线粒体表观遗传调控与阿尔茨海默病的研究进展

正线粒体表观遗传调控(mitoepigenetic regulation)是指对线粒体基因组编码基因的表观遗传学修饰调控,可引起线粒体基因组编码基因表达的改变,致使线粒体功能异常,导致多种疾病的发生。近年研究表明,线粒体表观遗传调控与阿尔茨海默病(Alzheimer disease,AD)发病机制密切相关。AD是一种中枢神经退行性疾病,典型神经病理变化是β-淀粉样蛋白(amyloid-β,Aβ)沉淀形成老年斑和神经原纤维     

microRNA在肿瘤表观遗传学中的研究进展

microRNA(miRNA)是一类长约22nt的非编码小RNA,转录后水平调节基因的表达,在个体发育、细胞的增殖、凋亡、分化中发挥重要的作用。近年来研究发现,miRNA的表达异常与肿瘤的发生关系密切。新近研究发现,属于广义表观遗传范畴的miRNA,其自身的表达不仅受到DNA甲基化等表观遗传的调控,而且两者可能存在相互作用,参与肿瘤的发生、发展。microRNA在肿瘤表观遗传学的研究将为肿瘤的诊断、治疗和预防开辟了新的思路和方向。     

肿瘤细胞中的表观遗传编码紊乱

不改变基因的DNA编码,通过改变DNA双链与组蛋白间紧密度来决定基因是否转录表达,这称为表观遗传编码机制。表观遗传编码的生理作用是通过组蛋白修饰和DNA甲基化,调控细胞在适当的时间、空间位置表达适当的基因,从而控制细胞的增殖状况和分化方向。在细胞发育过程中,细胞内DNA甲基化水平增龄性增高,基因转录活性逐渐降低,使细胞从幼稚增殖进入成熟分化。肿瘤细胞中出现表观遗传编码紊乱,致细胞增殖失控,不能进入分化成熟阶段。基因启动子出现甲基化重排,阻碍转录因子与启动子结合,导致基因转录丧失正常调控,合成成熟功能蛋白受阻。利用表观遗传机制(如,RNA干涉)可成为肿瘤治疗的新方法。     

结直肠癌发生发展中miRNAs机制的研究进展

microRNhs(miRNAs)是在动植物和病毒中发现的一个非编码单链小RNA,在肿瘤的发生和发展中起重要作用.目前认为,miRNAs对肿瘤的调控属于表观遗传学范畴.近年来,众多研究者开始关注人类结直肠癌的miRNAs表达谱,并深入探究miRNAs所处的调节网络.作者综述了有关结直肠癌miRNAs表达异常及作用机制的最新研究,以期为结直肠癌表观遗传学干预找到新的切入点.     

多发性硬化的表观遗传学研究进展北大核心CSCD

多发性硬化是一种以中枢神经系统白质脱髓鞘病变为主的自身免疫性疾病。表观遗传学是不影响DNA碱基序列,而基因表达发生变化。越来越多的研究表明,表观遗传学参与多发性硬化的发生和发展。碱基修饰、组蛋白翻译后修饰、微小RNA(miRNA)及长链非编码RNA(LncRNA)等表观遗传学过程影响多发性硬化的免疫调节。本文就相关研究进行综述,以期为多发性硬化的发病机制提供新的认识。     

hTERT表观调控及其与肿瘤相关性研究

hTERT基因编码人端粒酶催化亚基,该亚基以端粒酶RNA为模板反转录形成TTAGGG短串联重复,这些重复序列添加于染色体端粒DNA 3 '端以维护染色体稳定性.hTERT的转录受多种因素的影响,如以DNA甲基化为代表的表观遗传途径和多种转录因子的调控.hTERT表观异常修饰可能与肿瘤发生相关,探讨hTERT启动子甲基化改变有望为细胞衰老、死亡的调控以及肿瘤诊断提供重要的生物学指标.该文就hTERT不同层次的表观遗传调控改变及其与肿瘤的相关性进行概述.     

表观遗传学与肺癌的研究进展

表观遗传学是分子生物学研究领域内的一个新的研究内容。表观遗传改变调控基因表达并不改变DNA的序列，但又能够通过细胞分裂在代与代之间传递。本文主要阐述了DNA甲基化、组蛋白的共价修饰以及RNA介导的基因沉默以及microRNA等表观遗传相关因素在生物体生长发育过程中对基因表达的重要调控作用以及表观遗传事件对肺癌发生的作用。     

表观遗传修饰与神经系统疾病或精神类疾病相关性的研究进展

表观遗传修饰主要通过DNA甲基化、组蛋白修饰和小型非编码RNA调控等之间繁杂的相互作用, 进而影响基因的转录和表达。表观遗传调控介导了遗传和环境因素的相互作用, 是大脑适应环境应激的主要机制, 其对神经发育、神经干细胞命运的决定和神经系统生理功能的发挥具有重要的调节作用。异常的表观遗传修饰与阿尔茨海默病、帕金森病、神经分裂症和抑郁症等神经系统疾病或精神类疾病的发生和发展有密切关系。本文综述了表观基因组学在神经科学中的重要性, 以及其与神经系统疾病或精神类疾病的重要关系。     

肺癌与慢性阻塞性肺病的表观遗传学

肺癌是严重影响人类健康的恶性肿瘤之一,影响肺癌发病的表观遗传学机制已成为近年来的研究热点.慢性阻塞性肺病(chronic obstructive pulmonary disease,COPD)不但是肺癌的常见合并症,而且可能是肺癌的独立风险因素.肺癌和COPD在表观遗传学水平的改变主要涉及DNA甲基化、组蛋白修饰和非编码RNA调控等.探讨肺癌与COPD在表观遗传学水平的改变及其相互关系,可为肺癌及COPD的发病机制、疾病进展、疾病预后等提供更为广阔的视角,并为疾病的治疗开辟新的方向.     

抑郁症的表观学遗传改变的研究进展

抑郁症是以快感缺失、持续心境低落为特征,伴睡眠、饮食、认知与记忆障碍的精神心理疾病.据WHO报道2030年抑郁症将成为全球疾病负担的首要疾病,造成了极大的医疗、经济与社会负担.表观遗传是指在基因序列不改变的条件下使基因表达水平发生变化,包括DNA甲基化、组蛋白修饰、染色体重塑和非编码RNA调控等,主要通过对基因转录或翻译过程的调控,影响其功能和特性.近年来越来越多的研究表明遗传和环境在抑郁症发病中起重要作用,本文就抑郁症的表观遗传变化做一综述,以期为后续MDD表观遗传相关机制研究提供参考.     

Renal dysplasia and asplenia in two sibs

A family is reported in which two sibs, one male and the other female, both died within 24 hours of birth with enlarged polycystic kidneys. Postmortem histology in the second child showed gross renal dysplasia. In both children the pancreas was enlarged, nodular and cystic but the liver appeared macroscopically normal. In the second child, histological examination confirmed pancreatic fibrosis with cystic dilation of ducts, but showed portal fibrosis with bile duct proliferation in the liver.
This combination of findings is very reminiscent of those in a girl and her brother reported by Ivemark et al. (1959). The children reported here also showed absence or hypoplasia of the spleen, cardiac anomalies and other features of the Ivemark syndrome (Ivemark 1955), a quite different, usually sporadic, congenital disorder. It is suggested that the children described here have a distinct lethal congenital disorder, probably inherited in an autosomal recessive manner.     

Schizophrenia in a North Swedish geographical isolate, 1900–1977. Epidemiology, genetics and biochemistry

Over 200 schizophrenic patients belonging to three major and interrelated pedigree complexes have been investigated over the past 30 years in a North Swedish geographically isolated population, presently numbering about 6,000. An intensive investigation of a number of biochemical correlates and genetic markers in a few selected families belonging to one of the major pedigrees has indicated new strategies for the current research program.
Schizophrenia, as defined operationally, is significantly associated with decreased activities of two enzymes (1) blood platelet monoamine oxidase, (2) plasma dopamine-β-hydroxylase, and (3) with the genetic marker Gc² (group specific antigen). Both enzymes are subject to genetic variation. A positive score for linkage between schizophrenia and low plasma DBH activity has been calculated, but, so far, available data are insufficient for discrimination between linkage and partial contribution of genetically controlled low plasma DBH to the pathogenesis of the disease. Alternatively, both mechanisms could be involved.
As a model for continued research, schizophrenia is explained as based on a double dominant-recessive genotype (Aabb), representing a vulnerability which in about 50 % of cases develops into clinical schizophrenia. It is suggested that the dominant mutation (A) operates on or affects MAO activity, and that the recessive genotype (bb) is instrumental in low variates of DBH activity and very likely such variates within the normal range of physiological variation. Moreover, it is suggested that the combined effects of MAO- and DBH-reduced efficiency on the metabolism of e.g. dopamine could be an essential pathogenic mechanism for the schizophrenic illness which is segregating in this population.     

The dominant diseases of modernized societies as omega-3 essential fatty acid deficiency syndrome: Substrate beriberi

About 1900, modern food selection and processing caused widespread $\text{epidemics}$ of the B vitamin deficiency diseases of beriberi and pellagra which, for genetic reasons, often expressed as different diseases ranging from bowel and heart disease to dermatoses and psychoses. But the B vitamins merely help convert essential fatty acids (EFA) into the prostaglandin (PG) tissue regulators and it now turns out that, through hydrogenation, milling and selection of w3-poor southern foods, we have also been systematically depleting, by as much as 90%, a newly discovered trace Nordic EFA (w3) of special importance to primates and sole precursor of the PG3(4) series, even as a concurrent fiber deficiency increases body demand for EFA. Since substrate EFA is processed by many B vitamin catalysts, an EFA deficiency will mimic a $\text{panh}$ypovitaminosis B, i.e., a mixture of $\text{substrate}$ beriberi and $\text{substrate}$ pellagra resembling vitamin beriberi and pellagra but exhibiting as even more diverse $\text{endemic}$ disease. This would consitute a second stage of the Modern Malnutrition and explain why some workers now hold the dominant diseases of modermized societies to be new, nutritionally based, pellagraform yet lipid-related and to range, once again, from heart disease to psychosis. It is an assumption that our dominant diseases are unrelated to each other or are merely revealed by our diagnostic acumen and therapeutic success; and that hydrogenating millions of tons of food oils annually, to destroy the rancidity producing w3-EFA, is safe for $\text{primates}$. Extensive beriberiform disease is reported here in 32 typical cases taken from medical practice which responds strikingly to linseed oil supplements (60% w3-EFA) in confirmation of identical results in Capuchins.     

What will studies of Fulani individuals naturally exposed to malaria teach us about protective immunity to malaria?

There are an estimated over 200 million yearly cases of malaria worldwide. Despite concerted international effort to combat the disease, it still causes approximately half a million deaths every year, the majority of which are young children with Plasmodium falciparum infection in sub-Saharan Africa. Successes are largely attributed to malaria prevention strategies, such as insecticide-treated mosquito nets and indoor spraying, as well as improved access to existing treatments. One important hurdle to new approaches for the treatment and prevention of malaria is our limited understanding of the biology of Plasmodium infection and its complex interaction with the immune system of its human host. Therefore, the elimination of malaria in Africa not only relies on existing tools to reduce malaria burden, but also requires fundamental research to develop innovative approaches. Here, we summarize our discoveries from investigations of ethnic groups of West Africa who have different susceptibility to malaria.     

'Very sore nights and days': the child's experience of illness in early modern England, c.1580-1720

Sick children were ubiquitous in early modern England, and yet they have received very little attention from historians. Taking the elusive perspective of the child, this article explores the physical, emotional, and spiritual experience of illness in England between approximately 1580 and 1720. What was it like being ill and suffering pain? How did the young respond emotionally to the anticipation of death? It is argued that children’s experiences were characterised by profound ambivalence: illness could be terrifying and distressing, but also a source of emotional and spiritual fulfilment and joy. This interpretation challenges the common assumption amongst medical historians that the experiences of early modern patients were utterly miserable. It also sheds light on children’s emotional feelings for their parents, a subject often overlooked in the historiography of childhood. The primary sources used in this article include diaries, autobiographies, letters, the biographies of pious children, printed possession cases, doctors’ casebooks, and theological treatises concerning the afterlife.     

Guidelines for the Validation and Use of Immunoassays for Determination of Introduced Proteins in Biotechnology Enhanced Crops and Derived Food Ingredients

Recent advancements in agricultural biotechnology have created a need for analytical techniques to determine introduced proteins in crops enhanced through modern biotechnology techniques. These proteins are expressed in plant tissues and may be present in food ingredients. Immunoassays are ideally suited for protein detection and may be used as both quantitative and threshold methods. Microplate ELISA and lateral flow devices are two of the most commonly used immunoassay formats for agricultural biotechnology applications. This paper provides general background information and a discussion of criteria for the validation and application of immunochemical methods to the analysis of proteins introduced into plants and food ingredients using biotechnology methods. It is the result of a collaborative effort of members of the Analytical Environmental Immunochemical Consortium. This collaborative effort represents the combined expertise of several organizations to reach consensus on establishing guidelines for the validation and use of immunoassays. Further, the paper offers developers and users a consistent approach to adopting the technology as well as aid in producing accurate and meaningful results.     

Ultracryotomy: development and application (with examples from the yeast cytology) (author's transl)

The preparation steps usually necessary for obtaining ultrathin frozen sections of biological material (chemical prefixation, enclosing, cryoprotective treatment, freezing, sectioning, and post-staining the sections for transmission electron microscopy) are submitted to a critical analysis. The application of cryo-ultramicrotomy, in particularly for cytochemical purposes, is reviewed. Fundamental considerations of chemical prefixation and poststaining are supported by examples from yeast cytology. Furthermore, the efficiency of the cryo-ultramicrotomy (electron optical resolution of ultrastructural details) is demonstrated on yeast cells and protoplasts.     

HLA in North Colombia Chimila Amerindians

HLA-A,-B,-C,-DRB1 and -DQB1 alleles have been studied in Chimila Amerindians from Sabana de San Angel (North Colombian Coast) by using high resolution molecular typing. A frequent extended haplotype was found:HLA-A*24:02-B*51:10-C*15:02-BRB1*04:07-DQB1*03:02 (28.7%) which has also been described in Amerinndian Mayos Mexican population (Mexico, California Gulf, Pacific Ocean). Other haplotypes had already been found in Amerindians from Mexico (Pacific and Atlantic Coast), Peru (highlands and Amazon Basin), Bolivia and North USA. A geographic pattern according to HLA allele or haplotype frequencies is lacking in Amerindians, as already known. Also, five new extended haplotypes were found in Chimila Amerindians. Their HLA-A*24:02 high frequencies characteristic is shared with aboriginal populations of Taiwan; also, HLA-C*01:02 high frequencies are found in New Zealand Maoris, New Caledonians and Kimberly Aborigines from Australia. Finally, this study may show a model of evolutionary factors acting and rising one HLA allele frequency (-A*24:02), but not in others that belong to the same or different HLA loci.     

The case for allele‐specific recognition by the TCR

There is a sharp difference in how one views TCR structure–function–behaviour dependent on whether its recognition of major histocompatibility complex‐encoded restriction elements (R) is germline selected or somatically generated. The generally accepted or Standard model is built on the assumption that recognition of R is by the V regions of the αβ TCR, which is not driven by allele specificity, whereas the competing model posits that recognition of R is allele‐specific. The establishing of allele‐specific recognition of R by the TCR would rule out the Standard model and clear the road to a consideration of a competing construct, the Tritope model. Here, the case for allele‐specific recognition (germline selected) is detailed making it obvious that the Standard model is untenable.