Refine
Is part of the Bibliography
- yes (761)
Year of publication
Document Type
- Doctoral Thesis (753)
- Journal article (7)
- Book (1)
Language
- English (761) (remove)
Keywords
- Maus (32)
- Thrombozyt (29)
- Taufliege (19)
- Tissue Engineering (19)
- Genexpression (16)
- Dendritische Zelle (14)
- T-Lymphozyt (14)
- Entzündung (13)
- Angst (12)
- Biene (12)
- Signaltransduktion (12)
- Staphylococcus aureus (12)
- Drosophila (11)
- Fluoreszenzmikroskopie (11)
- Krebs <Medizin> (11)
- Serotonin (11)
- Microscopy (10)
- Mikroskopie (10)
- Myc (10)
- Thrombose (10)
- Transkriptionsfaktor (10)
- Aufmerksamkeit (9)
- Candida albicans (9)
- Megakaryozyt (9)
- Melanom (9)
- Motoneuron (9)
- Zellskelett (9)
- Zellzyklus (9)
- miRNS (9)
- platelets (9)
- ADHD (8)
- Angststörung (8)
- Arteriosklerose (8)
- DNS-Reparatur (8)
- Epigenetik (8)
- G-Protein gekoppelte Rezeptoren (8)
- GPCR (8)
- Immunologie (8)
- Induzierte pluripotente Stammzelle (8)
- Kernspintomografie (8)
- Regulation (8)
- Schlaganfall (8)
- Stress (8)
- Tagesrhythmus (8)
- DNS-Schädigung (7)
- Depression (7)
- Elektrophysiologie (7)
- Kutikula (7)
- Lernen (7)
- Neisseria meningitidis (7)
- Rezeptor (7)
- Small RNA (7)
- Spinale Muskelatrophie (7)
- Stammzelle (7)
- Transcription (7)
- Verhalten (7)
- Bacteria (6)
- Bildgebendes Verfahren (6)
- Diabetes mellitus (6)
- Drosophila melanogaster (6)
- EEG (6)
- Fuchsbandwurm (6)
- Furcht (6)
- Immuntherapie (6)
- Konditionierung (6)
- Lungenkrebs (6)
- MRI (6)
- MYC (6)
- Molekularbiologie (6)
- Oxidativer Stress (6)
- Platelet (6)
- Platelets (6)
- Synapse (6)
- Thrombosis (6)
- Transkription <Genetik> (6)
- Trypanosoma brucei (6)
- Virtuelle Realität (6)
- fMRI (6)
- Alzheimerkrankheit (5)
- Apoptosis (5)
- Arzneimitteldesign (5)
- Aspergillus fumigatus (5)
- Aufmerksamkeits-Defizit-Syndrom (5)
- Bakterien (5)
- Cataglyphis (5)
- Chronobiologie (5)
- Cytoskeleton (5)
- DNA damage (5)
- Entwicklung (5)
- Escherichia coli (5)
- Evolution (5)
- Fluoreszenz-Resonanz-Energie-Transfer (5)
- Funktionelle Kernspintomografie (5)
- Gephyrin (5)
- Herzinfarkt (5)
- Inhibitor (5)
- Kognition (5)
- Makrophage (5)
- Monoklonaler Antikörper (5)
- NFATc1 (5)
- Neuroethologie (5)
- Transkriptomanalyse (5)
- Transplantat-Wirt-Reaktion (5)
- Ubiquitin (5)
- Zellmigration (5)
- cancer (5)
- dendritic cells (5)
- platelet (5)
- virtual reality (5)
- 3D-Druck (4)
- Atherosclerosis (4)
- Aufmerksamkeitsdefizit-Syndrom (4)
- Biofabrication (4)
- Biofilm (4)
- Bioinformatics (4)
- Biologie (4)
- Brain-derived neurotrophic factor (4)
- CRISPR/Cas-Methode (4)
- CRISPR/Cas9 (4)
- Calcium (4)
- Cancer (4)
- Chlamydia trachomatis (4)
- Chromatin (4)
- Dendritic cell (4)
- Dendritic cells (4)
- Dünndarm (4)
- Einzelmolekülmikroskopie (4)
- Emotion (4)
- Fibroblastenwachstumsfaktor (4)
- G-Protein gekoppelter Rezeptor (4)
- GPVI (4)
- Gefühl (4)
- Genetics (4)
- Genregulation (4)
- Hippocampus (4)
- Hämostase (4)
- Immunmodulation (4)
- Immunsystem (4)
- Inflammation (4)
- Insulin (4)
- Knockout <Molekulargenetik> (4)
- MMB (4)
- Maschinelles Lernen (4)
- Meeresschwämme (4)
- Mitochondrium (4)
- Mitose (4)
- Molekulargenetik (4)
- Natürliche Killerzelle (4)
- Neurobiologie (4)
- Ratte (4)
- Regulatorischer T-Lymphozyt (4)
- SMN (4)
- Soziale Insekten (4)
- TFIIH (4)
- Therapie (4)
- Transkription (4)
- TrkB (4)
- Virulenz (4)
- Zelldifferenzierung (4)
- Zellkultur (4)
- division of labor (4)
- honeybee (4)
- neuroblastoma (4)
- olfaction (4)
- 3D tissue model (3)
- Actin (3)
- Adjuvans (3)
- Animal model (3)
- Anxiety (3)
- B-Lymphozyt (3)
- B-MYB (3)
- Bacillus subtilis (3)
- Biochemie (3)
- Biodiversität (3)
- Bioinformatik (3)
- Biologische Uhr (3)
- Biomarker (3)
- Blut-Hirn-Schranke (3)
- Blutstillung (3)
- Cadherine (3)
- Campylobacter jejuni (3)
- Darm (3)
- Ecology (3)
- Electroencephalographie (3)
- Elektroencephalographie (3)
- Emotionsregulation (3)
- Endocytose (3)
- Expansion Microscopy (3)
- Expositionstherapie (3)
- FRET (3)
- Fettsäurestoffwechsel (3)
- Fettzelle (3)
- Fibromyalgie (3)
- Fluorescence Microscopy (3)
- Gehirn (3)
- Gehirn-Computer-Schnittstelle (3)
- Genetik (3)
- Genmutation (3)
- Genom (3)
- Geruch (3)
- Geruchssinn (3)
- Glucosetransportproteine (3)
- Graft-versus-host disease (3)
- GvHD (3)
- HIV (3)
- Helicasen (3)
- Helicobacter pylori (3)
- Heubacillus (3)
- Histone (3)
- Hyaliner Knorpel (3)
- Hyaluronsäure (3)
- Immunsuppression (3)
- In-vitro-Kultur (3)
- Infektion (3)
- Inhibition (3)
- Ionenkanal (3)
- Jugend (3)
- Kristallstruktur (3)
- Kutikularwachs (3)
- Latrophilin (3)
- MAP-Kinase (3)
- MYCN (3)
- Malaria (3)
- Megakaryocyte (3)
- Metabolismus (3)
- Metagenom (3)
- Metalloproteinasen (3)
- Mitochondria (3)
- Molekulare Bildgebung (3)
- Multiproteinkomplex (3)
- Muscarinrezeptor (3)
- Nephroblastom (3)
- Nervennetz (3)
- Nervenzelle (3)
- Neuroanatomie (3)
- Neuronale Plastizität (3)
- Neuropeptide (3)
- Neurowissenschaften (3)
- Neutrophiler Granulozyt (3)
- Non-coding RNA (3)
- Obesity (3)
- Orientierung (3)
- Parkinson's disease (3)
- Parkinson-Krankheit (3)
- Pathogenität (3)
- Phospholipide (3)
- Pilzkörper (3)
- Plasmodium falciparum (3)
- Pneumolysin (3)
- Posttranskriptionelle Regulation (3)
- Proteine (3)
- Proteinkinase D (3)
- RNS (3)
- RNS-Bindungsproteine (3)
- Ribosom (3)
- Salmonella (3)
- Secretion (3)
- Stressreaktion (3)
- Structural Biology (3)
- Thrombozytenaggregation (3)
- Tiermodell (3)
- Transpiration <Pflanzen> (3)
- Treg (3)
- Tumor (3)
- Typ 1 (3)
- Ubiquitinierung (3)
- Visuelle Aufmerksamkeit (3)
- Zelle (3)
- Zellkern (3)
- Zentralnervensystem (3)
- active zone (3)
- adrenocortical carcinoma (3)
- atherosclerosis (3)
- cell wall (3)
- cytoskeleton (3)
- iPSC (3)
- inflammation (3)
- learning (3)
- learning and memory (3)
- magnetic resonance imaging (3)
- megakaryocyte (3)
- megakaryopoiesis (3)
- miRNA (3)
- microRNA (3)
- myocardial infarction (3)
- neurobiology (3)
- regulation (3)
- signalling (3)
- super-resolution microscopy (3)
- translation (3)
- virulence (3)
- 3D cell culture (2)
- 3D-Zellkultur (2)
- ADHS (2)
- ALS (2)
- ASM (2)
- Acetylation (2)
- Ackerschmalwand (2)
- Actin-bindende Proteine (2)
- Actinomyceten (2)
- Actinomycetes (2)
- Adenosinrezeptor (2)
- Adhesion GPCR (2)
- Adipogenesis (2)
- Adjuvant (2)
- Adrenerger Rezeptor (2)
- Affekt (2)
- Altern (2)
- Amygdala (2)
- Angeborene Immunität (2)
- Angiogenese (2)
- Angsterkrankungen (2)
- Antennallobus (2)
- Antiangiogenese (2)
- Antibody (2)
- Antigen CD28 (2)
- Antigen CD8 (2)
- Aorta (2)
- Apis mellifera (2)
- Arabidopsis thaliana (2)
- Arbeitsgedächtnis (2)
- Arbeitsteilung (2)
- Assoziation (2)
- Assoziatives Lernen (2)
- Astrozyt (2)
- Augenbewegung (2)
- Aurora-A (2)
- Autoaggressionskrankheit (2)
- Autoantikörper (2)
- Autoimmunität (2)
- Autophagy (2)
- Aversive Konditionierung (2)
- Axon (2)
- B cells (2)
- B-Zell-Lymphom (2)
- BAD (2)
- BCI (2)
- BOLD signal (2)
- Bacterial infection (2)
- Bakterielle Hirnhautentzündung (2)
- Bakteriengift (2)
- Bauchspeicheldrüsenkrebs (2)
- Bildverarbeitung (2)
- Biogenese (2)
- Bioinks (2)
- Biomechanics (2)
- Biomedicine (2)
- Bioprinting (2)
- Bioreactor (2)
- Bioreaktor (2)
- Blutgerinnung (2)
- Blutstammzelle (2)
- Brain-computer interface (2)
- Brustkrebs (2)
- CD1d (2)
- CD28 (2)
- CDH13 (2)
- CIDP (2)
- Camponotus floridanus (2)
- Cancer immunotherapy (2)
- Cardiomyocyte (2)
- Cartilage Tissue Engineering (2)
- Cell cycle (2)
- Cell migration (2)
- Cement (2)
- Chronophin (2)
- Ciliary neurotrophic factor (2)
- Circadian Rhythms (2)
- Crosstalk (2)
- Cushing-Syndrom (2)
- Cuticle (2)
- Cuticular waxes (2)
- DNA Repair (2)
- DNA repair (2)
- DNA-Reparatur (2)
- DNS (2)
- DRG (2)
- DROSHA (2)
- Deep sequencing (2)
- Dendritische Zellen (2)
- Differentiation (2)
- E. coli Nissle 1917 (2)
- Echinococcus (2)
- Echinococcus multilocularis (2)
- Einzelzellanalyse (2)
- Elektroencephalogramm (2)
- Enterobacteriaceae (2)
- Enzym (2)
- Epigenetic (2)
- Ereigniskorreliertes Potenzial (2)
- Erwachsener (2)
- Extrazelluläre Matrix (2)
- Fabry-Krankheit (2)
- Farbensehen (2)
- Fettsucht (2)
- Fettsäurebiosynthese (2)
- Fitness (2)
- Fluconazole (2)
- Fluorescence (2)
- Förster Resonanz Energie Transfer (2)
- G-protein-coupled receptors (2)
- GABA-Rezeptor (2)
- Gedächtnis (2)
- Gelenkknorpel (2)
- Genomics (2)
- Genotoxizität (2)
- Gerinnungsfaktor XII (2)
- Gewebemodell (2)
- Glioblastoma (2)
- Glukose (2)
- Glycinrezeptor (2)
- Golgi-Apparat (2)
- Graft-versus-host-disease (2)
- Growth (2)
- HUWE1 (2)
- Hemostasis (2)
- Herzfrequenzvariabilität (2)
- Herzinsuffizienz (2)
- Hfq (2)
- Hippo pathway (2)
- Hirnhautentzündung (2)
- Host-pathogen interaction (2)
- Hydrogel (2)
- Hypothalamus (2)
- Hypoxia (2)
- Hypoxie (2)
- Immunisierung (2)
- Immunological synapse (2)
- Immunology (2)
- Immunotherapy (2)
- Immuntoleranz (2)
- Impfung (2)
- In vitro (2)
- Induced pluripotent stem cells (2)
- Infektionsmodell (2)
- Inhibitorische Synapse (2)
- Inhibitory synapse (2)
- Innate immunity (2)
- Innere Uhr (2)
- Insekten (2)
- Interleukin 6 (2)
- Invasion (2)
- Ischemic stroke (2)
- Japankärpfling (2)
- K-Ras (2)
- Kardiologie (2)
- Kernspintomographie (2)
- Kind (2)
- Klimaänderung (2)
- Knochen-Morphogenese-Proteine (2)
- Knochenmark (2)
- Knochenmarktransplantation (2)
- Knockout (2)
- Knockout-Maus (2)
- Knorpel (2)
- Kontextkonditionierung (2)
- Krebsforschung (2)
- Krebsimmuntherapie (2)
- Larve (2)
- Learning (2)
- Leishmania (2)
- Leishmania major (2)
- Leishmaniose (2)
- Lidschlag (2)
- Lipide (2)
- Lung (2)
- Lunge (2)
- MRSA (2)
- MRT (2)
- Macrophages (2)
- Magnetische Resonanz (2)
- Marine sponges (2)
- Mechanosensation (2)
- Megakaryopoese (2)
- Melt Electrowriting (2)
- Meningitis (2)
- Mensch (2)
- Merkel cell carcinoma (2)
- Mesenchymzelle (2)
- Mikrotubuli (2)
- Miz1 (2)
- Monarchfalter (2)
- Motoneuron-Krankheit (2)
- Motorisches Lernen (2)
- Multidrug-Resistenz (2)
- Mutagenität (2)
- Mutation (2)
- Myatrophische Lateralsklerose (2)
- N-MYC (2)
- NIR-Spektroskopie (2)
- NaV1.9 (2)
- Nahrungserwerb (2)
- Nanoparticles (2)
- Natriumkanal (2)
- Navigation (2)
- Neisseria gonorrhoeae (2)
- Nervendegeneration (2)
- Nestbau (2)
- Neuroblastom (2)
- Neurogenese (2)
- Neuromodulation (2)
- Neuroscience (2)
- Neutrophils (2)
- Nicht-kleinzelliges Bronchialkarzinom (NSCLC) (2)
- Nociceptor (2)
- Nukleotid-Exzisions-Reparatur (2)
- Olfaction (2)
- Oligomerisation (2)
- Onkogen (2)
- Opiatrezeptor (2)
- Opioide (2)
- Optogenetik (2)
- Organoid (2)
- Osteogenesis (2)
- Oxidative stress (2)
- P300 (2)
- Panikstörung (2)
- Pathophysiologie (2)
- Peptide (2)
- Peptidsynthese (2)
- Permeabilität (2)
- Peyer's patch (2)
- Pflanzen (2)
- Pflanzenschutzmittel (2)
- Phosphatasen (2)
- Phosphoglykolatphosphatase (2)
- Phospholipase D (2)
- Phylogenie (2)
- Physiologie (2)
- Phänologie (2)
- Plant Protection (2)
- Plant cuticle (2)
- Plasmamembran (2)
- Plastizität (2)
- Post-transcriptional regulation (2)
- Probiotic (2)
- Probiotikum (2)
- Progenitor (2)
- Proliferation (2)
- Proteom (2)
- Präfrontaler Cortex (2)
- Psychische Störung (2)
- Psychologie (2)
- RNA (2)
- RNA helicase (2)
- RNA modifications (2)
- RNA polymerase II (2)
- RNS-Viren (2)
- ROS (2)
- Raf-Kinasen (2)
- Regenerative Medizin (2)
- Resilienz (2)
- Rheumatoid arthritis (2)
- Rho-Proteine (2)
- Rhodopsin (2)
- Ribosome (2)
- Röntgenkristallographie (2)
- SOCE (2)
- SPECT (2)
- Salmonella Typhimurium (2)
- Salmonella enterica (2)
- Schlaf (2)
- Schmerz (2)
- Schmerzforschung (2)
- Sekundärmetabolit (2)
- Sequenzanalyse (2)
- Sozialangst (2)
- Soziale Wahrnehmung (2)
- Sphingolipide (2)
- Spinal Muscular Atrophy (2)
- Stickstoff (2)
- Stoffwechsel (2)
- Streptococcus pneumoniae (2)
- Symbiose (2)
- Synthese (2)
- T cell activation (2)
- TFIIIC (2)
- TLR3 (2)
- TNF (2)
- Thrombo-inflammation (2)
- Thrombopoiesis (2)
- Tissue engineering (2)
- Toleranz (2)
- Transcriptome (2)
- Transforming Growth Factor beta (2)
- Transkriptom (2)
- Tuberkelbakterium (2)
- Ubiquitin-Protein-Ligase (2)
- VSG (2)
- Vaccine (2)
- Wahrnehmung (2)
- Wilms tumor (2)
- Wundheilung (2)
- X-ray crystallography (2)
- Zebrabärbling (2)
- Zebrafish (2)
- Zellteilung (2)
- Zement (2)
- adipocytes (2)
- antennal lobe (2)
- attention (2)
- autophagy (2)
- bee (2)
- behavior (2)
- behaviour (2)
- bioinformatics (2)
- biomedical applications (2)
- biomedicine (2)
- bioreactor (2)
- blood brain barrier (2)
- bone marrow (2)
- brain (2)
- chlamydia (2)
- circadian rhythms (2)
- cytokinesis (2)
- deep brain stimulation (2)
- depression (2)
- development (2)
- developmental differentiation (2)
- diet (2)
- dopamine (2)
- drug development (2)
- ecology (2)
- electron microscopy (2)
- electrophysiology (2)
- emotion (2)
- emotion processing (2)
- emotion regulation (2)
- endosomal trafficking (2)
- evolution (2)
- experimental autoimmune encephalomyelitis (2)
- expression (2)
- fMRI time series (2)
- fear generalization (2)
- funktionelle Kernspintomographie (2)
- genetics (2)
- genomics (2)
- genotoxicity (2)
- gephyrin (2)
- glucose (2)
- hippocampus (2)
- host-pathogen interaction (2)
- in vitro (2)
- infection (2)
- inflammatory pain (2)
- intestinal in vitro model (2)
- ischemic stroke (2)
- kinase (2)
- lipid rafts (2)
- lung cancer (2)
- malaria (2)
- measles virus (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)
- neuroethology (2)
- neuropathy (2)
- oligomerization (2)
- p53 (2)
- pancreas (2)
- peptide (2)
- perception (2)
- protease (2)
- regulatory T cells (2)
- small RNA (2)
- snRNP (2)
- social anxiety (2)
- social attention (2)
- social insects (2)
- sphingolipids (2)
- spontaneous blinks (2)
- symbiosis (2)
- synaptic plasticity (2)
- synaptic proteins (2)
- synaptische Proteine (2)
- targeted therapy (2)
- thrombopoiesis (2)
- tissue engineering (2)
- vascularization (2)
- virtuelle Realität (2)
- wild bees (2)
- working memory (2)
- Ökologie (2)
- Übergewicht (2)
- (hem)ITAM signaling (1)
- 177Lu-OPS201 (1)
- 18S rRNA (1)
- 2-point Dixon (1)
- 3 D bioprinting (1)
- 3-D liver model (1)
- 3D Gewebemodelle (1)
- 3D Modell (1)
- 3D Printing (1)
- 3D model (1)
- 3D models (1)
- 3D muscle (1)
- 3D spheroid culture (1)
- 3D-Gewebemodell (1)
- 3D-Modell (1)
- 4-HNE (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)
- ACC (1)
- ACL (1)
- ADGRL3 (1)
- AI (1)
- AMPK (1)
- AMP‐activated protein kinase (1)
- APOBEC3G (1)
- ARF6 GTPase (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)
- Adaptation (1)
- Adapterprotein (1)
- Adaptorproteine (1)
- Adenosine receptors (1)
- Adhesion and Invasion (1)
- Adhesion and degranulation promoting adapter protein (1)
- Adhesion-GPCR (1)
- Adhesive Hydrogels (1)
- Adipose (1)
- Adipose Tissue Engineering (1)
- Adipose-Derived Stromal/Stem Cells (1)
- Adipositas (1)
- Administered Activities (1)
- Adrenalin (1)
- Adrenergic receptor (1)
- Adrenocortical Carcinoma (1)
- Adrenokortikales Karzinom (1)
- Adultschlupfes (1)
- Adventitia (1)
- Affinity probe (1)
- Agarose (1)
- Aggregation (1)
- Agoraphobie (1)
- Airway epithelia (1)
- Aktivierungsenergie (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 Neurofeedback (1)
- Alpha-Aktivität (1)
- Alternative polyadenylation (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)
- Analgesie (1)
- Analyse (1)
- Anaphylatoxine (1)
- Anaphylatoxinrezeptoren (1)
- Ancistrocladaceae (1)
- Ancistrocladus (1)
- Androstadienon (1)
- Aneuploidy (1)
- Angewandte Mikrobiologie (1)
- Angiogenesis (1)
- Angiotensin II (1)
- Angst als Eigenschaft (1)
- Angst als Zustand (1)
- Angsterkrankung (1)
- Animal behavior IntelliCage system (1)
- Animales Nervensystem (1)
- Anisotropic structures (1)
- Annotation (1)
- Anoikis (1)
- Ant (1)
- Anthocyane (1)
- Anthropocene (1)
- Anti-infective (1)
- Antibiotikum (1)
- Antibodies (1)
- Antigen CD4 (1)
- Antigen CD40 (1)
- Antigen presentation (1)
- Antigen recognition (1)
- Antigenpräsentation (1)
- Antigenrezeptor (1)
- Antikörper (1)
- Antimicrobial activities (1)
- Antimicrobial activity (1)
- Antimicrobial proteins (1)
- Antimikrobielle Aktivitäten (1)
- Antimikrobieller Wirkstoff (1)
- Antioxidantien (1)
- Antworthemmung (1)
- Antwortverhalten (1)
- Anxiety Disorders (1)
- Anxiety disorder (1)
- Anxiety disorders (1)
- Aortenaneurysma (1)
- Apallisches Syndrom (1)
- Aplysina aerophoba (1)
- Apoptose (1)
- Approved immunomodulators (1)
- Archaea (1)
- Archaebakterien (1)
- Arginine (1)
- Arid biomes (1)
- Arrestine (1)
- ArsZ (1)
- Artefakt (1)
- Artenreichtum (1)
- Arterielles Blut (1)
- Artery Models (1)
- Artesunate (1)
- Arthrose (1)
- Arthrosis deformans (1)
- Associative learning (1)
- Assoziatives Gedächtnis (1)
- AstA (1)
- Atemwege (1)
- Atemwegsschleimhaut (1)
- Atherosklerose (1)
- Atmungsinsuffizienz (1)
- Atomic-force-microscopy (1)
- Atta vollenweideri (1)
- Attention deficit / hyperactivity disorder (1)
- Attraction (1)
- Attraktion (1)
- AuNPs (1)
- Audiologie (1)
- Aurora B (1)
- Ausbreitungsverhalten (1)
- Aussterbedynamik (1)
- Autofocus (1)
- Autoimmunity (1)
- Autoinhibition (1)
- Automatische Klassifikation (1)
- Autophagie (1)
- Autoproteolysis (1)
- Autotransporter (1)
- Axon Branching (1)
- B Lymphocytes (1)
- B-Lymphozyten (1)
- B-Zellen (1)
- B0 (1)
- B7-H1 (1)
- BCG (1)
- BCL-2 Familie (1)
- BCL-2 family (1)
- BDNF (1)
- BDNF stimulation (1)
- BH3-only proteins (1)
- BIN2 (1)
- BMP signaling pathway (1)
- BMP-2 (1)
- BMP-Signaltransduktionsweg (1)
- BRAF (1)
- BRCA1 (1)
- BRET (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)
- Baghdadite (1)
- Bahnung (1)
- Bakterielle Infektion (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)
- 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-Rezeptor (1)
- Beta-1-receptor (1)
- Beta-Adrenergic Receptor (1)
- Beta-Adrenozeptor (1)
- Bevacizumab (1)
- Bienen <Familie> (1)
- Bienen Dressur Lernen (1)
- Bierhefe (1)
- Bildanalyse (1)
- Bildbearbeitung (1)
- Bilderzeugung (1)
- Bildgebung intakten Knochens (1)
- Bimolekulare Lipidschicht (1)
- Bindegewebe (1)
- Biochemistry (1)
- Biodiversity assessment (1)
- Biodiversity conservation (1)
- Biofabrikation (1)
- Biofilm formation (1)
- Biofilmarchitektur (1)
- Biofilms (1)
- Bioink (1)
- Biokinetics (1)
- Biologie / Zellbiologie (1)
- Biologischer Abbau (1)
- Biologisches Modell (1)
- Biology (1)
- Bioluminescence resonance energy transfer (1)
- Biolumineszenzmessung (1)
- Biomaterial (1)
- Biomechanik (1)
- Bioprozessmethode (1)
- Biosynthese-Genclustern (1)
- Bipolar (1)
- Bipolar Disorder (1)
- Bitopic Ligands (1)
- Bitopische Liganden (1)
- Blick (1)
- Blickbewegung (1)
- Blickinteraktion (1)
- Blimp-1 (1)
- Blood nerve barrier (1)
- Blumeria graminis (1)
- Blut-Liquor-Schranke (1)
- Blutgefäßsystem (1)
- Bluthirnschranke (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)
- Bortezomib (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)
- Bärtierchen (1)
- C. elegans (1)
- C/EBP (1)
- C1-inibitor (1)
- CAMP production (1)
- CAR T Zellen (1)
- CAR T-cells (1)
- CAR-T cell (1)
- CAR-T-Zell-Therapie (1)
- CCR4 (1)
- CD11b+ myeloid cells (1)
- CD28 Superagonist (1)
- CD28 antigen (1)
- CD28-SA (1)
- CD28-Superagonist (1)
- CD28-superagonist (1)
- CD4+ T cell activation (1)
- CD40 gerichteter bifunktioneller scFv-TRAIL Fusionsproteine (1)
- CD40-targeted bifunctional scFv-TRAIL fusion proteins (1)
- CD8 T cell (1)
- CD8 T-Zelle (1)
- CD84 (1)
- CDC42 (1)
- CDK4 Inhibitor (1)
- CDK4 inhibitor (1)
- CLEC-2 (1)
- CLEC16A (1)
- CMT1A (1)
- CMV (1)
- CNBP (1)
- COMT polymorphism (1)
- COVID-19 (1)
- CRHR1 (1)
- CRISPR Cas9 (1)
- CRISPR Cas9 system (1)
- CTLA-4 (1)
- CVT (1)
- CXCL13 (1)
- CXCR4 (1)
- CXCR5 (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)
- Calciumkanal (1)
- Calciumphosphat (1)
- Calciumtransport (1)
- Camponotus (1)
- Camponotus rufipes (1)
- Cancer Immune Therapy (1)
- Cancer Metabolism (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)
- Cartiage Integration (1)
- Cartilage (1)
- Cartilage Regeneration (1)
- Cartilage defect (1)
- Cas9 (1)
- Catechol-O-Methyltransferase (1)
- Catecholmethyltransferase <Catechol-0-Methyltransferase> (1)
- Cation Homeostasis (1)
- Caveolin-1 (1)
- Ccr4-Not (1)
- Cdh13 (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)
- Ceramid (1)
- Ceramide (1)
- Ceramides (1)
- ChIP-sequencing (1)
- Chaetomium thermophilum (1)
- Chain-length distribution (1)
- Characterization (1)
- Charcot-Marie-Tooth 1A (1)
- Chemische Synapsen (1)
- Chemokin CXCL10 (1)
- Chemokine (1)
- Chemokine receptors (1)
- Chemotaxis (1)
- Chemotherapeutic resistance (1)
- Chemotherapie (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)
- Cholesterinstoffwechsel (1)
- Chondrogenic Differentiation (1)
- Chordontonal organ (1)
- Chromatinremodeling (1)
- Chromatinremodelling (1)
- Chromosom 6 (1)
- Chromosome 6 (1)
- Chronic Mild Stres (1)
- Chronische Nierenerkrankung (1)
- Chronische Niereninsuffizienz (1)
- Chronischer Schmerz (1)
- Chylomicron (1)
- Chylomicrons (1)
- Circadian (1)
- Circadian Clock (1)
- Circadian clock (1)
- Circadiane Uhr (1)
- Circadianer Rhythmus (1)
- Claudin (1)
- Click-Chemie (1)
- Climate change (1)
- Clonal competition assay (1)
- Clostridium difficile (1)
- Cluster (1)
- Co-Kultur (1)
- Co-culture (1)
- Co-culture system (1)
- CoQ10 (1)
- Coactosin-like (1)
- Cochlear-Implantat (1)
- Coffin-Lowry syndrome (1)
- Cognition (1)
- Cognitive Distortions (1)
- Collagen gels (1)
- Collybistin (1)
- Colon cancer (1)
- Commensalism (1)
- Comorbidity (1)
- Comoé National Park (1)
- Complement system (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)
- Contactin-1 (1)
- Contrast Agent Bolus Based Perfusion Magnetic Resonance Imaging (1)
- Convolutional Neural Network (1)
- Coronary heart disease (1)
- Corpus amygdaloideum (1)
- Correlative microscopy (1)
- Corti-Organ (1)
- Cortico-striatal projection neurons (1)
- Corticoliberin (1)
- Counting (1)
- Coxiella burnetii (1)
- Craving (1)
- Cryptochrom (1)
- CsrA (1)
- Cul4b (1)
- Cuticular transpiration (1)
- Cuticular water permeabilities (1)
- Cyanobacteria (1)
- Cyanobakterien (1)
- Cyclic peptides (1)
- Cyclics (1)
- Cystein (1)
- Cytokine (1)
- Cytologie (1)
- Cytomegalie-Virus (1)
- Cytotoxic T cell (1)
- DC (1)
- DEQCT (1)
- DExD/H box protein (1)
- DG diacyglycerol (1)
- DGCR8 (1)
- DHX30 (1)
- DNA Damage (1)
- DNA Schaden (1)
- DNA lesion (1)
- DNA methylation (1)
- DNA-Methylierung (1)
- DNA-Schaden (1)
- DNA-Schäden (1)
- DNS-Bindung (1)
- DNS-Schaden (1)
- DNS-Sequenz (1)
- DOT1 (1)
- DREAM (1)
- DREAM complex (1)
- DSIF (1)
- DTI (1)
- DYT-TOR1A (1)
- Danaus plexippus (1)
- Darmepithel (1)
- Darmflora (1)
- Darmwandnervensystem (1)
- Dasatinib (1)
- Datenbank (1)
- Decapping (1)
- Deep-sequencing (1)
- Deeplearning (1)
- Defensine (1)
- Deletion (1)
- Denaturierende Gradienten-Gelelektrophorese (1)
- Denaturing Gradient Gel Electrophoresis (1)
- Deoxyribozymes (1)
- Dephosphorylierung (1)
- Depletion (1)
- Dereplicaiton (1)
- Deubiquitination (1)
- Development (1)
- Diabetes (1)
- Diabetes Typ 1 (1)
- Diabetes mellitus Typ 1 (1)
- Diabetic painful neuropathy (1)
- Diabetic polyneuropathy (1)
- Diabetische Polyneuropathie (1)
- Diagnostic Imaging Exams (1)
- Diagnostik (1)
- Differential scanning calorimetry (1)
- Differentielle Ressourcenallokation (1)
- Differenzierung (1)
- Diffusion (1)
- Diffusion coefficient (1)
- Diffusionsgewichtete Magnetresonanztomografie (1)
- Dihydrooxazole (1)
- Dilated cardiomyopathy (1)
- Dimension 3 (1)
- Dimere (1)
- Dimeric Naphthylisoquinoline Alkaloids (1)
- Dimerisierung (1)
- Diphenylether (1)
- Dispersal (1)
- Disulfidbrücken (1)
- Diversifikation <Biologie> (1)
- Diversity (1)
- Dolutegravir (1)
- Domänenprotein (1)
- Dopamin (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 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)
- Dynamics of ribosome assembly (1)
- Dynamik (1)
- Dynamik von Membranrezeptoren (1)
- Dynein Light Chain (1)
- Dystonie (1)
- Dürrestress (1)
- E. coli Nissle (1)
- E1 inhibitoren (1)
- E1 inhibitors (1)
- E2 (1)
- ECAP (1)
- ECG-gated PET (1)
- EHEC (1)
- ER dynamics in axon terminals (1)
- ERK (1)
- Eap (1)
- Echocardiography (1)
- Echokardiographie (1)
- Echtzeit (1)
- Echtzeitbildgebung (1)
- Ecological Momentary Assessment (1)
- Ecological Momentary Assessments (1)
- Ecosystem services (1)
- Effect anticipation (1)
- Effektantizipation (1)
- Efflux pump (1)
- Eierstockkrebs (1)
- Eierstocktumor (1)
- Einfühlung (1)
- Einfühlung <Motiv> (1)
- Eingeweidewürmer (1)
- Einsamkeit (1)
- Einzel-Molekül (1)
- Einzelpartikelverfolgung (1)
- Electrochemical Impedance Spectroscopy (1)
- Electrode (1)
- Electroencephalography (1)
- Electromyography (1)
- Electrophysiology (1)
- Elektroakupunktur (1)
- Elektromyographie (1)
- Elektronencephalographie (1)
- Elektrostimulation (1)
- Elektrotherapie (1)
- Elevated Plus-Maze (1)
- Elongation (Transkription) (1)
- Embryo (1)
- Embryonale Stammzelle (1)
- Emotionales Verhalten (1)
- Emotionen (1)
- Emotionsverarbeitung (1)
- Encephalomyelitis (1)
- Endobrachyösophagus (1)
- Endocytosis (1)
- Endogenous clock (1)
- Endophenotype (1)
- Endophänotyp (1)
- Endophänotypen (1)
- Endoplasmatisches Retikulum (1)
- Endosomes (1)
- Endothel (1)
- Endothelium (1)
- Enoyl-Reduktase (1)
- Enoyl-acyl-carrier-protein-Reductase (1)
- Enoyl-acyl-carrier-protein-Reductase <Enoyl-[acyl-carrier-protein]-Reductase> (1)
- Enterische Glia (1)
- Enterohemorrhagic Escherichia coli (1)
- Entscheidungsverhalten (1)
- Entwicklung chimärer Antigenrezeptor T-Zellen (1)
- Entzündungsreaktion (1)
- Entzündungsschmerz (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)
- Expansion microscopy (1)
- Expansionsmikroskopie (1)
- Experimentellen Autoimmun-Enzephalomyelitis (1)
- Explainable AI (1)
- Explainable Artificial Intelligence (1)
- Explorationsverhalten (1)
- Exposure treatment (1)
- Extinktion (1)
- Extracellular Matrix (1)
- Extracellular Vesicles (1)
- Extracellular matrix proteins (1)
- Extrazellulärmatrix (1)
- FAS-II (1)
- FAT10ylation (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)
- 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)
- Fat Quantification (1)
- FeS cluster (1)
- Fear (1)
- Fear Conditioning (1)
- Fear Extinction (1)
- Fear Generalization (1)
- Fear Learning (1)
- Fear conditioning (1)
- Feedforward loop (1)
- Ferroptosis (1)
- Fertilization in angiosperm (1)
- Fettgewebe (1)
- Fettsäure-Synthase (1)
- Fibromyalgia (1)
- Fibromyalgia syndrome (1)
- Fibromyalgiesyndrom (1)
- Flavonoide (1)
- Flavonoids (1)
- Flippase (1)
- Flotillin (1)
- Flow (1)
- Fluconazol (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)
- Fluoreszenzkorrelationsspektroskopie (1)
- Fluoreszenzproteine (1)
- Fluoreszenzsonde (1)
- Fluoreszenzspektroskopie (1)
- Fluoxetin (1)
- Fluoxetine (1)
- Fluss (1)
- Folliculin (1)
- Forkhead Transcription Factors (1)
- Forkhead-Box-Proteine (1)
- Fox tapeworm (1)
- FoxO transcription factors (1)
- Foxo1 (1)
- Foxp3+CD4+ regulatory T cell (1)
- Französische Feldwespe (1)
- Freezing (1)
- Freies Molekül (1)
- Frizzled 5 (1)
- Frontal asymmetry (1)
- Froschlurche (1)
- Fructosebisphosphat-Aldolase (1)
- Fruit (1)
- Frühe Gene (1)
- Function (1)
- Functional analyses (1)
- Funktionelle Bildgebung (1)
- Funktionelle Kernspintomographie (1)
- Furagieraktivität (1)
- Furchkonditionierung (1)
- Furchtgeneralisierung (1)
- Furchtkonditionierung (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 receptors (1)
- G-Protein gekoppelte Rezeptor (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)
- GAS2L3 (1)
- GC1 cells (1)
- GDF-15 (1)
- GLA KO mouse model (1)
- GLP-1 (1)
- GPCR dimerisation (1)
- GPCR nanodomains (1)
- GPCR signaling (1)
- GRM8 (1)
- GWAS (1)
- Ga-68-labelled Peptides (1)
- Galactosidase <alpha-> (1)
- Galectin 1 (1)
- Galectine (1)
- Gambler's Fallacy (1)
- Gametocyt (1)
- Gametogenese (1)
- Gametozyt (1)
- Ganzkörperbestrahlung (1)
- Gap Junction (1)
- Gas chromatography (1)
- Gaschromatographie (1)
- Gastroesophageal reflux (1)
- Gastrointestinal tract (1)
- Gastrointestinaltrakt (1)
- Gauss Prozess Klassifikation (1)
- Gaussian Process Classification (1)
- Gaze interaction (1)
- Gb3 accumulation (1)
- Gefrierstrukturierung (1)
- Gefäßwand (1)
- Gehirn-Computer Schnittstelle (1)
- Gelernte Hilflosigkeit (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)
- Generalisierung (1)
- Genetic etiology (1)
- Genome Annotation (1)
- Genome Instability (1)
- Genome editing (1)
- Genomeditierung (1)
- Genomic Selection (1)
- Genomik (1)
- Genotoxicity (1)
- Genotyping (1)
- Geomagnetic Field (1)
- Gerinnungsfaktor (1)
- Germination and differentiation (1)
- Geruchswahrnehmung (1)
- Geschmack (1)
- Gestational diabetes (1)
- Gestationsdiabetes (1)
- Gewebe (1)
- Gewebemodelle (1)
- Glia (1)
- Glioblastom (1)
- Gliom (1)
- Glioma (1)
- Global change (1)
- Glucocorticoids (1)
- Glucose Starvation (1)
- Glucosetransporter (1)
- Glukosetransporter -1 (1)
- Glutamat-Decarboxylase (1)
- Glutamin (1)
- Glutathion (1)
- Glycin (1)
- Glycine Receptors (1)
- Glycocalyx (1)
- Glycolipid (1)
- Glycophyten (1)
- Glycoprotein GPV (1)
- Glycoprotein hormone (1)
- Glykobiologie (1)
- Glykokalyx (1)
- Glykomodifizierung (1)
- Glykosylierung (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-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)
- H2A.Z (1)
- HAD phosphatase (1)
- HASH (1)
- HBD2 (1)
- HCMV (1)
- HD5 (1)
- HDAC (1)
- HECTD1 (1)
- HFpEF (1)
- HIF1alpha (1)
- HIV Drug resistance (1)
- HIV South Africa (1)
- HIV-1 (1)
- HLA-G (1)
- HMBPP (1)
- HNE (1)
- HP1432, Hpn2 (1)
- HPLC-MS (1)
- HRV (1)
- HSV-1 (1)
- Habituationstraining (1)
- Haemostasis (1)
- Haloacid dehalogenase (1)
- Halophyten (1)
- Halophytes (1)
- Harnwegsinfektion (1)
- Harze (1)
- Hautkrebs (1)
- Hautleitfähigkeit (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)
- Herpesviren (1)
- Herpesviruses (1)
- Herz (1)
- Herzbildgebung (1)
- Herzfrequenz (1)
- Herzfunktion (1)
- Herzhypertrophie (1)
- Herzmuskel (1)
- Herzmuskelkrankheit (1)
- Herzmuskelzelle (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 throughput screening (1)
- High-thropughput screening (1)
- Himmelskompass (1)
- Hippokampus (1)
- Hirnendothelzellen (1)
- Hirnhaut (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)
- Hitzeschockprotein 90 (1)
- Hitzestress (1)
- Hochauflösende Mikroskopie (1)
- Hochauflösungsmikroskopie (1)
- Hochdurchsatz-Screening (1)
- Homing (1)
- Homöostase (1)
- Honeybee (1)
- Honigbiene (1)
- Honigbienen (1)
- Hormone Receptor Signaling (1)
- Hornhaut (1)
- Hospitalismus <Hygiene> (1)
- Host Colonization (1)
- Host Genome Integrity (1)
- Host defense (1)
- Hot Hand Fallacy (1)
- Human Herpesvirus 6 (1)
- Human Transcriptome (1)
- Human-pathogenic (1)
- Humanes Herpesvirus 6 (1)
- Humanparasitologie (1)
- Hyaluronic Acid (1)
- Hyaluronic acid (1)
- Hybrid-Molecules (1)
- Hydrogels (1)
- Hyperactivity (1)
- Hypertension (1)
- Hypertrophie (1)
- Hypertrophy (1)
- Hyrogels (1)
- Hämatopoetische Stammzelltransplantation (1)
- Hämodynamik (1)
- Hämsotase (1)
- Höhenangst (1)
- ICP22 (1)
- IE3 (1)
- IEG (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)
- Ibrutinib (1)
- Ideomotor gaze control (1)
- Ideomotorik (1)
- Ideomotorische Blickkontrolle (1)
- Ighmbp2 (1)
- Ileal Trasposition (1)
- Illumina HiSeq (1)
- Image Processing (1)
- Image Quality (1)
- Immunantwort (1)
- Immune Checkpoint Therapy (1)
- Immune System (1)
- Immune Thrombocytopenia (1)
- Immune cells (1)
- Immunität <Medizin> (1)
- Immunkardiologie (1)
- Immunocardiology (1)
- Immunologe (1)
- Immunomodulation (1)
- Immunreaktion (1)
- Immunthrombozytopenie (1)
- Impfstoff (1)
- Impulsivität (1)
- In vitro models (1)
- In vivo Imaging (1)
- Individual based model (IBM) (1)
- Infection imaging (1)
- Infection models (1)
- Infektionsbildgebung (1)
- Infektionsbiologie (1)
- Infektionsprozess (1)
- Infektionsstudien (1)
- Inflamamtion (1)
- Inflammatory Pain (1)
- Inflammatory pain (1)
- Informationsnutzung (1)
- Informationsverarbeitung (1)
- Infrared radiation (1)
- Inhibitory-postsynapse (1)
- Injectability (1)
- Insect (1)
- Insekt (1)
- Insektenstaaten (1)
- Insulin-like Growth (1)
- Insulin-like-Growth-Factor-Binding-Protein-5 (1)
- Insulinresistenz (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)
- Interaktion (1)
- Interferon <Gamma-> (1)
- Interferon <gamma-> (1)
- Interleukin (1)
- Interleukin 12 (1)
- Interleukin 17 (1)
- Interleukin 2 (1)
- Interleukin 5 (1)
- Interleukin-4 Antagonist (1)
- Interleukine (1)
- Internal Dosimetry (1)
- Intestinal metaplasia (1)
- Intestinal stem cell (1)
- Intracellular bacteria (1)
- Intracellular virulence (1)
- Intrazelluläre Bakterien (1)
- Intrazellulärraum (1)
- Ion channel function (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)
- JNK (1)
- Judgment (1)
- Jugendliche (1)
- Jun (1)
- K-RAS (1)
- K5 capsule (1)
- KDELR2 (1)
- Kardiomyozyt (1)
- Kation (1)
- Kationen-Homöostase (1)
- Keimzentrumsreaktion (1)
- Keratinozyt (1)
- Kern (1)
- Kilimandscharo (1)
- Kinasen (1)
- Kinder (1)
- Kindheit und Jugend (1)
- Kinetik (1)
- Klassifikations- und Regressionsbaum (1)
- Klassische Konditionierung (1)
- Kleine Proteine (1)
- Klima (1)
- Klimawandel (1)
- Kniegelenkarthrose (1)
- Knochenbildung (1)
- Knochenersatz (1)
- Knochenmarkzelle (1)
- Kognitive Inhibition (1)
- Kognitiver Prozess (1)
- Kognitives Lernen (1)
- Kohlendioxid (1)
- Kohlenwasserstoffe (1)
- Kollektive Invasion (1)
- Kolloid (1)
- Kolonieerkennung (1)
- Kommunikation (1)
- Kommunikationshilfe (1)
- Komorbidität (1)
- Kompass (1)
- Komplement (1)
- Komplement <Immunologie> (1)
- Komplement C3a (1)
- Komplement C5a (1)
- Komplexauge (1)
- Konfokale Mikroskopie (1)
- Kongestive Herzmuskelkrankheit (1)
- Kongo (1)
- Konnektivitätsschätzung (1)
- Konsolidierung (1)
- Kontingenz (1)
- Kontrastmittel (1)
- Kontrastmittel-gestützte MRT-Perfusionsmessung (1)
- Kontrolle (1)
- Kopienzahlvariation (1)
- Koronare Herzkrankheit (1)
- Korrelative Mikroskopie (1)
- Krankheit (1)
- Krebs (1)
- Kristallographie (1)
- Kuh (1)
- Künstliche Intelligenz (1)
- L-typ Calciumkanal Antagonist (1)
- LAD (1)
- LASP1 (1)
- LC-MS (1)
- LIS (1)
- LPS (1)
- LPS Biosynthese (1)
- LV Function (1)
- Labeling (1)
- Lactobacillus reuteri (1)
- Lambdoide Prophagen (1)
- Langerhans cells (1)
- Langzeitgedächtnis (1)
- Lateral root development (1)
- Latrophilin receptor (1)
- Latrophilin-3 (1)
- Leaf (1)
- Learning & Memory (1)
- Learning Walk (1)
- Learning walk (1)
- Lebensmittelchemie (1)
- Lebensqualität (1)
- Leber-Metabolismus (1)
- Leberepithelzelle (1)
- Lentiviral transgenesis (1)
- Leptomeningeal cells (1)
- Leptomeningealzellen (1)
- Lernverhalten (1)
- Letalität (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)
- Lipidumbau (1)
- Lipolysis (1)
- Locomotor activity (1)
- Lokalanästhesie (1)
- Luftfeuchtigkeit (1)
- Lung Cancer metastasis (1)
- Lung cancer (1)
- Lung squamous cancer cells (1)
- Lurche (1)
- Lysosom (1)
- Lysosome (1)
- M1 Muscarinic Receptor (1)
- MAP kinase (1)
- MAX (1)
- MCMV (1)
- MDR1 (1)
- MDSC (1)
- MDSCs (1)
- MEK5/ERK5 cascade (1)
- MET-T-box riboswitch (1)
- MIPs (1)
- MIZ1 (1)
- MLN7243 (1)
- MM (1)
- MMB complex (1)
- MND (1)
- MRR1 (1)
- MS2-affinity purification and RNA-seq (1)
- Machine Learning (1)
- Macromolecular machine (1)
- Macrophage (1)
- Macrophage extracellular traps (1)
- Macrophytes (1)
- Magenkrebs (1)
- Magnetic Resonance Imaging (1)
- Magnetic Resonance Relaxometry (1)
- Magnetic resonance imaging (1)
- Magnetresonanz-Relaxometrie (1)
- Magnetresonanztomographie (1)
- Major depression (1)
- Makrokolonie (1)
- Makrophagen (1)
- Makrophyten (1)
- Malaria tropica (1)
- Malignant melanoma (1)
- Mamma carcinoma (1)
- Mammakarzinom (1)
- Manisch-depressive Krankheit (1)
- Mantle cell lymphoma (1)
- Marine natural products (1)
- Marine sponge (1)
- Marine sponge-derived actinomycetes (1)
- Marker (1)
- Marrow (1)
- Masern-Virus (1)
- Masernvirus (1)
- Mass Spectrometry (1)
- Massenspektrometrie (1)
- Masspectrometry (1)
- Mast cells (1)
- Mastzelle (1)
- Mathematical modeling (1)
- Mathematische Modellierung (1)
- Mauerbiene (1)
- Mausmodell (1)
- Mc4r (1)
- Measles virus (1)
- Mechanical deformation (1)
- Mechanisms of Social Attention (1)
- Mechanismus (1)
- Mechanistic model (1)
- Mechanorezeptor (1)
- Medaka (1)
- Medium spiny neurons (1)
- Medizinprodukt (1)
- Megakaryocytes (1)
- Megakaryozytopoese (1)
- Melanin (1)
- Melanin release (1)
- Melanoma (1)
- Melanophor (1)
- Melt electrowriting (1)
- Membrane Receptor Dynamics (1)
- Membranlipide (1)
- Membranrezeptor (1)
- Memory (1)
- Memory B cells (1)
- Menaquinon-BIosynthese (1)
- Menaquinone Biosynthesis (1)
- Meninges (1)
- Meniskus (1)
- Meniskusimplantat (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)
- Metabolic Glycoengineering (1)
- Metabolism (1)
- Metabolomics (1)
- Metabolomik (1)
- Metagenomics (1)
- Metalloproteases (1)
- Metalloproteinase (1)
- Metapopulation (1)
- Metastase (1)
- Metastasierung (1)
- Metatranscriptomics (1)
- Methioninbiosynthese (1)
- Methylierung (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)
- Migration (1)
- Mikroglomeruli (1)
- Mikroorganismus (1)
- Mikrotubuli-assoziiertes Protein (MAP) (1)
- Mikrotubulus (1)
- Mimik (1)
- Minor histocompatibility antigen mismatch transplantation (1)
- Mitochondrien (1)
- Mobile Crowdsensing (1)
- Mobile Health (1)
- Moco biosynthesis (1)
- Model (1)
- Model Based Reconstruction Algorithms in Magnetic Resonance Imaging (1)
- Model simulation (1)
- Modell (1)
- Modellbasierte-Rekonstruktionsalgorithmen in der Magnetresonanztomografie (1)
- Modellierung (1)
- Moderator (1)
- Modification (1)
- Modifizierung (1)
- ModulationTregs (1)
- Molecular Pharmacology (1)
- Molecular Radiotherapy (1)
- Monitoring (1)
- Monoklonaler Antikoerper (1)
- Moonlight (1)
- Moosfaserterminalen (1)
- Morbus Alzheimer (1)
- Morbus Fabry (1)
- Morphology (1)
- Morris Water Maze (1)
- Motivation (1)
- Motoneuron diseases (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)
- Multi-Unit Aufnahmen (1)
- Multicellular aggregates (1)
- Multidrugresistant (1)
- Multilayered skin tissue model (1)
- Multiphotonenmikroskopie (1)
- Multiple Sklerose (1)
- Multiple myeloma (1)
- Multiples Myelom (1)
- Multizellulären Bakteriengemeinschaften (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)
- Myeloma (1)
- Myocardial Work (1)
- Myocardial infarction (1)
- Myokardinfarkt (1)
- Myokarditis (1)
- Myosin IIA (1)
- Myrmecology (1)
- N-Myc (1)
- N-RAS (1)
- N400 (1)
- NA (1)
- NEDMIAL (1)
- NES (1)
- NF-kB (1)
- NFAT (1)
- NK (1)
- NK cell (1)
- NK-DC cross-talk (1)
- NKT (1)
- NLS (1)
- NMJ (neuromuscular junction) (1)
- NMR-Tomographie (1)
- NNMT (1)
- NOS-I (1)
- NOS1AP (1)
- NRF2 (1)
- NSM2 (1)
- NTRK fusions (1)
- NaV1.9. oxidized phospholipids (1)
- Nachtschattengewächse (1)
- Nahrung (1)
- Nahrungsaufnahme (1)
- Nanofabrication (1)
- Nanofabrikation (1)
- Nanomedicine (1)
- Nanomedizin (1)
- Nanopartikel (1)
- Naphthochinonen (1)
- Naphthoquinones (1)
- Naphthylisochinolinalkaloide (1)
- Naphthylisoquinoline (1)
- Narrow escape problem (1)
- Natrium-abhängigen Glukosetransporter-1 (1)
- Natural pest control (1)
- Natural products (1)
- Nature-Insipired Synthesis (1)
- Naturschutz (1)
- Naturstoff (1)
- Near Miss (1)
- Nebenniere (1)
- Nebennierenrindenkarzinom (1)
- Nebennierenrindenkrebs (1)
- Nebennierentumor (1)
- Nephrogenese (1)
- Nervenstimulation (1)
- Nervensystem (1)
- Netzhaut (1)
- Netzwerkanalyse (1)
- Neurobiology (1)
- Neurodegeneration (1)
- Neurodegenerative Erkrankung (1)
- Neurodevelopment (1)
- Neurodevelopmental Disorder (1)
- Neurodevelopmental diseases (1)
- Neuroepigenomics (1)
- Neuroethology (1)
- Neurofascin (1)
- Neurofeedback (1)
- Neurofilament (1)
- Neurogenetik (1)
- Neuroligin 2 (1)
- Neuromuskuläre Endplatte (1)
- Neuronales visuelles System (1)
- Neuropathic Pain (1)
- Neuropathic pain (1)
- Neuropathie (1)
- Neuropathy (1)
- Neuropeptid S Rezeptor Gen (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)
- Nicht-kleinzelliges Bronchialkarzinom (1)
- Nicotiana tabacum (1)
- Nierenversagen (1)
- Nimodipin (1)
- Nitrogen (1)
- Non-conventional T cell (1)
- Non-invasive imaging (1)
- Non-ribosomal peptide synthetase (1)
- Non-viral genome engineering (1)
- Nosocomial Infections (1)
- Nosokomiale Infektionen (1)
- Notch Signalweg (1)
- Notch signalling (1)
- Nozizeption (1)
- Nozizeptor (1)
- Nuclar Medicine (1)
- Nuclear Medicine (1)
- Nuclear imaging (1)
- Nuclease (1)
- Nucleasen (1)
- Nucleotide excision repair (1)
- Nucleotide-Excision-Repair (1)
- Nucleus subthalamicus (1)
- Nukleäre Hormonrezeptoren (1)
- Numerische Fluidmechanik (1)
- OCT1 (1)
- OIS (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)
- Oncostatin M (1)
- Onkologie (1)
- Onkolyse (1)
- Open chromatin (1)
- Opioidpeptide (1)
- Optimal foraging (1)
- Optogenetics (1)
- Orai1 (1)
- Organ of Corti (1)
- Organische Synthese (1)
- Organoids (1)
- Orientia tsutsugamushi (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)
- PDI (1)
- PDXP (1)
- PE Phosphoethanolamine (1)
- PEG (1)
- PER (1)
- PET (1)
- PG neurons (1)
- PHMB (1)
- PI3K (1)
- PKA signaling (1)
- PLEKHG5 (1)
- PLP phosphatase (1)
- PRKACA (1)
- PTH1R (1)
- PTMs (1)
- PTPN22 (1)
- PVM (1)
- PacBio sequencing (1)
- Palbociclib (1)
- Panic Disorder (1)
- Paniksyndrom (1)
- Pankreas (1)
- Parasitology (1)
- Parathormon (1)
- Parc National de la Comoé (1)
- Parkinson Krankheit (1)
- Partial Agonists (1)
- Partialagonismus (1)
- Paternal age and BMI effects (1)
- Pathogene Bakterien (1)
- Pathogenesis (1)
- Pathogenicity (1)
- Pathogens (1)
- Pathologie (1)
- Pathology (1)
- Pathophysiologische Mechanismen (1)
- Patientenklassifikation (1)
- Pattern recognition receptors (1)
- Patulin (1)
- Pediatric Nuclear Medicine (1)
- Pediatric Patients (1)
- Peptides (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)
- 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)
- Phosphoantigen (1)
- Phosphoglykolat-Phosphatase (1)
- Phosphorylation (1)
- Phosphorylierung (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)
- Plasmozytom (1)
- Plastin 3 (1)
- Platelet activating Factor (1)
- Platelet count (1)
- Platelet granules (1)
- Platelet-Membranglykoprotein p62 (1)
- Pluripotenz (1)
- Pmn mutant mouse (1)
- Pneumoviruses (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)
- Polyneuropathie (1)
- Polyphosphate (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)
- Positronen-Emissions-Tomographie (1)
- Posttranslationale Änderung (1)
- Powdery mildew fungus (1)
- Prefrontal cortex (1)
- Prefrontalt Cortex (1)
- Primaten (1)
- Primär-basierte immortalisierte Zelllinie (1)
- Primärprevention (1)
- Primärtumor (1)
- ProQ (1)
- Problem Gambling (1)
- Processing fluency (1)
- Profilin (1)
- Prognose (1)
- Programmed Cell Death 1 (1)
- Programmed Cell Death Ligand 1 (1)
- Prosoziales Verhalten (1)
- Proteasen (1)
- Proteasom (1)
- Proteasomaler Abbau (1)
- Proteasome (1)
- Protein (1)
- Protein Disulfid Isomerase (1)
- Protein Kinase D2 (1)
- Protein TRPC6 (1)
- Protein chemistry (1)
- Protein folding (1)
- Protein interactor (1)
- Protein purification (1)
- Proteinen mit antimikrobieller Wirkung (1)
- Proteinfaltung (1)
- Proteinkinase A (1)
- Proteinmodifizierung (1)
- Proteinsynthese (1)
- Proteintyrosinphosphatase (1)
- Prozessierung (1)
- Pränatale Entwicklung (1)
- Prävention (1)
- Präzisionsmedizin (1)
- Pseudouridin (1)
- Psoriasis (1)
- Psychische Belastung (1)
- Psychische Gesundheit (1)
- Psychobiologie (1)
- Ptpn22 (1)
- Puberty (1)
- Pubertät (1)
- Pyridoxal 5'-phosphate phosphatase (1)
- Pyridoxalphosphat (1)
- Pyrrolidinderivate (1)
- Pyrrolidine carboxamides (1)
- Quadruplex-DNS (1)
- Qualitätsindikator (1)
- Quantifizierung (1)
- Quantitation (1)
- Quantitative Genetics (1)
- RAF (1)
- RAMP (1)
- REDD1 (1)
- REST-Complex (1)
- RESTORE protocol (1)
- RIL-seq (1)
- RNA Abbau (1)
- RNA G-quadruplex (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-Interferenz (1)
- RNS-Polymerase II (1)
- ROR2 (1)
- RS1 (1)
- RS1 Peptides (1)
- RS1 derived peptides (1)
- RSK2 (1)
- RSV (1)
- RYGB (1)
- Rac1 (1)
- Radiation Protection (1)
- Radiation-associated Cancer Risk (1)
- Radiologische Diagnostik (1)
- Raf <Biochemie> (1)
- Raf kinase inhibitor protein (1)
- Random Forest (1)
- Random-walk simulations (1)
- Ranvier-Schnürring (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)
- Regulatory T Cells (1)
- Regulatory T-cell (1)
- Rekombinante DNS (1)
- Rekonsolidierung (1)
- Rekonstruktion (1)
- Relaxation Parameter Mapping in Magnetic Resonance Imaging (1)
- Renaturierung <Ökologie> (1)
- Repeats (1)
- Reporter Cells (1)
- Reporterzellen (1)
- Repression (1)
- Repression <Genetik> (1)
- Reproducibility challenges (1)
- Reprogrammming (1)
- Rescue behaviour (1)
- Resistance (1)
- Resistenz (1)
- Response Inhibition (1)
- Ressourcenallokation (1)
- Resveratrol (1)
- Retinoesäure (1)
- Retinoic acid (1)
- Rezeptor Verankerung (1)
- Rezeptor-Tyrosinkinasen (1)
- Rezeptorblocker (1)
- Rezeptorpharmakologie (1)
- Rezidiv (1)
- Rgs2 (1)
- Rheologie (1)
- Rheology (1)
- Rheumatoider arthritis (1)
- Rho GTPase (1)
- Rho GTPasen (1)
- Rho GTPasw (1)
- RhoA (1)
- RhoGTPase (1)
- Rhodopseudomonas palustris (1)
- Ribonuclease H2 (1)
- Riboregulation (1)
- Ribosomale RNA (1)
- Ribosome biogenesis (1)
- Ribosome profiling (1)
- Ribozymes (1)
- Riesensynapsen (1)
- Risikofaktoren (1)
- Risk Assessment (1)
- Rodents (1)
- Rodung (1)
- Rossameise (1)
- Rotes Meer (1)
- Rothmund-Thomson-Syndrome (1)
- Räumliches Gedächtnis (1)
- SAP2 (1)
- SARS-CoV-2 (1)
- SCV maturation (1)
- SEPHCHC Synthase (1)
- SGLT1 (1)
- SIX1 (1)
- SLC2A3 (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)
- STD patients (1)
- STEC (1)
- STED (1)
- STIM2 (1)
- STP1 (1)
- SUMOylation (1)
- SWI/SNF (1)
- Saatgutbeizung (1)
- Salmonella typhimurium (1)
- Samenschale (1)
- Sandminen (1)
- Sap47 (1)
- Satellite glial cell (1)
- Scaffold bone implant (1)
- Scherstress (1)
- Schilddrüse (1)
- Schimpanse (1)
- Schizosaccharomyces pombe (1)
- Schließzellfunktion (1)
- Schmerztherapie (1)
- Schmetterlinge (1)
- Schreckreaktion (1)
- Schuppenflechte (1)
- Schwamm (1)
- Schwertkärpfling (1)
- Schwämme (1)
- Screening (1)
- Sehen (1)
- Sekretion von Aspartatproteasen (1)
- Sekundärkrankheit (1)
- Sekundärprävention (1)
- Selbstregulation (1)
- Selective extraction (1)
- Seneszenz (1)
- Sensory Gating (1)
- Sepsis (1)
- Sequence Analysis (1)
- Sequence-Structure (1)
- Sequenz (1)
- Sequenzanalyse <Chemie> (1)
- Sequenzdaten (1)
- Sequenzwiederholung (1)
- Serotonerge Nervenzelle (1)
- Serotonin Transporter (1)
- Serotonin transporter (1)
- Serotonintransporter (1)
- Setting Control (1)
- Sexuelle Entwicklung (1)
- Sglt1 (1)
- Shear Stress (1)
- Shigella flexneri (1)
- Shimming (1)
- Sialoadhesin (1)
- Signal-Übertragung (1)
- Signaling (1)
- Signalkette (1)
- Silica precursor (1)
- Simulation (1)
- Single Particle Tracking (1)
- Single-cell RNA-sequencing (1)
- Single-molecule (1)
- Sinneszelle (1)
- Sinusthrombose (1)
- Skin (1)
- Skin Tissue Engineering (1)
- Sleep (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)
- 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)
- Sphingomyelinase (1)
- Sphingosine-1-phosphate (1)
- Sphingosine-1-phosphats (1)
- Spielsucht (1)
- Spinal muscular Atrophy (1)
- Spinal muscular atrophy (1)
- Spinalganglion (1)
- Spirale (1)
- Spleen tyrosine kinase (1)
- Spliceosome (1)
- Splicing (1)
- Spo0A (1)
- Sponge diseases (1)
- Sponges (1)
- Sporenbildung (1)
- Sporulation (1)
- Squamous cell carcinoma (1)
- Ssl1 (1)
- Stammzellen (1)
- Staphylococci (1)
- Staphylococcus (1)
- Staphylococcus epidermidis (1)
- Stat3 (1)
- Stat5 (1)
- SteC (1)
- Stechameisen (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)
- Stofftransport <Biologie> (1)
- Store-Operated (1)
- Strahlenpilze (1)
- Streptomyces (1)
- Stressresistenz (1)
- Striatum (1)
- Stroke (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)
- 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)
- Synchronitätsmessung (1)
- Synthesis (1)
- Systematik (1)
- Systembiologie (1)
- Südafrika (1)
- Südostasien (1)
- T Helper Cell (1)
- T Lymphocyte (1)
- T Zell Selektion (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 cells (1)
- T zellen (1)
- T-Lymphozyten-Rezeptor (1)
- T-Zelle (1)
- T-Zellhoming (1)
- T-cell (1)
- T-cell engineering (1)
- T-cell therapy (1)
- TGF-ß (1)
- TGN1412 (1)
- TH2 Immunantwort (1)
- TLR signaling (1)
- TMEM16F (1)
- TNFR2 (1)
- TP53 (1)
- TP53 lesions (1)
- TRAIL mutants (1)
- TRPA1 (1)
- TRPA1 channel (1)
- TRPC6 (1)
- TRPM7 kinase (1)
- TRPV1 (1)
- TRRAP (1)
- TWEAK (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)
- Terpene (1)
- Test system (1)
- Tfb4 (1)
- Theoretical Ecology (1)
- Theory of Mind (1)
- Therapeutical application (1)
- Therapieresistenz (1)
- Therapiesimulation (1)
- Thermoregulation (1)
- Thermoresponsive Polymere (1)
- Thermotoleranz (1)
- Theta Burst Stimulation (1)
- Thigmotaxis (1)
- Think/No-Think (1)
- Thiolase (1)
- Thiostrepton (1)
- Thrombopoese (1)
- Thrombozyten (1)
- Thrombozytopathie (1)
- Thrombozytopenie (1)
- Thrombozytopoese (1)
- Thrombus (1)
- Thymocytes (1)
- Thymosin b4 (1)
- Thymus (1)
- Tierphysiologie (1)
- Tight Junction Proteins (1)
- Timing (1)
- Tissue staining (1)
- Tobacco smoking (1)
- Toll-like-Rezeptoren (1)
- Toxin (1)
- TraDIS (1)
- Transcranial Magnetic Stimulation (1)
- Transcription Factor (1)
- Transcription factor (1)
- Transgener Organismus (1)
- Transgenic mice (1)
- Transkriptomik anlyze (1)
- Transmissionsblockierende Impfstoffe (1)
- Transpiration barrier (1)
- Transportbarriere (1)
- Transporters (1)
- Transposon (1)
- Trauma (1)
- Traumatic neuropathy (1)
- Tree physiology (1)
- Trem2 (1)
- Trend (1)
- Triclosan (1)
- Triglyceride (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 microenvironment (1)
- Tumor-Nekrose-Faktor (1)
- Tumorangiogenese (1)
- Tumorgefäßmorphologie (1)
- Tumorimmunologie (1)
- Tumorwachstum (1)
- Tumorzelle (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)
- U snRNPs (1)
- U1 snRNA (1)
- UBA6 (1)
- UBE2S (1)
- UBE2Z (1)
- USA300 (1)
- USP (1)
- USP28 (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)
- Uremic cardiomyopathy (1)
- Urinary tract infection (1)
- Urteilen (1)
- Urämie (1)
- Urämische Kardiomyopathie (1)
- VCAM (1)
- VLA-1 (1)
- VSMC (1)
- Vaccinia-Virus (1)
- Vagusnervstimulation (1)
- Vakuole (1)
- Vakzinen (1)
- Validität (1)
- Valscularization (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)
- Vermeidungsreaktion (1)
- Vermeidungsverhalten (1)
- Verweildauer (1)
- Verwundbarkeit (1)
- Very-long-chain aliphatic (1)
- Vesikelbildung (1)
- Vessel wall (1)
- Vg9Vd2 T Zellaktivierung (1)
- Vg9Vd2 T cell (1)
- Vgamma9Vdelta2 T cell (1)
- Vgamma9Vdelta2 T cells (1)
- Vielfalt (1)
- Virology (1)
- Virus infection (1)
- Visual attention (1)
- Visuelle Orientierung (1)
- Visuelle Wahrnehmung (1)
- Visuelles Gedächtnis (1)
- Visuelles System (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)
- Wasser Fett Trennung (1)
- Wasted Work (1)
- Water stress (1)
- Web services (1)
- Wechselwirkungen (1)
- Wildbienen (1)
- Wilms Tumor (1)
- Wilms tumor protein 1 (1)
- Wilms-Tumor (1)
- Wirkstoff (1)
- Wirkstofftestung (1)
- Wirt-Erreger Interaktion (1)
- Wirtszelle (1)
- Wnt-Proteine (1)
- Würmer (1)
- Wüstenpflanze (1)
- X-ray Crystallography (1)
- X-ray diffraction (1)
- XPD (1)
- Xeroderma pigmentosum (1)
- Xiphophorus (1)
- Xmrk (1)
- YAP (1)
- Yb1 (1)
- Yeast (1)
- Yersinia (1)
- Yersinia pestis (1)
- YnaI (1)
- ZFAND1 (1)
- Zebrafisch (1)
- Zeitgeber (1)
- Zell Migration (1)
- Zelladhäsion (1)
- Zellkernarchitektur (1)
- Zelllinie (1)
- Zellteilung (Zytokinese) (1)
- Zelltod (1)
- Zelltransport (1)
- Zellwand (1)
- Zielstruktur (1)
- Zink-Finger-Proteine (1)
- Zytoskelett (1)
- Zählen (1)
- aGPCR (1)
- acceptance-based strategies (1)
- actin cytoskeleton (1)
- actin-binding proteins (1)
- actinomycetes (1)
- acute graft-versus host disease (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 neurogenesis (1)
- aggressive behavior (1)
- aging (1)
- agonist (1)
- airflow (1)
- alkaloids (1)
- allogen (1)
- allogeneic stem cell transplantation (1)
- allogenic (1)
- allografts (1)
- alloreactive T cells (1)
- alpha-IIb beta-3 (1)
- alternative intronic polyadenylation (1)
- ammonium (1)
- ammonium permease (1)
- amphibia (1)
- amphiphysin (1)
- amygdala (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)
- anxiety (1)
- anxiety conditioning (1)
- anxiety disorders (1)
- arf (1)
- articular cartilage progenitor cells (1)
- artificial diet (1)
- artificial human skin (1)
- asialoGM1 (1)
- aspergillus fumigatus (1)
- assembly (1)
- association studies (1)
- astrocytoma (1)
- asymptomatic bacteriuria (1)
- atomic force microscopy (1)
- atopic diseases (1)
- auditorisch (1)
- auditory (1)
- auditory cortex (1)
- autoantibody (1)
- autoimmunity (1)
- autophagocytose (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)
- 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)
- biased agonism (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)
- biological scaffolds (1)
- biology (1)
- bioluminescence imaging (1)
- biomaterials (1)
- bioprocessing (1)
- biosynthetic gene clusters (1)
- bitter taste (1)
- blood (1)
- blood cerebrospinal fluid barrier (1)
- blood glucose regulation (1)
- blood nerve barrier (1)
- bone marrow niche (1)
- bone marrow transplantation (1)
- bone regeneration (1)
- brood rearing (1)
- building behavior (1)
- bumblebee*s (1)
- butyrophilin 3A (1)
- c-Jun Phosphorylierung (1)
- c-myc (1)
- cAMP (1)
- cAMP signaling (1)
- cadherin-13 (1)
- calcium (1)
- calcium activity (1)
- calcium homeostasis (1)
- calcium imaging (1)
- cancer therapy (1)
- candida (1)
- candida albicans (1)
- carbon dioxide (1)
- cardiac hypertrophy (1)
- cardiac imaging (1)
- cardiac tissue (1)
- cardiovascular (1)
- carnivorous plants (1)
- cartilage regeneration (1)
- cell (1)
- cell adhesion (1)
- cell cycle (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)
- cine loop (1)
- circadian clock (1)
- circadian clocks (1)
- circuitopathies (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)
- cognitive decline (1)
- cognitive inhibition (1)
- cohesin (1)
- collective invasion (1)
- collybistin (1)
- colony recognition (1)
- color vision (1)
- compartments (1)
- compound eyes (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)
- 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)
- cytokine release syndrome (1)
- cytokines (1)
- dCIRL (1)
- dSTORM (1)
- decellularization (1)
- decision-making (1)
- defense (1)
- degeneratives Nervengewebe (1)
- delipidation (1)
- dendritic cells (1)
- dendritic cell (1)
- dendritic cell-targeting (1)
- desert plant (1)
- deubiquitinase (1)
- dexamethasone suppression test (1)
- diabetic cardiomyopathy (1)
- diagnostic Microarray (1)
- diagnostics (1)
- diagnostischer Microarray (1)
- diastolic dysfunction (1)
- differential RNA-seq (1)
- differential coverage binning (1)
- differential geneexpression (1)
- differenzielle Genexpression (1)
- dilated cardiomyopathy with ataxia (DCMA) (1)
- dimerer Naphthylisochinolin-Alkaloide (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)
- ecoli_VF_collection (1)
- ecological validity (1)
- ectopic bone formation (1)
- ectopic release (1)
- effector protein (1)
- electroacupuncture (1)
- electroencephalogram (1)
- electron cryomicroscopy (1)
- embryonale Maus (1)
- emojis (1)
- emotional feedback (1)
- emotional interference (1)
- emotionale Interferenz (1)
- endocytic recycling (1)
- endocytosis (1)
- endophyte (1)
- endothelial cells (1)
- enhancers (1)
- enoyl ACP reductase (1)
- enoyl reductase (1)
- enoyl-ACP reductase (1)
- entero-aggregative-haemorrhagic Escherichia coli (EAHEC) (1)
- eosinophil (1)
- epidemiology (1)
- epigenetic (1)
- epigenetics (1)
- epithelial to mesenchymal transition (1)
- epithelial-mesenchymal transition (1)
- ereigniskorreliertes Potential (1)
- etiology (1)
- exotische Pflanzen (1)
- experimentelle autoimmune Enzephalomyelitis (1)
- exposure therapy (1)
- extinction (1)
- extinction dynamics (1)
- extracellular matrix (1)
- eye contact (1)
- eye tracking (1)
- eye-tracking (1)
- fabry disease (1)
- facial expressions (1)
- fatty acid biosynthesis (1)
- fatty acid synthesis (1)
- fear conditioning (1)
- fear extinction (1)
- fear potentiated startle response (1)
- feral bees (1)
- fgf (1)
- fibroblast growth factors (1)
- fibromyalgia sydrome (1)
- fitness (1)
- fluorescence imaging (1)
- fluorescence microscopy (1)
- fluorescence resonance energy transfer (FRET) (1)
- flytrap (1)
- fmri activity (1)
- follicular regulatory T cell (1)
- follikuläre regulatorische T-Zelle (1)
- food craving (1)
- forager (1)
- foraging (1)
- foraging activity (1)
- forest landscape (1)
- foxtapeworm (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 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 modification (1)
- genetic screen (1)
- genome stability (1)
- genomic damage (1)
- genomic imaging (1)
- genomische Schäden (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)
- gp130 (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)
- hematopoiesis (1)
- hereditary spastic paraplegia (1)
- hiPSC aggregation (1)
- hibernation (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)
- 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)
- 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)
- imprinting. (1)
- imunology (1)
- in situ microscopy (1)
- in vitro Modelle (1)
- in vitro Testmodell (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)
- influenza A virus (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)
- insulin (1)
- insulin resistance (1)
- intact bone imaging (1)
- integrins (1)
- interaction stress and circadian system (1)
- interactions (1)
- interleukin-5 signaling (1)
- internal dosimetry (1)
- interphase gap (1)
- interpulse interval (1)
- intestinal mucus (1)
- intestine (1)
- intracellular calcium release (1)
- invasive meningococcal diseases (1)
- invasive pulmonary aspergillosis (1)
- ion channel (1)
- iron oxide contrast agent (1)
- ischemia reperfusion injury (1)
- islets of Langerhans (1)
- jasmonate (1)
- juvenile hormone (1)
- ketamine anaesthesia (1)
- kidney development (1)
- kinesin (1)
- knockout (1)
- knockout-mice (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)
- late enhancement (1)
- late gadolinium-enhancement (1)
- leaf cuticle (1)
- leaf-cutting ants (1)
- learned helplessness (1)
- learning and behaviour (1)
- leishmaniasis (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)
- mTOR (1)
- machine learning (1)
- macrocolony (1)
- macrophage (1)
- macrophages (1)
- malnourishment (1)
- marine sponges (1)
- mass spectrometry (1)
- mastitis (1)
- mastitis-associated Escherichia coli (MAEC) (1)
- mean first passage time (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)
- metapopulation (1)
- metatranscriptome (1)
- methionine biosynthesis (1)
- methylphenidate (1)
- miR-17~92 (1)
- miR-21 (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)
- microprocessor complex (1)
- microrna (1)
- mild cognitive impairment (1)
- minimum leaf conductance (1)
- mitochondria (1)
- mitogen cascade (1)
- molecular mechanism (1)
- monarch butterfly (1)
- monoclonal antibody (1)
- monoclonal antibody 103.2 (1)
- monoclonal antibody 20.1 (1)
- mossy fiber terminal (1)
- motoneurons (1)
- motor neuron (1)
- mouse models (1)
- mouse platelets (1)
- movement disorders (1)
- movement interaction (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)
- 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)
- myocarditis (1)
- myokardiale Arbeit (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)
- 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-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)
- oligopeptide transport (1)
- oncogenes (1)
- opening of chromatin (1)
- opioid peptide (1)
- opioid receptor (1)
- opioid receptors (1)
- optogenetics (1)
- orientation (1)
- oscillations (1)
- ovarian cancer (1)
- ovarian carcinoma (1)
- oxidative stress (1)
- oxidativer Stress (1)
- oxidierte Phospholipide (1)
- p34 (1)
- p44 (1)
- pICln (1)
- pain (1)
- pain regulation (1)
- pancreatic cancer (1)
- pancreatic differentiation (1)
- parasitology (1)
- parathyroid hormone (1)
- parkinson's disease (1)
- pathophysiological mechanisms (1)
- pathotypes (1)
- pea aphid (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)
- phage resistance (1)
- pharmacology (1)
- pheromone (1)
- phosphatase (1)
- phosphoantigen (1)
- phosphoglycolate phosphatase (1)
- phospholipase D (1)
- phosphorylation (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)
- polarization (1)
- polarized epithelium (1)
- pollen (1)
- pollen analysis (1)
- pollen foraging (1)
- pollen metabarcoding (1)
- pollinator friendly plants (1)
- polyethism (1)
- polymer (1)
- polyradiculoneuropathy (1)
- population dynamics (1)
- post-transcriptional regulation (1)
- potenzielles therapeutisches Target (1)
- precision medicine (1)
- preclinical PET (1)
- prefrontal cortex (1)
- prenatal stress (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)
- 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)
- pränataler Stress (1)
- psychophysiology (1)
- psychosocial resilience (1)
- psychosocial stress (1)
- pyrrolidine carboxamides (1)
- quiescence (1)
- rRNA processing (1)
- rac1 inhibitors (1)
- ranskranielle magnetische Stimulation (1)
- rapid evolution (1)
- rat (1)
- reactive oxygen species (1)
- real-time imaging (1)
- reception (1)
- receptor (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)
- replication (1)
- reporter screen (1)
- research software (1)
- resilience (1)
- resin (1)
- resistance (1)
- resolution (1)
- responsiveness (1)
- resting tremor (1)
- restriction factors (1)
- resveratrol (1)
- retinal development (1)
- reversible oxidation (1)
- rheumatoide Arthritis (1)
- rho gtpases (1)
- ribosomal RNA (1)
- ribosome biogenesis (1)
- ribosome profiling (1)
- riboswitch (1)
- risk factors (1)
- rodent model (1)
- salinen Wachstumsbedingungen (1)
- salt stress (1)
- sand mine (1)
- scale-up (1)
- schnelle Evolution (1)
- screening (1)
- second messenger (1)
- secondary metabolites (1)
- secondary prevention (1)
- secreted aspartic protease (1)
- secretion (1)
- secretory properties (1)
- seed coat (1)
- seed treatment (1)
- self-activation (1)
- self-regulation (1)
- self-targeting CRISPR-Cas (1)
- senescence (1)
- sensitivity (1)
- sequence-structure (1)
- serotonergic system (1)
- serotonin (1)
- serotonin deficiency (1)
- serotonin transporter (1)
- serum retention (1)
- sexual stage surface proteins (1)
- short neuropeptide F (1)
- sigma factor (1)
- signal transduction (1)
- signaling pathway (1)
- signaltransduction (1)
- similarity (1)
- single cell anatomy (1)
- single molecule microscopy (1)
- single particle tracking (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 equivalent (1)
- skin model (1)
- small RNA expression (1)
- small fiber pathology (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)
- solitary bee nests (1)
- somatic resilience (1)
- somatostatin receptor antagonists (1)
- soziale Insekten (1)
- spatial organization (1)
- specific phobia (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)
- stream (1)
- streptozotocin (1)
- stress response (1)
- striatum (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)
- superparamagnetische Eisenoxid Kontrastmittel (1)
- suspension culture (1)
- synaptische Plastizität (1)
- systemic inflammation (1)
- systems biology (1)
- t cell (1)
- t cells (1)
- tactil (1)
- tactile (1)
- tapeworm (1)
- telomere-associated protein (1)
- temperate zones (1)
- temporal information transfer (1)
- temporal organization (1)
- temporo-parietal junction (1)
- terpenes (1)
- th1/th2 polarization (1)
- therapy (1)
- therapy simulation (1)
- thermal orientation (1)
- thermotolerance (1)
- theta burst stimulation (1)
- think/no-think (1)
- thiostrepton (1)
- threat conditioning (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)
- transcription (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)
- transient dynamics (1)
- transkranielle Gleichstromstimulation (1)
- transmission blocking vaccine (1)
- transpiration barrier (1)
- transport (1)
- transporter regulator (1)
- tuberculosis (1)
- tumor angiogenesis (1)
- tumor metabolism (1)
- tumor vascular morphologie (1)
- tumour (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)
- vaccine (1)
- vacuole (1)
- variant surface glycoprotein (1)
- variational network (1)
- varroa (1)
- vascular cell adhesion molecules (1)
- vascular system (1)
- vaskuläre Adhäsionsmoleküle (1)
- vaskuläre glatte Muskelzelle (1)
- vasp (1)
- vav2 (1)
- venus (1)
- viral genome packaging (1)
- viral miRNAs (1)
- virtual reality T-maze (1)
- virulence factors (1)
- vision (1)
- visual attention (1)
- visual cue (1)
- visual perception (1)
- visuelles Langzeitgedächtnis (1)
- waggle dance (1)
- waggle dance decoding (1)
- water fat separation (1)
- water loss (1)
- wax (1)
- wild-living honey bees (1)
- workbench (1)
- wound healing (1)
- x-ray micro computed tomography (1)
- yeast (1)
- zeitgeber (1)
- zeitlich Informationsübertragung (1)
- zeitliche Organisation (1)
- zentrale Spindel und Mittelkörper (1)
- zonal Hydrogels (1)
- zyklische Peptide (1)
- Ätiologie (1)
- Ölpalmenanbau (1)
- Übertragungsfunktion (1)
- Übung (1)
- ΔNp63 (1)
- α-synuclein (1)
- β3 adrenergic receptor (1)
- γδ T cells (1)
Institute
- Graduate School of Life Sciences (761) (remove)
Sonstige beteiligte Institutionen
- Helmholtz Institute for RNA-based Infection Research (HIRI) (5)
- Rudolf Virchow Center for Integrative and Translational Bioimaging, University of Würzburg (2)
- Universitätsklinikum Münster (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)
- Carl-Ludwig-Institut für Physiologie, Universität Leipzig (1)
- Chair of Experimental Biomedicine I (1)
- DAAD - Deutscher Akademischer Austauschdienst (1)
Chlamydia trachomatis (Ct) is an obligate intracellular human pathogen. It causes blinding trachoma and sexually transmitted disease such as chlamydia, pelvic inflammatory disease and lymphogranuloma venereum. Ct has a unique biphasic development cycle and replicates in an intracellular vacuole called inclusion. Normally it has two forms: the infectious form, elementary body (EB); and the non-infectious form, reticulate body (RB). Ct is not easily amenable to genetic manipulation. Hence, to understand the infection process, it is crucial to study how the metabolic activity of Ct exactly evolves in the host cell and what roles of EB and RB play differentially in Ct metabolism during infection. In addition, Ct was found regularly coinfected with other pathogens in patients who got sexually transmitted diseases (STDs). A lack of powerful methods to culture Ct outside of the host cell makes the detailed molecular mechanisms of coinfection difficult to study.
In this work, a genome-scale metabolic model with 321 metabolites and 277 reactions was first reconstructed by me to study Ct metabolic adaptation in the host cell during infection. This model was calculated to yield 84 extreme pathways, and metabolic flux strength was then modelled regarding 20hpi, 40hpi and later based on a published proteomics dataset. Activities of key enzymes involved in target pathways were further validated by RT-qPCR in both HeLa229 and HUVEC cell lines. This study suggests that Ct's major active pathways involve glycolysis, gluconeogenesis, glycerolphospholipid biosynthesis and pentose phosphate pathway, while Ct's incomplete tricarboxylic acid cycle and fatty acid biosynthesis are less active. EB is more activated in almost all these carbohydrate pathways than RB. Result suggests the survival of Ct generally requires a lot of acetyl-CoA from the host. Besides, both EB and RB can utilize folate biosynthesis to generate NAD(P)H but may use different pathways depending on the demands of ATP. When more ATP is available from both host cell and Ct itself, RB is more activated by utilizing energy providing chemicals generated by enzymes associated in the nucleic acid metabolism. The forming of folate also suggests large glutamate consumption, which is supposed to be converted from glutamine by the glutamine-fructose-6-phosphate transaminase (glmS) and CTP synthase (pyrG).
Then, RNA sequencing (RNA-seq) data analysis was performed by me in a coinfection study. Metatranscriptome from patient RNA-seq data provides a realistic overview. Thirteen patient samples were collected and sequenced by our collaborators. Six male samples were obtained by urethral swab, and seven female samples were collected by cervicovaginal lavage. All the samples were Neisseria gonorrhoeae (GC) positive, and half of them had coinfection with Ct. HISAT2 and Stringtie were used for transcriptomic mapping and assembly respectively, and differential expression analysis by DESeq2, Ballgown and Cuffdiff2 are parallelly processed for comparison. Although the measured transcripts were not sufficient to assemble Ct's transcriptome, the differential expression of genes in both the host and GC were analyzed by comparing Ct positive group (Ct+) against Ct-uninfected group. The results show that in the Ct+ group, the host MHC class II immune response was highly induced. Ct infection is associated with the regulation of DNA methylation, DNA double-strand damage and ubiquitination. The analysis also shows Ct infection enhances host fatty acid beta oxidation, thereby inducing mROS, and the host responds to reduce ceramide production and glycolysis. The coinfection upregulates GC's own ion transporters and amino acid uptake, while it downregulates GC's restriction and modification systems. Meanwhile, GC has the nitrosative and oxidative stress response and also increases the ability for ferric uptake especially in the Ct+ group compared to Ct-uninfected group.
In conclusion, methods in bioinformatics were used here in analyzing the metabolism of Ct itself, and the responses of the host and GC respectively in a coinfection study with and without Ct. These methods provide metabolic and metatranscriptomic details to study Ct metabolism during infection and Ct associated coinfection in the human microbiota.
Plexus injury often occurs after motor vehicle accidents and results in lifelong disability with severe neuropathic pain. Surgical treatment can partially restore motor functions, but sensory loss and neuropathic pain persist. Regenerative medicine concepts, such as cell replacement therapies for restoring dorsal root ganglia (DRG) function, set high expectations. However, up to now, it is unclear which DRG cell types are affected by nerve injury and can be targeted in regenerative medicine approaches.
This study followed the hypothesis that satellite glial cells (SGCs) might be a suitable endogenous cell source for regenerative medicine concepts in the DRG. SGCs originate from the same neural crest-derived cell lineage as sensory neurons, making them attractive for neural repair strategies in the peripheral nervous system. Our hypothesis was investigated on three levels of experimentation. First, we asked whether adult SGCs have the potential of sensory neuron precursors and can be reprogrammed into sensory neurons in vitro. We found that adult mouse DRG harbor SGC-like cells that can still dedifferentiate into progenitor-like cells. Surprisingly, expression of the early developmental transcription factors Neurog1 and Neurog2 was sufficient to induce neuronal and glial cell phenotypes. In the presence of nerve growth factor, induced neurons developed a nociceptor-like phenotype expressing functional nociceptor markers, such as the ion channels TrpA1, TrpV1 and NaV1.9. In a second set of experiments, we used a rat model for peripheral nerve injury to look for changes in the DRG cell composition. Using an unbiased deep learning-based approach for cell analysis, we found that cellular plasticity responses after nerve injury activate SGCs in the whole DRG. However, neither injury-induced neuronal death nor gliosis was observed. Finally, we asked whether a severe nerve injury changed the cell composition in the human DRG. For this, a cohort of 13 patients with brachial plexus injury was investigated. Surprisingly, in about half of all patients, the injury-affected DRG showed no characteristic DRG tissue. The complete entity of neurons, satellite cells, and axons was lost and fully replaced by mesodermal/connective tissue. In the other half of the patients, the basic cellular entity of the DRG was well preserved. Objective deep learning-based analysis of large-scale bioimages of the “intact” DRG showed no loss of neurons and no signs of gliosis.
This study suggests that concepts for regenerative medicine for restoring DRG function need at least two translational research directions: reafferentation of existing DRG units or full replacement of the entire multicellular DRG structure. For DRG replacement, SGCs of the adult DRG are an attractive endogenous cell source, as the multicellular DRG units could possibly be rebuilt by transdifferentiating neural crest-derived sensory progenitor cells into peripheral sensory neurons and glial cells using Neurog1 and Neurog2.
The greatest problems faced during the 21st century is climate change which is a big threat to food security due to increasing number of people. The increase in extreme weather events, such as drought and heat, makes it difficult to cultivate conventional crops that are not stress tolerant. As a result, increasing irrigation of arable land leads to additional salinization of soils with plant-toxic sodium and chloride ions. Knowledge about the adaptation strategies of salt-tolerant plants to salt stress as well as detailed knowledge about the control of transpiration water loss of these plants are therefore important to guarantee productive agriculture in the future. In the present study, I have characterized salt sensitive and salt tolerant plant species at physiological, phenotypic and transcriptomic level under short (1x salt) and long-time (3x) saline growth conditions. Two approaches used for long-time saline growth conditions (i.e increasing saline conditions (3x salt) and constant high saline conditions (3x 200 mM salt) were successfully developed in the natural plant growth medium i.e soil. Salt sensitive plants, A. thaliana, were able to survive and successfully set seeds at the toxic concentrations on the increasing saline growth mediums, with minor changes in the phenotype. However, under constant high saline conditions they could not survive. This was due to keeping low potassium, and high salt ions (sodium and chloride) in the photosynthetic tissue i.e leaf. Similarly, high potassium and low salt ions in salt tolerant T. salsuginea on both saline environments were the key for survival of this plant species. Being salt tolerant, T. salsuginea always kept high potassium levels and low sodium (during 1x) and chloride levels (during both 1x and 3x) in the leaf tissue.
A strict control over transpirational water loss via stomata (formed by pair of guard cells) is important to maintain plant water balance. Aperture size of the stomata is regulated by the turgidity of the guard cells. More turgid the guard cells, bigger the apertures are and hence more transpiration. Under osmotic stress, the water loss is reduced which was evident in the salt sensitive A. thaliana plants under both short and long-time saline growth conditions. As the osmotic stress was only increased during long time saline growth conditions in T. salsuginea therefore, water loss was also decreased only under these saline conditions. Environmental CO2 assimilation also takes place via stomata in plants which then is used for photosynthesis. Stomatal apertures also influence CO2 assimilation. As the light absorbing photosynthetic pigments were more affected in A. thaliana, therefore photosynthetic activity of the whole plant was also reduced. Similarly, both short and long-time saline growth conditions also reduced the effective quantum yield of A. thaliana guard cells. Growth of the plant is dependent on energy which comes from photosynthesis. Reduced environmental CO2 assimilation would affect photosynthesis and hence growth, which was clearly observed in A. thaliana guard cells under long-time saline growth conditions.
Major differences in both guard cells types were observed in their chloride and potassium levels. Energy Dispersive X-Ray Analysis (EDXA) suggested strict control of chloride accumulation in T. salsuginea guard cells as the levels remain unchanged under all conditions. Similarly, use of sodium in place of potassium for osmotic adjustments seems to be dependent on Na+/K+ rations in both guard cell types. Increased salt ions and reduced potassium levels in A. thaliana guard cells posed negative effect on photochemistry which in turn increased ROS metabolism and reduced energy related pathways at transcriptomic level in this plant species. Moreover, photosynthesis was strongly affected in A. thaliana guard cells both at transcriptomic and physiological levels. Similarly, global phytohormones induced changes were more evident in A. thaliana guard cells especially on 3x salt medium. Among all phytohormones, genes under the control of auxin were more differentially expressed in A. thaliana guard cells which suggests wide changes in growth and development in this plant species under salinity.
Phytohormone, ABA is vital for closing the stomata under abiotic stress conditions. Increased levels of ABA during saline conditions led to efflux of potassium and counter anions (chloride, malate, nitrate) from the guard cells which caused the outward flow of water and hence reduction in turgor pressure. Reduced turgor pressure led to reduced water loss and CO2 assimilation especially in A. thaliana. Guard cells of both plant species synthesized ABA during saline conditions which was reflected from transcriptomic data and ABA quantification in the guard cells. ABA induced signaling in both plant species varied at the ABA receptor (PYL/PYR) levels where totally contrasting responses were observed. PYL2, PYL8 and PYL9 were specific to A. thaliana, furthermore, PYL2 was found to be differentially expressed only under 3x salt growth conditions thus suggesting its role during long term salt stress in this plant species. Protein phosphatases, which negatively regulate ABA signaling on one hand and act as ABA sensor on the other hand were found to be more differentially expressed in A. thaliana than T. salsuginea guard cells, which suggests their diverse role in both plant species under saline conditions. Differential expression of more ABA signaling players in long time saline conditions was prominent which could be because of darkness, as it is well known that rapid closure of stomata under dark conditions require ABA signaling. Moreover, representation of these components in dark also suggests that plants become more sensitive to dark under saline conditions which is also evident from the transpiration rates.
Altogether, increased salt ions in A. thaliana guard cells and leaves led to pigment degradation and ABA induced reduction in transpiration which in turn influenced its growth. In contrast, T. salsuginea is the salt excluder and therefore keeps low levels of salt ions especially the chloride both in leaves and guard cells which mildly affects its growth. Guard cells of A. thaliana encounter severe energy problems at physiological and transcriptomic level. Main differences in the ABA signalling between both plant species were observed at the ABA receptor level.
Summary
Bees, like many other organisms, evolved an endogenous circadian clock, which enables them to foresee daily environmental changes and exactly time foraging flights to periods of floral resource availability. The social lifestyle of a honey bee colony has been shown to influence circadian behavior in nurse bees, which do not exhibit rhythmic behavior when they are nursing. On the other hand, forager bees display strong circadian rhythms. Solitary bees, like the mason bee, do not nurse their offspring and do not live in hive communities, but face the same daily environmental changes as honey bees. Besides their lifestyle mason and honey bees differ in their development and life history, because mason bees overwinter after eclosion as adults in their cocoons until they emerge in spring. Honey bees do not undergo diapause and have a relatively short development of a few weeks until they emerge. In my thesis, I present a comparison of the circadian clock of social honey bees (Apis mellifera) and solitary mason bees (Osmia bicornis and Osmia cornuta) on the neuroanatomical level and behavioral output level.
I firstly characterized in detail the localization of the circadian clock in the bee brain via the expression pattern of two clock components, namely the clock protein PERIOD (PER) and the neuropeptide Pigment Dispersing Factor (PDF), in the brain of honey bee and mason bee. PER is localized in lateral neuron clusters (which we called lateral neurons 1 and 2: LN1 and LN2) and dorsal neuron clusters (we called dorsal lateral neurons and dorsal neurons: DLN, DN), many glia cells and photoreceptor cells. This expression pattern is similar to the one in other insect species and indicates a common ground plan of clock cells among insects. In the LN2 neuron cluster with cell bodies located in the lateral brain, PER is co-expressed with PDF. These cells build a complex arborization network throughout the brain and provide the perfect structure to convey time information to brain centers, where complex behavior, e.g. sun-compass orientation and time memory, is controlled. The PDF arborizations centralize in a dense network (we named it anterio-lobular PDF hub: ALO) which is located in front of the lobula. In other insects, this fiber center is associated with the medulla (accessory medulla: AME). Few PDF cells build the ALO already in very early larval development and the cell number and complexity of the network grows throughout honey bee development. Thereby, dorsal regions are innervated first by PDF fibers and, in late larval development, the fibers grow laterally to the optic lobe and central brain. The overall expression pattern of PER and PDF are similar in adult social and solitary bees, but I found a few differences in the PDF network density in the posterior protocerebrum and the lamina, which may be associated with evolution of sociality in bees.
Secondly, I monitored activity rhythms, for which I developed and established a device to monitor locomotor activity rhythms of individual honey bees with contact to a mini colony in the laboratory. This revealed new aspects of social synchronization and survival of young bees with indirect social contact to the mini colony (no trophalaxis was possible). For mason bees, I established a method to monitor emergence and locomotor activity rhythms and I could show that circadian emergence rhythms are entrainable by daily temperature cycles. Furthermore, I present the first locomotor activity rhythms of solitary bees, which show strong circadian rhythms in their behavior right after emergence. Honey bees needed several days to develop circadian locomotor rhythms in my experiments. I hypothesized that honey bees do not emerge with a fully matured circadian system in the hive, while solitary bees, without the protection of a colony, would need a fully matured circadian clock right away after emergence. Several indices in published work and preliminary studies support my hypothesis and future studies on PDF expression in different developmental stages in solitary bees may provide hard evidence.
Background
Acute graft-versus-host disease (aGVHD) poses a major limitation for broader therapeutic application of allogeneic hematopoietic cell transplantation (allo-HCT). Early diagnosis of aGVHD remains difficult and is based on clinical symptoms and histopathological evaluation of tissue biopsies. Thus, current aGVHD diagnosis is limited to patients with established disease manifestation. Therefore, for improved disease prevention it is important to develop predictive assays to identify patients at risk of developing aGVHD. Here we address whether insights into the timing of the aGVHD initiation and effector phases could allow for the detection of migrating alloreactive T cells before clinical aGVHD onset to permit for efficient therapeutic intervention.
Methods
Murine major histocompatibility complex (MHC) mismatched and minor histocompatibility antigen (miHAg) mismatched allo-HCT models were employed to assess the spatiotemporal distribution of donor T cells with flow cytometry and in vivo bioluminescence imaging (BLI). Daily flow cytometry analysis of peripheral blood mononuclear cells allowed us to identify migrating alloreactive T cells based on homing receptor expression profiles.
Results
We identified a time period of 2 weeks of massive alloreactive donor T cell migration in the blood after miHAg mismatch allo-HCT before clinical aGVHD symptoms appeared. Alloreactive T cells upregulated α4β7 integrin and P-selectin ligand during this migration phase. Consequently, targeted preemptive treatment with rapamycin, starting at the earliest detection time of alloreactive donor T cells in the peripheral blood, prevented lethal aGVHD.
Conclusions
Based on this data we propose a critical time frame prior to the onset of aGVHD symptoms to identify alloreactive T cells in the peripheral blood for timely and effective therapeutic intervention.
A mouse model for genetic deletion of presynaptic BDNF from adult hippocampal mossy fiber terminals
(2020)
Brain-derived neurotrophic factor (BDNF) is a modulator and mediator of structural and functional plasticity at synapses in the central nervous system. Despite our profound knowledge about the synaptic function of BDNF at synapses, it is still controversially discussed whether synaptic BDNF acts primarily from pre- or postsynaptic sites. In the central nervous system, several studies show that mossy fiber (MF) projections formed by hippocampal granule neurons store the highest amount of BDNF. However, immunofluorescence and RNA labelling studies suggest that MF BDNF is primarily produced by granule neurons. Multiple other studies prefer the view that BDNF is primarily produced by postsynaptic neurons such as CA3 pyramidal neurons. Here, we question whether the BDNF, which is stored in the mossy fiber synapse, is primarily produced by granule neurons or whether by other cells in the MF-CA3 microcircuit. After standardization of immunolabelling of BDNF, confocal imaging confirmed the localization of BDNF in presynaptic MF terminals. This anterograde location of synaptic BDNF was also found in distinct regions of the fear and anxiety circuit, namely in the oval nucleus of the bed nucleus stria terminals (ovBNST) and in the central amygdala. To find out whether the presynaptic BDNF location is due to protein translation in the corresponding presynaptic dentate gyrus (DG) granule neuron, we developed and characterized a mouse model that exhibits BDNF deletion specifically from adult DG granule neurons. In this mouse model, loss of presynaptic BDNF immunoreactivity correlated with the specific Creactivity in granule neurons, thus confirming that MF BDNF is principally released by granule neurons. After BDNF deletion from granule neurons, we observed more immature neurons with widely arborized dendritic trees. This indicated that local BDNF deletion also affects the local adult neurogenesis, albeit Cre-mediated BDNF deletion only occur in adult granule neurons. Since BDNF is a master regulator of structural synaptic plasticity, it was questioned whether it is possible to visualize presynaptic, synapse-specific, structural plasticity in mossy fiber synapses. It was established that a combination of Cre-techniques together with targeting of GFP to membranes with the help of palmitoylation / myristoylation anchors was able to distinctly outline the synaptic structure of the BDNF-containing MF synapse. In summary, the mouse model characterized in here is suited to investigate the synaptic signalling function of presynaptic BDNF at the mossy fiber terminal, a model synapse to investigate microcircuit information processing from molecule to behaviour.
Whereas G-protein coupled receptors (GPCRs) have been long believed to signal through cyclic AMP exclusively at cell surface, our group has previously shown that GPCRs not only signal at the cell surface but can also continue doing so once internalized together with their ligands, leading to persistent cAMP production. This phenomenon, which we originally described for the thyroid stimulating hormone receptor (TSHR) in thyroid cells, has been observed also for other GPCRs. However, the intracellular compartment(s) responsible for such persistent signaling and its consequences on downstream effectors were insufficiently characterized. The aim of this study was to follow by live-cell imaging the trafficking of internalized TSHRs and other involved signaling proteins as well as to understand the consequences of signaling by internalized TSHRs on the downstream activation of protein kinase A (PKA). cAMP and PKA
activity was measured in real-time in living thyroid cells using FRET-based sensors Epac1-camp and AKAR2 respectively. The results suggest that TSH co-internalizes with its receptor and that the internalized TSH/TSHR complexes traffic retrogradely to the trans-Golgi network (TGN). This study also provides evidence that these internalized TSH/TSHR complexes meet an intracellular pool of Gs proteins in sorting endosomes and in TGN and activate it there, as visualized in real-time using a conformational biosensor nanobody, Nb37. Acute Brefeldin A-induced Golgi collapse hinders the retrograde trafficking of TSH/TSHR complexes, leading to reduced cAMP production and PKA signaling. BFA pretreatment was also able to attenuate CREB phosphorylation suggesting that an intact Golgi/TGN organisation is essential
for an efficient cAMP/PKA signaling by internalized TSH/TSHR complexes. Taken together this data provides evidence that internalized TSH/TSHR complexes meet and activate Gs proteins in sorting endosomes and at the TGN, leading to a local activation of PKA and consequently increased CREB activation. These findings suggest unexpected functions for receptor internalization, with major pathophysiological and pharmacological implications.
The culture of human induced pluripotent stem cells (hiPSCs) at large-scale becomes feasible with the aid of scalable suspension setups in continuously stirred tank reactors (CSTRs). Suspension cul- tures of hiPSCs are characterized by the self-aggregation of single cells into macroscopic cell aggre- gates that increase in size over time. The development of these free-floating aggregates is dependent on the culture vessel and thus represents a novel process parameter that is of particular interest for hiPSC suspension culture scaling. Further, aggregates surpassing a critical size are prone to spon- taneous differentiation or cell viability loss. In this regard, and, for the first time, a hiPSC-specific suspension culture unit was developed that utilizes in situ microscope imaging to monitor and to characterize hiPSC aggregation in one specific CSTR setup to a statistically significant degree while omitting the need for error-prone and time-intensive sampling. For this purpose, a small-scale CSTR system was designed and fabricated by fused deposition modeling (FDM) using an in-house 3D- printer. To provide a suitable cell culture environment for the CSTR system and in situ microscope, a custom-built incubator was constructed to accommodate all culture vessels and process control devices. Prior to manufacture, the CSTR design was characterized in silico for standard engineering parameters such as the specific power input, mixing time, and shear stress using computational fluid dynamics (CFD) simulations. The established computational model was successfully validated by comparing CFD-derived mixing time data to manual measurements. Proof for system functionality was provided in the context of long-term expansion (4 passages) of hiPSCs. Thereby, hiPSC aggregate size development was successfully tracked by in situ imaging of CSTR suspensions and subsequent automated image processing. Further, the suitability of the developed hiPSC culture unit was proven by demonstrating the preservation of CSTR-cultured hiPSC pluripotency on RNA level by qRT-PCR and PluriTest, and on protein level by flow cytometry.
The adaptive immune system is known to provide highly specific and effective immunity against a broad variety of pathogens due to different effector cells. The most prominent are CD4+ T-cells which differentiate after activation into distinct subsets of effector and memory cells, amongst others T helper 1 (Th1) cells. We have recently shown that mouse as well as human Th1 cells depend on T cell receptor (TCR) signals concomitant with CD28 costimulation in order to secrete interferon (IFN) which is considered as their main effector function. Moreover, there is a class of anti-CD28 monoclonal antibodies that is able to induce T cell (re-)activation without concomitant TCR ligation. These so-called CD28-superagonists (CD28-SA) have been shown to preferentially activate and expand CD4+ Foxp3+ regulatory T (Treg) cells and thereby efficaciously conferring protection e.g. against autoimmune responses in rodents and non-human primates. Considering this beneficial effect, CD28-SA were thought to be of great impact for immunotherapeutic approaches and a humanized CD28-SA was subjected to clinical testing starting with a first-in-man trial in London in 2006. Unexpectedly, the volunteers experienced life-threatening side effects due to a cytokine release syndrome (CRS) that was unpredicted by the preclinical studies prior to the trial. Retrospectively, CD4+ memory T cells within the tissues were identified as source of pro-inflammatory cytokines released upon CD28-SA administration. This was not predicted by the preclinical testing indicating a need for more reliable and predictive animal models. Whether mouse CD4+ T cells are generally irresponsive to CD28-SA stimulation or rather the lack of a bona fide memory T cell compartment in cleanly housed specific-pathogen-free (SPF) mice is the reason why the rodent models failed to predict the risk for a CRS remained unclear. To provide SPF mice with a true pool of memory/effector T cells, we transferred in vitro differentiated TCR-transgenic OT-II Th1 cells into untreated recipient mice. Given that Treg cells suppress T cell activation after CD28- SA injection in vivo, recipients were either Treg-competent or Treg-deficient, wild type or DEREG mice, respectively. Subsequent CD28-SA administration resulted in induction of systemic pro-inflammatory cytokine release, dominated by IFN, that was observed to be much more pronounced and robust in Treg-deficient recipients. Employing a newly established in vitro system mirroring the in vivo responses to CD28-SA stimulation of Th1 cells revealed that antigen-presenting cells (APCs) amplify CD28-SAinduced IFN release by Th1 cells due to CD40/CD40L-interactions. Thus, these data are the first to show that mouse Th1 cells are indeed sensitive to CD28-SA stimulation in vivo and in vitro responding with strong IFN release accompanied by secretion of further pro-inflammatory cytokines, which is compatible with a CRS. In conclusion, this study will facilitate preclinical testing of immunomodulatory agents providing a mouse model constituting more “human-like” conditions allowing a higher degree of reliability and translationability.
From the simplest single-cellular organism to the most complex multicellular life forms, genetic information in form of DNA represents the universal basis for all biological processes and thus for life itself. Maintaining the structural and functional integrity of the genome is therefore of paramount importance for every single cell. DNA itself, as an active and complex macromolecular structure, is both substrate and product of many of these biochemical processes. A cornerstone of DNA maintenance is thus established by the tight regulation of the multitude of reactions in DNA metabolism, repressing adverse side reactions and ensuring the integrity of DNA in sequence and function. The family of RecQ helicases has emerged as a vital class of enzymes that facilitate genomic integrity by operating in a versatile spectrum of nucleic acid metabolism processes, such as DNA replication, repair, recombination, transcription and telomere stability. RecQ helicases are ubiquitously expressed and conserved in all kingdoms of life. Human cells express five different RecQ enzymes, RecQ1, BLM, WRN, RecQ4 and RecQ5, which all exhibit individual as well as overlapping functions in the maintenance of genomic integrity. Dysfunction of three human RecQ helicases, BLM, WRN and RecQ4, causes different heritable cancer susceptibility syndromes, supporting the theory that genomic instability is a molecular driving force for cancer development. However, based on their inherent DNA protective nature, RecQ helicases represent a double-edged sword in the maintenance of genomic integrity. While their activity in normal cells is essential to prevent cancerogenesis and cellular aging, cancer cells may exploit this DNA protective function by the overexpression of many RecQ helicases, aiding to overcome the disadvantageous results of unchecked DNA replication and simultaneously gaining resistance against chemotherapeutic drugs. Therefore, detailed knowledge how RecQ helicases warrant genomic integrity is required to understand their implication in cancerogenesis and aging, thus setting the stage to develop new strategies towards the treatment of cancer.
The current study presents and discusses the first high-resolution X-ray structure of the human RecQ4 helicase. The structure encompasses the conserved RecQ4 helicase core, including a large fraction of its unique C- terminus. Our structural analysis of the RecQ4 model highlights distinctive differences and unexpected similarities to other, structurally conserved, RecQ helicases and permits to draw conclusions about the functional implications of the unique domains within the RecQ4 C-terminus. The biochemical characterization of various RecQ4 variants provides functional insights into the RecQ4 helicase mechanism, suggesting that RecQ4 might utilize an alternative DNA strand separation technique, compared to other human RecQ family members. Finally, the RecQ4 model permits for the first time the analysis of multiple documented RecQ4 patient mutations at the atomic level and thus provides the possibility for an advanced interpretation of particular structure-function relationships in RecQ4 pathogenesis.
The learned helplessness phenomenon is a specific animal behavior induced by prior exposure to uncontrollable aversive stimuli. It was first found by Seligman and Maier (1967) in dogs and then has been reported in many other species, e.g. in rats (Vollmayr and Henn, 2001), in goldfishes (Padilla, 1970), in cockroaches (Brown, 1988) and also in fruit flies (Brown, 1996; Bertolucci, 2008). However, the learned helplessness effect in fruit flies (Drosophila melanogaster) has not been studied in detail. Thus, in this doctoral study, we investigated systematically learned helplessness behavior of Drosophila for the first time.
Three groups of flies were tested in heatbox. Control group was in the chambers experiencing constant, mild temperature. Second group, master flies were punished in their chambers by being heated if they stopped walking for 0.9s. The heat pulses ended as soon as they resumed walking again. A third group, the yoked fly, was in their chambers at the same time. However, their behavior didn’t affect anything: yoked flies were heated whenever master flies did, with same timing and durations. After certain amount of heating events, yoked flies associated their own behavior with the uncontrollability of the environment. They suppressed their innate responses such as reducing their walking time and walking speed; making longer escape latencies and less turning around behavior under heat pulses. Even after the conditioning phase, yoked flies showed lower activity level than master and control flies. Interestingly, we have also observed sex dimorphisms in flies. Male flies expressed learned helplessness not like female flies. Differences between master and yoked flies were smaller in male than in female flies. Another interesting finding was that prolonged or even repetition of training phases didn’t enhance learned helplessness effect in flies.
Furthermore, we investigated serotonergic and dopaminergic nervous systems in learned helplessness. Using genetic and pharmacological manipulations, we altered the levels of serotonin and dopamine in flies’ central nervous system. Female flies with reduced serotonin concentration didn’t show helpless behavior, while the learned helplessness effect in male flies seems not to be affected by a reduction of serotonin. Flies with lower dopamine level do not display the learned helplessness effect in the test phase, suggesting that with low dopamine the motivational change in learned helplessness in Drosophila may decline faster than with a normal dopamine level.
Tumor necrosis factor (TNF) receptor-2 (TNFR2) has attracted considerable interest as a target for immunotherapy. Indeed, using oligomeric fusion proteins of single chain-encoded TNFR2-specific TNF mutants (scTNF80), expansion of regulatory T cells and therapeutic activity could be demonstrated in various autoinflammatory diseases, including graft-versus-host disease (GvHD), experimental autoimmune encephalomyelitis (EAE) and collagen-induced arthritis (CIA). With the aim to improve the in vivo availability of TNFR2-specific TNF fusion proteins, we used here the neonatal Fc receptor (FcRn)-interacting IgG1 molecule as an oligomerizing building block and generated a new TNFR2 agonist with improved serum retention and superior in vivo activity.
Methods
Single-chain encoded murine TNF80 trimers (sc(mu)TNF80) were fused to the C-terminus of an in mice irrelevant IgG1 molecule carrying the N297A mutation which avoids/minimizes interaction with Fcγ-receptors (FcγRs). The fusion protein obtained (irrIgG1(N297A)-sc(mu)TNF80), termed NewSTAR2 (New selective TNF-based agonist of TNF receptor 2), was analyzed with respect to activity, productivity, serum retention and in vitro and in vivo activity. STAR2 (TNC-sc(mu)TNF80 or selective TNF-based agonist of TNF receptor 2), a well-established highly active nonameric TNFR2-specific variant, served as benchmark. NewSTAR2 was assessed in various in vitro and in vivo systems.
Results
STAR2 (TNC-sc(mu)TNF80) and NewSTAR2 (irrIgG1(N297A)-sc(mu)TNF80) revealed comparable in vitro activity. The novel domain architecture of NewSTAR2 significantly improved serum retention compared to STAR2, which correlated with efficient binding to FcRn. A single injection of NewSTAR2 enhanced regulatory T cell (Treg) suppressive activity and increased Treg numbers by > 300% in vivo 5 days after treatment. Treg numbers remained as high as 200% for about 10 days. Furthermore, a single in vivo treatment with NewSTAR2 upregulated the adenosine-regulating ectoenzyme CD39 and other activation markers on Tregs. TNFR2-stimulated Tregs proved to be more suppressive than unstimulated Tregs, reducing conventional T cell (Tcon) proliferation and expression of activation markers in vitro. Finally, singular preemptive NewSTAR2 administration five days before allogeneic hematopoietic cell transplantation (allo-HCT) protected mice from acute GvHD.
Conclusions
NewSTAR2 represents a next generation ligand-based TNFR2 agonist, which is efficiently produced, exhibits improved pharmacokinetic properties and high serum retention with superior in vivo activity exerting powerful protective effects against acute GvHD.
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.
Recently, it was shown that MDA-MB-231 breast cancer cells express very high levels of the A2BAR as the sole adenosine receptor subtype, and stimulation of the A2BAR in MDA-MB-231 cells triggers an unusual inhibitory signal on ERK1/2 phosphorylation. The ERK1/2 pathway is reported to be associated with the control of growth, proliferation and differentiation of cells and as such might serve as a promising target for tumor treatment. The present study investigated signaling mechanisms involved in linking A2BAR to ERK1/2 phosphorylation in MDA-MB-231 cells. The A2BAR mediated reduction of ERK1/2 phosphorylation and of proliferation of MDA-MB-231 cell is in good agreement with previous results from (Dubey et al., 2005). These observations provide support to the hypothesis that activation of A2BAR could attenuate the growth of some types of cancer cell and argue against a stimulation of proliferation resulting from the activation of A2BAR as discussed by (Fernandez-Gallardo et al., 2016). AC activation by forskolin has recently been shown to enhance the activity of the chemotherapeutic agent doxorubicin in TNBC cells via a mechanism dependent on the PKA-mediated inhibition of ERK1/2 phosphorylation. Furthermore, forskolin also increased the sensitivity of MDA-MB-231 and MDA-MB-468 triple negative breast cancer cells to 5-fluorouracil and taxol (Illiano et al., 2018), and sustains the evidence of anticancer activity mediated by cAMP/PKA-mediated ERK1/2 inhibition. Similar to these studies, a reduced amount of pERK1/2 was also observed after stimulation of AC with FSK, application of cAMP-AM or inhibition of PDE-4. The inhibition of ERK1/2 phosphorylation was mimicked by UTP and abolished with the PLC inhibitor U73122 or by chelating intracellular Ca2+ with BAPTA-AM. These results point to an important role for both cAMP and Ca2+ signaling in the pathway leading to a decrease in ERK1/2 phosphorylation. This study encourages the idea that A2BAR could be used as target in cancer therapy. But A2BAR did not only stimulate signaling cascades associated with cell survival and proliferation reduction, but also key phases relevant in angiogenesis like Ca2+ mobilization (Kohn et al., 1995). Whereas the potency toward AC and Ca2+ are similar for the diverse agonists, the potency to promote ERK1/2 reduction is much higher. Interestingly, the proliferation of MDA-MB-231 cells is inhibited by low nanomolar agonist concentration which is inactive in Ca2+ mobilization. This means that it is certainly possible to reduce the proliferation without promoting angiogenesis. LUF6210 is particularly interesting when considering that it preferentially stimulates a reduction in ERK1/2 phosphorylation over Ca2+ and therefore may not promote angiogenesis. LUF6210 is therapeutically appealing as adjuvant in treatment of cancer. Given that stimulation of AC can activate a reduction of ERK1/2 phosphorylation and proliferation in cancer cells, agonist bias toward Gs-AC-PKA-mediated ERK1/2 inhibition represent a potential therapy of various malignancies. The fact that the reduction of ERK1/2 phosphorylation followed by reduced proliferation observed in MDA-MB-231 cells were mediated by the activation of the A2BAR illustrates the importance of this receptor subtype in cancer. A2BARs must be considered as a key factor in cancer treatment and deserve attention for the development of new therapeutic strategies.
This work deals with the acceleration of cardiovascular MRI for the assessment
of functional information in steady-state contrast and for viability assessment
during the inversion recovery of the magnetization. Two approaches
are introduced and discussed in detail. MOCO-MAP uses an exponential
model to recover dynamic image data, IR-CRISPI, with its low-rank plus
sparse reconstruction, is related to compressed sensing.
MOCO-MAP is a successor to model-based acceleration of parametermapping
(MAP) for the application in the myocardial region. To this end, it
was augmented with a motion correction (MOCO) step to allow exponential
fitting the signal of a still object in temporal direction. Iteratively, this
introduction of prior physical knowledge together with the enforcement of
consistency with the measured data can be used to reconstruct an image
series from distinctly shorter sampling time than the standard exam (< 3 s
opposed to about 10 s). Results show feasibility of the method as well as
detectability of delayed enhancement in the myocardium, but also significant
discrepancies when imaging cardiac function and artifacts caused already by
minor inaccuracy of the motion correction.
IR-CRISPI was developed from CRISPI, which is a real-time protocol
specifically designed for functional evaluation of image data in steady-state
contrast. With a reconstruction based on the separate calculation of low-rank
and sparse part, it employs a softer constraint than the strict exponential
model, which was possible due to sufficient temporal sampling density via
spiral acquisition. The low-rank plus sparse reconstruction is fit for the use on
dynamic and on inversion recovery data. Thus, motion correction is rendered
unnecessary with it.
IR-CRISPI was equipped with noise suppression via spatial wavelet filtering.
A study comprising 10 patients with cardiac disease show medical
applicability. A comparison with performed traditional reference exams offer
insight into diagnostic benefits. Especially regarding patients with difficulty
to hold their breath, the real-time manner of the IR-CRISPI acquisition provides
a valuable alternative and an increase in robustness.
In conclusion, especially with IR-CRISPI in free breathing, a major acceleration
of the cardiovascular MR exam could be realized. In an acquisition
of less than 100 s, it not only includes the information of two traditional
protocols (cine and LGE), which take up more than 9.6 min, but also allows
adjustment of TI in retrospect and yields lower artifact level with similar
image quality.
In this work, accelerated non-Cartesian Magnetic Resonance Imaging (MRI) methods were established and applied to cardiovascular imaging (CMR) at different magnetic field strengths (3T and 7T).
To enable rapid data acquisition, highly efficient spiral k-space trajectories were created. In addition, hybrid sampling patterns such as the twisting radial lines (TWIRL) k-space trajectory were studied.
Imperfections of the dynamic gradient system of a MR scanner result in k-space sampling errors. Ultimately, these errors can lead to image artifacts in non-Cartesian acquisitions.
Among other reasons such as an increased reconstruction complexity, they cause the lack of spiral sequences in clinical routine compared to standard Cartesian imaging.
Therefore, the Gradient System Transfer Functions (GSTFs) of both scanners were determined and used for k-space trajectory correction in post-correction as well as in terms of a pre-emphasis.
The GSTF pre-emphasis was implemented as a fully automatic procedure, which enabled a precise correction of arbitrary gradient waveforms for double-oblique slice orientations.
Consequently, artifacts due to trajectory errors could be mitigated, which resulted in high image quality in non-Cartesian MRI.
Additionally, the GSTF correction was validated by measuring pre-emphasized spiral gradient outputs, which showed high agreement with the theoretical gradient waveforms.
Furthermore, it could be demonstrated that the performance of the GSTF correction is superior to a simple delay compensation approach.
The developed pulse sequences were applied to gated as well as real-time CMR. Special focus lied on the implementation of a spiral imaging protocol to resolve the beating heart of animals and humans in real time and free breathing.
In order to achieve real-time CMR with high spatiotemporal resolution, k-space undersampling was performed. For this reason, efficient sampling strategies were developed with the aim to facilitate compressed sensing (CS) during image reconstruction.
The applied CS approach successfully removed aliasing artifacts and yielded high-resolution cardiac image series. Image reconstruction was performed offline in all cases such that the images were not available immediately after acquisition at the scanner.
Spiral real-time CMR could be performed in free breathing, which led to an acquisition time of less than 1 minute for a whole short-axis stack.
At 3T, the results were compared to the gold standard of electrocardiogram-gated Cartesian CMR in breath hold, which revealed similar values for important cardiovascular functional and volumetric parameters.
This paves the way to an application of the developed framework in clinical routine of CMR.
In addition, the spiral real-time protocol was transferred to swallowing and speech imaging at 3T, and first images were presented.
The results were of high quality and confirm the straightforward utilization of the spiral sequence in other fields of MRI.
In general, the GSTF correction yielded high-quality images at both field strengths, 3T and 7T.
Off-resonance related blurring was mitigated by applying non-Cartesian readout gradients of short duration. At 7T, however, B1-inhomogeneity led to image artifacts in some cases.
All in all, this work demonstrated great advances in accelerating the MRI process by combining efficient, undersampled non-Cartesian k-space coverage with CS reconstruction.
Trajectory correction using the GSTF can be implemented at any scanner model and enables non-Cartesian imaging with high image quality.
Especially MRI of dynamic processes greatly benefits from the presented rapid imaging approaches.
G-protein-coupled receptors (GPCRs) are key biological switches that transmit both internal and external stimuli into the cell interior. Among the GPCRs, the “light receptor” rhodopsin has been shown to activate with a re-arrangement of the transmembrane helix bundle within ≈1 ms, while all other receptors are thought to become activated in subsecond range at saturating concentrations. Here we investigate activation kinetics of a dimeric GPCR, the metabotropic glutamate receptor-1 (mGluR1), and several class A GPCRs, as muscarinic receptor 3 (M3R), adrenergic (α2aAR and β1R) and opioid (µOR) receptors. We first used UV-light-triggered uncaging of glutamate in intact cells. Sub-millisecond Förster resonance energy transfer recordings between labels at intracellular receptor sites were used to record conformational changes in the mGluR1. At millimolar ligand concentrations the initial rearrangement between the mGluR1 subunits occurs at a speed of τ1≈1-2 ms. These rapid changes were followed by significantly slower conformational changes in the transmembrane domain (τ2≈20 ms). We further characterized novel photoswitchable negative allosteric modulators for mGluR1, which bind to its transmembrane core and block the conformational change as well as the downstream signaling. Effects of the compounds were quantified in pharmacological cell assays in the dark and using UV and green light illumination. We finally develop a framework for image-based kinetic analysis of GPCRs which allowed us to measure activation kinetics of several prototypical class A GPCRs and to discover membrane heterogeneities of GPCR activation. It appears that GPCR activation signal is not only dependent on the amount of activated receptors, but also has some level of correlation with the local density of activated receptors.
Barth Syndrome (BTHS) is an inherited X-chromosomal linked disorder, characterized by early development of cardiomyopathy, immune system defects, skeletal muscle myopathy and growth retardation. The disease displays a wide variety of symptoms including heart failure, exercise intolerance and fatigue due to the muscle weakness. The cause of the disease are mutations in the gene encoding for the mitochondrial transacylase Tafazzin (TAZ), which is important for remodeling of the phospholipid cardiolipin (CL). All mutations result in a pronounced decrease of the functional enzyme leading to an increase of monolysocardiolipin (MLCL), the precursor of mature CL, and a decrease in mature CL itself. CL is a hallmark phospholipid of mitochondrial membranes, highly enriched in the inner mitochondrial membrane (IMM). It is not only important for the formation of the cristae structures, but also for the function of different protein complexes associated with the mitochondrial membrane. Reduced levels of mature CL cause remodeling of the respiratory chain supercomplexes, impaired respiration, defects in the Krebs cycle and a loss of mitochondrial calcium uniporter (MCU) protein. The defective Ca2+ handling causes impaired redox homeostasis and energy metabolism resulting in cellular arrhythmias and defective electrical conduction. In an uncompensated situation, blunting mitochondrial Ca2+ uptake provokes increased mitochondrial emission of H2O2 during workload transitions, related to oxidation of NADPH, which is required to regenerate anti-oxidative enzymes. However, in the hearts and cardiac myocytes of mice with a global knock-down of the Taz gene (Taz-KD), no increase in mitochondrial ROS was observed, suggesting that other metabolic pathways may have compensated for reduced Krebs cycle activation.
The healthy heart produces most of its energy by consuming fatty acids. In this study, the fatty acid uptake into mitochondria and their further degradation was investigated, which showed a switch of the metabolism in general in the Taz-KD mouse model. In vivo studies revealed an increase of glucose uptake into the heart and decreased fatty acid uptake and oxidation. Disturbed energy conversion resulted in activation of retrograde signaling pathways, implicating overall changes in the cell metabolism. Upregulated integrated stress response (ISR) was confirmed by increased levels of the downstream target, i.e., the activating transcription factor 4 (ATF4). A Tafazzin knockout mouse embryonal fibroblast cell model (TazKO) was used to inhibit the ISR using siRNA transfection or pharmaceutical inhibition. This verified the central role of
II
the ISR in regulating the metabolism in BTHS. Moreover, an increased metabolic flux into glutathione biosynthesis was observed, which supports redox homeostasis. In vivo PET-CT scans depicted elevated activity of the xCT system in the BTHS mouse heart, which transports essential amino acids for the biosynthesis of glutathione precursors. Furthermore, the stress induced signaling pathway also affected the glutamate metabolism, which fuels into the Krebs cycle via -ketoglutarate and therefore supports energy converting pathways. In summary, this thesis provides novel insights into the energy metabolism and redox homeostasis in Barth syndrome cardiomyopathy and its regulation by the integrated stress response, which plays a central role in the metabolic alterations. The aim of the thesis was to improve the understanding of these metabolic changes and to identify novel targets, which can provide new possibilities for therapeutic intervention in Barth syndrome.
The cytokine interleukin-5 (IL-5) is part of the TH2-mediated immune response. As a key regulator of eosinophilic granulocytes (eosinophils), IL-5 controls multiple aspects of eosinophil life. Eosinophils play a pathogenic role in the onset and progression of atopic diseases as well as hypereosinophilic syndrome (HES). Here, cytotoxic proteins and pro-inflammatory mediators stored in intracellular vesicles termed granula are released upon activation thereby causing local inflammation to fight the pathogen. However, if such inflammation persists, tissue damage and organ failure can occur. Due to the close relationship between eosinophils and IL-5 this cytokine has become a major pharmaceutical target for the treatment of atopic diseases or HES. As observed with other cytokines, IL-5 signals by assembling a heterodimeric receptor complex at the cell surface in a stepwise mechanism. In the first step IL-5 binds to its receptor IL-5Rα (CD125). This membrane-located complex then recruits the so-called common beta chain βc (CD131) into a ternary ligand receptor complex, which leads to activation of intracellular signaling cascades. Based on this mechanism various strategies targeting either IL-5 or IL-5Rα have been developed allowing to specifically abrogate IL-5 signaling. In addition to the classical approach of employing neutralizing antibodies against IL 5/IL-5Rα or antagonistic IL-5 variants, two groups comprising small 18 to 30mer peptides have been discovered, that bind to and block IL-5Rα from binding its activating ligand IL-5. Structure-function studies have provided detailed insights into the architecture and interaction of IL-5IL-5Rα and βc. However, structural information for the ternary IL-5 complex as well as IL-5 inhibiting peptides is still lacking.
In this thesis three areas were investigated. Firstly, to obtain insights into the second receptor activation step, i.e. formation of the ternary ligand-receptor complex IL-5•IL-5Rα•βc, a high-yield production for the extracellular domain of βc was established to facilitate structure determination of the ternary ligand receptor assembly by either X-ray crystallography or cryo-electron microscopy.
In a second project structure analysis of the ectodomain of IL-5Rα in its unbound conformation was attempted. Data on IL-5Rα in its ligand-free state would provide important information as to whether the wrench-like shaped ectodomain of IL-5Rα adopts a fixed preformed conformation or whether it is flexible to adapt to its ligand binding partner upon interaction. While crystallization of free IL-5Rα failed, as the crystals obtained did not diffract X rays to high resolution, functional analysis strongly points towards a selection fit binding mechanism for IL-5Rα instead of a rigid and fixed IL-5Rα structure. Hence IL-5 possibly binds to a partially open architecture, which then closes to the known wrench-like architecture. The latter is then stabilized by interactions within the D1-D2 interface resulting in the tight binding of IL-5.
In a third project X-ray structure analysis of a complex of the IL-5 inhibitory peptide AF17121 bound to the ectodomain of IL-5Rα was performed. This novel structure shows how the small cyclic 18mer peptide tightly binds into the wrench-like cleft formed by domains D1 and D2 of IL-5Rα. Due to the partial overlap of its binding site at IL-5Rα with the epitope for IL-5 binding, the peptide blocks IL-5 from access to key residues for binding explaining how the small peptide can effectively compete with the rather large ligand IL-5. While AF17121 and IL-5 seemingly bind to the same site at IL-5Rα, functional studies however showed that recognition and binding of both ligands differ. With the structure for the peptide-receptor complex at hand, peptide design and engineering could be performed to generate AF17121 analogies with enhanced receptor affinity. Several promising positions in the peptide AF17121 could be identified, which could improve inhibition capacity and might serve as a starting point for AF17121-based peptidomimetics that can yield either superior peptide based IL-5 antagonists or small-molecule-based pharmacophores for future therapies of atopic diseases or the hypereosinophilic syndrome.
Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder with an estimated heritability of around 70%. In order to fully understand ADHD biology it is necessary to incorporate multiple different types of research. In this thesis, both human and animal model research is described as both lines of research are required to elucidate the aetiology of ADHD and development new treatments. The role of a single gene, Adhesion G protein-coupled receptor L3 (ADGRL3) was investigated using a knockout mouse model. ADGRL3 has putative roles in neuronal migration and synapse function. Various polymorphisms in ADGRL3 have been linked with an increased risk of attention deficit/hyperactivity disorder (ADHD) in human studies. Adgrl3-deficient mice were examined across multiple behavioural domains related to ADHD: locomotive activity, visuospatial and recognition memory, gait impulsivity, aggression, sociability and anxiety-like behaviour. The transcriptomic alterations caused by Adgrl3-depletion were analysed by RNA-sequencing of three ADHD-relevant brain regions: prefrontal cortex (PFC), hippocampus and striatum. Increased locomotive activity in Adgrl3-/- mice was observed across all tests with the specific gait analysis revealing subtle gait abnormalities. Spatial memory and learning domains were also impaired in these mice. Increased levels of impulsivity and sociability accompanying decreased aggression were also detected. None of these alterations were observed in Adgrl3+/- mice. The numbers of genes found to exhibit differential expression was relatively small in all brain regions sequenced. The absence of large scale gene expression dysregulation indicates a specific pathway of action, rather than a broad neurobiological perturbation. The PFC had the greatest number of differentially expressed genes and gene-set analysis of differential expression in this brain region detected a number of ADHD-relevant pathways including dopaminergic synapses as well as cocaine and amphetamine addiction. The most dysregulated gene in the PFC was Slc6a3 which codes for the dopamine transporter, a molecule vital to current pharmacological treatment of ADHD. The behavioural and transcriptomic results described in this thesis further validate Adgrl3 constitutive knockout mice as an experimental model of ADHD and provide neuroanatomical targets for future studies involving ADGRL3 modified animal models.
The study of ADHD risk genes such as ADGRL3 requires the gene to be first identified using human studies. These studies may be genome based such as genome wide association studies (GWAS) or transcriptome based using microarray or RNA sequencing technology. To explore ADHD biology in humans the research described in this thesis includes both GWAS and trancriptomic data. A two-step transcriptome profiling was performed in peripheral blood mononuclear cells (PBMCs) of 143 ADHD subjects and 169 healthy controls. We combined GWAS and expression data in an expression-based Polygenic Risk Score (PRS) analysis in a total sample of 879 ADHD cases and 1919 controls from three different datasets. Through this exploratory study we found eight differentially expressed genes in ADHD and no support for the genetic background of the disorder playing a role in the aberrant expression levels identified. These results highlight promising candidate genes and gene pathways for ADHD and support the use of peripheral tissues to assess gene expression signatures for ADHD.
This thesis illustrates how both human and animal model research is required to increase our understanding of ADHD. The animal models provide biological insight into the targets identified in human studies and may themselves provide further relevant gene targets. Only by combining research from disparate sources can we develop the thorough understanding on ADHD biology required for treatment development, which is the ultimate goal of translational science research.