乙肝病毒感染导致Mrell下调及基因组断裂

[目的]乙肝病毒的持续感染与肝细胞癌的发生密切相关.本文探讨了乙肝病毒感染后导致宿主蛋白Mrell的变化,并研究这种蛋白的变化可能导致肝癌发生的机制.[方法]本文通过Westernblot检测了乙肝病毒感染HL7702细胞及肝癌组织标本的Mrell蛋白的变化,并且通过RNA干涉的方法干扰了Mrell的表达,用连接介导PCR检测基因组的变化.[结果]本研究发现乙肝病毒感染细胞导致Mrell表达下调,肝癌组织也可以发现Mrell表达下调;下调Mrell表达可以导致细胞基因组的断裂增多.[结论]HBV感染导致Mrell表达下调导致基因组不稳定,这可能与HBV感染导致细胞恶性转化相关.     

群体融合对遗传方差的影响

探讨了群体融合对遗传方差的影响,无显性时基因型方差对群体中的基因频率为一凸函数,群体融合将导致它的增加,完全显性时,当群体中显性基因的频率时,群体融合导致基因型方差增加;而当时,融合导致基因型方差减小。超显性时,群体融合导致基因型方差增加,对加性方差和显性方差也分别进行了探讨。     

TCR途径引起T细胞活化与凋亡的信号事件

通过ＴＣＲ刺激Ｔ细胞可导致复杂的生化信号级联,其产生依赖于使用在其它细胞表面受体传播的共刺激信号。ＴＣＲ交联产生活化信号,可导致细胞增殖,细胞因子的产生,或诱导ＣＤ９５的其配体的表达,导致细胞凋亡或无能。     

蛋白质硝基化反应的途径

导致蛋白质发生硝基化反应的途径有多种,主要可以分为ONOO^-途径和非ONOO^-途径两类。ONOO^-途径导致的蛋白质硝基化可因金属离子或CO2的存在而强化,非ONOO^-途径导致的蛋白质硝基化则是亚硝酸盐或其它含氮物质在氧化剂存在下,经含铁卟啉的蛋白质催化而引发的。各种途径导致的蛋白质硝基化都伴随着蛋白质氧化的存在。     

研究称干细胞缺陷可能导致脱发

美国宾夕法尼亚大学的研究人员研究发现,毛囊干细胞缺陷使其无法产生让头发生长的源细胞,从而导致脱发。对男性来说．这种现象称为男性秃顶,其症状为头部开始掉发,发际线后退,最终导致全秃;对女性来说,其症状为头发越来越稀,但很少导致全秃。     

维生素在肿瘤干细胞信号传导通路中的作用机制探讨

肿瘤干细胞的形成是一个多环节、多步骤的过程,其中维生素缺乏,可导致细胞信号传导改变,使细胞发育不良。维生素长期缺乏导致的细胞适应性变化可能与肿瘤干细胞的形成和维持有关。本综述主要探讨维生素信号传导导致肿瘤干细胞形成的机制,为肿瘤的预防和治疗提供理论依据。     

井冈山自然保护区蛾类多样性及人为干扰的影响

对井冈山自然保护区蛾类群落的多样性及其受人为干扰的影响进行了研究。结果显示：（1）人为干扰导致井冈山自然保护区蛾类群落构成有较大差别,严重干扰导致蛾类科数明显降低;物种数和个体数呈现出随着人为干扰加强而降低的趋势;蛾类各优势科在不同人为干扰样点的相对多度存在差异。（2）人为干扰导致蛾类主要科的物种数和个体数变化不同：尺蛾科、夜蛾科、毒蛾科和舟蛾科的物种数和个体数在人为干扰下降低;轻度和中度干扰导致螟蛾科和天蛾科的物种数和个体数升高,重度干扰下物种数和个体数降低;人为干扰导致灯蛾科的物种数和苔蛾科的个体数升高。（3）人为干扰导致蛾类群落Shannon多样性指数、Pielou均匀度指数降低,Berger-Parker优势度指数升高。（4）人为干扰对蛾类群落的物种数和个体数的时间动态影响较大,对Shannon指数和Pielou均匀度指数时间动态影响较小,导致Berger-Parker优势度指数时间波动幅度增大。（5）人为干扰导致样点间蛾类群落相似性较低。     

昆虫乙酰胆碱酯酶基因变异抗药性机制研究

有机磷和氨基甲酸酯类杀虫剂的大量使用导致昆虫对其产生抗药性。乙酰胆碱酯酶是昆虫对这类杀虫剂产生抗性的重要的靶标酶,昆虫产生抗药性的重要原因之一,就是因为乙酰胆碱酯酶的基因表达量上升,或基因突变而导致其敏感性下降。文章简要论述昆虫乙酰胆碱酯酶基因发生变异而导致的抗药性,分析了变异对其结构和功能的影响。     

母乳成分改变影响子代脂肪肝发生的研究进展

近年来,哺乳期不良母体因素导致的乳汁成分改变对个体生长发育以及代谢性疾病发生的影响受到越来越多的关注。乳汁作为哺乳动物出生早期唯一的营养来源,其成分的改变可能会影响子代整体代谢稳态,进而导致子代代谢性疾病的发生。大量的动物实验表明,哺乳期不良母体因素可改变乳汁成分,同时导致哺乳期子代脂肪肝,并且可持续至成年。该文将就哺乳期不良母体因素导致乳汁成分改变对子代脂肪肝发生的影响及其可能机制进行综述,旨在更新哺乳期不良母体因素对子代肝脏脂代谢功能影响的认识,并为产妇的健康饮食提供参考。     

气调(CA)对储藏物害虫的作用机制

本文系统地介绍了气调措施对储藏物害虫的作用机制。在气调环境中 ,高CO2 和低O2 迫使昆虫的气门开启 ,导致体内水分过多散失和神经麻痹 ;吸入昆虫体内的CO2 能抑制昆虫的有氧代谢 ,导致昆虫体内能源物质的耗尽和有毒物质的积累。此外 ,气调还可导致储藏物害虫一些行为习性上的改变。     

中国浙江地区儿童下呼吸道感染KI多瘤病毒的鉴定

呼吸道病毒感染可以导致大面积人群致病[1],近些年,临床上由于不明原因导致的小儿下呼吸道感染病例屡见不鲜,对于该类患儿一般采取抗生素混合治疗的方法,但是治疗效果不佳.尽管过去几年开展的多项研究已经鉴定到了很多的病原体,如腺病毒,鼻病毒属病毒,冠状病毒属病毒,呼吸道合胞体病毒,流感病毒,副流感病毒等.     

急性呼吸道感染儿童中WU多瘤病毒基因组序列特征分析

为了解从北京地区急性呼吸道感染儿童中发现的WU多瘤病毒的基因组编码特征,并对其进行基因序列多样性分析,应用针对基因组5'端非编码区、衣壳蛋白VP1、VP2编码基因以及LTAg编码基因的引物对,从已确证为WU病毒阳性的来自北京地区急性呼吸道感染儿童的编号为BJF5276的临床标本中经聚合酶链反应扩增得到预期的基因片段,直接测序后将序列拼接得到全基因组序列,进而推导其基因组编码特征;随后从其它21例已确证为WU多瘤病毒阳性的急性呼吸道感染儿童标本中扩增得到衣壳蛋白VP2编码区基因,进行基因序列测定以及基因序列多样性分析。得到了WU病毒BJF5276全基因组序列。序列分析结果显示WU病毒BJF5276基因组序列全长为5229bp,共有5个主要的CDS(Coding domain sequences),分别编码衣壳蛋白VP2、VP3、VP1,并以其互补序列为模板,编码STAg和LTAg;所得到的22例VP2蛋白编码区基因序列同源性比较结果显示病毒VP2基因编码区序列与GenBank中已有的64个序列之间同源性很高;Mega4.0NJ进化树(Neighbor-joiningtree)分析显示这22个VP2基因序列分属于不同的基因进化簇,其中20个序列属于进化簇I中的Ia,另外2个序列属于进化簇III,其中的一个序列在IIIb基因进化簇中,另外一个序列独立成簇,不属于现有的IIIa或IIIb,暂时将其命名为IIIc。本研究结果提示北京地区的WU病毒具有多瘤病毒科的基因组编码特性;序列非常保守,有分属于不同基因进化簇的WU病毒在北京地区流行,与文献报道的以Ib流行为主所不同的是北京地区的WU病毒以Ia为主,且有新的基因进化簇出现。     

北京地区住院患儿WU多瘤病毒感染的流行病学研究

自2007年Gaynor A M等人通过高通量测序在肺炎患儿呼吸道样本中发现了WU多瘤病毒(Washington University polyomavirus,WUPyV)以来,WUPyV在世界各地被广泛检出。为了解北京地区急性呼吸道感染住院儿童中WUPyV感染情况及其临床特征,收集北京地区2017年4月至2018年3月共1 276份呼吸道感染住院患儿的鼻咽抽吸物样本,使用real time PCR方法对样本进行WUPyV检测,同时对WUPyV阳性样本进行17种常见呼吸道病毒筛查。共检出WUPyV阳性样本76份(5.96%,76/1 276),4岁以下儿童居多(92.11%,70/76);WUPyV感染全年可见,无显著季节性;多伴随其他呼吸道病毒混合感染(60.53%,46/76),最常见混合感染为鼻病毒和A型流感病毒;WUPyV单一感染者与混合感染者病毒载量无显著性差异,临床诊断和表现基本一致;WUPyV感染患儿的常见诊断为支气管炎(68.42%,52/76)和肺炎(30.26%,23/76);临床症状主要表现为高热、咳嗽、咳痰。研究结果提示WUPyV是北京地区急性呼吸道感染住院患儿呼吸道样本中常见病毒之一,多见于4岁以下儿童。     

Identification of a novel polyomavirus from patients with acute respiratory tract infections

We report the identification of a novel polyomavirus present in respiratory secretions from human patients with symptoms of acute respiratory tract infection. The virus was initially detected in a nasopharyngeal aspirate from a 3-year-old child from Australia diagnosed with pneumonia. A random library was generated from nucleic acids extracted from the nasopharyngeal aspirate and analyzed by high throughput DNA sequencing. Multiple DNA fragments were cloned that possessed limited homology to known polyomaviruses. We subsequently sequenced the entire virus genome of 5,229 bp, henceforth referred to as WU virus, and found it to have genomic features characteristic of the family Polyomaviridae. The genome was predicted to encode small T antigen, large T antigen, and three capsid proteins: VP1, VP2, and VP3. Phylogenetic analysis clearly revealed that the WU virus was divergent from all known polyomaviruses. Screening of 2,135 patients with acute respiratory tract infections in Brisbane, Queensland, Australia, and St. Louis, Missouri, United States, using WU virus-specific PCR primers resulted in the detection of 43 additional specimens that contained WU virus. The presence of multiple instances of the virus in two continents suggests that this virus is geographically widespread in the human population and raises the possibility that the WU virus may be a human pathogen.     

Whole-Genome Characterization and Genotyping of Global WU Polyomavirus Strains

Exploration of the genetic diversity of WU polyomavirus (WUV) has been limited in terms of the specimen numbers and particularly the sizes of the genomic fragments analyzed. Using whole-genome sequencing of 48 WUV strains collected in four continents over a 5-year period and 16 publicly available whole-genome sequences, we identified three main WUV clades and five subtypes, provisionally termed Ia, Ib, Ic, II, IIIa, and IIIb. Overall nucleotide variation was low (0 to 1.2%). The discriminatory power of the previous VP2 fragment typing method was found to be limited, and a new, larger genotyping region within the VP2/1 interface was proposed.In 2007, two new human polyomaviruses isolated from respiratory samples of pediatric patients suffering from respiratory disease were discovered, with one being KI polyomavirus (KIV) (2) and the other being WU polyomavirus (WUV) (8).WU polyomavirus shares most of the genomic characteristics of other polyomaviruses, with a noncoding control region (NCCR) separating the early and late coding regions on opposite strands. However, unlike for JCV and BKV, but similar to what was observed for KIV, a late-region-residing agnoprotein gene has not been identified in WUV (8).Despite being frequently detected in respiratory samples of ill patients, no distinct disease associations have so far been conclusively identified for WUV (1, 2, 4, 8, 10, 27). There have been some suggestions that sequence variation plays a role in disease severity and pathogenesis in other polyomaviruses (6, 24). Unfortunately, due to the early nature of research into WUV, there has been a dearth of available complete genomic sequences.In this study, we set out to investigate a large sample set of whole WUV genomes from diverse geographical, temporal, and clinical origins. Incorporating existing WUV genomes with this data set allowed us to investigate global WUV genomic diversity, to characterize the WUV genome, and to propose a new robust typing scheme.     

Real-time PCR test for detection and quantification of human polyomavirus BK (BKV) DNA

The human polyomavirus BK (BKV) is wide-spread pathogen, associated with urogenital tract disorders or even nephropathy in immunosuppressed patients. Nowadays molecular detection by real-time PCR (qPCR) is recognized as a method-of-choice for detecting human polyomaviruses in clinical samples. The aim of the study was development of real-time PCR assay for detection and quantification of polyomavirus BK DNA in clinical samples, using specific primers targeting a viral DNA VP3 gene and a TaqMan hydrolyzing probe. The analytical sensitivity of assay was tested using serial dilutions of BKV DNA in range between 13500 and 15 copies/ml. 27 urine samples and 23 plasma samples taken from a group of 22 adult recipients of allogeneic HSCT were tested for the presence of polyomavirus BK in the LightCycler system. Described in-house real-time PCR assay detected BKV DNA in 8 specimens (6 urine and 2 plasma). Detected average viral load was 170 copies/ml for plasma and 1250 copies/ml for urine samples, respectively. The results of this study show that developed TaqMan-based probe qPCR assay is very reliable and valuable for detection and quantification of BKV DNA, both in urine and plasma samples. These data, combined with its rapid turnaround time for results and decreased hands-on time, make the LightCycler PCR assay highly suitable for the rapid diagnostics of polyomavirus BK infections in the clinical laboratory.     

2株WU多瘤病毒全基因组序列测定和分析

WU多瘤病毒(WUPyV)是多瘤病毒科多瘤病毒属的新成员,近来发现与人呼吸道感染等有关。本研究对2株WUPyV进行全基因组序列测定和拼接,获得这2株病毒全基因组序列,并与已上传到GenBank的国内外几株WUPyV的全基因组序列和氨基酸序列进行比对和系统进化分析。这2株WUPyV是环状、双链DNA病毒,基因组全长5 228bp,比GenBank已知WUPyV全序列少1bp。缺失的一对碱基位于位点4 536处,属于大T抗原的非编码区。病毒全基因组编码5个蛋白,分别是3个衣壳蛋白VP2、VP3、VP1与大T抗原和小T抗原。系统进化分析显示相对中国福建福州的FZ18株,另一株FZTF株与参考株-澳大利亚的B0株关系较近。     

Infrequent detection of KI, WU and MC polyomaviruses in immunosuppressed individuals with or without progressive multifocal leukoencephalopathy

Conflicting prevalence of newly identified KI (KIPyV), WU (WUPyV) and Merkel Cell Carcinoma (MCPyV) polyomaviruses have been reported in progressive multifocal leukoencephalopathy (PML) patient samples, ranging from 0 to 14.3%. We analyzed the prevalence of these polyomaviruses in cerebrospinal fluid (CSF), peripheral blood mononuclear cells (PBMC), and bone marrow samples from PML patients, immunosuppressed individuals with or without HIV, and multiple sclerosis (MS) patients. Distinct PCR tests for KIPyV, WUPyV and MCPyV DNA performed in two independent laboratories detected low levels of MCPyV DNA only in 1/269 samples. The infrequent detections of these viruses in multiple samples from immunosuppressed individuals including those with PML suggest that their reactivation mechanisms may be different from that of JC polyomavirus (JCPyV) and that they do not play a role in the pathogenesis of PML.