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.     

Immunogenetics

Summary The 1985 Catalog of Mapped Genes (Human Gene Mapping 8; 33) has been used to pick out the known, immunologically important genes; these are then discussed in the following order: 1. genes controlling organs, tissues and cells of the immune apparatus, 2. genes determining self structures, 3. genes determining the structures of immunological specificity, 4. genes determining substances with immunoregulatory and effector properties. The symbols for the genes and the biological functions of their products are explained. The genetics of the ABO blood groups, of the HLA-system and of antibody formation are given in rather more detail.     

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.     

技能映射通过析取模型诱导的多分知识结构

基于程序性知识的评估,提出由项目自身的状态结构诱导多分知识结构的方法,以建立适用于问题解答的多分评估体系.首先,根据各项目的解答或操作步骤设定响应值集,通过项目状态转移函数定义项目状态空间;然后,用操作程序表示技能,由过程函数导出析取的技能映射;最后,讨论技能映射通过析取模型诱导的多分知识结构.结果表明：技能映射通过析取模型诱导的多分知识结构是多分知识空间.     

基于梯度加权类激活热力图的卷积神经网络故障诊断模型鲁棒性分析

深度学习近年来在故障诊断领域受到广泛应用,但基于深度学习的故障诊断模型缺乏工程上的物理解释性,难以保证其故障诊断结果的稳定性。以轴承为例,建立了以小波时频图像为故障诊断依据的卷积神经网络模型(convolutional neural network, CNN),提出了一种基于梯度加权类激活热力图(gradient-weighted class activation map, Grad-CAM)的网络模型鲁棒性分析方法,并利用美国凯斯西储大学(Case Western Reserve University, CWRU)轴承数据集进行验证。首先,将故障直径轴承数据以不同方式混合并训练大、小多个模型。其次,利用Grad-CAM方法,建立时频区域与故障模式之间的联系。最后,利用其他工况下的轴承故障数据,以及含噪数据进行测试,并根据结果结合模型最注重的时频区域进行分析。结果表明,基于深度学习的轴承故障诊断模型在参数较少时更加注重低频区域,并能使其具有更好的鲁棒性。     

基于CiteSpace的非物质文化遗产科技创新研究热点及趋势分析

非物质文化遗产（以下简称“非遗”）作为我国优秀传统文化的重要组成部分,非遗科技创新的研究逐渐成为学术界关注的热点。运用CiteSpace分析工具的可视化功能,以中国知网中CSSCI数据库收录的有关非遗科技创新的文献为样本,对年度发文量、研究力量、研究热点和趋势等进行分析。研究发现：2008~2021年非遗科技创新研究经历了3个阶段;研究热点集中在非遗、传承、创新和保护等方面;研究前沿主题聚焦互联网+、传播创新和活态传承等。