Refine
Is part of the Bibliography
- yes (999)
Year of publication
Document Type
- Doctoral Thesis (990)
- Journal article (8)
- Book (1)
Language
- English (773)
- German (225)
- Multiple languages (1)
Keywords
- Maus (38)
- Thrombozyt (33)
- T-Lymphozyt (29)
- Tissue Engineering (29)
- Taufliege (20)
- Dendritische Zelle (19)
- Genexpression (18)
- Angst (16)
- Entzündung (16)
- Myc (15)
- Signaltransduktion (15)
- Angststörung (14)
- Arteriosklerose (13)
- Aufmerksamkeit (13)
- Drosophila (13)
- Staphylococcus aureus (13)
- Biene (12)
- Candida albicans (12)
- G-Protein gekoppelte Rezeptoren (12)
- Immunologie (12)
- Kernspintomografie (12)
- Melanom (12)
- Schlaganfall (12)
- Serotonin (12)
- Fluoreszenzmikroskopie (11)
- Krebs <Medizin> (11)
- Mikroskopie (11)
- Stress (11)
- Depression (10)
- Epigenetik (10)
- GPCR (10)
- Microscopy (10)
- Regulation (10)
- Therapie (10)
- Thrombose (10)
- Transkriptionsfaktor (10)
- Zellskelett (10)
- miRNS (10)
- ADHD (9)
- Apoptosis (9)
- DNS-Reparatur (9)
- Escherichia coli (9)
- Fluoreszenz-Resonanz-Energie-Transfer (9)
- Furcht (9)
- Megakaryozyt (9)
- Motoneuron (9)
- Plasmozytom (9)
- Stammzelle (9)
- Tagesrhythmus (9)
- Zellzyklus (9)
- platelets (9)
- Aspergillus fumigatus (8)
- Elektrophysiologie (8)
- Fuchsbandwurm (8)
- Immuntherapie (8)
- Induzierte pluripotente Stammzelle (8)
- Konditionierung (8)
- Multiples Myelom (8)
- Neisseria meningitidis (8)
- Rezeptor (8)
- Spinale Muskelatrophie (8)
- Synapse (8)
- Alzheimerkrankheit (7)
- Arzneimitteldesign (7)
- Biomarker (7)
- DNS-Schädigung (7)
- EEG (7)
- Funktionelle Kernspintomografie (7)
- Genetik (7)
- Herzinfarkt (7)
- Herzinsuffizienz (7)
- Inhibitor (7)
- Kognition (7)
- Kutikula (7)
- Lernen (7)
- Lungenkrebs (7)
- Makrophage (7)
- Regulatorischer T-Lymphozyt (7)
- Small RNA (7)
- Transcription (7)
- Transkription <Genetik> (7)
- Transplantat-Wirt-Reaktion (7)
- Trypanosoma brucei (7)
- Verhalten (7)
- Zellkultur (7)
- dendritic cells (7)
- fMRI (7)
- Antigen CD28 (6)
- Bacteria (6)
- Bildgebendes Verfahren (6)
- Calcium (6)
- DNA damage (6)
- Diabetes mellitus (6)
- Drosophila melanogaster (6)
- Entwicklung (6)
- Hippocampus (6)
- Inflammation (6)
- MRI (6)
- MYC (6)
- Masernvirus (6)
- Molekularbiologie (6)
- Monoklonaler Antikörper (6)
- Multiple Sklerose (6)
- Oxidativer Stress (6)
- Platelet (6)
- Platelets (6)
- Ratte (6)
- Thrombosis (6)
- Tiermodell (6)
- Transkription (6)
- Transkriptomanalyse (6)
- Ubiquitin (6)
- Virtuelle Realität (6)
- Zellmigration (6)
- cancer (6)
- platelet (6)
- 3D-Druck (5)
- Atherosclerosis (5)
- Aufmerksamkeits-Defizit-Syndrom (5)
- Autoantikörper (5)
- B-Lymphozyt (5)
- Bakterien (5)
- Biologie (5)
- Brain-derived neurotrophic factor (5)
- Cancer (5)
- Cataglyphis (5)
- Chronobiologie (5)
- Cytoskeleton (5)
- Dendritic cells (5)
- Dünndarm (5)
- Einzelmolekülmikroskopie (5)
- Evolution (5)
- Gefühl (5)
- Genetics (5)
- Gephyrin (5)
- HIV (5)
- Immunsystem (5)
- In-vitro-Kultur (5)
- Inhibition (5)
- MAP-Kinase (5)
- Metabolismus (5)
- Mutagenität (5)
- NFATc1 (5)
- Neurodegeneration (5)
- Neuroethologie (5)
- Polymorphismus (5)
- Resistenz (5)
- Schmerz (5)
- Zelldifferenzierung (5)
- virtual reality (5)
- Actin (4)
- Anxiety (4)
- Aufmerksamkeitsdefizit-Syndrom (4)
- Aurora-A (4)
- Autoimmunität (4)
- Biofabrication (4)
- Biofilm (4)
- Bioinformatics (4)
- Biomaterial (4)
- Blut-Hirn-Schranke (4)
- Brustkrebs (4)
- CRISPR/Cas-Methode (4)
- CRISPR/Cas9 (4)
- Cadherine (4)
- Chlamydia trachomatis (4)
- Chromatin (4)
- Chronophin (4)
- Darm (4)
- Dendritic cell (4)
- Dendritische Zellen (4)
- Elektroencephalographie (4)
- Emotion (4)
- FRET (4)
- Fettsäurestoffwechsel (4)
- Fibroblastenwachstumsfaktor (4)
- Furchtgeneralisierung (4)
- Furchtkonditionierung (4)
- G-Protein gekoppelter Rezeptor (4)
- GPVI (4)
- Genotoxizität (4)
- Genregulation (4)
- Glucosetransportproteine (4)
- Graft-versus-host-disease (4)
- Herzmuskelzelle (4)
- Hämostase (4)
- Immunmodulation (4)
- Immunology (4)
- Immunreaktion (4)
- Immunsuppression (4)
- Infektion (4)
- Insulin (4)
- Interleukin 6 (4)
- Ionenkanal (4)
- Jugend (4)
- Kind (4)
- Knockout <Molekulargenetik> (4)
- MMB (4)
- MYCN (4)
- Malaria (4)
- Maschinelles Lernen (4)
- Mausmodell (4)
- Meeresschwämme (4)
- Mitochondrium (4)
- Mitose (4)
- Molekulargenetik (4)
- Myokardinfarkt (4)
- Natürliche Killerzelle (4)
- Neurobiologie (4)
- Neuroblastom (4)
- Neurowissenschaften (4)
- Opiatrezeptor (4)
- Panikstörung (4)
- Parkinson-Krankheit (4)
- Plasmodium falciparum (4)
- Posttranskriptionelle Regulation (4)
- Probiotikum (4)
- Proteasen (4)
- RNS-Bindungsproteine (4)
- Ribosom (4)
- SMN (4)
- Salmonella (4)
- Sepsis (4)
- Soziale Insekten (4)
- Stoffwechsel (4)
- TFIIH (4)
- Treg (4)
- TrkB (4)
- Tumor (4)
- Virulenz (4)
- Zelle (4)
- active zone (4)
- division of labor (4)
- genotoxicity (4)
- honeybee (4)
- inflammation (4)
- magnetic resonance imaging (4)
- measles virus (4)
- miRNA (4)
- microRNA (4)
- myocardial infarction (4)
- neuroblastoma (4)
- olfaction (4)
- regulation (4)
- 3D tissue model (3)
- ADHS (3)
- Adjuvans (3)
- Altern (3)
- Amygdala (3)
- Angiogenese (3)
- Angsterkrankungen (3)
- Animal model (3)
- Antibody (3)
- Antigen CD8 (3)
- Antikörper (3)
- Atherosklerose (3)
- B-MYB (3)
- B-Zell-Lymphom (3)
- Bacillus subtilis (3)
- Biochemie (3)
- Biodiversität (3)
- Bioinformatik (3)
- Biologische Uhr (3)
- Bioreaktor (3)
- Blutstammzelle (3)
- Blutstillung (3)
- CD1d (3)
- CD28 (3)
- CIDP (3)
- Campylobacter jejuni (3)
- Ceramid (3)
- Chemotherapie (3)
- Cyclo-AMP (3)
- Cytokine (3)
- Dimerisierung (3)
- E. coli Nissle 1917 (3)
- Echinococcus (3)
- Echinococcus multilocularis (3)
- Ecology (3)
- Electroencephalographie (3)
- Emotionsregulation (3)
- Endocytose (3)
- Endothel (3)
- Expansion Microscopy (3)
- Expositionstherapie (3)
- Extinktion (3)
- Fettzelle (3)
- Fibromyalgie (3)
- Fluorescence Microscopy (3)
- Gehirn (3)
- Gehirn-Computer-Schnittstelle (3)
- Generalisierung (3)
- Genmutation (3)
- Genom (3)
- Geruch (3)
- Geruchssinn (3)
- Gewebekultur (3)
- Gewebemodell (3)
- Glioblastom (3)
- Glycinrezeptor (3)
- Graft-versus-host disease (3)
- GvHD (3)
- Helicasen (3)
- Helicobacter pylori (3)
- Herzfrequenzvariabilität (3)
- Herzhypertrophie (3)
- Heubacillus (3)
- Histone (3)
- Hyaliner Knorpel (3)
- Hyaluronsäure (3)
- Immunotherapy (3)
- Immuntoleranz (3)
- In vitro (3)
- Informationsverarbeitung (3)
- Knorpel (3)
- Komplement <Immunologie> (3)
- Koronare Herzkrankheit (3)
- Kristallstruktur (3)
- Kutikularwachs (3)
- Latrophilin (3)
- Lunge (3)
- MRSA (3)
- MRT (3)
- Magnetresonanztomographie (3)
- Massenspektrometrie (3)
- Megakaryocyte (3)
- Metagenom (3)
- Metalloproteinasen (3)
- Mitochondria (3)
- Miz1 (3)
- Molekulare Bildgebung (3)
- Multiproteinkomplex (3)
- Muscarinrezeptor (3)
- N-Myc (3)
- NIR-Spektroskopie (3)
- NMR-Tomographie (3)
- Nephroblastom (3)
- Nervennetz (3)
- Nervenzelle (3)
- Neuroanatomie (3)
- Neurogenese (3)
- Neuroinflammation (3)
- Neuronale Plastizität (3)
- Neuropathischer Schmerz (3)
- Neuropeptide (3)
- Neutrophiler Granulozyt (3)
- Non-coding RNA (3)
- Obesity (3)
- Opioide (3)
- Orientierung (3)
- PDXP (3)
- PET (3)
- Paniksyndrom (3)
- Parkinson's disease (3)
- Pathogenität (3)
- Pathophysiologie (3)
- Permeabilität (3)
- Phosphatase (3)
- Phosphoglykolatphosphatase (3)
- Phospholipide (3)
- Phosphorylierung (3)
- Physiologie (3)
- Pilzkörper (3)
- Plastizität (3)
- Pneumolysin (3)
- Proteine (3)
- Proteinkinase D (3)
- Präfrontaler Cortex (3)
- Prävention (3)
- Psychische Störung (3)
- RNS (3)
- Raf-Kinasen (3)
- Rho-Proteine (3)
- Rhodopsin (3)
- Salmonella enterica (3)
- Schmerzforschung (3)
- Secretion (3)
- Sphingolipide (3)
- Stressreaktion (3)
- Structural Biology (3)
- T cell activation (3)
- T-Zelle (3)
- T-Zellen (3)
- TNF (3)
- Thrombozytenaggregation (3)
- Transpiration <Pflanzen> (3)
- Transposon (3)
- Tumorzelle (3)
- Typ 1 (3)
- Ubiquitinierung (3)
- Visuelle Aufmerksamkeit (3)
- Wundheilung (3)
- Zellkern (3)
- Zentralnervensystem (3)
- adrenocortical carcinoma (3)
- apoptosis (3)
- atherosclerosis (3)
- attention (3)
- cAMP (3)
- cell wall (3)
- circadian rhythms (3)
- cytoskeleton (3)
- dopamine (3)
- expression (3)
- fear conditioning (3)
- fear generalization (3)
- gp130 (3)
- iPSC (3)
- ischemic stroke (3)
- learning (3)
- learning and memory (3)
- lung cancer (3)
- megakaryocyte (3)
- megakaryopoiesis (3)
- neurobiology (3)
- pancreas (3)
- protease (3)
- regulatorische T-Zellen (3)
- regulatory T cells (3)
- signalling (3)
- super-resolution microscopy (3)
- translation (3)
- virulence (3)
- 3D cell culture (2)
- 3D-Zellkultur (2)
- 53BP1 (2)
- ALS (2)
- APOBEC3G (2)
- ASM (2)
- Acetylation (2)
- Ackerschmalwand (2)
- Actin-bindende Proteine (2)
- Actinomyceten (2)
- Actinomycetes (2)
- Adaptation (2)
- Adaptorproteine (2)
- Adenosinrezeptor (2)
- Adhesion GPCR (2)
- Adipogenesis (2)
- Adjuvant (2)
- Adrenalin (2)
- Adrenerger Rezeptor (2)
- Adventitia (2)
- Affekt (2)
- Analgesie (2)
- Angeborene Immunität (2)
- Angewandte Mikrobiologie (2)
- Antennallobus (2)
- Antiangiogenese (2)
- Antibiotikum (2)
- Antigen CD40 (2)
- Antigen CD95 (2)
- Aorta (2)
- Apis mellifera (2)
- Apoptose (2)
- Arabidopsis thaliana (2)
- Arbeitsgedächtnis (2)
- Arbeitsteilung (2)
- Arrestine (2)
- Aspergillus (2)
- Assoziation (2)
- Assoziatives Lernen (2)
- Astrozyt (2)
- Audiologie (2)
- Augenbewegung (2)
- Autoaggressionskrankheit (2)
- Autophagy (2)
- Aversive Konditionierung (2)
- Axon (2)
- B cells (2)
- B-Zellen (2)
- BAD (2)
- BCI (2)
- BOLD signal (2)
- BRET (2)
- Bacterial infection (2)
- Bakterielle Hirnhautentzündung (2)
- Bakterielle Infektion (2)
- Bakteriengift (2)
- Bauchspeicheldrüsenkrebs (2)
- Beta-1-Rezeptor (2)
- Beta-Rezeptor (2)
- Bildverarbeitung (2)
- Biogenese (2)
- Bioinks (2)
- Biomechanics (2)
- Biomedicine (2)
- Bioprinting (2)
- Bioreactor (2)
- Blickbewegung (2)
- Blut-Nerven-Barriere (2)
- Blutgerinnung (2)
- Bortezomib (2)
- Brain-computer interface (2)
- CD28 Superagonist (2)
- CD84 (2)
- CDH13 (2)
- COVID-19 (2)
- CRPS (2)
- CXCR4 (2)
- Calciumkanal (2)
- Calciumtransport (2)
- Camponotus floridanus (2)
- Cancer immunotherapy (2)
- Cardiomyocyte (2)
- Cartilage Tissue Engineering (2)
- Cell cycle (2)
- Cell migration (2)
- Cement (2)
- Ceramide (2)
- Cholesterinstoffwechsel (2)
- Chronische Niereninsuffizienz (2)
- Ciliary neurotrophic factor (2)
- Circadian Rhythms (2)
- Cochlear-Implantat (2)
- Cognition (2)
- Colonkrebs (2)
- Compressed Sensing (2)
- Contactin-1 (2)
- Corpus amygdaloideum (2)
- Corti-Organ (2)
- Crosstalk (2)
- Cryptochrom (2)
- Cushing-Syndrom (2)
- Cuticle (2)
- Cuticular waxes (2)
- DNA Repair (2)
- DNA repair (2)
- DNA-Reparatur (2)
- DNS (2)
- DNS-Bindung (2)
- DNS-Doppelstrangbruch (2)
- DRG (2)
- DROSHA (2)
- Darmwandnervensystem (2)
- Deep sequencing (2)
- Diabetische Polyneuropathie (2)
- Diagnostik (2)
- Dichtegewichtung (2)
- Differentiation (2)
- Diffusion coefficient (2)
- Diffusionsgewichtete Magnetresonanztomografie (2)
- Dopamin (2)
- Dosimetrie (2)
- E. coli Nissle (2)
- EHEC (2)
- Echokardiographie (2)
- Einzelzellanalyse (2)
- Elektroencephalogramm (2)
- Elektrospinning (2)
- Emotionen (2)
- Emotionsverarbeitung (2)
- Encephalomyelitis (2)
- Endozytose (2)
- Enterobacteriaceae (2)
- Enzym (2)
- Epigenetic (2)
- Ereigniskorreliertes Potenzial (2)
- Erwachsener (2)
- Extrazelluläre Matrix (2)
- FKBP52 (2)
- Fabry-Krankheit (2)
- Farbensehen (2)
- Fettsucht (2)
- Fettsäurebiosynthese (2)
- Fitness (2)
- Fluconazol (2)
- Fluconazole (2)
- Fluorescence (2)
- Fluoreszenzkorrelationsspektroskopie (2)
- Fluoxetin (2)
- Frühdiagnostik (2)
- Förster Resonanz Energie Transfer (2)
- G-protein-coupled receptors (2)
- GABA-Rezeptor (2)
- Galectine (2)
- Gametogenese (2)
- Gastrointestinaltrakt (2)
- Gedächtnis (2)
- Gelenkknorpel (2)
- Genomics (2)
- Gerinnungsfaktor XII (2)
- Glia (2)
- Glioblastoma (2)
- Gliom (2)
- Glukose (2)
- Glutamat-Decarboxylase (2)
- Glykosylierung (2)
- Golgi-Apparat (2)
- Growth (2)
- Guanylatcyclase (2)
- HUWE1 (2)
- Harnwegsinfektion (2)
- Hautleitfähigkeit (2)
- Hemostasis (2)
- Herz (2)
- Herzmuskel (2)
- Herzmuskelkrankheit (2)
- Herzschrittmacher (2)
- Hfq (2)
- High throughput screening (2)
- Hippo pathway (2)
- Hirnhautentzündung (2)
- Host-pathogen interaction (2)
- Hydrogel (2)
- Hypertrophie (2)
- Hypothalamus (2)
- Hypoxia (2)
- Hypoxie (2)
- Immunisierung (2)
- Immunological synapse (2)
- Impfung (2)
- Induced pluripotent stem cells (2)
- Infektionsmodell (2)
- Inhibitorische Synapse (2)
- Inhibitory synapse (2)
- Innate immunity (2)
- Innere Uhr (2)
- Insekten (2)
- Interaktion (2)
- Interferon (2)
- Interferon <gamma-> (2)
- Interleukin 2 (2)
- Intrazellulärraum (2)
- Invasion (2)
- Ischemic stroke (2)
- Japankärpfling (2)
- K-Ras (2)
- Kardiologie (2)
- Kardiomyozyt (2)
- Kardiovaskuläre Krankheit (2)
- Keratinozyt (2)
- Kernspintomographie (2)
- Klassische Konditionierung (2)
- Klimaänderung (2)
- Knochen-Morphogenese-Proteine (2)
- Knochenmark (2)
- Knochenmarktransplantation (2)
- Knockout (2)
- Knockout-Maus (2)
- Komplement C5a (2)
- Konfokale Mikroskopie (2)
- Kontextkonditionierung (2)
- Kostimulation (2)
- Kraniosynostose (2)
- Krankheit (2)
- Krebsforschung (2)
- Krebsimmuntherapie (2)
- LC-MS (2)
- Lactatdehydrogenase (2)
- Larve (2)
- Learning (2)
- Leishmania (2)
- Leishmania major (2)
- Leishmaniose (2)
- Lidschlag (2)
- Lipide (2)
- Lung (2)
- Lysosom (2)
- Macrophages (2)
- Magnetische Resonanz (2)
- Malaria tropica (2)
- Manisch-depressive Krankheit (2)
- Marine sponges (2)
- Mechanosensation (2)
- Medizinphysik (2)
- Megakaryopoese (2)
- Melt Electrowriting (2)
- Melt electrowriting (2)
- Meningitis (2)
- Mensch (2)
- Merkel cell carcinoma (2)
- Mesenchymzelle (2)
- Metabolomik (2)
- Metastase (2)
- Methylierung (2)
- Mikrotubuli (2)
- Monarchfalter (2)
- Monozyt (2)
- Motoneuron-Krankheit (2)
- Motorisches Lernen (2)
- Multidrug-Resistenz (2)
- Multiple Myeloma (2)
- Mutation (2)
- Myatrophische Lateralsklerose (2)
- N-MYC (2)
- NFAT (2)
- NNMT (2)
- Na+/K+-ATPase (2)
- NaV1.9 (2)
- Nahrungserwerb (2)
- Nanoparticles (2)
- Natriumkanal (2)
- Navigation (2)
- Neisseria gonorrhoeae (2)
- Nervendegeneration (2)
- Nervensystem (2)
- Nestbau (2)
- Neuralgie (2)
- Neurofascin (2)
- Neuromodulation (2)
- Neuropathie (2)
- Neuroscience (2)
- Neutrophils (2)
- Nicht-kleinzelliges Bronchialkarzinom (NSCLC) (2)
- Nociceptor (2)
- Nozizeptor (2)
- Nuklearmedizin (2)
- Nukleotid-Exzisions-Reparatur (2)
- Olfaction (2)
- Oligomerisation (2)
- Oncostatin M (2)
- Onkogen (2)
- Optogenetik (2)
- Organische Synthese (2)
- Organoid (2)
- Osteogenesis (2)
- Oxidative stress (2)
- P300 (2)
- PVM (2)
- Parathormon (2)
- Peptide (2)
- Peptidsynthese (2)
- Peyer's patch (2)
- Pflanzen (2)
- Pflanzenschutzmittel (2)
- Phosphatasen (2)
- Phospholipase D (2)
- Phylogenie (2)
- Phänologie (2)
- Plant Protection (2)
- Plant cuticle (2)
- Plasmamembran (2)
- Polyneuropathie (2)
- Positronen-Emissions-Tomographie (2)
- Post-transcriptional regulation (2)
- Probiotic (2)
- Progenitor (2)
- Prognose (2)
- Proliferation (2)
- Protein (2)
- Protein-Protein-Wechselwirkung (2)
- Proteinsynthese (2)
- Proteintyrosinphosphatase (2)
- Proteolyse (2)
- Proteom (2)
- Psychologie (2)
- RNA (2)
- RNA helicase (2)
- RNA modifications (2)
- RNA polymerase II (2)
- RNS-Interferenz (2)
- RNS-Viren (2)
- ROS (2)
- RS-Virus (2)
- RS1 (2)
- Radionuklid (2)
- Ranvier-Schnürring (2)
- Regenerative Medizin (2)
- Resilienz (2)
- Rheumatoid arthritis (2)
- RhoA (2)
- Ribosome (2)
- Risikofaktoren (2)
- Röntgenkristallographie (2)
- SARS-CoV-2 (2)
- SGLT1 (2)
- SOCE (2)
- SPECT (2)
- Salmonella Typhimurium (2)
- Salmonella typhimurium (2)
- Schlaf (2)
- Schwertkärpfling (2)
- Schädel-Hirn-Trauma (2)
- Screening (2)
- Sekundärkrankheit (2)
- Sekundärmetabolit (2)
- Sequenzanalyse (2)
- Serotonerge Nervenzelle (2)
- Signalkette (2)
- Sinneszelle (2)
- Sozialangst (2)
- Soziale Wahrnehmung (2)
- Sphingomyelin (2)
- Spinal Muscular Atrophy (2)
- Spred-Proteine (2)
- Staphylococcus (2)
- Stickstoff (2)
- Streptococcus pneumoniae (2)
- Symbiose (2)
- Synthese (2)
- T cells (2)
- T-Lymphozyten-Rezeptor (2)
- TFIIIC (2)
- TLR3 (2)
- TWEAK (2)
- Therapieresistenz (2)
- Thrombo-inflammation (2)
- Thrombopoiesis (2)
- Tissue engineering (2)
- Toleranz (2)
- Toll-like-Rezeptoren (2)
- Transcriptome (2)
- Transforming Growth Factor beta (2)
- Transgener Organismus (2)
- Transkriptom (2)
- Tuberkelbakterium (2)
- Tumor-Nekrose-Faktor (2)
- Turbo Spin Echo (2)
- Ubiquitin-Protein-Ligase (2)
- VSG (2)
- Vaccine (2)
- Wahrnehmung (2)
- Wilms tumor (2)
- Wirkstoffdesign (2)
- X-ray crystallography (2)
- Xiphophorus (2)
- Zebrabärbling (2)
- Zebrafish (2)
- Zellteilung (2)
- Zellwand (2)
- Zement (2)
- Zink-Finger-Proteine (2)
- Zytoskelett (2)
- adipocytes (2)
- adult neurogenesis (2)
- amygdala (2)
- antennal lobe (2)
- anxiety (2)
- anxiety disorders (2)
- autophagy (2)
- bee (2)
- behavior (2)
- behaviour (2)
- biased agonism (2)
- bioinformatics (2)
- biology (2)
- biomedical applications (2)
- biomedicine (2)
- bioreactor (2)
- blood brain barrier (2)
- bone marrow (2)
- brain (2)
- calcium (2)
- cardiac hypertrophy (2)
- cell (2)
- ceramide (2)
- chlamydia (2)
- cytokines (2)
- cytokinesis (2)
- deep brain stimulation (2)
- dendritic cell (2)
- dendritische Zelle (2)
- depression (2)
- development (2)
- developmental differentiation (2)
- diet (2)
- dosimetry (2)
- drug development (2)
- ecology (2)
- electron microscopy (2)
- electrophysiology (2)
- emotion (2)
- emotion processing (2)
- emotion regulation (2)
- endosomal trafficking (2)
- endothelial cells (2)
- epigenetics (2)
- evolution (2)
- experimental autoimmune encephalomyelitis (2)
- extracellular matrix (2)
- fMRI time series (2)
- fear extinction (2)
- foxtapeworm (2)
- funktionelle Kernspintomographie (2)
- gamma-H2AX (2)
- genetics (2)
- genomics (2)
- gephyrin (2)
- glucose (2)
- hippocampus (2)
- host-pathogen interaction (2)
- immunologische Synapse (2)
- in vitro (2)
- infection (2)
- inflammatory pain (2)
- insulin (2)
- intestinal in vitro model (2)
- kinase (2)
- lipid rafts (2)
- malaria (2)
- mass spectrometry (2)
- medical physics (2)
- melanoma (2)
- mesenchymal stem cells (2)
- metabolism (2)
- metagenomics (2)
- mitosis (2)
- mitotic gene expression (2)
- monoclonal antibodies (2)
- monoklonale Antikörper (2)
- motoneuron (2)
- mouse model (2)
- multi-unit recording (2)
- multiple myeloma (2)
- neuroethology (2)
- neuropathy (2)
- nuclear medicine (2)
- oligomerization (2)
- p53 (2)
- peptide (2)
- perception (2)
- phosphatase (2)
- receptor (2)
- regulatory t cells (2)
- resistance (2)
- serotonergic system (2)
- shRNA (2)
- signal transduction (2)
- single particle tracking (2)
- skin equivalent (2)
- small RNA (2)
- snRNP (2)
- social anxiety (2)
- social attention (2)
- social insects (2)
- sphingolipids (2)
- spontaneous blinks (2)
- stress (2)
- stroke (2)
- symbiosis (2)
- synaptic plasticity (2)
- synaptic proteins (2)
- synaptische Proteine (2)
- t cells (2)
- tDCS (2)
- targeted therapy (2)
- thrombopoiesis (2)
- tissue engineering (2)
- transcription (2)
- transkranielle Gleichstromstimulation (2)
- vascularization (2)
- virtuelle Realität (2)
- wild bees (2)
- working memory (2)
- wound healing (2)
- Ökologie (2)
- Übergewicht (2)
- "Lipid Rafts" (1)
- (hem)ITAM signaling (1)
- 13C-isotopologue profiling (1)
- 177Lu-OPS201 (1)
- 18S rRNA (1)
- 19F-NMR (1)
- 2-point Dixon (1)
- 3 D bioprinting (1)
- 3-D liver model (1)
- 3D Gewebemodelle (1)
- 3D Modell (1)
- 3D Printing (1)
- 3D Tumormodell (1)
- 3D image analysis (1)
- 3D model (1)
- 3D models (1)
- 3D muscle (1)
- 3D printing (1)
- 3D spheroid culture (1)
- 3D tumour model (1)
- 3D-Elektrode (1)
- 3D-Gewebemodell (1)
- 3D-Kultur (1)
- 3D-Modell (1)
- 4-HNE (1)
- 5-FU (1)
- 5`-UTR (1)
- 68Ga-OPS202 (1)
- 7 T (1)
- 7SK (1)
- 7T (1)
- A-RAF (1)
- A2B adenosine receptor (1)
- A2BAR (1)
- AAC (1)
- ABC-Transporter (1)
- ACC (1)
- ACL (1)
- ADGRL3 (1)
- ADORA2A (1)
- ADP (1)
- AI (1)
- AMPK (1)
- AMP‐activated protein kinase (1)
- ARF6 GTPase (1)
- ASM-Inhibition (1)
- ATF5 (1)
- ATGL (1)
- ATR-FTIR (1)
- ATRA (1)
- Absorbed Doses (1)
- Accelerated imaging (1)
- Acetylcholinrezeptor (1)
- Acetylierung (1)
- Acid adaptation (1)
- Actin Dynamics (1)
- Actin binding proteins (1)
- Actin cytoskeleton-related protein (1)
- Actinomyces (1)
- Acute myeloid leukemia (AML) (1)
- Acyrthosiphon pisum (1)
- Adapterprotein (1)
- Adenomatous-polyposis-coli-Protein (1)
- Adenosine receptors (1)
- Adhesion and Invasion (1)
- Adhesion and degranulation promoting adapter protein (1)
- Adhesion-GPCR (1)
- Adhesive Hydrogels (1)
- Adhärenz (1)
- Adhäsion (1)
- Adipose (1)
- Adipose Tissue Engineering (1)
- Adipose-Derived Stromal/Stem Cells (1)
- Adipositas (1)
- Administered Activities (1)
- Adrenergic receptor (1)
- Adrenocortical Carcinoma (1)
- Adrenokortikales Karzinom (1)
- Adulte Neurogenese (1)
- Adultschlupfes (1)
- Advanced Therapy Medicinal Products (ATMP) (1)
- Affinity probe (1)
- Agaphelin (1)
- Agarose (1)
- Aggregation (1)
- Agoraphobie (1)
- Agrobacterium vitis (1)
- Aiolos (1)
- Airway epithelia (1)
- Aktive Implantate (1)
- Aktivierung <Physiologie> (1)
- Aktivierungsenergie (1)
- Aktivitätstest (1)
- Akute lymphatische Leukämie (1)
- Akute myeloische Leukämie (1)
- Akzeptanz (1)
- Akzeptanz- und Commitment Therapie (1)
- Algorithmus (1)
- Aliphatics (1)
- Alkaloid (1)
- Allergie (1)
- Allergy (1)
- Allgemeine Zelle (1)
- Alloantigen (1)
- Alloantigen Expression (1)
- Allogene Zelle (1)
- Allogeneic stem cell transplantation (1)
- Allogenic hematopoietic stem cell transplantation (1)
- Allosterie (1)
- Alpaca (1)
- Alpha (1)
- Alpha Neurofeedback (1)
- Alpha power (1)
- Alpha-Aktivität (1)
- Alternative polyadenylation (1)
- Alternative zum Tierversuch (1)
- Altersunterschied (1)
- Alveolar Echinococcosis (1)
- Alveoläre Echinokokkose (1)
- Alzheimer's Dementia (1)
- Alzheimer's disease (1)
- Alzheimer`s disease (1)
- AmGr1, AmGr2, AmGr3 (1)
- Ambrosia beetles (1)
- Ambrosiakäfer (1)
- Ameise (1)
- Ameisen (1)
- Ameisenstaat (1)
- Aminobisphosphonat (1)
- Aminobisphosphonate (1)
- Aminobuttersäure <gamma-> (1)
- Ammoniumpermease (1)
- Amphibien (1)
- Amyotrophe Lateralsklerose (1)
- Amyotrophic lateral sclerosis (1)
- Analyse (1)
- Anaphylatoxine (1)
- Anaphylatoxinrezeptoren (1)
- Anastomoseninsuffizienz (1)
- Ancistrocladaceae (1)
- Ancistrocladus (1)
- Androstadienon (1)
- Aneuploidy (1)
- Angewandte Toxikologie (1)
- Angiogenesis (1)
- Angiotensin II (1)
- Angst als Eigenschaft (1)
- Angst als Zustand (1)
- Angsterkrankung (1)
- Angstreaktionen (1)
- Angstsensitivität (1)
- Angstverhalten (1)
- Animal behavior IntelliCage system (1)
- Animales Nervensystem (1)
- Anisotropic structures (1)
- Annotation (1)
- Anoikis (1)
- Anpassung (1)
- Ant (1)
- Anthocyane (1)
- Anthropocene (1)
- Anti-CD52-Antikörper (1)
- Anti-infective (1)
- Antibiotic (1)
- Antibodies (1)
- Antifungal (1)
- Antigen CD3 (1)
- Antigen CD4 (1)
- Antigen CD44 (1)
- Antigen presentation (1)
- Antigen recognition (1)
- Antigenpräsentation (1)
- Antigenrezeptor (1)
- Antikörper-Antwort (1)
- Antimicrobial activities (1)
- Antimicrobial activity (1)
- Antimicrobial proteins (1)
- Antimikrobielle Aktivitäten (1)
- Antimikrobieller Wirkstoff (1)
- Antimykotika (1)
- Antimykotikum (1)
- Antioxidantien (1)
- Antivirale Substanzen (1)
- Antworthemmung (1)
- Antwortverhalten (1)
- Anxiety Disorders (1)
- Anxiety disorder (1)
- Anxiety disorders (1)
- Aortenaneurysma (1)
- Apallisches Syndrom (1)
- Aplysina aerophoba (1)
- Apolipoprotein E (1)
- Approved immunomodulators (1)
- Archaea (1)
- Archaebakterien (1)
- Arginine (1)
- Arid biomes (1)
- ArsZ (1)
- Artefakt (1)
- Artenreichtum (1)
- Arterielles Blut (1)
- Artery Models (1)
- Artesunate (1)
- Arthrose (1)
- Arthrosis deformans (1)
- Arzneimittel (1)
- Arzneimittelzulassung (1)
- Aspartatprotease (1)
- Aspergillose (1)
- Aspergillosis (1)
- Associative learning (1)
- Assoziatives Gedächtnis (1)
- AstA (1)
- Atemwege (1)
- Atemwegsschleimhaut (1)
- Atherogenese (1)
- Atmungsinsuffizienz (1)
- Atomic-force-microscopy (1)
- Atriales natriuretisches Hormon (1)
- Atta vollenweideri (1)
- Attention (1)
- Attention deficit / hyperactivity disorder (1)
- Attentional Avoidance (1)
- Attentional Bias (1)
- Attentional bias (1)
- Attraction (1)
- Attraktion (1)
- AuNPs (1)
- Auditorische Neuropathie (1)
- Auditorischer Kortex (1)
- Aufmerksamkeitsprozesse (1)
- Aurora B (1)
- Aurora-A-MYCN-Komplex (1)
- Ausbreitungsverhalten (1)
- Aussterbedynamik (1)
- Autoantigen (1)
- Autofocus (1)
- Autoimmunity (1)
- Autoinhibition (1)
- Automatische Klassifikation (1)
- Autophagie (1)
- Autophagie <Physiologie> (1)
- Autophagosom (1)
- Autophagozytose (1)
- Autoproteolysis (1)
- Autotransporter (1)
- Autotransporterprotein (1)
- Awareness (1)
- Axon Branching (1)
- B Lymphocytes (1)
- B-Lymphozyten (1)
- B0 (1)
- B0 correction (1)
- B0-Korrektur (1)
- B7-H1 (1)
- BCG (1)
- BCL-2 Familie (1)
- BCL-2 family (1)
- BCMA (1)
- BDNF (1)
- BDNF stimulation (1)
- BH3-only proteins (1)
- BIN2 (1)
- BMP (1)
- BMP signaling pathway (1)
- BMP-2 (1)
- BMP-Signaltransduktionsweg (1)
- BMP2 (1)
- BMS-5 (1)
- BRAF (1)
- BRCA1 (1)
- BTB domain (1)
- BTN3A1 and Phospho-antigen presentation (1)
- Bach (1)
- Bacteria-Host Cell Interaction (1)
- Bacterial Toxins (1)
- Bacterial community analysis (1)
- Bacterial meningitis (1)
- Bacteroides thetaiotaomicron (1)
- Baff (1)
- Baghdadite (1)
- Bahnung (1)
- Bakterielle Nanocellulose (1)
- Bakterienzellwand (1)
- Bakteriophagen (1)
- Bandwürmer (1)
- Bariatric surgery (1)
- Barth Syndrome (1)
- Barth syndrome (1)
- Basal Ganglia (1)
- Basalganglien (1)
- Basalmembran (1)
- Basement membrane (1)
- Batten disease (1)
- Bauchspeicheldrüse (1)
- Baumphysiologie (1)
- Bcl-2-Proteinfamilie (1)
- Bed nucleus of stria terminalis (1)
- Behavior (1)
- Behaviour (1)
- Benzimidazolderivate (1)
- Benzoate (1)
- Benzoate degradation (1)
- Beschleunigte Bildgebung (1)
- Bestimmung des Relaxations-Parameters in der Magnetresonanztomografie (1)
- Bestrahlung (1)
- Bestärkendes Lernen <Künstliche Intelligenz> (1)
- Bestäubung (1)
- Bestäubung Pollination Honigbiene Hummel (1)
- Beta-1-receptor (1)
- Beta-2-Rezeptor (1)
- Beta-Adrenergic Receptor (1)
- Beta-Adrenozeptor (1)
- Bevacizumab (1)
- Bewegungsstörung (1)
- Bienen <Familie> (1)
- Bienen Dressur Lernen (1)
- Bierhefe (1)
- Bildanalyse (1)
- Bildartefakte (1)
- Bildbearbeitung (1)
- Bilderzeugung (1)
- Bildgebung intakten Knochens (1)
- Bimolekulare Lipidschicht (1)
- Bindegewebe (1)
- BioVaSc (1)
- Biochemische Analyse (1)
- Biochemistry (1)
- Biodistribution (1)
- Biodiversity assessment (1)
- Biodiversity conservation (1)
- Biofabrikation (1)
- Biofilm formation (1)
- Biofilmarchitektur (1)
- Biofilms (1)
- Bioink (1)
- Biokinetics (1)
- Biolayerinterferometrie (1)
- Biologie / Zellbiologie (1)
- Biologischer Abbau (1)
- Biologisches Modell (1)
- Biology (1)
- Bioluminescence resonance energy transfer (1)
- Biolumineszenzmessung (1)
- Biomechanik (1)
- Bioprozessmethode (1)
- Bioreaktorplattform (1)
- Biosynthese der aromatischen Aminosäuren (1)
- Biosynthese-Genclustern (1)
- Biotransformation (1)
- Bipolar (1)
- Bipolar Disorder (1)
- Bisphosphonate (1)
- Bitopic Ligands (1)
- Bitopische Liganden (1)
- Blick (1)
- Blickinteraktion (1)
- Blimp-1 (1)
- Blinatumomab (1)
- Blood nerve barrier (1)
- Blumeria graminis (1)
- Blut-Liquor-Schranke (1)
- Blut-Rückenmarkschranke (1)
- Blutgefäßsystem (1)
- Blutgerinnungsfaktor XII (1)
- Bluthirnschranke (1)
- Body movement (1)
- Bone (1)
- Bone Marrow Dosimetry (1)
- Bone Quantification (1)
- Bone marrow stromal cell (1)
- Bone marrow stromal cell (BMSC) (1)
- Bone marrow transplantation (1)
- Bone morphogenetic protein 2 (1)
- Bone morphogenetic proteins (1)
- Bone regeneration (1)
- Bone-replacement (1)
- Bordetella (1)
- Borkenkäfer (1)
- Borneo (1)
- Borrelia (1)
- Bovine Mastitis (1)
- Brain (1)
- Brain derived neurotorphic factor (1)
- Brain endothelial cells (1)
- Brownsche Bewegung (1)
- Bruchpilot (1)
- Brustdrüsenentzündung (1)
- Burkholderia (1)
- Burkholderia pseudomallei (1)
- Burkitt Lymphom (1)
- Burkitt Lymphoma (1)
- Butyrophilin (1)
- Bäckerhefe (1)
- Bärtierchen (1)
- C. albicans (1)
- C. elegans (1)
- C/EBP (1)
- C1-inibitor (1)
- C5aR1-Antagonist (1)
- CA3 (1)
- CAMP production (1)
- CAR T Zellen (1)
- CAR T cell (1)
- CAR T-Zelltherapie (1)
- CAR T-cells (1)
- CAR-T cell (1)
- CAR-T-Zell-Therapie (1)
- CCR4 (1)
- CD11b+ myeloid cells (1)
- CD150 (1)
- CD28 Molekül (1)
- CD28 Superagonisten (1)
- CD28 antigen (1)
- CD28-SA (1)
- CD28-Superagonist (1)
- CD28-superagonist (1)
- CD4 T-Zellen (1)
- CD4 positiv T cells (1)
- CD4+ (1)
- CD4+ T cell activation (1)
- CD40 gerichteter bifunktioneller scFv-TRAIL Fusionsproteine (1)
- CD40-targeted bifunctional scFv-TRAIL fusion proteins (1)
- CD44 (1)
- CD8 Effektorfunktionen (1)
- CD8 Gedächtnisreaktionen (1)
- CD8 T cell (1)
- CD8 T-Zelle (1)
- CD8 T-Zellen (1)
- CD8+ T cells (1)
- CD8+ T-Zellen (1)
- CD95 (1)
- CD95L (1)
- CDC42 (1)
- CDK4 Inhibitor (1)
- CDK4 inhibitor (1)
- CDR1-Effluxpumpe (1)
- CIP2A (1)
- CLEC-2 (1)
- CLEC16A (1)
- CMT1A (1)
- CMV (1)
- CNBP (1)
- COMT polymorphism (1)
- CRHR1 (1)
- CRISPR Cas9 (1)
- CRISPR Cas9 system (1)
- CTLA-4 (1)
- CVT (1)
- CX-5461 (1)
- CXCL13 (1)
- CXCR5 (1)
- CYP24A1 (1)
- CYP7A1 (1)
- CaCo-2 cell (1)
- Cadherin 13 (1)
- Cadherin-13 (1)
- Caenorhabditis elegans (1)
- Calcium Phosphate (1)
- Calcium phosphate-based biomaterials (1)
- Calcium signalling (1)
- Calcium-bindende Proteine (1)
- Calciumhomöostase (1)
- Calciumphosphat (1)
- Camponotus (1)
- Camponotus rufipes (1)
- Cancer Immune Therapy (1)
- Cancer Metabolism (1)
- Cancer biology (1)
- Cancer models (1)
- Cancer therapeutic resistance (1)
- Carabid beetles (1)
- Carcinogenese (1)
- Cardiac (1)
- Cardiac Efficiency (1)
- Cardiac MRI (1)
- Cardiac hypertrophy (1)
- Cardiac imaging (1)
- Cardiolipin (1)
- Cardiomyocytes (1)
- Cardiomyopathy (1)
- Carotis Intima Media Dicke (1)
- Cartiage Integration (1)
- Cartilage (1)
- Cartilage Regeneration (1)
- Cartilage defect (1)
- Cas9 (1)
- Caspr-1 (1)
- Catechol-0-Methyltransferase (1)
- Catechol-O-Methyltransferase (1)
- Catecholmethyltransferase <Catechol-0-Methyltransferase> (1)
- Cation Homeostasis (1)
- Caveolin-1 (1)
- Ccr4-Not (1)
- Cdh13 (1)
- Celecoxib (1)
- Cell (1)
- Cell Cycle (1)
- Cell Sheet Engineering (1)
- Cell adhesion (1)
- Cell culture (1)
- Cell differentiation (1)
- Cell line (1)
- Cell-Assisted Lipotransfer (1)
- Cells (1)
- Cellular invasion (1)
- Ceramides (1)
- Cerebrospinal fluid (CSF) (1)
- ChIP-Seq (1)
- ChIP-sequencing (1)
- Chaetomium thermophilum (1)
- Chain-length distribution (1)
- Characterization (1)
- Charcot-Marie-Tooth 1A (1)
- Chemische Synapsen (1)
- Chemokin CXCL10 (1)
- Chemokin CXCL12 (1)
- Chemokine (1)
- Chemokine receptors (1)
- Chemoresistenz (1)
- Chemotaxis (1)
- Chemotherapeutic resistance (1)
- Children (1)
- Chimeric Antigen Receptor (1)
- Chimeric antigen receptor (1)
- Chimeric antigen receptor (CAR) (1)
- Chimpanzee (1)
- Chimärer Antigenrezeptor (1)
- Chirurgie (1)
- Chlamydia (1)
- Chlamydienkrankheit (1)
- Cholesterintransporter (1)
- Chondrogenic Differentiation (1)
- Chordontonal organ (1)
- Chromatinremodeling (1)
- Chromatinremodelling (1)
- Chromosom 6 (1)
- Chromosome 6 (1)
- Chronic Mild Stres (1)
- Chronisch-myeloische Leukämie (1)
- Chronische Nierenerkrankung (1)
- Chronischer Schmerz (1)
- Chylomicron (1)
- Chylomicrons (1)
- Circadian (1)
- Circadian Clock (1)
- Circadian clock (1)
- Circadiane Uhr (1)
- Circadianer Rhythmus (1)
- Citalopram (1)
- Claudin (1)
- Click-Chemie (1)
- Climate change (1)
- Clonal competition assay (1)
- Clostridium difficile (1)
- Cluster (1)
- Co-Analgetika (1)
- Co-Kultur (1)
- Co-culture (1)
- Co-culture system (1)
- CoQ10 (1)
- Coactosin-like (1)
- Coffin-Lowry syndrome (1)
- Cofilin (1)
- Cognitive Distortions (1)
- Cognitive processing (1)
- Collagen gels (1)
- Colliculus inferior (1)
- Collybistin (1)
- Colon cancer (1)
- Commensalism (1)
- Comorbidity (1)
- Comoé National Park (1)
- Complement system (1)
- Complex Regional Pain Syndrome (1)
- Complexes (1)
- Complexome (1)
- Compound eyes (1)
- Compressed sensing (1)
- Computational Fluid Dynamics (1)
- Computational drug design (1)
- Computersimulation (1)
- Computerunterstütztes Verfahren (1)
- Conditioning (1)
- Contact-Kinin System (1)
- Contrast Agent Bolus Based Perfusion Magnetic Resonance Imaging (1)
- Convolutional Neural Network (1)
- Coronary heart disease (1)
- Correlative microscopy (1)
- Cortico-striatal projection neurons (1)
- Corticoliberin (1)
- Counting (1)
- Coxiella burnetii (1)
- Craniosynostosis (1)
- Craving (1)
- CsrA (1)
- Cul4b (1)
- Cuticular transpiration (1)
- Cuticular water permeabilities (1)
- Cyanobacteria (1)
- Cyanobakterien (1)
- Cyclic peptides (1)
- Cyclics (1)
- Cystein (1)
- Cysteinproteasen (1)
- Cytologie (1)
- Cytomegalie-Virus (1)
- Cytoplasma (1)
- Cytotoxic T cell (1)
- D-4F (1)
- DC (1)
- DC/T-Zell-Konjugate (1)
- DEQCT (1)
- DExD/H box protein (1)
- DG diacyglycerol (1)
- DGCR8 (1)
- DHX30 (1)
- DNA Barcoding (1)
- DNA Damage (1)
- DNA Doppelstrangbrüche (1)
- DNA Schaden (1)
- DNA Sekundärstruktur (1)
- DNA double strand breaks (1)
- DNA lesion (1)
- DNA methylation (1)
- DNA secondary structure (1)
- DNA-Methylierung (1)
- DNA-Schaden (1)
- DNA-Schäden (1)
- DNS-Bindungsproteine (1)
- DNS-Schaden (1)
- DNS-Sequenz (1)
- DOT1 (1)
- DREAM (1)
- DREAM complex (1)
- DSIF (1)
- DTI (1)
- DUB Mutante (1)
- DYT-TOR1A (1)
- Danaus plexippus (1)
- Danio rerio (1)
- Darmepithel (1)
- Darmflora (1)
- Dasatinib (1)
- Datenbank (1)
- Decapping (1)
- Deep-sequencing (1)
- Deeplearning (1)
- Defensine (1)
- Defäkographie (1)
- Degradation (1)
- Deletion (1)
- Denaturierende Gradienten-Gelelektrophorese (1)
- Denaturing Gradient Gel Electrophoresis (1)
- Density Weighting (1)
- Deoxyribozymes (1)
- Dephosphorylierung (1)
- Depletion (1)
- Dereplicaiton (1)
- Desmoglein 2 (1)
- Desmoglein 3 (1)
- Desmogleine (1)
- Desmosom (1)
- Deubiquitination (1)
- Development (1)
- Dexamethason (1)
- Diabetes (1)
- Diabetes Typ 1 (1)
- Diabetes mellitus Typ 1 (1)
- Diabetic painful neuropathy (1)
- Diabetic polyneuropathy (1)
- Diagnostic Imaging Exams (1)
- Dickdarmkrebs (1)
- Differential scanning calorimetry (1)
- Differentielle Genexpression (1)
- Differentielle Ressourcenallokation (1)
- Differenzierung (1)
- Differenzierungszustand (1)
- Diffusion (1)
- Diffusion Tensor Imaging (1)
- Diffusionskoeffizient (1)
- Dihydrooxazole (1)
- Dilated cardiomyopathy (1)
- Dimension 3 (1)
- Dimere (1)
- Dimeric Naphthylisoquinoline Alkaloids (1)
- Diphenylether (1)
- Diskriminationslernen (1)
- Diskriminationstraining (1)
- Dispersal (1)
- Disulfidbrücken (1)
- Diversifikation <Biologie> (1)
- Diversity (1)
- Dolutegravir (1)
- Domäne <Biochemie> (1)
- Domänenprotein (1)
- Dopamin-Transporter (1)
- Dopamine transporter (1)
- Dopaminstoffwechsel (1)
- Dopamintransporter (1)
- Dorsal Root Ganglion (1)
- Dorsal root ganglion (1)
- Dosimetry (1)
- Double Negative B cells (1)
- Droseraceae (1)
- Drosophila Larva (1)
- Drosophila Larve (1)
- Drosophila Myc transcription growth PAF1 (1)
- Drug delivery system (DDS) (1)
- Drug resistance (1)
- Drug targets (1)
- Drug testing (1)
- Dual RNA-seq (1)
- Dual RNA-seq data analysis (1)
- Dual-setting (1)
- Dualstere Liganden (1)
- Dualsteric Ligands (1)
- Duodenal Jejunal Bypass (1)
- Duplikation (1)
- Durchflusscytometrie (1)
- Dynabeads (1)
- Dynamic MR imaging (1)
- Dynamics of ribosome assembly (1)
- Dynamik (1)
- Dynamik von Membranrezeptoren (1)
- Dynamische MR-Bildgebung (1)
- Dynein Light Chain (1)
- Dystonie (1)
- Dürrestress (1)
- E.coli Nissle 1917 (1)
- E1 inhibitoren (1)
- E1 inhibitors (1)
- E2 (1)
- EAE (1)
- ECAP (1)
- ECG-gated PET (1)
- ELISA (1)
- EMT (1)
- ER dynamics in axon terminals (1)
- ERK (1)
- Eap (1)
- Early-Life Stress (1)
- Echo Planar Imaging (1)
- Echo planar imaging (1)
- Echocardiography (1)
- Echoplanar-Bildgebung (1)
- Echtzeit (1)
- Echtzeitbildgebung (1)
- Ecological Momentary Assessment (1)
- Ecological Momentary Assessments (1)
- Ecosystem services (1)
- Effect anticipation (1)
- Effektantizipation (1)
- Efflux pump (1)
- Effluxpumpen (1)
- Eierstockkrebs (1)
- Eierstocktumor (1)
- Einfühlung (1)
- Einfühlung <Motiv> (1)
- Eingeweidewürmer (1)
- Einsamkeit (1)
- Einzel-Molekül (1)
- Einzelpartikelverfolgung (1)
- Einzelzellgelelektrophorese (1)
- Electrochemical Impedance Spectroscopy (1)
- Electrode (1)
- Electroencephalography (1)
- Electromyography (1)
- Electrophysiology (1)
- Elektroakupunktur (1)
- Elektrode (1)
- Elektromyographie (1)
- Elektronencephalographie (1)
- Elektrospinnen (1)
- Elektrostimulation (1)
- Elektrotherapie (1)
- Elevated Plus-Maze (1)
- Elongation (Transkription) (1)
- Embryo (1)
- Embryonale Stammzelle (1)
- Emotionale Informationsverarbeitung (1)
- Emotionales Verhalten (1)
- Empfindlichkeit (1)
- Endobrachyösophagus (1)
- Endocytosis (1)
- Endogenous clock (1)
- Endokrinologie (1)
- Endophenotype (1)
- Endophänotyp (1)
- Endophänotypen (1)
- Endoplasmatisches Retikulum (1)
- Endorganschaden (1)
- Endosomes (1)
- Endothelium (1)
- Endothelzelle (1)
- Enoyl-Reduktase (1)
- Enoyl-acyl-carrier-protein-Reductase (1)
- Enoyl-acyl-carrier-protein-Reductase <Enoyl-[acyl-carrier-protein]-Reductase> (1)
- Enterische Glia (1)
- Enterisches Nervensystem (1)
- Enterohemorrhagic Escherichia coli (1)
- Entscheidungsverhalten (1)
- Entwicklung chimärer Antigenrezeptor T-Zellen (1)
- Entzündungschmerz (1)
- Entzündungsreaktion (1)
- Entzündungsschmerz (1)
- Enzymaktivierung (1)
- Enzyminhibitor (1)
- Eosinophiler Granulozyt (1)
- EphA2 (1)
- Ephrin ligand (1)
- Ephrine (1)
- Epidemiologie (1)
- Epigenetische Mechanismen (1)
- Epithel (1)
- Epithelial layer (1)
- Epithelial lineage (1)
- Epithelial-mesenchymale Transition (1)
- Epithelzelle (1)
- Erk1/2 (1)
- Erkennung (1)
- Erregbarkeit (1)
- Esophageal adenocarcinoma (1)
- Esophageal disease (1)
- Essgewohnheit (1)
- Essstörung (1)
- Essverhalten (1)
- Estrogens (1)
- Excitatory/inhibitory imbalance (1)
- Excitotoxicity (1)
- Exon Array (1)
- Expansion microscopy (1)
- Expansionsmikroskopie (1)
- Experimental Autoimmune Encephalomyelitis (EAE) (1)
- Experimentelle Autoimmune Enzephalomyelitis (1)
- Experimentelle Autoimmune Enzephalomyelitis (EAE) (1)
- Experimentelle autoimmune Enzephalomyelitis (1)
- Experimentellen Autoimmun-Enzephalomyelitis (1)
- Experimenteller Schlaganfall (1)
- Explainable AI (1)
- Explainable Artificial Intelligence (1)
- Explorationsverhalten (1)
- Exposition (1)
- Expositionslernen (1)
- Exposure treatment (1)
- Expression (1)
- Extracellular Matrix (1)
- Extracellular Vesicles (1)
- Extracellular matrix proteins (1)
- Extrazellulärmatrix (1)
- Exzitatorische Synapse (1)
- Eye irritation (1)
- FAS (1)
- FAS-II (1)
- FAT10ylation (1)
- FBXO6 (1)
- FCS (1)
- FGF (1)
- FGF Signaling (1)
- FLT3 inhibitor (1)
- FMMs (1)
- FMS-like tyrosine kinase 3 (FLT3) (1)
- FOXM1 (1)
- FOXP2 (1)
- FP635 (1)
- FRAP (1)
- FRET sensors (1)
- FT-IR-Spektroskopie (1)
- FabI (1)
- FabV (1)
- Fabry disease (1)
- Factor XII (1)
- Faktor XII (1)
- Fanconi Anemia (1)
- Fanconi-Anämie (1)
- Farnesyl Pyrophosphate Synthase (1)
- Farnesylpyrophosphatsynthase (FPPS) (1)
- Fas-Ligand (1)
- Fat Quantification (1)
- FcgR (1)
- FeS cluster (1)
- Fear (1)
- Fear Conditioning (1)
- Fear Extinction (1)
- Fear Generalization (1)
- Fear Learning (1)
- Fear conditioning (1)
- Fear generalization (1)
- Feedforward loop (1)
- FemX (1)
- Ferroptosis (1)
- Fertilization in angiosperm (1)
- Fettgewebe (1)
- Fettleber (1)
- Fettsäure-Synthase (1)
- Fibroblast (1)
- Fibroblasts (1)
- Fibromyalgia (1)
- Fibromyalgia syndrome (1)
- Fibromyalgiesyndrom (1)
- Fibrose (1)
- Filter (1)
- Flagelle (1)
- Flavonoide (1)
- Flavonoids (1)
- Flippase (1)
- Flotillin (1)
- Flow (1)
- Flugzeitmassenspektrometrie (1)
- FluidFM (1)
- Fluorescence Correlation Spectroscopy (1)
- Fluorescence Resonance Energy Transfer (1)
- Fluorescence correlation spectroscopy (1)
- Fluorescence microscopy (1)
- Fluorescence-resonance-energy-transfer (1)
- Fluorescent probes (1)
- Fluoreszenz (1)
- Fluoreszenzproteine (1)
- Fluoreszenzsonde (1)
- Fluoreszenzspektroskopie (1)
- Fluoxetine (1)
- Fluss (1)
- Foamyviren (1)
- Folliculin (1)
- Forkhead Transcription Factors (1)
- Forkhead-Box-Proteine (1)
- Fox tapeworm (1)
- FoxO transcription factors (1)
- Foxo1 (1)
- Foxp3+CD4+ regulatorische T-Zelle (1)
- Foxp3+CD4+ regulatory T cell (1)
- Fragebogen (1)
- Fragmentscreening (1)
- Französische Feldwespe (1)
- Freezing (1)
- Freies Molekül (1)
- Fremdkörpermodell (1)
- Frizzled 5 (1)
- Frontal asymmetry (1)
- Froschlurche (1)
- Fructosebisphosphat-Aldolase (1)
- Fruit (1)
- Frühe Gene (1)
- Function (1)
- Functional analyses (1)
- Functioning Assessment Short Test (1)
- Funktionelle Annotation (1)
- Funktionelle Bildgebung (1)
- Funktionelle Kernspintomographie (1)
- Funktionsausfälle (1)
- Furagieraktivität (1)
- Furchkonditionierung (1)
- Furchtentwicklung (1)
- Furchtextinktion (1)
- Fusarium (1)
- Fusobacterium nucleatum (1)
- Förster Resonance Energy Transfer (1)
- G Protein-Coupled Receptor (1)
- G Protein-Coupled Receptors (1)
- G Protein-coupled receptor (1)
- G glycoprotein (1)
- G protein coupled receptor (1)
- G protein-coupled receptor kinase (1)
- G protein-coupled receptor kinase 2 (GRK2) (1)
- G protein-coupled receptors (1)
- G protein-gekoppelte Rezeptor Kinase 2 (GRK2) (1)
- G-Protein (1)
- G-Protein gekoppelte Rezeptor (1)
- G-Protein-gekoppelte Rezeptoren (1)
- G-protein (1)
- G-quadruplex (1)
- G2/M genes (1)
- GABA (1)
- GABA A Receptors (1)
- GABA A Rezeptoren (1)
- GABA receptor (1)
- GABA(A) receptor (1)
- GABAA-Rezeptor (1)
- GABAerge Nervenzelle (1)
- GAD1 (1)
- GAD65 (1)
- GAS2L3 (1)
- GC1 cells (1)
- GDF-15 (1)
- GLA KO mouse model (1)
- GLP-1 (1)
- GMP (1)
- GPCR dimerisation (1)
- GPCR nanodomains (1)
- GPCR signaling (1)
- GPI-anchored protein (1)
- GRM8 (1)
- GWAS (1)
- Ga-68-labelled Peptides (1)
- Galactosidase <alpha-> (1)
- Galectin 1 (1)
- Gambler's Fallacy (1)
- Gametocyt (1)
- Gametozyt (1)
- Ganzkörperbestrahlung (1)
- Gap Junction (1)
- Gas chromatography (1)
- Gaschromatographie (1)
- Gastroesophageal reflux (1)
- Gastrointestinal tract (1)
- Gauss Prozess Klassifikation (1)
- Gaussian Process Classification (1)
- Gaze interaction (1)
- Gb3 accumulation (1)
- Gefrierstrukturierung (1)
- Gefäßalter (1)
- Gefäßwand (1)
- Gefäßwand-residente Stamm- und Vorläuferzellen (1)
- Gehirn-Computer Schnittstelle (1)
- Geißel <Biologie> (1)
- Gelernte Hilflosigkeit (1)
- Gemcitabin (1)
- Gen BRCA 1 (1)
- Gen Umweltinteraktion (1)
- Gen notch (1)
- Gen-Umwelt Interaktion (1)
- Gene by Environment (1)
- Gene expression regulation (1)
- Gene regulation (1)
- Gene therapy (1)
- General Transcription Factor II H (1)
- General amplifier model (1)
- Generalization (1)
- Genetic etiology (1)
- Genome Annotation (1)
- Genome Instability (1)
- Genome editing (1)
- Genomeditierung (1)
- Genomic Selection (1)
- Genomik (1)
- Genotoxicity (1)
- Genotyping (1)
- Gentoxizität (1)
- Geomagnetic Field (1)
- Gerinnungsfaktor (1)
- Germination and differentiation (1)
- Germinative Zellen (1)
- Geruchswahrnehmung (1)
- Geschlechtsunterschiede (1)
- Geschmack (1)
- Gestational diabetes (1)
- Gestationsdiabetes (1)
- Gewebe (1)
- Gewebemodelle (1)
- Glatte Muskulatur (1)
- Glatter Krallenfrosch (1)
- Glioblastomtherapie (1)
- Glioma (1)
- Global change (1)
- Glottoplastik (1)
- Glucocorticoids (1)
- Glucose Starvation (1)
- Glucose metabolism (1)
- Glucosetransport (1)
- Glucosetransporter (1)
- Glukosemetabolismus (1)
- Glukosetransporter -1 (1)
- Glutamin (1)
- Glutathion (1)
- Glycerin-3-phosphat (1)
- Glycerinphosphate (1)
- Glycin (1)
- Glycine Receptors (1)
- Glycocalyx (1)
- Glycolipid (1)
- Glycophyten (1)
- Glycoprotein GPV (1)
- Glycoprotein hormone (1)
- Glykane (1)
- Glykobiologie (1)
- Glykokalyx (1)
- Glykomodifizierung (1)
- Glykosyltransferase (1)
- Glyzin Rezeptoren (1)
- Glyzinrezeptor (1)
- Glücksspiel (1)
- Gold Nanoparticles (1)
- Golgi apparatus (1)
- Gonococcal invasion (1)
- Grad-seq (1)
- Gradient System Transfer Function (1)
- Graft versus Host Disease (1)
- Graft versus Host disease (1)
- Graft versus host disease (1)
- Graft-versus-host disease (GvHD) (1)
- Graft-versus-leukemia (1)
- Gram-positive (1)
- Gram-positive bacteria (1)
- Granulozyten (1)
- Growth-differentiation Factor 15 (1)
- Guanin Nukleotid Austauschfaktor (1)
- Guanine nucleotide exchange factor (GEF) (1)
- Guaninnucleotid-Austauschfaktoren (1)
- Guanylyl cyclase A (1)
- Guillain-Barré-Syndrom (1)
- GvL (1)
- Gvhd (1)
- H2A.Z (1)
- HAD phosphatase (1)
- HASH (1)
- HBD2 (1)
- HCMV (1)
- HD5 (1)
- HDAC (1)
- HECTD1 (1)
- HERV (1)
- HFO-1123 (1)
- HFpEF (1)
- HIF1alpha (1)
- HIV Drug resistance (1)
- HIV South Africa (1)
- HIV-1 (1)
- HIV-1 Vif (1)
- HIV-associated neurocognitive disorder (HAND) (1)
- HIV-assoziierte neurokognitive Störung (HAND) (1)
- HLA-G (1)
- HMBPP (1)
- HNE (1)
- HP1432, Hpn2 (1)
- HPLC-MS (1)
- HRV (1)
- HSF1 (1)
- HST1 (1)
- HSV-1 (1)
- Haarzelle (1)
- Habituationstraining (1)
- Haemostasis (1)
- Haloacid dehalogenase (1)
- Halophyten (1)
- Halophytes (1)
- Harze (1)
- Hautkrebs (1)
- Hautmodell (1)
- Hautverbrennung (1)
- Heart (1)
- Heart Failure (1)
- Heart Period (1)
- Heart development (1)
- Heart failure (1)
- Heat shock protein 90 (1)
- Heat stress (1)
- Heilmittel (1)
- Heilung (1)
- Heißhunger (1)
- Helferzelle (1)
- Helicase (1)
- Helikasen (1)
- Helminths (1)
- Hematopoietic Cell Transplantation (1)
- Hematopoietic Stem Cell (1)
- Hematopoietic cell transplantation (1)
- Hemmung der Proliferation schnell wachsender Krebszellen (1)
- Hemodynamics (1)
- Hemofiltration (1)
- Heparin (1)
- Hereditary spastic paraplegia (1)
- Hereditäre spastsiche Paraplegie (1)
- Herpes (1)
- Herpes simplex Virus DUB C65A (1)
- Herpes simplex virus C65A (1)
- Herpesviren (1)
- Herpesviruses (1)
- Herz-Kreislauf-Erkrankung (1)
- Herzbildgebung (1)
- Herzfrequenz (1)
- Herzfunktion (1)
- Herzratenvariabilität (1)
- Herzruptur (1)
- Heterogenität von Mikroorganismen (1)
- Hey Proteine (1)
- Hey proteins (1)
- Hi-C (1)
- Hic-5 (1)
- Hidden Markov Model (1)
- Hidden-Markov-Modell (1)
- High-thropughput screening (1)
- Himmelskompass (1)
- Hippokampus (1)
- Hirnendothelzellen (1)
- Hirnhaut (1)
- Hirnstimulation (1)
- Histatin 5 (1)
- Histon-Deacetylase (1)
- Histon-Methyltransferase (1)
- Histonacetyltransferase (1)
- Histone Acetylation (1)
- Histone modification (1)
- Histone variant (1)
- Histones (1)
- Hitzeschock Proteine (1)
- Hitzeschock-Proteine (1)
- Hitzeschockprotein 90 (1)
- Hitzeschocktranskriptionsfaktor (1)
- Hitzestress (1)
- Hochauflösende Mikroskopie (1)
- Hochauflösungsmikroskopie (1)
- Hochdurchsatz-Screening (1)
- Hochdurchsatzsequenzierung (1)
- Holobiont (1)
- Homing (1)
- Homöostase (1)
- Honeybee (1)
- Honigbiene (1)
- Honigbienen (1)
- Hormone Receptor Signaling (1)
- Hornhaut (1)
- Hornhautinfektionen (1)
- Hospitalismus <Hygiene> (1)
- Host Colonization (1)
- Host Genome Integrity (1)
- Host defense (1)
- Hot Hand Fallacy (1)
- Huh6 (1)
- Human Herpesvirus 6 (1)
- Human Transcriptome (1)
- Human-pathogenic (1)
- Humanes Herpesvirus 6 (1)
- Humanparasitologie (1)
- Huwe1 (1)
- Hyaluronic Acid (1)
- Hyaluronic acid (1)
- Hybrid-Molecules (1)
- Hydrocortison (1)
- Hydrogels (1)
- Hyperactivity (1)
- Hyperekplexie (1)
- Hypertension (1)
- Hypertrophy (1)
- Hypoparathyreoidismus (1)
- Hyrogels (1)
- Hämatopoetische Stammzellen (1)
- Hämatopoetische Stammzelltransplantation (1)
- Hämodynamik (1)
- Hämophilie A (1)
- Hämsotase (1)
- Höhenangst (1)
- Hörbahn (1)
- Hörrinde (1)
- ICP22 (1)
- IE3 (1)
- IEG (1)
- IFN-g (1)
- IFNAR (1)
- IKZF1 (1)
- IKZF3 (1)
- IL-12p70 (1)
- IL-2 (1)
- IL-23 (1)
- IL-4 (1)
- IL-4 Rezeptor alpha (1)
- IL-4 receptor alpha chain (1)
- IL-6 Inhibition (1)
- IMP1/ZBP1 (1)
- IP6 (1)
- IPP (1)
- IRAK2 (1)
- ITAM (1)
- ITAM-signalling (1)
- IVIG (1)
- Ibrutinib (1)
- Ideomotor gaze control (1)
- Ideomotorik (1)
- Ideomotorische Blickkontrolle (1)
- IgG-Subklasse (1)
- Ighmbp2 (1)
- Ikaros (1)
- Ileal Trasposition (1)
- Illumina HiSeq (1)
- Image Processing (1)
- Image Quality (1)
- Immunaktivierung (1)
- Immunantwort (1)
- Immune Checkpoint Therapy (1)
- Immune System (1)
- Immune Thrombocytopenia (1)
- Immune activation (1)
- Immune cell assays (1)
- Immune cells (1)
- Immunglobulin G (1)
- Immunität <Medizin> (1)
- Immunkardiologie (1)
- Immunocardiology (1)
- Immunologe (1)
- Immunomodulation (1)
- Immunophilin (1)
- Immunosuppressant (1)
- Immunozyt (1)
- Immunpathogenese (1)
- Immunsuppressiva (1)
- Immunthrombozytopenie (1)
- Immunzellassays (1)
- Immunzellrekrutierung (1)
- Impfstoff (1)
- Implantatentwicklung (1)
- Impulsivität (1)
- In vitro model (1)
- In vitro models (1)
- In vivo Imaging (1)
- Individual based model (IBM) (1)
- Individualisierte Medizin (1)
- Infection imaging (1)
- Infection models (1)
- Infectious diseases (1)
- Infektiologie (1)
- Infektionsbildgebung (1)
- Infektionsbiologie (1)
- Infektionsprozess (1)
- Infektionsstudien (1)
- Inferior colliculus (1)
- Inflamamtion (1)
- Inflammatory Pain (1)
- Inflammatory pain (1)
- Informationsnutzung (1)
- Infrared radiation (1)
- Inhibitory-postsynapse (1)
- Injectability (1)
- Insect (1)
- Insekt (1)
- Insektenstaaten (1)
- Instrumental Activities of Daily Living (1)
- Insulin-like Growth (1)
- Insulin-like-Growth-Factor-Binding-Protein-5 (1)
- Insulinresistenz (1)
- Insulinsekretion (1)
- Integrase inhibitor (1)
- Integrated Defensive States (1)
- Integrin (1)
- Integrine (1)
- Interaction analysis (1)
- Interaction of 7SK with the Smn complex modulates snRNP production (1)
- Interaktionsrezeptor (1)
- Interferon <Gamma-> (1)
- Interferonrezeptor (1)
- Interleukin (1)
- Interleukin 12 (1)
- Interleukin 17 (1)
- Interleukin 5 (1)
- Interleukin-4 Antagonist (1)
- Interleukine (1)
- Internal Dosimetry (1)
- Internalisierende Störung (1)
- Interozeption (1)
- Interozeptive Genauigkeit (1)
- Intestinal metaplasia (1)
- Intestinal stem cell (1)
- Intracellular bacteria (1)
- Intracellular virulence (1)
- Intratumorale Heterogenität (1)
- Intravoxel Incoherent Motion (1)
- Intrazelluläre Bakterien (1)
- Intrinsische Gerinnungskaskade (1)
- Ion channel function (1)
- Ionisierende Strahlung (1)
- Irradiation (1)
- Ischemia (1)
- Ischämischer Schlaganfall (1)
- Isolation (1)
- Isolation and Characterization (1)
- Isomer (1)
- Isopentenyl pyrophosphate (IPP) (1)
- Isopentenyl-pyrophosphat (IPP) (1)
- Isoprenoid Synthesis (1)
- Isoprenoide (1)
- Isoprenoidsynthese (1)
- Ixolaris (1)
- JNCL (1)
- JNK (1)
- JURKAT-Zelle (1)
- Judgment (1)
- Jugendliche (1)
- Jun (1)
- K-RAS (1)
- K5 capsule (1)
- KDELR2 (1)
- Kaliumkanal (1)
- Kallikrein-Kinin-System (1)
- Kardiale MR-Bildgebung (1)
- Kardiovaskuläre Komorbiditäten (1)
- Karotis-Intima-Media-Dicke (1)
- Kation (1)
- Kationen-Homöostase (1)
- Kehlkopfchirurgie (1)
- Keimzentrumsreaktion (1)
- Kern (1)
- Kidney (1)
- Kilimandscharo (1)
- Kinase (1)
- Kinase signaling (1)
- Kinasen (1)
- Kinder (1)
- Kinderpsychiatrie (1)
- Kinderschlaf (1)
- Kindesalter (1)
- Kindheit und Jugend (1)
- Kinetik (1)
- Klassifikations- und Regressionsbaum (1)
- Kleine Proteine (1)
- Kleinkern (1)
- Kleinkind (1)
- Klima (1)
- Klimawandel (1)
- Klinischer Behandlungspfad (1)
- Kniegelenkarthrose (1)
- Knochenbildung (1)
- Knochenersatz (1)
- Knochenmarkzelle (1)
- Knochenmetastase (1)
- Knochenmetastasen (1)
- Kofaktorbindung (1)
- Koffein (1)
- Kognitive Beeinträchtigung (1)
- Kognitive Inhibition (1)
- Kognitive Störung (1)
- Kognitiver Prozess (1)
- Kognitives Lernen (1)
- Kohlendioxid (1)
- Kohlenhydrate (1)
- Kohlenstoff (1)
- Kohlenstofffaser (1)
- Kohlenstoffstoffwechsel (1)
- Kohlenwasserstoffe (1)
- Kollektive Invasion (1)
- Kolloid (1)
- Kolonieerkennung (1)
- Kolonkarzinom (1)
- Kommunikation (1)
- Kommunikationshilfe (1)
- Komorbidität (1)
- Kompass (1)
- Komplement (1)
- Komplement C3a (1)
- Komplement C5a Rezeptor 1 (1)
- Komplementsystem (1)
- Komplexauge (1)
- Komplexes regionales Schmerzsyndrom (1)
- Komprimierte Abtastung (1)
- Kongestive Herzmuskelkrankheit (1)
- Kongo (1)
- Konnektivitätsschätzung (1)
- Konsolidierung (1)
- Kontingenz (1)
- Kontrastmittel (1)
- Kontrastmittel-gestützte MRT-Perfusionsmessung (1)
- Kontrolle (1)
- Kopfschmerz (1)
- Kopienzahlvariation (1)
- Korrelative Mikroskopie (1)
- Krebs (1)
- Kristallographie (1)
- Kryokonservierung (1)
- Kuh (1)
- Körperachsen (1)
- Körperliche Leistungsfähigkeit (1)
- Künstliche Ingelligenz (1)
- Künstliche Intelligenz (1)
- L-typ Calciumkanal Antagonist (1)
- LAD (1)
- LASP1 (1)
- LASP1 (LIM and SH3 Protein 1) (1)
- LASP1 (LIM und SH3 Protein 1) (1)
- LAT2 (1)
- LC-MS/MS (1)
- LIMK (1)
- LIS (1)
- LPS (1)
- LPS Biosynthese (1)
- LV Function (1)
- Labeling (1)
- Lactobacillus reuteri (1)
- Lambdoide Prophagen (1)
- Langerhans cells (1)
- Langzeitgedächtnis (1)
- Lasermikrodissektion (1)
- Lasiocarpin (1)
- Lateral root development (1)
- Latrophilin receptor (1)
- Latrophilin-3 (1)
- Ldlr-Knockout (1)
- Leaf (1)
- Learning & Memory (1)
- Learning Walk (1)
- Learning walk (1)
- Lebendzellmikroskopie (1)
- Lebenslauf (1)
- Lebensmittelchemie (1)
- Lebensqualität (1)
- Leber-Metabolismus (1)
- Leberepithelzelle (1)
- Leichte kognitive Beeinträchtigung (1)
- Leitlinien (1)
- Lenalidomid (1)
- Lentiviral transgenesis (1)
- Leptomeningeal cells (1)
- Leptomeningealzellen (1)
- Lernverhalten (1)
- Letalität (1)
- Leukaemia-inhibitory factor (1)
- Lgr5 (1)
- Library Screening (1)
- Library of Phytochemicals (1)
- Library of plant species (1)
- Licht (1)
- Lichtblattmikroskopie (1)
- Lichtscheibenmikroskopie (1)
- Licl (1)
- Ligand <Biochemie> (1)
- Ligand uncaging (1)
- Light Sheet Fluorescence Microscopy (1)
- Light sheet microscopy (1)
- Lipid Raft (1)
- Lipid Rafts (1)
- Lipid Transfer Protein (1)
- Lipidom (1)
- Lipidomics (1)
- Lipidomik (1)
- Lipidumbau (1)
- Lipolysis (1)
- Liquor (1)
- Locomotor activity (1)
- Lokalanästhesie (1)
- Luftfeuchtigkeit (1)
- Lung Cancer metastasis (1)
- Lung cancer (1)
- Lung squamous cancer cells (1)
- Lungenentzündung (1)
- Lungentumor (1)
- Lurche (1)
- Lysin-Oxidase (1)
- Lysosome (1)
- Lysyl oxidases (1)
- Lysyloxidasen (1)
- Ländlicher Raum (1)
- M1 Muscarinic Receptor (1)
- MAP kinase (1)
- MAX (1)
- MCMV (1)
- MDR1 (1)
- MDSC (1)
- MDSCs (1)
- MEK5/ERK5 (1)
- MEK5/ERK5 cascade (1)
- MET-T-box riboswitch (1)
- MGMT (1)
- MIPs (1)
- MIZ1 (1)
- MLN7243 (1)
- MM (1)
- MMB complex (1)
- MMN (1)
- MMP (Matrix-Metalloproteasen) (1)
- MMP (Matrix-Metalloproteases) (1)
- MND (1)
- MRR1 (1)
- MS2-affinity purification and RNA-seq (1)
- MT02 (1)
- MYCN-amplified (1)
- Machine Learning (1)
- Macromolecular machine (1)
- Macrophage (1)
- Macrophage extracellular traps (1)
- Macrophytes (1)
- Magen (1)
- Magenchirurgie (1)
- Magenkrankheit (1)
- Magenkrebs (1)
- Magnetic Resonance Imaging (1)
- Magnetic Resonance Relaxometry (1)
- Magnetic resonance imaging (1)
- Magnetresonanz-Relaxometrie (1)
- Major depression (1)
- Makrokolonie (1)
- Makrophagen (1)
- Makrophyten (1)
- Malignant melanoma (1)
- Mamma carcinoma (1)
- Mammakarzinom (1)
- Mantle cell lymphoma (1)
- Marine natural products (1)
- Marine sponge (1)
- Marine sponge-derived actinomycetes (1)
- Marker (1)
- Marketing authorisation of pharmaceuticals (1)
- Marrow (1)
- Masern (1)
- Masern-Virus (1)
- Masernvirus-Infektion (1)
- Mass Spectrometry (1)
- Mass spectrometry (1)
- Massenspektrometrie/Proteomics (1)
- Masspectrometry (1)
- Mast cells (1)
- Mastzelle (1)
- Mathematical modeling (1)
- Mathematische Modellierung (1)
- Matrix-Metalloprotease (1)
- Matrix-Metalloproteasen (1)
- Matrix-Metalloproteinase (1)
- Mauerbiene (1)
- Mc4r (1)
- Measles virus (1)
- Mechanical deformation (1)
- Mechanisms of Social Attention (1)
- Mechanismus (1)
- Mechanistic model (1)
- Mechanorezeptor (1)
- Medaka (1)
- Mediator Komplex (1)
- Medium spiny neurons (1)
- Medizinprodukt (1)
- Medizintechnik (1)
- Medulloblastom (1)
- Megakaryocytes (1)
- Megakaryozytopoese (1)
- Mek5/Erk5-Signalweg (1)
- Melanin (1)
- Melanin release (1)
- Melanoma (1)
- Melanophor (1)
- Membrane Receptor Dynamics (1)
- Membrane transporters (1)
- Membranlipide (1)
- Membranproteine (1)
- Membranrezeptor (1)
- Membrantransporter (1)
- Memory (1)
- Memory B cells (1)
- Menaquinon-BIosynthese (1)
- Menaquinone Biosynthesis (1)
- Meninges (1)
- Meningokokken-Sepsis (1)
- Meniskus (1)
- Meniskusimplantat (1)
- Meniskustransplantation (1)
- Mercapturic acid pathway (1)
- Merkel cell polyomavirus (1)
- Merkelzellkarzinom (1)
- Mesenchymal Stem Cell (1)
- Mesenchymal Stromal Cell (1)
- Mesenchymal Stromal Cells (1)
- Mesenchymal stem cell (1)
- Mesenchymal stromal cells (1)
- Mesenchymale Stammzelle (1)
- Mesenchymale Stromazelle (1)
- Messenger-RNS (1)
- Meta-barcoding (1)
- Metaanalyse (1)
- Metabolic Glycoengineering (1)
- Metabolic Labeling (1)
- Metabolism (1)
- Metabolite von Morphin (1)
- Metabolites of morphine (1)
- Metabolomics (1)
- Metagenomics (1)
- Metalloprotease (1)
- Metalloproteasen (1)
- Metalloproteases (1)
- Metalloproteinase (1)
- Metapopulation (1)
- Metastasierung (1)
- Metatranscriptomics (1)
- Methioninbiosynthese (1)
- Method development (1)
- Methodenentwicklung (1)
- Methylphenidat (1)
- Methyltransferase (1)
- Mevalonate Pathway (1)
- MgrB (1)
- MicF (1)
- MicroRNA (1)
- MicroRNAs (1)
- Microarray (1)
- Microbial community (1)
- Microbiota (1)
- Microglia (1)
- Micronucleus (1)
- Microvesicle (1)
- Microwave Assisted Extraction (1)
- Migraine (1)
- Migration (1)
- Migräne (1)
- Mikroarray basierte vergleichende Genomhybridisierung (Array-CGH) (1)
- Mikrobiota (1)
- Mikroglia (1)
- Mikroglomeruli (1)
- Mikrokerne (1)
- Mikroorganismus (1)
- Mikrotubuli-assoziiertes Protein (MAP) (1)
- Mikrotubulus (1)
- Mimik (1)
- Minor histocompatibility antigen mismatch transplantation (1)
- Mitochondrien (1)
- Mittelohrimplantat (1)
- Mobie EEG (1)
- Mobile Crowdsensing (1)
- Mobile Health (1)
- Mobiles Endgerät (1)
- Mobilfunkstrahlung (1)
- Moco biosynthesis (1)
- Model (1)
- Model Based Reconstruction Algorithms in Magnetic Resonance Imaging (1)
- Model Organism (1)
- Model simulation (1)
- Modell (1)
- Modellbasierte-Rekonstruktionsalgorithmen in der Magnetresonanztomografie (1)
- Modellierung (1)
- Modellorganismus (1)
- Modellsystem (1)
- Moderator (1)
- Modification (1)
- Modifizierung (1)
- ModulationTregs (1)
- Molecular Pharmacology (1)
- Molecular Radiotherapy (1)
- Molekulare Zielstrukturen (1)
- Mongolische Rennmaus (1)
- Monitoring (1)
- Monoklonale Gammopathie (1)
- Monoklonaler Antikoerper (1)
- Monoklonaler bispezifischer Antikörper (1)
- Moonlight (1)
- Moosfaserterminalen (1)
- Morbus Alzheimer (1)
- Morbus Fabry (1)
- Morphin (1)
- Morphology (1)
- Morris Water Maze (1)
- Motivation (1)
- Motoneuron diseases (1)
- Motoneuronenerkrankung (1)
- Motoneurons (1)
- Motor Memory (1)
- Motor learning (1)
- Motor neuron disease (1)
- Motorische Endplatte (1)
- Motorisches Gedächtnis (1)
- Mouse Model (1)
- Mrap2 (1)
- Mrr1 (1)
- MscS (1)
- Mucorales (1)
- Mucormycosis (1)
- Mucormykose (1)
- Multi-Unit Aufnahmen (1)
- Multicellular aggregates (1)
- Multidrug-Resistance-Related Proteine (1)
- Multidrugresistant (1)
- Multilayered skin tissue model (1)
- Multiphotonenmikroskopie (1)
- Multiple Sclerosis (1)
- Multiple myeloma (1)
- Multizellulären Bakteriengemeinschaften (1)
- Mundschleimhautzellen (1)
- Murine models of thrombosis and haemostasis (1)
- Muskelin (1)
- Muskelzelle (1)
- Mustererkennungsrezeptoren (1)
- Myb-MuvB complex (1)
- Mycobacterium tuberculosis (1)
- Mycobacterium tuberculosis InhA (1)
- Myeloblast (1)
- Myeloid (1)
- Myeloid-derived suppressor cells (1)
- Myeloide Suppressorzellen (1)
- Myelom (1)
- Myeloma (1)
- Myocardial Work (1)
- Myocardial infarction (1)
- Myokardiale Deformation (1)
- Myokarditis (1)
- Myosin IIA (1)
- Myrmecology (1)
- N-RAS (1)
- N2pc (1)
- N400 (1)
- NA (1)
- NAFLD (1)
- NEDMIAL (1)
- NES (1)
- NF-kB (1)
- NF-kappaB (1)
- NFATc3 (1)
- NHERF (1)
- NK (1)
- NK cell (1)
- NK-DC cross-talk (1)
- NKT (1)
- NLS (1)
- NMJ (neuromuscular junction) (1)
- NMR (1)
- NNMT activity assay (1)
- NO-GC (1)
- NOS-I (1)
- NOS1AP (1)
- NOTES <Chirurgie> (1)
- NRF2 (1)
- NSM2 (1)
- NTRK fusions (1)
- NaV1.9. oxidized phospholipids (1)
- Nachtschattengewächse (1)
- Nahrung (1)
- Nahrungsaufnahme (1)
- Nanofabrication (1)
- Nanofabrikation (1)
- Nanofaser (1)
- Nanomedicine (1)
- Nanomedizin (1)
- Nanopartikel (1)
- Nanotubes (1)
- Naphthalinderivate (1)
- Naphthochinonen (1)
- Naphthoquinones (1)
- Naphthylisochinolinalkaloide (1)
- Naphthylisoquinoline (1)
- Narrow escape problem (1)
- Nasenschleimhaut (1)
- Natrium-Kalium-Pumpe (1)
- Natrium-abhängigen Glukosetransporter-1 (1)
- Natriumoxamat (1)
- Natural pest control (1)
- Natural products (1)
- Natural walking (1)
- Nature-Insipired Synthesis (1)
- Naturschutz (1)
- Naturstoff (1)
- Near Miss (1)
- Nebenniere (1)
- Nebennierenrindenkarzinom (1)
- Nebennierenrindenkrebs (1)
- Nebennierentumor (1)
- Nectin4 (1)
- Neogenin-1 (1)
- Nephrogenese (1)
- Nerven (1)
- Nervenstimulation (1)
- Netrin-1 (1)
- Netzhaut (1)
- Netzwerkanalyse (1)
- Neuartige Arzneimittel (1)
- Neural Stem cells (1)
- Neurobiology (1)
- Neuroblastoma (1)
- Neurodegenerative Erkrankung (1)
- Neurodevelopment (1)
- Neurodevelopmental Disorder (1)
- Neurodevelopmental diseases (1)
- Neuroepigenomics (1)
- Neuroethology (1)
- Neurofeedback (1)
- Neurofilament (1)
- Neurogenesis (1)
- Neurogenetik (1)
- Neuroligin 2 (1)
- Neuromuskuläre Endplatte (1)
- Neuronale Stammzellen (1)
- Neuronales visuelles System (1)
- Neuropathic Pain (1)
- Neuropathic pain (1)
- Neuropathologie (1)
- Neuropathy (1)
- Neuropeptid S Rezeptor Gen (1)
- Neuropeptid Y (1)
- Neuropeptidom (1)
- Neurophysiologie (1)
- Neuroplasticity (1)
- Neuroprotection (1)
- Neuroprotektivum (1)
- Neurotransmitter Receptors (1)
- Neurotransmitter Rezeptoren (1)
- Neurotransmitter-Rezeptor (1)
- Neurotrophic factors (1)
- Neutrophil (1)
- Neutrophil granulocyte (1)
- Neutrophil granulocytes interaction (1)
- Newman strain sae (1)
- Next Generation Sequencing (NGS) (1)
- Nicht-kartesische Bildgebung (1)
- Nicht-kleinzelliges Bronchialkarzinom (1)
- Nichtionisierende Strahlung (1)
- Nichtstrukturproteine (1)
- Nicotiana tabacum (1)
- Niere (1)
- Niereninsuffizienz (1)
- Nierenversagen (1)
- Nimodipin (1)
- Nitrogen (1)
- Nodo-Paranodopathie (1)
- Non-Hodgkin-Lymphom (1)
- Non-conventional T cell (1)
- Non-invasive imaging (1)
- Non-ribosomal peptide synthetase (1)
- Non-viral genome engineering (1)
- Noonan-Syndrom (1)
- Noradrenalin (1)
- Noradrenalinstoffwechsel (1)
- Nosocomial Infections (1)
- Nosokomiale Infektionen (1)
- Notch Signalweg (1)
- Notch signalling (1)
- Nozizeption (1)
- Nuclar Medicine (1)
- Nuclear Factor of Activated T cells (NFAT) (1)
- Nuclear Medicine (1)
- Nuclear imaging (1)
- Nuclease (1)
- Nucleasen (1)
- Nucleotide excision repair (1)
- Nucleotide-Excision-Repair (1)
- Nucleus subthalamicus (1)
- Nuklearfaktor Kappa B (1)
- Nukleäre Hormonrezeptoren (1)
- Numerische Fluidmechanik (1)
- O(6)-Methylguanine-DNA Methyltransferase (1)
- OCT1 (1)
- OIS (1)
- OSM (1)
- OSMR (1)
- Oberflächenproteine der Sexualstadien (1)
- Olfaktion (1)
- Olfaktorik (1)
- Oligomerization (1)
- OmoMYC (1)
- Onchocerca volvulus (1)
- Onchozerkose (1)
- Oncogenes (1)
- Oncolytic Virotherapy (1)
- Oncoprotein (1)
- Onkologie (1)
- Onkolyse (1)
- Onkoprotein (1)
- Oozyte (1)
- Open chromatin (1)
- Opioidpeptide (1)
- Optimal foraging (1)
- Optogenetics (1)
- Orai1 (1)
- Organ of Corti (1)
- Organoids (1)
- Orientia tsutsugamushi (1)
- Osmr-Knockout (1)
- Osteoporose (1)
- OxPL (1)
- Oxidative Stress (1)
- Oxidized Phospholipids (1)
- Oxidized phospholipids (1)
- Oxygen partial pressure (1)
- Oxytocin (1)
- Oxytosis (1)
- P4-ATPase (1)
- PAF1c (1)
- PAR-CLIP (1)
- PCDHGC3 (1)
- PD-L1 (1)
- PDE (1)
- PDI (1)
- PE Phosphoethanolamine (1)
- PEG (1)
- PER (1)
- PG neurons (1)
- PGE2 (1)
- PHMB (1)
- PI3K (1)
- PKA signaling (1)
- PLEKHG5 (1)
- PLP phosphatase (1)
- PP2A (1)
- PRKACA (1)
- PROTAC (1)
- PROTACs (1)
- PRR (1)
- PTH1R (1)
- PTMs (1)
- PTPN22 (1)
- PacBio sequencing (1)
- Palbociclib (1)
- Panic Disorder (1)
- Panik (1)
- Pankreas (1)
- Paranodopathie (1)
- Parasitology (1)
- Parc National de la Comoé (1)
- Parkinson Krankheit (1)
- Partial Agonists (1)
- Partialagonismus (1)
- Paternal age and BMI effects (1)
- Pathogene Bakterien (1)
- Pathogenese (1)
- Pathogenesis (1)
- Pathogenicity (1)
- Pathogens (1)
- Pathologie (1)
- Pathology (1)
- Pathophysiologische Mechanismen (1)
- Patienten-orientierte Versorgung (1)
- Patientenklassifikation (1)
- Patientenorientierte Medizin (1)
- Pattern recognition receptors (1)
- Pattern-Recognition-Receptors (1)
- Patulin (1)
- Pause Release (1)
- Pediatric Nuclear Medicine (1)
- Pediatric Patients (1)
- Pemphigus (1)
- Peptides (1)
- Perforation <Medizin> (1)
- Perforine (1)
- Perfusion Bioreactor (1)
- Perianova, Irina (1)
- Periaqueductal gray (1)
- Period2 (1)
- Peripheral eosinophils (1)
- Periphere Analgesie (1)
- Peripheres Nervensystem (1)
- Permeability (1)
- Permeation (1)
- Peroxisomen-Proliferator-aktivierter Rezeptor (1)
- Persistence (1)
- Pertussis (1)
- Pesticide (1)
- Peyersche Plaques (1)
- Pflanzen-Bienen-Netzwerke (1)
- Pflanzenaussterben (1)
- Pflanzenhydraulik (1)
- Pflanzenzelle (1)
- Pflanzenzellkulturen (1)
- Pflanzenökologie (1)
- PhD thesis pharmacology (1)
- Pharmaceutische Biologie (1)
- Pharmacology (1)
- Pharmakodynamik (1)
- Phasenvariation (1)
- Phenotypic switch (1)
- Pheromon (1)
- Phonochirurgie (1)
- Phosphatidylinositolkinase <Phosphatidylinositol-3-Kinase> (1)
- Phosphoantigen (1)
- Phosphodiesterase (1)
- Phosphoglykolat (1)
- Phosphoglykolat-Phosphatase (1)
- Phospholamban (1)
- Phosphorylation (1)
- Photoreceptor (1)
- Photoswitch (1)
- Phyllosphere (1)
- Phyllosphäre (1)
- Phylogeny (1)
- Pilze (1)
- PinT (1)
- Plant Biology (1)
- Plant Ecology (1)
- Plant cell cultures (1)
- Plant extracts (1)
- Plant hydraulic (1)
- Plants (1)
- Plasmonic (1)
- Plastin 3 (1)
- Platelet activating Factor (1)
- Platelet count (1)
- Platelet granules (1)
- Platelet-Membranglykoprotein p62 (1)
- Platy (1)
- Pluripotenz (1)
- Pmn mutant mouse (1)
- Pneumonievirus der Maus (1)
- Pneumoviruses (1)
- Point Spread Function (1)
- Polistes (1)
- Pollen (1)
- Polo-like kinase 1 (1)
- Poly(2-oxazoline) (1)
- Poly(2-oxazoline)s (1)
- Poly(glycidol) (1)
- Polyadenylierung (1)
- Polyethism (1)
- Polymer Science (1)
- Polymere (1)
- Polymers (1)
- Polyphosphate (1)
- Polysaccharide (1)
- Polysaccharide intercellular adhesin (PIA) (1)
- Pore (1)
- Pore formation (1)
- Pore-formation (1)
- Porenbildung (1)
- Porifera (1)
- Porins (1)
- Positron emission tomography (1)
- Positronen-Emissions-Tomografie (1)
- Posttranslationale Änderung (1)
- Powdery mildew fungus (1)
- Pra1 (1)
- Preclinical studies (1)
- Prefrontal cortex (1)
- Prefrontalt Cortex (1)
- Primaten (1)
- Primär-basierte immortalisierte Zelllinie (1)
- Primäre Ziliendyskinesie (1)
- Primärelement (1)
- Primärprevention (1)
- Primärtumor (1)
- Primärzellen (1)
- ProQ (1)
- Problem Gambling (1)
- Processing fluency (1)
- Profilin (1)
- Programmed Cell Death 1 (1)
- Programmed Cell Death Ligand 1 (1)
- Promotor (1)
- Prosoziales Verhalten (1)
- Prostaglandin E2 (1)
- Protease (1)
- Proteaseaktivität (1)
- Proteaseinhibitor (1)
- Proteases (1)
- Proteasom (1)
- Proteasomaler Abbau (1)
- Proteasome (1)
- Protein Disulfid Isomerase (1)
- Protein Kinase D2 (1)
- Protein TRPC6 (1)
- Protein chemistry (1)
- Protein crosslinking (1)
- Protein folding (1)
- Protein interactions (1)
- Protein interactor (1)
- Protein purification (1)
- Protein-Protein Interaktion (1)
- Protein-Protein-Interaktion (1)
- Protein-Tyrosin-Kinasen (1)
- Proteinen mit antimikrobieller Wirkung (1)
- Proteinfaltung (1)
- Proteininteraktion (1)
- Proteininteraktionen (1)
- Proteinkinase A (1)
- Proteinkinase C (1)
- Proteinmodifizierung (1)
- Proteinquervernetzungen (1)
- Proteolysis (1)
- Proteolysis-Targeting-Chimera (1)
- Proteomics (1)
- Prozessierung (1)
- Prädiktoren und Korrelate (1)
- Präklinische Bildgebung (1)
- Präklinische Studien (1)
- Pränatale Entwicklung (1)
- Präzisionsmedizin (1)
- Pseudouridin (1)
- Psoriasis (1)
- Psychische Belastung (1)
- Psychische Gesundheit (1)
- Psychobiologie (1)
- Psychotherapie (1)
- Ptpn22 (1)
- Puberty (1)
- Pubertät (1)
- Pulswelle (1)
- Punktmutation (1)
- Purinozeptor (1)
- Pyridoxal 5'-phosphate phosphatase (1)
- Pyridoxalphosphat (1)
- Pyrrolidinderivate (1)
- Pyrrolidine carboxamides (1)
- Pyrrolizidinalkaloide (1)
- QPCR (1)
- QTOF (1)
- Quadruplex-DNS (1)
- Qualität (1)
- Qualitätsindikator (1)
- Qualitätssicherung (1)
- Quantifizierung (1)
- Quantitation (1)
- Quantitative Genetics (1)
- Quartäre Bisnaphthalimide (1)
- Quaternary Bisnaphthalimide (1)
- RAF (1)
- RAF Kinasen (1)
- RAMP (1)
- REDD1 (1)
- REST-Complex (1)
- RESTORE protocol (1)
- RIL-seq (1)
- RIM1α (1)
- RNA Abbau (1)
- RNA G-quadruplex (1)
- RNA Polymerase II (RNAPII) (1)
- RNA Sequencing (1)
- RNA binding potein CNBP (1)
- RNA binding proteins (1)
- RNA decay (1)
- RNA metabolism (1)
- RNA protein interactions (1)
- RNA secondary structures (1)
- RNA sequencing (1)
- RNA structures (1)
- RNA virus (1)
- RNA-Protein Interaktom (1)
- RNA-RNA interactions (1)
- RNA-Seq (1)
- RNA-Sequenzierung (1)
- RNA-bindendes Protein (1)
- RNA-binding protein (1)
- RNA-binding proteins (1)
- RNA-protein interactome (1)
- RNAi (1)
- RNS Polymerase I (1)
- RNS-Polymerase II (1)
- RNS-Spleißen (1)
- ROR2 (1)
- RS1 Peptides (1)
- RS1 derived peptides (1)
- RSK2 (1)
- RSV (1)
- RYGB (1)
- Rac1 (1)
- Radiale MR-Bildgebung (1)
- Radiation Protection (1)
- Radiation-associated Cancer Risk (1)
- Radiologische Diagnostik (1)
- Radionuklidtherapie (1)
- Raf <Biochemie> (1)
- Raf Kinase Inhibitor Protein (RKIP) (1)
- Raf kinase inhibitor protein (1)
- Raf1 (1)
- Random Forest (1)
- Random-walk simulations (1)
- Raphe (1)
- Raphe Kerne (1)
- Rasterionenmikroskop (1)
- Rasterkraft-Mikroskopie (1)
- Rauch (1)
- Rbm8a (1)
- Read-through transcription (1)
- Reaktive Sauerstoffspezies (1)
- Real-time imaging (1)
- RecQ helicase (1)
- Receptor (1)
- Receptor Anchoring (1)
- Receptor dynamics (1)
- Receptor internalization (1)
- Receptor signaling (1)
- Recombinant defensins (1)
- Recycling- Endosomen (1)
- Red Sea (1)
- Regenerative Medicine (1)
- Regulation of Gene Expression (1)
- Regulator of G protein signaling 2 (1)
- Regulatorische T-Zellen (1)
- Regulatory T Cells (1)
- Regulatory T-cell (1)
- Rekombinante DNS (1)
- Rekonsolidierung (1)
- Rekonstruktion (1)
- Relaxation Parameter Mapping in Magnetic Resonance Imaging (1)
- Remission (1)
- Remodeling (1)
- Renaturierung <Ökologie> (1)
- Repeats (1)
- Reperfusion (1)
- Reporter Cells (1)
- Reporterzellen (1)
- Repression (1)
- Repression <Genetik> (1)
- Reproducibility challenges (1)
- Reprogrammming (1)
- Rescue behaviour (1)
- Resistance (1)
- Resistenzmechanismen (1)
- Respiratorisches System (1)
- Response Inhibition (1)
- Ressourcenallokation (1)
- Restriktionsenzym (1)
- Resveratrol (1)
- Retinales S-Antigen (1)
- Retinoesäure (1)
- Retinoic acid (1)
- Reverse Transkriptase (1)
- Rezeptor Verankerung (1)
- Rezeptor-Tyrosinkinasen (1)
- Rezeptorblocker (1)
- Rezeptorpharmakologie (1)
- Rezidiv (1)
- Rgs2 (1)
- Rheologie (1)
- Rheology (1)
- Rheumatoider arthritis (1)
- Rhizopus arrhizus (1)
- Rho GTPase (1)
- Rho GTPasen (1)
- Rho GTPasw (1)
- Rho-GTPasen (1)
- Rho-Kinasen (1)
- RhoGTPase (1)
- Rhodopseudomonas palustris (1)
- Rhodopsin 7 (1)
- Ribonuclease H2 (1)
- Riboregulation (1)
- Ribosomale RNA (1)
- Ribosome biogenesis (1)
- Ribosome profiling (1)
- Ribozymes (1)
- Riesensynapsen (1)
- Risikoanalyse (1)
- Risk Assessment (1)
- Rituximab (1)
- Rodents (1)
- Rodung (1)
- Roscovitine (1)
- Rossameise (1)
- Rotes Meer (1)
- Rothmund-Thomson-Syndrome (1)
- Rupturen (1)
- Räumliches Gedächtnis (1)
- SAP2 (1)
- SCV maturation (1)
- SEPHCHC Synthase (1)
- SERCA2a (1)
- SET7 (1)
- SGLT (1)
- SHIP-TREND (1)
- SIS-muc (1)
- SIX1 (1)
- SLC2A3 (1)
- SLFN5 (1)
- SMARD1 (1)
- SMN complex (1)
- SNAP-Rezeptor (1)
- SNPs (1)
- SOC (1)
- SOD1 (1)
- SPECT/CT (1)
- SR proteins (1)
- SREBP (1)
- STAAB Cohort Study (1)
- STAAB study (1)
- STAAB-Studie (1)
- STD patients (1)
- STEC (1)
- STED (1)
- STIM2 (1)
- STP1 (1)
- SUMOylation (1)
- SWI/SNF (1)
- Saatgutbeizung (1)
- Saccharomyces cerevisiae (1)
- Salmonellose (1)
- Samenschale (1)
- Sandminen (1)
- Sap47 (1)
- Satellite glial cell (1)
- Sauerstoffkonzentration (1)
- Saure Sphingomyelinase (1)
- Scaffold bone implant (1)
- Schaumzelle (1)
- Scherstress (1)
- Schilddrüse (1)
- Schimmelpilze (1)
- Schimpanse (1)
- Schizosaccharomyces pombe (1)
- Schlafstörung (1)
- Schlaganfallversorgung (1)
- Schließzellfunktion (1)
- Schmerztherapie (1)
- Schmerzverarbeitung (1)
- Schmetterlinge (1)
- Schnelle MR-Bildgebung (1)
- Schreckreaktion (1)
- Schuppenflechte (1)
- Schwamm (1)
- Schwämme (1)
- Sehen (1)
- Sekretion (1)
- Sekretion von Aspartatproteasen (1)
- Sekundäre Inflammation (1)
- Sekundärprävention (1)
- Sekundärstruktur (1)
- Selbstregulation (1)
- Selective extraction (1)
- Selektiver Serotonin Wiederaufnahmehemmer / SSRI (1)
- Senecionin (1)
- Seneciphyllin (1)
- Seneszenz (1)
- Sensory Gating (1)
- Sequence Analysis (1)
- Sequence-Structure (1)
- Sequenz (1)
- Sequenzanalyse <Chemie> (1)
- Sequenzdaten (1)
- Sequenzwiederholung (1)
- Serinprotease (1)
- Serotonin Transporter (1)
- Serotonin transporter (1)
- Serotonin-Reuptake-Hemmer (1)
- Serotonin-Wiederaufnahmehemmer (1)
- Serotonindefizienz (1)
- Serotonintransporter (1)
- Sertralin (1)
- Setting Control (1)
- Sexuelle Entwicklung (1)
- Sezernierte Faktoren (1)
- Sglt1 (1)
- Shear Stress (1)
- Shigella (1)
- Shigella flexneri (1)
- Shimming (1)
- Sialoadhesin (1)
- Sicherheit (1)
- Signal-Übertragung (1)
- Signaling (1)
- Signalregenerierung (1)
- Silica precursor (1)
- Simulation (1)
- Single Particle Tracking (1)
- Single-cell RNA Sequencing (1)
- Single-cell RNA-sequencing (1)
- Single-molecule (1)
- Single-molecule fluorescence microscopy (1)
- Single-molecule tracking (1)
- Sinusthrombose (1)
- Skin (1)
- Skin Tissue Engineering (1)
- Skin conductance (1)
- Sleep (1)
- Sleep in children (1)
- Sleeping Beauty Transposon System (1)
- Sleeping Beauty transposon (1)
- Smad (1)
- Small angle X-ray scattering (1)
- Small intestine (1)
- Small non-messenger RNS (1)
- Small nuclear RNP (1)
- Small-angle X-ray Scattering (1)
- Smoke (1)
- SnRK1-bZIP complex (1)
- Snap25 (1)
- Social Buffering (1)
- Social Distancing (1)
- Social action effects (1)
- Social buffering (1)
- Sociomotor gaze control (1)
- Sodium dependent glucose transporter-1 (1)
- Sol-gel (1)
- Solanaceae (1)
- Solanum species (1)
- Solid-phase peptide synthesis (1)
- South Africa (1)
- Soziale Handlungseffekte (1)
- Soziale Phobie (1)
- Sozialer Kontakt (1)
- Soziobiologie (1)
- Soziomotorische Blickkontrolle (1)
- Spatial heterogeneity (1)
- Spatiotemporal analysis (1)
- Specialized pro resolving mediators (1)
- Species richness (1)
- Speckle Tracking (1)
- Speicheldrüse (1)
- Sphingolipidstoffwechsel (1)
- Sphingomyelinase (1)
- Sphingomyelinphosphodiesterase (1)
- Sphingosine-1-phosphate (1)
- Sphingosine-1-phosphats (1)
- Spielsucht (1)
- Spinal muscular Atrophy (1)
- Spinal muscular atrophy (1)
- Spinal muscular atrophy (DLC) (1)
- Spinalganglion (1)
- Spirale (1)
- Spleen tyrosine kinase (1)
- Spliceosome (1)
- Splicing (1)
- Spo0A (1)
- Sponge diseases (1)
- Sponges (1)
- Sporenbildung (1)
- Sporulation (1)
- Spumaviren (1)
- Squamous cell carcinoma (1)
- Ssl1 (1)
- Stack-of-Stars Sequenz (1)
- Stack-of-Stars sequence (1)
- Stammzellen (1)
- Stammzelltransplantation (1)
- Staphylococci (1)
- Staphylococcus epidermidis (1)
- Stat3 (1)
- Stat5 (1)
- Stathmin (1)
- Staupevirus (1)
- SteC (1)
- Stechameisen (1)
- Stem Cells (1)
- Stem cells (1)
- Sterblichkeit (1)
- Steroide (1)
- Steroidhormon (1)
- Stickstoffkontrolle (1)
- Stickstoffmetabolismus (1)
- Stickstoffmonoxid-Synthase (1)
- Stickstoffwechsel (1)
- Stiff person syndrome (1)
- Stiff-Person Syndrom (1)
- Stiff-person syndrome (1)
- Stimmbandchirurgie (1)
- Stimmerhöhung (1)
- Stimulation (1)
- Stimulationsversuche (1)
- Stk (1)
- Stofftransport <Biologie> (1)
- Stoffwechselinhibitoren (1)
- Store-Operated (1)
- Stp (1)
- Strahlenpilze (1)
- Streptomyces (1)
- Stressresistenz (1)
- Striatum (1)
- Stroke (1)
- Stroke Unit (1)
- Stroma (1)
- Stroop-Verfahren (1)
- Structural elucidation (1)
- Structural organisation (1)
- Structure-based (1)
- Structured Illumination Microscopy (1)
- Struktur (1)
- Struktur-basiertes Wirkstoff Design (1)
- Strukturanalyse (1)
- Strukturbiologie (1)
- Strumpellin (1)
- Störabstand (1)
- Störung des Sozialverhaltens (1)
- Subitizing (1)
- Subtyp C (1)
- Sumo (1)
- Sumoylierung (1)
- Super-Resolution Microscopy (1)
- Super-resolution microscopy (1)
- Super-resolution microsopy (1)
- Superhochauflösende Mikroskopie (1)
- Superparamagnetische Eisenoxid Kontrastmittel (1)
- Superresolution microscopy (1)
- Suppressorzelle (1)
- Survival Motor Neuron (1)
- Suspensionskultur (1)
- Syap1 (1)
- Symbionts (1)
- Symbiosis (1)
- Synapse-associated protein (1)
- Synapsen assoziiert (1)
- Synapses (1)
- Synapsine (1)
- Synaptic plasticity (1)
- Synaptische Plastizität (1)
- Synaptische Transmission (1)
- Synaptische Vesikel (1)
- Synchronitätsmessung (1)
- Syncytin (1)
- Synthesis (1)
- Systematik (1)
- Systembiologie (1)
- Säugerzellen (1)
- Säugetiere (1)
- Südafrika (1)
- Südostasien (1)
- T Helper Cell (1)
- T Lymphocyte (1)
- T Zell Selektion (1)
- T Zellen (1)
- T cell (1)
- T cell cytotoxicity (1)
- T cell engaging Antibody (1)
- T cell homing (1)
- T cell receptor (1)
- T cell selection (1)
- T cell specificity (1)
- T zellen (1)
- T-Zell-Aktivierung (1)
- T-Zellaktivierung (1)
- T-Zellhoming (1)
- T-Zellmigration (1)
- T-cell (1)
- T-cell engineering (1)
- T-cell therapy (1)
- TAC (1)
- TCTP (1)
- TGF-ß (1)
- TGF-β (1)
- TGN1412 (1)
- TH2 Immunantwort (1)
- TLR signaling (1)
- TMEM16F (1)
- TNBC (1)
- TNFR2 (1)
- TP53 (1)
- TP53 lesions (1)
- TRAIL mutants (1)
- TRPA1 (1)
- TRPA1 channel (1)
- TRPC (1)
- TRPC-Ionenkanäle (1)
- TRPC3 (1)
- TRPC6 (1)
- TRPM7 kinase (1)
- TRPV1 (1)
- TRRAP (1)
- TT-Fields (1)
- TTF (1)
- Tabakkonsum (1)
- Tageslänge (1)
- Tagesrhythmik (1)
- Tamoxifen (1)
- Tansania (1)
- Tanzania (1)
- Tapeworm (1)
- Targeted therapies (1)
- Targeted therapy (1)
- Tc-99m-MAG3 Scans (1)
- Telomer <Molekulargenetik> (1)
- Telomerase (1)
- Temperatur (1)
- Temperaturabhängigkeit (1)
- Temporal heterogeneity (1)
- Temporal predictability (1)
- Terahertzbereich (1)
- Terahertzstrahlung (1)
- Terpene (1)
- Test system (1)
- Tfb4 (1)
- Thebain (1)
- Theoretical Ecology (1)
- Theory of Mind (1)
- Therapeutical application (1)
- Therapieoutcome (1)
- Therapiesimulation (1)
- Therapy (1)
- Thermoregulation (1)
- Thermoresponsive Polymere (1)
- Thermotoleranz (1)
- Theta Burst Stimulation (1)
- Thigmotaxis (1)
- Think/No-Think (1)
- Thiolase (1)
- Thiostrepton (1)
- Thrombin (1)
- Thromboinflammation (1)
- Thrombopoese (1)
- Thrombozyten (1)
- Thrombozytenfunktion (1)
- Thrombozytenfunktionsanalyse (1)
- Thrombozytopathie (1)
- Thrombozytopenie (1)
- Thrombozytopoese (1)
- Thrombus (1)
- Thymocytes (1)
- Thymosin b4 (1)
- Thymus (1)
- Tierphysiologie (1)
- Tight Junction Proteins (1)
- Tight junction (1)
- Tight-Junction-Protein (1)
- Time-of-flight (1)
- Timing (1)
- Tissue staining (1)
- Tobacco smoking (1)
- Tolerance (1)
- Toleranz <Biologie> (1)
- Toxin (1)
- TraDIS (1)
- Tracer (1)
- Trailmaking Test (1)
- Transcranial Magnetic Stimulation (1)
- Transcription Factor (1)
- Transcription Regulation (1)
- Transcription factor (1)
- Transcriptional Stress Response (1)
- Transgenic mice (1)
- Transkriptomik anlyze (1)
- Translation <Genetik> (1)
- Transmission (1)
- Transmissionsblockierende Impfstoffe (1)
- Transpiration barrier (1)
- Transplantatabstoßung (1)
- Transportbarriere (1)
- Transporters (1)
- Transsexualismus (1)
- Transthorakale Echokardiographie (1)
- Trauma (1)
- Traumatic neuropathy (1)
- Tree physiology (1)
- Trem2 (1)
- Trend (1)
- Trennungsangst (1)
- Triclosan (1)
- Trifluoroethene (1)
- Triglyceride (1)
- Tripartite Model (1)
- Trockenstress (1)
- Trophic Factors (1)
- Tropomyosin receptor kinase B (1)
- TruD (1)
- Trypanosoma (1)
- Trypanosoma Brucei (1)
- Trypanosoma brucei brucei (1)
- Trypanosomiasis (1)
- Tryptophan hydroxylase (1)
- Tryptophan hydroxylase 2 (1)
- Tuberkulose (1)
- Tumor Treating Fields (1)
- Tumor microenvironment (1)
- Tumor-Nekrose-Faktor <alpha> (1)
- Tumorangiogenese (1)
- Tumorgefäßmorphologie (1)
- Tumorhypoxie (1)
- Tumorimmunologie (1)
- Tumormetabolismus (1)
- Tumormikroumgebung (1)
- Tumortherapiefeld (1)
- Tumorwachstum (1)
- Tumorzellen (1)
- Tumour (1)
- Tumour angiogenesis (1)
- Twilight (1)
- Typ 2 (1)
- Type 1 Diabetes (1)
- Type 1 diabetes (1)
- Type II-C CRISPR/Cas (1)
- Type VIIb secretion system (1)
- Tyrosinkinaseinhibitor (1)
- U snRNPs (1)
- U1 snRNA (1)
- UBA6 (1)
- UBE2S (1)
- UBE2Z (1)
- UNC5B (1)
- UPEC (1)
- USA300 (1)
- USP (1)
- USP28 (1)
- Ubiquitin Specific Protease 11 (1)
- Ubiquitin activating eznyme 1 (1)
- Ubiquitin system (1)
- Ubiquitin-PA (1)
- Ubiquitin-aktivierende Enzym 1 (1)
- Ubiquitin-conjugating enzyme (1)
- Ubiquitylation (1)
- Ultrahigh field (1)
- Ultraschall (1)
- Ultrashort echo time - UTE (1)
- Unidirectional Freezing (1)
- Untertyp (1)
- Uremic cardiomyopathy (1)
- Urinary tract infection (1)
- Urteilen (1)
- Urämie (1)
- Urämische Kardiomyopathie (1)
- VCAM (1)
- VE-Cadherin (1)
- VE-PTP (1)
- VLA-1 (1)
- VSMC (1)
- VW-SCs (1)
- Vaccinia-Virus (1)
- Vagus (1)
- Vagusnervstimulation (1)
- Vakuole (1)
- Vakzinen (1)
- Validierung (1)
- Validierungsstudie (1)
- Validität (1)
- Valscularization (1)
- Variant Surface Glycoprotein (1)
- Variant surface glycoprotein (1)
- Variants (1)
- Vascular system (1)
- Vaskularisation (1)
- Vaskularisierung (1)
- Vaskuläre Integrität (1)
- Vasopressin (1)
- Venusfliegenfalle (1)
- Verbreitungsökologie (1)
- Verhaltenplastizität (1)
- Verhaltenskontrolle (1)
- Verhaltensplastizität (1)
- Verhaltensstörung (1)
- Verkalkung (1)
- Vermehrung (1)
- Vermeidungsreaktion (1)
- Vermeidungsverhalten (1)
- Vernetzung <Chemie> (1)
- Versorgungsqualität (1)
- Verweildauer (1)
- Verwundbarkeit (1)
- Very-long-chain aliphatic (1)
- Vesikel (1)
- Vesikelbildung (1)
- Vessel wall (1)
- Vg9Vd2 T Zellaktivierung (1)
- Vg9Vd2 T cell (1)
- Vgamma9Vdelta2 T cell (1)
- Vgamma9Vdelta2 T cells (1)
- Vibrationstraining (1)
- Vielfalt (1)
- Virologische Synapse (1)
- Virology (1)
- Virulenzfaktor (1)
- Virus infection (1)
- Virus-Transmission (1)
- Virusreplikation (1)
- Visual attention (1)
- Visuelle Orientierung (1)
- Visuelle Wahrnehmung (1)
- Visuelles Gedächtnis (1)
- Visuelles System (1)
- Vitamin D (1)
- Vitamin D-Rezeptor (1)
- Vitamin D3 (1)
- Voltage-Clamp-Methode (1)
- Vorhersage (1)
- Vorläufer (1)
- Vulnerable plaque (1)
- Vγ9Vδ2 T cells (1)
- WASH complex (1)
- WNT (1)
- WNT signaling (1)
- Wachstum (1)
- Wachstumsfaktor (1)
- Waiting Impulsivity (1)
- Walking (1)
- Warburg, Otto (1)
- Warburg-Effekt (1)
- Wasser Fett Trennung (1)
- Wasted Work (1)
- Water stress (1)
- Web services (1)
- Wechselwirkungen (1)
- Weinrebe (1)
- Wildbienen (1)
- Wilms Tumor (1)
- Wilms tumor protein 1 (1)
- Wilms-Tumor (1)
- Wirbelströme (1)
- Wirkstoff (1)
- Wirkstofftestung (1)
- Wirt-Erreger Interaktion (1)
- Wirtszelle (1)
- Wnt-Proteine (1)
- Wnt-Signalweg (1)
- Wnt-pathway (1)
- Wurzelhalsgalle (1)
- Würmer (1)
- Wüstenpflanze (1)
- X-ray Crystallography (1)
- X-ray diffraction (1)
- XPD (1)
- Xenograft (1)
- Xeroderma pigmentosum (1)
- Xerostomie (1)
- Xiphophorus Melanom (1)
- Xmrk (1)
- YAP (1)
- YB-1 (1)
- Yb1 (1)
- Yeast (1)
- Yersinia (1)
- Yersinia pestis (1)
- YnaI (1)
- ZFAND1 (1)
- Zebrafisch (1)
- Zeitgeber (1)
- Zell Migration (1)
- Zell-Migration (1)
- Zelladhäsion (1)
- Zellfilamente (1)
- Zellkernarchitektur (1)
- Zellkontakt (1)
- Zelllinie (1)
- Zellteilung (Zytokinese) (1)
- Zelltod (1)
- Zelltransport (1)
- Zielstruktur (1)
- Zink-Cluster-Transkriptionsfaktoren (1)
- Zytokin (1)
- Zytokingenpolymorphismus (1)
- Zytoskelettreorganisation (1)
- Zählen (1)
- aGPCR (1)
- acceptance-based strategies (1)
- acid sphingomyelinase (1)
- actin cytoskeleton (1)
- actin-binding proteins (1)
- actinomycetes (1)
- acute brain slices (1)
- acute graft-versus host disease (1)
- acute lymphoblastic leukaemia (1)
- adhesion (1)
- adhesion-GPCR (1)
- adipogenic differentiation (1)
- adipose (1)
- adipose-derived (1)
- adolescents (1)
- adrenal gland (1)
- adrenal incidentaloma (1)
- adrenerge Rezeptoren (1)
- adrenergic receptor (1)
- adrenergic receptors (1)
- adrenocortical adenoma (1)
- adult ADHD (1)
- adult attention deficit hyperactivity disorder (aADHD) (1)
- adult development (1)
- adulte Neurogenese (1)
- aggressive behavior (1)
- aging (1)
- agonist (1)
- airflow (1)
- airways (1)
- akute lymphatische Leukämie bei Kindern (1)
- alfa-cyano-4-hydroxycinnamat (1)
- alkaloids (1)
- allogen (1)
- allogeneic stem cell transplantation (1)
- allogenic (1)
- allogenic stem cell transplantation (1)
- allografts (1)
- alloreactive T cells (1)
- alltägliche Funktionsfähigkeit (1)
- alpha-IIb beta-3 (1)
- alternative intronic polyadenylation (1)
- ammonium (1)
- ammonium permease (1)
- amphibia (1)
- amphiphysin (1)
- amyotrophic lateral sclerosis (1)
- anaerobe (1)
- analysis (1)
- anaphylatoxin receptors (1)
- androstadienone (1)
- anoikis (1)
- anterior insula (1)
- anthocyanins (1)
- anti-hDEC205-WT1 antibody fusion protein (1)
- anti-infective (1)
- antigen (1)
- antigenic variation (1)
- antileukemia vaccine (1)
- antimicrobial (1)
- antithrombotic (1)
- antivirale Gene (1)
- anxiety conditioning (1)
- arf (1)
- aromatic amino acid biosynthesis (1)
- articular cartilage progenitor cells (1)
- artificial diet (1)
- artificial human skin (1)
- artifizielle Aktivierung (1)
- artifizielle Hautmodelle (1)
- asialoGM1 (1)
- aspartic protease (1)
- aspergillus fumigatus (1)
- assembly (1)
- association studies (1)
- astrocytoma (1)
- asymptomatic bacteriuria (1)
- atomic force microscopy (1)
- atopic diseases (1)
- atrial natriuretic peptide (1)
- attributable fraction (1)
- attributable risk (1)
- auditorisch (1)
- auditory (1)
- auditory cortex (1)
- auditory pathway (1)
- autoantibodies (1)
- autoantibody (1)
- autoimmunity (1)
- autophagocytose (1)
- autophagocytosis (1)
- autophagosome (1)
- autotransporter (1)
- bSSFP (1)
- bac-genomics-scripts (1)
- bacterial cancer therapy (1)
- bacterial fatty-acid biosynthesis (1)
- bacterial lipid rafts (1)
- bacterial nanocellulose (1)
- bacterial tumor targeting (1)
- bakterielle Flora (1)
- balanced steady state free precession (1)
- bark beetles (1)
- bee microbiota (1)
- bee-associated bacteria (1)
- bee-lining (1)
- bees (1)
- behavioral maturation (1)
- behavioral rhythms (1)
- beige adipocytes (1)
- benzimidazole (1)
- bestäuberfreundliche Pflanzen (1)
- beta actin (1)
- beta cell (1)
- beta-Arrestin2 (1)
- beta-Catenin (1)
- beta-adrenerge Signalwege (1)
- bicuculline (1)
- bilateral BAS model (1)
- binding mode (1)
- biochemistry (1)
- biodistribution (1)
- biodiversity (1)
- biofabrication (1)
- biofilm architecture (1)
- bioimage analysis (1)
- bioink (1)
- biokinetics (1)
- biolayerinterferometry (1)
- biological scaffolds (1)
- bioluminescence imaging (1)
- biomaterials (1)
- bioprocessing (1)
- bioreactor plattform (1)
- biosynthetic gene clusters (1)
- bipolar disorder (1)
- bipolare Störung (1)
- bispecific (1)
- bispezifisch (1)
- bitter taste (1)
- blood (1)
- blood cerebrospinal fluid barrier (1)
- blood glucose regulation (1)
- blood nerve barrier (1)
- blood-brain barrier (1)
- body axis (1)
- bone marrow niche (1)
- bone marrow transplantation (1)
- bone metastases (1)
- bone regeneration (1)
- brood rearing (1)
- building behavior (1)
- bumblebee*s (1)
- burn wound (1)
- butyrophilin 3A (1)
- c-Jun Phosphorylierung (1)
- c-myc (1)
- cAMP signaling (1)
- cadherin-13 (1)
- caffeine (1)
- calcium activity (1)
- calcium homeostasis (1)
- calcium imaging (1)
- cancer therapy (1)
- candida (1)
- candida albicans (1)
- canine (1)
- carbon dioxide (1)
- cardiac imaging (1)
- cardiac magnetic resonance imaging (1)
- cardiac tissue (1)
- cardiac tissue engineering (1)
- cardiovascular (1)
- carnivorous plants (1)
- cartilage (1)
- cartilage regeneration (1)
- cd28 superagonists (1)
- cell adhesion (1)
- cell cycle (1)
- cell filaments (1)
- cell migration (1)
- cell therapy (1)
- cellular model (1)
- cellular-trafficking (1)
- central complex (1)
- chaperone (1)
- chemotherapy (1)
- children (1)
- chimeric antigen receptor (1)
- chlamydia trachomatis (1)
- chondrogene Differenzierung (1)
- chromatin accessibility (1)
- chromosome conformation capture (1)
- chronic kidney disease (1)
- chronic pain (1)
- chronophin (1)
- cine loop (1)
- circadian clock (1)
- circadian clocks (1)
- circuitopathies (1)
- classical conditioning (1)
- claudin-12 (1)
- climate change (1)
- climate control (1)
- clock genes (1)
- closing of chromatin (1)
- co-culture (1)
- co-dependent expression (1)
- co-infection (1)
- coagulation factor XII (1)
- cochlea implant (1)
- cofactorbinding (1)
- cognitive decline (1)
- cognitive deficits (1)
- cognitive inhibition (1)
- cognitive remediation (1)
- cohesin (1)
- collective invasion (1)
- collybistin (1)
- colony recognition (1)
- color vision (1)
- comet assay (1)
- compartments (1)
- compound eyes (1)
- compressed sensing (1)
- conditional Knockout (1)
- confocal microscopy (1)
- conformational activation (1)
- context conditioning (1)
- contextual conditioning (1)
- contingency awareness (1)
- continuous wavelet analysis (1)
- control (1)
- convolutional neural network (1)
- corneal confocal microscopy (1)
- coronary heart disease (1)
- correlation (1)
- corticosteroids and cyclophosphamide (1)
- cryokonservation (1)
- crystal structure (1)
- ctr (1)
- current source density (1)
- cushing's syndrome (1)
- cuticular hydrocarbons (1)
- cuticular leaf wax (1)
- cuticular transpiration barrier (1)
- cuticular water permeability (1)
- cuticular waxes (1)
- cyclase-associated protein (1)
- cyclase-associated protein 2 (1)
- cyclo-AMP (1)
- cytokine release syndrome (1)
- cytoskeletal reorganisation (1)
- dCIRL (1)
- dSTORM (1)
- decellularization (1)
- decision-making (1)
- defense (1)
- degeneratives Nervengewebe (1)
- delipidation (1)
- dendritic cells (1)
- dendritic cell-targeting (1)
- density weighting (1)
- desert plant (1)
- deubiquitinase (1)
- dexamethasone suppression test (1)
- diabetes (1)
- diabetic cardiomyopathy (1)
- diagnostic Microarray (1)
- diagnostic accuracy (1)
- diagnostics (1)
- diagnostischer Microarray (1)
- diastolic dysfunction (1)
- differential RNA-seq (1)
- differential coverage binning (1)
- differential geneexpression (1)
- differentiation status (1)
- differenzielle Genexpression (1)
- dilated cardiomyopathy with ataxia (DCMA) (1)
- dimerer Naphthylisochinolin-Alkaloide (1)
- discrimination training (1)
- disease model (1)
- dispersal (1)
- distance (1)
- distribution (1)
- disulfide bonds (1)
- diversity (1)
- double-strand break repair (1)
- drift-diffusion model (1)
- drug (1)
- drug repurposing (1)
- dual RNA-seq (1)
- early detection (1)
- early neural precursors (1)
- early-life stress (1)
- early-onset isolated dystonia (1)
- eating behavior (1)
- eating disorders (1)
- echocardiography (1)
- ecoli_VF_collection (1)
- ecological validity (1)
- ectopic bone formation (1)
- ectopic release (1)
- effector protein (1)
- efflux pump (1)
- electroacupuncture (1)
- electrode scaffold (1)
- electroencephalogram (1)
- electron cryomicroscopy (1)
- electron tomography (1)
- electrospinning (1)
- embryonale Maus (1)
- emojis (1)
- emotional (1)
- emotional feedback (1)
- emotional information processing (1)
- emotional interference (1)
- emotional processing (1)
- emotionale Anspannung (1)
- emotionale Interferenz (1)
- emotions (1)
- endocytic recycling (1)
- endocytosis (1)
- endophyte (1)
- enhancers (1)
- enoyl ACP reductase (1)
- enoyl reductase (1)
- enoyl-ACP reductase (1)
- entero-aggregative-haemorrhagic Escherichia coli (EAHEC) (1)
- enteroinvasive (1)
- eosinophil (1)
- epidemiology (1)
- epigenetic (1)
- epithelial to mesenchymal transition (1)
- epithelial-mesenchymal transition (1)
- ereigniskorreliertes Potential (1)
- etiology (1)
- evozierte Potentiale (1)
- exotische Pflanzen (1)
- experimentelle autoimmune Enzephalomyelitis (1)
- exposition training (1)
- exposure therapy (1)
- extinction (1)
- extinction dynamics (1)
- extracellular signal–regulated kinases 1/2 (1)
- extrazelluläre Matrix (1)
- eye contact (1)
- eye tracking (1)
- eye-tracking (1)
- eyetracking (1)
- fabry disease (1)
- facial expressions (1)
- fast MR imaging (1)
- fatty acid biosynthesis (1)
- fatty acid synthesis (1)
- fear potentiated startle response (1)
- feasibility (1)
- feral bees (1)
- fgf (1)
- fibroblast growth factors (1)
- fibromyalgia sydrome (1)
- filtering (1)
- fitness (1)
- flagellum (1)
- fluorescence imaging (1)
- fluorescence microscopy (1)
- fluorescence resonance energy transfer (1)
- fluorescence resonance energy transfer (FRET) (1)
- flytrap (1)
- fmri activity (1)
- foamy viruses (1)
- follicular regulatory T cell (1)
- follikuläre regulatorische T-Zelle (1)
- food craving (1)
- forager (1)
- foraging (1)
- foraging activity (1)
- forest landscape (1)
- fragment screening (1)
- frameshifting (1)
- freezing of gait (1)
- frequency modulation (1)
- frogs (1)
- fruit cuticle (1)
- frühe neurale Vorläufer (1)
- functional connectivity (1)
- functional imaging (1)
- functional membrane microdomains (1)
- functional modules (1)
- functional neuroimaging (1)
- functional resting-state connectivity (1)
- functional selectivity (1)
- functional studies (1)
- fungal endophytes of grasses (1)
- fungi (1)
- fungus (1)
- funktionale Bildgebung (1)
- funktionelle Magnetresonanztomographie (1)
- funktionelle Module (1)
- funktionelle Resting-State Konnektivität (1)
- g-factor (1)
- gait analysis (1)
- gait initiation (1)
- gametocyt (1)
- gametocyte (1)
- gametogenesis (1)
- gamma delta T cells (1)
- gastrointestinal infection (1)
- gastronintestinal microbiota (1)
- gene environment interaction (1)
- gene-environmental interaction (1)
- genetic cytokine polymorphism (1)
- genetic modification (1)
- genetic screen (1)
- genome stability (1)
- genomic damage (1)
- genomic imaging (1)
- genomische Schäden (1)
- genotoxic agents (1)
- genotoxische Agenzien (1)
- gepaarte Vagusnerv-Stimulation (1)
- germinal center (1)
- germinative cell (1)
- gezielte Therapie (1)
- glioblastoma multiforme (1)
- glioma (1)
- glutamate decarboxylase 65 (1)
- glycine receptor (1)
- glycine receptor autoantibodies (1)
- glycophytes (1)
- glycoprotein GPV (1)
- gonococcal (1)
- gonococcal infection (1)
- grass (1)
- guanine nucleotide exchange factor (1)
- guanylyl cyclase (GC) (1)
- guard cells (1)
- gustation (1)
- habitat (1)
- haloacid dehalogenase phosphatase (1)
- hearing (1)
- heart failure (1)
- heat shock proteins (1)
- hematopoiesis (1)
- hereditary spastic paraplegia (1)
- hiPSC aggregation (1)
- hibernation (1)
- high-pressure freezing/freeze substitution (1)
- high-throughput sequencing (1)
- histone variants (1)
- hnRNP (1)
- hnRNP R (1)
- homeostasis (1)
- homoFRET (1)
- honey bee density (1)
- honey bees (1)
- honeybee*s (1)
- honeybees (1)
- host colonization (1)
- huh6 (1)
- human (1)
- human adipose tissue (1)
- human chromosome 6 (1)
- human factor H (1)
- human induced pluripotent stem cells (1)
- human intestinal epithelium (1)
- human parthenogenetic neural stem cells (1)
- human parthenogenetic stem cells (1)
- human plasma (1)
- human primary cells (1)
- humanen induzierte pluripotente Stammzellen (1)
- humaner Faktor H (1)
- humans (1)
- hyaline cartilage (1)
- hyaluronic acid (1)
- hybrid (1)
- hybrid assembly (1)
- hydrogel (1)
- hyperekplexia (1)
- iNKT cell (1)
- iPSC-derived CMs (iPSC-CMs) (1)
- iPSCs (1)
- icaADBC (1)
- imaging (1)
- immediate early genes (1)
- immune cell recruitment (1)
- immune escape (1)
- immune evasion (1)
- immune response (1)
- immune system (1)
- immunologic tolerance (1)
- immunological synapse (1)
- immunotherapy (1)
- imprinting. (1)
- imunology (1)
- in situ microscopy (1)
- in vitro Kulturmodelle (1)
- in vitro Modelle (1)
- in vitro Testmodell (1)
- in vitro Testsystem (1)
- in vitro model (1)
- in vitro model system of inherited cardiomyopathies (1)
- in vitro neural differentiation (1)
- in vitro-Testsystem (1)
- in vivo study (1)
- induced pluripotent stem cells (1)
- induced pluripotent stem cells (iPSCs) (1)
- induzierte Phosphatasen MKP-1 und MKP-2 (1)
- infection biology (1)
- infectionmodel (1)
- infectionprocess (1)
- inferior frontal gyrus (1)
- inferiore frontale Gyrus (1)
- inflammatorische Gewebeschäden (1)
- influenza A virus (1)
- information processing (1)
- information use (1)
- inherited macrothrombocytopenia (1)
- inhibitor residence time (1)
- inhibitory postsynapse (1)
- innate immunity (1)
- insect visual learning (1)
- insects (1)
- insertion-site deep sequencing (1)
- instrumentelle Aktivitäten des täglichen Lebens (1)
- insulin resistance (1)
- intact bone imaging (1)
- integrins (1)
- interaction stress and circadian system (1)
- interactions (1)
- interferon (1)
- interleukin-5 signaling (1)
- internal dosimetry (1)
- interphase gap (1)
- interpulse interval (1)
- intestinal mucus (1)
- intestine (1)
- intracellular calcium release (1)
- intracellular domain (1)
- intraoperative Ankopplungseffizienz (1)
- intravenöse Immunglobuline (1)
- intrazelluläre Domäne (1)
- invariant NKT cells (1)
- invariante NKT Zellen (1)
- invasive meningococcal diseases (1)
- invasive pulmonary aspergillosis (1)
- ion channel (1)
- iron oxide contrast agent (1)
- ischemia reperfusion injury (1)
- ischämischer Schlaganfall (1)
- islets of Langerhans (1)
- jasmonate (1)
- juvenile hormone (1)
- kardiales Gewebe (1)
- kardiales Tissue Engineering (1)
- kardiovaskuläre Risikofaktoren (1)
- ketamine anaesthesia (1)
- kidney development (1)
- kinesin (1)
- knockout (1)
- knockout-mice (1)
- kognitive Defizite (1)
- kognitive Remediation (1)
- kolorektale Karzinomzelllinien (1)
- konventionelle CD4 T Zellen (1)
- koronare Herzerkrankung (1)
- kutikuläre Kohlenwasserstoffe (1)
- kutikuläre Wasserpermeabilität (1)
- kutikuläres Blattwachs (1)
- l-type calcium channel antagonist (1)
- labeling techniques (1)
- lambdoid phage resistance (1)
- lambdoid prophage (1)
- laminar recording (1)
- lasiocarpine (1)
- lasp (1)
- late enhancement (1)
- late gadolinium-enhancement (1)
- leaf cuticle (1)
- leaf-cutting ants (1)
- learned helplessness (1)
- learning and behaviour (1)
- leishmaniasis (1)
- light sheet fluorescence microscopy (1)
- lightsheet microscopy (1)
- lipid remodeling (1)
- liver (1)
- local point-spread function (1)
- local translation (1)
- locomotor network (1)
- logging (1)
- lokale Proteinsynthese (1)
- long-term memory formation (1)
- luciferase assay (1)
- lymph node stromal cells (1)
- lymph node transplantation (1)
- lysosome (1)
- lytic infection (1)
- lytic phage resistance (1)
- mRNA (1)
- mRNA processing (1)
- mRNA translation (1)
- mRNA-Translation (1)
- mTOR (1)
- machine learning (1)
- macrocolony (1)
- macrophage (1)
- macrophages (1)
- malnourishment (1)
- mammalian cells (1)
- marine sponges (1)
- mastitis (1)
- mastitis-associated Escherichia coli (MAEC) (1)
- mean first passage time (1)
- measles virus infection (1)
- mechanistische Modellierung (1)
- mechanosensing (1)
- mechanosensitive channels (1)
- medaka (1)
- medical device (1)
- megachilid bees (1)
- megakaryocytes (1)
- melanocytic nevi (1)
- melanoma cancer (1)
- melanoma dedifferentiation (1)
- melt electrowriting (1)
- membrane dynamics (1)
- membrane trafficking (1)
- memory (1)
- memory B cells (1)
- meniscus implant (1)
- menschliches Darmepithel (1)
- mental health (1)
- mesenteric lymph node (1)
- mesoscopic (1)
- metabolic modelling (1)
- metabolic theory of ecology (1)
- metabolite repair (1)
- metabolomics (1)
- metallo protease (1)
- metapopulation (1)
- metatranscriptome (1)
- methionine biosynthesis (1)
- methylphenidate (1)
- miR-17~92 (1)
- miR-21 (1)
- miR-223-5p (1)
- miR-23a cluster (1)
- miR-26 (1)
- miRNA Biogenesis (1)
- miRNA target (1)
- mice (1)
- micro processor complex (1)
- microRNA biogenesis (1)
- microbial transmission (1)
- microbiology (1)
- microbiota (1)
- microcircuitry (1)
- microelectrode array (1)
- microglomeruli (1)
- microinjection (1)
- micronuclei (1)
- microphysiologic 3D tumour model (1)
- microprocessor complex (1)
- microrna (1)
- mild cognitive impairment (1)
- minimum leaf conductance (1)
- mitochondria (1)
- mitogen cascade (1)
- mobil phone radiation (1)
- molecular biology of cytokines (1)
- molecular mechanism (1)
- monarch butterfly (1)
- monoclonal antibody (1)
- monoclonal antibody 103.2 (1)
- monoclonal antibody 20.1 (1)
- monocyte-derived dendritic cells (1)
- monozytenderivierte dendritische Zellen (1)
- mossy fiber synapse (1)
- mossy fiber terminal (1)
- motoneurons (1)
- motor neuron (1)
- mouse models (1)
- mouse platelets (1)
- movement disorders (1)
- movement interaction (1)
- mucormycosis (1)
- mukosale Immunantwort (1)
- multi-drug-resistance (1)
- multi-modal stimuli (1)
- multi-photon microscopy (1)
- multi-pinhole collimation (1)
- multiphoton microscopy (1)
- multiple sclerosis (1)
- murine (1)
- murine leishmaniasis (1)
- murines Modell der aufsteigenden Harnwegsinfektion (1)
- muscarinic m ACh receptors (1)
- mushroom body (1)
- mushroom body calyx microglomeruli (1)
- muskarinische Rezeptoren (1)
- mutualism (1)
- mutually exclusive expression (1)
- myelin barrier (1)
- myeloablation (1)
- myeloid derived suppressor cells (1)
- myocardial deformation (1)
- myocarditis (1)
- myokardiale Arbeit (1)
- nanotubes (1)
- ncRNA (1)
- near-infrared spectroscopy (1)
- nest climate (1)
- nesting behaviour (1)
- networkanalysis (1)
- neuer anti-infektiver Substanzen (1)
- neural biomarkers (1)
- neurodevelopment (1)
- neurodevelopmental disorders (1)
- neuroepithelial progenitors (1)
- neuroepitheliale Vorläufer (1)
- neurogenesis (1)
- neuroinflammation (1)
- neurologin-2 (1)
- neuromodulation (1)
- neuron (1)
- neuronal activation (1)
- neuronal cell death (1)
- neuronal excitability (1)
- neuronal network (1)
- neuronal nitric oxide synthase (1)
- neuronal visual system (1)
- neuronale Stickstoffmonoxidsynthase (1)
- neuropathic pain (1)
- neuropaticher Schmerz (1)
- neuropeptide S receptor gene (1)
- neuropeptide Y (1)
- neuropeptides (1)
- neuroprotection (1)
- neuropsychiatric disorders (1)
- neuropsychiatrische Störungen (1)
- neuroscience (1)
- neutrophil (1)
- neutrophils (1)
- next generation sequencing (1)
- nicht-viraler Gentransfer (1)
- nicht-visuell (1)
- nichtinvasive Bildgebung (1)
- nitric oxide (1)
- nitrogen regulation (1)
- nociception (1)
- nociceptors (1)
- non-coding RNA (1)
- non-ionizing radiation (1)
- non-visual (1)
- nuclear architecture (1)
- nuclear export signal (1)
- nuclear localization signal (1)
- nuclesosome positioning (1)
- nucleus (1)
- nurse bee (1)
- nutrients (1)
- nutrition (1)
- object segmentation (1)
- oilpalm plantation (1)
- older adults (1)
- oligopeptide transport (1)
- oncogenes (1)
- oncogenic signalling network (1)
- onkogenes Signalnetzwerk (1)
- opening of chromatin (1)
- opioid peptide (1)
- opioid receptor (1)
- opioid receptors (1)
- optical clearing (1)
- optogenetics (1)
- orientation (1)
- oscillations (1)
- ovarian cancer (1)
- ovarian carcinoma (1)
- oxidative stress (1)
- oxidativer Stress (1)
- oxidierte Phospholipide (1)
- p34 (1)
- p38MAPK (1)
- p44 (1)
- p97 (1)
- pICln (1)
- pain (1)
- pain regulation (1)
- pancreatic cancer (1)
- pancreatic differentiation (1)
- panic disorder (1)
- parasitology (1)
- parathyroid hormone (1)
- parkinson's disease (1)
- pathophysiological mechanisms (1)
- pathotypes (1)
- pdxp (1)
- pea aphid (1)
- pediatric hematology oncology (1)
- peptide engineering (1)
- peptide-based interleukin-5 inhibitor (1)
- performance evaluation (1)
- perfused hydrogel (1)
- peripheral analgesia (1)
- peripheral nerve trauma (1)
- peripheral nervous system (1)
- permeability (1)
- permeance (1)
- permeation (1)
- personality traits (1)
- pflegende Angehörige (1)
- phage resistance (1)
- pharmacology (1)
- pheromone (1)
- phosphoantigen (1)
- phosphoglycolate phosphatase (1)
- phospholipase D (1)
- phosphorylation (1)
- phosphorylation sites (1)
- photoinduced electron transfer (1)
- photoinduzierter Elektronentransfer (1)
- phylogeny (1)
- plant defense (1)
- plant-bee visitation networks (1)
- platelet aggregation (1)
- platelet biogenesis (1)
- pluripotency (1)
- podosome formation (1)
- point-of-care (1)
- polarization (1)
- polarized epithelium (1)
- pollen (1)
- pollen analysis (1)
- pollen foraging (1)
- pollen metabarcoding (1)
- pollinator friendly plants (1)
- polyethism (1)
- polymer (1)
- polymorphism (1)
- polyradiculoneuropathy (1)
- population attributable fraction (1)
- population dynamics (1)
- post-transcriptional regulation (1)
- postradiogene Xerostomie (1)
- posttranscriptional regulation (1)
- potenzielles therapeutisches Target (1)
- precision medicine (1)
- preclinical PET (1)
- predictors and correlates (1)
- prefrontal cortex (1)
- prenatal stress (1)
- presynaptic (1)
- primary ciliary dyskinesia (1)
- primary-cell-derived immortalized cell line (1)
- primate (1)
- probiotica (1)
- proboscis extension response (1)
- profiles (1)
- progenitors (1)
- programmed ribosomal frameshifting (1)
- promoter invasion (1)
- proplatelets (1)
- prosocial (1)
- prosocial behavior (1)
- prosociality (1)
- protease activity (1)
- protease inhibitor (1)
- proteasome (1)
- protein (1)
- protein disulfide isomerase (1)
- protein folding (1)
- protein immobilization (1)
- protein kinase D1 (1)
- protein kinase a (1)
- protein regulation and expression (1)
- protein-DNA interactions (1)
- protein-lipid interactions (1)
- protein-protein-interaction (1)
- pränataler Stress (1)
- psychophysiology (1)
- psychosocial resilience (1)
- psychosocial stress (1)
- psychotherapeutic intervention (1)
- psychotherapeutische Intervention (1)
- pyrrolidine carboxamides (1)
- quiescence (1)
- rIFG (1)
- rRNA processing (1)
- rac1 inhibitors (1)
- radial MR imaging (1)
- radionuclide (1)
- radionuclide therapy (1)
- ranskranielle magnetische Stimulation (1)
- rapid evolution (1)
- rat (1)
- reactive oxygen species (1)
- real-time imaging (1)
- reception (1)
- receptor signaling (1)
- reciprocity (1)
- reconstruction (1)
- recurrence (1)
- reduction of ERK1/2 phosphorylation (1)
- reduction of cells proliferation (1)
- regenerative medicine (1)
- regional analgesia (1)
- regulatorische T Zellen (1)
- regulatory RNA (1)
- reinforcement sensitivity theory (1)
- relapse (1)
- renale Kalzifikationen (1)
- replication (1)
- reporter screen (1)
- research software (1)
- resilience (1)
- resin (1)
- resolution (1)
- responsiveness (1)
- resting tremor (1)
- resting-state fMRT (1)
- restriction factors (1)
- resveratrol (1)
- retinal development (1)
- reverse Transkription (1)
- reverse genetics (1)
- reverse transcription (1)
- reversible oxidation (1)
- rheumatoide Arthritis (1)
- rho gtpases (1)
- ribosomal RNA (1)
- ribosomale RNS (1)
- ribosome biogenesis (1)
- ribosome profiling (1)
- riboswitch (1)
- risk factors (1)
- rodent model (1)
- rtPA (1)
- salinen Wachstumsbedingungen (1)
- salt stress (1)
- sand mine (1)
- saure Sphingomyelinase (1)
- scale-up (1)
- schnelle Evolution (1)
- screening (1)
- second messenger (1)
- secondary metabolites (1)
- secondary prevention (1)
- secreted aspartic protease (1)
- secreted factors (1)
- secretion (1)
- secretory properties (1)
- seed coat (1)
- seed treatment (1)
- self-activation (1)
- self-regulation (1)
- self-targeting CRISPR-Cas (1)
- senecionine (1)
- seneciphylline (1)
- senescence (1)
- sensitivity (1)
- sensorische Neurone (1)
- sequence-structure (1)
- serine protease (1)
- serotonerges System (1)
- serotonin (1)
- serotonin deficiency (1)
- serotonin transporter (1)
- serum retention (1)
- sexual stage surface proteins (1)
- short neuropeptide F (1)
- sifA (1)
- sigma factor (1)
- signaling pathway (1)
- signaltransduction (1)
- similarity (1)
- single cell anatomy (1)
- single molecule microscopy (1)
- single-cell RNA sequencing (1)
- single-cell genomics (1)
- single-molecule imaging (1)
- single-molecule localization microscopy (1)
- single-molecule microscopy (1)
- site directed immobilization (1)
- site-specific immobilization (1)
- skin (1)
- skin biopsy (1)
- skin cancer (1)
- skin model (1)
- small RNA expression (1)
- small fiber pathology (1)
- small intestinal submucosa (1)
- small proteins (1)
- small-animal SPECT (1)
- smell (1)
- smells (1)
- snoRNA (1)
- social cognition (1)
- social interaction (1)
- social stimuli (1)
- social understanding (1)
- solid tumour (1)
- solitary bee nests (1)
- somatic resilience (1)
- somatostatin receptor antagonists (1)
- soziale Insekten (1)
- spatial organization (1)
- specific phobia (1)
- speckle tracking (1)
- spezifische Phobie (1)
- sphingolipid (1)
- spider phobia (1)
- spiral trajectory (1)
- splicing (1)
- sponge microbiome (1)
- spontaneous neuronal activity (1)
- ssVEP (1)
- stachellose Biene (1)
- stachellose Bienen (1)
- steady-state visually evoked potentials (1)
- stem (1)
- stem cells (1)
- stiff person syndrome (1)
- stingless bees (1)
- store-operated calcium entry (1)
- strain (1)
- strain rate (1)
- stream (1)
- streptozotocin (1)
- stress response (1)
- striatum (1)
- stroop task (1)
- structural mechanism (1)
- structure analysis (1)
- structure based drug design (1)
- structure-based drug design (1)
- structure-function relationships (1)
- stx-Phagen (1)
- stx-phages (1)
- subcutaneous implanation (1)
- subthalamic nucleus (1)
- sugar perception (fructose, sucrose) (1)
- sugar receptor (1)
- sumo (1)
- sumoylation (1)
- superagonistische Funktion (1)
- superparamagnetische Eisenoxid Kontrastmittel (1)
- suspension culture (1)
- sustained fear (1)
- synaptische Plastizität (1)
- synthetic lethal interaction (1)
- synthetisch lethale Interaktion (1)
- systemic inflammation (1)
- systems biology (1)
- t cell (1)
- tactil (1)
- tactile (1)
- tapeworm (1)
- tdcs (1)
- telomere-associated protein (1)
- temperate zones (1)
- temporal information transfer (1)
- temporal organization (1)
- temporo-parietal junction (1)
- terahertz radiation (1)
- terpenes (1)
- test system (1)
- th1/th2 polarization (1)
- therapeutic strategy (1)
- therapeutisches Target (1)
- therapy (1)
- therapy of glioblastoma (1)
- therapy outcome (1)
- therapy simulation (1)
- thermal orientation (1)
- thermotolerance (1)
- theta burst stimulation (1)
- think/no-think (1)
- thiostrepton (1)
- threat conditioning (1)
- thrombin (1)
- thrombo-inflammation (1)
- thrombosis (1)
- thyroid stimulating hormone receptor (1)
- time-correlated single photon counting (TCSPC) (1)
- time-resolved anisotropy (1)
- timing (1)
- tissue model (1)
- tolerance (1)
- tolerogen (1)
- tolerogenic (1)
- tool (1)
- tool-use (1)
- torque meter (1)
- tracheal cytotoxin (1)
- trachomatis (1)
- trade-offs (1)
- trans-Golgi network (1)
- transcranial Direct Current Stimulation (tDCS) (1)
- transcranial direct current stimulation (1)
- transcription elongation factor A (SII)-like 1 (TCEAL1) (1)
- transcription factor (1)
- transcription regulator (1)
- transcription/replication conflicts (1)
- transcriptional termination site (1)
- transcriptome (1)
- transcriptome analysis (1)
- transcriptome data analysis (1)
- transcriptome profiling (1)
- transcriptomic analysis (1)
- transcutaneous vagus nerve stimulation (1)
- transfer (1)
- transgenes Modell (1)
- transient dynamics (1)
- transmission blocking vaccine (1)
- transpiration barrier (1)
- transport (1)
- transporter regulator (1)
- tuberculosis (1)
- tumor angiogenesis (1)
- tumor metabolism (1)
- tumor microenvironment (1)
- tumor vascular morphologie (1)
- tumorspezifische Therapie (1)
- tumour (1)
- tumour microenvironment (1)
- tumour stroma (1)
- two-component (1)
- type 1 diabetes (1)
- tyrosine kinase (1)
- ubiquitin (1)
- ubiquitin chain formation (1)
- ubiquitin linkage specificity (1)
- ubiquitin recognition (1)
- ultimatum game (1)
- unconventional T cells (1)
- unklarer Signifikanz (1)
- vaccine (1)
- vacuole (1)
- validation study (1)
- variant surface glycoprotein (1)
- variational network (1)
- varroa (1)
- vascular cell adhesion molecules (1)
- vascular smooth muscle cells (1)
- vascular structure (1)
- vascular system (1)
- vaskuläre Adhäsionsmoleküle (1)
- vaskuläre glatte Muskelzelle (1)
- vaskuläre glatte Muskelzellen (1)
- vasp (1)
- vav2 (1)
- vdr (1)
- ve-cadherin (1)
- venus (1)
- viral genome packaging (1)
- viral miRNAs (1)
- virological synapse (1)
- virtual reality T-maze (1)
- virulence factors (1)
- virus transmission (1)
- vision (1)
- visual attention (1)
- visual cue (1)
- visual perception (1)
- visuelles Langzeitgedächtnis (1)
- vitamin d (1)
- vitamin d receptor (1)
- vmPFC (1)
- waggle dance (1)
- waggle dance decoding (1)
- water fat separation (1)
- water loss (1)
- wax (1)
- wild-living honey bees (1)
- workbench (1)
- x-ray micro computed tomography (1)
- xiphophorus (1)
- yeast (1)
- zeitgeber (1)
- zeitlich Informationsübertragung (1)
- zeitliche Organisation (1)
- zeitliche Trends (1)
- zentrale Spindel und Mittelkörper (1)
- zielgerichtete Therapien (1)
- zonal Hydrogels (1)
- zyklische Peptide (1)
- µ-Opioid Rezeptor (1)
- Ängstliche Depression (1)
- Ätiologie (1)
- Ölpalmenanbau (1)
- Überexpression (1)
- Übertragungsfunktion (1)
- Übung (1)
- ß-adrenerge Rezeptoren (1)
- ß-adrenergic Receptors (1)
- ΔNp63 (1)
- α-synuclein (1)
- β cell (1)
- β3 adrenergic receptor (1)
- γδ T cells (1)
Institute
- Graduate School of Life Sciences (999) (remove)
Sonstige beteiligte Institutionen
- Helmholtz Institute for RNA-based Infection Research (HIRI) (5)
- Universitätsklinikum Münster (3)
- Rudolf Virchow Center for Integrative and Translational Bioimaging, University of Würzburg (2)
- Zentrum für Infektionsforschung (ZINF) Würzburg (2)
- Bio-Imaging Center Würzburg (1)
- Biomedical Center Munich, Department of Physiological Chemistry, Ludwig-Maximilians-Universität München (1)
- CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - the development agency of the Brazilian Federal Government (1)
- CBIO, University of Cape Town, South Africa (1)
- Carl-Ludwig-Institut für Physiologie, Universität Leipzig (1)
- Chair of Experimental Biomedicine I (1)
The majority of rapid cell-to-cell communication mechanisms and information processing within the nervous system makes use of chemical synapses. Fast neurotransmission on these sites not only requires very close apposition of pre- and postsynaptic partners, but also depends on an effective structural arrangement of cellular components on both sides of the synaptic cleft. Synaptic vesicles fuse at active zones (AZs), characterized by an electron-dense protein mesh of insufficiently characterized composition and function. EM analysis of synapses identified electron dense structures thought (but not proven) to play an important role for vesicle release efficacy. The molecular organization of presynaptic AZs during Ca2+ influx–triggered neurotransmitter release is currently a focus of intense investigation. Due to its appearance in electron micrographs, dense bodies at Drosophila synapses were named T-bars. Together with the lab of Erich Buchner, we recently showed that Bruchpilot (BRP) of the Drosophila melanogaster, homologous to the mammalian CAST/ERC family in its N-terminal half, is essential for the T-bar assembly at AZs and efficient neurotransmitter release respectively. The question, in which way BRP contributes to functional and structural organization of the AZ, was a major focus of this thesis. First, stimulated emission depletion microscopy (STED), featuring significantly increased optical resolution, was used to achieve first insights into ‘cytoarchitecture’ of the AZ compartment. In addition, in vivo live imaging experiments following identified populations of synapses over extended periods were preformed to address the trafficking of protein at forming synapses and thereby providing a temporal sequence for the AZ assembly process. Apart from BRP, two additional AZ proteins, DLiprin-α and DSyd-1, were included into the analysis, which were both shown to contribute to efficient AZ assembly. Drosophila Syd-1 (DSyd-1) and Drosophila Liprin-α (DLiprin-α) clusters initiated AZ assembly, finally forming discrete ‘quanta’ at the AZ edge. ELKS-related Bruchpilot, in contrast, accumulated late from diffuse pools in the AZ center, where it contributed to the electron dense specialization by adopting an extended conformation vertical to the AZ membrane. We show that DSyd-1 and DLiprin-α are important for efficient AZ formation. The results of this thesis describe AZ assembly as a sequential protracted process, with matured AZs characterized by sub-compartments and likely quantal building blocks. This step-wise, in parts reversible path leading to mature AZ structure and function offers new control possibilities in the development and plasticity of synaptic circuits.
Marine sponges (Porifera) harbor diverse microbial communities within their mesohyl, among them representatives of the phylum Actinobacteria, commonly known as actinomycetes. Actinomycetes are prolific producers of pharmacologically important compounds and are responsible for producing the majority of antibiotics. The main aim of this Ph.D. study was to investigate the metabolic potential of the sponge-associated actinomycetes to produce novel anti-infective agents. The first aim was to cultivate actinomycetes derived from different marine sponges. 16S rDNA sequencing revealed that the strains belonged to diverse actinomycete genera such as Gordonia, Isoptericola, Micromonospora, Nocardiopsis, Saccharopolyspora and Streptomyces. Phylogenetic analyses and polyphasic characterization further revealed that two of these strains represent new species, namely Saccharopolyspora cebuensis strain SPE 10-1T (Pimentel-Elardo et al. 2008a) and Streptomyces axinellae strain Pol001T (Pimentel-Elardo et al. 2008b). Furthermore, secondary metabolite production of the actinomycete strains was investigated. The metabolites were isolated using a bioassay-guided purification scheme followed by structure elucidation using spectroscopic methods and subjected to an elaborate anti-infective screening panel. Several interesting compounds were isolated namely, the novel polyketides cebulactam A1 and A2 (Pimentel-Elardo et al. 2008c), a family of tetromycin compounds including novel derivatives, cyclodepsipeptide valinomycin, indolocarbazole staurosporine, diketopiperazine cycloisoleucylprolyl and butenolide. These compounds exhibited significant anti-parasitic as well as protease inhibitory activities. The third aim of this Ph.D. study was to identify biosynthetic gene clusters encoding for nonribosomal peptide synthetases (NRPS) and polyketide synthases (PKS) present in the actinomycete strains. Genomic library construction and sequencing revealed insights into the metabolic potential and biosynthetic pathways of selected strains. An interesting NRPS system detected in Streptomyces sp. strain Aer003 was found to be widely distributed in several sponge species, in an ascidian and in seawater and is postulated to encode for a large peptide molecule. Sequencing of the PKS gene cluster of Saccharopolyspora cebuensis strain SPE 10-1T allowed the prediction of the cebulactam biosynthetic pathway which utilizes 3-amino-5-hydroxybenzoic acid as the starter unit followed by successive condensation steps involving methylmalonyl extender units and auxiliary domains responsible for the polyketide assembly. In conclusion, this Ph.D. study has shown that diverse actinomycete genera are associated with marine sponges. The strains, two of them novel species, produced diverse chemical structures with interesting anti-infective properties. Lastly, the presence of biosynthetic gene clusters identified in this study substantiates the biosynthetic potential of actinomycetes to produce exploitable natural products and hopefully provides a sustainable supply of anti-infective compounds.
The yeast Candida albicans is a member of the normal microflora on the mucosal surfaces of the gastrointestinal and urogenital tract in healthy persons. However, it is an opportunistic pathogen that can cause a range of infections from superficial to disseminated, in response to perturbation of the normal microflora or alterations in the host immunity. C. albicans exhibits a variety of characteristics such as adhesion, morphogenetic switching and secreted aspartic protease production that contribute to its virulence. Expression of many of these virulence factors is controlled by the availability of essential element, nitrogen. C. albicans undergoes morphogenetic transition to form filaments under nitrogen starvation conditions and this switch is controlled by the ammonium permease Mep2p. However, little is known about how this signaling function of Mep2p is regulated. Mutational analysis of Mep2p was carried out to identify the residues that confer signaling activity to this permease. The C-terminal cytoplasmic tail of Mep2p contains a signaling domain that is dispensable for ammonium transport but essential for the signaling activity of Mep2p. In this work, progressive C-terminal truncations analysis demonstrated that a MEP2DC433 allele was still able to induce filamentation while nitrogen starvation-induced filamentous growth was abolished in cells expressing a MEP2DC432 allele. Therefore, tyrosine at position 433 (Y433) is the last amino acid in Mep2p that is essential for signaling. To gain insights into how the signaling activity of Mep2p is regulated by ammonium availability and transport, conserved residues that have been implicated in ammonium binding or uptake were mutated. Mutation of D180, which has been proposed to mediate initial contact with extracellular ammonium, or the pore-lining residues H188 and H342 abolished Mep2p expression, indicating that these residues are important for protein stability. Mutation of F239, which together with F126 is predicted to form an extracytosolic gate to the conductance channel, abolished both ammonium uptake and Mep2p-dependent filamentation, despite proper localization of the protein. On the other hand, mutation of W167, which is assumed to participate along with Y122, F126, and S243 in the recruitment and coordination of the ammonium ion at the extracytosolic side of the cell membrane, also abolished filamentation without having a strong impact on ammonium transport, demonstrating that extracellular alterations in Mep2p can affect intracellular signaling. Mutation of Y122 reduced ammonium uptake much more strongly than mutation of W167 but still allowed efficient filamentation, indicating that the signaling activity of Mep2p is not directly correlated with its transport activity. An important aspect in the ability of Mep2p to stimulate filamentation in response to nitrogen limitation is its high expression levels. The cis-acting sequences and trans-acting regulators that mediate MEP2 induction in response to nitrogen limitation were identified. Promoter analysis revealed that two putative binding sites for GATA transcription factors have a central role in MEP2 expression, as deletion of the region containing these sites or mutation of the GATAA sequences in the full-length MEP2 promoter strongly reduced MEP2 expression. To elucidate the roles of the GATA transcription factors GLN3 and GAT1 in regulating MEP2 expression, mutants lacking one or both of these transcription factors were constructed. Mep2p expression was strongly reduced in gln3D and gat1D single mutants and virtually abolished in gln3D gat1D double mutants. Deletion of GLN3 strongly inhibited filamentous growth under limiting nitrogen conditions, which could be rescued by constitutive expression of MEP2 from the ADH1 promoter. In contrast, inactivation of GAT1 had no effect on filamentation. Surprisingly, filamentation became partially independent of the presence of a functional MEP2 gene in the gat1D mutants, indicating that the loss of GAT1 function results in the activation of other pathways that induce filamentous growth. These findings demonstrated that the GATA transcription factors Gln3p and Gat1p control expression of the MEP2 ammonium permease and that GLN3 is also an important regulator of nitrogen starvation-induced filamentous growth in C. albicans. C. albicans mutants lacking both the GATA transcription factors Gln3p and Gat1p were unable to grow in a medium containing an alternative nitrogen source, bovine serum albumin (BSA) as the sole nitrogen source. The ability to utilize proteins as sole source of nitrogen for growth of C. albicans is conferred by the secreted aspartic protease Sap2p, which degrades the proteins, and oligopeptide transporters that mediate uptake of the proteolytic products into cell. The growth defect of gln3D gat1D mutants was mainly caused by their inability to express the SAP2 gene, as SAP2 expression from the constitutive ADH1 promoter restored the ability of the mutants to grow on BSA. Expression of STP1, which encodes a transcription factor that is required for SAP2 induction in the presence of proteins, was regulated by Gln3p and Gat1p. Forced expression of STP1 from a tetracycline-inducible promoter bypassed the requirement of the GATA transcription factors for growth of C. albicans on proteins. When preferred nitrogen sources are available, SAP2 is repressed and this nitrogen catabolite repression of SAP2 was correlated with downregulation of STP1 under these conditions. Tetracycline-induced STP1 expression abolished nitrogen catabolite repression of SAP2, demonstrating that regulation of STP1 expression levels by the GATA transcription factors is a key aspect of both positive and negative regulation of SAP2 expression. Therefore, by using a regulatory cascade in which expression of the specific transcription factor Stp1p is controlled by the general regulators Gln3p and Gat1p, C. albicans places SAP2 expression under nitrogen control and ensures proper expression of this virulence determinant. In summary, the present study illustrated how GATA factors, Gln3p and Gat1p, play partially overlapping, but distinct roles, in mediating the appropriate responses of C. albicans to the availability of different nitrogen sources. These responses are also determinants of pathogenicity of the fungus. The relative contributions of Gln3p and Gat1p vary with their target genes and the availability of nitrogen source. Overall, these findings provide us with a better understanding of the molecular basis of some of the important processes that help in adaptation of C. albicans to various environmental conditions. The yeast Candida albicans is a member of the normal microflora on the mucosal surfaces of the gastrointestinal and urogenital tract in healthy persons. However, it is an opportunistic pathogen that can cause a range of infections from superficial to disseminated, in response to perturbation of the normal microflora or alterations in the host immunity. C. albicans exhibits a variety of characteristics such as adhesion, morphogenetic switching and secreted aspartic protease production that contribute to its virulence. Expression of many of these virulence factors is controlled by the availability of essential element, nitrogen. C. albicans undergoes morphogenetic transition to form filaments under nitrogen starvation conditions and this switch is controlled by the ammonium permease Mep2p. However, little is known about how this signaling function of Mep2p is regulated. Mutational analysis of Mep2p was carried out to identify the residues that confer signaling activity to this permease. The C-terminal cytoplasmic tail of Mep2p contains a signaling domain that is dispensable for ammonium transport but essential for the signaling activity of Mep2p. In this work, progressive C-terminal truncations analysis demonstrated that a MEP2DC433 allele was still able to induce filamentation while nitrogen starvation-induced filamentous growth was abolished in cells expressing a MEP2DC432 allele. Therefore, tyrosine at position 433 (Y433) is the last amino acid in Mep2p that is essential for signaling. To gain insights into how the signaling activity of Mep2p is regulated by ammonium availability and transport, conserved residues that have been implicated in ammonium binding or uptake were mutated. Mutation of D180, which has been proposed to mediate initial contact with extracellular ammonium, or the pore-lining residues H188 and H342 abolished Mep2p expression, indicating that these residues are important for protein stability. Mutation of F239, which together with F126 is predicted to form an extracytosolic gate to the conductance channel, abolished both ammonium uptake and Mep2p-dependent filamentation, despite proper localization of the protein. On the other hand, mutation of W167, which is assumed to participate along with Y122, F126, and S243 in the recruitment and coordination of the ammonium ion at the extracytosolic side of the cell membrane, also abolished filamentation without having a strong impact on ammonium transport, demonstrating that extracellular alterations in Mep2p can affect intracellular signaling. Mutation of Y122 reduced ammonium uptake much more strongly than mutation of W167 but still allowed efficient filamentation, indicating that the signaling activity of Mep2p is not directly correlated with its transport activity. An important aspect in the ability of Mep2p to stimulate filamentation in response to nitrogen limitation is its high expression levels. The cis-acting sequences and trans-acting regulators that mediate MEP2 induction in response to nitrogen limitation were identified. Promoter analysis revealed that two putative binding sites for GATA transcription factors have a central role in MEP2 expression, as deletion of the region containing these sites or mutation of the GATAA sequences in the full-length MEP2 promoter strongly reduced MEP2 expression. To elucidate the roles of the GATA transcription factors GLN3 and GAT1 in regulating MEP2 expression, mutants lacking one or both of these transcription factors were constructed. Mep2p expression was strongly reduced in gln3D and gat1D single mutants and virtually abolished in gln3D gat1D double mutants. Deletion of GLN3 strongly inhibited filamentous growth under limiting nitrogen conditions, which could be rescued by constitutive expression of MEP2 from the ADH1 promoter. In contrast, inactivation of GAT1 had no effect on filamentation. Surprisingly, filamentation became partially independent of the presence of a functional MEP2 gene in the gat1D mutants, indicating that the loss of GAT1 function results in the activation of other pathways that induce filamentous growth. These findings demonstrated that the GATA transcription factors Gln3p and Gat1p control expression of the MEP2 ammonium permease and that GLN3 is also an important regulator of nitrogen starvation-induced filamentous growth in C. albicans. C. albicans mutants lacking both the GATA transcription factors Gln3p and Gat1p were unable to grow in a medium containing an alternative nitrogen source, bovine serum albumin (BSA) as the sole nitrogen source. The ability to utilize proteins as sole source of nitrogen for growth of C. albicans is conferred by the secreted aspartic protease Sap2p, which degrades the proteins, and oligopeptide transporters that mediate uptake of the proteolytic products into cell. The growth defect of gln3D gat1D mutants was mainly caused by their inability to express the SAP2 gene, as SAP2 expression from the constitutive ADH1 promoter restored the ability of the mutants to grow on BSA. Expression of STP1, which encodes a transcription factor that is required for SAP2 induction in the presence of proteins, was regulated by Gln3p and Gat1p. Forced expression of STP1 from a tetracycline-inducible promoter bypassed the requirement of the GATA transcription factors for growth of C. albicans on proteins. When preferred nitrogen sources are available, SAP2 is repressed and this nitrogen catabolite repression of SAP2 was correlated with downregulation of STP1 under these conditions. Tetracycline-induced STP1 expression abolished nitrogen catabolite repression of SAP2, demonstrating that regulation of STP1 expression levels by the GATA transcription factors is a key aspect of both positive and negative regulation of SAP2 expression. Therefore, by using a regulatory cascade in which expression of the specific transcription factor Stp1p is controlled by the general regulators Gln3p and Gat1p, C. albicans places SAP2 expression under nitrogen control and ensures proper expression of this virulence determinant. In summary, the present study illustrated how GATA factors, Gln3p and Gat1p, play partially overlapping, but distinct roles, in mediating the appropriate responses of C. albicans to the availability of different nitrogen sources. These responses are also determinants of pathogenicity of the fungus. The relative contributions of Gln3p and Gat1p vary with their target genes and the availability of nitrogen source. Overall, these findings provide us with a better understanding of the molecular basis of some of the important processes that help in adaptation of C. albicans to various environmental conditions.
Cancer immune therapy represents a promising alternative to conventional anti tumour therapy like radiation, surgical excision of the tumour or classical chemotherapy. The biggest advantage of cancer immune therapy is specificity, achieved by targeting tumour-associated antigens with the effector arms of the host immune system. This is believed to result in less adverse effects than standard therapy and reaches presumably also metastatic lesions at distant sites from the primary tumour. However, cancer immune therapy by vaccination against tumour antigens failed to translate into clinical success, yet. Furthermore, despite tremendous clinical efforts malignant disease still results in high mortalities giving rise to the need for novel vaccination-based therapies against cancer. An interesting approach in this respect is the use of bacteria like attenuated salmonellae as carriers for heterologous cancer antigens. In numerous preclinical studies Salmonella-based vaccines could elicit cell mediated immune responses of the CD4+ and CD8+ type against own and heterologous antigens which make them ideally suited for anti tumour therapy. Special delivery systems in Salmonella carriers like surface display or secretion of antigens were shown to be advantageous for the immunological outcome. This work focussed on developing novel Salmonella carriers for immune therapy against cancer. In a first project, TolC, a multifunctional outer membrane protein of E. coli was utilized as membrane anchor for 3 heterologous antigens. Respective TolC fusion proteins encoded on plasmids were analysed for expression, functionality and plasmid stability in different engineered Salmonella strains. The amount of membrane localized recombinant TolC was enhanced in tolC-deficient strains. Furthermore, fusion proteins were functional and plasmid stability was very high in vitro and in vivo. Disappointingly, neither specific CD4+/CD8+ T-cell responses against the model antigen ovalbumin nor CD8+ responses against the cancer antigen BRAFV600E were detectable in murine model systems. However, mice immunized with Salmonella strains displaying an immunodominant epitope of the cancer related prostate specific antigen (PSA) were partially protected from subsequent tumour challenge with a PSA expressing melanoma cell line. Tumour growth in mice immunized with the respective strain was significantly decelerated compared to controls, thus indicating that this surface display system confers protective immunity against tumours. In a second study, the approved typhoid vaccine strain Salmonella enterica serovar Typhi Ty21a (Ty21a) was improved for the hemolysin type I secretion system of E. coli. This secretion system is widely used for heterologous antigen delivery in live bacterial vaccines. It was demonstrated throughout this work that a mutation of rpoS in Ty21a correlated with decreased ability for hemolysin secretion compared to other Salmonella strains. Complementation with rpoS or the presumed downstream target of rpoS, rfaH resulted in enhanced expression and secretion of heterologous hemolysin in Ty21a. Presumably by raising the amount of free antigen, rfaHcomplemented Ty21a elicited higher antibody titres against heterologous hemolysin in immunized mice than controls and even rpoS-positive Ty21a. Therefore, rfaHcomplemented Ty21a could form the basis of a novel generation of vaccines for human use based on (cancer) antigen secretion.
Echinococcus multilocularis is the causative agent of alveolar echinococcosis (AE), a life-threatening disease with limited options of chemotherapeutic treatment. Anti-AE chemotherapy is currently based on a single class of drugs, the benzimidazoles. Although acting parasitocidic in vitro, benzimidazoles are merely parasitostatic during in vivo treatment of AE and cause severe site effects. In the case of operable lesions, the resection of parasite tissue needs to be supported by a prolonged chemotherapy. Thus, the current treatment options for AE are inadequate and require alternatives. In the present work, the flatworm signaling pathways were analyzed to establish potential targets for novel therapeutic approaches. I focused on factors that are involved in development and proliferation of E. multilocularis using molecular, biochemical and cell biological methods. Among the analysed factors were three MAP kinases of the parasite, EmMPK1, an Erk-1/2 orthologue, EmMPK2, a p38 orthologue and EmMPK3, an Erk7/8 orthologue. Further, I identified and characterized EmMKK2, a MEK1/2 orthologue of the parasite, which, together with the known kinases EmRaf and EmMPK1, forms an Erk1/2-like MAPK module. Moreover, I was able to demonstrate several influences of host growth factors such as EGF (epidermal growth factor) and insulin on worm signaling mechanisms and larval growth, including the phosphorylation of Elp, an ezrin-radixin-moesin like protein, EmMPK1, EmMPK3 and increased mitotic activity of Echinococcus cells. In addition, several substances were examined for their efficacy against the parasite including (i) general tyrosine kinase inhibitors (PP2, leflunamide), (ii) compounds designed to inhibit the activity of receptor tyrosine kinases, (iii) anti-neoplastic agents (miltefosine, perifosine), (iv) serine/threonine kinase inhibitors that have been designed to block the Erk1/2 MAPK cascade and (v) inhibitors of p38 MAPKs. In these studies, EmMPK2 proved to be a promising drug target for the following reasons. Amino acid sequence analysis disclosed several differences to human p38 MAPKs, which is likely to be the reason for the observed enhanced basal activity of recombinant EmMPK2 towards myelin basic protein in comparison to human recombinant p38 MAPK-α. In addition, the prominent auto-phosphorylation activity of the recombinant EmMPK2 protein together with the absence of an interaction with the Echinococcus MKKs suggest a different mechanism of regulation compared to the human enzyme. EmMPK2 activity could be effectively inhibited in vitro and in cultivated metacestode vesicles by treatment with SB202190 and ML3403, two ATP-competitive pyridinyl imidazole inhibitors of p38 MAPKs, in a concentration-dependent manner. Moreover, both compounds, in particular ML3403, caused parasite vesicle inactivation at concentrations which did not affect cultured mammalian cells. Likewise, during the cultivation of Echinococcus primary cells, the presence of ML3403 prevented the generation of new vesicles. Targeting members of the EGF signaling pathway, particulary of the Erk1/2-like MAPK cascade, with Raf and MEK inhibitors prevented the phosphorylation of EmMPK1 in metacestodes cultivated in vitro. However, although parasite growth was prevented under these conditions, the structural integrity of the metacestode vesicles maintained during long-term cultivation in the presence of the MAPK cascade inhibitors. Similar results were obtained when studying the effects of other drugs mentioned above. Taken together, several targets could be identified that reacted with high sensitivity to the presence of inhibitory substances, but did not cause the parasite’s death with one exception, the pyridinyl imidazoles. Based on the presented data, I suggest pyridinyl imidazoles as a novel class of anti-Echinococcus drugs and imply EmMPK2 as survival signal mediating factor, the inhibition of which could be used for the treatment of AE.
The proteins of the RAF family (A-RAF, B-RAF, and C-RAF) are serine/threonine-kinases that play important roles in development, mature cell regulation and cancer. Although it is widely held that their localization on membranes is an important aspect of their function, there are few data addressing this aspect of their mode of action. Here, we report that each member of the RAF family exhibits a specific distribution at the level of cellular membranes, and that C-RAF is the only isoform that directly targets mitochondria. We find that the RAF kinases exhibit intrinsic differences in terms of mitochondrial affinity, and that C-RAF is the only isoform that binds this organelle efficiently. This affinity is conferred by the C-RAF amino-terminal domain, and does not depend on the presence of RAS GTPases on the surface of mitochondria. Furthermore, we analyze the consequences of C-RAF activation on the cellular and molecular level. C-RAF activation on mitochondria dramatically changes their morphology and their subcellular distribution. On the molecular level, we examine the role of C-RAF in the regulation of the pro-apoptotic Bcl-2 family member BAD. This protein exhibits the original mode of regulation by phosphorylation. Although several reports addressed the regulation of BAD by C-RAF, the exact mode of action as well as the consequences of C-RAF activation on BAD are still not completely understood. We show that the inducible activation of C-RAF promotes the rapid phosphorylation of BAD on Serine-112 (Ser-75 in the human protein), through a cascade involving the kinases MEK and RSK. Our findings reveal a new aspect of the regulation of BAD protein and its control by the RAF pathway: we find that C-RAF activation promotes BAD poly-ubiquitylation in a phosphorylation-dependent fashion, and increases the turn-over of this protein through proteasomal degradation.
Platelet activation induces cytoskeletal rearrangements involving a change from discoid to spheric shape, secretion, and eventually adhesion and spreading on immobilized ligands. Small GTPases of the Rho family, such as Rac1 and Cdc42, are known to be involved in these processes by facilitating the formation of lamellipodia and filopodia, respectively. This thesis focuses on the role Rac1 and Cdc42 for platelet function and formation from their precursor cells, the megakaryocytes (MKs), using conditional knock-out mice. In the first part of the work, the involvement of Rac1 in the activation of the enzyme phospholipase (PL) C2 in the signaling pathway of the major platelet collagen receptor glycoprotein (GP) VI was investigated. It was found that Rac1 is essential for PLC2 activation independently of tyrosine phosphorylation of the enzyme, resulting in a specific platelet activation defect downstream of GPVI, whereas signaling of other activating receptors remains unaffected. Since Rac1-deficient mice were protected from arterial thrombosis in two different in vivo models, the GTPase might serve as a potential target for the development of new drugs for the treatment and prophylaxis of cardio- and cerebrovascular diseases. The second part of the thesis deals with the first characterization of MK- and platelet-specific Cdc42 knock-out mice. Cdc42-deficient mice displayed mild thrombo-cytopenia and platelet production from mutant MKs was markedly reduced. Unexpectedly, Cdc42-deficient platelets showed increased granule content and release upon activation, leading to accelerated thrombus formation in vitro and in vivo. Furthermore, Cdc42 was not generally required for filopodia formation upon platelet activation. Thus, these results indicate that Cdc42, unlike Rac1, is involved in multiple signaling pathways essential for proper platelet formation and function. Finally, the outcome of combined deletion of Rac1 and Cdc42 was studied. In contrast to single deficiency of either GTPase, platelet production from double-deficient MKs was virtually abrogated, resulting in dramatic macrothrombocytopenia in the animals. Formed platelets were largely non-functional leading to a severe hemostatic defect and defective thrombus formation in double-deficient mice in vivo. These results demonstrate for the first time a functional redundancy of Rac1 and Cdc42 in the hematopoietic system.
Diverse roles of B cells in the pathophysiology of rheumatoid arthritis are now well established. B cells contribute to autoimmunity by producing autoantibodies, processing autoantigen and the production of different cytokines which are involved in the inflammatory cascade. Therefore approaches to target B lymphocytes directly or indirectly are developed for clinical practice to treat autoimmune diseases including rheumatoid arthritis. Transient B cell depletion by rituximab (anti-CD20 antibody) has gained prime importance in recent years. Meanwhile anti-CD20 mediated transient B cell depletion therapy is now used with clinical efficiency in the treatment of patients with rheumatoid arthritis. Rituximab induces noteworthy changes in the homeostasis of peripheral B cell subpopulations during the repletion phase with emerging immature B cells in peripheral blood followed by normalization of the naïve B cell pool and a longterm delay in memory B cell subsets in patients with rheumatoid arthritis. Particularly IgD+CD27+ memory B cells repopulate very slowly during B cell regeneration. In a prospective clinical study, our laboratory has shown that the overall number of memory B cells correlates well to the duration of clinical response to rituximab. Little is known about the particular molecular changes in the memory B cell repertoire after rituximab therapy. To better understand peripheral memory B cell subsets, we explored in detail the somatic mutational frequency and pattern of Ig-VH3 gene rearrangements by using a single B cell sorting technique followed by nested PCR before and up to 6 years after rituximab therapy in 18 RA patients. We compared rituximab inflicted dynamics of mutational acquisition to memory B cell repopulation in 4 healthy donors and 6 non RA patients undergoing high dose chemotherapy followed by autologous or allogeneic stem cell transplantation (SCT). Firstly we analyzed the peripheral composition of memory B cell subsets. The phenotypic analysis of peripheral pre-switch (IgD+CD27+) and post-switch (IgD-CD27+) memory B cells did not reveal any quantitative differences in RA patients prior to B cell depletion therapy compared to healthy donors. However extending those studies in directly analysing the B cell immunoglobulin receptor from individual B cells of RA patients and healthy controls brought interesting results. Pre-switched and post-switched memory B cells showed a highly significant difference in the amount of mutations/sequence. The population of IgD+CD27+ memory B cells is comprised of non-mutated, low and highly mutated (median= 9 mutations/ sequence) rearranged Ig receptors whereas the IgD-CD27+ memory B cell compartment shows quite uniformly highly mutated (median 18 mutations/ sequence) sequences indicating a significant difference between these two groups (mutational frequencies 3.83±0.19% vs. 7.1±0.53%; P=0.0001). Profound changes were noted in the re-emerging pre-switch memory B cells (IgD+/ CD27+) after transient B cell depletion with rituximab. These cells showed over a time period of 6 years after treatment with rituximab significantly delayed acquisition of mutations in Ig receptors on the single B cell level. One year after a single course of rituximab 84% of single repopulating IgD+/CD27+ B cells were unmutated and no highly mutated Ig-VH gene rearrangements were found(P=0.0001). Over time increasing numbers of mutations could be detected i-e 7.8% during 2nd year of regeneration (P=0.0001), 14% after 4 years (n=2). Nevertheless even 6 years after rituximab, VH mutations in IgD+ memory B cells were still reduced with 27% highly mutated sequences compared to 52% pre therapy(P=0.0001). Post-therapy analysis of CDR3 length of regenerated IgD+ memory B cells revealed increased CDR3 length which also correlates well with elevated number of non-mutated VH gene rearrangements observed during repletion phase. In comparison patients undergoing high dose chemotherapy followed by allogeneic stem cell transplantation repopulated IgD+ memory cells earlier with higher numbers of mutations in IgD+ memory B cells. One year after transplantation Ig receptors showed already 22% highly mutated and 42 % unmutated VH rearrangements. These findings indicated that anti-CD20 mediated B cell depletion seems not only to delay the production of pre-switch memory B cells but also significantly affects the acquisition of mutations in the IgD+ memory B cell pool. In contrary to the mutational pattern of IgD+ memory B cells after rituximab class switched memory B cells repopulate in the periphery with quantitatively normal mutations in their Ig receptors. Although the numeric replenishment of these recirculating class-switched memory B cells was also reduced after rituximab, we found no delay in quantitative acquisition of mutations also an increased proportion of IgA expressing B cells in this memory B cell subset was detected. Our data showed that post-therapy mutational targeting in RGYW/WRCY motifs were significantly increased as compared with that of pre-treatment (27% before rituximab vs. 43% after therapy, P=0.0003) indicating that affinity maturation may operate differently in class-switched memory B cells before and after B cell depletion. These results indicate a normal development process with an unimpaired mechanism of mutational acquisition in class-switched memory B cells. These data argue for different requirements to undergo somatic hypermutations in IgD+ memory B cells in comparison to class switched memory B cells. To conclude, our work has demonstrated for the first time a delayed acquisition of somatic hypermutations at single Ig receptor VH gene rearrangements of IgD+ memory B cells in comparison to class-switched memory B cells. These results demonstrate that IgD+ memory B cells are particularly susceptible to anti-CD20 treatment in patients with rheumatoid arthritis. In addition antigenic pressure and/or selection are substantially reduced by rituximab therapy which is basically not seen in the class-switched memory compartment. These data are in line with the hypothesis that IgD+ memory B cells have distinct requirements for activating their mutational machinery compared to class-switched memory B cells which recover normal mutations during regeneration phase. The results have implications in understanding the pathophysiology of memory B cell in rheumatoid arthritis and may be helpful in designing new targeted therapies.
An increase in cytosolic Ca2+ levels ([Ca2+]i) is a key event that occurs downstream of many signaling cascades in response to an external stimulus and regulates a wide range of cellular processes, including platelet activation. Eukaryotic cells increase their basal [Ca2+]i allowing extracellular Ca2+ influx into the cell, which involves different mechanisms. Store-operated Ca2+ entry (SOCE) is considered the main mechanism of extracellular Ca2+ influx in electrically non-excitable cells and platelets, and comprises an initial Ca2+ depletion from intracellular Ca2+ stores prior to activation of extracellular Ca2+ influx. Although the close relation between Ca2+ release from intracellular stores and extracellular Ca2+ influx was clear, the nature of the signal that linked both events remained elusive until 2005, when Stromal Interaction Molecule 1 (STIM1) was identified as an endoplasmic reticulum (ER) Ca2+ sensor essential for inositol (1,4,5)-trisphosphate (IP3)-mediated SOCE in vitro. However, the function of its homologue STIM2 in Ca2+ homeostasis was in general unknown. Therefore, mice lacking STIM2 (Stim2-/-) were generated in this work to study initially STIM2 function in platelets and in cells of the immune system. Stim2-/- mice developed normally in size and weight to adulthood and were fertile. However, for unknown reasons, they started to die spontaneously at the age of 8 weeks. Unexpectedly, Stim2-/- mice did not show relevant differences in platelets, revealing that STIM2 function is not essential in these cells. However, STIM2 seems to be involved in mammary gland development during pregnancy and is essential for mammary gland function during lactation. CD4+ T cells lacking STIM2 showed decreased SOCE. Our data suggest that STIM2 has a very specific function in the immune system and is involved in Experimental Autoimmune Encephalomyelitis (EAE) at early stages of the disease progression. Stim2-/- neurons were also defective in SOCE. Surprisingly, our results evidenced that STIM2 participates in mechanisms of neuronal damage after ischemic events in brain. This is the first time that the involvement of SOCE in ischemic neuronal damage has been reported. This finding may serve as a basis for the development of novel neuroprotective agents for the treatment of ischemic stroke, and possibly other neurodegenerative disorders in which disturbances in cellular Ca2+ homeostasis are considered a major pathophysiological component.
Der Parathormonrezeptor Typ 1 (PTHR) ist ein G-Protein-gekoppelter Rezeptor der Gruppe 2 und wichtigster Regulator des Kalziumstoffwechsels. Im ersten Teil der Arbeit wurde eine neuartige posttranslationale Modifikation des PTHR in Form einer proteolytischen Spaltung der Ektodomäne identifiziert, charakterisiert und deren Regulation beschrieben. Nach langanhaltender Stimulation des Rezeptors mit Agonisten – aber nicht mit Antagonisten – wurde eine Massen- und Mengenzunahme des Rezeptorproteins beobachtet. Es konnte gezeigt werden, dass der Rezeptor unter basalen Bedingungen einer Spaltung unterliegt. Der Massenunterschied entsteht durch die proteolytische Spaltung der Ektodomäne des PTHR, was nachfolgend die Stabilität des Rezeptors beeinträchtigt. Die Spaltung erfolgte innerhalb einer unstrukturierten Schleife der Ektodomäne, welche die Bereiche für die Ligandenbindung miteinander verbindet. Hierbei handelt es sich um eine Region, die im Vergleich zu anderen Gruppe 2-Rezeptoren spezifisch für den PTHR ist. Das durch die Spaltung entstandene N-terminale Fragment bleibt durch eine Disulfidbrücke mit dem Transmembranteil des Rezeptors verbunden. Durch Versuche mit verschiedenen Proteaseinhibitoren konnte die verantwortliche Protease der Familie der zinkabhängigen extrazellulären Proteasen zugeordnet werden. Diese Ergebnisse beschreiben einen Mechanismus wie die Homoöstase des PTHR reguliert sein könnte. In einem zweiten Abschnitt wurde die Interaktion der Adapterproteine NHERF1 und beta-Arrestin2 mit dem PTHR untersucht. Beide Proteine interagierten unabhängig mit dem Rezeptor, wobei NHERF1 über eine PDZ-Domäne konstitutiv an den C-Terminus des Rezeptors bindet. beta-Arrestin2 hingegen bindet nach Aktivierung des Rezeptors und führt zur Desensitisierung des Rezeptors. Mittels biochemischer und mikroskopischer Methoden konnte gezeigt werden, dass beide Proteine gemeinsam einen ternären Komplex mit dem PTHR bilden, welcher durch die direkte Interaktion zwischen NHERF1 und beta-Arrestin2 vermittelt wird. Dies hat zur Folge, dass beta-Arrestin im basalen Zustand durch NHERF1 an den Rezeptor gekoppelt wird. Durch Analyse der Assoziationskinetik mittels Fluoreszenz-Resonanz-Energietransfer-Messungen zeigte sich, dass diese Kopplung zu einer zweifach erhöhten Rekrutierungsgeschwindigkeit von beta-Arrestin2 an den PTHR führt. Somit stellt unterstützt NHERF1 die beta-Arrestin2-vermittelte Desensitisierung des PTHR.
Das Endothel bildet eine einschichtige Zellbarriere zwischen Blut und interstitiellem Gewebe, deren Durchlässigkeit entscheidend durch die sekundären Botenstoffe Ca2+ und cAMP reguliert wird. Während Ca2+ durch eine verstärkte Kontraktion der Endothelzellen die Permeabilität erhöht, fördert cAMP die Adhäsion der Zellen und unterstützt somit die Barrierefunktion. Es ist bekannt, dass Thrombin durch einen Anstieg der intrazellulären Ca2+-Konzentration und vermutlich auch durch eine Hemmung der cAMP-Konzentration zu einer Permeabilitätserhöhung führt. Ziel dieser Arbeit war es, Thrombin-induzierte Änderungen der cAMP-Konzentration in Echtzeit in lebenden Endothelzellen mittels Fluorescence-Resonance-Energy-Transfer (FRET) zu untersuchen. Hierfür wurden Human-Umbilical-Vein-Endothelial-Cells (HUVECs) mit dem FRET-basierten cAMP-Sensor Epac1-camps transfiziert. Die Bindung von cAMP an Epac1-camps führt zu einer Konformationsänderung des Sensors und damit zu einer Abschwächung des FRET. Mit Hilfe dieses Sensors kann die cAMP-Konzentration mit hoher zeitlicher Auflösung in einzelnen lebenden Zellen gemessen werden. Untersucht wurde der Effekt von Thrombin auf die cAMP-Konzentration in Endothelzellen, deren cAMP-Konzentration durch Stimulierung endogener β-Rezeptoren erhöht war. Thrombin erniedrigte Ca2+-abhängig die cAMP-Konzentration um ca. 30 %. Dieser Abfall der cAMP-Konzentration folgte zeitlich verzögert dem Thrombin-induzierten Ca2+-Signal. Die cAMP-Konzentration erreichte ca. 30 s nach der Thrombinzugabe ein Minimum und stieg danach wieder an. Durch die Herunterregulierung der durch Ca2+ direkt inhibierten Adenylatzyklase 6 (AC6) mittels siRNA wurde die Thrombin-induzierte Abnahme der cAMP-Konzentration vollständig aufgehoben. Dies bestätigte, dass Thrombin durch die Ca2+-vermittelte Inhibierung der AC6 eine Abnahme der cAMP-Konzentration verursacht. Ohne β-adrenerge Stimulation führte die Applikation von Thrombin zu einem langsamen Anstieg der cAMP-Konzentration, der mehrere Minuten anhielt. Dieser cAMP-Konzentrationsanstieg beruhte auf der Ca2+-abhängigen Aktivierung der Phospholipase A2 (PLA2). Diese setzt Arachidonsäure aus Membranphospholipiden frei, die als Substrat für die Synthese verschiedener Prostaglandine dient. Durch die pharmakologische Beeinflussung von Zyklooxygenasen und Prostazyklinrezeptoren konnte gezeigt werden, dass die Synthese von Prostazyklin und die anschließende Stimulation Gs-gekoppelter Prostazyklinrezeptoren zum Thrombin-induzierten Anstieg der cAMP-Konzentration führte. Da die Physiologie der Endothelzellen im Gefäß stark von Faktoren aus der unmittelbaren Umgebung beeinflusst wird, ist die Messung der Änderungen der cAMP-Konzentration in Endothelzellen, die sich innerhalb eines Gewebes befinden, von sehr großer Bedeutung. Deshalb war die Generierung transgener Mäuse mit einer gewebespezifischen Expression des FRET-Sensors Epac1-camps in Endothelzellen ein weiteres Ziel dieser Arbeit. Durch Anwendung eines Cre-Rekombinase/loxP-Ansatzes konnten transgene Mäuse generiert werden, die Epac1-camps spezifisch in Endothelzellen exprimierten. An isolierten pulmonären Endothelzellen konnte die Funktionalität des transgen exprimierten Sensors Epac1-camps nachgewiesen werden. Die Echtzeitmessung der Thrombin-induzierten Änderungen der cAMP-Konzentration verdeutlichte ein zeitlich sehr komplexes Wechselspiel zwischen Ca2+- und cAMP-Signalen, das die Barrierefunktion des Endothels maßgeblich beeinflussen wird. Die transgene Expression von Epac1-camps in Endothelzellen ermöglicht in Zukunft die Untersuchung der Thrombin-verursachten Änderungen der cAMP-Konzentration und der Permeabilität innerhalb eines intakten Gefäßes.
Extracellular signals are translated and amplified via cascades of serially switched protein kinases, MAP kinases (MAPKs). One of the MAP pathways, the classical RAS/RAF/MEK/ERK pathway, transduces signals from receptor tyrosine kinases and plays a central role in regulation of cell proliferation. RAF kinases (A-, B- and C-RAF) function atop of this cascade and convert signals emanating from conformational change of RAS GTPases into their kinase activity, which in turn phosphorylates their immediate substrate, MEK. Disregulated kinase activity of RAF can result in tumor formation, as documented for many types of cancer, predominantly melanomas and thyroid carcinomas (B-RAF). A-RAF is the least characterized RAF, possibly due to its low intrinsic kinase activity and comparatively mild phenotype of A-RAF knockout mice. Nevertheless, the unique phenotype of araf -/- mice, showed predominantly neurological abnormalities such as cerebellum disorders, suggesting that A-RAF participates in a specific process not complemented by activities of B- and CRAF. Here we describe the role of A-RAF in membrane trafficking and identify its function in a specific step of endocytosis. This work led to the discovery of a C-terminally truncated version of A-RAF, AR149 that strongly interfered with cell growth and polarization in yeast and with endocytosis and actin polymerization in mammalian cells. As this work was in progress two splicing isoforms of ARAF, termed DA-RAF1 and DA-RAF2 were described that act as natural inhibitors of RAS-ERK signaling during myogenic differentiation (Yokoyama et al., 2007). DA-RAF2 contains the first 153 aa of A-RAF and thus is nearly identical with AR149. AR149 localized specifically to the recycling endosomal compartments as confirmed by colocalization and coimmunoprecipitation with ARF6. Expression of AR149 interferes with recycling of endocytosed transferrin (Tfn) and with actin polymerization. The endocytic compartment, where internalized Tfn is trapped, was identified as ARF6- and RAB11- positive endocytic vesicles. We conclude that the inhibition of Tfn trafficking in the absence of A-RAF or under overexpression of AR149 occurs between tubular- and TGNassociated recycling endosomal compartments. siRNA-mediated depletion of endogenous A-RAF or inhibition of MEK by U0126 mimic the AR149 overexpression phenotype, supporting a role of ARAF regulated ERK signalling at endosomes that is controlled by AR149 and targets ARF6. Our data additionally suggest EFA6 as a partner of A-RAF during activation of ARF6. The novel findings on the A-RAF localization and the interaction with ARF6 have led to a new model of ARAF function were A-RAF via activation of ARF6 controls the recycling of endocytic vesicles.Endocytosis and rapid recycling of synaptic vesicles is critically important for the physiological function of neurons. The finding, that A-RAF regulates endocytic recycling open a new perspective for investigation of the role of A-RAF in the nervous system.
Viele Membranrezeptoren liegen als über Disulfidbrücken-verbundene Dimere vor. Ein Nachweis der Dimerisierung ist in diesen Fällen methodisch klar und einfach zu erbringen. Für die meisten G-Protein-gekoppelten Rezeptoren dagegen ist weder die Existenz von Di- oder Oligomeren noch deren Funktion eindeutig belegt. Meist wurden Methoden wie Coimmunopräzipitation und Resonanz-Energie-Transfer-Verfahren wie BRET oder FRET verwendet, um Protein-Protein-Interaktionen zu untersuchen. Trotz ihrer hohen Sensitivität besitzen diese Methoden einige Grenzen und können je nach experimentellem Ansatz und Verwendung verschiedener Kontrollen, unterschiedliche Ergebnisse hinsichtlich des Vorliegens einer Protein-Protein-Interaktion liefern. Weder die Stabilität der Interaktion, noch die Fraktion der interagierenden Proteine kann mittels Resonanz-Energie-Transfer-Assays zuverlässig ermittelt werden. Auch die Größe der Komplexe ist nicht oder nur technisch aufwendig bestimmbar. Deshalb wurde in dieser Arbeit eine neue, unabhängige Methode entwickelt, um Rezeptor-Rezeptor-Interaktionen in lebenden Zellen genauer untersuchen zu können. Diese auf „Fluorescence Recovery after Photobleaching“ basierende Mikroskopie-Methode erlaubt die Mobilität von Proteinen zu bestimmen. Um Homointeraktionen zwischen Proteinen messen zu können, müssen zwei Protein-Fraktionen mit unterschiedlicher Mobilität vorliegen. Deshalb wurde eine Rezeptor-Fraktion extrazellulär mit YFP markiert und mit Hilfe polyklonaler Antikörper gegen YFP spezifisch immobilisiert. Die andere Rezeptorfraktion wurde intrazellulär mit CFP oder Cerulean markiert und wurde deshalb nicht von extrazellulären Antikörpern erkannt. So konnten mittels Zwei-Farben-FRAP potenzielle Interaktionen zwischen den immobilisierten extrazellulär-markierten Rezeptoren und den intrazellulär-markierten Rezeptoren durch eine Mobilitätsänderung letzterer detektiert werden. Diese Methode wurde mittels eines monomeren (CD86) und kovalent dimeren (CD28) Rezeptors validiert. Es zeigte sich, dass eine spezifische Immobilisierung extrazellulär-markierter Proteine nur durch polyklonale, nicht aber durch monoklonale Antikörper gegen YFP erreicht werden konnte. Intrazellulär-markierte Proteine wurden hierbei in ihrer Mobilität nicht durch die extrazellulären Antikörper beeinflusst. Bei Immobilisierung des extrazellulär-markierten CD86 war das coexprimierte, intrazellulär-markierte CD86-CFP weiterhin voll mobil. Außerdem zeigte das Monomer CD86 eine vom relativen CFP-YFP-Expressionsverhältnis unabhängige Mobilität. Dieses Ergebnis ließ den Schluss zu, dass extra- und intrazellulär-markiertes CD86 nicht miteinander interagieren und als Monomer vorliegen. Die Mobilität des kovalenten Dimers CD28 war dagegen abhängig vom CFP–YFP-Expressionsverhältnis und stimmte gut mit theoretisch erwarteten Werten für ein Dimer überein. Die Anwendung der Zwei-Farben-Methode zur Untersuchung von Interaktionen zwischen ß1- und ß2-adrenergen Rezeptoren zeigte Unterschiede zwischen beiden Rezeptor-Subtypen. ß1-AR zeigte eine spezifische transiente Interaktion, ß2-AR dagegen lagen als stabile Oligomere höherer Ordnung vor. Die transiente Interaktion zwischen ß1-AR und die stabile Oligomerisierung von ß2-AR wurde nicht nur in HEK 293T-Zellen sondern auch in neonatalen Rattenkardiomyozyten und bei 37 °C beobachtet. Ferner hatte der Aktivierungszustand des jeweiligen Rezeptors keinen Einfluß auf das Ausmaß der Interaktion. Zwischen ß1- und ß2-AR wurde nur eine sehr schwache und instabile Heterointeraktion mittels der Zwei-Farben-FRAP-Methode beobachtet. Um zu überprüfen, ob eine direkte Interaktion zwischen den adrenergen Rezeptoren vorliegt, wurde die BRET-Methode verwendet. Mittels BRET wurde eine direkte Interaktion zwischen ß2-AR festgestellt, jedoch konnte nicht zwischen Dimeren und Oligomeren höherer Ordnung unterschieden werden. Bei ß1-AR fand bei höheren YFP-Rluc-Expressionsverhältnissen ein spezifischer Energietransfer statt. Bei niedrigeren Expressionsverhältnissen lag das Signal jedoch im unspezifischen Bereich. Auch bei Untersuchung der Heterointeraktion zwischen ß1- und ß2-AR konnte keine klare Aussage über eine spezifische Interaktion zwischen beiden Rezeptor-Subtypen getroffen werden.
The RS1 protein (gene RSC1A1) participates in regulation of Na+-D-glucose cotransporter SGLT1 and some other solute carriers. In subconfluent LLC-PK1 cells, RS1 inhibits release of SGLT1 from the trans-Golgi network and transcription of SGLT1. In subconfluent cells, RS1 is localized in the nucleus and the cytoplasm whereas confluent cells contain predominantly cytoplasmic RS1. In the present study, the mechanism and regulation of confluence-dependent nuclear location of RS1 was investigated. Confluence dependent nuclear location of RS1 was shown to be regulated by the cell cycle. A nuclear shuttling signal (NS) in pRS1 was identified that ensures confluence-dependent distribution of pRS1 and comprises nuclear localization signal (NLS) and nuclear export signal (NES). The NLS and NES of RS1 mediate translocation into and out of the nucleus via importin ß1 and CRM1, respectively, and the nuclear/cytoplasmic distribution of the RS1 protein is determined by the nuclear export activity. The adjacent protein kinase C (PKC) phosphorylation site at serine 370 of pRS1 was shown to control nuclear localization driven by NS and is necessary for the differential localization of RS1 in quiescent versus proliferating cells. Basing on the data of site-directed mutagenesis, PKC activation experiments and mass spectrometry analysis of RS1 phosphorylation, the following model of the regulation of RS1 nuclear location in LLC-PK1 cells was proposed. In subconfluent cells, RS1 is actively imported into the nucleus whereas nuclear export of RS1 is not active leading to accumulation of RS1 in the nucleus. After confluence, phosphorylation of serine 370 of pRS1 by PKC takes place leading to enhancement of RS1 nuclear export and predominantly cytoplasmic distribution of the protein in the confluent cells. The confluence-dependent regulation of RS1 localization may control SGLT1 expression during regeneration of enterocytes in small intestine and during regeneration of renal tubular cells after hypoxemic stress. Moreover, the gene expression profiling of mouse embryonic fibroblasts with RS1-/- genotype suggests that transcriptional regulation by RS1 might be important for the cell cycle and cell division. Since RS1 localization depends on the cell cycle, RS1 might play a role in the regulation of the solute carriers during specific phases of the cell cycle.
Malaria stellt mit einer Mortalität von über einer Million Menschen pro Jahr die bedeutsamste Tropenkrankheit für den Menschen dar. Wachsende Resistenzen der Malariaerreger gegenüber den verfügbaren Medikamenten erhöhen mehr denn je den Druck, neue Therapiemöglichkeiten sowie einen Impfstoff gegen diese Krankheit zu entwickeln. Eine Unterbrechung des sexuellen Fortpflanzungszyklus im Laufe der Transmission von Mensch zu Stechmücke würde zu einem Verbreitungsstopp des Erregers führen. Sowohl die Identifizierung von molekularen Wechselwirkungen als auch die Erforschung von an Fertilisationsereignissen beteiligten Prozessen sind wichtige Schritte, um die Sexualphase des Erregers aufzuklären und neue Angriffspunkte für Medikamente oder Vakzine zu entwickeln. Dem Genom von P. falciparum konnten 92 putative Proteasen zugeordnet werden, von denen nur ein geringer Bruchteil charakterisiert worden ist. Unter Anwendung von Protease-Inhibitoren konnte in dieser Arbeit gezeigt werden, dass die Exflagellation der männlichen Gameten die Beteiligung von Proteasen verschiedener Kategorien benötigt. Die Ergebnisse belegten, dass die Aktivität von zwei oder mehr Serinproteasen, von Falcipain-ähnlichen Cysteinproteasen, von nicht-Thermolysin-ähnlichen Zink-Metalloproteasen und von Aspartatproteasen für den erfolgreichen Abschluss der männlichen Gametogenese eine wichtige Voraussetzung ist. Die Lokalisation des Cysteinproteasen- und Falcipain-hemmenden Inhibitors bADA konnte erstmals im Zytosol von Sexualstadien nachgewiesen werden. In dieser Arbeit wurden zusätzlich die Proteasen Calpain, DPAP2, GPI8, Metacaspase 2, Plasmepsin 6 und PfSub3 näher untersucht. RT-PCR-Analysen konnten die Transkription der sechs ausgesuchten Proteasen in gemischten asexuellen Parasiten sowie zum Großteil in Gametozyten, Gameten und Zygoten belegen. Die Transformation von asexuellen Parasiten mit entsprechenden knockout-Konstrukten deckte für Metacaspase 2 und PfSub3 auf, dass sie im asexuellen Vermehrungszyklus nicht essentiell und die entsprechenden Genloci für Rekombinationsereignisse zugänglich sind. Die Ergebnisse der übrigen Transformationen deuteten darauf hin, dass Calpain essentiell im asexuellen Vermehrungszyklus und dass der Genlocus von Plasmepsin 6 für Rekombinationsereignisse unzugänglich ist. Proteinexpressionsstudien anhand von Western-Blot-Analysen und Immunfluoreszenzstudien für PfSub3 konnten Hinweise darauf liefern, dass diese Serinprotease in asexuellen Parasiten, nicht-aktivierten sowie aktivierten Sexualstadien exprimiert wird. Aufgrund der in dieser Arbeit generierten Ergebnisse konnten im Laufe der Gametogenese auftretende Gametenfilamente morphologisch beschrieben sowie Hinweise auf ihre mögliche Funktion erlangt werden. Durch die Anwendung von Immunfluoreszenzstudien, rasterelektronenmikroskopischen Aufnahmen sowie die Analyse lebender Gameten konnte gezeigt werden, dass die bis zu 180 µm langen Filamente am Ende geschlossen sind und einen Durchmesser von ca. 200 nm aufweisen. Die tubulären Zellausläufer konnten weiterhin als verzweigte sowie nicht-verzweigte Ausläufer der parasitären Plasmamembran dargestellt werden, die mit Zytoplasma gefüllt sind. Es konnte belegt werden, dass die Aktin-assoziierten Filamente in periodischen Abständen von beulenartigen Auswölbungen unterbrochen werden und dass sie in rasterelektronenmikroskopischen Analysen ein perlschnurartiges Erscheinungsbild aufweisen. Weiterhin wurde dokumentiert, dass die Zellausläufer mit typischen sexualstadienspezifischen Proteinen wie Pfs25, Pfs230, Pfs48/45 und PfCCp4 assoziiert vorliegen, wobei das Fehlen einzelner dieser Proteine jedoch nicht das Ausbilden der Gametenfilamente verhinderte. Als typisches Charakteristikum der Filamente konnte ihre Eigenschaft beschrieben werden, mehrere Makrogameten und zum Teil Gametozyten in einem Zellkluster miteinander netzartig zu verbinden, wobei bis zu neun Filamente von einem Makrogameten ausgehend beobachtet werden konnten. Die Gametenfilamente zeigten ebenfalls die Fähigkeit, an umliegende nicht-infizierte Erythrozyten sowie mit asexuellen Parasiten infizierte Erythrozyten zu adhärieren. Die Filamente waren bereits fünf Minuten nach der Aktivierung der Gametozyten und im Laufe der Gametogenese bei 33 bis 73 % der Zellen nachweisbar. Die Gametenfilamente blieben bis zu 12 Stunden nach Aktivierung der Gametozyten mit der Zelloberfläche verbunden. Der aktive Einzug eines Zellfilaments sowie die Bildung der Gametenfilamente im Mitteldarm der Stechmücke konnte ebenfalls demonstriert werden. Die in dieser Arbeit dargestellten Ergebnisse lieferten unter anderem den Grundbaustein einer formulierten Funktionshypothese für diese Gametenfilamente. Es wird angenommen, dass die Filamente aufgrund ihrer adhäsiven Eigenschaften im Laufe der Befruchtung von Plasmodium im Mitteldarm der Stechmücke auftreten. Möglicherweise bedienen sich vitale Gameten dieser Strukturen, um andere Sexualstadien zu finden und sie zu verbinden.
Recent progresses and developments in molecular biology provide a wealth of new but insufficiently characterised data. This fund comprises amongst others biological data of genomic DNA, protein sequences, 3-dimensional protein structures as well as profiles of gene expression. In the present work, this information is used to develop new methods for the characterisation and classification of organisms and whole groups of organisms as well as to enhance the automated gain and transfer of information. The first two presented approaches (chapters 4 und 5) focus on the medically and scientifically important enterobacteria. Its impact in medicine and molecular biology is founded in versatile mechanisms of infection, their fundamental function as a commensal inhabitant of the intestinal tract and their use as model organisms as they are easy to cultivate. Despite many studies on single pathogroups with clinical distinguishable pathologies, the genotypic factors that contribute to their diversity are still partially unknown. The comprehensive genome comparison described in Chapter 4 was conducted with numerous enterobacterial strains, which cover nearly the whole range of clinically relevant diversity. The genome comparison constitutes the basis of a characterisation of the enterobacterial gene pool, of a reconstruction of evolutionary processes and of comprehensive analysis of specific protein families in enterobacterial subgroups. Correspondence analysis, which is applied for the first time in this context, yields qualitative statements to bacterial subgroups and the respective, exclusively present protein families. Specific protein families were identified for the three major subgroups of enterobacteria namely the genera Yersinia and Salmonella as well as to the group of Shigella and E. coli by applying statistical tests. In conclusion, the genome comparison-based methods provide new starting points to infer specific genotypic traits of bacterial groups from the transfer of functional annotation. Due to the high medical importance of enterobacterial isolates their classification according to pathogenicity has been in focus of many studies. The microarray technology offers a fast, reproducible and standardisable means of bacterial typing and has been proved in bacterial diagnostics, risk assessment and surveillance. The design of the diagnostic microarray of enterobacteria described in chapter 5 is based on the availability of numerous enterobacterial genome sequences. A novel probe selection strategy based on the highly efficient algorithm of string search, which considers both coding and non-coding regions of genomic DNA, enhances pathogroup detection. This principle reduces the risk of incorrect typing due to restrictions to virulence-associated capture probes. Additional capture probes extend the spectrum of applications of the microarray to simultaneous diagnostic or surveillance of antimicrobial resistance. Comprehensive test hybridisations largely confirm the reliability of the selected capture probes and its ability to robustly classify enterobacterial strains according to pathogenicity. Moreover, the tests constitute the basis of the training of a regression model for the classification of pathogroups and hybridised amounts of DNA. The regression model features a continuous learning capacity leading to an enhancement of the prediction accuracy in the process of its application. A fraction of the capture probes represents intergenic DNA and hence confirms the relevance of the underlying strategy. Interestingly, a large part of the capture probes represents poorly annotated genes suggesting the existence of yet unconsidered factors with importance to the formation of respective virulence phenotypes. Another major field of microarray applications is gene expression analysis. The size of gene expression databases rapidly increased in recent years. Although they provide a wealth of expression data, it remains challenging to integrate results from different studies. In chapter 6 the methodology of an unsupervised meta-analysis of genome-wide A. thaliana gene expression data sets is presented, which yields novel insights in function and regulation of genes. The application of kernel-based principal component analysis in combination with hierarchical clustering identified three major groups of contrasts each sharing overlapping expression profiles. Genes associated with two groups are known to play important roles in Indol-3 acetic acid (IAA) mediated plant growth and development as well as in pathogen defence. Yet uncharacterised serine-threonine kinases could be assigned to novel functions in pathogen defence by meta-analysis. In general, hidden interrelation between genes regulated under different conditions could be unravelled by the described approach. HMMs are applied to the functional characterisation of proteins or the detection of genes in genome sequences. Although HMMs are technically mature and widely applied in computational biology, I demonstrate the methodical optimisation with respect to the modelling accuracy on biological data with various distributions of sequence lengths. The subunits of these models, the states, are associated with a certain holding time being the link to length distributions of represented sequences. An adaptation of simple HMM topologies to bell-shaped length distributions described in chapter 7 was achieved by serial chain-linking of single states, while residing in the class of conventional HMMs. The impact of an optimisation of HMM topologies was underlined by performance evaluations with differently adjusted HMM topologies. In summary, a general methodology was introduced to improve the modelling behaviour of HMMs by topological optimisation with maximum likelihood and a fast and easily implementable moment estimator. Chapter 8 describes the application of HMMs to the prediction of interaction sites in protein domains. As previously demonstrated, these sites are not trivial to predict because of varying degree in conservation of their location and type within the domain family. The prediction of interaction sites in protein domains is achieved by a newly defined HMM topology, which incorporates both sequence and structure information. Posterior decoding is applied to the prediction of interaction sites providing additional information of the probability of an interaction for all sequence positions. The implementation of interaction profile HMMs (ipHMMs) is based on the well established profile HMMs and inherits its known efficiency and sensitivity. The large-scale prediction of interaction sites by ipHMMs explained protein dysfunctions caused by mutations that are associated to inheritable diseases like different types of cancer or muscular dystrophy. As already demonstrated by profile HMMs, the ipHMMs are suitable for large-scale applications. Overall, the HMM-based method enhances the prediction quality of interaction sites and improves the understanding of the molecular background of inheritable diseases. With respect to current and future requirements I provide large-scale solutions for the characterisation of biological data in this work. All described methods feature a highly portable character, which allows for the transfer to related topics or organisms, respectively. Special emphasis was put on the knowledge transfer facilitated by a steadily increasing wealth of biological information. The applied and developed statistical methods largely provide learning capacities and hence benefit from the gain of knowledge resulting in increased prediction accuracies and reliability.
Mycobacterium tuberculosis is the causative agent of tuberculosis and responsible for more than eight million new infections and about two million deaths each year. Novel chemotherapeutics are urgently needed to treat the emerging threat of multi drug resistant and extensively drug resistant strains. Cell wall biosynthesis is a widely used target for chemotherapeutic intervention in bacterial infections. In mycobacteria, the cell wall is comprised of mycolic acids, very long chain fatty acids that provide protection and allow the bacteria to persist in the human macrophage. The type II fatty acid biosynthesis pathway in Mycobacterium tuberculosis synthesizes fatty acids with a length of up to 56 carbon atoms that are the precursors of the critical mycobacterial cell wall components mycolic acids. KasA, the mycobacterial ß-ketoacyl synthase and InhA, the mycobacterial enoyl reductase, are essential enzymes in the fatty acid biosynthesis pathway and validated drug targets. In this work, KasA was expressed in Mycobacterium smegmatis, purified and co-crystallized in complex with the natural thiolactone antibiotic thiolactomycin (TLM). High-resolution crystal structures of KasA and the C171Q KasA variant, which mimics the acyl enzyme intermediate of the enzyme, were solved in absence and presence of bound TLM. The crystal structures reveal how the inhibitor is coordinated by the enzyme and thus specifically pinpoint towards possible modifications to increase the affinity of the compound and develop potent new drugs against tuberculosis. Comparisons between the TLM bound crystal structures explain the preferential binding of TLM to the acylated form of KasA. Furthermore, long polyethylene glycol molecules are bound to KasA that mimic a fatty acid substrate of approximately 40 carbon atoms length. These structures thus provide the first insights into the molecular mechanism of substrate recognition and reveal how a wax-like substance can be accommodated in a cytosolic environment. InhA was purified and co-crystallized in complex with the slow, tight binding inhibitor 2-(o-tolyloxy)-5-hexylphenol (PT70). Two crystal structures of the ternary InhA-NAD+-PT70 were solved and reveal how the inhibitor is bound to the substrate binding pocket. Both structures display an ordered substrate binding loop and corroborate the hypothesis that slow onset inhibition is coupled to loop ordering. Upon loop ordering, the active site entrance is more restricted and the inhibitor is kept inside more tightly. These studies provide additional information on the mechanistic imperatives for slow onset inhibition of enoyl ACP reductases.
Studies on platelet cytoskeletal dynamics and receptor regulation in genetically modified mice
(2009)
Platelets are produced by bone marrow megakaryocytes in a process involving actin dynamics. Actin-depolymerizing factor (ADF) and cofilin are actin-binding proteins that act as key regulators in actin turnover by promoting filament severing and depolymerization. The overall significance of ADF/cofilin function and actin turnover in platelet formation is presently unclear. In the first part of this thesis, platelet formation and function were studied in mice constitutively lacking ADF and/or mice with a conditional deficiency (Cre/loxP) in n-cofilin. To delete cofilin exclusively in megakaryocytes and platelets, cofilinfl/fl mice were crossed with PF4 (platelet factor 4)-Cre mice. While a single-deficiency in ADF or n-cofilin resulted in no or only a minor platelet formation defect, respectively, a double-deficiency in ADF and n-cofilin led to an almost complete loss of platelets. Bone marrow megakaryocytes of ADF/n-cofilin-deficient mice showed defective platelet zone formation. Interestingly, in vitro and ex vivo megakaryocyte differentiation revealed reduced proplatelet formation and absence of platelet-forming swellings. These data establish that ADF and n-cofilin have redundant but essential roles in the terminal step of platelet formation in vitro and in vivo. In the second part of the thesis, mechanisms underlying cellular regulation of the major platelet collagen receptor, glycoprotein VI (GPVI), were studied. GPVI mediates platelet activation on exposed subendothelial collagens at sites of vascular injury, and thereby contributes to normal hemostasis but also to occlusion of diseased vessels in the setting of myocardial infarction or stroke. Thus, GPVI is an attractive target for anti-thrombotic therapy, particularly because previous studies have shown that anti-GPVI antibodies induce irreversible down-regulation of the receptor in circulating platelets by internalization and ectodomain shedding. Metalloproteinases of the ADAM (a disintegrin and metalloproteinase domain) family are suspected to mediate this ectodomain shedding, but in vivo evidence for this is lacking. To study the mechanism of GPVI regulation in vivo, two mouse lines, Gp6 knock-out and Adam10fl/fl, PF4-Cre mice, were generated and in addition low TACE (TNFalpha converting enzyme) mice were analyzed. It was shown that GPVI can be cleaved in vitro by ADAM10 or TACE depending on the shedding-inducing signaling pathway. Moreover, GPVI was down-regulated in vivo upon antibody injection in ADAM10-deficient and low TACE mice suggesting that either both or an additional metalloproteinase is involved in GPVI regulation in vivo.
Integrating neurobiological markers of depression: an fMRI-based pattern classification approach
(2010)
While depressive disorders are, to date, diagnosed based on behavioral symptoms and course of illness, the interest in neurobiological markers of psychiatric disorders has grown substantially in recent years. However, current classification approaches are mainly based on data from a single biomarker, making it difficult to predict diseases such as depression which are characterized by a complex pattern of symptoms. Accordingly, none of the previously investigated single biomarkers has shown sufficient predictive power for practical application. In this work, we therefore propose an algorithm which integrates neuroimaging data associated with multiple, symptom-related neural processes relevant in depression to improve classification accuracy. First, we identified the core-symptoms of depression from standard classification systems. Then, we designed and conducted three experimental paradigms probing psychological processes known to be related to these symptoms using functional Magnetic Resonance Imaging. In order to integrate the resulting 12 high-dimensional biomarkers, we developed a multi-source pattern recognition algorithm based on a combination of Gaussian Process Classifiers and decision trees. Applying this approach to a group of 30 healthy controls and 30 depressive in-patients who were on a variety of medications and displayed varying degrees of symptom-severity allowed for high-accuracy single-subject classification. Specifically, integrating biomarkers yielded an accuracy of 83% while the best of the 12 single biomarkers alone classified a significantly lower number of subjects (72%) correctly. Thus, integrated biomarker-based classification of a heterogeneous, real-life sample resulted in accuracy comparable to the highest ever achieved in previous single biomarker research. Furthermore, investigation of the final prediction model revealed that neural activation during the processing of neutral facial expressions, large rewards, and safety cues is most relevant for over-all classification. We conclude that combining brain activation related to the core-symptoms of depression using the multi-source pattern classification approach developed in this work substantially increases classification accuracy while providing a sparse relational biomarker-model for future prediction.
Schlagwörter: Salmonella , Salmonella enterica , Salmonella typhimurium , Salmonellose , Escherichia coli , Shigella , Infektion , Bakterielle Infektion , Zellkultur , HeLa-Zelle , Apoptosis , Metabolismus , Stoffwechsel , Glucose , Glucosetransport , Glucosestoffwechsel , Katabolismus , Kohlenstoff , Kohlenstoffbedarf , Kohlenstoffhaushalt , Kohlenstoffstoffwechsel , Kohlenstoff-13 , Kohlenstoffisotop Salmonella Typhimurium und enteroinvasive E. coli (EIEC) sind fakultativ intrazelluläre Bakterien aus der Familie der Enterobacteriaceae. Während erstere sich nach der Internalisierung durch eukaryotische Zellen normalerweise in einem spezialisierten Phagosom, der Salmonella-enthaltenden Vakuole (SCV), vermehren, replizieren EIEC im Zytoplasma der Wirtszellen. In der vorliegenden Arbeit wurde zunächst durch Mikroinjektion die Fähigkeit von S. Typhimurium 14028s untersucht, ebenfalls im Zytoplasma von Caco-2-Zellen replizieren zu können. Dabei wurde festgestellt, daß ein früher als S. Typhimurium 14028s WT bezeichneter Stamm eine Insertion eines Desoxythymidins an Position 76 des offenen Leserasters von rfbP trägt, einem Gen, dessen Protein an der LPS-Synthese beteiligt ist. Weiterhin synthetisierte dieser Stamm ein rauhes LPS. Aufgrund von Agglutination konnte der Rauh-Stamm nur mit geringem Erfolg mikroinjiziert werden. Hingegen lag 5 h nach der Mikroinjektion einer nicht invasiven Mutante von Salmonella mit vollständigem LPS der Anteil an Caco-2-Zellen, die mehr als 32 Bakterien enthielten, bei etwa 30 %. Der Anteil war 2-3 mal höher als bei früheren Mikroinjektionen in HeLa-Zellen. Daher wurde das Verhalten von HeLa-Zellen nach einer Infektion durch S. Typhimurium ΔsifA - einer Mutante, die aus der SCV ins Zytoplasma entkommt - untersucht. Dabei wurde festgestellt, daß die sifA-Mutante 10 h nach der Infektion die Aktivität der Caspasen 9 und 3 in HeLa-Zellen, aber nicht in Caco-2-Zellen induziert. In weiteren Versuchen wurde die Bedeutung von Glukose, Glukose-6-phosphat und Mannose als Kohlenstoffquellen für die extra- und intrazelluläre Replikation zweier Isolate enteroinvasiver E. coli und eines S. Typhimurium Stammes analysiert. Zu diesem Zweck wurden zunächst definierte Mutanten in den beiden wichtigsten Phosphoenolpyruvat-abhängigen Phosphotransferasesystemen (PTS) für die Aufnahme von Glukose und Mannose, ptsG und manXYZ, sowie im Antiporter für die Aufnahme von Glukose-6-phosphat, uhpT, konstruiert. Bei Wachstum im Minimalmedium mit Glukose als einziger C-Quelle waren die Generationszeiten aller ΔptsG- und ΔptsG, manXYZ-Mutanten im Vergleich zu den Wildstämmen deutlich verlängert. Ebenso wuchsen ΔmanXYZ-Mutanten bzw. ΔuhpT-Mutanten deutlich langsamer auf Mannose bzw. Glukose-6-phosphat. Jedoch ergaben sich hierbei Stamm-spezifische Unterschiede. So erreichte EIEC 4608-58 ΔuhpT in der stationären Phase eine ähnliche Zelldichte wie der Wildstamm in Gegenwart von Glukose-6-phosphat und eine ΔptsG, manXYZ-Mutante von S. Typhimurium 14028s konnte immer noch effizient mit Glukose wachsen. Infektionsversuche mit Caco-2-Zellen zeigten weiterhin, daß die Deletion von ptsG zu einer signifikanten Erhöhung der Adhärenz und Invasivität von EIEC 4608-58 führt, während sich die intrazellulären Generationszeiten aller hier untersuchten Mutanten kaum veränderten. Selbst die ΔptsG, manXYZ, uhpT-Dreifachmutanten der drei hier verwendeten Enterobakterien und die ΔptsG, manXYZ, glk-Mutante von S. Typhimurium 14028s konnten immer noch in Caco-2-Zellen replizieren, wenn auch mit Stamm-spezifisch verringerten Geschwindigkeiten. 13C-Markierungsexperimente mit [U-13C6]-Glukose als Substrat ergaben jedoch, daß in der Tat alle hier untersuchten enterobakteriellen Wildstämme Glukose während der Replikation in Caco-2-Zellen unter Zellkulturbedingungen verwerten. Glukose-6-phosphat, Glukonat oder Fettsäuren konnten dagegen als wichtigste Kohlenstoffquellen für das intrazelluläre Wachstum ausgeschlossen werden. EIEC 4608-58 metabolisierte Glukose jedoch weniger effizient als EIEC HN280 und schien zudem noch zusätzlich C3-Substrate aus der Wirtszelle aufzunehmen. Das Markierungsmuster zeigte einen Stamm-spezifischen Kohlenstofffluß durch Glykolyse und/oder Entner-Doudoroff-Weg, Pentosephosphatzyklus, Citratzyklus und den anaplerotischen Reaktionen zwischen PEP und Oxalacetat. Mutanten mit Deletionen in ptsG und manXYZ konnten auf alternative C3-Substrate wechseln und glichen dies durch eine erhöhte Aufnahme von Aminosäuren aus den Wirtszellen aus.