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The mRNA Binding Proteome of Proliferating and Differentiated Muscle Cells

Genomics, Proteomics & Bioinformatics 2020年第4期18卷 384-396页

作者： Monika Hiller Miriam Geissler george janssen Peter van Veelen Annemieke Aartsma-Rus Pietro Spitali Department of Human Genetics Leiden University Medical CenterLeiden 2333 ZCthe Netherlands Center for Proteomics and Metabolomics Leiden University Medical CenterLeiden 2333 ZCthe Netherlands

Muscle formation is a coordinated process driven by extensive gene expression changes where single cells fuse together to form multinucleated muscle fibers. Newly synthesized m RNAs are then regulated by RNA binding proteins(RBPs), affecting post-transcriptional transcript metabolism. Here, we determined how large-scale gene expression changes affect the catalog of RBPs by studying proliferating and differentiated muscle cells in healthy and dystrophic conditions. Transcriptomic analysis showed that the expression of more than 7000 genes was affected during myogenesis. We identified 769 RBPs, of which 294 were muscle-specific and 49 were uniquely shared with cardiomyocytes. A subset of 32 RBPs(half of which were muscle-specific) was found to be preferentially associated with target mRNAs in either myoblasts(MBs) or myotubes(MTs). A large proportion of catalytic proteins were bound to mRNAs even though they lack classical RNA binding domains. Finally, we showed how the identification of cell-specific RBPs enabled the identification of biomarkers that can separate healthy individuals from dystrophic patients. Our data show how interactome data can shed light on new basic RNA biology as well as provide cell-specific data that can be used for diagnostic purposes.

关键词： RNA binding protein Interactome Duchenne muscular dystrophy Proteomics Skeletal muscle

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Three-dimensional modeling with national coverage:case of The Netherlands

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Geo-Spatial Information Science 2013年第4期16卷 267-276页

作者： Jantien STOTER Linda van den BRINK Jakob BEETZ Hugo LEDOUX Marcel REUVERS Paul janssen Friso PENNING george VOSSELMAN Sander OUDE ELBERINK Kadaster Hofstraat 1107311ApeldoornThe Netherlands OTB-Section GIS Technology)Delft University of Technology Jaffalaan 92600 AADelftKZThe Netherlands Geonovum Barchman Wuytierslaan 103818 LH AmersfoortThe Netherlands Department of the Built Environment Eindhoven University of TechnologyVRT 9.08Postbus 5135600 MBEindhovenThe Netherlands Department GeoInformation City of The HagueThe Netherlands Faculty of Geo-Information Science and Earth Observation–ITC University of TwenteHengelosestraat 997514 AEEnschedeThe Netherlands

Three-dimensional technologies have matured over the years.At the same time,3D information is becoming increasingly important in many applications.Still it is not straightforward to apply the solutions that work on prototypes,small areas or for specific projects to 3D modeling of a whole nation.In the Netherlands,two initiatives are ongoing to address the issues of nation-wide 3D modeling.First,the initiative that aims at establishing and implementing a national 3D standard for large-scale topography with support of all stakeholders.Collecting and maintaining the large-scale data are the responsibility of local governments(mainly municipalities).The second initiative is led by the Kadaster(the organization responsible for topographic mapping in the Netherlands)and aims at automatically generating a 3D version of the 1:10 k object-oriented data-set based on a smart combination of the two-dimensional data with high-resolution laser data.Both initiatives are presented in this paper including results,open issues,and future plans.

关键词： 3D modeling 3D standard country wide 3D mapping

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Interferon-free regimens for the treatment of hepatitis C virus in liver transplant candidates or recipients

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World Journal of Gastroenterology 2015年第32期21卷 9526-9533页

作者： Evangelos Cholongitas Chrysoula Pipili george Papatheodoridis 4~(th) Department of Internal Medicine Medical School of Aristotle University Hippokration General Hospital of Thessaloniki Division of Nephrology Royal Infirmary of Edinburgh Department of Gastroenterology Athens University Medical School Laiko General Hospital of Athens

The goal of therapy in chronic hepatitis C virus(HCV) infection is sustained virological response(SVR) which reflects HCV eradication. Treatment against HCV has dramatically improved with the recent availability of direct-acting antivirals(DAAs) including sofosbuvir, simeprevir, daclatasvir, ledipasvir/sofosbuvir, paritaprevir/ombitasvir and dasabuvir. Carefully selected combinations of these DAAs offer the potential for highly effective all-oral safe regimens even for patients with decompensated cirrhosis or liver transplant(LT) recipients. Like all current protease inhibitors, simeprevir and paritaprevir should not be used in patients with Child C cirrhosis, while sofosbuvir and ledipasvir/sofosbuvir should not be given in patients with severe renal impairment and glomerular filtration rate less than 30 m L/min. Drug-drug interactions may still occur with the current DAAs particularly in postLT patients, in whom simeprevir should not be coadministered with cyclosporine and dose adjustments of calcineurin inhibitors are required in case of regimens including the ritonavir boosted paritaprevir. Phase Ⅱ clinical trials and real life cohort studies have shown that sofosbuvir based combinations are safe and can achieve improvements of clinical status, high SVR rates and even prevention of post-LT HCV recurrence in patients with decompensated cirrhosis or LT-candidates. In the post-LT setting, sofosbuvir based regimens and the combination of paritaprevir/ombitasvir and dasabuvir have been reported to be safe and achieve high SVR rates, similar to those in non-transplantpatients, being effective even in cases with cholestatic fibrosing hepatitis. Ongoing clinical trials and rapidly emerging real life data will further clarify the safety and efficacy of the new regimens in these settings.

关键词： Hepatitis C Direct acting antiviral agents Liver t

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Managing Hepatitis C Patients in Greece: A Budget Impact Analysis of Simeprevir plus Pegylated Interferon/Ribavirin Regimen at Early Stages of the Disease

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Health 2017年第11期9卷 1482-1493页

作者： Mary Geitona Hara Kousoulakou Ioannis Goulis Spilios Manolakopoulos Themistoclis Vasiliadis Dimitrios Christodoulou Charalabos Gogos Spyridon Dourakis Ioannis george Koskinas Alexandra Papadokostopoulou Aris Lathouris george Papatheodoridis University of Peloponnese Corinth Greece Aristotle University of Thessaloniki Thessaloniki Greece National and Kapodistrian University of Athens Athens Greece University of Ioannina Ioannina Greece University of Patras Patra Greece janssen-Cilag Pharmaceutical SACI Athens Greece

Objectives: To identify local resource use such as pharmaceutical treatment, medical follow-up, and patient hospitalization and estimate the budget impact of simeprevir (SMV) plus pegylated interferon (P)/ribavirin (R) as a treatment option in the early stages of the disease in Greece. Methods: A budget impact tool was developed with a two-year time horizon, which estimated the impact on the Social Insurance Funds (SIFs) of introducing SMV + PR in the management of the early disease stages. Total direct and indirect costs were estimated for each of the following health states: non-cirrhotic chronic Hepatitis C (and within that by fibrosis stage), compensated cirrhosis, decompensated cirrhosis, and hepatocellular carcinoma. Data gaps on treatment algorithms, resource use and productivity losses were covered via an expert panel of eight leading hepatologists. Epidemiology data were taken from the published literature. Unit costs were obtained from the Ministry of Health and SIFs. The perspective was that of the SIF and the cost base year was 2015. Results: The total (direct and indirect) cost per patient per year (excluding cost of antiviral treatment) was estimated at €647, €703, €5,753, €16,313 and €37,237 for non-cirrhotic CHC, compensated cirrhosis, decompensated cirrhosis, HCC and liver transplantation, respectively. The budget impact analysis showed that adding SMV to PR in the early stages of the disease would lead to an increase in the cost of antiviral treatment by €2.03 million. Conclusions: Costs of managing CHC increase dramatically with disease severity. SMV + PR for naive patients at early disease stages has a significant but manageable budget impact, and could prevent high costs in advanced stages.

关键词： Hepatitis C Budget Impact Analysis Simeprevir Greece

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Next generation MHC multimer technology for detection of antigen-specific T cells

Next generation MHC multimer technology for detection of ant...

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第十二届全国免疫学学术大会

作者： Garstka Malgorzata Luimstra Jolien J Roex Marthe CJ Redeker Anke janssen george MC Van Veelen Peter A Arens Ramon Falkenburg Frederik JH Neefjes Jacques Ovaa Huib Xi'an Jiaotong University Second Affiliated Hospital Department of Chemical Immunology Leiden University Medical Center Department of Hematology Leiden University Medical Center Department of Immunohematology and Blood Transfusion Leiden University Medical Center Center for Proteomics and Metabolomics Leiden University Medical Center

Peptide ligand presentation by MHC class I molecules is a key element of immunodominance in antiviral and antitumor immune responses.MHC multimers are oligomeric forms of MHC-peptide monomers,generally tagged with a f... 详细信息

关键词： MHC multimers cytotoxic T cells immunodiagnostics

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Innovative education and training in high power laser plasmas(PowerLaPs) for plasma physics, high power laser matter interactions and high energy density physics: experimental diagnostics and simulations

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High Power Laser Science and Engineering 2020年第1期8卷 30-36页

作者： John Pasley Georgia Andrianaki Andreas Baroutsos Dimitri Batani Emmanouil PBenis Andrea Ciardi Donna Cook Vasilios Dimitriou Brendan Dromey Ioannis Fitilis Giancarlo Gatti Anastasios Grigoriadis Marine Huault Jose Antonio Pérez Hernández Evaggelos Kaselouris Ondrej Klimo Michel Koenig george Koundourakis Milan Kucharik Jiri Limpouch Richard Liska Carlos Salgado Lopez Sophia Malko Susana Olmos-Miguelanez Yannis Orphanos Valeria Ospina Nektarios APapadogiannis Stelios Petrakis Jan Psikal Maria Serena Rivetta Maria-ose Rodriguez-Conde Joao Jorge Santos Milan Sinor Alexandros Skoulakis Ioannis Tazes Laura Tejada Pascual Calliope Tsitou Pavel Vachal Luca Volpe Jiri Vyskocil Steven White Mark Yeung Ghassan Zerouli Michael Tatarakis York Plasma Institute University of YorkHeslingtonYork YO105DQUK Hellenic Mediterranean University Institute of Plasma Physics and Lasers-IPPL74100 Rethymnon73133 ChaniaCreteGreece University of Bordeaux CNRSCEACELIA(Centre Lasers Intenses et Applications)UMR 5107F-33405 TalenceFrance Department of Physics University of IoanninaGR 45110 IoanninaGreece LULI-CNRS CEASorbonne UniversiesEcole PolytechniqueInstitut Polytechnique de Paris-F-91128 Palaiseau CedexFrance Observatoire de Paris 5 Place J JanssenMeudon 92195France Centre for Plasma Physics School of Mathematics and PhysicsQueen’s University BelfastBelfast BT71NNUK Centro de Láseres Pulsados(CLPU) Edificio M5Parque CientficoC/Adaja 837185 VillamayorSalamancaSpain University of Salamanca 37008 SalamancaSpain Faculty of Nuclear Sciences and Physical Engineering Czech Technical University in PragueBrehova 711519Prague 1Czech Republic University Institute for Educational Sciences University of Salamanca37008 SalamancaSpain Group of Research“Interaction and e Learning”(GRIAL) University of Salamanca37008 SalamancaSpain CLPU Laser-Plasma Chair at University of Salamanca 37008 SalamancaSpain

The second and final year of the Erasmus Plus programme’Innovative Education and Training in high power laser plasmas’,otherwise known as PowerLaPs,is described.The PowerLaPs programme employs an innovative paradigm in that it is a multi-centre programme,where teaching takes place in five separate institutes with a range of different aims and styles of delivery.The’in-class’time is limited to 4 weeks a year,and the programme spans 2 years.PowerLaPs aims to train students from across Europe in theoretical,applied and laboratory skills relevant to the pursuit of research in laser plasma interaction physics and inertial confinement fusion.Lectures are intermingled with laboratory sessions and continuous assessment activities.The programme,which is led by workers from the Hellenic Mediterranean University and supported by co-workers from the Queen’s University Belfast,the University of Bordeaux,the Czech Technical University in Prague,Ecole Polytechnique,the University of Ioannina,the University of Salamanca and the University of York,has just finished its second and final year.Six Learning Teaching Training activities have been held at the Queen’s University Belfast,the University of Bordeaux,the Czech Technical University,the University of Salamanca and the Institute of Plasma Physics and Lasers of the Hellenic Mediterranean University.The last of these institutes hosted two 2-week-long Intensive Programmes,while the activities at the other four universities were each 5 days in length.In addition,a’Multiplier Event’was held at the University of Ioannina,which will be briefly described.In this second year,the work has concentrated on training in both experimental diagnostics and simulation techniques appropriate to the study of plasma physics,high power laser matter interactions and high energy density physics.The nature of the programme will be described in detail,and some metrics relating to the activities carried out will be presented.In particular,this paper will focus on the overall assessment of the programme.

关键词： laser plasma interactions postgraduate education

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