Refine
Year of publication
Document Type
- Doctoral Thesis (8826)
- Journal article (8161)
- Complete part of issue (703)
- Book article / Book chapter (479)
- Book (217)
- Conference Proceeding (202)
- Preprint (127)
- Review (115)
- Working Paper (104)
- Master Thesis (103)
- Report (91)
- Jahresbericht (69)
- Other (34)
- Study Thesis (term paper) (22)
- Bachelor Thesis (16)
- Habilitation (4)
Language
- English (10623)
- German (8538)
- French (58)
- Multiple languages (22)
- Spanish (22)
- Russian (6)
- Italian (2)
- Portuguese (2)
Keywords
- Würzburg (736)
- Universität (668)
- Wuerzburg (666)
- Wurzburg (659)
- University (608)
- Organische Chemie (135)
- Psychologie (127)
- Anorganische Chemie (124)
- Maus (124)
- Toxikologie (123)
Institute
- Theodor-Boveri-Institut für Biowissenschaften (2232)
- Graduate School of Life Sciences (992)
- Physikalisches Institut (783)
- Institut für Anorganische Chemie (672)
- Medizinische Klinik und Poliklinik I (631)
- Institut für Psychologie (572)
- Institut für Organische Chemie (545)
- Medizinische Klinik und Poliklinik II (534)
- Klinik und Poliklinik für Allgemein-, Viszeral-, Gefäß- und Kinderchirurgie (Chirurgische Klinik I) (492)
- Neurologische Klinik und Poliklinik (492)
Schriftenreihe
- Cultural Animal Studies, Band 3 (24)
- Spezielle Didaktik der Sportarten (2)
- Aesthetische Eigenzeiten, 17 (1)
- Akten des ... Symposiums des Mediävistenverbandes; 13,2 (1)
- Alter Orient und Altes Testament : Sonderreihe Veröffentlichungen zur Kultur und Geschichte des Alten Orients ; 3 (1)
- Aventiuren; 13 (1)
- Berichte aus der Informatik (1)
- Deuterocanonical and Cognate Literature Studies (1)
- Deuterocanonical and Cognate Literature Yearbook (1)
- Epistemata. Reihe Literaturwissenschaft ; 483 (1)
- European Journal of Clinical Nutrition ; 70 (1)
- Forum Junge Romanistik 18 (1)
- Frontiers in Psychology (2023) 14:1219915. https://doi.org/10.3389/fpsyg.2023.1219915 (1)
- Frontiers in Public Health (2023) 11:1153088. https://doi.org/10.3389/fpubh.2023.1153088 (1)
- GenderCodes - Transkriptionen zwischen Wissen und Geschlecht; 17 (1)
- Grundzüge ; 45 (1)
- Image ; 185 (1)
- International Archives of the History of Ideas / Archives internationales d’histoire des idées 242 (1)
- Jahrbuch der Oswald-von-Wolkenstein-Gesellschaft; 17 (1)
- Journal of Neuroimaging; Volume 28 (1)
- Kaleidogramme ; 183 (1)
- Macht und Herrschaft; 15 (1)
- Methods in Molecular Biology 2533 (1)
- Methods in Molecular Biology; 2643 (1)
- Palingenesia; 112 (1)
- Philologica Germanica; 39 (1)
- Pirckheimer-Jahrbuch für Renaissance- und Humanismusforschung; 23 (1)
- Pirckheimer-Jahrbuch für Renaissance- und Humanismusforschung; 29 (1)
- Pluralisierung & Autorität; 27 (1)
- Redox Biology (2024) 70:103011. DOI: 10.1016/j.redox.2023.103011 (1)
- Schriften des Vereins für Reformationsgeschichte; 207 (1)
- Sozialwissenschaften heute ; 2 (1)
- Studien zur Literatur und Erkenntnis; 6 (1)
- Studien zur historisch-vergleichenden Sprachwissenschaft; 20 (1)
- Studien zur historischen Poetik; 23 (1)
- Trends in Medieval Philology; 5 (1)
- Universitätsforschungen zur Prähistorischen Archäologie ; 259 (1)
- Wirtschaftsrecht und Wirtschaftspolitik ; Bd. 207 (1)
- Wissenschaftliche Schriften der WWU Münster / Reihe XII ; 25 (1)
- Wolfenbütteler Forschungen ; 160 (1)
- Würzburger Geographische Manuskripte, Heft 88 (1)
- culturae ; 19 (1)
- spectrum Literaturwissenschaft / spectrum Literature; 22 (1)
Sonstige beteiligte Institutionen
- VolkswagenStiftung (24)
- Johns Hopkins School of Medicine (18)
- Fraunhofer-Institut für Silicatforschung ISC (8)
- IZKF Nachwuchsgruppe Geweberegeneration für muskuloskelettale Erkrankungen (7)
- Akademie der Wissenschaften und der Literatur, Mainz (6)
- DFG Forschungsgruppe 2757 / Lokale Selbstregelungen im Kontext schwacher Staatlichkeit in Antike und Moderne (LoSAM) (6)
- Clinical Trial Center (CTC) / Zentrale für Klinische Studien Würzburg (ZKSW) (5)
- Helmholtz Institute for RNA-based Infection Research (HIRI) (5)
- Johns Hopkins University School of Medicine (5)
- Universität Leipzig (5)
- Universitätsklinikum Würzburg (5)
- Wilhelm-Conrad-Röntgen-Forschungszentrum für komplexe Materialsysteme (5)
- Bernhard-Heine-Centrum für Bewegungsforschung (4)
- Johns Hopkins School of Medicine, Baltimore, MD, U.S. (4)
- Universität Bayreuth (4)
- Cologne Game Lab (3)
- Deutsches Archäologisches Institut (3)
- Fraunhofer Institut für Silicatforschung ISC (3)
- Fraunhofer-Institut für Silicatforschung (3)
- Klinikum Fulda (3)
- König-Ludwig-Haus Würzburg (3)
- Professur für Museologie (3)
- Technische Hochschule Nürnberg Georg Simon Ohm (3)
- The Italian Federation of Parks and Nature Reserves (3)
- Universitätsklinikum Münster (3)
- Zentraleinheit Klinische Massenspektrometrie (3)
- ALPARC - The Alpine Network of Protected Areas (2)
- CHC Würzburg (Comprehensive Hearing Center) (2)
- Center for Interdisciplinary Clinical Research, Würzburg University, Würzburg, Germany (2)
- Comprehensive Cancer Center Mainfranken (2)
- Department of Biomedical Imaging, National Cerebral and Cardiovascular Research Center, Suita, Japan (2)
- Deutsches Zentrum für Herzinsuffizienz (2)
- Deutsches Zentrum für Luft- und Raumfahrt (DLR), Institut für Raumfahrtsysteme (2)
- Deutsches Zentrum für Luft- und Raumfahrt e.V. (2)
- Division of Medical Technology and Science, Department of Medical Physics and Engineering, Course of Health Science, Osaka University Graduate School of Medicine, Suita Japan (2)
- EMBL Heidelberg (2)
- Eurac research (2)
- Fraunhofer ISC (2)
- Fraunhofer-Institut für Silicatforschung ISC, Würzburg (2)
- Hochschule Aalen (2)
- Institut for Molecular Biology and CMBI, Department of Genomics, Stem Cell Biology and Regenerative Medicine, Leopold-Franzens-University Innsbruck, Innsbruck, Austria (2)
- Institut für Optik und Atomare Physik, Technische Universität Berlin, 10623 Berlin, Germany (2)
- Institut für Tierökologie und Tropenbiologie (2)
- Interdisciplinary Center for Clinical Research (2)
- Interdisziplinäres Zentrum für Klinische Forschung (IZKF) (2)
- International Max Planck Research School Molecular Biology, University of Göttingen, Germany (2)
- Johns Hopkins School of Medicine, The Russell H Morgan Department of Radiology and Radiological Science, Baltimore, MD, USA (2)
- Joslin Diabetes Center (Harvard Medical School) (2)
- Klinik für Kinder- und Jugendmedizin des Caritas-Krankenhauses Bad Mergentheim (2)
- Klinische Studienzentrale (Universitätsklinikum) (2)
- Krankenhaushygiene und Antimicrobial Stewardship (2)
- Krankenhaushygiene und Antimicrobial Stewardship (Universitätsklinikum) (2)
- Krankenhaushygiene und Antimicrobial Stewardship, Universitätsklinikum Würzburg (2)
- Laboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology, Yokohama 226-8503, Japan (2)
- Lehrkrankenhaus II. Medizinische Klinik Klinikum Coburg (2)
- Mildred Scheel Early Career Center (2)
- Mildred-Scheel-Nachwuchszentrum (2)
- Naturalis Biodiversity Centre (2)
- Open University of the Netherlands (2)
- Orthopädische Klinik König-Ludwig-Haus (2)
- Orthopädische Klinik und Poliklinik der Universität Würzburg (2)
- Rudolf Virchow Center for Integrative and Translational Bioimaging, University of Würzburg (2)
- Röntgen Center for Complex Material Systems (RCCM), Am Hubland, 97074 W¨urzburg, Germany (2)
- Salzburg Institute for Regional Planning and Housing (2)
- Siemens AG (2)
- Universität Belgrad, Serbien (2)
- Urban Planning Institute of the Republic of Slovenia (2)
- Würzburg-Dresden Cluster of Excellence ct.qmat (2)
- ZVES Würzburg (Zentrum für vorsprachliche Entwicklung und Entwicklungsstörungen) (2)
- Zentrallabor, Universitätsklinikum Würzburg (2)
- Zentrum für Infektionsforschung (ZINF) Würzburg (2)
- Zentrum für Lehrerbildung und Bildungsforschung (2)
- Zentrum für Telematik e.V. (2)
- Ökologische Station Fabrikschleichach (2)
- ACC GmbH Analytical Clinical Concepts (1)
- ALPARC - Das Netzwerk Alpiner Schutzgebiete (1)
- ATLAS Collaboration (1)
- Abteilung Molekulare Innere Medizin (1)
- Abteilung für Molekulare Onkoimmunologie (1)
- Adam Opel AG (1)
- Agricultural Center, BASF SE, 67117 Limburgerhof, Germany (1)
- Airbus Defence and Space GmbH (1)
- Albert-Ludwigs-Universität Freiburg im Breisgau (1)
- Albert-Ludwigs-Universität Freiburg (1)
- Alte Geschichte (1)
- Anthropology Department University of Tennessee, Knoxville (1)
- Apotheke, Universitätsklinikum Würzburg (1)
- Arizona State University, Tempe, Arizona, USA (1)
- Auftrag der Rummelsberger Dienste für Menschen mit Behinderung gGmbH; Aktion Mensch (1)
- BMBF (1)
- Badisches Landesmuseum Karlsruhe (1)
- Bavarian Center for Applied Energy Research (ZAE Bayern), 97074 Würzburg, Germany (1)
- Bavarian Center for Applied Energy Research e.V. (ZAE Bayern) (1)
- Bayer AG, Research & Development, Pharmaceuticals, Investigational Toxicology (1)
- Bayerische Museumsakademie (1)
- Bayerisches Geoinstitut, Universität Bayreuth (1)
- Bayerisches Zentrum für Angewandte Energieforschung e.V. (1)
- Betriebsärztlicher Dienst der Universität Würzburg (1)
- Beuth Hochschule für Technik Berlin (1)
- Bezirk Unterfranken (1)
- Bio-Imaging Center Würzburg (1)
- Biomedical Center Munich, Department of Physiological Chemistry, Ludwig-Maximilians-Universität München (1)
- Biomedizinische NMR Forschungs GmbH am Max-Planck-Institut fuer biophysikalische Chemie (1)
- Birmingham City University (1)
- Blindeninstitut, Ohmstr. 7, 97076, Wuerzburg, Germany (1)
- Boehringer Ingelheim Pharma GmbH & Co. KG (1)
- Boston Children's Hospital (1)
- Broad Institute, USA (1)
- Brown University (1)
- Bugando Medical Center in Mwanza, Tansania (1)
- Bundesinstitut für Arzneimittel und Medizinprodukte (1)
- Bundeswehr Institute of Radiobiology affiliated to the University of Ulm, Munich, Germany (1)
- Bungando Medical Centre, Mwanza, Tanzania (1)
- CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - the development agency of the Brazilian Federal Government (1)
- CBIO, University of Cape Town, South Africa (1)
- CERN (1)
- CERN (Geneva, Switzerland) (1)
- CIBSS Centre for Integrative Biological Signalling Studies, University of Freiburg (1)
- CUHAS Catholic University of Health and Allied Sciences Mwanza (1)
- CUHAS Catholic university of health and allied science, Mwanza, Tanzania (1)
- Caritas-Krankenhaus Bad Mergentheim (1)
- Carl-Ludwig-Institut für Physiologie, Universität Leipzig (1)
- Catholic University of Health and Allied Sciences in Mwanza, Tansania (1)
- Center for Computational and Theoretical Biology (CCTB), Universität Würzburg (1)
- Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), Göttingen, Germany (1)
- Center for Nanosystems Chemistry (1)
- Center for Nanosystems Chemistry (CNC), University of Würzburg (1)
- Center for Nanosystems Chemistry (CNC), Universität Würzburg (1)
- Center for Nanosystems Chemistry (CNC), Universität Würzburg, Am Hubland, 97074 Würzburg, Germany (1)
- Center of Excellence for Science and Technology - Integration of Mediterranean region (STIM), Faculty of Science, University of Split, Poljička cesta 35, 2100 Split, Croatia (1)
- Centre for Political Studies, Jawaharlal Nehru University, New Delhi (1)
- Chair of Experimental Biomedicine I (1)
- Charles University, Faculty of Mathematics and Physics, Ke Karlovu 5, 121 16 Prague, Czech Republic (1)
- Chemical Biology Laboratory, National Cancer Institue, Frederick (USA) (1)
- Cheng Lab, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA (1)
- Cluster of Excellence "Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells, Göttingen (1)
- Comprehensive Cancer Center Mainfranken, University Hospital Würzburg, Würzburg, Germany (1)
- Comprehensive Hearing Center (1)
- Comprehensive Hearing Center, Department of ORL, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, Würzburg, Germany (1)
- Comprehensive Heart Failure Center Wuerzburg (CHFC) (1)
- Core Unit Systemmedizin (1)
- DAAD - Deutscher Akademischer Austauschdienst (1)
- DATE Lab, KITE Research Insititute, University Health Network, Toronto, Canada (1)
- DFG (1)
- DLR (1)
- DNA Analytics Core Facility, Biocenter, University of Wuerzburg, Wuerzburg, Germany (1)
- DNA Analytics Core Facility, Biocenter, University of Würzburg, Würzburg, Germany (1)
- Datenintegrationszentrum Würzburg (DIZ) (1)
- Deakin University, Australia (1)
- Departamento de Química, Facultad de Ciencias, Universidad Autónoma de Madrid, 28049 Madrid, Spain (1)
- Department Pharmazie - Zentrum für Pharmaforschung, Ludwig-Maximilians-Universität München (1)
- Department of Animal Ecology and Tropical Biology, University of Würzburg, Würzburg, Germany (1)
- Department of Biochemistry (1)
- Department of Cellular Biochemistry, University Medical Center Göttingen (1)
- Department of Cellular Biochemistry, University Medical Centre Göttingen (1)
- Department of Cellular Therapies, University of Navarra, Pamplona, Spain (1)
- Department of Chemistry, Humboldt Universität zu Berlin, Brook-Taylor-Strasse 2, 12489 Berlin, Germany (1)
- Department of Chemistry, Sungkyunkwan University, 440-746 Suwon, Republic of Korea (1)
- Department of English, Jamia Millia Islamia (A Central University), New Delhi (1)
- Department of Hematology and Oncology, Sana Hospital Hof, Hof, Germany (1)
- Department of Laboratory Medicine and Medicine Huddinge, Karolinska Institutet and University Hospital, Stockholm, Sweden (1)
- Department of Mathematical Analysis, Faculty of Mathematics and Physics, Charles University in Prague (1)
- Department of Medicinal Chemistry, University of Vienna, Althanstraße 14, 1090 Vienna, Austria (1)
- Department of Medicine A, University Hospital of Münster, Münster, Germany (1)
- Department of Molecular Biology, University Medical Center Göttingen, Germany (1)
- Department of Molecular Biology, University Medical Centre Göttingen (1)
- Department of Molecular Biology, University Medical Centre Göttingen, Göttingen 37073, Germany (1)
- Department of Nuclear Medicine, Kanazawa University (1)
- Department of Nuclear Medicine, Philipps University Marburg, Marburg, Germany (1)
- Department of Paediatric Radiology, Institute of Diagnostic and Interventional Radiology, Josef-Schneider-Straße 2, Wuerzburg 97080, Germany (1)
- Department of Pediatrics, Pediatrics I, Innsbruck Medical University, Anichstr. 35, 6020, Innsbruck, Austria (1)
- Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Althanstraße 14, 1090 Vienna, Austria (1)
- Department of Veterinary Sciences, Experimental Parasitology, Ludwig-Maximilians-Universität München (1)
- Department of X-ray Microscopy, University of Würzburg, Würzburg, Germany (1)
- Deutscher Akademischer Austauschdienst (DAAD) (1)
- Deutsches Archäologisches Institut, Istanbul (1)
- Deutsches Klimaservice Zentrum (GERICS) (1)
- Deutsches Krebsforschungszentrum Heidelberg (1)
- Deutsches Zentrum für Luft & Raumfahrt (DLR) (1)
- Deutsches Zentrum für Luft- und Raumfahrt (1)
- Deutsches Zentrum für Luft- und Raumfahrt (DLR) (1)
- Deutsches Zentrum für Luft- und Raumfahrt (DLR), Deutsches Fernerkundungsdatenzengrum (DFD) (1)
- Deutsches Zentrum für Präventionsforschung Psychische Gesundheit (DZPP) (1)
- Didaktik der Chemie (1)
- Didaktik der Physik (1)
- Dissertation am Institut für Sportwissenschaft, Universität Bayreuth (1)
- Département de géographie, Université Abdou Moumouni Dioffo de Niamey, Niger (1)
- EMBL Mouse Biology Unit, Monterotondo, Italien (1)
- EMBL, Structural and Computational Biology Unit, Heidelberg, Germany (1)
- ESPCI Paris (1)
- Early Clinical Trial Unit, Comprehensive Cancer Center Mainfranken (1)
- Eberhard Karls Universität Tübingen (1)
- Endokrinologie (1)
- English Department, University of Zurich (1)
- Ernst Strüngmann Institute for Neuroscience in Cooperation with Max Planck Society (ESI) (1)
- Eurac Research (1)
- Eurac Research – Istituto per lo sviluppo regionale (1)
- European Molecular Biology Laboratory, Heidelberg, Germany (1)
- European Space Agency (1)
- Evangelisches Studienwerk e.V. (1)
- Experimental Physics V, University of Wuerzburg (1)
- Experimental Radiation Oncology, Department of Radiation Oncology, University Medical Center Mannheim (1)
- Experimentelle Tumorimmunologie, Frauenklinik, Universität Würzburg (1)
- Expertenkreis zur Erarbeitung eines Stufenplans zur Diagnose und Therapie von Angsterkrankungen (1)
- FHNW Hochschule für Musik / Schola Cantorum Basiliensis (1)
- Fachbereich Physik, Universität Konstanz, D-78464 Konstanz, Germany (1)
- Fachgebiet für Populationsgenomik bei Nutztieren, Universität Hohenheim (1)
- Fachhochschule Kaiserslautern, Campus Zweibrücken (1)
- Fakultät für Chemie und chemische Biologie, Technische Universität Dortmund (1)
- Fakultät für Physik, Universität Bielefeld (1)
- Federazione Italiana Parchi e Riserve Naturali (Federparchi) (1)
- Forschungsstation Fabrikschleichach (1)
- Forschungsverbund ForChange des Bayrischen Kultusministeriums (1)
- Fraunhofer (1)
- Fraunhofer IGB - Institutsteil Würzburg Translationszentrum Regenerative Therapien für Krebs- und Muskuloskelettale Erkrankungen (1)
- Fraunhofer IGB Stuttgart (1)
- Fraunhofer IOF (1)
- Fraunhofer Insitut für Silicatforschung ISC (1)
- Fraunhofer Institut für Integrierte Schaltungen (IIS) (1)
- Fraunhofer Institut für Silicatforschung (Würzburg) (1)
- Fraunhofer Institute Interfacial Engineering and Biotechnology (IGB) (1)
- Fraunhofer Institute for Integrierte Schaltungen (IIS) (1)
- Fraunhofer Institute for Silicate Research ISC in Würzburg (1)
- Fraunhofer-Institut Würzburg (1)
- Fraunhofer-Institut für Chemische Technologie (ICT) (1)
- Fraunhofer-Institut für Silcatforschung ISC in Würzburg (1)
- Fraunhofer-Institut für Silicatforschung (ISC) in Würzburg (1)
- Fraunhofer-Institut für Silicatforschung, Würzburg (1)
- Fraunhofer-Institute for Applied Optics and Precision Engineering IOF Jena, Germany (1)
- Fraunhofer-Institute for Silicate Research ISC (1)
- Friedrich Schiller University Jena, Germany (1)
- Friedrich-Schiller-Universität Jena (1)
- GEOMAR Helmholtz-Zentrum für Ozeanforschung Kiel (1)
- Genelux Corporation, San Diego Science Center, 3030 Bunker Hill Street, Suite 310, San Diego, California 92109, USA (1)
- Geographisches Institut (Humboldt Universität zu Berlin) (1)
- Geographisches Institut (Universität zu Köln) (1)
- Geographisches Institut der Universität zu Köln (1)
- Geographisches Institut, Johannes Gutenberg-Universität Mainz (1)
- Georg August University School of Science (1)
- Goethe-Universität Frankfurt (1)
- Göttingen Center for Molecular Biosciences, Georg- August University Göttingen, Göttingen 37077, Germany (1)
- Göttingen Center for Molecular Biosciences, University of Göttingen (1)
- Hans-Knöll-Institut Jena (1)
- Harvard Medical School, Boston, USA (1)
- Heimatmuseum Ebern (1)
- Helmholtz Center for RNA-based Infection Research (1)
- Helmholtz Institut für RNA-basierte Infektionsforschung (1)
- Helmholtz Institute for RNA-based Infection Biology (HIRI), Josef-Schneider-Straße 2/D15, DE-9708 Wuerzburg, Germany (1)
- Helmholtz Institute for RNA-based Infection Biology (HIRI), Josef-Schneider-Straße 2/D15, DE-97080 Wuerzburg, Germany (1)
- Helmholtz Institute for RNA-based Infection Research (1)
- Helmholtz-Institut für RNA-basierte Infektionsforschung (1)
- Hochschule Wismar (1)
- Hochschule für angewandte Wissenschaften München, Fakultät für Tourismus (1)
- Hospital Augsburg, Augsburg, Germany (1)
- IBMP - Institut für Biomedizinische und Pharmazeutische Forschung in Nürnberg-Heroldsberg (1)
- IFT Institut für Therapieforschung München (1)
- INAF Padova, Italy (1)
- IZKF (Interdisziplinäres Zentrum für Klinische Forschung), Universität Würzburg (1)
- IZKF Laboratory for Microarray Applications, University Hospital of Wuerzburg, Wuerzburg, Germany (1)
- IZKF Research Laboratory Dept. Medicine II & Pediatrics (1)
- IZKF Universität Würzburg (1)
- Institut Ruđer Bošković, Zagreb, Croatia (1)
- Institut für Biopsychologie, Universität Dresden (1)
- Institut für Diagnostische und Interventionelle Radiologie des Universitätsklinikums Würzburg (1)
- Institut für Evangelische Theologie und Religionspädagogik (1)
- Institut für Humangeographie, Goethe-Universität Frankfurt am Main (1)
- Institut für Hygiene und Mikrobiologie (1)
- Institut für Klinische Epidemiologie und Biometrie des Universitätsklinikums Würzburg (1)
- Institut für Medizinische Lehre und Ausbildungsforschung, Universität Würzburg (1)
- Institut für Medizinische Mikrobiologie in Göttingen (1)
- Institut für Medizinische Mikrobiologie und Hygiene der Eberhard-Karls-Universität Tübingen (1)
- Institut für Medizintechnik Schweinfurt (IMeS) (1)
- Institut für Mikrobiologie, Universität Göttingen (1)
- Institut für Molekulare Infektionsbiologie (MIB) der Universität Würzburg (1)
- Institut für Musikphysiologie und Musiker-Medizin der Hochschule für Musik, Theater und Medien, Hannover (1)
- Institut für Neurowissenschaften der Universität Mailand (1)
- Institut für Organische Chemie, RWTH Aachen (1)
- Institut für Pathologie, Universität Würzburg (1)
- Institut für Ur- und Frühgeschichtiche Archäologie und Vorderasiatische Archäologie der Universität Heidelberg (1)
- Institut für diagnostische und interventionelle Radiologie, Klinikum Ingolstadt (1)
- Institut für klinische Neurobiologie (1)
- Institute for Biochemistry I, University of Cologne (1)
- Institute for Sustainable Chemistry & Catalysis with Boron (1)
- Institute of Cancer Research (ICR) London (1)
- Institute of Organic Chemistry and Center for Molecular Biosciences Innsbruck, CMBI, Leopold-Franzens University Innsbruck, Austria (1)
- Institute of Physics and Center for Nanotechnology, University of Münster (1)
- Institute of Transformative Bio-Molecules, Nagoya University, Nagoya, Japan (1)
- Instituto de Higiene, Universidad de la República, Montevideo, Uruguay (1)
- Instituto de Hygiene Montevideo, Uruguay (1)
- Interdisciplinary Bank of Biological Material and Data Würzburg (IBDW) (1)
- Interdisciplinary Center for Clinical Research (IZKF), Würzburg, Germany (1)
- Interdisziplinäre Biomaterial- und Datenbank Würzburg (ibdw) (1)
- Interdisziplinäre Zentrum für Klinische Forschung (IZKF) (1)
- Interdisziplinäres Zentrum für Klinische Forschung (IZKF) Würzburg (1)
- Interdisziplinäres Zentrum für Klinische Forschung (ZIKF), Würzburg (1)
- International Society for Nutritional Psychiatric Research (1)
- Istituto di Chimica dei Composti Organometallici (ICCOM–CNR), Area della Ricerca del CNR, Via Moruzzi 1, I-56124 Pisa, Italy. (1)
- Istituto di Salisburgo per la pianificazione regionale e le abitazioni (SIR) (1)
- Istituto di pianificazione urbana della Repubblica di Slovenia (UIRS) (1)
- Jacobs University Bremen, Germany (1)
- Johns Hopkins Medicine (1)
- Johns Hopkins School of Medicine, Baltimore, MD, USA (1)
- Johns Hopkins University School of Medicine, Baltimore, MD, U.S. (1)
- Johns Hopkins University, Baltimore, MD, U.S. (1)
- Johns Hopkis School of Medicine (1)
- Joslin Diabetes Center, Harvard Medical School (1)
- Julius-Maximilians-Universität Würzburg (JMU), Department of English and American Studies (1)
- Julius-von-Sachs-Institut für Biowissenschaften Lehrstuhl für Botanik II - Ökophysiologie und Vegetationsökologie (1)
- Juliusspital, Würzburg (1)
- Kardiologie (Klinik für Innere Medizin I) (1)
- KfH Nierenzentrum (1)
- Kinderklinik Bad Mergentheim (1)
- Klinik für Anästhesiologie, Universität Mainz (1)
- Klinik für Handchirurgie Bad Neustadt a.d. Saale (1)
- Klinik für Handchirurgie Bad Neustadt an der Saale (1)
- Klinik für Handchirurgie Bad Neustadt, Rhön-Klinikum, Bad Neustadt a.d. Saale (1)
- Klinik für Handchirurgie Rhön-Klinikum Campus Bad Neustadt (1)
- Klinik für Handchirurgie des Rhön-Klinikums Bad Neustadt an der Saale (1)
- Klinik für Handchirurgie, Rhön Klinikum Campus Bad Neustadt (1)
- Klinik für Kardiologie und Angiologie der Medizinischen Hochschule Hannover (1)
- Klinik für Kinder- und Jugendmedizin, Caritas-Krankenhaus Bad Mergentheim (1)
- Klinik für Kinder- und Jugendpsychiatrie, Psychosomatik und Psychotherapie des Leopoldina Krankenhaus Schweinfurt (1)
- Klinik für Psychiatrie und Psychotherapie, Universität Würzburg (1)
- Klinik für Transfusionsmedizin (1)
- Klinik für Tropenmedizin am Klinikum Würzburg Mitte gGmbH (1)
- Klinik und Poliklinik für Anästhesiologie, Intensivmedizin, Notfallmedizin und Schmerztherapie des Universitätsklinikums Würzburg (1)
- Klinikum Aschaffenburg-Alzenau (1)
- Klinikum Fulda gAG (1)
- Klinikum Main-Spessart Lohr (1)
- Klinikum Würzburg Mitte (Akademisches Lehrkrankenhaus der Uni Würzburg) (1)
- Klinische Mikrobiologie am Universitätsklinikum Erlangen (1)
- Kreisarchäologie Straubing-Bogen (1)
- König Ludwig Haus Würzburg (1)
- König Ludwig Haus, Würzburg (1)
- König-Ludwig Haus (1)
- König-Ludwig-Haus, Orthopedic Clinic, Würzburg (1)
- LIDYL, CEA, CNRS, Université Paris-Saclay, CEA Saclay 91191 Gif-sur-Yvette France (1)
- LMU München (1)
- La rete di aree protette alpine (ALPARC) (1)
- Lehrkrankenhaus der Universität Würzburg: Klinikum Main-Spessart (1)
- Lehrstuhl für Anorganische Chemie I, Universität Bayreuth (1)
- Lehrstuhl für BioMolekulare Optik, Ludwig-Maximilians-Universität München (1)
- Lehrstuhl für Biochemie und molekulare Biologie (1)
- Lehrstuhl für Bioinformatik (1)
- Lehrstuhl für Biotechniologie und Biophysik am Biozentrum der Universität Würzburg (1)
- Lehrstuhl für Chemie, Brooklyn College, City University of New York, Brooklyn (1)
- Lehrstuhl für Europäische Ethnologie/Volkskunde der Julius-Maximilians-Universität Würzburg (1)
- Lehrstuhl für Fernerkundung der Uni Würzburg, in Kooperation mit dem Deutschen Fernerkundungsdatenzentrum (DFD) des Deutschen Zentrums für Luft- und Raumfahrt (DLR) (1)
- Lehrstuhl für Immunologie, Würzburg (1)
- Lehrstuhl für Physiologische Chemie (1)
- Lehrstuhl für Regeneration Muskuloskelettaler Gewebe (1)
- Lehrstuhl für Röntgenmikroskopie (1)
- Lehrstuhl für Tierökologie und Tropenbiologie, Universität Würzburg (1)
- Lehrstuhl für Tissue Engineering und Regenerative Medizin (TERM) (1)
- Lehrstuhl für Tissue Engineering und Regenerative Medizin der Universität Würzburg (1)
- Lehrstuhl für Translationale Onkologie (1)
- Leibniz-Institut für Analytische Wissenschaften - ISAS - e.V. (1)
- Leibniz-Institut für Katalyse Rostock (1)
- Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie Hans-Knöll-Institut (1)
- Leuphana Universität Lüneburg (1)
- Ludwig-Maximilians-Universität München, Fakultät für Physik (1)
- MRB Forschungszentrum für Magnet-Resonanz-Bayern e.V., Am Hubland, D-97074 Würzburg (1)
- MRB Research Center for Magnetic-Resonance-Bavaria (1)
- Maastricht University, Department of Psychiatry and Neuropsychology (1)
- Maastricht University, Maastricht, the Netherlands (1)
- Mathematical Institute, Czech Academy of Sciences (1)
- Max Delbrück Center for Molecular Medicine (1)
- Max Planck Institute for Biophysical Chemistry (1)
- Max Planck Institute for Biophysical Chemistry, Am Faßberg 11, DE-37077 Goetingen, Germany (1)
- Max Planck Institute for Biophysical Chemistry, Department of Molecular Biology, Göttingen (1)
- Max Planck Institute for Biophysical Chemistry, Research Group Structure and Function of Molecular Machines, Göttingen (1)
- Max Planck School of Photonics Jena, Germany (1)
- Max-Delbrück-Center für molekulare Medizin, Berlin (1)
- Max-Planck Institute for Biophysical Chemistry, Department of Molecular Biology, Göttingen (1)
- Medizinische Hochschule Hannover, Kardiologie (1)
- Medizinische Klinik II des Klinikums Aschaffenburg - Alzenau (1)
- Medizinische Klinik und Poliklinik 1, Abteilung Kardiologie (1)
- Medizinische Klinik und Poliklinik 1, Abteilung Nephrologie (1)
- Medizinische Universität Innsbruck (1)
- Medizinischen Klinik II des Klinikums Aschaffenburg, Prof. Dr. med. W. Fischbach (1)
- Mediävistenverband (1)
- Michigan State University (1)
- Microarray Core Unit, Interdisciplinary Center for Clinical Science, University of Würzburg, Versbacher Straße, Würzburg 97080, Germany (1)
- Microarray Core Unit, Universität Würzburg (1)
- Ministeriums für Schule und Weiterbildung des Landes Nordrhein-Westfalen (1)
- Missionsärztliches Institut (MI); Catholic University of Health and Allied Sciences Mwanza, Tansania (CUHAS); Medizinische Virologie der Stellenboschuniversität, Südafrika (1)
- Missionsärztliches Institut Würzburg (1)
- Molecular Nutrition Research, Interdisciplinary Research Center, Justus-Liebig-University of Giessen (1)
- Museum am Dom (1)
- Muskuloskelettalen Zentrum Würzburg (MCW) (1)
- Muskuloskelettales Centrum Würzburg (MCW) (1)
- Märkisches Klinikum Lüdenscheid (1)
- NanoOptics & Biophotonics Group, Experimental Physics 5, Universität Würzburg (1)
- National Cardiovascular and Cerebral Center, Suita, Japan (1)
- National Institute for Materials Science, Tsukuba, Japan (1)
- National Park "Bavarian Forest" (1)
- Nationales Referenzzentrum für Invasive Pilzinfektionen (NRZMyk) (1)
- Nationales Referenzzentrum für invasive Pilzinfektionen (1)
- Neurologische Klinik, Klinikum Ingolstadt (1)
- Neurologische Klinik, Universitätsklinikum Würzburg (1)
- New York Blood Center (1)
- Novartis AG (1)
- Novartis Pharma AG, Lichtstrasse 35, CH-4056 Basel, Switzerland (1)
- Novartis Pharma AG, Switzerland (1)
- OTH Regensburg (1)
- Opel Automobile GmbH (1)
- Orthopädische Klinik König-Ludwig-Haus Würzburg (1)
- Orthopädische Klinik und Poliklinik "König-Ludwig-Haus" der Uni Würzburg (1)
- Ostbayerische Technische Hochschule Regensburg (1)
- Paul Scherrer Institut (1)
- Paul-Scherrer-Institut, Villigen, CH (1)
- Pharmacology, University of Stellenbosch, South Africa (1)
- Pharmakologie, Universität Bonn (1)
- Pharmazie, Universität Mailand (1)
- Physiologisches Institut Universität Würzburg (1)
- Politecnico di Milano (1)
- Professional School of Education (1)
- Professur für Mueologie der Julius-Maximilians-Universität Würzburg (1)
- Professur für Museologie der JMU (1)
- Queensland University of Technology (1)
- Radiologie (1)
- Research Center for Infectious Diseases (ZINF), University of Wuerzburg, Wuerzburg, Germany, (1)
- Research Center for Infectious Diseases (ZINF), University of Würzburg, Würzburg, Germany (1)
- Research Center for Infectious Diseases, University of Wuerzburg, Wuerzburg 97080, Germany (1)
- Research Center for Infectious Diseases, University of Würzburg (1)
- Research Center for Magnetic-Resonance-Bavaria (MRB), Wuerzburg, Germany (1)
- Research Center of Infectious Diseases (ZINF) of the University of Wurzburg, Germany (1)
- Rhön-Klinikum Campus Bad Neustadt (1)
- Rhön-Klinikum Campus Bad Neustadt an der Saale, Klinik für Handchirurgie (1)
- Roche Diagnostics GmbH Penzberg (1)
- Rudolf-Virchow-Zentrum DFG-Forschungszentrum für Experimentelle Biomedizin der Universität Würzburg (1)
- Rudolf-Virchow-Zentrum für Experimentelle Biomedizin der Universität Würzburg (1)
- Röntgen Research Center for Complex Material Systems, Hubland Campus Nord, Emil-Fischer-Straße 42, D-97074 Würzburg, Germany (1)
- SKZ – Das Kunststoff-Zentrum (1)
- Sahin Lab, F.M. Kirby Neurobiology Center Boston Children’s Hospital, Department of Neurology, Harvard Medical School (1)
- Salzburger Institut für Raumordnung und Wohnen (1)
- Schifffahrtmedizinisches Institut der Marine (1)
- Service Centre InterNational Transfer (Universität Würzburg) (1)
- Servicezentrum Medizin-Informatik (1)
- Servicezentrum Medizin-Informatik (Universitätsklinikum) (1)
- Siemens Corporate Technology Munich (1)
- Siemens Corporate Technology, Erlangen (1)
- Social and Technological Systems (SaTS) lab, School of Art, Media, Performance and Design, York University, Toronto, Canada (1)
- Sonderforschungsbereich Re-Figuration von Räumen (Technische Universität Berlin) (1)
- South African National Biodiversity Institute (SANBI) (1)
- Spanish National Center for Biotechnology (CNB-CSIC) (1)
- Spectral Service AG (1)
- Sportzentrum der Universität Würzburg (1)
- Stanford University (1)
- Stellenbosch University - Division of Medical Virology (1)
- Synchrotron SOLEIL, Gif-sur-Yvette (1)
- TH Köln (1)
- Tanzania Food and Drugs Authority (1)
- Technical University of Denmark (1)
- Technische Hochschule Wildau (1)
- Technische Hochschule Würzburg-Schweinfurt, Fakultät Angewandte Sozialwissenschaften (1)
- Technische Universität Darmstadt (1)
- Technische Universität Dortmund, Fakultät für Informatik, Computer Graphics Group (1)
- Technische Universität Dresden (1)
- Technische Universität München (1)
- Tecnologico de Monterrey (1)
- The Chinese University of Hong Kong (1)
- The University of Sussex (1)
- The project was founded by IZKF (1)
- Translationale soziale Neurowissenschaften (1)
- Tropenmedizin, Klinikum Würzburg Mitte gGmbH, Missioklinik (1)
- Tropenmedizinische Abteilung der Missionsärztlichen Klinik Würzburg (Lehrkrankenhaus der Univ. Würzbug) (1)
- Tropenmedizinische Abteilung der Missionärztlichen Klinik (1)
- Universidade de São Paulo, Programa de Pós-Graduação em Letras Clássicas, São Paulo, Brasil (1)
- University Medical Center Göttingen, Department of Cellular Biochemistry, Göttingen (1)
- University of Applied Sciences Aschaffenburg (1)
- University of Applied Sciences Potsdam (1)
- University of Applied Sciences and Arts Western Switzerland, Fribourg (1)
- University of Bari Medical School, Bari, Italy (1)
- University of Birmingham, Medical School, Institute of Biomedical Research (1)
- University of Cologne (1)
- University of Duisburg-Essen (1)
- University of Iceland (Human Behaviour Laboratory) (1)
- University of Leipzig, Faculty of Life Sciences, Institute for Biology (1)
- University of Oldenburg, Germany (1)
- University of Padova, Italy (1)
- University of Santa Cruz do Sul, Brazil (1)
- University of Science and Technology of China, Hefei, China (1)
- University of Stellenbosch, Division of Medical Virology (1)
- University of Twente (The Netherlands) (1)
- Universität Bielefeld (1)
- Universität Duisburg-Essen, Institut für Molekularbiologie, AG Becker-Flegler (1)
- Universität Erlangen, Institut für Geschichte und Ethik der Medizin (1)
- Universität Göttingen (1)
- Universität Hamburg (1)
- Universität Jaén (1)
- Universität Jena (1)
- Universität Kassel, Fachbereich Gesellschaftswissenschaften, Mittelalterliche Geschichte (1)
- Universität Salzburg, Fachbereich Germanistik (1)
- Universität Würzburg GmbH für Bildungs- und Campusdienstleistungen (1)
- Universitätsklinikum Düsseldorf, Institut für Toxikologie (1)
- Universitätsklinikum Würzburg (UKW) (1)
- Universitätsklinkium Magdeburg (1)
- Université Paris I Panthéon-Sorbonne (1)
- Université d'Abomey-Calavi, Benin (1)
- Université de Bordeaux, Bordeaux, France (1)
- Université de Montréal (1)
- Université de Paris-Saclay (1)
- Urbanistični inštitut Republike Slovenije (1)
- VIGEA, Italy (1)
- Wilhelm Conrad Röntgen-Center for Complex Material Systems, Würzburg (1)
- Women Writers Project (1)
- Wurzburg Fabry Center for Interdisciplinary Therapy (FAZIT), Wurzburg, Germany (1)
- Würzburg Fabry Center for Interdisciplinary Therapy (FAZIT), University of Würzburg, Würzburg, Germany (1)
- Würzburger Institut für Verkehrswissenschaften (WIVW GmbH) (1)
- ZINF Research Center for Infectious Diseases (1)
- Zahnmedizin (1)
- Zentrale Abteilung für Mikroskopie, Universität Würzburg (1)
- Zentrum für Infektionsforschung (ZINF): Nachwuchsgruppe 2 (1)
- Zentrum für Infektionsforschung ZINF Würzburg (1)
- Zentrum für Infektionsforschung, Universität Würzburg (1)
- Zentrum für Innere Medizin I, Städtisches Klinikum Brandenburg GmbH, Hochschulklinikum der MHB Theodor Fontane (1)
- Zentrum für Interdisziplinäre Medizin der Uni Würzburg (1)
- Zentrum für Lehrerbildung und Bildungsforschung der JMU (1)
- Zentrum für Luft- und Raumfahrtmedizin der Luftwaffe (1)
- Zentrum für Soziale Implikationen künstlicher Intelligenz (SOCAI) (1)
- Zentrum für experimentelle und molekulare Medizin (Würzburg) (1)
- Zentrum für soziale Implikationen künstlicher Intelligenz (SOCAI) (1)
- Zentrum für vorsprachliche Entwicklung und Entwicklungsstörungen (1)
- Zentrum für vorsprachliche Entwicklung und Entwicklungsstörungen (ZVES) (1)
- eXcorLab GmbH (1)
- http://www.bsb-muenchen.de (1)
- iDiv (1)
- École Pratique des Hautes Études - PSL, Paris (1)
- Ökologische Station, Fabrikschleichach (1)
ResearcherID
- B-1911-2015 (1)
- B-4606-2017 (1)
- C-2593-2016 (1)
- D-1221-2009 (1)
- D-1250-2010 (1)
- D-3057-2014 (1)
- I-5818-2014 (1)
- J-8841-2015 (1)
- M-1240-2017 (1)
- N-2030-2015 (1)
We study the influence of nodal structures in two-dimensional quantum mechanical densities on wave packet entanglement. This is motivated by our recent study [Entropy, 25, 970 (2023)], which showed that the mutual information derived from the momentum-space probability density of a coupled two-particle system exhibits an unusual time dependence, which is not encountered if the position-space density is employed in the calculation. In studying a model density, here, we identify cases where the mutual information increases with the number of nodes in the wave function and approaches a finite value, whereas in this limit, the linear correlation vanishes. The results of the analytical model are then applied to interpret the correlation measures for coupled electron-nuclear dynamics, which are treated by numerically solving the time-dependent Schrödinger equation.
In DNA-encoded library synthesis, amine-substituted building blocks are prevalent. We explored isocyanide multicomponent reactions to diversify DNA-tagged amines and reported the Ugi-azide reaction with high yields and a good substrate scope. In addition, the Ugi-aza-Wittig reaction and the Ugi-4-center-3-component reaction, which used bifunctional carboxylic acids to provide lactams, were explored. Five-, six-, and seven-membered lactams were synthesized from solid support-coupled DNA-tagged amines and bifunctional building blocks, providing access to structurally diverse scaffolds.
The binding of drugs to plasma proteins is an important process in the human body and has a significant influence on pharmacokinetic parameter. Human serum albumin (HSA) has the most important function as a transporter protein. The binding of ketamine to HSA has already been described in literature, but only of the racemate. The enantiomerically pure S-ketamine is used as injection solution for induction of anesthesia and has been approved by the Food and Drug Administration for the therapy of severe depression as a nasal spray in 2019. The question arises if there is enantioselective binding to HSA. Hence, the aim of this study was to investigate whether there is enantioselective binding of S-and R-ketamine to HSA or not. Ultrafiltration (UF) followed by chiral capillary electrophoretic analysis was used to determine the extent of protein binding. Bound fraction to HSA was 71.2 % and 64.9 % for enantiomerically pure R- and S-ketamine, respectively, and 66.5 % for the racemate. Detailed binding properties were studied by Saturation Transfer Difference (STD)-, waterLOGSY- and Carr-Purcell-Meiboom-Gill (CPMG)-NMR spectroscopy. With all three methods, the aromatic ring and the N-methyl group could be identified as the structural moieties most strongly involved in binding of ketamine to HSA. pK\(_{aff}\) values determined using UF and NMR indicate that ketamine is a weak affinity ligand to HSA and no significant differences in binding behavior were found between the individual enantiomers and the racemate.
The hallmark oncoprotein Myc is a major driver of tumorigenesis in various human cancer entities. However, Myc’s structural features make it challenging to develop small molecules against it. A promising strategy to indirectly inhibit the function of Myc is by targeting its interactors. Many Myc-interacting proteins have reported scaffolding functions which are difficult to target using conventional occupancy- driven inhibitors. Thus, in this thesis, the proteolysis targeting chimera (PROTAC) approach was used to target two oncoproteins interacting with Myc which promote the oncogenicity of Myc, Aurora-A and WDR5. PROTACs are bifunctional small molecules that bind to the target protein with one ligand and recruit a cellular E3- ligase with the other ligand to induce target degradation via the ubiquitin- proteasome system. So far, the most widely used E3-ligases for PROTAC development are Cereblon (CRBN) and von Hippel–Lindau tumor suppressor (VHL). Furthermore, there are cases of incompatibility between some E3-ligases and proteins to bring about degradation. Hence there is a need to explore new E3- ligases and a demand for a tool to predict degradative E3-ligases for the target protein in the PROTAC field.
In the first part, a highly specific mitotic kinase Aurora-A degrader, JB170, was developed. This compound utilized Aurora-A inhibitor alisertib as the target ligand and thalidomide as the E3-ligase CRBN harness. The specificity of JB170 and the ternary complex formation was supported by the interactions between Aurora-A and CRBN. The PROTAC-mediated degradation of Aurora-A induced a distinct S- phase defect rather than mitotic arrest, shown by its catalytic inhibition. The finding demonstrates that Aurora-A has a non-catalytic role in the S-phase. Furthermore, the degradation of Aurora-A led to apoptosis in various cancer cell lines.
In the second part, two different series of WDR5 PROTACs based on two protein- protein inhibitors of WDR5 were evaluated. The most efficient degraders from both series recruited VHL as a E3-ligase and showed partial degradation of WDR5. In addition, the degradation efficiency of the PROTACs was significantly affected by the linker nature and length, highlighting the importance of linker length and composition in PROTAC design. The degraders showed modest proliferation defects at best in cancer cell lines. However, overexpression of VHL increased the degradation efficiency and the antiproliferative effect of the PROTACs.
In the last part, a rapamycin-based assay was developed to predict the degradative E3-ligase for a target. The assay was validated using the WDR5/VHL and Aurora- A/CRBN pairs. The result that WDR5 is degraded by VHL but not CRBN and Aurora-A is degraded by CRBN, matches observations made with PROTACs. This technique will be used in the future to find effective tissue-specific and essential E3-ligases for targeted degradation of oncoproteins using PROTACs.
Collectively, the work presented here provides a strategy to improve PROTAC development and a starting point for developing Aurora-A and WDR5 PROTACs for cancer therapy.
1,1,2-trifluoroethene (HFO-1123) is intended for use as a refrigerant. Inhalation studies on HFO-1123 in rats suggested a low potential for toxicity, with no-observed-adverse-effect levels greater then 20,000 ppm. However, single inhalation exposure of Goettingen Minipigs and New Zealand White Rabbits resulted in mortality. It was assumed that conjugation of HFO-1123 with glutathione, via glutathione S-transferase, gives rise to S-(1,1,2-trifluoroethyl)-L-glutathione (1123-GSH), which is then transformed to the corresponding cysteine S-conjugate (S-(1,1,2-trifluoroethyl)-L-cysteine, 1123-CYS). Subsequent beta-lyase mediated cleavage of 1123-CYS may result in monofluoroacetic acid, a potent inhibitor of aconitase. Species-differences in 1123-GSH formation and 1123-CYS cleavage to MFA may explain species-differences in HFO-1123 toxicity.
This study was designed to test the hypothesis, that GSH-dependent biotransformation and subsequent beta-lyase mediated formation of monofluoroacetic acid, a potent inhibitor of aconitase in the citric acid cycle, may play a key role in HFO-1123 toxicity and to evaluate if species-differences in the extent of MFA formation may account for the species-differences in HFO-1123 toxicity. The overall objective was to determine species-differences in HFO-1123 biotransformation in susceptible vs. less susceptible species and humans as a basis for human risk assessment.
To this end, in vitro biotransformation of HFO-1123 and 1123-CYS was investigated in renal and hepatic subcellular fractions of mice, rats, humans, Goettingen Minipigs and NZW Rabbits. Furthermore, cytotoxicity and metabolism of 1123-CYS was assessed in cultured renal epithelial cells. Enzyme kinetic parameters for beta-lyase mediated cleavage of 1123-CYS in renal and hepatic cytosolic fractions were determined, and 19F-NMR was used to identify fluorine containing metabolites arising from 1123-CYS cleavage. Quantification of 1123-GSH formation in hepatic S9 fractions after incubation with HFO-1123 was performed by LC-MS/MS and hepatic metabolism of HFO-1123 was monitored by 19F-NMR.
Rates of 1123-GSH formation were increased in rat, mouse and NZW Rabbit compared to human and Goettingen hepatic S9, indicating increased GSH dependent biotransformation in rats, mouse and NZW Rabbits. NZW Rabbit hepatic S9 exhibited increased 1123-GSH formation in the presence compared to the absence of acivicin, a specific gamma-GT inhibitor. This indicates increased gamma-GT mediated cleavage of 1123-GSH in NZW Rabbit hepatic S9 compared to the other species. 19F-NMR confirmed formation of 1123-GSH as the main metabolite of GSH mediated biotransformation of HFO-1123 in hepatic S9 fractions next to F-. Increased F- formation was detected in NZW Rabbit and Goettingen Minipig hepatic S9 in the presence of an NADPH regenerating system, indicating a higher rate of CYP-450 mediated metabolism in these species. Based on these findings, it is possible that CYP-450 mediated metabolism may contribute to HFO-1123 toxicity.
In contrast to the increased formation of 1123-GSH in rat, mouse and NZW Rabbit hepatic S9 (compared to human and Goettingen Minipig), enzyme kinetic studies revealed a significantly higher beta-lyase activity towards 1123-CYS in renal cytosol of Goettingen Minipigs compared to cytosol from rats, mice, humans and NZW Rabbits. However, beta-lyase cleavage in renal NZW Rabbit cytosol was slightly increased compared to rat, mouse and human renal cytosols. 19F-NMR analysis confirmed increased time-dependent formation of MFA in renal Goettingen Minipig cytosol and NZW Rabbit (compared to human and rat cytosolic fractions). Three structurally not defined MFA-derivatives were detected exclusively in NZW Rabbit and Goettingen Minipig cytosols. Also, porcine kidney cells were more sensitive to cytotoxicity of 1123-CYS compared to rat and human kidney cells.
Overall, increased beta-lyase mediate cleavage of 1123-CYS to MFA in Goettingen Minipig and NZW Rabbit kidney (compared to human and rat) may support the hypothesis that enzymatic cleavage by beta-lyases may account for the species-differences in HFO-1123 toxicity. However, the extent of GST mediated biotransformation in the liver as the initial step in HFO-1123 metabolism does not fully agree with this hypothesis, since 1123-GSH formation occurs at higher rates in rat, mouse and NZW Rabbit S9 as compared to the Goettingen Minipig.
Based on the inconsistencies between the extent of GST and beta-lyase mediated biotransformation of HFO-1123 obtained by this study, a decisive statement about an increased biotransformation of HFO-1123 in susceptible species with a direct linkage to the species-specific toxicity cannot be drawn. Resulting from this, a clear and reliable conclusion regarding the risk for human health originating from HFO-1123 cannot be made. However, considering the death of Goettingen Minipigs and NZW Rabbits after inhalation exposure of HFO-1123 at concentrations great than 500 ppm and greater than 1250 ppm, respectively, this indicates a health concern for humans under peak exposure conditions. For a successful registration of HFO-1123 and its use as a refrigerant, further in vitro and in vivo investigations addressing uncertainties in the species-specific toxicity of HFO-1123 are urgently needed.
Darf es etwas mehr sein? Neuroenhancement im Studium – eine Befragung an Würzburger Hochschulen
(2024)
Neuroenhancement (NE) bezeichnet die Einnahme psychotroper Substanzen mit dem Ziel der geistigen Leistungssteigerung oder Beruhigung. NE wird durch gesunde Perso- nen genutzt. Es besteht somit keine Indikation zur Einnahme psychotroper Wirkstoffe. Zum NE genutzte Substanzen sind z.B. Koffeintabletten, verschreibungspflichtige Medi- kamente oder illegale Substanzen. Die bisherige Forschung findet Hinweise auf einen Zusammenhang zwischen NE und ADHS-Symptomen, einigen Aspekten psychischer Gesundheit, sowie Substanzkonsum. Bisher gibt es keine Forschung zu NE am Hoch- schulstandort Würzburg.
Es wurde eine anonyme online Querschnittsbefragung im ersten Quartal 2021 durchge- führt. Eingeladen waren 5600 Studierende der Julius-Maximilians-Universität Würzburg und der Hochschule für angewandte Wissenschaften Würzburg Schweinfurt. Der Frage- bogen bestand aus 53 Items und enthielt u. a. die folgenden validierten Messinstrumente: ASRS, PSS-10, PHQ-4 und AUDIT-C.
Die Response Rate lag bei 18% (n = 1011). Das Wissen über NE war weit unter den Stu- dierenden verbreitet. Die Prävalenz für Neuroenhancement im Studium lag bei 12.7%. Die drei meistgenannten Substanzen waren Koffeintabletten (6.6%), Cannabis (4.5%) und Methylphenidat (4.3%). Häufigster Anlass für NE war die Prüfungsvorbereitung. Es zeigten sich deutliche Unterschiede zwischen den Fachbereichen, u.a. hinsichtlich der Prävalenz von NE. ADHS-Symptomen, Stress, Ängstlichkeit, und Depressivität waren positiv mit NE assoziiert. Ein stärkerer Effekt ergab sich für den Zusammenhang zwi- schen NE und riskanten Alkoholkonsum bzw. Tabakkonsum. Diese Ergebnisse wurden durch eine binomial logistische Regression bestätigt.
Die konsumierten Substanzen, das Wissen über NE, die Prävalenz von NE und die Gründe für dessen Nutzung fügen sich nahtlos in die bisherige Forschung ein. Auch die Assoziation zwischen ADHS-Symptomen, Stress, Ängstlichkeit, Depressivität, riskan- tem Alkoholkonsum und Tabakkonsum bestätigt bisherige Forschungsergebnisse.
Es konnte gezeigt werden, dass rund ein Zehntel der Studierenden NE bereits genutzt haben. In Anbetracht der gesundheitlichen Gefahren, die mit NE einhergehen ist die Etab- lierung bzw. der Ausbau von Aufklärung-, Beratungs- und Hilfsangeboten für Studie- rende anzustreben sowie weitere Forschung zum Thema indiziert.
DNA alkyltransferase and alkyltransferase-like family proteins are responsible for the repair of highly mutagenic and cytotoxic O\(^6\)-alkylguanine and O\(^4\)-alkylthymine bases in DNA. Their mechanism involves binding to the damaged DNA and flipping the base out of the DNA helix into the active site pocket in the protein. Alkyltransferases then directly and irreversibly transfer the alkyl group from the base to the active site cysteine residue. In contrast, alkyltransferase-like proteins recruit nucleotide excision repair components for O\(^6\)-alkylguanine elimination. One or more of these proteins are found in all kingdoms of life, and where this has been determined, their overall DNA repair mechanism is strictly conserved between organisms. Nevertheless, between species, subtle as well as more extensive differences that affect target lesion preferences and/or introduce additional protein functions have evolved. Examining these differences and their functional consequences is intricately entwined with understanding the details of their DNA repair mechanism(s) and their biological roles. In this review, we will present and discuss various aspects of the current status of knowledge on this intriguing protein family.
Highlights
• Synthesis of a new tracer molecule.
• Robust and easy screening method for a broad range of compound activities.
• FP assay validation considering limited use of starting material, DMSO tolerance, variation in incubation time and temperature.
• Possibility of extension to HTP assay.
Abstract
The macrophage infectivity potentiator (Mip) protein belongs to the immunophilin superfamily. This class of enzymes catalyzes the interconversion between the cis and trans configuration of proline-containing peptide bonds. Mip has been shown to be important for the virulence of a wide range of pathogenic microorganisms, including the Gram-negative bacterium Burkholderia pseudomallei. Small molecules derived from the natural product rapamycin, lacking its immunosuppression-inducing moiety, inhibit Mip's peptidyl-prolyl cis-trans isomerase (PPIase) activity and lead to a reduction in pathogen load in vitro. Here, a fluorescence polarization assay (FPA) to enable the screening and effective development of BpMip inhibitors was established. A fluorescent probe was prepared, derived from previous pipecolic scaffold Mip inhibitors labeled with fluorescein. This probe showed moderate affinity for BpMip and enabled a highly robust FPA suitable for screening large compound libraries with medium- to high-throughput (Z factor ∼ 0.89) to identify potent new inhibitors. The FPA results are consistent with data from the protease-coupled PPIase assay. Analysis of the temperature dependence of the probe's binding highlighted that BpMip's ligand binding is driven by enthalpic rather than entropic effects. This has considerable consequences for the use of low-temperature kinetic assays.
Anxious depression represents a subtype of major depressive disorder and is associated with increased suicidality, severity, chronicity and lower treatment response. Only a few studies have investigated the differences between anxious depressed (aMDD) and non-anxious depressed (naMDD) patients regarding treatment dosage, serum-concentration and drug-specific treatment response. In our naturalistic and prospective study, we investigated whether the effectiveness of therapy including antidepressants (SSRI, SNRI, NaSSA, tricyclics and combinations) in aMDD patients differs significantly from that in naMDD patients. In a sample of 346 patients, we calculated the anxiety somatization factor (ASF) and defined treatment response as a reduction (≥50%) in the Hamilton Depression Rating Scale (HDRS)-21 score after 7 weeks of pharmacological treatment. We did not observe an association between therapy response and the baseline ASF-scores, or differences in therapy outcomes between aMDD and naMDD patients. However, non-responders had higher ASF-scores, and at week 7 aMDD patients displayed a worse therapy outcome than naMDD patients. In subgroup analyses for different antidepressant drugs, venlafaxine-treated aMDD patients showed a significantly worse outcome at week 7. Future prospective, randomized-controlled studies should address the question of a worse therapy outcome in aMDD patients for different psychopharmaceuticals individually.
Dimethyl fumarate attenuates lymphocyte infiltration and reduces infarct size in experimental stroke
(2023)
Ischemic stroke is associated with exacerbated tissue damage caused by the activation of immune cells and the initiation of other inflammatory processes. Dimethyl fumarate (DMF) is known to modulate the immune response, activate antioxidative pathways, and improve the blood–brain barrier (BBB) after stroke. However, the specific impact of DMF on immune cells after cerebral ischemia remains unclear. In our study, male mice underwent transient middle cerebral artery occlusion (tMCAO) for 30 min and received oral DMF (15 mg/kg) or a vehicle immediately after tMCAO, followed by twice-daily administrations for 7 days. Infarct volume was assessed on T2-weighted magnetic resonance images on days 1 and 7 after tMCAO. Brain-infiltrating immune cells (lymphocytes, monocytes) and microglia were quantified using fluorescence-activated cell sorting. DMF treatment significantly reduced infarct volumes and brain edema. On day 1 after tMCAO, DMF-treated mice showed reduced lymphocyte infiltration compared to controls, which was not observed on day 7. Monocyte and microglial cell counts did not differ between groups on either day. In the acute phase of stroke, DMF administration attenuated lymphocyte infiltration, probably due to its stabilizing effect on the BBB. This highlights the potential of DMF as a therapeutic candidate for mitigating immune cell-driven damage in stroke.