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.     

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。     

关于高斯函数[x]的几个恒等式的探讨

本文先给出关于［ｘ］的几个恒等式,然后对张宁生、周春荔《关于含［ｘ］的不等式与恒等式的探讨》文中的一个问题作了进一步探讨．     

苯甲酰三氟丙酮与稀土配合物的合成及性质研究

本文合成了苯甲酰三氟丙酮（Ｌ）和三苯基氧膦（ＴＰＰＯ）、联吡啶（Ｂｉｐｙ）、邻菲罗啉（ｐｈｅｎ）、四甲基氢化铵（ＮＭｅ４ＯＨ）与稀土Ｙ、Ｌａ、Ｅｕ、Ｔｂ离子的混合型配合物。测定配合物的Ｈ１ＮＭＲ谱及质谱,并对测定结果进行了分析。     

含双二苯基膦戊烷铜(Ⅰ)配合物的合成与性质

室温,氮气氛下,铜（Ⅱ）盐和双二苯基膦戊烷（ｄｐｐｐ５）在溶液中通过还原取代反应合成了８种铜（Ⅰ）配合物（１．［Ｃｕ（ｄｐｐｐ５）］２（ＢＦ４）２,２．［Ｃｕ２（ｄｐｐｐ５）２（Ｃ８Ｈ３Ｏ２ＳＦ３）２］,３．［Ｃｕ２（ｄｐｐｐ５）３］（ＣＣｌ３ＣＯＯ）２,４．［ＣｕＢｒ（ｄｐｐｐ５）］２,５．［Ｃｕ２（ｄｐｐｐ５）Ｃｌ２］,６．［Ｃｕ２（ｄｐｐｐ５）３］（ＣＨ３ＣＯＯ）２,７．［Ｃｕ（ｄｐｐｐ５）（ＮＯ３）］,８．［Ｃｕ２（ｄｐｐｐ５）３］（ＣｌＯ４）２）。通过元素分析、红外光谱、热重、摩尔电导测定对其进行表征,表明这是一种行之有效的有机膦配合物的合成方法。