鳜碱性肌球蛋白轻链基因cDNA的克隆及其发育表达分析

肌球蛋白轻链是构成鱼类肌纤维主要组成部分,在鱼类肌肉生长和收缩过程中具有重要作用。鳜鱼具有生长快、肉质细嫩、味道鲜美、营养成分高等优良的性状。研究通过构建鳜肌肉组织cDNA文库分离到两个碱性肌球蛋白轻链基因,即MLC1和MLC3基因。序列分析显示MLC1和MLC3基因cDNA序列全长分别为1237bp和1070bp,分别编码192和150个氨基酸,除去MLC1N端多出的42个氨基酸残基,MLC1与MLC3氨基酸序列同源性为80.3%。通过PROSITEtools软件预测显示两种轻链都具有两个保守的EF-手相结构,其中第二个EF-hand结构除前三个氨基酸外同源性达100%。鱼类MLC3轻链N端没有高等脊椎动物MLC3特有标志序列。采用实时荧光定量PCR方法对鳜鱼MLC1和MLC3发育性表达分析表明,在原肠期开始有低量表达,与原肠期、尾芽期和肌肉效应期相比,心搏期和仔鱼期MLC1和MLC3表达量显著升高。研究结果首次提供了鳜肌肉组织肌球蛋白主要结构基因的分子生物学信息以及它们在鳜肌肉组织发生和功能的相关性。       

Synthesis, characterization and supramolecular structures of two Ni(II) complexes with potentially heptadentate ligand N,N-bis(2-hydroxybenzyl)-1,3-bis[(2-aminoethyl)amino]-2-propanol

A potentially heptadentate ligand H₃L (N,N^′-bis(2-hydroxybenzyl)-1,3-bis[(2-aminoethyl)amino]-2-propanol) and its two Ni(II) complexes, [Ni(H₂L)H₂O](H₂O)₃ClO₄ (1) and [Ni(H₂L)(H₂O)](H₂O)Cl (2) were prepared and characterized. X-ray structural analyses indicate that complex 1 has a distorted octahedral coordination geometry, with four amine N atoms of H₂L⁻ defining the equatorial plane, one aqua O atom and one phenoxo O atom of the ligand occupying two axial positions, respectively. The Ni(II) center of 2 has coordination geometry similar to that of 1. IR and electronic spectra of 1 and 2 are in agreement with their crystal structural features. Approximately along the ab plane, 2D supramolecular structure of 1 is assembled through multiple hydrogen bonds between hydroxy groups of the ligands, coordinated and crystal lattice H₂O and π-π stacking interactions between adjacent phenyl rings of the ligands, while for that of 2, probably along the a axis, 1D chain structure is also formed by multiple hydrogen bonds, but lack of π-π stacking interactions.     

Discovery of thieno[2,3-c]pyridines as potent COT inhibitors

Evaluation of hit chemotypes from high throughput screening identified a novel series of 2,4-disubstituted thieno[2,3-c]pyridines as COT kinase inhibitors. Structural modifications exploring SAR at the 2- and 4-positions resulting in inhibitors with improved enzyme potency and cellular activity are disclosed.     

Association of single-nucleotide polymorphisms in RHOB and TXNDC3 with knee osteoarthritis susceptibility: two case-control studies in East Asian populations and a meta-analysis

Introduction

Conflicting findings on the association of single nucleotide polymorphisms (SNPs) in RHOB and TXNDC3 with susceptibility to knee osteoarthritis (OA) have been reported in European Caucasians. To examine the associations of these SNPs with OA in East Asian populations and to evaluate their global significance, we conducted two case-control studies in 955 Chinese and 750 Japanese patients.

Methods

We genotyped the previously implicated SNPs rs585017 (in RHOB) and rs4720262 (in TXNDC3) in patients with primary symptomatic knee OA with radiographic confirmation and in matched control individuals, and analyzed their associations. We further conducted a meta-analysis of the study findings together with those of previously reported European studies using the DerSimonian-Laird procedure.

Results

A significant association of RHOB with knee OA was observed in male Chinese patients (P = 0.02). No significant associations were found for RHOB in any other comparisons in the East Asian populations. The association of TXNDC3 was replicated in Chinese female (P = 0.04) and Japanese (P = 0.03) patients, although none of these associations persisted after Bonferroni correction. Significant association (P = 0.02 for the allelic frequency) with nonsignificant heterogeneity was found in the East Asian replication study. No significant association was found in any comparison in the meta-analysis for all studies.

Conclusion

Our study replicates the association, previously reported in European Caucasians, of TXNDC3 with knee OA susceptibility in an East Asian population.     

Anti-adhesive Property of Maize Leaf Surface Related with Temperature and Humidity

The anti-adhesive surfaces have always aroused great interest of worldwide scientists and engineers.But in practical applications,it often faces the threat and impact of temperature and humidity.In this work,the excellent anti-adhesive performance of maize leaf under high temperature and humidity were investigated in detail.Firstly,the adhesion forces of the maize leaf surface under different temperature and humidity were measured by using Atomic Force Microscopy (AFM).The temperature of the substrate was varied between 23 ℃ to 100 ℃,and the ambient relative humidity is from 18％ to 100％.It was found that the adhesion force of maize leaf decreased with the increase of temperature and humidity.The mechanism of its excellent anti-adhesive performance of maize leaf under high temperature and relative humidity was revealed.The transverse and longitudinal ridges on maize leaf surface interlace with each other,forming small air pockets,which reduces the actual contact area between the object and the maize leaf.With the increase of humidity,the liquid film will be formed in the air pockets gradually and so much water vapor is produced with increase of temperature.Then the air flow rate increases though the wavy top of transverse ridges,inducing the dramatic decrease of adhesion force.Inspired by this mechanism,four samples with this bionic structure were made.This functional "biomimetic structure" would have potential value in the wide medical equipments such as high frequency electric knife with anti-adhesion surface under high temperature and high humidity.     

Psychological stress induces chemoresistance in breast cancer by upregulating mdr1

Psychological distress reduces the efficacy of chemotherapy in breast cancer patients. The mechanism may be related to the altered neuronal or hormonal secretions during stress. Here, we reported that adrenaline, a hormone mediating the biological activities of stress, upregulates mdr1 gene expression in MCF-7 breast cancer cells via alpha(2)-adrenergic receptors in a dose-dependent manner. Mdr1 upregulation can be specifically inhibited by pretreatment with mdr1-siRNA. Consequently, adrenergic stimulation enhances the pump function of P-glycoprotein and confers resistance of MCF-7 cells to paclitaxel. In vivo, restraint stress increases mdr1 gene expression in the MCF-7 cancers that are inoculated subcutaneously into the SCID mice and provokes resistance to doxorubicin in the implanted tumors. The effect can be blocked by injection of yohimbine, an alpha(2)-adrenergic inhibitor, but not by metyrapone, a corticosterone synthesis blocker. Therefore, we conclude that breast cancers may develop resistance against chemotherapeutic drugs under psychological distress by over-expressing mdr1 via adrenergic stimulation.     

重组人粒细胞-巨噬细胞集落刺激因子包涵体提取、复性和纯化的研究

由基因工程大肠杆菌表达的重组人粒细胞－巨噬细胞集落刺激因子（ｒｈＧＭ－ＣＳＦ）以包涵体的形式存在于细胞中,通过破菌、洗涤获得包涵体,再经过溶解、凝胶过滤、复性、疏水和离子交换柱导析得到了均一的产品,经高压液相和ＳＤＳ－ＰＡＧＥ电泳测定纯度均大于９８％,ｒｈＧＭ－ＣＳＦ的比活为３．２×１０＾７ＩＵ／ｍｇ,纯化获得的ｒｈＧＭ－ＣＳＦ为一酸性蛋白,等电点约为５．２,ＮＨ２－末端有２０个氨基酸序列测定结果