神经肌肉性疾病患者线粒体DNA突变的分析 Analysis on the Mitochondrial DNA of Patients with Neuromuscular Diseases

为了探讨神经肌肉性疾病的发病与线粒体DNA突变的关系,采用PCR技术检测了 20例患有不同神经肌肉性疾病儿童的外周血和骨骼肌细胞中的线粒体DNA(mtDNA),发现其中6例患儿有mtDNA缺失,其中1例至少有2968bp片段的缺失, 另5例至少有2000bp片段的缺失,此缺失区位于线粒体呼吸链复合物1、 4、5、编码区,表明该突变对神经肌肉性疾病的发生有一定作用。 Abstract:To understand the relation to mechanism of neuromuscular disease and mtDNA mutation,using PCR technique,we investigated blood and /or skeletal muscle of 20 patients with neuromuscular diseases.A deletion in the length of 2000~2968bp was found in blood mitochondrial DNA of 6 patients with neuromuscular disease.The deletion region partially lies in the coding region of resoiratony chain complex 1,4,5.It is suggested that this mutation ois related with neuromuscular diseases.     

神经肌肉性疾病患者线粒体DNA突变的分析

为了探讨神经肌肉性疾病的发病与线粒体DNA突变的关系,采用PCR技术检测了 20例患有不同神经肌肉性疾病儿童的外周血和骨骼肌细胞中的线粒体DNA(mtDNA),发现其中6例患儿有mtDNA缺失,其中1例至少有2968bp片段的缺失, 另5例至少有2000bp片段的缺失,此缺失区位于线粒体呼吸链复合物1、 4、5、编码区,表明该突变对神经肌肉性疾病的发生有一定作用。 Abstract:To understand the relation to mechanism of neuromuscular disease and mtDNA mutation,using PCR technique,we investigated blood and /or skeletal muscle of 20 patients with neuromuscular diseases.A deletion in the length of 2000~2968bp was found in blood mitochondrial DNA of 6 patients with neuromuscular disease.The deletion region partially lies in the coding region of resoiratony chain complex 1,4,5.It is suggested that this mutation ois related with neuromuscular diseases.     

肥厚型心肌病患者心肌mtDNA大片段缺失的探讨

应用Long PCR及Primer Shift Long PCR 技术对3例肥厚型心肌病(HCM）患者和10例正常引产胎儿的13份心肌标本予以线粒体 DNA缺失检测,结果在1例HCM患者心肌线粒体DNA中发现约5.0kb缺失,而在正常引产胎儿的标本未见该缺失,提示HCM的发生可能与mtDNA缺失相关。 Astract　Using long PCR and primer shift long PCR techniques, we analyzed the mitochondrial DNA (mtDNA) isolated from the heart muscles of 3 hypertrophic cardiomyopathy (HCM) patients and 10 normal abortive fetuses. Almost 5.0kb deletion was found in the heart mtDNA of one HCM patient, while no deletion was detected in that of 10 fetuses. It is concluded that HCM may correlate with mtDNA deletion.     

线粒体基因突变与NIDDM发生的关系

采用PCR-SSCP、PCR-RFLP及PCR产物直接测序等技术对90例NIDDM(即非胰岛素依赖型糖尿病)及80例正常对照个体的血细胞线粒体DNA进行了突变分析。结果在2例患者中发现线粒体DNA(mitochondrial DNA,mtDNA) ND1 (NaDH Dehydrogenase subunitⅠ)基因上3316位点存在G→A的点突变,导致丙氨酸错义突变成苏氨酸,而在80例正常对照个体中均不存在此位点突变。国内外已证实的和1.5%NIDDM发生有关的mtDNA tRNA Leu^(UUR)|基因上3243位点A→G的突变在本实验中并未发现。由此推断,3316位点G→A的突变可能与NIDDM的发生在关,3243位点A→G的突变率确实很低,可见糖尿病的发生在线粒体遗传上具有广泛的异质性。 Abstract:Using PCR-SSCP,PCR-RFLP and PCR product direct sequencing techniques,we analysed the mitochondrial DNAs(mtDNAs)of 90 patients with NIDDM (Non Insulin-Dependent Diabetes Mellitus)and those of 80 normal controls.The results showed that a G to A mutation which leads alanine’s missence mutaton to threonine in the mitochondrial ND1(NaDH Dehydrogenase subunit I) gene at nucleotide pair 3316 occurred in the blood cells of 2 patients.We have not however,indentified with the A to G mutation at nucleotide pair 3243 of the mitochondrial tRNA Leu(UUR) gene,which has been reported to associate with NIDDM in about 1.5% of the diabetic population.We infer that the mutation at position 3316 is perhaps associated with the development of NIDDM,the occurance of the mutation at position 3243 is actually rare,and NIDDM has an intensive mitochondrial genetic heterogenous background.     

Hypoglycemic effect of catalpol on high-fat diet/streptozotocin-induced diabetic mice by increasing skeletal muscle mitochondrial biogenesis

Catalpol, an iridoid glycoside, exists in the root of Radix Rehmanniae. Some studies have shown that catalpol has a remarkable hypoglycemic effect in the streptozotocin- induced diabetic model, but the underlying mechanism for this effect has not been fully elucidated. Because mito- chondrial dysfunction plays a vital role in the pathology of diabetes and because improving mitochondrial function may offer a new approach for the treatment of diabetes, this study was designed. Catalpol was orally administered together with metformin to high-fat diet/streptozotocin （HFD/STZ）-induced diabetic mice daily for 4 weeks. Body weight （BW）, fasting blood glucose （FBG） level, and glucose disposal （IPGTT） were measured during or after the treatment. The results showed a dose-dependent re- duction of FBG level with no apparent changes in BW through four successive weeks of catalpol administration. Catalpol treatment substantially reduced serum total chol- esterol and triglyceride levels in the diabetic mice. In add- ition, catalpol efficiently increased mitochondrial ATP production and reversed the decrease of mitochondrial membrane potential and mtDNA copy number in skeletal muscle tissue. Furthermore, catalpol （200 mg/kg） rescued mitochondrial ultrastructure in skeletal muscle, as detected with transmission electron microscopy. The relative mRNA level of peroxisome proliferator-activated receptor gamma co-activator 1 （PGC1） α was significantly decreased in muscle tissue of diabetic mice, while this effect was reversed by catalpol. resulting in a dose-dependent up-regulation. Taken together, we found that catalpol was capable of lowering FBG level via improving mitochondrial function in skeletal musde of HFD/STZ-induced diabetic mice.     

Preliminary DNA identification for the tsunami victims in Thailand

The 2004 Southeast Asia Tsunami killed nearly 5,400 people in Southern Thailand, including foreign tourists and local residents. To recover DNA evidence as much as possible from the seriously decomposed bodies, we explored procedures of sample preparation from both bone and tooth samples as well as both mitochondrial and nuclear markers. Despite having failed to recover enough DNA for nuclear marker typing, we succeeded in obtaining fully informative results for mitochondrial markers （HV1 and HV2） from 258 tooth samples with a success rate of 51% （258/507）. Using an organic DNA extraction method coupled with an ultrafiltration step, we obtained 16 STR （including 13 CODIS loci, one sex discrimination locus, and two Identifiler loci） profiles for 834 samples with a success rate of 79% （834/1,062）. In addition, by comparing the allelic frequencies between the typed samples as a group and other index populations, we conclude that the Thai tsunami victims are a combined group of several populations. Our results provide valuable evidence and protocols for the future forensic practice.     

一个氨基糖苷类抗生素致聋家系线粒体DNA突变研究

应用PCR、PCR－SSCP和DNA序列分析等分子生物学技术,对一个有明确氨基糖苷类抗生素应用史的母系遗传耳聋家系共8人(包括聋人和听力正常者) 的线粒体DNA进行研究,结果显示,家系中有4份样品存在线粒体DNA 12S rRNA 1 555位点A→G的突变。提示线粒体DNA点突变是导致该家系致聋的主要因素之一。 Abstract:Blood samples were obtained from a pedigree with aminoglycoside antibiotic induced deafness.DNA was extracted from the isolated leukocytes.The mitochondrial DNA fragments were detected by PCR－SSCP and DNA sequencing.It was found that four individuals from the pedigree carried 1 555 A→G mutation.From our results,mitochondrial DNA mutation may be one of major factors in aminoglycoside antibiotic induced deafness.     

线粒体DNA修复系统相关酶的研究进展

线粒体DNA（mtDNA）编码线粒体电子传递系统的亚单位以及构建翻译机器所需的各种rRAN和tRNA。mtDNA编码的每一个亚单位都是线粒体完成正常的氧化磷酸化过程所必需的,因此,线粒体DNA的完整性对于生物体的生存十分重要。长期以来,人们一直认为线粒体中不存在DNA的修复。近年来在线粒体提取物中却检测到了一定数量的修复因子,提示线粒体中存在DNA的修复。主要对线粒体修复系统中相关酶的研究进展进行综述。Abstract: Mitochondrial DNA（mtDNA） encodes subunits of the mitochondrial electron transport system and the rRNAs and tRNAs required for constructing the mitochondrial tranlational machinery.Each subunit encoded by mtDNA is essential for normal oxidative phosphorylation.Thus,integrity of the mtDNA is crucial for the survival of organisms.It has long been held that there is no DNA repair in mitochondria.But in recent years,a number of repair factors have been found in mitochondrial extracts,suggesting the presence of DNA repair in mitochondria.This review summarized recent progress of enzyme in mitochondrial DNA repair processes.     

A Matrilineal Genetic Legacy from the Last Glacial Maximum Confers Susceptibility to Schizophrenia in Han Chinese

Mitochondrial dysfunction has been widely reported in schizophrenia patients. To dissect the matrilineal structure of Han Chinese with or without schizophrenia and to decipher the maternal influence and evolutionary history of schizophrenia, a total of 1212 schizophrenia patients and 1005 matched healthy controls, all of Han Chinese origin, were recruited in Hunan Province, China. We classified haplogroup for each individual based on mitochondrial DNA （mtDNA） sequence variations and compared the haplogroup distribution pattern between cases and controls. Haplogroup B5a presented a higher frequency in cases than in controls （P = 0.02, OR = 1.67, 95% CI = [1.09, 2.56]）, and this result could be confirmed by permutation analysis. Age estimation of haplogroup B5a in cases revealed a much younger age than that of controls, which was coincident with the Northern Hemisphere deglaciation at the end of the Last Glacial Maximum. Analysis of complete mtDNA in five patients belonging to haplogroup B5a showed that this background effect might be caused by haplogroup- defining variants m.8584G〉A and m.10398A〉G. Our results showed that matrilineal risk factor for schizophrenia had an ancient origin and might acquire a predisposing effect on schizophrenia due to the environment change and/or orchestration with other nuclear genetic factors appeared recently in human evolutionary history.     

载脂蛋白E基因多态性与动脉粥样硬化性脑梗塞关系的研究

应用聚合酶链反应(PCR)扩增ApoE基因外显子4中编码112位和158位氨基酸的 DNA片段,将该长为292bp的PCR产物以HhaI酶切,根据其限制性片段长度多态性图谱确定ApoE基因型。对广东汉族人群的50例动脉粥样硬化脑梗塞(ACI)患者和50例健康对照者的ApoE基因多态性频率的研究结果表明:所研究的人群中,ApoE基因多态性频率与ACI没有关联。ACI患者中各基因型亚组之间血清TG和TC浓度无显著性差异。 Abstract:The polymerase chain reaction(PCR)and restriction fragment length polymorphism techniques(RFLPs)were used to study the relation between apolipoprotein E gene polymorphism and atherosclerotic cerebral infarction(ACI).A 292 bp DNA fragment containing codes for the 112 and 158 amino acid residues in the fourth exon of ApoE gene was amplified by PCR.The PCR products were digested with HhaI.The polymorphism patterns of Apo E gene,allele frequencies in 50 Chinese healthy and 50 patients with ACI,and the serum levels of TG and TC in the different subgenotypes of 50 patients with ACI were detected.,no statistical significant differences of alleles frequencies were found between the cases with ACI and the control,and no statistical significant differences of the serum levels of TG and TC were found among the different subgenotypes of 50 patients with ACI.These results suggested that ApoE gene polymorphism was not associated with the development of ACI.     

Curcuminoids as inhibitors of thioredoxin reductase: A receptor based pharmacophore study with distance mapping of the active site

Curcumin is the yellow pigment of turmeric that interacts irreversibly forming an adduct with thioredoxin reductase (TrxR), an enzyme responsible for redox control of cell and defence against oxidative stress. Docking at both the active sites of TrxR was performed to compare the potency of three naturally occurring curcuminoids, namely curcumin, demethoxy curcumin and bis-demethoxy curcumin. Results show that active sites of TrxR occur at the junction of E and F chains. Volume and area of both cavities is predicted. It has been concluded by distance mapping of the most active conformations that Se atom of catalytic residue SeCYS498, is at a distance of 3.56 from C13 of demethoxy curcumin at the E chain active site, whereas C13 carbon atom forms adduct with Se atom of SeCys 498. We report that at least one methoxy group in curcuminoids is necessary for interation with catalytic residues of thioredoxin. Pharmacophore of both active sites of the TrxR receptor for curcumin and demethoxy curcumin molecules has been drawn and proposed for design and synthesis of most probable potent antiproliferative synthetic drugs.     

A Unique Protease Cleavage Site Predicted in the Spike Protein of the Novel Pneumonia Coronavirus (2019-nCoV) Potentially Related to Viral Transmissibility

正Dear Editor,In December 2019, a novel human coronavirus caused an epidemic of severe pneumonia(Coronavirus Disease 2019,COVID-19) in Wuhan, Hubei, China(Wu et al. 2020; Zhu et al. 2020). So far, this virus has spread to all areas of China and even to other countries. The epidemic has caused 67,102 confirmed infections with 1526 fatal cases     

Comparative morphology of the carpel in the Liliaceae: Hewardieae, Petrosavieae, and Tricyrteae

The young pistils in the melanthioid tribes, Hewardieae, Petrosavieae and Tricyrteae, are uniformly tricarpellate and syncarpous. They lack raphide idioblasts. All are multiovulate, with bitegmic ovules. The Petrosavieae are marked by the presence of septal glands and incomplete syncarpy. Tepals and stamens adhere to the ovary in the Hewardieae and the Petrosavieae but not in the Tricyrteae. Two vascular bundles occur in the stamens of the Hewartlieae and Tricyrtis latifolia. Ventral bundles in the upper part of the ovary of the Hewardieae are continuous with compound septal bundles and placental bundles in the lower part. Putative ventral bundles occur in the alternate position in the Tricyrteae and putative placental bundles in the opposite. position in the Petrosavieae. The dichtomously branched stigma in each carpel of the Tricyrteae is supplied by a bifurcated dorsal bundle.     

鸡传染性法氏囊病病毒研究进展

传染性法氏囊病(Infection bursal disease, IBD)是由鸡传染性法氏囊病毒(Infectious bursal disease virus, IBDV)引起的鸡和火鸡的一种高度接触性传染病,给世界各国的禽养殖业带来了巨大损失.自IBDV发现至今新的变异株不断出现,分子结构的改变导致病毒致病力的改变及宿主对疫苗应答的改变,使得传统的疫苗已不能控制其流行,因此各国学者对其基因组结构和功能进行了广泛深入的研究,并积极研制新型有效的疫苗以达到防治的目的.     

Development of a Novel Reverse Transcription Loop-Mediated Isothermal Amplification Method for Rapid Detection of SARS-CoV-2

In conclusion, the novel visual RT-LAMP assay is a simple, rapid, and sensitive approach for detection of SARS-CoV-2, and it is ready for application in primary care and community hospitals or health care centers, and even patients' own houses in response to the current SARS-CoV-2 epidemic because the assay does not require sophisticated equipment and skilled personnel. Furthermore, it is also ready to be used in fields for screening samples from wild animals and environments to facilitate the identification of potential intermediate hosts that mediate the cross-species transmission of SARS-CoV-2 from bats to humans.     

Perinatal Vertical Transmission of Chikungunya Virus in Ruili,a Town on the Border between China and Myanmar

正Dear Editor,Chikungunya virus (CHIKV), an arbovirus in the family of Togaviridae, genus Alphavirus, is transmitted by the A.aegyptii or A. albopictus mosquito, and causes disease in humans characterized by fever, rash, and arthralgia (Silva and Dermody 2017; Suhrbier 2019). It was first reported in 1953 in Tanzania, and caused only a few outbreaks and sporadic cases in Africa and Asia in last century. However, in the epidemic in 2004, CHIKV acquired mutations that conferred enhanced transmission by the A. albopictus mosquito(Schuffenecker et al. 2006). Since then, it has successively caused outbreaks in Africa, the Indian Ocean, South East Asia, the South America, and Europe (Zeller et al. 2016).     

Enterovirus 71 3C proteolytically processes the histone H3 N-terminal tail during infection

Highlights
1. The N-terminal tail of histone H3 is specifically cleaved during EV71 infection.
2. Viral protease 3C is identified as a protease responsible for proteolytically processing the N-terminal H3 tail.
3. Our finding reveals a new epigenetic regulatory mechanism for Enterovirus 71 in virus-host interactions.