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- Fagus sylvatica (17)
- Fehler (17)
- Filmographie (17)
- Florida (17)
- Französische Revolution (17)
- Freie Gewerkschaft (17)
- Frühe Neuzeit (17)
- Frühneuhochdeutsch (17)
- Genetics (17)
- Grillparzer, Franz (17)
- Gutzkow, Karl (17)
- Horrorfilm (17)
- Industriearbeiterin (17)
- Islamismus (17)
- Judentum (17)
- Kajkavisch (17)
- Kapitalmarktrecht (17)
- Komödie (17)
- Lewald, Fanny (17)
- Methode (17)
- Mundart (17)
- Natur <Motiv> (17)
- Nearctic (17)
- Oesterle, Günter (17)
- Photographie (17)
- Portugal (17)
- Presse (17)
- Professionalisierung (17)
- Pronomen (17)
- Präposition (17)
- Rezensionen (17)
- Schriftstellerin (17)
- Schule (17)
- Shakespeare, William (17)
- Social System (17)
- Spieltheorie (17)
- Sprachkritik (17)
- Synergie (17)
- Tabu (17)
- Teoria crítica (17)
- Textverstehen (17)
- Turkey (17)
- Vielfalt (17)
- Wertpapieremission (17)
- Wettbewerb (17)
- climate (17)
- equation of state (17)
- gene therapy (17)
- glioma (17)
- host plants (17)
- mortality (17)
- parasitoid (17)
- schizophrenia (17)
- stroke (17)
- tumor microenvironment (17)
- vegetation classification (17)
- Adverb (16)
- Angiogenesis (16)
- Anthologie (16)
- Biomarkers (16)
- Caribbean (16)
- CiNyungwe (16)
- Distribution (16)
- EBA (16)
- Euro (16)
- Finanzwirtschaft (16)
- Fiscal Policy (16)
- Gene expression (16)
- Genossenschaftsbewegung (16)
- Gesprochene Sprache (16)
- Gewerkverein der Heimarbeiterinnen Deutschlands für Kleider- und Wäschekonfektion und verwandte Berufe (1900-) (16)
- Gleichberechtigung (16)
- Grammatikalisation (16)
- Grass, Günter (16)
- Hausarbeit (16)
- Hegel, Georg Wilhelm Friedrich (16)
- Herrschaft (16)
- Imagologie (16)
- Industriearbeit (16)
- Infektionsabwehr (16)
- Infrarot (16)
- Journalismus (16)
- Kollokation (16)
- Koti (16)
- Kreditwesen (16)
- Krim (16)
- Marx, Karl (16)
- Memory (16)
- Migration <Motiv> (16)
- Modellierung (16)
- Mähren (16)
- Müller, Heiner (16)
- Nibelungenlied (16)
- Nordrhein-Westfalen (16)
- Nyungwe (16)
- Open Access (16)
- Outcome (16)
- Podospora anserina (16)
- Prostitution (16)
- Pädagogik (16)
- Relativistic heavy-ion collisions (16)
- Selbstdarstellung (16)
- Sicherheit (16)
- Sicherheitspolitik (16)
- Sprachpolitik (16)
- Sprachstatistik (16)
- Stil (16)
- Surgery (16)
- Synthesis (16)
- Systematics (16)
- Terminologie (16)
- Transparenz (16)
- Transylvanian Saxons (16)
- Ungarisch (16)
- Unternehmen (16)
- Vergleich (16)
- Wahlkampf (16)
- Wirklichkeit (16)
- Zeitung (16)
- asset pricing (16)
- cryptic species (16)
- culture (16)
- financial stability (16)
- inflation (16)
- memory (16)
- miRNA (16)
- new genera (16)
- ordination (16)
- phenology (16)
- populism (16)
- proteomics (16)
- terrorism (16)
- uncertainty (16)
- word order (16)
- Ägypten (16)
- ALICE (15)
- Alphabetisierung (15)
- Altgermanistik (15)
- Arbeitslosigkeit (15)
- Asia (15)
- Außenpolitik (15)
- Bildnis (15)
- Börne, Ludwig (15)
- Carabidae (15)
- Chuwabu (15)
- Cirrhosis (15)
- Contagion (15)
- Culture (15)
- Das Ganze (15)
- Datenschutz (15)
- EKoti (15)
- Echuwabo (15)
- Erzählforschung (15)
- Finanzierung (15)
- France (15)
- Fußball (15)
- Gefühl <Motiv> (15)
- Geschichte 1800-1900 (15)
- Grammatiktheorie (15)
- Historismus (15)
- Hochschuldidaktik (15)
- Hochschule (15)
- Hymenoptera (15)
- ISIS (15)
- Ideologie (15)
- Indogermanische Sprachen (15)
- Interkulturelles Lernen (15)
- Konsumgenossenschaft (15)
- Korruption (15)
- Kritische Theorie (15)
- Kulturanthropologie (15)
- Kulturwissenschaft (15)
- Kulturwissenschaftliche Bibliothek Warburg (15)
- Landarbeiterin (15)
- Lehrbuch (15)
- Lepidoptera (15)
- Literaturgeschichte (15)
- Macht (15)
- Maschinelle Übersetzung (15)
- Mimesis (15)
- Mitgliederwerbung (15)
- Morphosyntax (15)
- Muttersprache (15)
- Nachhaltigkeit (15)
- Nationalbewusstsein (15)
- Nominalphrase (15)
- Obama (15)
- Palaearctic (15)
- Pension Insurance (15)
- Politische Verfolgung (15)
- Preußen (15)
- Prophetie (15)
- Protest (15)
- QCD (15)
- QGP (15)
- Quantitative Easing (15)
- Sarawak (15)
- Simulation (15)
- Solvency II (15)
- Sprechakt (15)
- Stadt <Motiv> (15)
- Stilistik (15)
- Topikalisierung (15)
- Twitter (15)
- Verlag (15)
- Wahlagitation (SPD) (15)
- Warburg, Aby Moritz (15)
- Westafrika (15)
- Wiederholung (15)
- Wikileaks (15)
- Wolf, Christa (15)
- gene expression (15)
- heavy-ion collisions (15)
- hippocampus (15)
- human rights (15)
- introduced species (15)
- key to species (15)
- mass spectrometry (15)
- multiple sclerosis (15)
- obesity (15)
- oxidative stress (15)
- parasitoids (15)
- recognition (15)
- reduction of pain (15)
- structural biology (15)
- systemic risk (15)
- temperature (15)
- teoria crítica (15)
- tissue oxygen partial pressure (15)
- tissue temperature (15)
- treatment (15)
- Übersetzerin (15)
- Agamben, Giorgio (14)
- Anglizismus (14)
- Arabisch (14)
- Artikulatorische Phonetik (14)
- Asset Pricing (14)
- Aussprache (14)
- Australia (14)
- Barock (14)
- Biogeography (14)
- Bitcoin (14)
- Bürgertum (14)
- Chewa-Sprache (14)
- Children (14)
- Chwabo (14)
- DNA (14)
- Demography (14)
- Döblin, Alfred (14)
- ESR Spectra (14)
- Epistemologie (14)
- Epoche (14)
- Erzählperspektive (14)
- European Central Bank (14)
- Flüchtlinge (14)
- Form (14)
- Fortschritt (14)
- Frieden (14)
- Gegenwart (14)
- Genossenschaft (14)
- Gentherapie (14)
- Griechenland (14)
- Habermas (14)
- Hadron (14)
- Held (14)
- Homosexualität (14)
- Humanismus (14)
- Immunology (14)
- Indien (14)
- Infrastruktur (14)
- Inszenierung (14)
- Interrogativsatz (14)
- Israel (14)
- Jean Paul (14)
- Joyce, James (14)
- Kapitalmarkt (14)
- Kindersprache (14)
- Klima (14)
- Kommentar (14)
- Lernen (14)
- Literarische Gestalt (14)
- Literarische Übersetzung (14)
- Ludwig (14)
- Magnetic resonance imaging (14)
- Mathematik (14)
- Molinio-Arrhenatheretea (14)
- Mortality (14)
- Mörike, Eduard (14)
- Mündlichkeit (14)
- Nachkriegszeit (14)
- Nachlass (14)
- New Zealand (14)
- Nungisch (14)
- Parodie (14)
- Pension (14)
- Philhellenismus (14)
- Reformation (14)
- Risikomanagement (14)
- Russia (14)
- Sauerstoffversorgung (14)
- Schwedisch (14)
- Schönheit (14)
- Slowakisch (14)
- South Africa (14)
- Spitteler, Carl (14)
- Sprachverstehen (14)
- Sprichwort (14)
- Strategie (14)
- Subjektivität (14)
- Taxonomie (14)
- Terror (14)
- Topographie <Kulturwissenschaft> (14)
- Transformation (14)
- Trauma (14)
- Vokal (14)
- Wagner, Richard (14)
- Walther <von der Vogelweide> (14)
- Widerstand (14)
- Wissenschaftskommunikation (14)
- Wortschatz (14)
- X-ray crystallography (14)
- banking (14)
- credit risk (14)
- endothelial cells (14)
- epigenetics (14)
- eutrophication (14)
- extracellular matrix (14)
- financial crisis (14)
- focus (14)
- insurance (14)
- interculturality (14)
- lectotype (14)
- macrophages (14)
- planthopper (14)
- tissue blood flow (14)
- ubiquitination (14)
- wound healing (14)
- Analyse (13)
- Andes (13)
- Apoidea (13)
- Ausländer (13)
- Bachtin, Michail M. (13)
- Barbar <Motiv> (13)
- Bayern (13)
- Biopolitik <Motiv> (13)
- Borges, Jorge Luis (13)
- Bourdieu, Pierre (13)
- Capsule endoscopy (13)
- Clearing (13)
- Cognition (13)
- Croatian language (13)
- Cryptocurrency (13)
- Das Andere (13)
- Deutschlehrer (13)
- Ding <Motiv> (13)
- Ecocriticism (13)
- Ecuador (13)
- Energie (13)
- Epigenetik (13)
- Faschismus (13)
- Filmtheorie (13)
- Finanzkrise (13)
- Fremdbild (13)
- Gattungstheorie (13)
- Gesicht <Motiv> (13)
- Großstadt <Motiv> (13)
- Habitat (13)
- Handel (13)
- Heinrich von (13)
- Herder (13)
- Herwegh, Georg (13)
- Identity (13)
- Immunotherapy (13)
- Karikatur (13)
- Kasus (13)
- Kinder- und Hausmärchen (13)
- Kinderschutz (13)
- Klein- und Mittelbetrieb (13)
- Kompositum (13)
- Kreativität (13)
- Kulturpolitik (13)
- Lehrmittel (13)
- Literaturkanon (13)
- Machine Learning (13)
- Mammakarzinom (13)
- Medientheorie (13)
- Middle East (13)
- Moral (13)
- Motivation (13)
- Multikulturelle Gesellschaft (13)
- Multistable figures (13)
- Museum (13)
- NADPH oxidase (13)
- Nation (13)
- Negation (13)
- Neoliberalismus (13)
- Netzpolitik (13)
- New species (13)
- Oncology (13)
- Oriental Region (13)
- Paul (13)
- Performativität <Kulturwissenschaften> (13)
- Phylogeny (13)
- Possessivität (13)
- Prag (13)
- Predigt (13)
- R2P (13)
- ROS (13)
- Radiotherapy (13)
- Rezeptionsästhetik (13)
- Rothacker, Erich (13)
- Römisches Reich (13)
- Saving (13)
- Schrift (13)
- Screening (13)
- Souveränität (13)
- Sozialer Wandel (13)
- Spanien (13)
- Sprachgebrauch (13)
- Sprachkompetenz (13)
- Sprachlehrbuch (13)
- Sprachvariante (13)
- Suttner, Bertha von (13)
- Tagalog (13)
- Transylvania (13)
- Ungarn (13)
- Vergangenheitsbewältigung (13)
- Vergesellschaftung (13)
- Verkehr (13)
- Vertrauen (13)
- Volkserzählung (13)
- Weiblichkeit (13)
- Zeitgenössische Kunst (13)
- caves (13)
- cirrhosis (13)
- communication (13)
- cytokines (13)
- endemic (13)
- epidemiology (13)
- fiscal policy (13)
- flora (13)
- fungi (13)
- genitalia (13)
- globalization (13)
- hrvatski jezik (13)
- ideology (13)
- islamic state (13)
- liquidity (13)
- lung cancer (13)
- meiofauna (13)
- metabolism (13)
- neurodegeneration (13)
- radical prostatectomy (13)
- red riječi (13)
- review (13)
- signal transduction (13)
- species delimitation (13)
- spider (13)
- survival (13)
- synaptic plasticity (13)
- Öffentlichkeit (13)
- ABS (12)
- Aesthetics (12)
- Afghanistan (12)
- Allegorie (12)
- Anti-Utopie (12)
- Arbeiterinnenfrage (12)
- Arbeiterinnenverein (12)
- Argentina (12)
- Asymmetrische Information (12)
- Auslandsgermanistik (12)
- Bank Lending (12)
- Behavior (12)
- Berliner Kindheit um neunzehnhundert (12)
- Buch (12)
- Bulgarisch (12)
- Börsenrecht (12)
- Bürgerliche Frauenbewegung (12)
- Chronotopos (12)
- Comments disabled (12)
- Computerspiel (12)
- Consumption (12)
- Cryoelectron microscopy (12)
- Datenbank (12)
- Deutsches Sprachgebiet (12)
- Diagnostik (12)
- Divina Commedia (12)
- Ecology (12)
- Einfühlung (12)
- Endothelial cells (12)
- England (12)
- Epidemiology (12)
- Familienname (12)
- Faust (12)
- Florenz (12)
- Frauenliteratur (12)
- George, Stefan (12)
- Germanist (12)
- Geschichte 1450-1650 (12)
- Geschlechterverhältnis (12)
- Gewalt <Motiv> (12)
- Greece (12)
- Grundschule (12)
- HCV (12)
- Heros (12)
- Historische Sprachwissenschaft (12)
- History (12)
- Idealisierung (12)
- Intellektueller (12)
- Investmentfonds (12)
- Kamerun (12)
- Kapitalertrag (12)
- Katastrophe <Motiv> (12)
- Kleidung (12)
- Klimaänderung (12)
- Kommunismus (12)
- Konsonant (12)
- Kopula (12)
- Krise (12)
- Lexikografie (12)
- Luther, Martin (12)
- Massenmedien (12)
- Membranproteine (12)
- MiFID II (12)
- Militär (12)
- Modalverb (12)
- Myanmar (12)
- NMR-Spektroskopie (12)
- Namibia (12)
- Nationalsozialismus <Motiv> (12)
- Neuer Markt (12)
- Neugriechisch (12)
- Pandemie (12)
- Paratext (12)
- Parkinson’s disease (12)
- Personenname (12)
- Pinus sylvestris (12)
- Portfolio Selection (12)
- Portugiesisch / Brasilien (12)
- Private Investment (12)
- Proust, Marcel (12)
- Psychologie (12)
- Publizistik (12)
- Rechtsradikalismus (12)
- Referenzidentität (12)
- Reise (12)
- Repräsentation (12)
- Revolution (12)
- Rheinland-Pfalz (12)
- Romania (12)
- Rumänien (12)
- Sage (12)
- Sehen (12)
- Semantics (12)
- Sozialgeschichte (12)
- Spannung (12)
- Stadtentwicklung (12)
- Standardsprache (12)
- Struktur (12)
- Subjekt (12)
- Suffix (12)
- Suicide (12)
- Tanz (12)
- Tempus (12)
- Theodor Adorno (12)
- Topik (12)
- Training (12)
- Transfer (12)
- United States (12)
- Vendée (France) (12)
- Verbreitung (12)
- Vereinte Nationen (12)
- Walser, Robert (12)
- Wirtschaftssprache (12)
- Zeit <Motiv> (12)
- Zustandsgleichung (12)
- alien species (12)
- alphabetisation (12)
- artificial intelligence (12)
- barcoding (12)
- cell death (12)
- child (12)
- colorectal cancer (12)
- disturbance (12)
- dry grassland (12)
- financial literacy (12)
- first record (12)
- health (12)
- human (12)
- language (12)
- leukemia (12)
- mouse (12)
- orthography (12)
- prevalence (12)
- restoration (12)
- risk (12)
- semantics (12)
- simulation (12)
- spiders (12)
- stress (12)
- surgery (12)
- syntax (12)
- Ableitung <Linguistik> (11)
- Adjunkt <Linguistik> (11)
- Aktivismus (11)
- Alphabet (11)
- Ambiguität (11)
- Arbeitsmarkt (11)
- Arbeitsmarktpolitik (11)
- Arzneimittel (11)
- Aspekt (11)
- Autophagy (11)
- Bioenergetics (11)
- Bloch, Ernst (11)
- Bolivia (11)
- Bryophytes (11)
- Bundesverfassungsgericht (11)
- Börsenordnung (11)
- Canguilhem, Georges (11)
- Cerambycidae (11)
- Chatten <Kommunikation> (11)
- Chemotherapy (11)
- Cisena (11)
- Computerphilologie (11)
- Czech Republic (11)
- Derivatives (11)
- Deutsch als Zweitsprache (11)
- Diabetes mellitus (11)
- Dienstmädchen (11)
- Diplomatie (11)
- Diskriminierung (11)
- Dissertation (11)
- Dokumentation (11)
- Droste-Hülshoff, Annette von (11)
- Dürrenmatt, Friedrich (11)
- EIOPA (11)
- Einkommensverteilung (11)
- Elektronische Zeitschrift (11)
- Emotions (11)
- Endoscopy (11)
- Europäische Zentralbank (11)
- Evangelischer Arbeiterinnenverein (11)
- Federal Reserve (11)
- Freundschaft (11)
- Geburtenregelung (11)
- Germanistenverband (11)
- Geschichte <Motiv> (11)
- Globalization (11)
- Grimm, Wilhelm (11)
- Guatemala (11)
- Hadron-Hadron scattering (experiments) (11)
- Hegel (11)
- Heidegger, Martin (11)
- Hofmannsthal (11)
- Imagination (11)
- In vitro (11)
- Inversionsfigur (11)
- Italienbild (11)
- Jahrhundertwende (11)
- Jesus Christus (11)
- Joseph von (11)
- Jürgen Habermas (11)
- Konnotation (11)
- Kontrastive Phraseologie (11)
- Kredit (11)
- Kulturvermittlung (11)
- Kurzgeschichte (11)
- Lacan, Jacques (11)
- Legende (11)
- Leidenschaft (11)
- Life Insurance (11)
- Literaturgattung (11)
- Low Interest Rates (11)
- Makonde-Sprache (11)
- Mali (11)
- Mediterranean (11)
- Melancholie (11)
- Menschenrechte (11)
- Molecular biology (11)
- Mollusca (11)
- Mutterschaft (11)
- Mutterschaftsversicherung (11)
- Optionspreistheorie (11)
- Ovidius Naso, Publius (11)
- Peter (11)
- Peter Tauber (11)
- Politische Bildung (11)
- Pop-Kultur (11)
- Preis <Auszeichnung> (11)
- Primary care (11)
- Psychology (11)
- Quark Gluon Plasma (11)
- Quark-Gluon Plasma (11)
- RHIC (11)
- Rechtssprache (11)
- Rousseau, Jean-Jacques (11)
- Saccharomyces cerevisiae (11)
- Schizophrenia (11)
- Schutzverantwortung (11)
- Selbstbild (11)
- Sena (11)
- Silbe (11)
- TLAC (11)
- Textgeschichte (11)
- Theatertheorie (11)
- Tieck, Ludwig (11)
- Tiere <Motiv> (11)
- Transkulturalität (11)
- Uncertainty (11)
- VEGF (11)
- Verfassung (11)
- Verfilmung (11)
- Wahrnehmungswechsel (11)
- Waldgesellschaften (11)
- Weerth, Georg (11)
- Wohnverhältnisse (11)
- Wortfeld (11)
- Zeichen (11)
- Zweig, Stefan (11)
- al-Qaida (11)
- asymmetric information (11)
- bees (11)
- bladder cancer (11)
- crisis (11)
- forest management (11)
- grammar (11)
- grazing (11)
- habitat (11)
- hydrogen bonding (11)
- integrins (11)
- intercultural communication (11)
- justice (11)
- macrophage polarization (11)
- male genitalia (11)
- metastasis (11)
- model uncertainty (11)
- new synonym (11)
- outcome (11)
- p53 (11)
- participation (11)
- physical activity (11)
- psoriasis (11)
- public debt (11)
- quark gluon plasma (11)
- radiotherapy (11)
- real-time data (11)
- responsibility (11)
- risk factors (11)
- targeted therapy (11)
- transparency (11)
- validity (11)
- vegetation (11)
- Ästhetische Wahrnehmung (11)
- Österreich-Ungarn (11)
- Überwachung (11)
- 19. Jahrhundert (10)
- 5-lipoxygenase (10)
- ACLF (10)
- Achtundsechziger (10)
- Aktienkurs (10)
- Anthrozoologie (10)
- Arbeit <Motiv> (10)
- Arbeitsrecht (10)
- Arbeitsverhältnisse (10)
- Archivierung (10)
- Asset Allocation (10)
- Autor (10)
- Bankenaufsicht (10)
- Barrierefreiheit (10)
- Barthes, Roland (10)
- Baudelaire, Charles (10)
- Big Data (10)
- Bildungsroman (10)
- Biopolitik (10)
- Boko Haram (10)
- Bratoljub Klaić (10)
- Brustkrebs (10)
- Bundestag (10)
- C. elegans (10)
- CDU (10)
- COPD (10)
- Chile (10)
- Conservation (10)
- Costa Rica (10)
- Cyberwar (10)
- Deutsch-Ostafrika (10)
- Diagnostic markers (10)
- Dialektik (10)
- Ding (10)
- Disclosure (10)
- Disticha Catonis (10)
- Diversity (10)
- EGFR (10)
- Educação (10)
- Egypt (10)
- Eichendorff (10)
- Einkommen (10)
- Ellenberg indicator values (10)
- Energieumsatz <Medizin> (10)
- Entstehung (10)
- Erlebnisbericht (10)
- Evolutionspsychologie (10)
- Facebook (10)
- Fachinformationsdienst (10)
- Fauna (10)
- Fintech (10)
- Fragebogen (10)
- Frankfurt / Universität (10)
- Frankfurt <Main> / Universität / Poelzig-Bau (10)
- Frauenpolitik (SPD) (10)
- Frauenpresse (10)
- Freedom (10)
- GARCH-Prozess (10)
- Geld (10)
- Geld <Motiv> (10)
- Generative Grammatik (10)
- Gerechtigkeit (10)
- Geschichtsbild (10)
- Gesundheitswesen (10)
- Goethe-Universität Frankfurt am Main (10)
- Grenze (10)
- Hamburg (10)
- Heart failure (10)
- Heavy-ion collisions (10)
- Hepatocellular carcinoma (10)
- IR Spectra (10)
- Immunologie (10)
- Inclusion (10)
- Integriertes Lernen (10)
- Investor Protection (10)
- Ionenstrahl (10)
- Joachim Wittstock (10)
- Jugendsprache (10)
- Justice (10)
- Kapitalmarkteffizienz (10)
- Kinderarbeit (10)
- Klitisierung (10)
- Knowledge (10)
- Kolumbien (10)
- Kommunikationsanalyse (10)
- Konfektion (10)
- Kontext (10)
- Konzentrationslager (10)
- Kooperation (10)
- Koreanisch (10)
- Kracauer, Siegfried (10)
- Kubrick, Stanley (10)
- Kuratieren (10)
- Künstliche Intelligenz (10)
- Law (10)
- Learning (10)
- Legitimation (10)
- Leipzig (10)
- Lektüre (10)
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- ubiquitin (8)
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- Äquivalenz (8)
- 500-1500 (7)
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- Adaptation (7)
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- Aktionär (7)
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- CRISPR/Cas9 (7)
- Cancer treatment (7)
- Capital-Asset-Pricing-Modell (7)
- Cerrado (7)
- Charakterisierung (7)
- Chemiker (7)
- Chewa (7)
- Chichewa (7)
- Christliche Arbeiterbewegung (7)
- Colorectal cancer (7)
- Corporate Social Responsibility (7)
- Culicidae (7)
- Curculionidae (7)
- Cyanobacteria (7)
- Das Böse (7)
- Das Heilige (7)
- Das Sakrale (7)
- Data processing (7)
- Data science (7)
- Deflation (7)
- Derivat, Wertpapier (7)
- Deutscher Einwanderer (7)
- Deutschland / Vereinigung (7)
- Deutschland <Bundesrepublik> (7)
- Deutschland <DDR> / Revolution <1989> (7)
- Deutschlandbild (7)
- Development (7)
- Diagnose (7)
- Dienstmädchenverein (7)
- Digital Rights (7)
- Digital Services Act (7)
- Discourse (7)
- Dodd-Frank Act (7)
- Drogenkonsum (7)
- Drogenszene (7)
- Drung (7)
- EZB (7)
- Eastern Arc (7)
- Eco, Umberto (7)
- Einstellung (7)
- Electroencephalography (7)
- Elektronische Bibliothek (7)
- Empfindsamkeit (7)
- Empirische Ästhetik (7)
- Engel <Motiv> (7)
- Enzensberger, Hans Magnus (7)
- Epigenetics (7)
- Episches Theater (7)
- Epos (7)
- Erwerbslosigkeit (7)
- Essayismus (7)
- Ethica ordine geometrico demonstrata (7)
- Ethnizität (7)
- Euro Area (7)
- Expedition Brochure (7)
- Expeditionsbericht (7)
- Exposure (7)
- Fachportal (7)
- Fantastische Literatur (7)
- Fassbinder, Rainer Werner (7)
- Feldforschung (7)
- Fernunterricht (7)
- Fichte, Johann Gottlieb (7)
- Filmkritik (7)
- Finance (7)
- Financial Regulation (7)
- Finanzierungsstruktur (7)
- Flaubert, Gustave (7)
- Foreign language teaching (7)
- Forensic entomology (7)
- Forschungsbericht (7)
- Frauenemanzipation (7)
- Frauenpolitik (SDAP) (7)
- Freidenker (7)
- Freie Liebe (7)
- Freizeit (7)
- GARCH (7)
- GIS (7)
- GPCR (7)
- Gegenwartsliteratur (7)
- Genauigkeit (7)
- Gene regulation (7)
- Genossenschaftliche Frauenbewegung (7)
- Genus verbi (7)
- German literature (7)
- Gerontologie (7)
- Geschichte 1933-1945 (7)
- Geschichtsunterricht (7)
- Geschlechterbeziehung (7)
- Gesundheitspolitik (7)
- Gewerbeaufsicht (7)
- Goethe-Universität Frankfurt (7)
- Griechenland (Altertum) (7)
- Guattari, Félix (7)
- HCC (7)
- Harz (7)
- Heart (7)
- Heavy-ion collision (7)
- Hemiptera (7)
- Hepatitis C (7)
- Herb induced liver injury (7)
- Herta Müller (7)
- Hilfsverb (7)
- Hitchcock (7)
- Hungary (7)
- Identification key (7)
- Identifikation (7)
- Identitätspolitik (7)
- Ikone (7)
- Immunohistochemistry (7)
- Immunological methods (7)
- Immunologische Methoden (7)
- Indochina (7)
- Indústria cultural (7)
- International Financial Reporting Standards (7)
- Internationale Politik (7)
- Internationaler Vergleich (7)
- Jena (7)
- John (7)
- Johnson, Uwe (7)
- Kannibalismus <Motiv> (7)
- Kapitalgewinn (7)
- Kardiovaskuläre Krankheit (7)
- Karl Philipp (7)
- Karriere (7)
- Kaschnitz, Marie Luise (7)
- Kasperl (7)
- Katholische Arbeiterinnenbewegung (7)
- Kausalität (7)
- Kenya (7)
- Komposition <Wortbildung> (7)
- Konflikt (7)
- Konfliktlösung (7)
- Kreditwürdigkeit (7)
- Kriegsfürsorge (7)
- Kritische Ausgabe (7)
- Kulturerbe (7)
- Kunstpädagogik (7)
- Kybernetik (7)
- Latein (7)
- Laudatio (7)
- Lebensstil (7)
- Lesekompetenz (7)
- Liberdade (7)
- Linguistische Datenverarbeitung (7)
- Linkshegelianer (7)
- Lycosidae (7)
- MLL (7)
- Macaronesia (7)
- Macht <Motiv> (7)
- Makonde (7)
- Malaise trap (7)
- Manipulation (7)
- Mann (7)
- Marcuse (7)
- Martin (7)
- Martyrium (7)
- Mass spectrometry (7)
- Mechanisms of disease (7)
- Medialität (7)
- Medienkompetenz (7)
- Mediensprache (7)
- Meinungsfreiheit (7)
- Metabolism (7)
- Metafiktion (7)
- Metallindustrie (7)
- Metonymie (7)
- Mitgliedsstaaten (7)
- Modalpartikel (7)
- Molecular neuroscience (7)
- Molekulardynamik (7)
- Monte-Carlo-Simulation (7)
- Moose (7)
- Moral Hazard (7)
- Morphonologie (7)
- Mygalomorphae (7)
- Märtyrer <Motiv> (7)
- Müller (7)
- Mündliche Kommunikation (7)
- NK cells (7)
- Nationenbildung (7)
- Naturphilosophie (7)
- Nebenläufigkeit (7)
- Neoliberalism (7)
- Nestroy, Johann (7)
- Neurology (7)
- Neuronales Netz (7)
- Neurons (7)
- Nietzsche (7)
- Normative Ordnungen (7)
- Normativität (7)
- Numerale (7)
- Nyanja (7)
- Nyanja-Sprache (7)
- Obesity (7)
- Odonata checklist (7)
- Orchidaceae (7)
- Organische Synthese (7)
- Osteoporosis (7)
- Othering (7)
- Oxidative stress (7)
- PD-L1 (7)
- Palästina (7)
- Pathogenesis (7)
- Performance (7)
- Pharmazie (7)
- Phase Diagrams (7)
- Philosoph (7)
- Pholcidae (7)
- Plato (7)
- Politics (7)
- Politikberatung (7)
- Politische Identität (7)
- Polytrauma (7)
- Popliteratur (7)
- Popmusik (7)
- Pregnancy (7)
- Preisbildung (7)
- Privacy (7)
- Privatisierung des Krieges (7)
- Programmiersprache (7)
- Proteins (7)
- Proteomanalyse (7)
- Präsenzlehre (7)
- Psycholinguistik (7)
- QCD phase diagram (7)
- Qualität (7)
- Quanten-Chromodynamik (7)
- Quantenchromodynamik (7)
- Quark (7)
- Quercus (7)
- Quercus robur (7)
- RFQ (7)
- Reaction time (7)
- Reactive oxygen species (7)
- Reduktion (7)
- Referenz <Linguistik> (7)
- Refugees (7)
- Register (7)
- Rehabilitation (7)
- Rekonstruktion (7)
- Religionskritik (7)
- Responsibility to protect (7)
- Retirement (7)
- Rhinotragini (7)
- Risk assessment (7)
- Risk factors (7)
- Rolle (7)
- Romanistik (7)
- Rote-Liste-Arten (7)
- Rubus (7)
- Rumänisch (7)
- Russisch-Ukrainischer Krieg (7)
- Römische Geschichte (7)
- Schwangerschaftsabbruch (7)
- Seizure (7)
- Senegal (7)
- Sensory processing (7)
- Short story (7)
- Sichtbarkeit (7)
- Simmel, Georg (7)
- Slovakia (7)
- Snowden (7)
- Software (7)
- Sozialdemokratische Partei Deutschlands (SPD, 1890-) (7)
- Sparkasse (7)
- Species distribution modelling (7)
- Speech (7)
- Sprachgeschichte (7)
- Sprachproduktion (7)
- Stadtplanung (7)
- Stummfilm (7)
- Substantiv (7)
- Sudan (7)
- Synspermiata (7)
- Systematik (7)
- Systemic risk (7)
- Säuglingssterblichkeit (7)
- Technologie (7)
- Tension (7)
- Terrorism (7)
- Textkohärenz (7)
- Theoriegeschichte (7)
- Therapie (7)
- Transfusion (7)
- Transitivität (7)
- Transkription (7)
- Traum <Motiv> (7)
- Tschechien (7)
- Ungeheuer (7)
- Unsterblichkeit (7)
- Unterhaltung (7)
- Vergütung (7)
- Verhalten (7)
- Vermittlung (7)
- Versammlungsfreiheit (7)
- Verschlusslaut (7)
- Vision (7)
- Visuelle Wahrnehmung (7)
- Volksaufklärung (7)
- Vulnerability (7)
- War (7)
- Werbesprache (7)
- Werbung (7)
- Willensfreiheit (7)
- Wolfram <von Eschenbach> (7)
- Wöchnerinnenschutz (7)
- X-Ray (7)
- X-Ray Structure Analysis (7)
- acute lymphoblastic leukemia (7)
- antiviral therapy (7)
- anxiety (7)
- aortic stenosis (7)
- aquatic insects (7)
- art (7)
- asthma (7)
- atrial fibrillation (7)
- beetles (7)
- biophysics (7)
- bipolar disorder (7)
- breeding (7)
- cGMP (7)
- capital structure (7)
- cell cycle (7)
- childhood (7)
- citizen science (7)
- cloud forest (7)
- cluster analysis (7)
- cochlear implant (7)
- colon cancer (7)
- concurrency (7)
- conduct disorder (7)
- convergence (7)
- cooperation (7)
- cytotoxicity (7)
- decision making (7)
- deep learning (7)
- deliberative democracy (7)
- density functional theory (7)
- descriptions (7)
- diet (7)
- diffusion tensor imaging (7)
- dung beetles (7)
- emancipation (7)
- expectations (7)
- fibrosis (7)
- financial system (7)
- forensic entomology (7)
- forward guidance (7)
- freshwater (7)
- functional magnetic resonance imaging (7)
- functional traits (7)
- genetics (7)
- global change (7)
- heart failure (7)
- hematopoietic stem cell transplantation (7)
- hermeneutics (7)
- human capital (7)
- immunology (7)
- indicator values (7)
- innovation (7)
- intertextuality (7)
- islamism (7)
- karst (7)
- leafhoppers (7)
- legal pluralism (7)
- leverage (7)
- liver cirrhosis (7)
- liverworts (7)
- longhorned beetles (7)
- machine-learning (7)
- mathematical modeling (7)
- membrane protein (7)
- mice (7)
- modeling (7)
- molecular phylogenetics (7)
- morphometrics (7)
- natural history (7)
- natural killer cells (7)
- neophytes (7)
- network analysis (7)
- new subspecies (7)
- nitric oxide (7)
- oligomerization (7)
- parasitoid wasps (7)
- particulate matter (7)
- perception (7)
- pest (7)
- phylogeography (7)
- phytodiversity (7)
- polypharmacy (7)
- predictive coding (7)
- pregnancy (7)
- prognosis (7)
- prophylaxis (7)
- prudential supervision (7)
- qualitative research (7)
- quality control (7)
- racism (7)
- representation (7)
- resilience (7)
- rna (7)
- screening (7)
- seizure (7)
- shadow banking (7)
- signaling (7)
- sleep (7)
- social security (7)
- solitary bees (7)
- stability (7)
- subjectivity (7)
- terminology (7)
- text book (7)
- thermal and non-thermal effects (7)
- thermische und nicht-thermische Effekte (7)
- trade (7)
- training (7)
- transcription (7)
- transcriptome (7)
- tumor-associated macrophages (7)
- vector (7)
- venture capital (7)
- visual cortex (7)
- whiteflies (7)
- wound exudation (7)
- zoogeography (7)
- Ökosystem (7)
- 3D printing (6)
- 401(k) plan (6)
- Abduktion <Logik> (6)
- Abnehmer (6)
- Achim von (6)
- Acinetobacter baumannii (6)
- Addition Compounds (6)
- Adenocarcinoma (6)
- Adhesion (6)
- Adverse Selection (6)
- Affect (6)
- Affix (6)
- Afrikanische Sprachen (6)
- Agitation (SDAP) (6)
- Agitation (SPS) (6)
- Akustik (6)
- Akzent (6)
- Alemannisch (6)
- Altern (6)
- Altertum (6)
- Altes Testament (6)
- Alzheimer (6)
- Amazon (6)
- Amerikabild (6)
- Analogie (6)
- Andreas (6)
- Anna Amalia <Sachsen-Weimar-Eisenach (6)
- Antike <Motiv> (6)
- Antiviral therapy (6)
- Anxiety (6)
- Apoptose (6)
- Arbeitsgedächtnis (6)
- Arbeitsloser (6)
- Arbeitswelt (6)
- Archaeology (6)
- Argentinien (6)
- Arnim (6)
- Atherosclerosis (6)
- Atlantic (6)
- Atlantic Ocean (6)
- Attitude (6)
- Auerbach, Berthold (6)
- Aufführung (6)
- Ausland (6)
- Ausländer, Rose (6)
- Autism (6)
- Autismus (6)
- BRD4 (6)
- Balloon enteroscopy (6)
- Balzac, Honoré de (6)
- Basel III (6)
- Bavaria (6)
- Belletristische Darstellung (6)
- Benin (6)
- Berichterstattung (6)
- Beschaffungsmarketing (6)
- Bestimmungsbuch (6)
- Bevölkerungspolitik (6)
- Beziehungsmanagement (6)
- Biological control (6)
- Biophysik (6)
- Biozönose (6)
- Blindheit (6)
- Blindheit <Motiv> (6)
- Blockchain (6)
- Blog (6)
- Boden (6)
- Bodensee-Gebiet (6)
- Borstgrasrasen (6)
- Brasilienbild (6)
- Brentano (6)
- Buchmarkt (6)
- Böhmische Länder (6)
- Böll, Heinrich (6)
- C-reactive protein (6)
- CDK4/6 (6)
- COSMO-CLM (6)
- Calcium (6)
- Cameraria ohridella (6)
- Canada (6)
- Canary Islands (6)
- Canetti, Elias (6)
- Caretta caretta (6)
- Carl Schmitt (6)
- Carmen Sylva (6)
- Cassirer, Ernst (6)
- Caucasus (6)
- Cetacea (6)
- Chemistry (6)
- Christoph Martin (6)
- Citizenship (6)
- Climate (6)
- Clinical trial (6)
- Community ecology (6)
- Complications (6)
- Computational chemistry (6)
- Computational models (6)
- Conflict (6)
- Consensus (6)
- Consumers (6)
- Corporate governance (6)
- Cortex (6)
- Croatia (6)
- Croatian (6)
- Crohn’s disease (6)
- Crítica (6)
- Curriculum (6)
- Cyborg (6)
- Cytochromoxidase (6)
- D. A. (6)
- DMEK (6)
- Das Kunstwerk im Zeitalter seiner technischen Reproduzierbarkeit (6)
- Das Passagen-Werk (6)
- Death rates (6)
- Decision making (6)
- Deixis (6)
- Demokratisierung (6)
- Der Turm (6)
- Design (6)
- Deskriptivität (6)
- Deutsche <Motiv> (6)
- Deutscher Textilarbeiter-Verband (1906-) (6)
- Diabetes (6)
- Dialética negativa (6)
- Didactics (6)
- Differenz (6)
- Differenzierung (6)
- Digitale Lehre (6)
- Digitale Revolution (6)
- Digitalization (6)
- Distanz (6)
- Donald Trump (6)
- Dopamine (6)
- Dragonflies (6)
- Druckgrafik (6)
- Dung beetles (6)
- Dänemark (6)
- E2 enzyme (6)
- Elderly (6)
- Electronic Commerce (6)
- Elektronisches Publizieren (6)
- Elektrophysiologie (6)
- Emerging Market (6)
- Endothelium (6)
- Enteroscopy (6)
- Entrepreneurship (6)
- Entropie (6)
- Enzyme mechanisms (6)
- Ergativ (6)
- Erzähler (6)
- Erzähltextanalyse (6)
- Eschatologie (6)
- Ethnische Identität (6)
- Ethnobotanik (6)
- Europabild (6)
- Europäische Währungsunion (6)
- Exotismus (6)
- Extracellular matrix (6)
- FT-IR-Spektroskopie (6)
- Fabaceae (6)
- Fabrikarbeit (6)
- Fair value accounting (6)
- Familienroman (6)
- Feldlinguistik (6)
- Feuilleton (6)
- Fichte, Hubert (6)
- Filmtechnik (6)
- Financial Crises (6)
- Financial literacy (6)
- Finanzierungstheorie (6)
- Flirt (6)
- Forschungsreise (6)
- Forster, Georg (6)
- Frage (6)
- Fragmentation (6)
- Frankfurt <Main, 2003> (6)
- Frankfurter Schule (6)
- Fränkisches Reich (6)
- Fulgoromorpha (6)
- Functional connectivity (6)
- Fungi (6)
- Funktion (6)
- Funktionale Kategorie (6)
- Fusion (6)
- Fühmann, Franz (6)
- Garten <Motiv> (6)
- Gedenken (6)
- Genregulation (6)
- Geobotanik (6)
- Gerechtigkeit <Motiv> (6)
- Germanistische Linguistik (6)
- Geschichtsdarstellung (6)
- Geschlechterrolle <Motiv> (6)
- Gesellschaftsrecht (6)
- Gesetz (6)
- Gesundheitserziehung (6)
- Ghana (6)
- Glioblastoma (6)
- Glioma (6)
- Goethe, Johann Wolfgang von / Die Leiden des jungen Werthers (6)
- Goethe-Universität (6)
- Goethe-Universität Frankfurt am Main. Fachbereich Humanmedizin (6)
- Grimmelshausen, Hans Jakob Christoffel von (6)
- Grünbein, Durs (6)
- HADES (6)
- Handelsvolumen (6)
- Hausarbeitsgesetz (6)
- Hausgehilfin (6)
- Haushaltsführung (6)
- Health economics (6)
- Heavy Ion Collisions (6)
- Hebel, Johann Peter (6)
- Hedging (6)
- Heidegger (6)
- Heine (6)
- Hermann (6)
- Herzogin> (6)
- Heterotopie (6)
- Histology (6)
- Historische Semantik (6)
- Hochschullehre (6)
- Hodgkin lymphoma (6)
- Hoffmann von Fallersleben, August Heinrich (6)
- Hoffmann, Ernst T. A. (6)
- Hoftheater (6)
- Hong Kong (6)
- Horkheimer (6)
- Hydroptilidae (6)
- Höflichkeit (6)
- Hören (6)
- Hörrinde (6)
- ISA (6)
- Iberian Peninsula (6)
- Ich (6)
- Idealismus (6)
- Identification (6)
- Ikonographie (6)
- Ikonologie (6)
- Illokutiver Akt (6)
- Illustration (6)
- Image (6)
- Immobilienfonds (6)
- Imperialismus (6)
- Indonesien (6)
- Indústria Cultural (6)
- Inequality (6)
- Infection (6)
- Informatik (6)
- Informationstechnologie (6)
- Interaction (6)
- Interbankenabkommen (6)
- Interest Rates (6)
- International Accounting Standards (6)
- Internationale Arbeiterhilfe (IAH, 1921-) (6)
- Internationale Rote Hilfe (IRH, 1922-) (6)
- Internationaler Frauentag (6)
- Internationaler Kreditmarkt (6)
- Internationalisierung (6)
- Intersubjectivity (6)
- Ionenkanal (6)
- Isländisch (6)
- Jandl, Ernst (6)
- Jugendfürsorge (6)
- Kaiserreich (6)
- Kaiserzeit (6)
- Kapitalstruktur (6)
- Kassner, Rudolf (6)
- Katholische Kirche (6)
- Keller, Gottfried (6)
- Kinases (6)
- Klopstock, Friedrich Gottlieb (6)
- Kollision (6)
- Kommunistische Partei Deutschlands (KPD, 1918-) (6)
- Kompetenz (6)
- Konjunktur (6)
- Konsumverein (6)
- Kontingenz (6)
- Kontrastive Phonologie (6)
- Kraus, Karl (6)
- Kreatives Schreiben (6)
- Kriminalgeschichte (6)
- Kuba (6)
- Kunstmärchen (6)
- Kunstwerk (6)
- Kurden (6)
- Kurdistan (6)
- König Ottokars Glück und Ende (6)
- Lamiinae (6)
- Langzeitarchivierung (6)
- Lattice QCD (6)
- Lautmalerei (6)
- Leaking (6)
- Legs (6)
- Lehnübersetzung (6)
- Leibniz, Gottfried Wilhelm (6)
- Leistungsbilanz (6)
- Lessing (6)
- Lexem (6)
- Lexicalized Tree Adjoining Grammar (6)
- Libyen (6)
- Liebeslyrik (6)
- Lieferung (6)
- Ligand <Biochemie> (6)
- Lindgren funnel (6)
- Litauisch (6)
- Literarischer Stil (6)
- Literatura austríaca (6)
- Liturgie (6)
- Liver transplantation (6)
- Lokativ (6)
- London (6)
- MEMOs (6)
- MRT (6)
- MSC (6)
- Machtstruktur (6)
- Malagassi-Sprache (6)
- Manga (6)
- Manuskript (6)
- Marxismus (6)
- Massenkultur (6)
- Massenspektrometrie (6)
- Mauritius (6)
- Mauthner, Fritz (6)
- Max Weber (6)
- Medical education (6)
- Medienphilosophie (6)
- Medium (6)
- Medizin und Gesundheit (6)
- Medizinstudium (6)
- Meteorologie (6)
- Michel Foucault (6)
- Millipedes (6)
- Model Uncertainty (6)
- Modus (6)
- Molekularbiologie (6)
- Moníková, Libuše (6)
- Morbidity (6)
- Morphogenesis (6)
- Mother tongue (6)
- Multivariate analysis (6)
- Mystik <Motiv> (6)
- Mündliche Literatur (6)
- Mündliche Überlieferung (6)
- NLP (6)
- NMR-Tomographie (6)
- NS-Zeit (6)
- Nachahmung (6)
- Nachhaltige Entwicklung (6)
- Natural Language Processing (6)
- Nature (6)
- Netzwerk (6)
- Neurolinguistik (6)
- New World (6)
- Niederdeutsch (6)
- Nitric oxide (6)
- Non-coding RNA (6)
- Non-small cell lung cancer (6)
- Normative reconstruction (6)
- Novemberrevolution (6)
- Numerical accuracy (6)
- Nutzungsintensivierung (6)
- OSCE (6)
- OTC markets (6)
- Oaxaca (6)
- Objekt (6)
- Online-Publizieren (6)
- Opposition (6)
- Oral anticoagulation (6)
- Ost-West-Konflikt (6)
- PD1/PDL1 (6)
- PELDOR (6)
- PI3K (6)
- PTSD (6)
- Pakistan (6)
- Palatalisierung (6)
- Parabel <Literatur> (6)
- Paracelsus (6)
- Paramilitärs (6)
- Parkinson's disease (6)
- Partizip (6)
- Parzival (6)
- Pathos (6)
- Pathosformel (6)
- Patient blood management (6)
- Pennebaker (6)
- Perfekt (6)
- Performanz <Linguistik> (6)
- Personalpronomen (6)
- Personennamenkunde (6)
- Philosophische Anthropologie (6)
- Photosynthese (6)
- Phraseodidaktik (6)
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- Picea abies (6)
- Pierre Bourdieu (6)
- Plasma (6)
- Pneumonia (6)
- Poe, Edgar Allan (6)
- Poetry (6)
- Politische Literatur (6)
- Politische Theorie (6)
- Politisches Theater (6)
- Pornographie (6)
- Portal hypertension (6)
- Portfolio Choice (6)
- Posttraumatic stress disorder (6)
- Postural control (6)
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- Digitalität (4)
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- Diorama (4)
- Dirac (4)
- Disability (4)
- Discretion (4)
- Diskurstheorie (4)
- Displacement (4)
- Disposition Effect (4)
- Dispositiv (4)
- Disziplin <Wissenschaft> (4)
- Divina commedia (4)
- Docking (4)
- Doderer, Heimito von (4)
- Doku Mittelstufe (4)
- Doku Oberstufe (4)
- Dokumentarliteratur (4)
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- Drug discovery (4)
- Duineser Elegien (4)
- Dylan (4)
- Dynamical systems (4)
- Dynamisches Gleichgewicht (4)
- Dyserinck, Hugo (4)
- Dyson–Schwinger equations (4)
- Döblin, Alfred / Berlin Alexanderplatz (4)
- Düffel, John von (4)
- E. coli (4)
- EPR (4)
- ER stress (4)
- Early Carboniferous (4)
- Eastern Arc Mountains (4)
- Ebola (4)
- Eginald Schlattner (4)
- Ehe <Motiv> (4)
- Ehe- und Familienrecht (4)
- Ehrung (4)
- Eich, Günter (4)
- Eichendorff, Joseph von (4)
- Eigenkapital (4)
- Einbahnstraße (4)
- Einfluss (4)
- Einheit (4)
- Einkommensteuer (4)
- Einsamkeit <Motiv> (4)
- Electroencephalography – EEG (4)
- Electron microscopy (4)
- Elektra (4)
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- Embryos (4)
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- Emotion regulation (4)
- Endocrinology (4)
- Endoscopic retrograde cholangiopancreatography (4)
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- Epirrita autumnata (4)
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- Erasmus, Desiderius (4)
- Ergänzung <Linguistik> (4)
- Erlenbruch (4)
- Erwartungsbildung (4)
- Essayist (4)
- Estudios organizacionales (4)
- Ethiopia (4)
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- Eugenik (4)
- Europa <Motiv> (4)
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- Evidence-based medicine (4)
- Evolutionary biology (4)
- Exotic options (4)
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- Expectations (4)
- Expedition (4)
- Experimentelle Lyrik (4)
- Exponential smoothing (4)
- Eyes (4)
- FEBID (4)
- FOMC (4)
- FPGA (4)
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- Face (4)
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- Figur (4)
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- Fisher information (4)
- Floristisch-Soziologische Arbeitsgemeinschaft (4)
- Flow (4)
- Flugschrift (4)
- Flusser, Vilém (4)
- Flusssediment (4)
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- Formale Sprache (4)
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- Frankfurt <Main> / Institut für Kernphysik (4)
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- Frankfurt school (4)
- Frankliniella occidentalis (4)
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- Fremdsprachenkenntnis (4)
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- Freud, Sigmund: Zeitgemäßes über Krieg und Tod (4)
- Freundschaft <Motiv> (4)
- Friede <Motiv> (4)
- Friedensbewegung (4)
- Friedenskonferenz (4)
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- Functional magnetic resonance imaging (4)
- Funktionalismus <Linguistik> (4)
- Fußnote (4)
- Fähigkeit (4)
- Fälschung (4)
- Führungskraft (4)
- G-quadruplexes (4)
- GABA (4)
- GC-MS (4)
- GMYC (4)
- Gabor lens (4)
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- Gewerkschaft (4)
- Gewerkschaftsbund der Angestellten (GdA, 1920-) (4)
- Gewinn (4)
- Giorgio Agamben (4)
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- Glucose (4)
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- Gläubiger (4)
- Goethe (4)
- Goethe, Johann Wolfgang von / Die Wahlverwandtschaften (4)
- Google (4)
- Gott (4)
- Gottfried August (4)
- Gotthelf, Jeremias (4)
- Gotthold Ephraim (4)
- Gottsched, Johann Christoph (4)
- Graphic Novel (4)
- Greater Antilles (4)
- Greek (4)
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- Grillparzer, Franz / König Ottokars Glück und Ende (4)
- Gross-Neveu model (4)
- Grundrechte (4)
- Gruša, Jiří (4)
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- Guinea (4)
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- HER2 (4)
- HIF (4)
- HPLC (4)
- Hadloub, Johannes (4)
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- Haus <Motiv> (4)
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- Herzl, Theodor (4)
- Herzogin Anna Amalia Bibliothek (4)
- Hesse, Hermann (4)
- Heterogeneity (4)
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- Hispaniola (4)
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- Hobbes, Thomas (4)
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- Homosexualität <Motiv> (4)
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- Houellebecq, Michel (4)
- Household Crisis Barometer (4)
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- Huber, Therese (4)
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- Hugo, Victor (4)
- Hultschiner Ländchen (4)
- Humanism (4)
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- Humanität <Motiv> (4)
- Humboldt, Alexander von (4)
- Hunsrückisch (4)
- Husserl, Edmund (4)
- Hybridisierung (4)
- Höfische Kultur (4)
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- IAP proteins (4)
- ICC (4)
- ICT (4)
- ICZN (4)
- ISGylation (4)
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- Ich-Identität <Motiv> (4)
- Identitätsfindung (4)
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- Juden <Motiv> (4)
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- Kehlmann, Daniel (4)
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- Klee, Paul (4)
- Klemperer, Victor (4)
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- Meyer, Conrad Ferdinand (4)
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- PGE2 (4)
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- Parenthese (4)
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- Patient safety (4)
- Paul, Jean (4)
- Pediatric (4)
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- Queensland (4)
- RCT (4)
- RDF (4)
- REM sleep (4)
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- RNA processing (4)
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- RUCAM (4)
- Rap (4)
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- Schelling, Friedrich Wilhelm Joseph von (4)
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- Schmitt, Carl (4)
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- Schwarzenbach, Annemarie (4)
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- Science-Fiction-Literatur (4)
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- Se questo è un uomo (4)
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- Solution NMR spectroscopy (4)
- Solution NMR-spectroscopy (4)
- Sondersammelgebiet (4)
- Sophocles (4)
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The little-known Roman gold mining site "Gralheira" is located near the well-explored mine of Tresminas. The 2.5 km long, almost dead straight archaeological monument from the first and second centuries AD is currently under threat from possible mining activities on the one hand and from modern waste disposal in the pits on the other. Since 2019, the Roman mining traces have been investigated by means of intensive field inspections, terrestrial 3d laser scanning and aerial photography. The following article will present first impressions and findings on this structure, as well as questions and preliminary interpretations.
Die vorliegende Studie beschäftigt sich mit der Konstituierung von amicitia im Mythos und fragt nach der Erzählung als Gabe im amikalen Gabentauschzyklus. Die Hinweise auf amicitia als eine der zentralen Bindungstypen des römischen Gemeinwesens sind über verschiedene Werke verstreut, lassen aber bereits die Wirkkraft erahnen, weil sie rückblickend in die Frühzeit hineingeschrieben wurden. In diesem Zusammenhang wird auch die Bedeutung der Erzählung als Gabe im Gabentauschzyklus untersucht, da diese die Transformation vom Fremden zum Anderen ermöglichen kann; erst auf diese Weise wird eine Grundlage für amicitia geschaffen. Darüber hinaus gelingt erst in der Urvergangenheit des Mythos’ die Perpetuierung von amicitia und dem sie konstituierenden amikalen Gabentausch.
Endogenous nitro-fatty acids (NFA) are potent electrophilic lipid mediators that exert biological effects in vitro and in vivo via selective covalent modification of thiol-containing target proteins. The cytoprotective, anti-inflammatory, and anti-tumorigenic effects of NFA in animal models of disease caused by targeted protein nitroalkylation are a valuable basis for the development of future anti-phlogistic and anti-neoplastic drugs. Considering the complexity of diseases and accompanying comorbidities there is an urgent need for clinically effective multifunctional drugs. NFA are composed of a fatty acid backbone containing a nitroalkene moiety triggering Michael addition reactions. However, less is known about the target-specific structure–activity relationships and selectivities comparing different NFA targets. Therefore, we analyzed 15 NFA derivatives and compared them with the lead structure 9-nitro-oleic acid (9NOA) in terms of their effect on NF-κB (nuclear factor kappa B) signaling inhibition, induction of Nrf-2 (nuclear factor erythroid 2-related factor 2) gene expression, sEH (soluble epoxide hydrolase), LO (lipoxygenase), and COX-2 (cyclooxygenase-2) inhibition, and their cytotoxic effects on colorectal cancer cells. Minor modifications of the Michael acceptor position and variation of the chain length led to drugs showing increased target preference or enhanced multi-targeting, partly with higher potency than 9NOA. This study is a significant step forward to better understanding the biology of NFA and their enormous potential as scaffolds for designing future anti-inflammatory drugs.
The complex and adaptive nature of malignant neoplasm constitute a major challenge for the development of effective anti-oncogenic therapies. Emerging evidence has uncovered the pivotal functions exerted by the small leucine-rich proteoglycans, decorin and biglycan, in affecting tumor growth and progression. In their soluble forms, decorin and biglycan act as powerful signaling molecules. By receptor-mediated signal transduction, both proteoglycans modulate key processes vital for tumor initiation and progression, such as autophagy, inflammation, cell-cycle, apoptosis, and angiogenesis. Despite of their structural homology, these two proteoglycans interact with distinct cell surface receptors and thus modulate distinct signaling pathways that ultimately affect cancer development. In this review, we summarize growing evidence for the complex roles of decorin and biglycan signaling in tumor biology and address potential novel therapeutic implications.
Effect of Chemotherapy on Overall Survival in Contemporary Metastatic Prostate Cancer Patients
(2021)
Introduction: Randomized clinical trials demonstrated improved overall survival in chemotherapy exposed metastatic prostate cancer patients. However, real-world data validating this effect with large scale epidemiological data sets are scarce and might not agree with trials. We tested this hypothesis.
Materials and Methods: We identified de novo metastatic prostate cancer patients within the Surveillance, Epidemiology, and End Results (SEER) database (2014-2015). Kaplan-Meier plots and Cox regression models tested for overall survival differences between chemotherapy-exposed patients vs chemotherapy-naïve patients. All analyses were repeated in propensity-score matched cohorts. Additionally, landmark analyses were applied to account for potential immortal time bias.
Results: Overall, 4295 de novo metastatic prostate cancer patients were identified. Of those, 905 (21.1%) patients received chemotherapy vs 3390 (78.9%) did not. Median overall survival was not reached at 30 months follow-up. Chemotherapy-exposed patients exhibited significantly better overall survival (61.6 vs 54.3%, multivariable HR:0.82, CI: 0.72-0.96, p=0.01) at 30 months compared to their chemotherapy-naïve counterparts. These findings were confirmed in propensity score matched analyses (multivariable HR: 0.77, CI:0.66-0.90, p<0.001). Results remained unchanged after landmark analyses were applied in propensity score matched population.
Conclusions: In this contemporary real-world population-based cohort, chemotherapy for metastatic prostate cancer patients was associated with better overall survival. However, the magnitude of overall survival benefit was not comparable to phase 3 trials.
Introduction: To evaluate the oncological outcome of high dose rate (HDR) brachytherapy (BRT) as monotherapy for clinically localised prostate cancer (PCA).
Material and Methods: Between January 2002 and February 2004, 141 consecutive patients with clinically localised PCA were treated with HDR-BRT monotherapy. The cohort comprised 103 (73%) low-, 32 (22.7%) intermediate- and 6 (4.3%) high risk patients according to D’Amico classification or 104 (73.8%) low-, 24 (17.0%) intermediate favourable-, 12 (8.5%) intermediate unfavourable- and one (0.7%) very high risk patient according to National Comprehensive Cancer Network (NCCN) one. Patients received four fractions of 9.5 Gy delivered within a single implant up to a total physical dose of 38 Gy. Catheter-implantation was transrectal ultrasound-based whereas treatment planning CT-based. Thirty-three patients (23.4%) received ADT neoadjuvantly and continued concurrently with BRT. Biochemical relapse-free survival (BRFS) was defined according to the Phoenix Consensus Criteria and genitourinary (GU)/gastrointestinal (GI) toxicity evaluated using the Common Toxicity Criteria for Adverse Events version 5.0.
Results: Median age at treatment and median follow-up time was 67.2 and 15.2 years, respectively. Twenty-three (16.3%) patients experienced a biochemical relapse and 5 (3.5%) developed distant metastases, with only one patient dying of PCA. The BRFS was 85.1% at 15 years and 78.7% at 18 years. The corresponding overall survival, metastases-free survival, and prostate cancer specific mortality at 15- and 18-years was 73.9%/59.1%, 98.3%/90.6%, and 100%/98.5% respectively. Late grade 3 GI and GU toxicity was 4.2% and 5.6% respectively. Erectile dysfunction grade 3 was reported by 27 (19%) patients. From the prognostic factors evaluated, tumor stage (≤T2b compared to ≥T2c) along with the risk group (low-intermediate vs. high) when using the D’Amico classification but not when the NCCN one was taken into account, correlated significantly with BRFS.
Conclusion: Our long-term results confirm HDR-BRT to be a safe and effective monotherapeutic treatment modality for low- and intermediate risk PCA.
Biological as well as advanced artificial intelligences (AIs) need to decide which goals to pursue. We review nature's solution to the time allocation problem, which is based on a continuously readjusted categorical weighting mechanism we experience introspectively as emotions. One observes phylogenetically that the available number of emotional states increases hand in hand with the cognitive capabilities of animals and that raising levels of intelligence entail ever larger sets of behavioral options. Our ability to experience a multitude of potentially conflicting feelings is in this view not a leftover of a more primitive heritage, but a generic mechanism for attributing values to behavioral options that can not be specified at birth. In this view, emotions are essential for understanding the mind. For concreteness, we propose and discuss a framework which mimics emotions on a functional level. Based on time allocation via emotional stationarity (TAES), emotions are implemented as abstract criteria, such as satisfaction, challenge and boredom, which serve to evaluate activities that have been carried out. The resulting timeline of experienced emotions is compared with the “character” of the agent, which is defined in terms of a preferred distribution of emotional states. The long-term goal of the agent, to align experience with character, is achieved by optimizing the frequency for selecting individual tasks. Upon optimization, the statistics of emotion experience becomes stationary.
Establishing management programs to preserve the benthic communities along the NW Pacific and the Arctic Ocean (AO) requires a deep understanding of the composition of communities and their responses to environmental stressors. In this study, we thus examine patterns of benthic community composition and patterns of species richness along the NW Pacific and Arctic Seas and investigate the most important environmental drivers of those patterns. Overall we found a trend of decreasing species richness toward higher latitudes and deeper waters, peaking in coastal waters of the eastern Philippines. The most dominant taxa along the entire study area were Arthropoda, Mollusca, Cnidaria, Echinodermata, and Annelida. We found that depth, not temperature, was the main driver of community composition along the NW Pacific and neighboring Arctic Seas. Depth has been previously suggested as a factor driving species distribution in benthic fauna. Following depth, the most influential environmental drivers of community composition along the NW Pacific and the Arctic Ocean were silicate, light, and currents. For example, silicate in Hexactinellida, Holothuroidea, and Ophiuroidea; and light in Cephalopoda and Gymnolaemata had the highest correlations with community composition. In this study, based on a combination of new samples and open-access data, we show that different benthic communities might respond differently to future climatic changes based on their taxon-specific biological, physiological, and ecological characteristics. International conservation efforts and habitat preservation should take an adaptive approach and apply measures that take the differences among benthic communities in responding to future climate change into account. This facilitates implementing appropriate conservation management strategies and sustainable utilization of the NW Pacific and Arctic marine ecosystems.
The analysis of ethanol and of its congeners in blood plays an important role in forensic cases, especially when allegations are made that alcohol has been consumed after an accident. In alcoholic beverages, congener alcohols are by-products and are generated during fermentation. The assay of these compounds in serum samples and beverages has been previously performed using headspace-gas chromatography-flame ionization detection methods (HS-GC-FID). As an alternative, a robust headspace-gas chromatography-mass spectrometry (HS-GC-MS) procedure was developed and validated, which has the following advantages:
- Simultaneous determination of ethanol, congener alcohols and other
endogenous substances.
- Reduction of matrix interference by increasing selectivity and
specificity.
- Clear separation of the positional isomers 3-methyl-1-butanol and
2-methyl-1-butanol.
Peracarid data were collected in the Southern Ocean and South Atlantic Ocean. Sampling was performed during nine different expeditions on board of RRS James Clark Ross and RV Polarstern, using epibenthic sledges (EBS) at depth ranging between 160–6348 m at 109 locations. The correlation between environmental variables and peracarid abundance was investigated. Abundance data comprise a total of 128570 peracarids (52366 were amphipods, 28516 were cumaceans, 36142 isopods, 5676 mysidaceans and 5870 were tanaidaceans). The presented data are useful to investigate the composition and abundance patterns of peracarid orders at a wide depth range and spatial scale in the Southern Ocean. They can also be reused to compare their abundance with that of other taxa in broader ecological surveys.
Insects with aquatic life stages can transfer sediment and water pollutants to terrestrial ecosystems, which has been described for metals, polyaromatic hydrocarbons, and polychlorinated chemicals. However, knowledge of the transfer of aquatic micropollutants released by wastewater treatment plants is scarce despite some preliminary studies on their occurrence in riparian spiders. In our study, we address a major analytical gap focusing on the transfer of the micropollutant carbamazepine from the larvae to the adult midges of Chironomus riparius using an optimized QuEChERS extraction method and HPLC–MS/MS applicable to both life stages down to the level of about three individuals. We show that the uptake of carbamazepine by larvae is concentration-dependent and reduces the emergence rate. Importantly, the body burden remained constant in adult midges. Using this information, we estimated the daily exposure of insectivorous tree swallows as terrestrial predators to carbamazepine using the energy demand of the predator and the energy content of the prey. Assuming environmentally relevant water concentrations of about 1 μg/L, the daily dose per kilogram of body weight for tree swallows was estimated to be 0.5 μg/kg/day. At places of high water contamination of 10 μg/L, the exposure may reach 5 μg/kg/day for this micropollutant of medium polarity. Considering body burden changes upon metamorphosis, this study fills the missing link between aquatic contamination and exposure in terrestrial habitats showing that wastewater pollutants can impact birds’ life. Clearly, further analytical methods for biota analysis in both habitats are urgently required to improve risk assessment.
Tectonics and geothermal gradients from subduction to collision in the NW Variscan Iberian Massif
(2022)
The earliest tectonometamorphic record of tectonic slices incorporated to the base of an orogen holds the key to understand how an orogen is built. The tectonic pile of the NW Iberian section of the Variscan Orogen includes tectonic slices separated by crustal-scale thrusts. The earliest tectonometamorphic record in the uppermost parautochthon is calculated at 11–14 kbar and 450–500°C (P-T gradient about 13°C/km), suggesting a subduction-related metamorphic recrystallization at lower pressure than the overlying Lower Allochthon. Early conditions calculated in the autochthon (9–10 kbar and 425–450°C; 16°C/km) point to a relatively ‘cold’ collisional setting. Higher thermal gradients obtained from some sections of the autochthon (11–12 kbar and 700–725°C; 21°C/km) and the Lower Parautochthon (7.5 kbar and 550–700°C; 24–31°C/km), correspond to more advanced and ‘hot’ stages of collision. New U–Pb monazite geochronology indicates a 318–311 Ma age for the final formation of HT domes in the region. We propose the rapid decrease in P-T gradient (from <10 to 16°C/km) documents a fail to sustain further burial along a regular subduction zone. We consider the subsequent increase in the geothermal gradient (from 16 to 31°C/km) as the culmination of previous crustal accretion and the onset of crustal underthrusting and later processes in a collisional stage. We propose these switches in the early tectonometamorphic record of individual tectonic slices as potential markers to track the transition from subduction to collision in collisional orogens.
Aim
In the CheckRad-CD8 trial patients with locally advanced head and neck squamous cell cancer are treated with a single cycle of induction chemo-immunotherapy (ICIT). Patients with pathological complete response (pCR) in the re-biopsy enter radioimmunotherapy. Our goal was to study the value of F-18-FDG PET/CT in the prediction of pCR after induction therapy.
Methods
Patients treated within the CheckRad-CD8 trial that additionally received FDG- PET/CT imaging at the following two time points were included: 3–14 days before (pre-ICIT) and 21–28 days after (post-ICIT) receiving ICIT. Tracer uptake in primary tumors (PT) and suspicious cervical lymph nodes (LN +) was measured using different quantitative parameters on EANM Research Ltd (EARL) accredited PET reconstructions. In addition, mean FDG uptake levels in lymphatic and hematopoietic organs were examined. Percent decrease (Δ) in FDG uptake was calculated for all parameters. Biopsy of the PT post-ICIT acquired after FDG-PET/CT served as reference. The cohort was divided in patients with pCR and residual tumor (ReTu).
Results
Thirty-one patients were included. In ROC analysis, ΔSUVmax PT performed best (AUC = 0.89) in predicting pCR (n = 17), with a decline of at least 60% (sensitivity, 0.77; specificity, 0.93). Residual SUVmax PT post-ICIT performed best in predicting ReTu (n = 14), at a cutpoint of 6.0 (AUC = 0.91; sensitivity, 0.86; specificity, 0.88). Combining two quantitative parameters (ΔSUVmax ≥ 50% and SUVmax PT post-ICIT ≤ 6.0) conferred a sensitivity of 0.81 and a specificity of 0.93 for determining pCR. Background activity in lymphatic organs or uptake in suspected cervical lymph node metastases lacked significant predictive value.
Conclusion
FDG-PET/CT can identify patients with pCR after ICIT via residual FDG uptake levels in primary tumors and the related changes compared to baseline. FDG-uptake in LN + had no predictive value.
Trial registry
ClinicalTrials.gov identifier: NCT03426657.
Bird-mediated seed dispersal is crucial for the regeneration and viability of ecosystems, often resulting in complex mutualistic species networks. Yet, how this mutualism drives the evolution of seed dispersing birds is still poorly understood. In the present study we combine whole genome re-sequencing analyses and morphometric data to assess the evolutionary processes that shaped the diversification of the Eurasian nutcracker (Nucifraga), a seed disperser known for its mutualism with pines (Pinus). Our results show that the divergence and phylogeographic patterns of nutcrackers resemble those of other non-mutualistic passerine birds and suggest that their early diversification was shaped by similar biogeographic and climatic processes. The limited variation in foraging traits indicates that local adaptation to pines likely played a minor role. Our study shows that close mutualistic relationships between bird and plant species might not necessarily act as a primary driver of evolution and diversification in resource-specialized birds.
Background and Aims
Prothrombin induced by vitamin K absence-II (PIVKA-II) is a serum biomarker linked to hepatocellular carcinoma (HCC), showing superiority to alpha-fetoprotein (AFP) for early disease detection. We aimed to assess the clinical and analytical performance of the Elecsys® PIVKA-II immunoassay in diagnosing HCC and evaluate PIVKA-II's technical performance.
Methods
Serum samples from adult cases (i.e. patients with a first-time HCC diagnosis; n = 168) and disease controls (i.e. patients without HCC with an at-risk condition; n = 208) were assessed. An AFP cut-off of 20 ng/mL was used to differentiate between HCC cases and disease controls. Clinical performance of the Elecsys PIVKA-II assay was compared with that of comparator assays (Lumipulse G PIVKA-II, μTASWako DCP, ARCHITECT PIVKA-II) using receiver operating characteristic curve analysis to determine the area under the curve (AUC) values.
Results
The Elecsys PIVKA-II assay compared favorably with comparator assays. Using a 28.4 ng/mL cut-off, the Elecsys PIVKA-II assay detected HCC with 86.9% sensitivity and 83.7% specificity. Clinical performance of the Elecsys PIVKA-II assay (AUC: 90.8%) was equivalent to that of comparator assays (AUC: 88.3–89.6%). Relatively high PIVKA-II concentrations were observed for cholangiocarcinoma and pancreatic cancer with the Elecsys assay in specificity panel analyses, indicating that high PIVKA-II concentrations should not be used alone in the absence of other clinical data.
Conclusions
The Elecsys PIVKA-II assay showed good analytical performance under routine laboratory conditions, comparing favorably with comparator assays. These findings support the suitability of the Elecsys PIVKA-II assay as an aid in HCC diagnosis.
In narratology, a widely recognized method involves exploring the connection between implied authors and implied readers. It entails correlating abstract narrative components within a text to understand the conveyed message and the multitude of interpretations it can offer. The present study adopts an implied reader-oriented approach to analyze three selected novels from the twentieth and twenty-first centuries—one Nigerian, one Caribbean, and one Kurdish. The aim is to explore the potential readings within these texts, considering the hermeneutic process of critical reading. The selected texts include Chinua Achebe’s Things Fall Apart, (1958), Same Selvon’s The Lonely Londoners, (1956), and Karwan Kakesur’s The Channels of the Armed Monkeys, (2011). This approach closely examines the communication between the author and reader of the text, with a special focus on the varying levels of communication between the components of the narration, including fictional and implied fictional communication.
The implied fictional communication occurs between a narrative agent known as ‘the implied author’ and its fictional counterpart ‘the implied reader’ rather than between the real, flesh and blood authors and readers. I argue that this level of communication is coded, and the act of decoding it is part of the reading process performed by the reader. Certain texts can propose different and sometimes opposing readings which are initially and purposefully designed by the implied author and addressed to different implied readers. These readings are not necessarily the results of different real readers but rather incorporated ones predetermined by the implied author only to be acknowledged and uncovered by the readers. In other words, the latent meaning is and always was an integral part of the text and is not something created by the imaginative reader or critic. The core interest of my thesis lies in identifying prompts and suggestions within the narrative of the selected texts and ultimately understanding the readerships prestructured in them. Identifying the different readers within those texts will provide new reinterpretations that can add undetected values to the reading process and sometimes suggests opposing readings to how those texts have so far been read. Additionally, it is the objective of this thesis to propose new ways that readers can interact with reading literature that would result in a more aesthetic and entertaining reading experience besides providing ways to be more informed and aware of the cues certain narrative texts contain.
There have been numerous critical studies on both narratology and postcolonial or minority literatures; however, there has been little scholarly work that attempts to utilize narratology as a theoretical foundation for understanding postcolonial and minority fiction.
This study examines fictional texts from Nigerian, Caribbean, and Kurdish literature, employing the narratological concept known as ‘Multiple Implied Readers’. By incorporating concepts from Brian Richardson’s ‘Singular Text, Multiple Implied Readers’, and Peter J. Rabinowitz’s ‘authorial audiences’, I explore the various readerships that the texts could encompass. This exploitation may lead to the discovery of new readings, interpretations, and meanings that would otherwise remain undetected. These structures introduce provocative indeterminacies that challenge the reader’s synthesis of information into coherent configurations of meaning. Consequently, this approach not only enhances the reading experience but also opens doors to new interpretations of the text. In some cases, these interpretations could even dismantle prior understandings and propose entirely new readings.
The concepts of the implied author and implied reader have been studied before in relation to various disciplines of narratology. However, by applying them in conjunction with the relatively less researched subject of multiple implied readers, I aim to shed light on important aspects of these readings. This exploration could prove beneficial for literature students as well as critical readers of literary texts, revealing the potential of these texts to accommodate more than one implied reader within their narratives.
Annotationes Epigraphicae XIII. Zu einigen Inschriften aus der römischen Provinz Gallia Lugdunensis
(2023)
Die seit einigen Jahren andauernde Arbeit an einem kommentierenden Onomastikon für die römische Provinz Gallia Lugdunensis, das in absehbarer Zeit erscheinen soll, lenkte die Aufmerksamkeit des Autors auf mehrere bemerkenswerte Inschriften aus der zentralgallischen Provinz, die ausführlichere Betrachtungen rechtfertigen. Alle folgenden Anmerkungen zu 15 ausgewählten Inschriften beziehen sich auf epigraphische und onomastische Denkwürdigkeiten, die in wesentlich kürzerer Form auch in dem angekündigten Namenskatalog verschriftlicht wurden.
Im Bellum Iudaicum des Flavius Josephus geht es sehr häufig um Schuldzuweisungen und Niederlagenerklärungen bzw. Deutungen und Umdeutungen von Scheitern: Das eigene Versagen des Josephus als Feldherr der Juden in Galiläa, das Scheitern des syrischen Statthalters Cestius Gallus und dessen Niederlage bei Beth Horon, das ‚Versagen‘ (?) des Titus als Kommandeur beim Brand des Tempels. Josephus nimmt durchaus verschiedene Perspektiven ein, die es genauer zu betrachten gilt. Was war die Absicht hinter seinen Deutungen, Umdeutungen, bei eventuellem Verschweigen und Verdrängen? Wer war jeweils sein Publikum? Wie kann man insbesondere die Darstellung des Titus verstehen? Mit Bezug auf die Zerstörung des Tempels von Jerusalem, schließlich religiöses wie politisches Symbol jüdischer Integrität und Identität, ist die Darstellung des Feldherrn jedenfalls objektiv vernichtend – er verliert die Kontrolle über die Truppen. Josephus findet die Lösung zur Entlastung des Titus, aber auf Kosten seines Renommees als Feldherr!
Hintergrund: Bei steigender Lebenserwartung ergibt sich in Zukunft eine steigende Prävalenz der degenerativen Aortenklappenstenose (AS). Die Transkathether-Aortenklappenimplantation (TAVI) erfährt immer größere Bedeutung in der Behandlung der symptomatischen, hochgradigen AS. Eine paravalvuläre Leckage (PVL) ist ein anerkannter Risikofaktor für eine erhöhte Mortalität und sollte periinterventionell adäquat erkannt und behandelt werden. Eine Postdilatation als typische korrigierende Intervention (CI) kann allerdings zu schwerwiegenden Komplikationen führen. Weitere Instrumente zur Entscheidung über die Notwendigkeit einer CI sind erstrebenswert. Für die Aortenregurgitationsindex-Ratio (ARI-Ratio) und für die präprozedurale Kalklast, gemessen mit der Mehrschicht-Computertomografie (MSCT), wurde gezeigt, dass beide prädiktiv sind für die Notwendigkeit einer periinterventionellen CI.
Ziele: Die ARI-Ratio und der Kalkstatus wurde in Hinblick auf ihren prädiktiven Wert für die Notwendigkeit einer CI miteinander verglichen.
Methoden: Von 199 Patienten nach TAVI erhielten 38,9 % eine Portico™, 29,5 % eine Symetis Acurate™, 21,5 % eine Sapien 3™ und 10,1 % eine Evolut™. Es wurde retrospektiv der postinterventionell erhobene systolische (SB), diastolische (DB) und linksventrikuläre enddiastolische Blutdruck (LVEDP) im ARI zusammengefasst: [(DBP - LVEDP) / SBP] × 100. Die ARI-Ratio wurde berechnet als Quotient zwischen ARI nach und vor dem Eingriff. Des Weiteren wurden die MSCTs mittels „3mensio Structural Heart“ analysiert insbesondere in Hinblick auf die Verkalkung des linksventrikulären Ausflusstrakts, der Aortenklappe (gesamt sowie der einzelnen Taschen) und des sinotubulären Übergang. Dabei wurde der Kalzium-Volumen-Score auf Basis drei verschiedener Thresholds benutzt (500 Hounsfield Einheiten (HU), 800 HU und visuell-individuell). Im Folgenden wurden ROC-Kurven für den ARI-Ratio und für die verschiedenen Kalklastparameter erstellt um die Notwendigkeit einer CI zu beurteilen. Schließlich wurde die Area under the curve (AUC) der ARI-Ratio mit denen der Kalklastsurrogatparameter verglichen.
Ergebnisse: Die ARI-Ratio zeigte mit einer AUC von 0,747 das beste Ergebnis. Bei den Verkalkungsparametern zeigte die Verkalkung der noncoronaren Aortenklappentasche die beste AUC, nachfolgend die der gesamten Aortenklappe. Der 800-HU-Threshold zeigte bessere AUCs als 500 HU. Von 19 Verkalkungssurrogatparametern zeigten elf einen statistisch signifikanten Vorhersagewert auf. Die ARI-Ratio zeigte eine signifikante Überlegenheit gegenüber sechs dieser Parameter. Für die fünf Verbliebenen konnte kein signifikanter Unterschied nachgewiesen werden.
Schlussfolgerung: Die ARI-Ratio ist ein besserer Prädiktor für die Notwendigkeit einer CI als die Kalzifikationsparameter. Auch diverse Kalzifikationsparameter haben diesbezüglich eine Aussagekraft. Die Kalzifikationsparameter können bereits präinterventionell beurteilt werden können, die ARI-Ratio nur periinterventionell. Es sollte neben der Anschauung von bereits etablierten Methoden ein integrativer Ansatz gewählt werden, der Kalklast und ARI-Ratio für die Entscheidung zur Notwendigkeit einer CI miteinschließt. Weitere Studien zur Standardisierung der Verkalkungsparameter sind notwendig für eine weitere Einordnung deren Vorhersagekraft. Es bestanden teils erhebliche Unterschiede zwischen den verwendeten Klappenprothesentypen. Weitere Studien mit einer größeren Anzahl an verschiedenen Prothesentypen könnten richtungsweisende Subgruppenanalysen möglich machen.
To evade the host's immune response, herpes simplex virus employs the immediate early gene product ICP47 (IE12) to suppress antigen presentation to cytotoxic T-lymphocytes by inhibition of the ATP-binding cassette transporter associated with antigen processing (TAP). ICP47 is a membrane-associated protein adopting an alpha-helical conformation. Its active domain was mapped to residues 3-34 and shown to encode all functional properties of the full-length protein. The active domain of ICP47 was reconstituted into oriented phospholipid bilayers and studied by proton-decoupled 15N and 2H solid-state NMR spectroscopy. In phospholipid bilayers, the protein adopts a helix-loop-helix structure, where the average tilt angle of the helices relative to the membrane surface is approximately 15 degrees (+/- 7 degrees ). The alignment of both structured domains exhibits a mosaic spread of approximately 10 degrees . A flexible dynamic loop encompassing residues 17 and 18 separates the two helices. Refinement of the experimental data indicates that helix 1 inserts more deeply into the membrane. These novel insights into the structure of ICP47 represent an important step toward a molecular understanding of the immune evasion mechanism of herpes simplex virus and are instrumental for the design of new therapeutics.
The majority of bacterial membrane-bound NiFe-hydrogenases and formate dehydrogenases have homologous membrane-integral cytochrome b subunits. The prototypic NiFe-hydrogenase of Wolinella succinogenes (HydABC complex) catalyzes H2 oxidation by menaquinone during anaerobic respiration and contains a membrane-integral cytochrome b subunit (HydC) that carries the menaquinone reduction site. Using the crystal structure of the homologous FdnI subunit of Escherichia coli formate dehydrogenase-N as a model, the HydC protein was modified to examine residues thought to be involved in menaquinone binding. Variant HydABC complexes were produced in W. succinogenes, and several conserved HydC residues were identified that are essential for growth with H2 as electron donor and for quinone reduction by H2. Modification of HydC with a C-terminal Strep-tag II enabled one-step purification of the HydABC complex by Strep-Tactin affinity chromatography. The tagged HydC, separated from HydAB by isoelectric focusing, was shown to contain 1.9 mol of heme b/mol of HydC demonstrating that HydC ligates both heme b groups. The four histidine residues predicted as axial heme b ligands were individually replaced by alanine in Strep-tagged HydC. Replacement of either histidine ligand of the heme b group proximal to HydAB led to HydABC preparations that contained only one heme b group. This remaining heme b could be completely reduced by quinone supporting the view that the menaquinone reduction site is located near the distal heme b group. The results indicate that both heme b groups are involved in electron transport and that the architecture of the menaquinone reduction site near the cytoplasmic side of the membrane is similar to that proposed for E. coli FdnI.
We analyzed a eukaryotically encoded rubredoxin from the cryptomonad Guillardia theta and identified additional domains at the N- and C-termini in comparison to known prokaryotic paralogous molecules. The cryptophytic N-terminal extension was shown to be a transit peptide for intracellular targeting of the protein to the plastid, whereas a C-terminal domain represents a membrane anchor. Rubredoxin was identified in all tested phototrophic eukaryotes. Presumably facilitated by its C-terminal extension, nucleomorph-encoded rubredoxin (nmRub) is associated with the thylakoid membrane. Association with photosystem II (PSII) was demonstrated by co-localization of nmRub and PSII membrane particles and PSII core complexes and confirmed by comparative electron paramagnetic resonance measurements. The midpoint potential of nmRub was determined as +125 mV, which is the highest redox potential of all known rubredoxins. Therefore, nmRub provides a striking example of the ability of the protein environment to tune the redox potentials of metal sites, allowing for evolutionary adaption in specific electron transport systems, as for example that coupled to the PSII pathway.
In Archaea, bacteria, and eukarya, ATP provides metabolic energy for energy-dependent processes. It is synthesized by enzymes known as A-type or F-type ATP synthase, which are the smallest rotatory engines in nature (Yoshida, M., Muneyuki, E., and Hisabori, T. (2001) Nat. Rev. Mol. Cell. Biol. 2, 669-677; Imamura, H., Nakano, M., Noji, H., Muneyuki, E., Ohkuma, S., Yoshida, M., and Yokoyama, K. (2003) Proc. Natl. Acad. Sci. U. S. A. 100, 2312-2315). Here, we report the first projected structure of an intact A(1)A(0) ATP synthase from Methanococcus jannaschii as determined by electron microscopy and single particle analysis at a resolution of 1.8 nm. The enzyme with an overall length of 25.9 nm is organized in an A(1) headpiece (9.4 x 11.5 nm) and a membrane domain, A(0) (6.4 x 10.6 nm), which are linked by a central stalk with a length of approximately 8 nm. A part of the central stalk is surrounded by a horizontal-situated rodlike structure ("collar"), which interacts with a peripheral stalk extending from the A(0) domain up to the top of the A(1) portion, and a second structure connecting the collar structure with A(1). Superposition of the three-dimensional reconstruction and the solution structure of the A(1) complex from Methanosarcina mazei Gö1 have allowed the projections to be interpreted as the A(1) headpiece, a central and the peripheral stalk, and the integral A(0) domain. Finally, the structural organization of the A(1)A(0) complex is discussed in terms of the structural relationship to the related motors, F(1)F(0) ATP synthase and V(1)V(0) ATPases.
The cell division cycle protein 37 (Cdc37) and the 90-kDa heat shock protein (Hsp90) are molecular chaperones, which are crucial elements in the protein signaling pathway. The largest class of client proteins for Cdc37 and Hsp90 are protein kinases. The catalytic domains of these kinases are stabilized by Cdc37, and their proper folding and functioning is dependent on Hsp90. Here, we present the x-ray crystal structure of the 16-kDa middle domain of human Cdc37 at 1.88 angstroms resolution and the structure of this domain in complex with the 23-kDa N-terminal domain of human Hsp90 based on heteronuclear solution state NMR data and docking. Our results demonstrate that the middle domain of Cdc37 exists as a monomer. NMR and mutagenesis experiments reveal Leu-205 in Cdc37 as a key residue enabling complex formation. These findings can be very useful in the development of small molecule inhibitors against cancer.
Through its role in intron cleavage, tRNA splicing endonuclease (TSEN) plays a critical function in the maturation of intron-containing pre-tRNAs. The catalytic mechanism and core requirement for this process is conserved between archaea and eukaryotes, but for decades, it has been known that eukaryotic TSENs have evolved additional modes of RNA recognition, which have remained poorly understood. Recent research identified new roles for eukaryotic TSEN, including processing or degradation of additional RNA substrates, and determined the first structures of pre-tRNA-bound human TSEN complexes. These recent discoveries have changed our understanding of how the eukaryotic TSEN targets and recognizes substrates. Here, we review these recent discoveries, their implications, and the new questions raised by these findings.
Membrane-bound complex I (NADH:ubiquinone oxidoreductase) of the respiratory chain is considered the main site of mitochondrial radical formation and plays a major role in many mitochondrial pathologies. Structural information is scarce for complex I, and its molecular mechanism is not known. Recently, the 49-kDa subunit has been identified as part of the "catalytic core" conferring ubiquinone reduction by complex I. We found that the position of the 49-kDa subunit is clearly separated from the membrane part of complex I, suggesting an indirect mechanism of proton translocation. This contradicts all hypothetical mechanisms discussed in the field that link proton translocation directly to redox events and suggests an indirect mechanism of proton pumping by redox-driven conformational energy transfer.
We have isolated and characterized the cDNA encoding a Ca(2+)-dependent nucleoside diphosphatase (EC ) related to two secreted ATP- and ADP-hydrolyzing apyrases of the bloodsucking insects, Cimex lectularius and Phlebotomus papatasi. The rat brain-derived cDNA has an open reading frame of 1209 bp encoding a protein of 403 amino acids and a calculated molecular mass of 45.7 kDa. The mRNA was expressed in all tissues investigated, revealing two major transcripts with varying preponderance. The immunohistochemical analysis of the Myc-His-tagged enzyme expressed in Chinese hamster ovary cells revealed its association with the endoplasmic reticulum and also with pre-Golgi intermediates. Ca(2+)-dependent nucleoside diphosphatase is a membrane protein with its catalytic site facing the organelle lumen. It hydrolyzes nucleoside 5'-diphosphates in the order UDP >GDP = IDP >>>CDP but not ADP. Nucleoside 5'-triphosphates were hydrolyzed to a minor extent, and no hydrolysis of nucleoside 5'-monophosphates was observed. The enzyme was strongly activated by Ca(2+), insensitive to Mg(2+), and had a K(m) for UDP of 216 microm. Ca(2+)-dependent nucleoside diphosphatase may support glycosylation reactions related to quality control in the endoplasmic reticulum.
Importance: The entry of artificial intelligence into medicine is pending. Several methods have been used for the predictions of structured neuroimaging data, yet nobody compared them in this context.
Objective: Multi-class prediction is key for building computational aid systems for differential diagnosis. We compared support vector machine, random forest, gradient boosting, and deep feed-forward neural networks for the classification of different neurodegenerative syndromes based on structural magnetic resonance imaging.
Design, setting, and participants: Atlas-based volumetry was performed on multi-centric T1-weighted MRI data from 940 subjects, i.e., 124 healthy controls and 816 patients with ten different neurodegenerative diseases, leading to a multi-diagnostic multi-class classification task with eleven different classes.
Interventions: N.A.
Main outcomes and measures: Cohen’s kappa, accuracy, and F1-score to assess model performance.
Results: Overall, the neural network produced both the best performance measures and the most robust results. The smaller classes however were better classified by either the ensemble learning methods or the support vector machine, while performance measures for small classes were comparatively low, as expected. Diseases with regionally specific and pronounced atrophy patterns were generally better classified than diseases with widespread and rather weak atrophy.
Conclusions and relevance: Our study furthermore underlines the necessity of larger data sets but also calls for a careful consideration of different machine learning methods that can handle the type of data and the classification task best.
It is generally recognized that large-scale whaling in the 19th and 20th century led to a substantial reduction of the size of many cetacean populations, particularly those of the baleen whales (Mysticeti). The impact of these operations on genomic diversity of one of the most hunted whales, the fin whale (Balaenoptera physalus), has remained largely unaddressed because of the paucity of adequate samples and the limitation of applicable techniques. Here, we have examined the effect of whaling on the North Atlantic fin whale based on genomes of 51 individuals from Icelandic waters, representing three temporally separated intervals, 1989, 2009 and 2018 and provide a reference genome for the species. Demographic models suggest a noticeable drop of the effective population size of the North Atlantic fin whale around a century ago. The present results suggest that the genome-wide heterozygosity is not markedly reduced and has remained comparable with other baleen whale species. Similarly, there are no signs of apparent inbreeding, as measured by the proportion of long runs of homozygosity, or of a distinctively increased mutational load, as measured by the amount of putative deleterious mutations. Compared with other baleen whales, the North Atlantic fin whale appears to be less affected by anthropogenic influences than other whales such as the North Atlantic right whale, consistent with the presence of long runs of homozygosity and higher levels of mutational load in an otherwise more heterozygous genome. Thus, genome-wide assessments of other species and populations are essential for future, more specific, conservation efforts.
Background: The use of patient-reported outcome measures (PROM) and caregiver-reported outcome measures can raise the patient centeredness of treatment and improve the quality of palliative care. Nevertheless, the everyday implementation of self-report in patients and caregivers is complex, and should be adapted for use in specific settings. We aimed to implement a set of outcome measures that included patient and caregiver self- and proxy-reported outcome measures in specialised outpatient palliative care (SOPC). In this study, we explore how the Integrated Palliative Outcome Scale (IPOS), IPOS Views on Care (IPOS VoC) and the Short-form Zarit Caregiver Burden Interview (ZBI-7) can be feasibly, acceptably and appropriately implemented in the daily care routines of SOPC.
Methods: Five SOPC teams were trained, and used the outcome measures in daily practice. Team members were mainly nurses and physicians. To investigate their feedback, we used a multi-method qualitative design consisting of focus groups with SOPC-team members (n = 14), field notes of meetings and conversations with the SOPC teams. In an iterative process, we analysed the findings using qualitative content analysis and refined use of the outcome measures.
Results: We found that integrating patient and caregiver outcome measures into daily care routines in SOPC is feasible. To improve feasibility, acceptability and appropriateness, the resulting burden on patients and relatives should be kept to a minimum, the usefulness of the measures must be understood, they should be used considerately, and administration must be manageable. We removed ZBI-7 from the set of measures as a result of feedback on its content and wording.
Conclusions: SOPC-team members have reservations about the implementation of PROM in SOPC, but with appropriate adjustments, its application in daily care is feasible, accepted and perceived as appropriate. Previous to use, SOPC-team members should be trained in how to apply the measures, in the design of manageable processes that include integration into electronic documentation systems, and in ongoing evaluation and support. They should also be taught how useful the measures can be.
Acute kidney injury is associated with mortality in COVID-19 patients. However, host cell changes underlying infection of renal cells with SARS-CoV-2 remain unknown and prevent understanding of the molecular mechanisms that may contribute to renal pathology. Here, we carried out quantitative translatome and whole-cell proteomics analyses of primary renal proximal and distal tubular epithelial cells derived from human donors infected with SARS-CoV-2 or MERS-CoV to disseminate virus and cell type–specific changes over time. Our findings revealed shared pathways modified upon infection with both viruses, as well as SARS-CoV-2-specific host cell modulation driving key changes in innate immune activation and cellular protein quality control. Notably, MERS-CoV infection–induced specific changes in mitochondrial biology that were not observed in response to SARS-CoV-2 infection. Furthermore, we identified extensive modulation in pathways associated with kidney failure that changed in a virus- and cell type–specific manner. In summary, we provide an overview of the effects of SARS-CoV-2 or MERS-CoV infection on primary renal epithelial cells revealing key pathways that may be essential for viral replication.
While high-quality climate reconstructions of some past warm periods in the Cenozoic era now exist, the geological processes responsible for driving the observed longterm changes in atmospheric CO2 are not sufficiently well understood. The long-term change in atmospheric CO2 across the Cenozoic has been proposed to be driven by processes such as terrestrial weathering, organic carbon production and burial, reverse weathering, and volcanic degassing. One way of constraining the relative importance of the various driving forces proposed so far is to better understand the degree to which ocean chemistry has changed because the chemistry of seawater responds to geologic processes that drive atmospheric CO2. In addition, knowledge of the concentration of the major elements in seawater is crucial for accurately applying proxies such as those based on the boron isotopic composition and Mg/Ca of marine carbonates (a proxy for palaeo pH/CO2 and palaeotemperature, respectively). Previously reported records of seawater composition are primarily derived from fluid inclusions in marine evaporites; however, the results are sparse due to the limited availability of such deposits. In this thesis, changes in the Eocene seawater chemistry were reconstructed using trace element (elements/Ca) and isotopic (δ26Mg) proxies in a Larger Benthic Foraminifera (LBFs), i.e., Nummulites sp., to constrain the driving processes of long-term changes in seawater chemistry.
To achieve the objective of this thesis, first, a measurement protocol was established using LA-ICPMS to measure the K/Ca ratio simultaneously with other element/calcium ratios, which is challenging due to the interference of ArH+ on K+. Utilising this newly established measurement protocol, laboratory-cultured Operculina ammonoides grown at different seawater calcium concentrations ([Ca2+]), repeated at different temperatures, as well as modern O. ammonoides collected from different regions exhibiting a range of seawater parameters, were investigated. A significant correlation was observed between K/Casw and K/CaLBF, allowing K/CaLBF to potentially be used as a proxy for seawater major ion reconstructions. In addition, modern O. ammonoides demonstrated no significant influence of most seawater parameters (temperature, salinity, pH, or [CO32-]) on K/CaLBF. Modern O.
ammonoides were also assessed for their Mg isotopic composition (δ26Mg), revealing no significant effect of temperature or salinity on δ26MgLBF. Furthermore, the Mg isotopic fractionation in O. ammonoides was found to be close to that of inorganic calcite, indicating minimal vital effects in these large benthic foraminifera.
Operculina ammonoides is the nearest living relative of the abundant Eocene genus Nummulites, enabling the reconstruction of seawater chemistry using the calibration based on O. ammonoides. The trace elemental/calcium proxies, including Na/Ca, K/Ca, and Mg/Ca, as well as the δ26Mg proxy, were investigated in Eocene Nummulites. The result showed that during the Eocene, [Ca2+]sw was 1.6-2 times higher, while [K+]sw was ~2 times lower than the modern seawater composition. Furthermore, [Mg2+]sw decreased from the early Eocene (54.3− +9 7..69 mmol kg-1 at ~55 Ma) to Late Eocene (37.8− +4 4..3 4 mmol kg-1 at ~31 Ma), followed by
an increase toward modern seawater [Mg]. In contrast, the variability in δ26Mgsw values remained within a narrow range of ~0.3 ‰ throughout the Cenozoic. The reconstructed [Ca2+]sw agrees with the suggestion that Cenozoic seawater chemistry changes can be explained via a change in the seafloor spreading rate. When combined with existing records, the observed minimal change in δ26Mgsw with an increase in [Mg2+]sw suggests an additional possible role of a decrease in the formation of authigenic clay minerals coincident with the Cenozoic decline in deep ocean temperature, which is also supported by the increase in the [K+]sw reconstructed here for the first time. This finding highlights that the reduction in seafloor-spreading rate and decline in reverse weathering during the Cenozoic era has played a significant role in the evolution of seawater chemistry, emphasizing the importance of these processes in driving long-term changes in the carbon cycle.
Die vorliegende Dissertation befasst sich mit der Synthese und Untersuchung funktioneller Materialien für die Modifizierung von Grenz- und Oberflächen. Einen wichtigen Einfluss auf die Bildung der untersuchten, hochgeordneten Strukturen hat das Konzept der Selbstanordnung, dessen Grundlage schwache Wechselwirkungen sind. Ihre Ausbildung erfordert das Vorliegen geeigneter, funktioneller Gruppen in den Präkursoren und damit die Nutzung der vielfältigen Möglichkeiten der chemischen Synthese zur Bereitstellung maßgeschneidert funktionalisierter Moleküle. Den fünf Projekten dieser Arbeit gemeinsam ist daher die Synthese und Untersuchung für den jeweiligen Anwendungszweck geeigneter, dipolarer Präkursor-Moleküle, die zur Ausbildung funktioneller Koordinationspolymere (CPs) bzw. Metall-organischer Gerüstverbindungen (MOFs) und selbstanordnender Monolagen (SAMs) genutzt werden können. In Zusammenarbeit mit Kooperationspartnern wurden auf dieser Grundlage Untersuchungen zur Anwendbarkeit der erhaltenen Materialien in der Sensorik und zur Oberflächenfunktionalisierung durchgeführt.
Im ersten Projekt dieser Dissertation erfolgte die Untersuchung der Bildungs- und Phasenumwandlungsreaktionen von zehn verschiedenen Kupfer-Terephthalat Koordinationspolymeren. Neben bereits bekannten Koordinationspolymeren konnten so auch drei bisher literaturunbekannte CPs hergestellt und ihre Strukturen durch Kooperationspartner gelöst bzw. Strukturvorschläge gemacht werden. Die Identifikation und Auseinandersetzung mit strukturstabilisierenden Wechselwirkungen schließen dieses Projekt ab und bilden die Grundlage für die Untersuchung der Synthese und Stabilität abgeleiteter, komplexerer Koordinationspolymere.
Im Fokus des zweiten Projekts steht 𝛽-Cu2(bdc)(OH)2, ein Kupfer-Terephthalat Koordinationspolymer, dessen Kristallstruktur zuvor nicht bekannt war, im vorliegenden Projekt aber durch Kooperationspartner auf Basis des Röntgenpulverdiffraktogramms des Materials gelöst werden konnte. Der Vergleich der analytischen Daten von 𝛽-Cu2(bdc)(OH)2 mit der Literatur zeigte gute Übereinstimmungen u. a. der Diffraktogramme und IR-Spektren mit dem in der Literatur als SURMOF-2 bezeichneten, oberflächengebundenen Schichtmaterial. Aufgrunddessen kann davon ausgegangen werden, dass es sich bei SURMOF-2 um 𝛽-Cu2(bdc)(OH)2 handelt, und folglich dessen Kristallstrukturlösung die beiden bisher in der Literatur vorhandenen Strukturvorschläge für SURMOF-2 ersetzt.
Im Rahmen des dritten Projekts sollten für die Sensorik anwendbare, MOF-basierte Dünnschichtsysteme hergestellt werden. Das Sensorkonzept, das auf der Änderung des dielektrischen Verhaltens der MOFs bei Einlagerung dipolarer Analytmoleküle beruht, erfordert den Einsatz dipolarer Liganden in den entsprechenden Koordinationsnetzwerken. Hierfür wurden mehrere teilweise dipolare pillar-Liganden synthetisiert und diese für den Aufbau von Kupfer(II)terephthalat-basierten pillared-layer MOFs eingesetzt. Im Rahmen des Projekts konnten so auf Grundlage der Erkenntnisse aus Projekt 1 und in Zusammenarbeit mit Kooperationspartnern neue pillared-layer MOFs hergestellt und ihre Kristallstrukturen gelöst werden. Die abschließend durch Kooperationspartner erfolgte Abscheidung dünner, oberflächengebundener Schichten dieser MOFs und erste Untersuchungen hinsichtlich ihrer Eignung für die geplante Sensorikanwendung runden das Projekt ab.
Im vierten Projekt sollte eine geeignete, in situ abspaltbare Schutzgruppe für die Thiolgruppe etabliert und ihr Einfluss auf die Bildung von Terphenylthiolat-SAMs untersucht werden. Diese Voraussetzung erfüllt die im Rahmen dieser Arbeit am Beispiel von CH3-, F- und CF3-terminierten Terphenylthiolen etablierte 3,4-Dimethoxybenzyl-Gruppe, die sich durch den Zusatz von Trifluoressigsäure in der Abscheidungslösung in situ abspalten lässt. Zum Vergleich wurden von Kooperationspartner Monolagen aus den entsprechenden freien Thiolen abgeschieden und untersucht. Schichtdicken, Packungsdichten, Kippwinkel und Elementarzellen von Monolagen aus freien und geschützten Terphenylthiolen zeigen gute Übereinstimmungen. Im Gegensatz zu anderen, ebenfalls in situ abspaltbaren Gruppen hat die Anwesenheit der 3,4-Dimethoxybenzyl-Gruppe folglich keinen negativen Einfluss auf die Struktur und Qualität der gebildeten Monolagen.
In Fortführung des vorangegangenen Projekts wurde im abschließenden Projekt in Zusammenarbeit mit Kooperationspartnern der Einfluss verschiedener Kopfgruppen (H-, CH3-, F-, CF3- und SF5-) und der Länge des aromatischen Rückgrats (Phenyl-, Biphenyl- und Terphenyl-) auf die Ladungstransporteigenschaften der entsprechenden SAMs untersucht. Mit Ausnahme einiger Benzolthiole, lieferten alle betrachteten Präkursoren hochgeordnete, dicht gepackte Schichten aus aufrecht angeordneten Molekülen. Wie erwartet korreliert die Austrittsarbeit der modifizierten Oberflächen mit dem Dipolmoment der jeweiligen Kopfgruppe, wobei der Effekt der SF5-Gruppe mit einer erzielten Austrittsarbeit von annähernd 6 eV besonders hervorzuheben ist. Den Erwartungen entsprechend, sinkt die elektrische Stromdichte bei gleichbleibender Kopfgruppe mit steigender Moleküllänge. Die Stromdichte ist außerdem von der Kopfgruppe abhängig und nimmt von CH3- über H-, CF3- und SF5- bis hin zu F- ab, korreliert aber folglich nicht mit der Austrittsarbeit oder dem Dipolmoment.
Excessive accumulation of the extracellular matrix is a hallmark of many inflammatory and fibrotic diseases, including those of the kidney. This study addresses the question whether NO, in addition to inhibiting the expression of MMP-9, a prominent metalloprotease expressed by mesangial cells, additionally modulates expression of its endogenous inhibitor TIMP-1. We demonstrate that exogenous NO has no modulatory effect on the extracellular TIMP-1 content but strongly amplifies the early increase in cytokine-induced TIMP-1 mRNA and protein levels. We examined whether transforming growth factor beta (TGFbeta), a potent profibrotic cytokine, is involved in the regulation of NO-dependent TIMP-1 expression. Experiments utilizing a pan-specific neutralizing TGFbeta antibody demonstrate that the NO-induced amplification of TIMP-1 is mediated by extracellular TGFbeta. Mechanistically, NO causes a rapid increase in Smad-2 phosphorylation, which is abrogated by the addition of neutralizing TGFbeta antisera. Similarly, the NO-dependent increase in Smad-2 phosphorylation is prevented in the presence of an inhibitor of TGFbeta-RI kinase, indicating that the NO-dependent activation of Smad-2 occurs via the TGFbeta-type I receptor. Furthermore, activation of the Smad signaling cascade by NO is corroborated by the NO-dependent increase in nuclear Smad-4 level and is paralleled by increased DNA binding of Smad-2/3 containing complexes to a TIMP-1-specific Smad-binding element (SBE). Reporter gene assays revealed that NO activates a 0.6-kb TIMP-1 gene promoter fragment as well as a TGFbeta-inducible and SBE-driven control promoter. Chromatin immunoprecipitation analysis also demonstrated DNA binding activity of Smad-3 and Smad-4 proteins to the TIMP-1-specific SBE. Finally, by enzyme-linked immunosorbent assay, we demonstrated that NO causes a rapid increase in TGFbeta(1) levels in cell supernatants. Together, these experiments demonstrate that NO by induction of the Smad signaling pathway modulates TIMP-1 expression.
Ubiquitin (Ub)-mediated regulation of plasmalemmal ion channel activity canonically occurs via stimulation of endocytosis. Whether ubiquitination can modulate channel activity by alternative mechanisms remains unknown. Here, we show that the transient receptor potential vanilloid 4 (TRPV4) cation channel is multiubiquitinated within its cytosolic N-terminal and C-terminal intrinsically disordered regions (IDRs). Mutagenizing select lysine residues to block ubiquitination of the N-terminal but not C-terminal IDR resulted in a marked elevation of TRPV4-mediated intracellular calcium influx, without increasing cell surface expression levels. Conversely, enhancing TRPV4 ubiquitination via expression of an E3 Ub ligase reduced TRPV4 channel activity but did not decrease plasma membrane abundance. These results demonstrate Ub-dependent regulation of TRPV4 channel function independent of effects on plasma membrane localization. Consistent with ubiquitination playing a key negative modulatory role of the channel, gain-of-function neuropathy-causing mutations in the TRPV4 gene led to reduced channel ubiquitination in both cellular and Drosophila models of TRPV4 neuropathy, whereas increasing mutant TRPV4 ubiquitination partially suppressed channel overactivity. Together, these data reveal a novel mechanism via which ubiquitination of an intracellular flexible IDR domain modulates ion channel function independently of endocytic trafficking and identify a contributory role for this pathway in the dysregulation of TRPV4 channel activity by neuropathy-causing mutations.
The signal transducer and activator of transcription (Stat) gene family comprises seven members with similarities in their domain structure and a common mode of activation. Members of this gene family mediate interferon induction of gene transcription and the response to a large number of growth factors and hormones. Extracellular ligand binding to transmembrane receptors causes the intracellular activation of associated tyrosine kinases, phosphorylation of Stat molecules, dimerization, and translocation to the nucleus. Prolactin-induced phosphorylation of Stat5 is a key event in the development and differentiation of mammary epithelial cells. In addition to the crucial phosphorylation at tyrosine 694, we have identified an O-linked N-acetylglucosamine (O-GlcNAc) as another secondary modification essential for the transcriptional induction by Stat5. This modification was only found on nuclear Stat5 after cytokine activation. Similar observations were made with Stat1, Stat3, and Stat6. Glycosylation of Stat5, however, does not seem to be a prerequisite for nuclear translocation. Mass spectrometric analysis revealed a glycosylated peptide in the N-terminal region of Stat5. Replacement of threonine 92 by an alanine residue (Stat5a-T92A) strongly reduced the prolactin induction of Stat5a glycosylation and abolished transactivation of a target gene promoter. Only the glycosylated form of Stat5 was able to bind the coactivator of transcription CBP, an essential interaction for Stat5-mediated gene transcription.
Rat renal mesangial cells express high levels of matrix metalloproteinase 9 (MMP-9) in response to inflammatory cytokines such as interleukin 1beta (IL-1beta). We tested whether ligands of the peroxisome proliferator-activated receptor (PPARalpha) could influence the cytokine-induced expression of MMP-9. Different PPARalpha agonists dose-dependently inhibited the IL-1beta-triggered increase in gelatinolytic activity mainly by decreasing the MMP-9 steady-state mRNA levels. PPARalpha agonists on their own had no effects on MMP-9 mRNA levels and gelatinolytic activity. Surprisingly, the reduction of MMP-9 mRNA levels by PPARalpha activators contrasted with an amplification of cytokine-mediated MMP-9 gene promoter activity and mRNA expression. The potentiation of MMP-9 promoter activity functionally depends on an upstream peroxisome proliferator-responsive element-like binding site, which displayed an increased DNA binding of a PPARalpha immunopositive complex. In contrast, the IL-1beta-induced DNA-binding of nuclear factor kappaB was significantly impaired by PPARalpha agonists. Most interestingly, in the presence of an inducible nitric-oxide synthase (iNOS) inhibitor, the PPARalpha-mediated suppression switched to a strong amplification of IL-1beta-triggered MMP-9 mRNA expression. Concomitantly, activators of PPARalpha potentiated the cytokine-induced iNOS expression. Using actinomycin D, we found that NO, but not PPARalpha activators, strongly reduced the stability of MMP-9 mRNA. In contrast, the stability of MMP-9 protein was not affected by PPARalpha activators. In summary, our data suggest that the inhibitory effects of PPARalpha agonists on cytokine-induced MMP-9 expression are indirect and primarily due to a superinduction of iNOS with high levels of NO reducing the half-life of MMP-9 mRNA.
The neuronal adaptor protein Fe65 is involved in brain development, Alzheimer disease amyloid precursor protein (APP) signaling, and proteolytic processing of APP. It contains three protein-protein interaction domains, one WW domain, and a unique tandem array of phosphotyrosine-binding (PTB) domains. The N-terminal PTB domain (Fe65-PTB1) was shown to interact with a variety of proteins, including the low density lipoprotein receptor-related protein (LRP-1), the ApoEr2 receptor, and the histone acetyltransferase Tip60. We have determined the crystal structures of human Fe65-PTB1 in its apo- and in a phosphate-bound form at 2.2 and 2.7A resolution, respectively. The overall fold shows a PTB-typical pleckstrin homology domain superfold. Although Fe65-PTB1 has been classified on an evolutionary basis as a Dab-like PTB domain, it contains attributes of other PTB domain subfamilies. The phosphotyrosine-binding pocket resembles IRS-like PTB domains, and the bound phosphate occupies the binding site of the phosphotyrosine (Tyr(P)) within the canonical NPXpY recognition motif. In addition Fe65-PTB1 contains a loop insertion between helix alpha2 and strand beta2(alpha2/beta2 loop) similar to members of the Shc-like PTB domain subfamily. The structural comparison with the Dab1-PTB domain reveals a putative phospholipid-binding site opposite the peptide binding pocket. We suggest Fe65-PTB1 to interact with its target proteins involved in translocation and signaling of APP in a phosphorylation-dependent manner.
Unlike other eukaryotes, plants possess a complex family of heat stress transcription factors (Hsfs) with usually more than 20 members. Among them, Hsfs A4 and A5 form a group distinguished from other Hsfs by structural features of their oligomerization domains and by a number of conserved signature sequences. We show that A4 Hsfs are potent activators of heat stress gene expression, whereas A5 Hsfs act as specific repressors of HsfA4 activity. The oligomerization domain of HsfA5 alone is necessary and sufficient to exert this effect. Due to the high specificity of the oligomerization domains, other class A Hsfs are not affected. Pull-down assay and yeast two-hybrid interaction tests demonstrate that the tendency to form HsfA4/A5 heterooligomers is stronger than the formation of homooligomers. The specificity of interaction between Hsfs A4 and A5 was confirmed by bimolecular fluorescence complementation experiments. The major role of the representatives of the HsfA4/A5 group, which are not involved in the conventional heat stress response, may reside in cell type-specific functions connected with the control of cell death triggered by pathogen infection and/or reactive oxygen species.
Host cell invasion by the facultative intracellular pathogen Listeria monocytogenes requires the invasion protein InlB in many cell types. InlB consists of an N-terminal internalin domain that binds the host cell receptor tyrosine kinase Met and C-terminal GW domains that bind to glycosaminoglycans (GAGs). Met binding and activation is required for host cell invasion, while the interaction between GW domains and GAGs enhances this effect. Soluble InlB elicits the same cellular phenotypes as the natural Met ligand hepatocyte growth factor/scatter factor (HGF/SF), e.g. cell scatter. So far, little is known about the central part of InlB, the B-repeat. Here we present a structural and functional characterization of the InlB B-repeat. The crystal structure reveals a variation of the β-grasp fold that is most similar to small ubiquitin-like modifiers (SUMOs). However, structural similarity also suggests a potential evolutionary relation to bacterial mucin-binding proteins. The B-repeat defines the prototype structure of a hitherto uncharacterized domain present in over a thousand bacterial proteins. Generally, this domain probably acts as a spacer or a receptor-binding domain in extracellular multi-domain proteins. In cellular assays the B-repeat acts synergistically with the internalin domain conferring to it the ability to stimulate cell motility. Thus, the B-repeat probably binds a further host cell receptor and thereby enhances signaling downstream of Met.
ADAM15 protein amplifies focal adhesion kinase phosphorylation under genotoxic stress conditions
(2012)
ADAM15, a disintegrin and metalloproteinase, is capable of counteracting genotoxic stress-induced apoptosis by the suppression of caspase-3 activation. A cell line expressing the membrane-bound ADAM15 without its cytoplasmic tail, however, lost this anti-apoptotic property, suggesting a crucial role of the intracellular domain as a scaffold for recruitment of survival signal-transducing kinases. Accordingly, an enhanced phosphorylation of FAK at Tyr-397, Tyr-576, and Tyr-861 was detected upon genotoxic stress by camptothecin in ADAM15-transfected T/C28a4 cells, but not in transfectants expressing an ADAM15 mutant without the cytoplasmic tail. Accordingly, a specific binding of the cytoplasmic ADAM15 domain to the C terminus of FAK could be shown by mammalian two-hybrid, pulldown, and far Western studies. In cells expressing full-length ADAM15, a concomitant activation of Src at Tyr-416 was detected upon camptothecin exposure. Cells transfected with a chimeric construct consisting of the extracellular IL-2 receptor α-chain and the cytoplasmic ADAM15 domain were IL-2-stimulated to prove that the ADAM15 tail can transduce a percepted extracellular signal to enhance FAK and Src phosphorylation. Our studies further demonstrate Src binding to FAK but not a direct Src interaction with ADAM15, suggesting FAK as a critical intracellular adaptor for ADAM15-dependent enhancement of FAK/Src activation. Moreover, the apoptosis induction elicited by specific inhibitors (PP2, FAK 14 inhibitor) of FAK/Src signaling was significantly reduced by ADAM15 expression. The newly uncovered counter-regulatory response to genotoxic stress in a chondrocytic survival pathway is potentially also relevant to apoptosis resistance in neoplastic growth.
The Arp2/3 complex nucleates and cross-links actin filaments at the leading edge of motile cells, and its activity is stimulated by C-terminal regions of WASP/Scar proteins, called VCA domains. VCA domains contain a verprolin homology sequence (V) that binds monomeric actin and central (C) and acidic sequences (A) that bind the Arp2/3 complex. Here we show that the C domain binds to monomeric actin with higher affinity (K(d) = 10 microm) than to the Arp2/3 complex (K(d) > 200 microm). Nuclear magnetic resonance spectroscopy reveals that actin binds to the N-terminal half of the C domain and that both the V and C domains can bind actin independently and simultaneously, indicating that they interact with different sites. Mutation of conserved hydrophobic residues in the actin-binding interface of the C domain disrupts activation of the Arp2/3 complex but does not alter affinity for the complex. By chemical cross-linking the C domain interacts with the p40 subunit of the Arp2/3 complex and, by fluorescence polarization anisotropy, the binding of actin and the Arp2/3 complex are mutually exclusive. Our results indicate that both actin and Arp2/3 binding are important for C domain function but that the C domain does not form a static bridge between the two. We propose a model for activation of the Arp2/3 complex in which the C domain first primes the complex by inducing a necessary conformational change and then initiates nucleus assembly by bringing an actin monomer into proximity of the primed complex.
The carnitine transporter CaiT from Escherichia coli belongs to the betaine, choline, and carnitine transporter family of secondary transporters. It acts as an L-carnitine/gamma-butyrobetaine exchanger and is predicted to span the membrane 12 times. Unlike the other members of this transporter family, it does not require an ion gradient and does not respond to osmotic stress (Jung, H., Buchholz, M., Clausen, J., Nietschke, M., Revermann, A., Schmid, R., and Jung, K. (2002) J. Biol. Chem. 277, 39251-39258). The structure and oligomeric state of the protein was examined in detergent and in lipid bilayers. Blue native gel electrophoresis indicated that CaiT was a trimer in detergent solution. This result was further supported by gel filtration and cross-linking studies. Electron microscopy and single particle analysis of the protein showed a triangular structure of three masses or two parallel elongated densities. Reconstitution of CaiT into lipid bilayers yielded two-dimensional crystals that indicated that CaiT was a trimer in the membrane, similar to its homologue BetP. The implications of the trimeric structure on the function of CaiT are discussed.
The subunit composition of the mitochondrial ATP synthase from Saccharomyces cerevisiae was analyzed using blue native gel electrophoresis and high resolution SDS-polyacrylamide gel electrophoresis. We report here the identification of a novel subunit of molecular mass of 6,687 Da, termed subunit j (Su j). An open reading frame of 127 base pairs (ATP18), which encodes for Su j, was identified on chromosome XIII. Su j does not display sequence similarity to ATP synthase subunits from other organisms. Data base searches, however, identified a potential homolog from Schizosaccharomyces pombe with 51% identity to Su j of S. cerevisiae. Su j, a small protein of 59 amino acid residues, has the characteristics of an integral inner membrane protein with a single transmembrane segment. Deletion of the ATP18 gene encoding Su j led to a strain (Deltasu j) completely deficient in oligomycin-sensitive ATPase activity and unable to grow on nonfermentable carbon sources. The presence of Su j is required for the stable expression of subunits 6 and f of the F0 membrane sector. In the absence of Su j, spontaneously arising rho- cells were observed that lacked also ubiquinol-cytochrome c reductase and cytochrome c oxidase activities. We conclude that Su j is a novel and essential subunit of yeast ATP synthase.