Regulation of the CRL4Cdt2 Ubiquitin Ligase and Cell-Cycle Exit by the SCFFbxo11 Ubiquitin Ligase

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Highlights? FBXO11 targets CDT2, a CRL4 substrate receptor, for proteasomal degradation ? CDK-mediated phosphorylation of CDT2 degron inhibits recognition by FBXO11 ? FBXO11-mediated degradation of CDT2 controls the timing of cell-cycle exit ? FBXO11-CDT2 functional interaction is evolutionary conserved from worms to humans     

蛇神经毒素的研究进展

蛇毒是由许多种蛋白质、多肽、酶类以及其他小分子物质组成的混合物.在蛇毒中已经分离了许多种毒素分子,其中有一大类分子对哺乳动物的神经系统具有毒性效应,习惯上把这类分子成为蛇神经毒素.蛇神经毒素根据其作用位点的不同可以分为四大类:突触前蛇神经毒素、突触后蛇神经毒素、抗胆碱酯酶的蛇神经毒素和离子通道蛇神经毒素.许多蛇神经毒素已经分离纯化并进行了结构与功能的研究,几十近百种蛇神经毒素一级结构和空间结构已经得到测定.近几年来一些蛇神经毒素的基因文库以及cDNA文库已经构建出来,从中分离出的基因已经用于重组蛇神经毒素的生产研究.蛇神经毒素的分子结构与其功能具有较好的对应关系,即作用机制相同的毒素具有类似的空间结构.天然的蛇神经毒素以及重组的蛇神经毒素都已广泛应用于理论研究和一些临床应用.分离新的蛇神经毒素及其基因以及根据需要设计新的蛇神经毒素分子已成为该领域的热点,采用生物工程的方法规模生产蛇神经毒素也是当前及今后的研究方向.     

miRNA‐182/Deptor/mTOR axis regulates autophagy to reduce intestinal ischaemia/reperfusion injury

It had been reported miR‐182 was down‐regulated after intestinal ischaemia/reperfusion (I/R) damage. However, its role and potential mechanisms are still unknown. This study was aimed to elucidate the function of miR‐182 in intestinal I/R injury and the underlying mechanisms. The model of intestinal injury was constructed in wild‐type and Deptor knockout (KO) mice. Haematoxylin‐eosin staining, Chiu's score and diamine oxidase were utilized to detect intestinal damage. RT‐qPCR assay was used to detected miR‐182 expression. Electronic microscopy was used to detect autophagosome. Western blot was applied to detect the expression of Deptor, S6/pS6, LC3‐II/LC3‐I and p62. Dual‐luciferase reporter assay was used to verify the relationship between miR‐182 and Deptor. The results showed miR‐182 was down‐regulated following intestinal I/R. Up‐regulation of miR‐182 reduced intestinal damage, autophagy, Deptor expression and enhanced mTOR activity following intestinal I/R. Moreover, suppression of autophagy reduced intestinal damage and inhibition of mTOR by rapamycin aggravated intestinal damage following intestinal I/R. Besides, damage of intestine was reduced and mTOR activity was enhanced in Deptor KO mice. In addition, Deptor was the target gene of miR‐182 and was indispensable for the protection of miR‐182 on intestine under I/R condition. Together, our research implicated up‐regulation of miR‐182 inhibited autophagy to alleviate intestinal I/R injury via mTOR by targeting Deptor.     

黄芪、硫酸锌对肠缺血/再灌注后红细胞膜微粘度的影响

目的 :探讨黄芪、硫酸锌对肠缺血 /再灌注 (I/R)后红细胞 (RBC)膜微粘度的影响并探讨其作用机制。方法 :复制家兔肠I/R损伤模型 ,检测给予黄芪、硫酸锌后肠I/R损伤家兔RBC膜微粘度的变化 ,同时检测RBC超氧化物歧化酶 (SOD)、RBC膜及重要器官组织丙二醛 (MDA)含量及血浆黄嘌呤氧化酶 (XO)活性 ,并与I/R组及假手术组比较。分析膜微粘度与SOD、MDA、XO之间的关系。结果 :黄芪、硫酸锌可使RBC膜微粘度、膜和器官组织MDA及血浆XO活性降低 ,且可防止SOD减少 (P <0 .0 1 )。结论 :黄芪、硫酸锌通过抗脂质过氧化能稳定RBC膜 ,改善RBC膜微粘度 ,进而改善重要器官的血流动力学 ,避免了I/R损伤的进行性加剧     

模拟海平面上升对海滨木槿渗透调节的影响

通过模拟海平面上升对海滨木槿主要渗透调节物质可溶性蛋白、可溶性糖和淀粉的影响发现,可溶性糖和可溶性蛋白均随水淹时间的延长呈现先升高后下降的变化,且变化较一致。而淀粉则呈先升高后下降再升高的N型曲线变化。另外通过对各个处理的分析比较发现,海滨木槿在海水淹浸35 cm·d^-1和6 h·d^-1环境下在渗透调节水平上仍然表现出较强的抗性。研究发现海滨木槿水淹胁迫程度较小的情况下可溶性糖与可溶性蛋白含量呈显著正相关,可溶性糖与淀粉呈显著负相关,说明海滨木槿在一定程度的水淹胁迫下主要渗透调节物质具有协同性,且水淹第21 d后存在可溶性糖向淀粉转化的可能。     

海藻糖生产菌株筛选过程中产物鉴定的研究

在海藻糖生产菌的筛选过程中,微生物胞内酶转化淀粉生成的产物复杂,将产物逐一纯化是非常烦琐的,但又必须确证产物中是否含有海藻糖。本文将薄层层析、高效液相电喷雾电离质谱联用及核磁共振等分析手段综合应用于海藻糖生产菌株的筛选,在酶反应产物不必被纯化的前提下,准确、快捷地鉴定了酶反应产物中的未知糖组分,最终证明食尼古丁节杆菌（Arthrobacter nicotinovorus）D97利用淀粉或麦芽寡糖的酶反应产物中含有海藻糖。该方法在筛选海藻糖及其它功能性葡二糖生产菌株时较为严密。     

模拟氮沉降和灌草去除对杉木人工林地土壤微生物群落结构的影响

土壤微生物是陆地生态系统重要的分解者和地上-地下相互作用的纽带。本文以亚热带杉木(Cunninghamia lanceolateata)人工林为对象, 通过模拟林冠层氮沉降和林下灌草去除, 设置4种处理, 包括: 对照(CK)、灌草去除(UR)、氮沉降(N)和氮沉降加灌草去除(N × UR)的野外控制实验, 研究土壤微生物群落结构的响应。本实验分别于2016年4月(春季)和10月(秋季)采集0-10 cm层土壤样品, 运用磷脂脂肪酸法(PLFAs)分析土壤微生物群落结构。结果表明: (1) 10月份土壤微生物总PLFAs量及其他类群土壤微生物PLFAs量显著高于4月份(P < 0.05), 真菌/细菌比值没有显著差异。土壤微生物PLFAs中细菌占优势, 其次为真菌, 放线菌的占比最小; (2)相比CK处理, UR处理下土壤微生物总PLFAs量、细菌PLFAs量、革兰氏阴性菌PLFAs量和放线菌PLFAs量有增加趋势, 但未达到显著差异水平(P > 0.05); (3)相对CK, UR、N和N × UR处理降低了4月份土壤微生物多样性(H°)和均匀度指数(J), 但提高了10月份土壤微生物多样性指数; (4)冗余分析表明, 土壤硝态氮和总磷含量与土壤微生物群落之间呈现显著相关。本研究表明土壤微生物PLFAs在各处理下都表现出明显的季节动态; 短期内林下灌草去除对土壤微生物PLFAs影响表现出一定的促进作用, 氮沉降对土壤微生物群落影响还不甚明显, 需要长期的监测研究来评估两者及其交互作用对土壤微生物群落及其功能的影响。     

The interplay between m6A modification and non-coding RNA in cancer stemness modulation: mechanisms,signaling pathways,and clinical implications

Cancer stemness, mainly consisting of chemo-resistance, radio-resistance, tumorigenesis, metastasis, tumor self-renewal, cancer metabolism reprogramming, and tumor immuno-microenvironment remodeling, play crucial roles in the cancer progression process and has become the hotspot of cancer research field in recent years. Nowadays, the exact molecular mechanisms of cancer stemness have not been fully understood. Extensive studies have recently implicated that non-coding RNA (ncRNA) plays vital roles in modulating cancer stemness. Notably, N6-methyladenosine (m6A) modification is of crucial importance for RNAs to exert their biological functions, including RNA splicing, stability, translation, degradation, and export. Emerging evidence has revealed that m6A modification can govern the expressions and functions of ncRNAs, consequently controlling cancer stemness properties. However, the interaction mechanisms between ncRNAs and m6A modification in cancer stemness modulation are rarely investigated. In this review, we elucidate the recent findings on the relationships of m6A modification, ncRNAs, and cancer stemness. We also focus on some key signaling pathways such as Wnt/β-catenin signaling, MAPK signaling, Hippo signaling, and JAK/STAT3 signaling to illustrate the underlying interplay mechanisms between m6A modification and ncRNAs in cancer stemness. In particular, we briefly highlight the clinical potential of ncRNAs and m6A modifiers as promising biomarkers and therapeutic targets for indicating cancer stemness properties and improving the diagnostic precision for a wide variety of cancers.