An Iris-Like Mechanism of Pore Dilation in the CorA Magnesium Transport System

Magnesium translocation across cell membranes is essential for numerous physiological processes. Three recently reported crystal structures of the CorA magnesium transport system revealed a surprising architecture, with a bundle of giant α-helices forming a 60-Å-long pore that extends beyond the membrane before widening into a funnel-shaped cytosolic domain. The presence of divalent cations in putative intracellular regulation sites suggests that these structures correspond to the closed conformation of CorA. To examine the nature of the conduction pathway, we performed 110-ns molecular-dynamics simulations of two of these structures in a lipid bilayer with and without regulatory ions. The results show that a 15-Å-long hydrophobic constriction straddling the membrane-cytosol interface constitutes a steric bottleneck whose location coincides with an electrostatic barrier opposing cation translocation. In one of the simulations, structural relaxation after the removal of regulatory ions led to concerted changes in the tilt of the pore helices, resulting in iris-like dilation and spontaneous hydration of the hydrophobic neck. This simple and robust mechanism is consistent with the regulation of pore opening by intracellular magnesium concentration, and explains the unusual architecture of CorA.     

Pairwise Variable Selection for High‐Dimensional Model‐Based Clustering

Summary Variable selection for clustering is an important and challenging problem in high‐dimensional data analysis. Existing variable selection methods for model‐based clustering select informative variables in a “one‐in‐all‐out” manner; that is, a variable is selected if at least one pair of clusters is separable by this variable and removed if it cannot separate any of the clusters. In many applications, however, it is of interest to further establish exactly which clusters are separable by each informative variable. To address this question, we propose a pairwise variable selection method for high‐dimensional model‐based clustering. The method is based on a new pairwise penalty. Results on simulated and real data show that the new method performs better than alternative approaches that use ?₁ and ?_∞ penalties and offers better interpretation.     

Liquid-liquid phase separation of a monoclonal antibody and nonmonotonic influence of Hofmeister anions

Liquid-liquid phase separation was studied for a monoclonal antibody in the monovalent salt solutions of KF, KCl, and KSCN under different pH conditions. A modified Carnahan-Starling hard-sphere model was utilized to fit the experimental data, establish the liquid-liquid coexistence curve, and determine antibody-antibody interactions in the form of T_c (critical temperature) under the different solution conditions. The liquid-liquid phase separation revealed the complex relationships between antibody-antibody interactions and different solution conditions, such as pH, ionic strength, and the type of anion. At pH 7.1, close to the pI of the antibody, a decrease of T_c versus ionic strength was observed at low salt conditions, suggesting that the protein-protein interactions became less attractive. At a pH value below the pI of the antibody, a nonmonotonic relationship of T_c versus ionic strength was apparent: initially as the ionic strength increased, protein-protein interactions became more attractive with the effectiveness of the anions following the inverse Hofmeister series; then the interactions became less attractive following the direct Hofmeister series. This nonmonotonic relationship may be explained by combining the charge neutralization by the anions, perhaps with the ion-correlation force for polarizable anions, and their preferential interactions with the antibody.     

不同干预时间正弦电磁场对大鼠骨髓基质干细胞成骨性分化的影响

目的:研究不同治疗时间正弦电磁场(50 Hz,1.8mT)对体外培养大鼠骨髓间充质干细胞成骨性分化的影响,筛选出最佳临床治疗时间.方法:采用贴壁筛选法培养原代大鼠骨髓间充质干细胞,每天在频率为50 Hz,强度为1.8 mT的磁场环境中处理0.5 h、1.0h、1.5 h、2.0h和2.5h;同时设立未经电磁场处理的细胞作为对照组.于处理后的第3 d、6d、9d和12 d分别测定细胞碱性磷酸酶活性、骨钙素分泌量、钙化结节数以及Ⅰ型胶原表达量,并比较各组间差异;于处理后12 h提取细胞总RNA,用RT Real-Time PCR法检测成骨性分化基因Osterix表达情况.结果:正弦电磁场干预1.0h能明显促进骨髓间充质干细胞的成骨性分化,表现在该组的碱性磷酸酶活性、骨钙素分泌量、钙化结节数、Ⅰ型胶原表达量以及成骨性分化基因的表达量最高,亦显著高于对照组(P＜0.05).结论:50Hz、1.8mT强度的正弦电磁场能促进骨髓间充质干细胞的成骨性分化,以作用1.0h成骨效果最为明显.     

癔症发作诱发因素以及复发几率分析

目的:探讨导致癔症发病病因和复发几率之间的联系,以便为研究、预防和治疗癔症工作提供科学依据。方法:以近30年国内外有关癔症危险因素的研究成果为基础,对符合CCMD-3诊断标准的100例癔症患者进行回顾性分析及前瞻性观察。结果:癔症相关的危险因素比较多,患者多内向,神经质影响心理症状最大,情绪明显不稳定;他们的父母较正常人的父母对子女缺乏情感温暖,并有过度的拒绝和过度保护,家庭不和睦,其在发病前一年内负性生活事件数目与严重程度均高于一般人;情绪表达受限,生活单调乏味,父母采取不良教养方式,人际关系紧张等。且患者性格因素引起的癔症复发几率较高,而因负性生活事件的原因复发几率在几种情况中最低。结论:癔症病因主要有人格特征,家庭环境,生活事件,教养方式,人际关系等,正确教育方式和朋友良好的关系,以及和谐的家庭及社会环境,及时治疗相关的并发症,可明显减少发病和复发概率。     

两种龈下刮治和根面平整术对2型糖尿病伴慢性牙周炎疗效的比较

目的:比较一次法龈下刮治和根面平整术(FM-SRP)和常规的四分法龈下刮治和根面平整术(Q-SRP)治疗2型糖尿病伴慢性牙周炎的临床疗效,并观察慢性牙周炎治疗对2型糖尿病患者血糖控制的影响。方法:将48例2型糖尿病伴慢性牙周炎患者随机分为2组:FM-SRP组在l天内完成全口所有象限的刮治和根面平整,Q-SRP组每周进行1个象限的刮治,连续4周完成全口治疗。于治疗前、治疗3个月和6个月时,检测菌斑指数(PLI)、牙周探诊深度(PD)、临床附着水平(CAL)、探诊出血(BOP)及空腹血糖(FPG)与糖化血红蛋白(HbAlc)的变化。结果:有3例患者被剔除。与治疗前相比,2种治疗方式在3个月和6个月时的PLI、PD、CAL和BOP均有显著改善(P<0.05),FPG和HbAlc无显著性改变(P>0.05)。但各项指标的变化在2组间均无显著性差异(P>0.05)。结论:本组资料,FM-SRP和Q-SRP两种方法治疗2型糖尿病伴慢性牙周炎均可达到相同的临床效果,但对2型糖尿病患者血糖控制无明显影响。     

短期身心训练可以引起大脑灰质变化吗

持续数月的运动学习或者工作记忆训练可以引发成年人大脑灰质的变化,其结构变化的区域与任务有关.是否短期身心训练可以引起类似的大脑大脑灰质变化尚不清楚.在前期工作基础上,本文研究了连续两周的整体身心调节法训练以及放松训练对大脑可塑性的影响.结果表明:采用基于像素的形态学方法,没有发现两周整体身心调节法训练以及放松训练可以引起大脑结构变化.下一步的研究将以大样本并增加训练时间采探索训练引发的神经可塑性规律.     

mirRNA-17-5p抑制物对骨肉瘤细胞系SOSP_9607增殖和凋亡的影响

目的:探讨miR-17-5p抑制物对于骨肉瘤细胞系SOSP_9607细胞增殖和凋亡的影响.方法:四甲基偶氮唑蓝(MTT)法测定细胞增殖,进一步计算抑制率,流式细胞仪测定细胞凋亡.将SOSP_9607细胞分为对照组和实验组,对照组分为阴性对照和正常细胞对照组.实验组采用miR-17-5p抑制物(hsa-miR-17-5p inhibitors)抑制SOSP_9607细胞内miR-17-5p的活性.结果:与对照组相比,实验组显著抑制SOSP_9607细胞的增殖,有明显的剂量依赖性(P<0.01).随着浓度从50 nmol/L逐渐增加至200 nmol/L,抑制率逐渐增高(P<0.01).实验组凋亡率(9.6±1.8)%与阴性对照组凋亡率(3.5±0.4)%相比明显增高(P<0.01).结论:miR-17-5p抑制物通过抑制SOSP_9607细胞中miR-17-5p的活性对SOSP_9607细胞的增殖和凋亡发挥重要作用.     

四川省遂宁地区吸烟人群的城乡对比

目的:了解四川省遂宁地区城乡自然人群中吸烟者的分布特征,比较城市及农村的吸烟人群在吸烟状况等方面的差异,为今后在该地区的不同人群中开展戒烟干预活动提供基础数据。方法:采用访谈和问卷调查相结合的形式,对四川省遂宁市下辖的五区城乡常住人口进行随机抽样。被调查者年龄范围为18岁至65岁。调查项目包括:一般情况、吸烟率、吸烟量、戒烟意愿和戒烟原因等。结果:从总体上看,男性吸烟率高于女性,文化程度越高在吸烟者中所占比例越小。城乡之间有统计学显著意义的差异如下:1.农村人群的吸烟率高于城市人群(男性:农村64.7%,城市45.7%;女性:农村4.6%,城市3.1%);2.农村吸烟群体的文化程度明显低于城市;3.农村吸烟者的日平均吸烟量高于城市吸烟者;4.农村吸烟者的烟龄比城市吸烟者烟龄长;5.城乡之间的戒烟原因各自不同。结论:城乡之间的吸烟者有着各自不同的特征和吸烟情况,在开展戒烟或控烟等宣称防治工作时应针对不同群体有不同的工作策略与方法。     

renalase在人近曲肾小管上皮细胞系的表达与分泌

目的:探讨renalase在人近曲肾小管上皮细胞系(HK-2)的表达与分泌,为进一步研究细胞水平renalase及其通路建立稳定的实验平台。方法:以HK-2细胞系作为研究材料。①应用Westernblot方法检测renalase蛋白的表达。②用real-timePCR方法检测renalasemRNA表达的变化。③用ELISA方法检测细胞上清液中renalase的浓度。结果:在mRNA水平及蛋白水平均检测到renalase表达。结论:首次在mRNA水平及蛋白水平证实了HK-2细胞能够表达renalase,为进一步研究儿茶酚胺或缺血缺氧刺激下细胞renalase的表达奠定了基础。