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A combined computational pipeline to detect circular RNAs in human cancer cells under hypoxic stress

Journal of Molecular Cell Biology 2019年第10期11卷 829-844页

作者： Antonella Di Liddo Camila de Oliveira Freitas Machado Sandra Fischer stefanie Ebersberger Andreas WHeumliller Julia EWeigand Michaela Muller-McNicoll Kathi Zarnack Buchmann Institute for Molecular Life Sciences Goethe University FrankfurtFrankfurt am MainGermany Institute of Cell Biology and Neuroscience Goethe University FrankfurtFrankfurt am MainGermany Institute for Cardiovascular Regeneration Goethe University FrankfurtFrankfurt am MainGermany Department of Biology Technical University DarmstadtGermany Institute of Molecular Biology(IMB) MainzGermany

Hypoxia is associated with several diseases,including *** that are deprived of adequate oxygen supply trigger tran-scriptional and post-transcriptional responses,which control cellular pathways such as angiogenesis,proliferation,and metabolic *** RNAs(circRNAs)are a novel class of mainly non-coding RNAs,which have been implicated in multiple cancers and attract increasing attention as potential ***,we characterize the circRNA signatures of three different cancer cell lines from cervical(HeLa),breast(MCF-7),and lung(A549)cancer under *** order to reliably detect circRNAs,we integrate available tools with custom approaches for quantification and statistical analysis?Using this consolidated computational pipeline,we identify?12000 circRNAs in the three cancer *** molecular characteristics point to an involvement of complementary RNA sequences as well as trans-acting factors in circRNA biogenesis,such as the RNA-binding protein HNRNPC-Notably,we detect a number of circRNAs that are more abundant than their linear *** addition,64 circRNAs significantly change in abundance upon hypoxia,in most cases in a cell type-specific *** summary,we present a comparative circRNA profiling in human cancer cell lines,which promises novel insights into the biogenesis and function of circRNAs under hypoxic stress.

关键词： circular RNA computational pipeline differential expression cancer cells hypoxia RNA-Seq

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Hepatocyte cytoskeleton during ischemia and reperfusion -influence of ANP-mediated p38 MAPK activation

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World Journal of Gastroenterology 2005年第47期11卷 7418-7429页

作者： Melanie Keller Alexander L Gerbes stefanie Kulhanek-Heinze Tobias Gerwig Uwe Grützner Nico van Rooijen Angelika M Vollmar Alexandra K Kiemer Department of Pharmacy Centre of Drug ResearchUniversity of MunichButenandtstr. 5-1381377 MunichGermany Department of Medicine Ⅱ Klinikum GroβhadernUniversity of MunichMarchionistr. 1781377 MunichGermany Angelika M Vollmar Alexandra K KiemerDepartment of PharmacyCentre of Drug ResearchUniversity of MunichButenandtstr. 5-1381377 MunichGermany Department of Pharmacy Centre of Drug ResearchUniversity of MunichButenandtstr. 5-1381377 MunichGermany Department of Medicine ⅡKlinikum GroβhadernUniversity of MunichMarchionistr. 1781377 MunichGermany Institute for Surgical Research Klinikum GroβhadernUniversity of MunichMarchionistr. 1781377 MunichGermany Vrije Universiteit VUMCDepartment of Molecular Cell BiologyFaculty of Medicine1081 BT AmsterdamThe Netherlands

AIM： To determine functional consequences of this activation, whereby we focused on a potential regulation of the hepatocyte cytoskeleton during ischernia and reperfusion. METHODS： For in vivo experiments, animals received ANP （5 μg/kg） intravenously. In a different experimental setting, isolated rat livers were perfused with KH-buffer ＋ANP （200 nmol/L）＋SB203580 （2 μmol/L）. Livers were then kept under ischernic conditions for 24 h, and either transplanted or reperfused. Actin, Hsp27, and phosphorylated Hsp27 were determined by Western blotting, p38 MAPK activity by in vitro phosphorylation assay. F-actin distribution was determined by confocal microscopy. RESULTS： We first confirmed that ANP preconditioning leads to an activation of p38 MAPK and observed alterations of the cytoskeleton in hepatocytes of ANP- preconditioned organs. ANP induced an increase of hepatic F-actin after ischemia, which could be prevented by the p38 MAPK inhibitor SB203580 but had no effect on bile flow. After ischemia untreated livers showed a translocation of Hsp27 towards the cytoskeleton and an increase in total Hsp27, whereas ANP preconditioning prohibited translocation but caused an augmentation of Hsp27 phosphorylation. This effect is also mediated via p38 MAPK, since it was abrogated by the p38 MAPK inhibitor SB203580. CONCLUSION： This study reveals that ANP-mediated p38 MAPK activation leads to changes in hepatocyte cytoskeleton involving an elevation of phosphorylated Hsp27 and thereby for the first time shows functional consequences of ANP-induced hepatic p38 MAPK activation.

关键词： Hormonal preconditioning Atrial natriuretic peptide Hsp 27 Actin Polymerization

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隐君者女

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作者： stefanie Chow

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Moving beyond the opposition of diverse knowledge systems for food security and nutrition

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Journal of Integrative Agriculture 2020年第1期19卷 291-293页

作者： Nathanaël PINGAULT Patrick CARON Alicia KOLMANS stefanie LEMKE Carol KALAFATIC Sabine ZIKELI Ann WATERS-BAYER Carolin CALLENIUS QIN Yong-jun High Level Panel of Experts Committee on World Food SecurityFood and Agriculture Orgnization of the United NationsRome 00153Italy Universitéde Montpellier Montpellier 34090France Research Center Global Food Security and Ecosystems University of HohenheimStuttgart 70599Germany Centre for Agroecology Water and ResilienceCoventry UniversityCV83LG CoventryUK Center for Organic Farming University of HohenheimStuttgart 70593Germany Agrecol Association Guggenhausen 88379Germany Shanxi Academy of Agricutural Sciences Taiyuan 030031P.R.China

Food Security and Nutrition(FSN) is influenced by diverse and complex factors, and therefore requires a holistic approach to agriculture and food systems plus integration of knowledge from diverse sources in science and society. Using the results of a colloquium held at the University of Hohenheim(Germany) in September 2016 leading up to the recent High Level Panel of Experts(HLPE) Note on Critical and Emerging Issues for Food Security and Nutrition, this article underlines the role of research and innovation as a social and political process and draws attention to neglected types of knowledge. It illustrates the potential of knowledge co-production and co-innovation to transform food systems in order to achieve the Sustainable Development Goals.

关键词： food security nutrition innovation Sustainable Development Goals

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Application of light sheet microscopy for qualitative and quantitative analysis of bronchus-associated lymphoid tissue in mice

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Cellular & Molecular Immunology 2018年第10期15卷 875-887页

作者： David Twapokera Mzinza Henrike Fleige Kristin Laarmann stefanie Willenzon Jasmin Ristenpart Julia Spanier Gerd Sutter Ulrich Kalinke Peter Valentin-Weigand Reinhold Förster Institute of Immunology Hannover Medical SchoolHannoverGermany Institute for Microbiology University of Veterinary Medicine HannoverHannoverGermany Institute for Experimental Infection Research TWINCORECentre for Experimental and Clinical Infection Researcha joint venture between the Helmholtz-Centre for Infection Research and the Hannover Medical SchoolHannoverGermany Institute for Infectious Diseases and Zoonoses University of Munich LMUMunichGermany

Bronchus-associated lymphoid tissue(BALT)develops at unpredictable locations around lung bronchi following pulmonary *** formation and composition of BALT have primarily been investigated by immunohistology that,due to the size of the invested organ,is usually restricted to a limited number of histological *** assess the entire BALT of the lung,other approaches are urgently ***,we introduce a novel light sheet microscopy-based approach for assessing lymphoid tissue in the *** antibody staining of whole lung lobes and optical clearing by organic solvents,we present a method that allows in-depth visualization of the entire bronchial tree,the lymphatic vasculature and the immune cell composition of the induced ***,three-dimensional analysis of the entire lung allows the qualitative and quantitative enumeration of the induced *** this approach,we show that a single intranasal application of the replication-deficient poxvirus MVA induces BALT that constitutes up to 8%of the entire lung volume in mice deficient in CCR7,in contrast to wild type mice(WT).Furthermore,BALT induced by heat-inactivated *** is dominated by a pronounced T cell infiltration in Cxcr5-deficient mice,in contrast to WT mice.

关键词： Lung BALT light sheet microscopy E.coli MVA

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E-Cigarette Vapor Decreases Cellular Proliferation through Nicotine-Dependent Mechanisms

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Journal of Biosciences and Medicines 2019年第7期7卷 121-134页

作者： stefanie Rigg Lindsay M. Gielda Purdue University Northwest Westville IN USA

Electronic cigarette (e-cigarette) use has risen as individuals look for healthier nicotine delivery systems than conventional cigarettes, but recent studies have demonstrated variable physiological responses to e-cigarette vapor. The safety of e-cigarette vapor remains an open question. We investigated the molecular cellular response of adenocarcinoma human alveolar basal epithelial (A549) cells to flavored e-cigarette vapor. E-cigarette and cigarette vapor were extracted via a vacuum-percolating system into PBS. The effects of a flavored e-liquid containing nicotine (eCSE) and nicotine free e-liquid (NFeCSE) were compared to cigarette smoke extract (CSE), pure nicotine, glycerol, and PBS. Cells exposed to eCSE and NFeCSE had decreased cell viability and proliferation. An increase in active caspase-3 was observed in cells exposed to NFeCSE, while cells exposed to eCSE and CSE displayed no change, suggesting nicotine-mediated protection from apoptosis. However, phosphorylated Akt, which regulates cellular proliferation, was elevated in response to eCSE, NFeCSE, CSE, and glycerol. As the glutathione-oxidative stress response was known to integrate cellular factors including carcinogenesis, inflammation, and cell proliferation, GSH/GSSG levels were measured in cells exposed to e-cigarette smoke. An increase in oxidative stress was observed in cells treated with CSE, but not eCSE, suggesting components in CSE independent of nicotine may be contributing to an imbalance in the stress response. These results indicate e-cigarette vapor affects A549 cell viability dependent on nicotine, and is distinct from CSE-induced mechanisms of oxidative-stress.

关键词： E-Cigarettes Oxidative Stress Nicotine Apoptosis

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The Essential Oil Content and Composition of Selected Salvia Species, Sage Teas, and Sage Drops

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Journal of Food Science and Engineering 2012年第8期2卷 427-436页

作者： stefanie Oelschlaigel Sabine Quaas Karl Speer Food Chemistry Technical University Dresden Dresden Saxony 01069 Germany

Sage is popular for its manifold applications and has always been used in herbalism. The Salvia genus encompasses up to 900 species, but only a few of them have been investigated. Hence, the objective was to investigate the essential oil content as well as the terpene composition of a number of Saliva species. In this context, S. officinalis var. Extrakta, S. officinalis ＂Aurea＂ and S. patens were investigated for the first time. To some extent, it was also possible to associate the terpene distribution of the investigated commercial sage teas and drops with the processed sage oil. Furthermore, an ultrasonic extraction with ethyl acetate seems to be an efficient quick-method for extracting the essential oil.

关键词： Essential oil Salvia officinalis sage tea sage drops thujone.

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论肖邦《c小调夜曲Op.48 No.1》的演奏分析

论肖邦《c小调夜曲Op.48 No.1》的演奏分析

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作者： stefanie Limbara 中央音乐学院

学位级别：硕士

“夜曲”这种体裁在浪漫时期占有重要的地位,是爱尔兰钢琴家,作曲家约翰·菲尔德首创。菲尔德的“夜曲”是旋律优美,柔情并多情善感的沙龙情调,而肖邦在菲尔德基础上不断对“夜曲”进行发展,扩大了夜曲的表现力,丰富情感和创作技法。肖... 详细信息

“夜曲”这种体裁在浪漫时期占有重要的地位,是爱尔兰钢琴家,作曲家约翰·菲尔德首创。菲尔德的“夜曲”是旋律优美,柔情并多情善感的沙龙情调,而肖邦在菲尔德基础上不断对“夜曲”进行发展,扩大了夜曲的表现力,丰富情感和创作技法。肖邦的二十一首“夜曲”是这一体裁最为出色的代表。在“夜曲”中,肖邦用他自己的创作风格,将“夜曲”发展成为了一种抒情性,戏剧性相结合的音乐作品。本文将从夜曲的创作背景,曲式结构,演奏方法进行研究。笔者希望通过本研究分析,能更深入地了解这首作品,并将研究成果运用到钢琴演奏中。

关键词：肖邦夜曲演奏方法戏剧性

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Increased liver stiffness in alcoholic liver disease:Differentiating fibrosis from steatohepatitis

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World Journal of Gastroenterology 2010年第8期16卷 966-972页

作者： Sebastian Mueller Gunda Millonig Lucie Sarovska stefanie Friedrich Frank M Reimann Maria Pritsch Silke Eisele Felix Stickel Thomas Longerich Peter Schirmacher Helmut Karl Seitz Department of Medicine and Center for Alcohol Research Salem Medical Center University of Heidelberg Institute of Medical Biometry and Informatics University of Heidelberg Institute of Clinical Pharmacology University of Bern Department of Pa-thology University of Heidelberg

AIM:To test if inflammation also interferes with liver stiffness (LS) assessment in alcoholic liver disease (ALD) and to provide a clinical algorithm for reliable fibrosis assessment in ALD by FibroScan (FS).METHODS:We first performed sequential LS analysis before and after normalization of serum transaminases in a learning cohort of 50 patients with ALD admitted for alcohol detoxification. LS decreased in almost all patients within a mean observation interval of 5.3 d. Six patients (12%) would have been misdiagnosed with F3and F4 fibrosis but LS decreased below critical cut-off values of 8 and 12.5 kPa after normalization of trans-aminases. RESULTS:Of the serum transaminases,the decrease in LS correlated best with the decrease in glutamic oxaloacetic transaminase (GOT). No significant chang-es in LS were observed below GOT levels of 100 U/L. After establishing the association between LS and GOT levels,we applied the rule of GOT 100 U/L at the time of LS assessment from this cohort,the area under the receiver operating characteristic (AUROC) for cirrhosis detection by FS improved from 0.921 to 0.945 while specificity increased from 80% to 90% at a sensitivity of 96%. A similar AUROC could be obtained for lower F3 fibrosis stage if LS measurements were restricted to patients with GOT ting steatohepatitis markedly increases LS in patients with ALD independent of fibrosis stage. Postponing cirrhosis assessment by FS during alcohol withdrawal until GOT decreases to < 100 U/mL signif icantly improves the diagnostic accuracy.

关键词： Alcoholic liver disease Alcoholic steatohep-atitis Liver cirrhosis Bilirubin Tissue elasticity imaging FibroScan

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Determinants of PHGPx Expression in a Cultured Endothelial Cell Line

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Biomedical and Environmental Sciences 1997年第2期10卷 163-176页

作者： REGINA BRIGELIUS-FLOHE B■RBEL FRIEDRICHS stefanie MAURER AND RUDIGER STREICHER (German Institute of Human Nutrition,D-14558 Potsdam-Rehbrucke, Germany) German Institute of Human Nutrition Potsdam-Rehbrücke Germany.

Selenoprotein biosynthesis may not only be affected by the availability of selenium and the transcription rate of pertinent genes but also by the activity of components of the selenocysteine incorporation complex, SelA, B, C, or D. Incorporation of selenocysteine into selenoproteins requires a complex co-translational mechanism guaranteeing the correct recoding of the termination codon TGA as selenocysteine codon. A particular tRNASer(Sec) is enzyrnatically transformed by selenophosphate into tRNAsec which recognizes the UGA codon by means of a specific elongation factor (SelB) and a peculiar mRNA secondary structure. Selenophosphate is formed from selenide and ATP by the SelD gene product, selenophosphate synthase (SelD). To further elucidate the biological role of phospholipid hydroperoxide GPx (PHGPx), we transformed cells with a heterologous (pig) PHGPx gene and/or an additional (human) SelD gene and studied the behaviour of these cells under selenium depletion and repletion. Transfection of the endothelial cell line ECV 304 with either PHGPx cDNA or SelD cDNA did not result in a substantial increase of PHGPx activities, independent of selenium supply. However, cells co-trans fected with both, PHGPx and SelD cDNA, expressed significantly higher PHGPx activlty. This effect was much more pronounced under selenium limiting conditions. The enhanced PHGPx activity correlated with two functional pararneters, increased capability to reduce hydroperoxides and less sensitivity against H2O2-induced cytotoxicity. Thus, the ECV cells, stably transfected with PHGPx and SelD cDNA, provide a model to specifically investigate the role of PHGPx in endothelial cell function

关键词： ECV Determinants of PHGPx Expression in a Cultured Endothelial Cell Line

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