Mitochondrial ND5 12338T>C variant is associated with maternally inherited hypertrophic cardiomyopathy in a Chinese pedigree

Hypertrophic cardiomyopathy is a primary disorder characterized by asymmetric thickening of the septum and left ventricular wall, which affects 1 in 500 individuals in the general population. Mutations in mitochondrial DNA have been found to be one of the most important causes of hypertrophic cardiomyopathy. Here we report the clinical, genetic and molecular characterization of a Han Chinese family with a likely maternally transmitted hypertrophic cardiomyopathy. Four (2 men/2 women) of 5 matrilineal relatives in this 3-generation family exhibited the variable severity and age at onset of 44 to 79years old. Sequence analysis of the entire mitochondrial DNA in this pedigree identified the known homoplasmic ND5 12338T>C variant. This mitochondrial DNA haplogroup belongs to the Eastern Asian F2a. The 12338T>C variant, highly evolutionarily conserved, resulted in the replacement of the translation initiating methionine with a threonine, shortening the ND5 polypeptide by 2 amino acids. The occurrence of ND5 12338T>C variant exclusively in maternal members of this Chinese family suggested that the 12338T>C variant is associated with maternally inherited hypertrophic cardiomyopathy. Our findings will provide theoretical basis for genetic counseling of maternally inherited hypertrophic cardiomyopathy.     

Apolipoprotein E gene polymorphism and the risk of left ventricular dysfunction among Egyptian β-thalassemia major

In Egypt, β-thalassemia is the most common hereditary hemolytic anemia. Cardiac dysfunction, secondary to iron overload with formation of oxygen free radicals, is the most common cause of death in β-thalassemia patients. This study was designed to determine whether the allelic genotype of apolipoprotein E (Apo E), which exhibits antioxidant properties, could represent a genetic risk factor for the development of left ventricular (LV) dysfunction in β-thalassemia major. Fifty Egyptian β-thalassemia major patients were subjected to echocardiography to assess LV function. Apo E genotyping by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) was done for all patients in addition to 50 age and sex matched healthy control subjects. Patients were classified into three groups. Group I and II were clinically asymptomatic. Group II subjects had evidence of LV dilatation, while Group III patients had clinical and echocardiographic findings of LV failure. Apo E4 allele was significantly higher among Group II and III than in controls. In conclusion, Apo E4 allele can be considered as a genetic risk factor for LV dysfunctions in β-thalassemic patients. It could be used as predictive indicator for additional risk of LV failure, particularly in asymptomatic patients with LV dilatation, requiring a closer follow-up, to prevent further disease progression.     

Heat shock protein 60 modified with O-linked N-acetylglucosamine is involved in pancreatic beta-cell death under hyperglycemic conditions

The objective of this study was to identify proteins modified with O-linked N-acetylglucosamine (O-GlcNAc) in pancreatic beta-cells and to understand their roles in cell death under hyperglycemic conditions. Here we report that heat shock protein 60 (HSP60) is modified with O-GlcNAc. Levels of O-GlcNAcylated HSP60 increased twofold in response to hyperglycemic conditions. HSP60 is a chaperonin known to bind to Bax in the cytoplasm under normoglycemic conditions. Under hyperglycemic conditions, Bax detached from O-GlcNAcylated HSP60 and translocated to mitochondria. Hyperglycemic conditions were also associated with cytochrome c release, caspase-3 activation, and cell death, suggesting that elevated O-GlcNAcylation of HSP60 interferes with HSP60-Bax interactions, leading to pancreatic beta-cell death.     

Yeast GPCR signaling reflects the fraction of occupied receptors,not the number

According to receptor theory, the effect of a ligand depends on the amount of agonist–receptor complex. Therefore, changes in receptor abundance should have quantitative effects. However, the response to pheromone in Saccharomyces cerevisiae is robust (unaltered) to increases or reductions in the abundance of the G‐protein‐coupled receptor (GPCR), Ste2, responding instead to the fraction of occupied receptor. We found experimentally that this robustness originates during G‐protein activation. We developed a complete mathematical model of this step, which suggested the ability to compute fractional occupancy depends on the physical interaction between the inhibitory regulator of G‐protein signaling (RGS), Sst2, and the receptor. Accordingly, replacing Sst2 by the heterologous hsRGS4, incapable of interacting with the receptor, abolished robustness. Conversely, forcing hsRGS4:Ste2 interaction restored robustness. Taken together with other results of our work, we conclude that this GPCR pathway computes fractional occupancy because ligand‐bound GPCR–RGS complexes stimulate signaling while unoccupied complexes actively inhibit it. In eukaryotes, many RGSs bind to specific GPCRs, suggesting these complexes with opposing activities also detect fraction occupancy by a ratiometric measurement. Such complexes operate as push‐pull devices, which we have recently described.     

Rescuing infusion of miRNA-1 prevents cardiac remodeling in a heart-selective miRNA deficient mouse

Objective

The decreased expression of muscle-specific microRNA-1 (miR-1) has been found in many cardiovascular diseases and is considered to contribute to heart failure (HF). Here we investigated the role of miR-1 in myocardium protection by infusion of miR-1 in a cardiac global miRNA-deficient mouse.

湖南会同不同年龄杉木人工林土壤磷素特征

对湖南会同不同年龄(7年生、17年生、25年生)杉木人工林土壤全磷、有效磷、无机磷组分和有机磷进行了研究,结果表明:3种不同林龄杉木林土壤全磷和有效磷的含量分别在317.06—398.56 mg/kg和0.82—1.38 mg/kg之间,土壤全磷和速效磷含量均属低水平;杉木林土壤全磷含量从7年生幼龄林到25a近熟林出现先升高后降低的规律,并且17年生和25年生林分比7年生林分分别增加了19.68%、15.75%,土壤有效磷含量17年生和25年生林分比7年生林分提高了45.55%左右;土壤磷素活化系数均小于2.0%,这表明本研究区土壤全磷向速效磷转化较难,土壤中磷素的有效性较低,但该值随着林分年龄的增加而出现增大的现象;无机磷含量分别为:7年生169.50 mg/kg、17年生182.03 mg/kg、25年生175.94 mg/kg,从幼龄林到中龄林增高,中龄林以后降低;土壤中无机磷组分以O-P含量最高,其次是Fe-P,Ca-P,Al-P最少;杉木不同生长发育阶段对无机磷形态的吸收是有选择性的,幼龄林到中龄林阶段林木以吸收Al-P为主,近熟林阶段林木以吸收Fe-P和Ca-P为主;有机磷含量在全磷所占比例随林龄的变化来看,杉木生长过程中有部分的有机磷矿化为无机磷。土壤不同形态磷的相关性分析结果显示,土壤有效磷与有机磷相关系数为0.667,呈极显著相关性,是研究区杉木人工林土壤有效磷的主要来源。     

荧光漂白后恢复技术及其在活细胞分子机制研究中的应用

荧光漂白后恢复（FRAP）是一项利用荧光探针研究活体细胞中各类分子迁移特性的技术。简要介绍了FRAP技术的原理和具体实施要求,列出了动态比和扩散系数的计算公式,并例举了近几年FRAP技术在细胞分子机制研究中的应用。     

景观格局指数间相关关系对植被覆盖度等级分类数的响应

运用景观指数进行景观格局分析已成为景观生态学的主要研究方法。但是,由于景观本身的复杂性以及景观格局指数之间的相关性,其应用与发展受到制约。选用面积/周长/密度、形状和蔓延度等3类共28个指数,以广州市中心城区为研究区域,以TM遥感影像为数据源形成植被覆盖度等级图,在景观类型水平上探讨各类型内指数之间的相关性及其对景观分类数的敏感程度。相关性分析表明:景观格局指数间都存在一定的相关性,但是相关程度差异较大,其中面积/周长/密度类指数间的相关性最强,蔓延度类指数其次,形状类指数间独立性相对较强。敏感性分析结果显示:117个指数对的相关关系都随景观分类数发生变化,根据其变化类型和程度,可以分为简单型、分段型、复杂型等3种指数关系响应的类型,分别包括12、31和74对指数;敏感曲线还表明4或5是指数对之间相关关系最敏感的分类数;不仅如此,分类数对景观格局指数之间相关关系的影响程度因景观格局指数所属的类别而异,面积/周长/密度类型指数不敏感,其次是蔓延度类指数,最敏感的是形状类指数;最后,研究结果表明景观格局指数间的相关性对分类数的敏感性存在较大的空间变异。     

普罗布考联合家庭心脏康复训练对冠心病患者射血分数、血脂的影响分析

目的 探讨普罗布考联合家庭康复训练对冠心病患者射血分数及血脂水平的影响.方法 选择2018年6月 ～2020年6月我院收治的冠心病患者110例,按随机数字表法分成对照组和实验组,对照组给予瑞舒伐他汀治疗,实验组在对照组的基础上联合应用普罗布考及家庭康复训练.对两组患者治疗前及治疗后3个月的心功能指标、血脂水平进行检测比...