain areas, which are reviewed here, are gamma-aminobutyric acid (GABA), glutamate, the main biogenic amines (dopamine, noradrenaline and serotonin), acetylcholine and opioids. We show that all of these neurotransmitter systems can be modulated differentially in each brain area by the activation or deactivation of cannabinoid CB1 brain receptors. Specifically, most of the studies relate to the hippocampus and nucleus accumbens. Moreover, the neurotransmitter with the fewest number of related studies is acetylcholine (excepting in the hippocampus), whereas there is a large number that evaluates GABA, glutamate and dopamine. Finally, we propose a possible interpretation of the role of the endocannabinoid system in the phenomenon of addiction.
    背景与目标: :成瘾是一种慢性,复发性和复杂性疾病。它的特征是异常行为,这些行为与永久或持久的神经生物学改变有关。此外,内源性大麻素系统在介导神经递质释放中起着至关重要的作用,它是哺乳动物中枢神经系统的主要神经调节剂之一。本文的目的是指导读者在成瘾的背景下,内源性大麻素系统与中枢神经系统主要神经递质系统之间的功能和结构相互作用。为此,我们系统地回顾了大多数现有文献的主要发现,这些文献探讨了最传统地与成瘾有关的五个大脑区域的串扰:杏仁核,前额叶皮层,伏隔核,海马和腹侧被盖区域(VTA) )。在这些大脑区域中,受内源性大麻素系统的药理学影响的神经传递系统如下:γ-氨基丁酸(GABA),谷氨酸,主要的生物胺(多巴胺,去甲肾上腺素和5-羟色胺),乙酰胆碱和阿片类药物。我们显示,所有这些神经递质系统都可以通过大麻素CB1脑受体的激活或失活在每个大脑区域中被不同地调节。具体而言,大多数研究与海马和伏隔核有关。此外,相关研究最少的神经递质是乙酰胆碱(海马除外),而大量评估GABA,谷氨酸和多巴胺的神经递质。最后,我们提出了对内源性大麻素系统在成瘾现象中作用的可能解释。
  • 12 EGF-ERBB signalling: towards the systems level. 复制标题 收藏 收藏

    【EGF-ERBB信号:朝系统水平发展。】 复制标题 收藏 收藏
    DOI:10.1038/nrm1962 复制DOI
    作者列表:Citri A,Yarden Y
    BACKGROUND & AIMS: :Signalling through the ERBB/HER receptors is intricately involved in human cancer and already serves as a target for several cancer drugs. Because of its inherent complexity, it is useful to envision ERBB signalling as a bow-tie-configured, evolvable network, which shares modularity, redundancy and control circuits with robust biological and engineered systems. Because network fragility is an inevitable trade-off of robustness, systems-level understanding is expected to generate therapeutic opportunities to intercept aberrant network activation.
    背景与目标: :通过ERBB / HER受体进行信号传递与人类癌症错综复杂,并且已经成为多种抗癌药物的靶标。由于其固有的复杂性,将ERBB信令设想为领结式配置,可演进的网络非常有用,该网络与健壮的生物和工程系统共享模块化,冗余性和控制电路。由于网络脆弱性是鲁棒性的必然折衷,因此系统级的理解有望产生治疗机会,以拦截异常的网络激活。
  • 【妇科手术中主动摄像机控制系统的评估:结构,处理,舒适度,手术和结果。】 复制标题 收藏 收藏
    DOI:10.1007/s00404-013-3004-8 复制DOI
    作者列表:Beckmeier L,Klapdor R,Soergel P,Kundu S,Hillemanns P,Hertel H
    BACKGROUND & AIMS: OBJECTIVE:Surgeon-controlled endoscope leading assistance systems are a novelty in endoscopic surgery. These systems were evaluated for their applicability and reliability in operative gynecology. In this regard, we evaluated possible methods of operation, operative time, setup time, and comfort for the surgeon, complications, blood transfusions, length of stay, hemoglobin levels, and demographic data. METHODS:Two systems with technically identical camera control systems were applied, the SOLOASSISTTM system and the Einstein VisionTM 3D system. The arm systems are attached to the operating table and controlled by surgeon via a manual control, a remote control or a foot switch. Comfort for the surgeon was evaluated using a questionnaire (scale 1-5; 1 "very good", 5 "poor"). All data were collected prospectively in a database (IBM SPSS Statistics 20) and evaluated. RESULTS:One hundred and four patients underwent surgery supported by an active control system. In 43 (41 %) cases, oncological interventions were performed. Average setup time was 7 (3-30) min. There was a significant learning curve regarding the mounting of the system after 20 operations (p = 0.045). Overall comfort was rated as "good", divided into control 2.2 (2-4), physical effort 2.1 (1-4), picture quality 1.6 (1-3), and overall satisfaction 2.1 (1-4). About 75 unwanted camera movements were noticed in 104 surgeries. Complications occurred in no case (0 %). CONCLUSION:The application of an active camera control system was evaluated to be safe for all gynecological laparoscopies. Picture blur is avoided even during prolonged complex procedures. Moreover, the assistant is able to support the surgeon with two instruments, with the result that the presence of a second assistant is not required for complex interventions. Causing only minimal setup time, the examined active control systems improve the effectiveness of surgeries. The physical effort required for the assistant decreases and, by reducing tiring operations and tremor, subsequently, higher precision is reached.
    背景与目标: 目的:外科医生控制的内窥镜前导辅助系统在内窥镜手术中是一种新颖的技术。对这些系统在妇科手术中的适用性和可靠性进行了评估。在这方面,我们评估了可能的手术方法,手术时间,准备时间和外科医生的舒适度,并发症,输血,住院时间,血红蛋白水平和人口统计学数据。
    方法:使用了两个技术上相同的相机控制系统的系统,即SOLOASSISTTM系统和Einstein VisionTM 3D系统。手臂系统安装在手术台上,并由外科医生通过手动控制,远程控制或脚踏开关进行控制。使用问卷调查表评估外科医生的舒适度(1-5分; 1分“非常好”,5分“差”)。所有数据均前瞻性地收集在数据库中(IBM SPSS Statistics 20)并进行了评估。
    结果:104例患者接受了主动控制系统支持的手术。在43例(41%)病例中,进行了肿瘤干预。平均设置时间为7(3-30)分钟。在20次操作后,有关系统安装的学习曲线非常显着(p = 0.045)。总体舒适度被评为“良好”,分为对照组2.2(2-4),体力2.1(1-4),图像质量1.6(1-3)和总体满意度2.1(1-4)。在104个手术中,发现约75次不必要的摄像机移动。没有发生并发症(0%)。
    结论:对所有妇科腹腔镜检查应用主动相机控制系统的安全性进行了评估。即使在长时间的复杂过程中也可以避免图像模糊。而且,该助手能够用两种仪器来支持外科医生,结果是复杂的干预不需要第二助手的存在。经过检查的主动控制系统仅造成最短的设置时间,从而提高了手术的效率。助手所需的体力减少,并且通过减少疲劳操作和震颤,随后达到了更高的精度。
  • 【[机械心肌支持系统1997:植入式左心室支持系统对主动脉球囊反搏的概述]。】 复制标题 收藏 收藏
    DOI:10.1007/s001010050418 复制DOI
    作者列表:Hammel D,Möllhoff T,Soepawata R,van Aken H,Scheld HH
    BACKGROUND & AIMS: The development of cardiopulmonary bypass (CPB) to support the systemic circulation during cardiac surgical procedures became a clinical reality in 1953. Although the use of CPB for the treatment of post-infarction cardiogenic shock met with little success, intra-aortic balloon counterpulsation was used successfully in 1968 to reduce ischaemic injury in a patient with cardiogenic shock. Today, a broad spectrum of circulatory assist devices for short- and long-term application is available. Three major indication groups for the use of support devices are established. In low-cardiac-output syndrome after cardiac surgical procedures, short-term devices are utilised to enable myocardial recovery. In transplantation candidates suffering from drug-resistant pump failure, the implantation of long-term devices as a bridge to heart transplantation is indicated, and in NYHA class IV patients with contraindications to heart transplantation, the implantation of long-term devices as an alternative to transplantation is under discussion. In the literature, post-cardiotomy support survival is less than 30% on average. About 70% of mechanically bridged patients have survived to undergo heart transplantation and were transplanted with over 90% survival. Major problems during mechanical support are infection, bleeding, and thromboembolism. In view of patients' natural course without support, these clinical results are favourable.

    背景与目标: 1953年,在心脏外科手术期间开发支持体外循环的体外循环(CPB)成为临床现实。尽管使用CPB治疗梗死后心源性休克几乎没有成功,但仍使用了主动脉内球囊反搏1968年成功地减少了心源性休克患者的缺血性损伤。如今,有各种各样的短期和长期应用的循环辅助设备可供使用。建立了使用支持设备的三个主要指示组。在心脏外科手术后的低心输出量综合征中,使用短期设备可使心肌恢复。在患有耐药性泵衰竭的候选移植患者中,需要植入长期器械以作为心脏移植的桥梁;在有心脏移植禁忌症的NYHA IV级患者中,可以采用长期器械替代移植正在讨论中。在文献中,心脏切开术后支持生存率平均不到30%。机械桥接患者中约有70%幸存下来接受心脏移植,并且移植后的存活率超过90%。机械支持期间的主要问题是感染,出血和血栓栓塞。考虑到患者的自然病程而没有支持,这些临床结果是有利的。

  • 【两种专业用途的血糖即时检测系统的测量精度。】 复制标题 收藏 收藏
    DOI:10.1515/cclm-2019-0549 复制DOI
    作者列表:Baumstark A,Jendrike N,Kamecke U,Liebing C,Pleus S,Freckmann G
    BACKGROUND & AIMS: :Background The professional-use systems HemoCue® Glucose 201+ (HC201+) and HemoCue® Glucose 201 RT (HC201RT) are widely used for point-of-care testing (POCT) of blood glucose (BG). HC201RT utilizes unit-use microcuvettes which can be stored at room temperature, whereas HC201+ microcuvettes have to be stored at <8 °C. In this study, system accuracy of HC201+ and HC201RT was evaluated using capillary and venous blood samples. Methods For each system, two reagent system lots were evaluated within a period of 2 years based on testing procedures of ISO 15197:2013, a standard applicable for self-monitoring of blood glucose (SMBG) systems. For each reagent system lot, the investigation was performed by using 100 capillary and 95 to 99 venous blood samples. Comparison measurements were performed with a hexokinase laboratory method. Accuracy criteria of ISO 15197:2013 and POCT12-A3 were applied. In addition, bias was analyzed according to Bland and Altman, and error grid analysis was performed. Results When measuring capillary samples, both systems fulfilled accuracy requirements of ISO 15197:2013 and POCT12-A3 with the investigated reagent system lots. When measuring venous samples, only HC201+ fulfilled these requirements. Bias between HC201+ and reference measurements was more consistent over venous and capillary samples and microcuvette lots than for HC201RT. Error grid analysis showed that clinical actions might have been different depending on which system was used. Conclusions In this study, HC201+ showed a high level of accuracy irrespective of the sample type (capillary or venous). In contrast, HC201RT measurement results were markedly affected by the type of sample.
    背景与目标: :背景专业用途系统HemoCue®葡萄糖201(HC201)和HemoCue®葡萄糖201 RT(HC201RT)被广泛用于血糖(BG)的即时检验(POCT)。 HC201RT利用可以在室温下存储的单位使用型微池,而HC201的微池必须在<8°C的温度下存储。在这项研究中,使用毛细血管和静脉血样本评估了HC201和HC201RT的系统准确性。方法对于每个系统,根据ISO 15197:2013(适用于血糖自我监测(SMBG)系统的标准)的测试程序,在2年内评估了两个试剂系统批次。对于每个试剂系统批次,使用100个毛细管和95至99个静脉血样本进行研究。用己糖激酶实验室方法进行比较测量。应用了ISO 15197:2013和POCT12-A3的准确性标准。另外,根据Bland和Altman分析了偏差,并进行了误差网格分析。结果在测量毛细管样品时,两个系统都满足所检测试剂系统批次的ISO 15197:2013和POCT12-A3的精度要求。在测量静脉样本时,只有HC201满足这些要求。与HC201RT相比,静脉和毛细管样品以及微量比色皿批次之间HC201和参考测量之间的偏差更加一致。错误网格分析表明,根据所使用的系统,临床行为可能有所不同。结论在本研究中,HC201显示出高水平的准确性,而与样品类型(毛细管或静脉)无关。相反,HC201RT的测量结果受到样品类型的显着影响。

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