Evaluation of the hepatotoxicological effects of a drug in an in vivo/in vitro model

Both in vivo and in vitro models have certain disadvantages for the study of the chronic hepatotoxicity of drugs. The aim of this work was to evaluate a new approach based on an in vivo/in vitro model. After chronic in vivo treatment of rats with Vincamine and Vindeburnol (an eburnamenine derivative which exhibits hepatotoxic properties in man) liver cells were isolated, and functional and metabolic disorders (metabolic utilization of fructose and protein biosynthesis) were studied to determine injury. The results showed no modification of blood parameters, but a direct relationship between the dose of Vindeburnol administered in vivo and the metabolic disorders observed in vitro, evidencing the high sensitivity and reliability of this model.     

Biosynthesis of 1-aminocyclopropanecarboxylic acid: Steric course of the reaction at the C-4 position

Summary Under the action of the appropriate synthase from ripe tomatoes a 11 mixture of (3S, 4R)-[3,4-²H₂] and (3R, 4S)-[3,4-²H₂]-(2S)-adenosylmethionine is transformed into a 11 mixture of the two meso forms of [²H₂]-1-aminocyclopropanecarboxylic acid, a result which proves the operation of an inversion mechanism and which is consistent with direct nucleophilic displacement of the leaving group in the substrate.     

Quantitative genetic models of sexual selection

Summary Quantitative genetic models of sexual selection have disporven some of the central tenets of both the handicap mechanism and the sexy son hypothesis. These results suggest that the good genes approach to sexual selection may generally lead to erroneous results.Runaway sexual selection seems possible under a wide variety of circumstances. Quantittive genetic models have revealed runaway processes for sexually selected attributes expressed in both sexes and for attributes of parental care. Furthermore, the runaway could occur simultaneously in a series of populations that straddle an environmental gradient. While the models support the feasibility of runaway processes, empirical studies are needed to evaluate whether runaways actually happen. Estimates of critical genetic parameters are particularly needed, as well as measures of natural and sexual selection acting on the same population.The models also show that sexual selection has tremendous potential to produce population differentiation, particularly in epigamic traits. Differentiation is promoted by indeterminancy of evolutionary outcome, transient differences among populations during the final slow approach to equilibrium, sampling drift among equilibrium populations, and the tendency of sexual selection to amplify geographic variation arising from spatial differences in natural selection. Recent work with two- and three-locus models of sexual selection has produced results that parallel the results of the polygenic models^36–38,58. Thus the feature of indeterminate equilibria (outcome dependent on initial conditions) is common to both types of model.     

A major metabolite of Δ1-tetrahydrocannabinol reduces its cataleptic effect in mice

Summary The results described here demonstrate that THC-induced catalepsy in mice can be substantially inhibited by the prior administration of ¹-THC-7-oic acid, the major metabolite of THC in most species including humans. This raises the possibility that the intensity and duration of action of THC may depend to a large degree on the levels of this metabolite at the sites of action.We thank the National Institute on Drug Abuse for supporting this project by grants DA-02043 and DA-02052 and for supplying all of the cannabinoids. One of us (S.B.) is also the recipient of a Research Scientist Award from NIDA. We are grateful to Kristen Carlson and Thomas Honeyman for helpful suggestions in preparing this report.     

Structure of the human CLC-7/Ostm1 complex reveals a novel state

CLC-7 functions as a Cl?/H+ exchanger in lysosomes. Defects in CLC-7 and its β-subunit, Ostm1, result in osteopetrosis and neurodegeneration. Here, we present the cryogenic electron microscopy (cryo-EM) structure of the human CLC-7/Ostm1 complex (HsCLC-7/Ostm1) at a resolution of 3.6 ?. Our structure reveals a new state of the CLC-7/Ostm1 heterotetramer, in which the cytoplasmic domain of CLC-7 is absent, likely due to high flexibility. The disordered cytoplasmic domain is probably not able to restrain CLC-7 subunits and thus allow their relative movements. The movements result in an approximately half smaller interface between the CLC-7 transmembrane domains than that in a previously reported CLC-7/Ostm1 structure with a well-folded cytoplasmic domain. Key interactions involving multiple osteopetrosis-related residues are affected by the interface change.     

基于PiggyBac转座系统的低溢漏诱导型Tet-On过表达体系的建立及应用

为避免诱导基因稳定表达的Tet-On诱导表达系统溢漏表达,实现简便且高效的外源基因稳定诱导表达, 本研究拟在Tet-On调控的转录水平基础上,将基于稳定配体Shield-1的不稳定结构域FK506结合蛋白引入目的基因的N端,从蛋白水平控制其本底表达水平.为验证该系统的效果,本研究以荧光蛋白TdTomato为报告基因,经流式分析结果证明优化后的体系较原体系的溢漏表达在蛋白水平上降低7倍左右.将该系统应用于基于小鼠胚胎干细胞的体外牙向分化模型,在诱导因子Dox和稳定配体Shield-1的协同作用下,诱导表达牙齿发育相关转录因子Hand2提高了牙向分化诱导的完成度.     

涂装车间漆雾过滤设备内流场数值模拟与设计优化

涂装车间在喷涂过程中会产生大量含有漆雾的喷涂废气,在处理喷涂废气之前需对其中的漆雾进行预过滤,在干式喷房中纸盒式漆雾过滤器由于更经济环保,越来越多地被投入使用。针对运行参数对过滤器过滤效率的影响,利用计算流体力学对折流板式纸盒过滤器的过滤效果进行了数值模拟研究,对过滤器的设计参数提出了优化建议。结果表明:设计参数对过滤器过滤效率的影响较大,过滤器对10 μm以下的漆雾颗粒过滤效率在10%~20%,过滤效率较低,对于10 μm以上的漆雾颗粒,过滤效率随粒径的增大而升高,对60 μm及以上的漆雾颗粒过滤效率达99%以上,部分大颗粒漆雾掉落至过滤器内,可实现漆雾储存;过滤器过滤效率随进口流速的增大而降低,随漆雾浓度的增大而升高,设备进出口压差随进口流速的增大而增大,但远低于喷房压阻限制。     

3—己烯—1—醇及其酯类的合成和香气研究

介绍了叶醇(cis-3-己烯-1-醇)及其异构体的实用合成路线。由顺反混合(或全反式)3-己烯-1-醇制备了一系列羧酸酯,研究了这些化合物的结构与香气的关系,从中发现一些有实用价值的新香料。     

回流充气法处理中,高量含铁地下水的研究

本文介绍一种深井回流充气工艺,它兼具充氧和除铁综合性能的新型工艺形式,能改善含铁地下水的过滤性能.在此基础上提出了深井回流充气稳定期的概念,建立了深井回流充气系统中氧量的平衡关系.通过正交试验,提出了处理中、高量含铁地下水的推荐工艺流程和工艺参数.采用χ—射线衍射方法测试了井内铁泥和成熟滤料表面滤膜的成分和形态,分析了"充气"和"过滤》两过程中的除铁机理.     

神经网络校正的EKF在高超声速目标跟踪中的应用

针对临近空间高超声速目标高度非线性、强耦合、高机动、时变参数、和独特气动特性等特点,综合运用军事运筹学理论与方法、系统建模技术、神经网络技术以及计算机仿真等,提出基于神经网络校正的扩展卡尔曼滤波(EKF)算法,并在高超声速目标跟踪中进行了应用研究。采取神经网络的学习能力来克服卡尔曼滤波发散问题,通过卡尔曼滤波后加一级误差处理环节使滤波收敛。仿真结果表明:该算法在目标发生较大机动时仍能保持较高的跟踪精度。