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HPV18 Utilizes Two Alternative Branch Sites for E6*I Splicing to Produce E7 Protein

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Virologica Sinica 2019年第2期34卷 211-221页

作者： Ayslan Castro Brant Vladimir Majerciak Miguel Angelo Martins Moreira Zhi-Ming Zheng Tumor Virus RNA Biology Section RNA Biology Laboratory Center for Cancer Research National Cancer Institute NIH Frederick MD 21702 USA genetics post-graduation program Rio de Janeiro Federal University Rio de Janeiro Brazil genetics program Nacional Cancer Institute INCA Rio de Janeiro 20231-050 Brazil

Human papillomavirus 18(HPV18) E6 and E7 oncogenes are transcribed as a single bicistronic E6 E7 pre-mRNA. The E6 ORF region in the bicistronic E6 E7 pre-mRNA contains an intron. Splicing of this intron disrupts the E6 ORF integrity and produces a spliced E6*I RNA for efficient E7 translation. Here we report that the E6 intron has two overlapped branch point sequences(BPS) upstream of its 30 splice site, with an identical heptamer AACUAAC, for E6*I splicing. One heptamer has a branch site adenosine(underlined) at nt 384 and the other at nt 388. E6*I splicing efficiency correlates to the expression level of E6 and E7 proteins and depends on the selection of which branch site. In general, E6*I splicing prefers the 30 ss-proximal branch site at nt 388 over the distal branch site at nt 384. Inactivation of the nt 388 branch site was found to activate a cryptic acceptor site at nt 636 for aberrant RNA splicing. Together, these data suggest that HPV18 modulates its production ratio of E6 and E7 proteins by alternative selection of the two mapped branch sites for the E6*I splicing, which could be beneficial in its productive or oncogenic infection according to the host cell environment.

关键词： Human papillomavirus 18 (HPV18) HPV splicing Branch point E6,E7,E6 intron HPV oncogenes

A novel Rad gene polymorphism combined with obesity increases risk for type 2 diabetes mellitus

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Chinese Medical Journal 2004年第5期117卷 770-771页

作者：王国英牛天华陈常忠李琼芳徐希平 Department of Endocrinology program for Population genetics

The ras-associated diabetes (Rad) was initially identified by subtraction cloning from the skeletal muscle of humans with non-insulin dependent diabetes mellitus (type 2 DM).1 Rad mRNA expression is markedly increased... 详细信息

关键词： Rad gene·obesity · polymorphism·type 2 diabetes mellitus

Identification of patients at-risk for Lynch syndrome in a hospital-based colorectal surgery clinic

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World Journal of Gastroenterology 2011年第6期17卷 766-773页

作者： Patrícia Koehler-Santos Patricia Izetti Jamile Abud Carlos Eduardo Pitroski Silvia Liliana Cossio Suzi Alves Camey Cláudio Tarta Daniel C Damin Paulo Carvalho Contu Mario Antonello Rosito Patricia Ashton-Prolla Joāo Carlos Prolla Genomic Medicine Laboratory Experimental Research CenterHospital de Clínicas de Porto Alegre post-Graduate program in Medical Sciences Federal University of Rio Grande do Sul National Institute for Populational Medical genetics Medical School Federal University of Rio Grande do Sul post-Graduate program in Gastroenterological Sciences Federal University of Rio Grande do Sul Department of Statistics Federal University of Rio Grande do Sul post-Graduate program in Epidemiology Federal University of Rio Grande do Sul Research and post-graduation Group Hospital de Clínicas de Porto Alegre Division of Coloproctology Hospital de Clínicas de Porto Alegre Department of Surgery Federal University of Rio Grande do Sul Medical genetics Service Hospital de Clínicas de Porto Alegre Department of genetics Federal University of Rio Grande do Sul Service of Pathology Hospital de Clínicas de Porto AlegrePorto Alegre-RS90035-903Brazil

AIM:To determine the prevalence of a family history suggestive of Lynch syndrome (LS) among patients with colorectal cancer (CRC) followed in a coloproctology outpatient clinic in Southern ***:A consecutive sample of patients with CRC were interviewed regarding personal and family histories of *** data and pathology features of the tumor were obtained from chart ***:Of the 212 CRC patients recruited,61 (29%) reported a family history of CRC,45 (21.2%) were diagnosed under age 50 years and 11 (5.2%) had more than one primary *** histories consistent with Amsterdam and revised Bethesda criteria for LS were identified in 22 (10.4%) and 100 (47.2%) patients,*** percent of the colorectal tumors had features of the high microsatellite instability phenotype,which was associated with younger age at CRC diagnosis and with Bethesda criteria (P < 0.001).Only 5.3% of the patients above age 50 years had been previously submitted for CRC screening and only 4% of patients with suspected LS were referred for genetic risk ***:A significant proportion of patients with CRC were at high risk for *** and training of health care professionals are essential to ensure proper management.

关键词： Colorectal cancer Family history Hereditary cancer Lynch syndrome Microsatellite instability phenotype

Neotropical electric fishes(Gymnotiformes)as model organisms for bioassays

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Journal of Coastal Life Medicine 2015年第4期 253-258页

作者： Milena Ferreira Isac Silva de Jesus Eliana Feldberg JoséAntônio Alves-Gomes graduation program in genetics Conservation and Evolutionary BiologyNational Institute of Amazon ResearchManausAmazonasBrazil

Electric fishes(Gymnotiformes)inhabit Central and South America and form a relatively large group with more than 200 *** a taxonomic challenge due to their still unresolved systematic,wide distribution and the variety of habitats they occupy,these fishes have been intensively studied due to their peculiar use of bioelectricity for electrolocation and *** analysis of cells,tissues and organs have been complemented with the studies on the electric organ discharges of these *** review compiles the results of 13 bioassays developed during the last 50 years,which used the quickness,low costs and functionality of the bioelectric data collection of Gymnotiformes to evaluate the effects of environmental contaminants and neuroactive drugs.

关键词： Electric fish Bioassays Potassium cyanide Petroleum products Mercury contamination Neuroactive drugs

Effects of P301L-TAU on post-translational modifications of microtubules in human iPSC-derived cortical neurons and TAU transgenic mice

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Neural Regeneration Research 2025年第8期20卷 2348-2360页

作者： Mohamed Aghyad Al Kabbani Christoph Köhler Hans Zempel Institute of Human genetics Faculty of Medicine and University Hospital CologneUniversity of CologneCologneGermany Center for Molecular Medicine Cologne(CMMC) University of CologneCologneGermany Center Anatomy Department ⅡMedical FacultyUniversity of CologneCologneGermany

TAU is a microtubule-associated protein that promotes microtubule assembly and stability in the *** is missorted and aggregated in an array of diseases known as *** are essential for neuronal function and regulated via a complex set of post-translational modifications,changes of which affect microtubule stability and dynamics,microtubule interaction with other proteins and cellular structures,and mediate recruitment of microtubule-severing *** impairment of microtubule dynamics causes neuronal dysfunction,we hypothesize cognitive impairment in human disease to be impacted by impairment of microtubule *** therefore aimed to study the effects of a disease-causing mutation of TAU(P301L)on the levels and localization of microtubule post-translational modifications indicative of microtubule stability and dynamics,to assess whether P301L-TAU causes stability-changing modifications to *** investigate TAU localization,phosphorylation,and effects on tubulin post-translational modifications,we expressed wild-type or P301L-TAU in human MAPT-KO induced pluripotent stem cell-derived neurons(i Neurons)and studied TAU in neurons in the hippocampus of mice transgenic for human P301L-TAU(p R5 mice).Human neurons expressing the longest TAU isoform(2N4R)with the P301L mutation showed increased TAU phosphorylation at the AT8,but not the p-Ser-262 epitope,and increased polyglutamylation and acetylation of microtubules compared with endogenous TAU-expressing neurons.P301L-TAU showed pronounced somatodendritic presence,but also successful axonal enrichment and a similar axodendritic distribution comparable to exogenously expressed 2N4R-wildtype-TAU.P301L-TAU-expressing hippocampal neurons in transgenic mice showed prominent missorting and tauopathy-typical AT8-phosphorylation of TAU and increased polyglutamylation,but reduced acetylation,of microtubules compared with non-transgenic *** sum,P301L-TAU results in changes in micr

关键词： human induced pluripotent stem cell microtubules P301L pR5 mice TAU tauopathy tubulin code

Toward pluripotency by reprogramming:mechanisms and application

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Protein & Cell 2013年第11期4卷 820-832页

作者： Tao Wang Stephen TWarren Peng Jin Department of Human genetics Emory UniversityAtlantaGA 30322USA genetics and Molecular Biology Graduate program Emory UniversityAtlantaGA 30322USA

The somatic epigenome can be reprogrammed to a pluri-potent state by a combination of transcription *** cell fate involves transcription factors coopera-tion,epigenetic reconfi guration,such as DNA methylation and histone modification,posttranscriptional regulation by microRNAs,and so ***,such reprogram-ming is *** suggests that during the early stage of reprogramming,the process is stochastic,but by the late stage,it is *** addition to con-ventional reprogramming methods,dozens of small mol-ecules have been identifi ed that can functionally replace reprogramming factors and signifi cantly improve induced pluripotent stem cell(iPSC)***,iPS cells have been created recently using chemical com-pounds *** are thought to display subtle genetic and epigenetic variability;this variability is not random,but occurs at hotspots across the *** we dis-cuss the progress and current perspectives in the fi *** into the reprogramming process today will pave the way for great advances in regenerative medicine in the future.

关键词： epigenetic reprogramming induced pluripo-tent stem cells embryonic stem cells disease modeling

Cancer epigenetics: a perspective on the role of DNA methylation in acquired endocrine resistance

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Chinese Journal of Cancer 2011年第11期30卷 749-756页

作者： Michael P. Trimarchi Mary Mouangsavanh Tim Hui-Ming Huang Human Cancer genetics program Department of Molecular Virology Immunology and Medical Genetics The Ohio State University Columbus Ohio 43210 USA

Epigenetic mechanisms, including DNA methylation, are responsible for determining and maintaining cell fate, stably differentiating the various tissues in our bodies. Increasing evidence shows that DNA methylation plays a significant role in cancer, from the silencing of tumor suppressors to the activation of oncogenes and the promotion of metastasis. Recent studies also suggest a role for DNA methylation in drug resistance. This perspective article discusses how DNA methylation may contribute to the development of acquired endocrine resistance, with a focus on breast cancer. In addition, we discuss DNA methylome profiling and how recent developments in this field are shedding new light on the role of epigenetics in endocrine resistance. Hormone ablation is the therapy of choice for hormone-sensitive breast tumors, yet as many as 40% of patients inevitably relapse, and these hormone refractory tumors often have a poor prognosis. Epigenetic studies could provide DNA methylation biomarkers to predict and diagnose acquired resistance in response to treatment. Elucidation of epigenetic mechanisms may also lead to the development of new treatments that specifically target epigenetic abnormalities or vulnerabilities in cancer cells. Expectations must be tempered by the fact that epigenetic mechanisms of endocrine resistance remain poorly understood, and further study is required to better understand how altering epigenetic pathways with therapeutics can promote or inhibit endocrine resistance in different contexts. Going forward, DNA methylome profiling will become increasingly central to epigenetic research, heralding a network-based approach to epigenetics that promises to advance our understanding of the etiology of cancer in ways not previously possible.

关键词： DNA甲基化作用表观遗传学内分泌癌症收购甲基化分析遗传机制肿瘤抑制

Heat shock factor 1 is a direct anti-amyloid factor:connecting neurodegeneration and uncontrolledgrowth

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Neural Regeneration Research 2022年第3期17卷 559-560页

作者： Zijian Tang Chengkai Dai Mouse Cancer genetics program Center for Cancer ResearchNational Cancer InstituteFrederickMDUSA

Worldwide,more than 40 million people are afflicted with Alzheimer's disease(AD)(Esquerda-Canals et al.,2017).AD is a devastating neurodegenerative disroder characterized by progressive decline in cognitive abilities.A hallmark of AD and other neurodegenerative disorders in humans is the aggregation of proteins into amyloid fibrils and their deposition into plaques and intracellular inclusions(Iadanza et al.)。

关键词： amyloid al. Alzheimer

From filaments to function: The role of the plant actin cytoskeleton in pathogen perception,signaling and immunity

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Journal of Integrative Plant Biology 2016年第4期58卷 299-311页

作者： Katie Porter Brad Day Graduate program in Cell and Molecular Biology Michigan State University Department of Plant Soil and Microbial Sciences Michigan State University Graduate program in genetics Michigan State University

The eukaryotic actin cytoskeleton is required for numerous cellular processes, including cell shape, development and movement, gene expression and signal transduction, and response to biotic and abiotic stress. In recent years,research in both plants and animal systems have described a function for actin as the ideal surveillance platform, linking the function and activity of primary physiological processes to the immune system. In this review, we will highlight recent advances that have defined the regulation and breadth of function of the actin cytoskeleton as a network required for defense signaling following pathogen infection. Coupled with an overview of recent work demonstrating specific targeting of the plant actin cytoskeleton by a diversity of pathogens,including bacteria, fungi and viruses, we will highlight the importance of actin as a key signaling hub in plants, one that mediates surveillance of cellular homeostasis and the activation of specific signaling responses following pathogen perception. B4 ased on the studies highlighted herein, we propose a working model that posits changes in actin filament organization is in and of itself a highly specific signal, which induces, regulates and physically directs stimulus-specific signaling processes, most importantly, those associated with response to pathogens.

关键词： Actin cytoskeleton immunity pathogen plant Pseudomonas syringae surveillance