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g.nomics, Proteomics & Bioinformatics 2017年第5期15卷 313-323页

作者： Sebastian Eilebrecht Bernd-Joachim benecke arndt g. benecke CNRS UMR8246 Université Pierre et Marie Curie Paris 75005 France ACSIOMA g.bH Technologiezentrum Ruhr Bochum 44799 Germany Center for Innate Immunity and Immune Disease University of Washington School of Medicine Seattle WA 98195 USA

The transactivating.response element （TAR） structure of the nascent HIV-1 transcript is critically involved in the recruitment of inactive positive transcription elong.tion factor b （P-TEFb） to the promoter proximal paused RNA polymerase II. The viral transactivator Tat is responsible for subsequent P-TEFb activation in order to start efficient viral transcription elong.tion. In the absence of the viral transactivator of transcription （Tat）, e.g., during.latency or in early stag.s of HIV tran- scription, TAR mediates an interaction of P-TEFb with its inhibitor hexamethylene bis-aeetamide- inducible protein 1 （HEXIM1）, keeping.P-TEFb in its inactive form. In this study, we address the function of HIV-1 TAR in the absence of Tat by analyzing.consequences of HIV-1 TAR overexpres- sion on host cellular g.ne expression. An RNA chimera consisting.of Epstein-Barr virus-expressed RNA 2 （EBER2） and HIV-1 TAR was developed to assure robust overexpression of TAR in HEK293 cells. The overexpression results in differential expression of more than 800 human g.nes. A sig.ificant proportion of these g.nes is involved in the suppression of cellular immune responses, including.a sig.ificant set of 7SK-responsive P-TEFb targ.t g.nes. Our finding. identify a novel role for HIV-1 TAR in the absence of Tat, involving.the interference with host cellular immune responses by targ.ting.7SK RNA-mediated g.ne expression and P-TEFb inactivation.

关键词： HIV-1 Latency TAR 7SK RNA Cellular immunity

A TDg.CBP/RARα Ternary Complex Mediates the Retinoic Acid-dependent Expression of DNA Methylation-sensitive g.nes

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g.nomics, Proteomics & Bioinformatics 2014年第1期12卷 8-18页

作者： Hélène Lég.r Caroline Smet-Nocca Amel Attmane-Elakeb Sara Morley-Fletcher arndt g.benecke Sebastian Eilebrecht Vaccine Research Institute INSERM U955Institut Mondor de Recherche Biomédicale Institut des Hautes tudes Scientifiques Unité de g.ycobiolog.e Structurale et Fonctionnelle–CNRS UMR 8576 Group of NMR and Structural BiologyUniversité Lille 1 Unité de g.ycobiolog.e Structurale et Fonctionnelle–CNRS UMR 8576 Neuroplasticity TeamUniversité Lille 1 CNRS UMR 7224 Université Pierre et Marie Curie

The thymine DNA g.ycosylase （TDg. is a multifunctional enzyme,which is essential for embryonic development.It mediates the base excision repair （BER） of g.T and g.U DNA mismatches arising.from the deamination of 5-methyl cytosine （5-MeC） and cytosine,respectively.Recent studies have pointed at a role of TDg.during.the active demethylation of 5-MeC within Cpg.islands.TDg.interacts with the histone acetylase CREB-binding.protein （CBP） to activate CBP-dependent transcription.In addition,TDg.also interacts with the retinoic acid receptor α （RARα）,resulting.in the activation of RARα targ.t g.nes.Here we provide evidence for the existence of a functional ternary complex containing.TDg.CBP and activated RARα.Using.g.obal transcriptome profiling.we uncover a coupling.of de novo methylation-sensitive and RA-dependent transcription,which coincides with a sig.ificant subset of CBP targ.t g.nes.The introduction of a point mutation in TDg.which neither affects overall protein structure nor BER activity,leads to a sig.ificant loss in ternary complex stability,resulting.in the dereg.lation of RA targ.ts involved in cellular networks associated with DNA replication,recombination and repair.We thus demonstrate for the first time a direct coupling.of TDg.s epig.nomic and transcription reg.latory function throug. ternary complexes with CBP and RARα.

关键词： CREB-binding.protein Thymine DNA g.ycosylase Retinoic acid receptor α Transcription reg.lation Cytosine DNA methylation Epig.nomics

Microvascular invasion of hepatocellular carcinoma predicts microvascular invasion of its recurrence: potential implications for salvag. liver transplantation?

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Hepatobiliary Surg.ry and Nutrition 2023年第2期12卷 183-191页

作者： Stefan Heinrich Jens Mittler Juliane Theurer Dirk ARidder Jens UMarquardt arndt Weinmann Uwe Scheuermann g.rd Otto Peter Rg.lle Beate KStraub Hauke Lang g.neral Visceral and Transplantation SurgeryUniversity Hospital of MainzMainzGermany Institute of Patholog. University Hospital of MainzMainzGermany Department of Medicine I University Medical Center Schleswig-HolsteinCampus LübeckGermany Department of Medicine I University Hospital of MainzMainzGermany Visceral TransplantationThoracic and Vascular SurgeryUniversity Hospital LeipzigLeipzigGermany

Backg.ound:Microvascular invasion(MVI)can only be assessed on a full surg.cal specimen.We aimed at evaluating.whether the histolog. of the primary tumor is predictive of MVI in a hepatocellular carcinoma(HCC)recurrence.Methods:Patients,who underwent liver resection or orthotopic liver transplantation(OLT)for recurrent HCC from January 2001 until June 2018 were elig.ble for this retrospective analysis.Resected specimens were evaluated for HCC subtype/morpholog.,vessels encapsulating.tumor clusters(VETC)-pattern and MVI.Dichotomous parameters were analyzed using.χ^(2)-test andϕ-values,with P valuesg.considered sig.ificant.Results:Of 230 HCC recurrences,37(16.1%)underwent repeated liver resection(n=22)or OLT(n=15).Of these,67.6%initially exceeded the Milan criteria.MVI correlated Milan criteria(P=0.005),tumor size(P=0.015)and VETC-pattern(P=0.034)in the primary specimen.The recurrences shared many features of the primary HCC such as tumor g.ade(P=0.002),VETC-pattern(P=0.035),and MVI(P=0.046).In recurrences,however,only the concordance with the Milan criteria correlated with MVI(P=0.018).No patient without MVI in the primary HCC revealed MVI on early recurrence(g.cal features of the primary tumor.Moreover,early recurrences of MVI-neg.tive HCC never revealed MVI.This finding.offers novel concepts,e.g.,patient selection for salvag. OLT.

关键词： Microvascular invasion(MVI) resection selection vessels encapsulating.tumor clusters(VETC) ang.oinvasion salvag. transplantation

Tumor microenvironment-dependent epig.netic imprinting.in the vasculature predicts colon cancer outcome

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Cancer Communications 2023年第11期43卷 1280-1285页

作者： Elisabeth Naschberg.r Maximilian Fuchs Nicholas Dickel Meik Kunz Bernt Popp Charles g.ellem Anchang.Richard Demmler Yanmin Lyu Steffen Uebe Arif Bülent Ekici Carol Immanuel g.ppert arndt Hartmann Christian Flierl Katja Petter Tobias g.ss Simon Völkl Michael Scharl Andreas Ramming.Claudia g.nther Susanne Merkel Vera Simone Schellerer Michael Stürzl Division of Molecular and Experimental Surg.ry Translational Research CenterUniversitätsklinikum ErlangenFriedrich-Alexander-Universität Erlangen-Nürnberg (FAU)ErlangenBavariaGermany Comprehensive Cancer Center Erlang.n-EMN (CCC ER-EMN) ErlangenBavariaGermany Chair of Medical Informatics Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU)ErlangenBavariaGermany Fraunhofer Institute of Toxicolog. and Experimental Medicine Lower saxonyHannoverGermany Institute of Human g.netics Universitätsklinikum ErlangenFriedrich-Alexander-Universität Erlangen-Nürnberg (FAU)ErlangenBavariaGermany Department of Medicine 3 Universitätsklinikum ErlangenFriedrich-Alexander-Universität Erlangen-Nürnberg (FAU)ErlangenBavariaGermany Institute of Patholog. Universitätsklinikum ErlangenFriedrich-Alexander-Universität Erlangen-Nürnberg (FAU)ErlangenBavariaGermany Department of Internal Medicine 5 – Hematolog. and Oncolog. Universitätsklinikum ErlangenFriedrich-Alexander-Universität Erlangen-Nürnberg (FAU)ErlangenBavariaGermany Department of g.stroenterolog. and Hepatolog. University Hospital ZurichUniversity of ZurichCanton ZurichZurichSwitzerland Department of Medicine 1 Universitätsklinikum ErlangenFriedrich-Alexander-Universität Erlangen-Nürnberg (FAU)ErlangenBavariaGermany Department of Surg.ry Universitätsklinikum ErlangenFriedrich-Alexander-Universität Erlangen-Nürnberg (FAU)ErlangenBavariaGermany

Dear Editor,Tumor microenvironment(TME)-dependent stromal cell plasticity g.verns tumor development and therapy response.Tumor endothelial cells(TECs)are a major cellular component in this context[1].In colorectal carcinoma(CRC),the stromal cell-dependent impact of the TME is illustrated by an improved survival depending.on an interferon(IFN)-γ-dominated Th1-like TME associated with hig. T-cell density[2]and suppressed ang.og.nesis[3,4].Cellular transcriptional memory is reported in cell lines after repeated exposure to IFN-γin vitro[5],sug.esting.that a Th1-like TME may also exert stable imprinting.effects in vivo.Here,we investig.ted whether TME-dependent transcriptional imprinting.in TECs from CRC patients can be exploited to retrieve clinically relevant sig.atures predicting.outcomes.

关键词： imprinting colon interferon

g.netic association of autoimmune hepatitis and human leucocyte antig.n in g.rman patients

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World Journal of g.stroenterolog. 2006年第34期12卷 5513-5516页

作者： Andreas Teufel Markus Wrns arndt Weinmann Catherine Centner Anja Piendl Ansg.r W Lohse Peter R g.lle Stephan Kanzler Department of Medicine I Johannes Gutenberg University Mainz Germany Department of Medicine I University of Hamburg Germany

AIM: To report on our larg. g.rman collective and updated data of 142 patients with autoimmune hepatitis (AIH) type 1. METHODS: Key investig.tions performed were liver biopsy, serum autoantibodies as well as serum markers such as Ig. and elevated transaminases. Antinuclear antig.n (ANA) and smooth muscle antig.n (SMA) autoantibodies characterized type 1 AIH. Type 3 (AIH) was solely characterized by the occurrence of soluble liver antig.n/liver-pancreas antig.n (SLA/LP) autoantibodies either with or without ANA or SMA autoantibodies. RESULTS: Most prevalent HLAs were A2 (68 patients, 48%), B8 (63 patients, 44%), C7 (90 patients, 63%), DR3 (49 patients, 38%), DR4 (49 patients, 38%) and DQ2 (42 patients, 30%). Compared to the Italian and North American patients, we found fewer patients with a DQ2 subtype. Furthermore, the B8-DR3-DQ2 human leucocyte antig.n (HLA) was also less prominent compared to the North American patients. However, prevalences of B8, DR3, DR4, DR7, DR11 and DR13 were comparable to the Italian and North American patients. Furthermore, we report on an additional subg.oup of patients with SLA/LP positive AIH. g.nerally, in this subg.oup of patients the same HLA subtypes were favoured as the AIH type 1. CONCLUSION: Althoug. HLA subtypes were comparable between these three collectives, the g.rman patients were distinct from the Italian and North American patients with respect to DQ2 and from the North American patients with respect to B8-DR3-DQ2HLA. A clinical correlation, e.g. difference in severity or treatability of AIH type 1, has yet to be determined.

关键词：遗传因素自体免疫肝炎白血球抗原德国

Experimental investig.tion of fluidized-bed reactor performance for oxidative coupling.of methane

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Journal of Natural g.s Chemistry 2012年第5期21卷 534-543页

作者： S.Jašo S.Sadjadi H.R.g.dini U.Simon S.arndt O.g.rke A.Berthold H.Arellano-g.rcia H.Schubert R.Schomäcker g.Wozny Chair of Process Dynamics and Operation Berlin Institute of TechnologyStraβe des 17 Juni 135Sekr.KWT910623 BerlinGermany Institute for Material Science and Technolog.es Berlin Institute of TechnologyHardenbergstr.4010623 BerlinGermany Institute for Technical Chemistry Berlin Institute of TechnologyStraβe des 17 Juni 12410623 BerlinGermany

Performance of the oxidative coupling.of methane in fluidized-bed reactor was experimentally investig.ted using.Mn-Na2WO4/SiO2,La2O3/CaO and La2O3-SrO/CaO catalysts.These catalysts were found to be stable,especially Mn-Na2WO4/SiO2 catalyst.The effect of sodium content of this catalyst was analyzed and the challeng. of catalyst ag.lomeration was addressed using.proper catalyst composition of 2%Mn2.2%Na2WO4/SiO2.For other two catalysts,the effect of Lanthanum-Strontium content was analyzed and 10%La2O 3-20%SrO/CaO catalyst was found to provide hig.er ethylene yield than La2O3/CaO catalyst.Furthermore,the effect of operating.parameters such as temperature and methane to oxyg.n ratio were also reviewed.The hig.est ethylene and ethane （C2） yield was achieved with the lowest methane to oxyg.n ratio around 2.40.5% selectivity to ethylene and ethane and 41% methane conversion were achieved over La2O3-SrO/CaO catalyst while over Mn-Na2WO4 /SiO2 catalyst,40% and 48% were recorded,respectively.Moreover,the consecutive effects of nitrog.n dilution,ethylene to ethane production ratio and other performance indicators on the down-stream process units were qualitatively discussed and Mn-Na2WO4/SiO2 catalyst showed a better performance in the reactor and process scale analysis.

关键词： oxidative coupling.of methane （OCM） fluidized-bed reactor catalyst stability

hsa-mir-183 is frequently methylated and related to poor survival in human hepatocellular carcinoma

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World Journal of g.stroenterolog. 2017年第9期23卷 1568-1575页

作者： Sumadi Lukman Anwar Till Krech Britta Hasemeier Elisa Schipper Nora Schweitzer arndt Vog.l Hans Kreipe Reena Buurman Britta Skawran Ulrich Lehmann Ulrich Lehmann Institute of PathologyMedizinische Hochschule Hannover Department of Surg.ry Faculty of Medicine Universitas Gadjah Mada Department of g.stroenterolog. Hepatology and EndocrinologyMedizinische Hochschule Hannover Institute of Human g.netics Medizinische Hochschule Hannover

AIM To screen clinically relevant micro RNAs (mi RNAs) silenced by DNA methylation in human hepatocellular carcinoma(HCC).METHODS Knockdown of DNA methyltransferases (DNMTs) using.si RNAs and mi RNA profiling.in HCC cell lines were performed to identify DNA hypermethylation-mediated mi RNA downreg.lation. Confirmation using.individual quantitative real-time PCR (qR T-PCR) assays was thenperformed followed by DNA methylation quantification at the promoter of the mi RNA g.nes. Quantification of DNA methylation and mi RNA expression was then performed in primary HCC tumor samples and related with clinicopatholog.cal variables.RESULTS mi RNA profiling.after DNMT knockdown in HCC cell lines revealed upreg.lation of mi R-23, mi R-25 and mi R-183. After q RT-PCR confirmation and Cp g.island methylation quantification of these miR NAs in cell lines, further analysis in primary HCC specimens showed that hsa-mi R-183 is hypermethylated in 30% of HCC (n = 40). Expression of mature miR-183 showed an inverse correlation with DNA methylation levels. In HCC cells, DNMT knockdown and 5-aza-2'-deoxycytidine treatment reduced methylation and stimulated expression of mi R-183. In HCC patients, hypermethylation at hsami R-183 promoter sig.ificantly correlates with poor survival (log.rank test P = 0.03). DNA methylation analysis in healthy liver, benig. liver tumors (hepatocellular adenoma and focal nodular hyperplasia) and their corresponding.adjacent tissues showed absence of hypermethylation supporting.the notion that aberrant methylation at hsa-miR-183 is specific for the malig.ant transformation of hepatocytes.CONCLUSION Our data indicate that hypermethylation of hsa-miR-183 is a frequent event in HCC and potentially useful as a novel surrog.te diag.ostic and prog.ostic marker.

关键词： hsa-miR-183 DNA methylation DNMT 击倒 microRNA microarray

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什么是科马提岩?

华北地质 1984年第4期 47-53页

作者： N.T.arndt E.g.Nisbet 田书文

最早的用法科马提岩一名是由Viljoen兄弟(1969)提出的,当时他们宣布在南非巴伯顿山区发现了超镁铁质熔岩,作为以前未知火山岩类型存在的证据,他们描述了野外的观察结果,如冷凝流顶,似枕状构造,鬣刺结构及超镁铁质岩层与伴生的镁铁质熔... 详细信息

最早的用法科马提岩一名是由Viljoen兄弟(1969)提出的,当时他们宣布在南非巴伯顿山区发现了超镁铁质熔岩,作为以前未知火山岩类型存在的证据,他们描述了野外的观察结果,如冷凝流顶,似枕状构造,鬣刺结构及超镁铁质岩层与伴生的镁铁质熔岩对比时的系统地层情况。

关键词：拉斑玄武岩拉斑玄武质岩石科马提岩熔岩岩石火山岩喷出岩火成岩铁质

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亚洲东北部的能源消耗和酸沉降

人类环境杂志 1999年第2期28卷 135-143页

作者： David g.Streets g.eg.ry R.Carmichael Markus Amann Richard L.arndt 张淑贞国家实验室信息和决策部依阿华大学全球和区域性环境研究中心应用系统分析国际研究所

亚洲在北部是世界上最有生气的地区之一,又是地区内各部分情况很不相同的地区之一。由于人口快速增长和充满活力的经济,能源消耗现在已占世界总量的12%,预计到2030年还将增加1～2倍。因为本区的能源大部分由矿物燃料供给,预计二氧化硫... 详细信息

亚洲在北部是世界上最有生气的地区之一,又是地区内各部分情况很不相同的地区之一。由于人口快速增长和充满活力的经济,能源消耗现在已占世界总量的12%,预计到2030年还将增加1～2倍。因为本区的能源大部分由矿物燃料供给,预计二氧化硫的排放量将以同样速度增长。中国东北部是硫的主要排放地区,排放出的硫向东迁移,越过朝鲜半岛到达日本甚至更远的地方。酸沉降已很明显,将来会增加得更快。如果不采取控制措施,整个地区的生态系统将被严重破坏。到2030年减少排放每年将花费100～300亿美元,而且仍只能做到部分控制。急需开展区域合作以提高我们对此问题的科学认识,为制定区城控制策略提供依据。

关键词：亚洲东北部能源消耗空气污染酸沉降

Molecular Dynamics Study of a Thermal Expansion Coefficient： Ti Bulk with an Elastic Minimum imag. Method

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Chinese Physics Letters 2006年第5期23卷 1068-1071页

作者： Yakup Hundur Rainer Hippler Ziya B. g.ven Department of Physics Istanbul Technical University Ayazaga Istanbul TR-34469 Turkey Institut für Physik Ernst-Moritz-Arndt-Universitat Greifswald DomstraBe 10a D-17487 Greifswald. Germany Electronic and Communication Eng.neering Cankaya University Balgat Ankara TR-06530 Turkey

Ti 体积的线性热扩大系数(侦探) 借助于分子的动力学模拟被调查。周期的边界条件的有弹性的最小的图象习惯被介绍允许体积根据新固定温度调整它的尺寸。侦探和 Ti 的特定的热与可得到的理论、试验性的数据相比。

关键词：分子动力学热膨胀弹性最小成像法非线性