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single-cell trajectories of melanoma cell resistance to targeted treatment

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Cancer Biology & Medicine 2022年第1期19卷 56-73页

作者： Maria schmidt Lena sünke Mortensen Henry Loeffler-Wirth Corinna Kosnopfel Knut Krohn hans Binder Manfred Kunz Interdisciplinary Centre for Bioinformatics University of LeipzigLeipzig 04107Germany Department of Dermatology Venereology and AllergologyUniversity of WürzburgWürzburg 97074Germany Core Unit DNA Technologies Medical FacultyUniversity of LeipzigLeipzig 04103Germany Department of Dermatology Venereology and AllergologyUniversity of Leipzig Medical CenterLeipzig 04103Germany

Objective:Cellular heterogeneity is regarded as a major factor affecting treatment response and resistance in malignant *** developments in single-cell sequencing technology have provided deeper insights into these ***:Here,we analyzed a BRAFV600 E-mutant melanoma cell line by single-cell RNA-seq under various conditions:cells sensitive to BRAF inhibition with BRAF inhibitor vemurafenib and cells resistant to BRAF inhibition with vemurafenib alone or vemurafenib in combination with the MEK1/2 inhibitors cobimetinib or *** reduction by t-distributed stochastic neighbor embedding and self-organizing maps identified distinct trajectories of resistance development clearly separating the 4 treatment conditions in cell and gene state ***:Trajectories associated with resistance to single-agent treatment involved cell cycle,extracellular matrix,and de-differentiation *** contrast,shifts detected in double-resistant cells primarily affected translation and mitogen-activated protein kinase pathway reactivation,with a small subpopulation showing markers of *** findings were validated in pseudotime analyses and RNA velocity ***:The single-cell transcriptomic analyses reported here employed a spectrum of bioinformatics methods to identify mechanisms of melanoma resistance to single-and double-agent *** study deepens our understanding of treatmentinduced cellular reprogramming and plasticity in melanoma cells and identifies targets of potential relevance to the management of treatment resistance.

关键词： Melanoma single-cell transcriptome sequencing treatment response

Cardiotrophin-1 induces intercellular adhesion molecule-1 expression by nuclear factor κB activation in human umbilical vein endothelial cells

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Chinese Medical Journal 2008年第24期121卷 2592-2598页

作者： Michael Fritzenwanger Martin Foerster Katharina Meusel christian Jung hans R. Figulla Department of Internal Medicine I Friedrich-Schiller-University Jena Erlanger Allee 101 07740 Jena Germany

Background In addition to elevated concentrations of cytokines, patients with congestive endothelial dysfunction and increased plasma concentrations of adhesion molecules heart failure （CHF） show ke intercellular adhesion molecule-1 （ICAM-1）. Furthermore, the concentration of cardiotrophin-1 （CT-1） - a cytokine of the interleukin-6 superfamily - is increased in CHF. We tested the hypothesis whether CT-1 is able to induce ICAM-1 in human umbilical vein endothelial cells （HUVEC）. Furthermore we examined the signalling mechanisms of CT-1 mediated ICAM-1 expression. Methods Confluent layers of HUVEC were incubated with increasing concentrations of CT-1 （5 to 100 ng/ml） for different periods. ICAM-1 mRNA was determined by real-time polymerase chain reaction （PCR） and ICAM-1 surface expression by fluorescence-activated cell sorter （FACs） analysis and soluble ICAM-1 （slCAM-1） in the culture supernatant by enzyme linked immunosorbent assay （ELIsA）. To clarify the signalling pathway of CT-1 induced ICAM-1 expression we used various inhibitors of possible signal transducing molecules, electromobility shift assay （EMsA） and Western blot analysis. Results CT-1 induced ICAM-1 mRNA （1.8±0.8 fold increase compared to unstimulated cells after 6 hours） and protein （1.4±0.2 fold increase compared to unstimulated cells after 48 hours） in HUVEC in a time- and concentration-dependent manner. EMsA experiments show that CT-1 causes nuclear factor （NF） κB activation. Because parthenolide could inhibit CT-1 induced ICAM-1 expression NFκB activation is required in this pathway. CT-1 did not activate extracellular signal regulated kinases （ERK）, c-Jun N-terminal kinase （JNK） and p38. Conclusion CT-1 is able to induce ICAM-1 in endothelial cells by NFκB activation. These results may explain in part elevated ICAM-1 concentrations in patients with CHF and endothelial dysfunction.

关键词： cardiotrophin-1 intercellular adhesion molecule-1 nuclear factor κB human umbilical vein endothelial cells

Low Energy Certificate——An exploration on optimization and evaluation of energy-efficient building envelope

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science China(Technological sciences) 2011年第6期54卷 1639-1644页

作者： ZHANG Hui hans-Peter LEIMER school of Architecture Southeast University Nanjing 210096 China Hochschule fuer angewandte Wissenschaft und Kunst Hildesheim 31134 Hildesheim Germany

Energy saving is the crucial task of green architecture,energy-saving design and evaluation should be *** Energy Certificate(LEC),an interactive computer program for energy efficiency and certification of building envelope,is briefly introduced in this paper in aspects of certification standards,procedure,methods *** the evaluation report of Innovation-pavilion PoI features,reference values of LEC are presented.

关键词： optimization and evaluation of energy efficiency Low Energy Certificate(LEC) energy performance of building enve-lope interactive

Activated Natural Killer Cells Hit Neurogenesis in the Aging Brain

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Neuroscience Bulletin 2021年第7期37卷 1072-1074页

作者： Angelica Cuapio hans-Gustaf Ljunggren Center of Infectious Medicine Department of Medicine HuddingeKarolinska Institutet14152 StockholmSweden

Why neurogenesis is attenuated in elderly individuals is an intriguing question that has raised renewed *** associated with declined neurogenesis in the aged brain have been attributed to inflammatory cytokines[1].More recently,a specific role for interferon-y(IFN-y)produced by CD8-expressing cytotoxic T cells has been implicated[2].These observations suggest a scenario in which neurogenesis,at least in part,is regulated by immune cells within the aging *** raises several interesting questions with regards to the characteristics of specific immune cells within the brain,the signals for their expansion and maintenance,and their role in affecting neurogenesis and cognition during normal brain aging.

关键词： interferon Killer attributed

Cystine oligomers successfully attached to peptide cysteine- rich fibrils

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Frontiers of Chemical science and Engineering 2016年第1期10卷 99-102页

作者： christian Bortolini Mingdong Dong Interdisciplinary Nanoscience Center (iNANO) Aarhus University Aarhus C 8000 Denmark

Amyloid peptides are renowned to be related to neurodegenerative diseases, however, a fruitful avenue is to employ them as high-performance nanomaterials. These materials benefit from the intrinsic outstanding mechanical robustness of the amyloid backbone made of r-strands. In this work, we exploited amyloid-like fibrils as functional material to attach pristine L-cysteine aggregates （cystine oligomers） and gold nanoparticles, without the need of templating compounds. This work will open new avenues on functional materials design and their realisation.

关键词： cysteine peptide fibrils gold nanoparticles amyloids oligomers nanomaterials

Vulnerability and Resilience Research:A Critical Perspective

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International Journal of Disaster Risk science 2014年第1期5卷 86-87页

作者： Hannes Taubenbock christian Geiв German Remote sensing Data Center German Aerospace CenterOberpfaffenhofen82234 WesslingGermany

‘‘Vulnerability’’and‘‘resilience’’are terms of such broad conceptual meaning as to be almost useless for careful scientific communication,except as rhetorical indicators of areas of greatest *** is a reflection of the complexity of their meaning,an uncoordinated search among different fields for a common understanding,and maybe the difficulty of systematizing these complicated issues among the various involved parties.

关键词： Resilience difficulty coordinated

西花蓟马、二斑叶螨与黄瓜新小绥螨的相互关系研究

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应用昆虫学报 2011年第3期48卷 579-587页

作者：徐学农 christian Borgemeister hans-Michael Poehling 中国农业科学院植物保护研究所/农业部生物防治重点开放实验室北京100193 德国汉诺威莱布尼茨大学植物病害与植物保护研究所德国汉诺威30419 国际昆虫生理生态中心肯尼亚内罗毕

西花蓟马Frankliniella occidentalis(Pergande)和二斑叶螨Tetranychus urticae Koch是温室花卉与蔬菜上的重要害虫(螨)。植物常被两者同时危害。黄瓜新小绥螨Amblyseius cucumeris(Oudemans)是世界上广泛应用的温室蓟马的生物防治物,有时也被用来防治二斑叶螨。本研究中,在人工气候室盆栽条件下利用黄瓜新小绥螨防治西花蓟马和/或二斑叶螨。结果显示,当每豆株上接入10或20头二斑叶螨时,按照1∶4的益害比释放黄瓜新小绥螨可有效控制二斑叶螨。同样密度比的情况下,5和10头黄瓜新小绥螨的释放量可显著控制西花蓟马的接入量。二斑叶螨密度的增加没有显著影响到黄瓜新小绥螨对西花蓟马的控制作用。西花蓟马可捕食黄瓜新小绥螨的卵,日捕食量达1.2粒。本文对利用黄瓜新小绥螨防治温室中西花蓟马进行了讨论。

关键词：二斑叶螨西花蓟马黄瓜新小绥螨相互关系生物防治

Associations between C-Reactive Protein and Apolipoproteins, Lipoprotein (a) and Conventional serum Lipids in Outpatients: Correlations and Time Trends

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Open Journal of Clinical Diagnostics 2015年第2期5卷 33-40页

作者： christian Lowbeer Lena Martensson Elisabeth Berg hans Wallinder Department of Clinical Chemistry Aleris MedilabTabySweden Division of Clinical Chemistry Department of Laboratory MedicineKarolinska InstitutetStockholmSweden Medical statistics Unit Department of LearningInformaticsManagement and EthicsKarolinska InstitutetStockholmSweden

Background: Correlations between CRP and serum lipids are weak, and there are conflicting and incomplete results in the literature. The aim of the present study was to clarify the strength and independence of relationships between CRP and serum lipids in outpatients. Methods: Inclusion criteria were outpatients where all the following analyses were requested in clinical routine: high sensitivity CRP, total cholesterol, triglycerides, LDL-cholesterol, HDL-cholesterol, ApoB, ApoA-1 and Lp(a). Data for patients meeting the above criteria during a period of six years (2004-2010) were copied from Aleris Medilab’s Laboratory Information system to the software statistica. Basic statistics and correlations were calculated for 2771 patients. In patients with two (n = 959) or more sampling times changes over time were calculated. The study was a quality assurance project without access to patient files. Results: Median age was 59 years and median serum CRP concentration was 1.5 mg/L. The strongest correlations (spearman R) were seen between CRP and triglycerides (0.25), ApoB/ApoA-1 ratio (0.21) and HDL-cholesterol (−0.18). stepwise regression analysis showed that ApoB, total cholesterol, log triglycerides and log Lp(a) together explained 8% of the variation in log CRP. Unfavourable time trends for CRP and triglycerides counteracted a significant decrease in LDL-cholesterol and total cholesterol. Conclusion: In a large cohort of outpatients CRP showed stronger correlation with triglycerides and ApoB/ApoA-1 ratio than with LDL-cholesterol and Lp(a). LDL-cholesterol concentrations changed favorably over time whereas CRP and triglycerides did not.

关键词： CRP Cholesterol LDL HDL ApoB ApoA-1 Triglycerides Lp(a) Outpatients Risk Factors

Interaction of the α2A domain of integrin with small collagen fragments

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Protein & Cell 2010年第4期1卷 393-405页

作者： hans-christian siebert Monika Burg-Roderfeld Thomas Eckert sabine stötzel Ulrike Kirch Tammo Diercks Martin J.Humphries Martin Frank Rainer Wechselberger Emad Tajkhorshid steffen Oesser Institut für Biochemie und Endokrinologie Veterinärmedizinische FakultätJustus-Liebig-Universität GießenFrankfurter Str.10035392 GießenGermany CiC bioGUNE Parque Tecnológico de BizkaiaEdificio 80048160 DerioSpain Utrecht Facility for High-resolution NMR Bijvoetcenter for Biomolecular Research Utrecht UniversityPadualaan 83584CH UtrechtThe Netherlands Wellcome Trust Centre for Cell-Matrix Research School of Biological SciencesUniversity of Manchester2.205 Stopford BuildingOxford RoadManchester M139PTUK Molecular structure Analysis Core Facility Deutsches KrebsforschungszentrumIm Neuenheimer Feld 28069120 HeidelbergGermany Department of Biochemistry Beckman Instituteand Center for Biophysics and Computational BiologyUniversity of Illinois at Urbana-ChampaignUrbanaILUSA Collagen Research Institute Schauenburgerstr.116D-24118 KielGermany

We here present a detailed study of the ligand-receptor interactions between single and triple-helical strands of collagen and the α2A domain of integrin(α2A),providing valuable new insights into the mechanisms and dynamics of collagen-integrin binding at a sub-molecular *** occurrence of single and triple-helical strands of the collagen fragments was scrutinized with atom force microscopy(AFM)*** interactions of the triple-stranded fragments comparable to those of collagen can only be detected for the 42mer triple-helical collagen-like peptide under study(which contains 42 amino acid residues per strand)by solid phase assays as well as by surface plasmon resonance(sPR)***,changes in NMR signals during titration and characteristic saturation transfer difference(sTD)NMR signals are also detectable whenα2A is added to a solution of the 21mer single-stranded collagen *** dynamics(MD)simulations employing different sets of force field parameters were applied to study the interaction between triple-helical or single-stranded collagen fragments withα*** is remarkable that even single-stranded collagen fragments can form various complexes withα2A showing significant differences in the complex stability with identical *** results of MD simulations are in agreement with the signal alterations in our NMR experiments,which are indicative of the formation of weak complexes between single-stranded collagen andα2A in *** results provide useful information concerning possible interactions ofα2A with small collagen fragments that are of relevance to the design of novel therapeutic A-domain inhibitors.

关键词： integrin-collagen interaction NMR sPR AFM molecular modeling