人巨细胞病毒基因突变与耐药性的相关性研究进展

人巨细胞病毒是人群中感染非常广泛的一类病毒,近年来其感染引发的严重疾病日益增加.为了预防和控制该痰病,须反复长期使用抗病毒药物,从而导致该药耐药性的出现.本文介绍了巨细胞病毒基因突变与耐药性的相关性研究进展,结合药物的作用机制和病毒的结构特点对人巨细胞病毒的主要耐药突变区域UL97基因和UL54基因的突变位点进行了统计分析,提出了耐药突变的高发区域,对进一步研究耐药蛋白空间结构的变化及新药的研制有重要的指导意义.最后对交又耐药的研究进行了分析综述,对耐药人巨细胞病毒的研究方向及关注的问题提出了自己的看法.     

Strong population genetic structure of an invasive species,Rhynchophorus ferrugineus (Olivier), in southern China

The red palm weevil (RPW), Rhynchophorus ferrugineus (Olivier), was initially reported in China in the 1990s and is now considered one of the most successful invasive pests of palm plants in the country. A total of 14 microsatellite loci and one mitochondrial cytochrome oxidase subunit Ι (cox I) gene fragment were used to investigate the genetic characteristics and structure of R. ferrugineus in southern China. High levels of genetic differentiation among populations and significant correlations between genetic and geographical distances indicated an important role of geographical distance in the distribution of the RPW in southern China. High gene flow between Fujian and Taiwan province populations illustrated the increased effects of frequent anthropogenic activities on gene flow between them. Genetic similarity (i.e., haplotype similarity) indicated that RPW individuals from Taiwan and Fujian invaded from a different source than those from Hainan. To some extent, the genetic structure of the RPW in southern China correlated well with the geographic origins of this pest. We propose that geographical distance, anthropogenic activities, and the biological attributes of this pest are responsible for the distribution pattern of the RPW in southern China. The phylogenetic analysis suggests that the most likely native sources of the RPW in southern China are India, the Philippines, and Vietnam.     

Identification of an endogenous glutamatergic transmitter system controlling excitability and conductivity of atrial cardiomyocytes

As an excitatory transmitter system, the glutamatergic transmitter system controls excitability and conductivity of neurons. Since both cardiomyocytes and neurons are excitable cells, we hypothesized that cardiomyocytes may also be regulated by a similar system. Here, we have demonstrated that atrial cardiomyocytes have an intrinsic glutamatergic transmitter system, which regulates the generation and propagation of action potentials. First, there are abundant vesicles containing glutamate beneath the plasma membrane of rat atrial cardiomyocytes. Second, rat atrial cardiomyocytes express key elements of the glutamatergic transmitter system, such as the glutamate metabolic enzyme, ionotropic glutamate receptors (iGluRs), and glutamate transporters. Third, iGluR agonists evoke iGluR-gated currents and decrease the threshold of electrical excitability in rat atrial cardiomyocytes. Fourth, iGluR antagonists strikingly attenuate the conduction velocity of electrical impulses in rat atrial myocardium both in vitro and in vivo. Knockdown of GRIA3 or GRIN1, two highly expressed iGluR subtypes in atria, drastically decreased the excitatory firing rate and slowed down the electrical conduction velocity in cultured human induced pluripotent stem cell (iPSC)-derived atrial cardiomyocyte monolayers. Finally, iGluR antagonists effectively prevent and terminate atrial fibrillation in a rat isolated heart model. In addition, the key elements of the glutamatergic transmitter system are also present and show electrophysiological functions in human atrial cardiomyocytes. In conclusion, our data reveal an intrinsic glutamatergic transmitter system directly modulating excitability and conductivity of atrial cardiomyocytes through controlling iGluR-gated currents. Manipulation of this system may open potential new avenues for therapeutic intervention of cardiac arrhythmias.Subject terms: Cell biology, Molecular biology     

BAC TransgeneOmics: a high-throughput method for exploration of protein function in mammals

The interpretation of genome sequences requires reliable and standardized methods to assess protein function at high throughput. Here we describe a fast and reliable pipeline to study protein function in mammalian cells based on protein tagging in bacterial artificial chromosomes (BACs). The large size of the BAC transgenes ensures the presence of most, if not all, regulatory elements and results in expression that closely matches that of the endogenous gene. We show that BAC transgenes can be rapidly and reliably generated using 96-well-format recombineering. After stable transfection of these transgenes into human tissue culture cells or mouse embryonic stem cells, the localization, protein-protein and/or protein-DNA interactions of the tagged protein are studied using generic, tag-based assays. The same high-throughput approach will be generally applicable to other model systems.     

VGLUT3 neurons in median raphe control the efficacy of spatial memory retrieval via ETV4 regulation of VGLUT3 transcription

Science China Life Sciences - The raphe nucleus is critical for feeding, rewarding and memory. However, how the heterogenous raphe neurons are molecularly and structurally organized to engage their...     

Memory Susceptibility to Retroactive Interference Is Developmentally Regulated by NMDA Receptors

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三种组成型启动子调控的鼠李糖脂基因在防御假单胞菌中的异源表达及活性研究

本研究利用Red/ETDNA重组技术对实验室已有的含鼠李糖基转移酶基因RhlAB的分泌表达载体pBBR1-genta-RhlAB进行修饰,将3种不同强度组成型启动子(Papra、Ptac和PrhaB)成功替换了RhlAB基因在铜绿假单胞菌中的原始启动子,成功获得了表达载体pBBR1-genta-Papra-RhlAB,pBBR1-kan-Ptac-RhlAB和pBBR1-kan-PrhaB-RhlAB,并将这些表达载体分别在防御假单胞菌Pf-5中异源表达,通过LB培养基发酵42h后,Pf-5/pBBR1-genta-RhlAB的鼠李糖脂产量为17.56mg/L,而Pf-5/pBBR1-genta-Papra-RhlAB,Pf-5/pBBR1-kan-Ptac-RhlAB和Pf-5/pBBR1-kan-PrhaB-RhlAB分别是11.135mg/L,441.135mg/L,557.764mg/L,启动子优化后产量分别是原始启动子的0.63,25.12和31.76倍。对发酵产物进行高效液相色谱-质谱联用技术分析,共检出相对含量变化的4类质核比不同的鼠李糖脂同系物。并通过实时荧光定量PCR检测RhlAB基因的表达量,发现启动子替换为Ptac和PrhaB后RhlAB基因表达量分别是原始启动子的2.16和2.77倍。本研究初步实现了RhlAB基因在Pf-5中的表达,发现组成型启动子Ptac和PrhaB比RhlAB的原始启动子表达效率更高,可为异源合成鼠李糖脂提供重要参考。     

Tau overexpression impairs neuronal endocytosis by decreasing the GTPase dynamin 1 through the miR‐132/MeCP2 pathway

Tauopathies are a class of neurodegenerative diseases that are characterized by pathological aggregation of tau protein, which is accompanied by synaptic disorders. However, the role of tau in endocytosis, a fundamental process in synaptic transmission, remains elusive. Here, we report that forced expression of human tau (hTau) in mouse cortical neurons impairs endocytosis by decreasing the level of the GTPase dynamin 1 via disruption of the miR‐132‐MeCP2 pathway; this process can also be detected in the brains of Alzheimer's patients and hTau mice. Our results provide evidence for a novel role of tau in the regulation of presynaptic function.