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Correlative CD4 and CD8 T-cell immunodominance in humans and mice:Implications for preclinical testing

Cellular & Molecular Immunology 2023年第11期20卷 1328-1338页

作者： Tertuliano Alves Pereira Neto john sidney Alba Grifoni Alessandro Sette Center for Infectious Disease and Vaccine Research La Jolla Institute for Immunology(LJI)La JollaCA92037USA Department of Medicine Division of Infectious Diseases and Global Public HealthUniversity of CaliforniaSan DiegoLa JollaCA92037USA

Antigen-specific T-cell recognition is restricted by Major Histocompatibility Complex(MHC)molecules,and differences between CD4 and CD8 immunogenicity in humans and animal species used in preclinical vaccine testing are yet to be fully *** this study,we addressed this matter by analyzing experimentally identified epitopes based on published data curated in the Immune Epitopes DataBase(IEDB)*** first analyzed SARS-CoV-2 spike(S)and nucleoprotein(N),which are two common targets of the immune response and well studied in both human and mouse *** observed a weak but statistically significant correlation between human and H-2^(b)mouse T-cell responses(CD8 S specific(r=0.206,p=1.37×10^(−13));CD4 S specific(r=0.118,p=2.63×10^(−5))and N specific(r=0.179,p=2.55×10^(−4))).Due to intrinsic differences in MHC molecules across species,we also investigated the association between the immunodominance of common Human Leukocyte Antigen(HLA)alleles for which HLA transgenic mice are available,namely,A*02:01,B*07:02,DRB1*01:01,and DRB1*04:01,and found higher significant correlations for both CD8 and CD4(maximum r=0.702,p=1.36×10^(−31)and r=0.594,p=3.04−122,respectively).Our results further indicated that some regions are commonly immunogenic between humans and mice(either H-2^(b)or HLA transgenic)but that others are human ***,we noted a significant correlation between CD8 and CD4 S-(r=0.258,p=7.33×10^(21))and N-specific(r=0.369,p=2.43×10^(14))responses,suggesting that discrete protein subregions can be simultaneously recognized by T *** findings were confirmed in other viral systems,providing general guidance for the use of murine models to test T-cell immunogenicity of viral antigens destined for human use.

关键词： T cells SARS-CoV-2 Vaccine Animal testing HLA

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Correction:Correlative CD4 and CD8 T-cell immunodominance in humans and mice:implications for preclinical testing

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Cellular & Molecular Immunology 2023年第12期20卷 1534-1534页

作者： Tertuliano Alves Pereira Neto john sidney Alba Grifoni Alessandro Sette Center for Infectious Disease and Vaccine Research La Jolla Institute for Immunology (LJI) La Jolla CA 92037 USA Department of Medicine Division of Infectious Diseases and Global Public Health University of California San Diego La Jolla CA 92037 USA

The article"Correlative CD4 and CD8 T-cell immunodominance in humans and mice:Implications for preclinical testing",written by Tertuliano Alves Pereira Neto,john sidney,Alba Grifoni&Alessandro Sette,was originally published electronically on the publisher's internet portal on i9 September 2023 without open *** the author(s)'decision to opt for Open Choice the copyright of the article changed on 26 October 2023 to@The Authors 2023 and the article is forthwith distributed under a Creative Commons Attribution 4.0 International License,which permits use,sharing,adaptation,distribution and reproduction in any medium or format.

关键词： clinical testing dominance

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Nature:研究首次证实帕金森病部分上是一种自身免疫疾病

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现代生物医学进展 2017年第27期17卷 I0002-I0002页

作者： David Sulzer, Francesca Garretti, Ellen Kanter, Julian Agin-Liebes, Elizabeth Phillips, Simon Mallal David Sulzer, Roy N. Alcalay, Lucien Cote, Christopher Liong, Elizabeth Phillips, Simon Mallal David Sulzer Curtis McMurtrey, William H. Hildebrand Xiaobo Mao, Valina L. Dawson, Ted M. Dawson Xiaobo Mao, Valina L. Dawson, Ted M. Dawson Valina L. Dawson Valina L. Dawson, Ted M. Dawson Ted M. Dawson Carla Oseroff, john Pham, john sidney, Myles B. Dillon, Chelsea Carpenter, Daniela Weiskopf, Bjoern Peters, April Frazier, Cecilia S. Lindestam Arlehamn, Alessandro Sette Elizabeth Phillips, Simon Mallal Departments of Psychiatry Columbia University Division of Molcular Therapeutics New York State Psychiatric Institute New York New York 10032 USA Department of Neurology Columbia University New York New York 10032 USA Department of Pharmacology Columbia University New York New York 10032 USA Department of Microbiology and Immunology University of Oklahoma Oklahoma City Oklahoma 73104 USA Neuroregeneration and Stem Cell Program Institute for Cell Engineering and the Department of Neurology Johns Hopkins University School of Medicine Baltimore Maryland 21205 USA Adrienne Helis Malvin Medical Research Foundation New Orleans Louisiana 70130-2685 USA Department of Physiology Johns Hopkins University School of Medicine Baltimore Maryland 21205 USA Solomon H. Snyder Department of Neuroscience Johns Hopkins University School of Medicine Baltimore Maryland 21205 USA Department of Pharmacology & Molecular Sciences Johns Hopkins University School of Medicine Baltimore Maryland 21205 USA Division of Vaccine Discovery La Jolla Institute for Allergy and Immunology La Jolla California 92037 USA Institute for Immunology and Infectious Diseases Murdoch University Perth Western Australia 6150 Australia Vanderbilt University School of Medicine Nashville Tennessee 37235 USA

帕金森病是一种神经退行性疾病。这种疾病的一种关键特征是受损的a-突触核蛋白（alpha-synuclein）在帕金森病患者体内的一种被称作多巴胺能神经元的脑细胞中堆积。在一项新的研究中，来自美国哥伦比亚大学医学中心和拉荷亚过敏症与免... 详细信息

帕金森病是一种神经退行性疾病。这种疾病的一种关键特征是受损的a-突触核蛋白（alpha-synuclein）在帕金森病患者体内的一种被称作多巴胺能神经元的脑细胞中堆积。在一项新的研究中，来自美国哥伦比亚大学医学中心和拉荷亚过敏症与免疫学研究所等研究机构的研究人员发现首个直接的证据证实自身免疫反应在帕金森病中发挥着作用。

关键词：自身免疫疾病帕金森病神经退行性疾病多巴胺能神经元哥伦比亚大学免疫反应研究人员研究机构

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Author Spotlight

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CCS Chemistry 2022年第5期4卷 1461-1464页

作者： Hecht, sidney Wang, Ruibing Huang, Jing Zheng, Haoquan Univ Wisconsin Mol Biol Madison WI 53706 USA MIT Fac Chem Cambridge MA 02139 USA Univ Virginia Chem Charlottesville VA 22903 USA Univ Virginia Biol Charlottesville VA 22903 USA Smith Kline & French Lab Preclin Res & Dev R&D Philadelphia PA USA Smith Kline & French Lab Preclin Chem R&D Philadelphia PA USA Arizona State Univ Ctr Bioenerget Biodesign Inst Tempe AZ 85287 USA Arizona State Univ Chem Tempe AZ 85287 USA Queens Univ Kingston ON Canada Natl Res Council Canada Ottawa ON Canada Univ Macau Taipa Macau Peoples R China NIH Bldg 10 Bethesda MD 20892 USA Hunan Univ Changsha Hunan Peoples R China Shaanxi Normal Univ Sch Chem & Chem Engn Xian Shaanxi Peoples R China Stockholm Univ Prof Xiaodong Zous Grp Stockholm Sweden

sidney Hecht *** obtained his *** chemistry at the University of Illinois,*** studies as a National Institutes of Health(NIH)Postdoctoral Fellow in molecular biology at the University of Wisconsin(USA),he became a member of the Massachusetts Institute of Technology(MIT)Chemistry Faculty from 1971 to 1979,john *** Professor of Chemistry and Professor of Biology at the University of Virginia(USA)from 1978 to 2008.

关键词： doctor Fellow Illinois

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Breeding system and its consequence on fruit set of a rare sand dune shrub Eremosparton songoricum(Fabaceae:Papilionoideae):implications for conservation

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Journal of Arid Land 2011年第4期3卷 231-239页

作者： DaoYuan ZHANG Xiang SHI JianCheng WANG HuiLiang LIU john F GASKIN Key Laboratory of Biogeography and Bioresources in Arid Land Xinjiang Institute of Ecology and Geography Chinese Academy of Sciences Urumqi 830011 China Turpan Eremophytes Botanical Garden Chinese Academy of Sciences Turpan 838008 China Forestry College College of Agriculture in Shihezi University Shihezi 832011 China USDA Agricultural Research Service Sidney Montana 59270 USA

The breeding system and its consequence on fruit set of Eremosparton songoricum（Litv.） Vass.,a rare shrubby legume occurring in moving or semi-fixed sand dunes of Central Asian deserts,were examined by manipulative experiments and observational studies in natural populations during the period of *** results showed that *** exhibits a mixed mating *** is self-compatible,but depends strictly on pollinators to set *** two effective pollinators were detected and they triggered the specialized pollination mechanism（a ＇brush type＇ and ＇tripping mechanism＇）.Geitonogamy becomes predominant in natural populations,because（74.5±1.3）% of visiting activity happened within or between inflorescences and（24.3±1.4）% occurred between *** a result,inbreeding depression caused by geitonogamous selfing inevitably happened under natural conditions,showing 2.36 times less fruit set than was achieved by hand *** results explained the rarity of the species due to its breeding system,and will assist to develop suitable conservation strategies in severe desert environments.

关键词： geitonogamy inbreeding depression inland sand dunes self-fertilization pollen brush tripping mechanism

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对约翰·杜威的一些回忆（1859-1952)

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大学教育科学 2019年第5期 105-110页

作者：西德尼·胡克勾月沈阳师范大学教育科学学院

在《对约翰·杜威的一些回忆》中,杜威的学生西德尼·胡克没有将杜威作为一位哲学家来描述,而是回忆了杜威本人生活中的点滴。其中包括其真诚和为他人着想的品格,稍显矛盾的个性;还有杜威对宗教的态度;杜威对年轻人的鼓励和信任。同时,... 详细信息

在《对约翰·杜威的一些回忆》中,杜威的学生西德尼·胡克没有将杜威作为一位哲学家来描述,而是回忆了杜威本人生活中的点滴。其中包括其真诚和为他人着想的品格,稍显矛盾的个性;还有杜威对宗教的态度;杜威对年轻人的鼓励和信任。同时,文中还忆及杜威与他的一位学生、杜威与罗素、杜威与巴恩斯之间的交往;杜威承受压力去墨西哥担任托洛斯基审判案调查委员会主席的往事。并且,文中还提到杜威晚年对他自己思想和观点的反思,以及他的教育思想与进步教育思想的分歧。在胡克看来,杜威就是一位公民、一位邻居、一位教师、一位朋友和一位哲学家。

关键词：回忆生活哲学教育杜威

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Albumin-linked prostate-specific antigen-activated thapsigargin- and niclosamide-based molecular grenades targeting the microenvironment in metastatic castration-resistant prostate cancer

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Asian Journal of Urology 2019年第1期6卷 99-108页

作者： Emmanuel S.Akinboye W.Nathaniel Brennen Samuel R.Denmeade john T.Isaacs Department of Oncology Prostate Cancer ProgramThe Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsThe Johns Hopkins University School of MedicineBaltimoreMDUSA

Localized prostate cancer is curable via annihilation of the entire cancer neighborhood by surgery or local ***,once metastatic,no available therapy is *** vast majority will die despite aggressive systemic combinational androgenablation ***,there is an urgent need for effective systemic therapeutics that sterilize the entire microenvironment in metastatic castration-resistant prostate cancer(mCRPC).To accomplish this goal,advantage can be taken of the unique biology of mCRPC *** their normal cell of origin,mCRPCs retain expression of the prostate-specific differentiation protein,prostate-specific antigen(PSA),which they abundantly secrete into their extracellular fluid(ECF).This unique,and essentially universal,secretion of enzymatically active PSA into the ECF by mCRPCs creates an exploitable therapeutic index for activation of systemically delivered highly lipophilic toxins as“molecular grenades”covalently linked to cysteine-34 of human serum albumin(HSA)via a stable maleimide containing PSA cleavable peptide such that PSA-dependent hydrolysis(i.e.,“detonation”)releases the grenades restrictively within the ECF of *** approach decreases dose-limiting host toxicity while enhancing plasma half-life from minutes to days(i.e.,pharmacokinetic effect)and increasing the tissue concentration of the maleimide coupled albumin delivery(MAD)in the ECF at sites of cancer due to the enhanced permeability of albumin at these sites(i.e.,enhanced permeability and retention effect).This allows the MAD-PSA detonated grenades to circulate throughout the body in a non-toxic *** within sites of mCRPC is there a sufficiently high level of enzymatically active PSA to efficiently“pull the pin”on the grenades releasing their lipophilic cellpenetrant toxins from ***,if a sufficient level of“detonation”occurs,this will kill mCRPC cells,and sterilize the entire PSA-rich metastatic sites via a bystander *** this review,two

关键词： Albumin-linked prodrug Maleimide coupled albumin delivery Thapsigargin Niclosamide

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Molecularly specific detection of bacterial lipoteichoic acid for diagnosis of prosthetic joint infection of the bone

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Bone Research 2018年第2期6卷 189-196页

作者： Julie E.Pickett john M.Thompson Agnieszka Sadowska Christine Tkaczyk Bret R.Sellman Andrea Minola Davide Corti Antonio Lanzavecchia Lloyd S.Miller Daniel LJ Thorek Division of Nuclear Medicine and Molecular Imaging Department of Radiology and Radiological ScienceJohns Hopkins University School of MedicineGaithersburgMDUSA Department of Orthopaedic Surgery Johns Hopkins University School of MedicineBaltimoreMD 21205USA Department of Infectious Disease MedImmune LLCGaithersburgMDUSA Humabs Bio Med SA BellinzonaSwitzerland Institute for Research in Biomedicine Universitàdella Svizzera italianaBellinzonaSwitzerland Department of Dermatology Johns Hopkins University School of MedicineBaltimoreMD 21205USA Division of Infectious Disease Department of MedicineJohns Hopkins University School of MedicineBaltimoreMDUSA Cancer Molecular and Functional Imaging Program Department of OncologySidney Kimmel Comprehensive Cancer CenterJohns Hopkins University School of MedicineBaltimoreMD 21205USA

Discriminating sterile inflammation from infection, especially in cases of aseptic loosening versus an actual prosthetic joint infection, is challenging and has significant treatment implications. Our goal was to evaluate a novel human monoclonal antibody（mAb） probe directed against the Gram-positive bacterial surface molecule lipoteichoic acid（LTA）. Specificity and affinity were assessed in vitro. We then radiolabeled the anti-LTA mAb and evaluated its effectiveness as a diagnostic imaging tool for detecting infection via immuno PET imaging in an in vivo mouse model of prosthetic joint infection（PJI）. In vitro and ex vivo binding of the anti-LTA mAb to pathogenic bacteria was measured with Octet, ELISA, and flow cytometry. The in vivo PJI mouse model was assessed using traditional imaging modalities, including positron emission tomography（PET） with [^（18）F]FDG and [^（18）F]Na F as well as X-ray computed tomography（CT）, before being evaluated with the zirconium-89-labeled antibody specific for LTA（[^（89）Zr]SAC55）.The anti-LTA mAb exhibited specific binding in vitro to LTA-expressing bacteria. Results from imaging showed that our model could reliably simulate infection at the surgical site by bioluminescent imaging, conventional PET tracer imaging, and bone morphological changes by CT. One day following injection of both the radiolabeled anti-LTA and isotype control antibodies, the anti-LTA antibody demonstrated significantly greater（P 〈 0.05） uptake at S. aureus-infected prosthesis sites over either the same antibody at sterile prosthesis sites or of control non-specific antibody at infected prosthesis sites. Taken together, the radiolabeled anti-LTA mAb, [^（89）Zr]SAC55, may serve as a valuable diagnostic molecular imaging probe to help distinguish between sterile inflammation and infection in the setting of PJI. Future studies are needed to determine whether these findings will translate to human PJI.

关键词： Zr Molecularly specific detection bacterial lipoteichoic acid diagnosis prosthetic infection bone LTA SAC PET FDG tracer

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Blood:血管系统变化可能会导致阿兹海默症

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现代生物医学进展 2017年第15期17卷 I0003-I0003页

作者： Zu-Lin Chen Alexey S. Revenko Pradeep Singh A. Robert MacLeod Erin H. Norris sidney Strickland Patricia and john Rosenwald Laboratory of Neurobiology and Genetics The Rockefeller University New York NY Department of Antisense Drug Discovery Ionis Pharmaceuticals Inc. Carlsbad CA Patricia and john Rosenwald Laboratory of Neurobiology and Genetics The Rockefeller University New York NY Department of Antisense Drug Discovery Ionis Pharmaceuticals Inc. Carlsbad CA Patricia and john Rosenwald Laboratory of Neurobiology and Genetics The Rockefeller University New York NY Patricia and john Rosenwald Laboratory of Neurobiology and Genetics The Rockefeller University New York NY and

随着人口老龄化的趋势不断上升，阿兹海默症的发病成为越来越重要的健康问题。最近，科学家们试图利用各种手段清除患者大脑中造成疾病的斑块，但是药物的结果往往不尽如人意。来自洛克菲勒大学的科学家们利用一项最新的技术对阿兹海默... 详细信息

随着人口老龄化的趋势不断上升，阿兹海默症的发病成为越来越重要的健康问题。最近，科学家们试图利用各种手段清除患者大脑中造成疾病的斑块，但是药物的结果往往不尽如人意。来自洛克菲勒大学的科学家们利用一项最新的技术对阿兹海默症发病的生物学机制进行了解。意想不到的是，他们发现了一种常见于血栓以及炎症反应中的血浆成分在一些患者体内也检查得到。这并不是第一次将阿兹海默症与心血管疾病联系在了一起。”有大量证据表明锻炼身体能够帮助维持血管的健康以及血流的稳定，同时也能够有效避免阿兹海默症的发生”，神经生物学家sidney Strickland说道：”另外。我们知道阿兹海默症会影响血管系统，就像糖尿病那样，提高人们血管疾病的发生风险”。

关键词：血管系统心血管疾病健康问题人口老龄化生物学机制血浆成分炎症反应生物学家

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代谢综合征的诊断和治疗——美国心脏协会/国立心肺血液研究所指南概要

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世界核心医学期刊文摘（心脏病学分册） 2006年第4期2卷 8-11页

作者： Scott M. Grundy James I. Cleeman Stephen R. Daniels Karen A. Donato Robert H. Eckel Barry A.Franklin David J. Gordon Ronald M. Krauss Peter J. Savage sidney C. Smith john A. Spertus Fernando Costa

近几年,代谢综合征越来越受到人们的关注。它包括了可能直接促进动脉粥样硬化性心血管疾病(ASCVD)的多种相关代谢性危险因素。这些代谢性危险冈素与2型糖尿病及其风险具有强相关性。这些代谢性危险因素包括致粥样硬化性血脂异常(甘油三... 详细信息

近几年,代谢综合征越来越受到人们的关注。它包括了可能直接促进动脉粥样硬化性心血管疾病(ASCVD)的多种相关代谢性危险因素。这些代谢性危险冈素与2型糖尿病及其风险具有强相关性。这些代谢性危险因素包括致粥样硬化性血脂异常(甘油三酯、载脂蛋白B及小LDL颗粒升高,HDL-C浓度降低)、血压升高、血糖升高以及血栓前状态、前炎性状态。[第一段]

关键词：代谢综合征美国心脏协会动脉粥样硬化性心血管疾病血液研究所血栓前状态概要指南心肺治疗诊断

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