Institutes
Refine
Year of publication
Document Type
- Article (306)
- Doctoral Thesis (173)
- Preprint (41)
- Book (1)
Language
- English (521) (remove)
Has Fulltext
- yes (521)
Is part of the Bibliography
- no (521)
Keywords
- Podospora anserina (8)
- aging (8)
- SARS-CoV-2 (7)
- Cyanobacteria (5)
- Membrane Proteins (5)
- Phylogeny (5)
- mitochondria (5)
- Acetogenesis (4)
- Ecology (4)
- Haloferax volcanii (4)
- Saccharomyces cerevisiae (4)
- Synechococcus (4)
- alternative splicing (4)
- bats (4)
- fungi (4)
- Acetogen (3)
- Bioenergetics (3)
- COVID19-NMR (3)
- Carotenoids (3)
- Evolution (3)
- Lipid and Fatty Acid Composition (3)
- Marine Diatoms (3)
- Membrane Transport (3)
- Microbiology (3)
- Oxidoreductases (3)
- Photooxidation (3)
- Pigmentation (3)
- Protein Structure (3)
- RNA (3)
- Solution NMR spectroscopy (3)
- Taxonomy (3)
- Thermophile (3)
- biodiversity (3)
- structural biology (3)
- zebrafish (3)
- 14CO2 Fixation (2)
- 5′-UTR (2)
- Acetogenic bacteria (2)
- Acinetobacter (2)
- Adhesion (2)
- Aloe (2)
- Amino Acid Pools (2)
- Archaea (2)
- Asphodelaceae (2)
- Bioaccumulation (2)
- Biodiversity (2)
- Biogeography (2)
- Biomarker (2)
- Biomarkers (2)
- Biosynthesis (2)
- Bleaching Herbicides (2)
- Climate change (2)
- Covid19-NMR (2)
- DNA Transformation (2)
- DNA uptake (2)
- Desiccation resistance (2)
- Dicarboxylic acids (2)
- Downy mildew (2)
- Ecological modelling (2)
- Ecotoxicogenomics (2)
- Electron Bifurcation (2)
- Electron Transfer (2)
- Electron Transport (2)
- Energy Conservation (2)
- Energy Metabolism (2)
- Energy conservation (2)
- Entomology (2)
- Enzyme Mechanisms (2)
- European beech (2)
- Host-parasite interaction (2)
- Iron-Sulfur Protein (2)
- Land cover (2)
- Light-sheet microscopy (2)
- MICOS (2)
- Magnetic compass (2)
- Maxent (2)
- Membrane Biogenesis (2)
- Metabolic Engineering (2)
- Metabolic engineering (2)
- Metabolism (2)
- Metalloenzymes (2)
- Methylorubrum extorquens (2)
- Methylorubrum extorquens AM1 (2)
- Microplastic (2)
- Mitochondria (2)
- Modification (2)
- Morphogenesis (2)
- Morphology (2)
- NMR (2)
- NMR spectroscopy (2)
- Non-invasive sampling (2)
- Oaks (2)
- Oomycetes (2)
- Peronosporaceae (2)
- Photosynthesis (2)
- Phycocyanin-Free Lamellae (2)
- Protein Translocation (2)
- Psychology (2)
- Risk assessment (2)
- Solution NMR-spectroscopy (2)
- Species distribution modelling (2)
- Synaptic transmission (2)
- Synchron Cultures (2)
- Thermus (2)
- Transcriptomics (2)
- Trypanosoma cruzi (2)
- UV-B Stress (2)
- Wood-Ljungdahl pathway (2)
- Wood–Ljungdahl pathway (2)
- Xenorhabdus (2)
- Zebrafish (2)
- angiogenesis (2)
- aroma (2)
- autophagy (2)
- bacteria (2)
- biodiversity protection (2)
- biosynthesis (2)
- carotenoid biosynthesis (2)
- climate (2)
- climate change (2)
- color (2)
- community composition (2)
- conservation (2)
- conservation funding (2)
- conservation genetics (2)
- conservation planning (2)
- cox2 (2)
- cristae (2)
- cryptochrome (2)
- decision making (2)
- development (2)
- environmental attitudes (2)
- environmental education (2)
- extremophile (2)
- gene expression (2)
- genomics (2)
- global change (2)
- heat stress (2)
- inclination compass (2)
- integrins (2)
- long non-coding RNA (2)
- metabarcoding (2)
- microglia (2)
- morphology (2)
- nuclear magnetic resonance (NMR) (2)
- peroxisomes (2)
- population genetics (2)
- population genomics (2)
- post-2020 biodiversity targets (2)
- pre-mRNA (2)
- prefrontal cortex (2)
- prostate carcinoma cells (2)
- sleep (2)
- strategic site selection (2)
- structure–activity relationships (2)
- tumor microenvironment (2)
- 14C- and 15N-Assimilation (1)
- 15N-Labelled Amino Acids (1)
- 16S rRNA gene (1)
- 18S rRNA gene (1)
- 2030 Agenda (1)
- 3-Hydroxybutyric acid (1)
- 5'-UTR (1)
- 5-Hydroxyaloin A (1)
- 5_SL4 (1)
- ABR (1)
- AChE (1)
- ADAM15 (1)
- ADCD (1)
- ALE (1)
- AMPK (1)
- ATG24 (1)
- ATP (1)
- Absorption Spectra (1)
- Acetobacterium (1)
- Acetogenic metabolism (1)
- Acid transporters (1)
- Active Particles (1)
- Adenosine (1)
- Aedes (1)
- Agent-based modeling (1)
- Aging (1)
- Aging Phenomenon (1)
- Aichi targets (1)
- Air Pollutants (1)
- Alien species (1)
- Allohormone pheromones (1)
- Alphaproteobacteria (1)
- Amino Acids (1)
- Amphibia (1)
- Amplexus (1)
- Anabaena flos-aquae (1)
- Anacystis (1)
- Anaerobes (1)
- Anaerobic bacteria (1)
- Androst-4-en-3,17-dione (1)
- Anion Transport System (1)
- Anthraquinones (1)
- Anthropocene (1)
- Antibiotic Resistance (1)
- Antibiotics and Metabolite Export (1)
- Antioxidants (1)
- Aphanomyces astaci (1)
- Apoptosis (1)
- Aposematism (1)
- Aquilegia (1)
- Arabidopsis thaliana (1)
- Arctic Ocean (1)
- Ascomycota (1)
- Assignment (1)
- Assimilation of 15N-Nitrate (1)
- Asymmetrie Reconstitution (1)
- Auditory midbrain (1)
- Autism Spectrum Disorder (1)
- Autism Spectrum disorder (1)
- Automobile Exhaust (1)
- B chromosome (1)
- Bacillariaphyceae (1)
- Bacillus (1)
- Background expression (1)
- Bacteria (1)
- Bacterial Metabolism (1)
- Bacterial genes (1)
- Bacterial physiology (1)
- Bacterial structural biology (1)
- Bacteriology (1)
- Baleen whales (1)
- Band 3 Protein (1)
- Bartonella henselae (1)
- Basidiomycota (1)
- Benin (1)
- Benthic environment (1)
- Biochemistry (1)
- Biodiversity tools and pipelines (1)
- Bioenergetics/Electron Transfer Complex (1)
- Bioengineering (1)
- Biofuels (1)
- Biohydrogen (1)
- Biological anthropology (1)
- Bioreactor (1)
- Biosecurity (1)
- Biotechnology (1)
- Biotic interactions (1)
- Biotransformation (1)
- Body burden (1)
- Bogert’s rule (1)
- Bolivia (1)
- Bovidae (1)
- Brain-stimulus synchrony (1)
- Breeding glands (1)
- Brudenell River (1)
- Bungarus (1)
- Bungarus niger (1)
- Bungarus walli (1)
- Business strategy in drug development (1)
- Butyrate (1)
- CAZy (1)
- CLP protease (1)
- CNV 16p11.2 (1)
- COVID-19 (1)
- CRISPR-Cas9 (1)
- CRISPR-Cas9 gene conversion (1)
- CXCL12 (1)
- CXCR4 (1)
- CaMPARI (1)
- Caffeate Respiration (1)
- Calathea (1)
- Calmodulin (1)
- Canada (1)
- Canis lupus (1)
- Canis lupus familiaris (1)
- Carbohydrates (1)
- Carbon capture (1)
- Carbon cycling (1)
- Cardiac regeneration (1)
- Cardiac remodeling (1)
- Carnivora (1)
- Carnivores (1)
- Carotene Isomerase (1)
- Carotenoid Desaturation (1)
- Castor bean tick (1)
- Catalase (1)
- Cation Proton Antiporter (1)
- Cell Wall (1)
- Cellular microbiology (1)
- Cellulase gene expression (1)
- Cercospora (1)
- Chagas disease (1)
- Chaperone Chaperonin (1)
- Chaperones (1)
- Chemical communication (1)
- Chemical dispersant (1)
- Chemical dispersants (1)
- Chemistry (1)
- Chemotaxonomy (1)
- Chironomus riparius (1)
- Chlorophyll (1)
- Chlorophyll Fluorescence (1)
- Chlorophyll Formation (1)
- Chlorophyll fluorescence (1)
- Chloroplast (1)
- Chlorosis (1)
- Chromatin (1)
- Chromones (1)
- Chrysops (1)
- Climate (1)
- Climate Change (1)
- Climate-change ecology (1)
- Climatic conditions (1)
- Closely related fungal species (1)
- ClpB (1)
- Coevolution (1)
- Colorectal Cancer (1)
- Community barcoding (1)
- Community ecology (1)
- Computational model (1)
- Conservation (1)
- Conservation biology (1)
- Coronaries (1)
- Cortex (1)
- Cortical column (1)
- Costs (1)
- Crude oil (1)
- Crustacea (1)
- Crystal Structure (1)
- Cucumis sativus (Cucumber) (1)
- Cumate (1)
- D. magna (1)
- DCMU-Type Inhibitors (1)
- DCMU-Type Inhibitors Shade Adaptation (1)
- DEPDC5 (1)
- DNA Amplification Fingerprinting (1)
- DNA metabarcoding (1)
- DNA-Specific Labelling (1)
- Daboia russelii (1)
- Dark fermentation (1)
- Data standard (1)
- Data standards (1)
- Dehydration (medicine) (1)
- Dental Tissues (1)
- Depth (1)
- Development (1)
- Diatomophthora (1)
- Dicellomyces (1)
- Dimer Yield Ratio (1)
- Dimerization domain (1)
- Dioscorea (1)
- Diosgenin Production (1)
- Direct seeding (1)
- Discovery (1)
- Diseases (1)
- Dispersal capacity (1)
- Dissemination (1)
- Diversity (1)
- Drought (1)
- Drought reaction (1)
- Drug discovery (1)
- Drug therapy (1)
- Dynamics (1)
- E-NTPDase (1)
- ER (1)
- ERAL1 (1)
- EROD (1)
- Earth sciences (1)
- EcNhaA (1)
- Ech (1)
- Ecological niche modelling (1)
- Ecological requirements (1)
- Ecosystem Services (1)
- Ecotoxicology (1)
- Ecto-5'-nucleotidase (1)
- Ectrogella (1)
- Electron Microscopy (1)
- Electron transport chain (1)
- Electron-bifurcating hydrogenase (1)
- Electrophysiology (1)
- Elimination of Rho Factor (1)
- Embryo toxicity (1)
- Embryogenesis (1)
- Emerging insect model organisms (1)
- Endocrine-disrupting compounds (1)
- Endothelial (1)
- Endothelial-to-mesenchymal transition (1)
- Engineering (1)
- Entolomataceae (1)
- Entorrhizales (1)
- Envelope (1)
- Environmental factors (1)
- Environmental fate (1)
- Environmental partitioning (1)
- Environmental studies (1)
- Enzyme Induction (1)
- Enzyme Kinetics (1)
- Enzyme engineering (1)
- EphrinB2 (1)
- Equilibrium partitioning theory (1)
- Erythrocyte Membrane (1)
- Ethiopia (1)
- Ethylmalonyl-CoA (1)
- Eubacterium (1)
- European Beech (1)
- European Union (1)
- Evolutionary biology (1)
- Evolutionary developmental biology (1)
- Evolutionary genetics (1)
- Excretion (1)
- Extracellular matrix (1)
- Extremophile (1)
- Extremophiles (1)
- F1Fo-ATP-synthase (1)
- FAD (1)
- FAD synthase (1)
- FAD1 (1)
- Fabaceae (1)
- Fabclavine (1)
- Fagaceae (1)
- Far UV (1)
- Felidae (1)
- Filamentous fungi (1)
- Flavoproteins (1)
- Fluorescence imaging (1)
- Folic Acid Antagonists (1)
- Foraminiferal (1)
- Freshwater (1)
- Freshwater Ecosystems (1)
- Freshwater invertebrate (1)
- Functional Ecology (1)
- Functional genomics (1)
- Functional traits (1)
- Fungal pan-genomes (1)
- G protein-coupled receptor (GPCR) (1)
- G3BP1 (1)
- GRAND-SLAM (1)
- Gal2 (1)
- Galakturonsäure (1)
- Gas Vacuoles (1)
- Gene sll0033 (1)
- Genetic variation (1)
- Genetic vectors (1)
- Genetics (1)
- Genome (1)
- Genome sequence (1)
- Genotoxicity (1)
- Genotyping and haplotyping (1)
- Geoffrey Burnstock (1)
- Geomagnetic field (1)
- Global warming (1)
- Glucose-6-phosphate- and 6-phosphogluconate dehydrogenase (1)
- Glycolate Oxidase (1)
- Glycophorin A dimerization (1)
- Graminicolous downy mildews (1)
- H+ transport (1)
- HARS2 (1)
- HCMV (1)
- HER (1)
- HWC database (1)
- Habitat transfer (1)
- Haematopota (1)
- Hazard assessment (1)
- Health care (1)
- Heart (1)
- Heat-Bleaching (of Plastids) (1)
- Hematophagous arthropods (1)
- Herbicide Resistance (1)
- Herbicide Resistant Mutants (1)
- Herbicide-Tolerant Mutants (1)
- Herbivores (1)
- Hi-C (1)
- High Performance Liquid (1)
- Hippocampal development (1)
- Hippocampus (1)
- History (1)
- Hominins (1)
- Host jump (1)
- Hybridization (1)
- Hydrogen storage (1)
- Hydrogen-dependent CO2 reductase (1)
- Hydrogen-dependent CO2 reductase (HDCR) (1)
- Hydrogenase (1)
- Hypercolumn (1)
- Hypothermia (1)
- I50 Value (1)
- IDP (1)
- ITS (1)
- IUCN protection categories (1)
- In situ burning (1)
- In vivo electrophysiology (1)
- Inducible Promoter (1)
- Infectious diseases (1)
- Inferior colliculus (1)
- Influenza (1)
- International survey (1)
- Intestinal bacterial community (1)
- Inthraszentin (1)
- InvaCost (1)
- Invasive species (1)
- Isoprenoids (1)
- Isozyme Pattern (1)
- Ixodes ricinus (1)
- Kinetics of Dimer Formation (1)
- Klebsiella (1)
- Kordyana (1)
- LARS2 (1)
- LASSO algorithm (1)
- LanI Protein (1)
- Lantibiotic (1)
- Lantibiotic Immunity (1)
- Larmor frequency (1)
- Larva (1)
- Latent Injury (1)
- Laurasiatheria (1)
- Leaf Peroxisomes (1)
- Leguminosae (1)
- Life-Satisfaction (1)
- Life-history (1)
- Lifespan (1)
- Light sheet-based fluorescence microscopy (1)
- Limonene-3-hydroxylase (1)
- Lineage Through Time (1)
- Lipoprotein (1)
- Long-term potentiation (1)
- MARTINI force field (1)
- MEK inhibition (1)
- MMN (1)
- Macrobenthosda (1)
- Macroevolution (1)
- Macrotermes (1)
- Macrozoobenthos (1)
- Magnetic conditioning (1)
- Magnetic map (1)
- Marantaceae (1)
- Marine biodiversity (1)
- Marine ecosystem (1)
- Marine invertebrates (1)
- Mass spectrometry (1)
- Mawson Bank (1)
- Mechanisms of disease (1)
- Mediterranean plants (1)
- Meliolales (1)
- Membrane Energetics (1)
- Membrane Enzymes (1)
- Membrane Protein Complex (1)
- MetVF (1)
- Metabolomics (1)
- Metagenomic shotgun sequencing (1)
- Metamorphosis (1)
- Methylene-THF reductase (1)
- Methylene-tetrahydrofolate reductase (1)
- Methylotroph (1)
- Methyltransferase (1)
- Mevalonic Acid (1)
- Microbiota (1)
- Microbotryales (1)
- Microenvironment (1)
- Microscopy (1)
- Mikroplastik (1)
- Mineralization (1)
- Mitochondrial Transport (1)
- Mitochondrial proteases (1)
- MjNhaP1 (1)
- Model (1)
- Molecular biology (1)
- Monoterpenoid (1)
- Monoterpenoid tolerance (1)
- Montane forest (1)
- Mount Kilimanjaro (1)
- Museum samples (1)
- Mutual information (1)
- Myocardial infarction (1)
- Myotis bechsteinii (1)
- NMR solution structure (1)
- NW Pacific (1)
- Na Gradient (1)
- Na+ transport (1)
- Naja (1)
- Nanoplastic (1)
- Natural Products (1)
- Natural products (1)
- Natural sounds (1)
- Nature Contributions to People (1)
- Nature Interest Scale (NIS) (1)
- Nature Valuation (1)
- Nature conservation (1)
- Nature's Contributions to People (1)
- Naturstoffe (1)
- Neocaridina palmata (1)
- Neotropic (1)
- Neural circuits (1)
- Neural map (1)
- Neuroligins (1)
- Neuronal Differentiation (1)
- Neurotoxicity (1)
- New host (1)
- New species (1)
- Niche (1)
- Nitrogen Metabolism (1)
- Noctuidae (1)
- Non-canonical terpenes (1)
- Non-ribosomal peptide synthetases (1)
- Non-structural protein (1)
- Norflurazon (1)
- Normative dimension (1)
- Nothopassalora (1)
- Nuclear Magnetic Resonance (1)
- Nucleic acid-binding domain (1)
- Nucleocapsid (1)
- Nucleus reuniens (1)
- Nyctalus leisleri (1)
- O-CAS assay (1)
- OXPHOS (1)
- Obituary (1)
- Oil spills (1)
- Olfactory Receptors (1)
- Olpidiopsis (1)
- Omp85-independent OMP Insertion (1)
- Optimal wiring (1)
- Optimization (1)
- Organic micropollutants (1)
- Organoids (1)
- Orientation preference (1)
- Oxidation-Reduction (1)
- Oxidative Stress (1)
- Oxidative stress (1)
- Oxygen (1)
- Oxygen Evolution (1)
- Ozone (1)
- P 700 (1)
- P. anserina (1)
- P. maximowiczii Henry x P. nigra L. cv. Rochester (1)
- POTRA Domains (1)
- PaCRD1 (1)
- PaIAP (1)
- Panama (1)
- Panolis flammea (1)
- Parkinson (1)
- Parkinson’s disease (1)
- Particle toxicity (1)
- Passalora (1)
- Pathogenesis (1)
- Pathways (1)
- Peptide natural products (1)
- Pesticides (1)
- Pheromone Inhibitor (1)
- Pheromones (1)
- Phosphohydrolases (1)
- Photoinactivation (1)
- Photorhabdus (1)
- Photosynthetic CO2 Fixation (1)
- Photosynthetic Reaction Center (1)
- Photosystem II (1)
- Phvtoene Desaturase (1)
- Phvtofluene (1)
- Phylogenetics (1)
- Physical chemistry (1)
- Physiology (1)
- Phytoene (1)
- Pigment Composition (1)
- Pigment and Protein Content (1)
- Pink1 (1)
- Pinnotheres (1)
- Pinwheel (1)
- Planetary boundaries (1)
- Plant regeneration (1)
- Plant regeneration; community assembly; diversity (1)
- Plant sciences (1)
- Plant stress (1)
- Plastic pollution (1)
- Plastic response (1)
- Plasticity (1)
- Plastics (1)
- Plastid rRNA (1)
- Podocarpus National Park (1)
- Polyhedral Bodies (1)
- Polyketides (1)
- Polymer (1)
- Polypeptides (1)
- Population density (1)
- Population dynamics (1)
- Populus nigra L. cv. Loenen (1)
- Porin (1)
- Potato Tuber Slices (1)
- Potato Tuber Tissue (1)
- Prediction (1)
- Premature Leaf Drop (1)
- Prenyl pyrophosphates (1)
- Product reuptake (1)
- Protein Assembly (1)
- Protein Complexes (1)
- Protein DNA-Interaction (1)
- Protein Purification (1)
- Protein Shape (1)
- Protein Sorting (1)
- Protein drugability (1)
- Protein druggability (1)
- Proteomics (1)
- Pseudocercospora (1)
- Pseudomonas (1)
- Pseudomonas putida (1)
- Pure Cultures of Marine Diatoms (1)
- Purkinje cell (1)
- Pyrophosphatase (1)
- QuEChERS (1)
- Quality of life (1)
- Quantum Requirement (1)
- Quarantine (1)
- Quercus (1)
- Quercus frainetto (1)
- Quercus frainetto Ten. (Ungarische Eiche) (1)
- Quercus ilex L. (Steineiche) (1)
- Quercus pubescens (1)
- Quercus pubescens Willd. (Flaumeiche) (1)
- Quercus robur L. (Stieleiche) (1)
- Quercus rubra L. (Roteiche) (1)
- Quinolinate Phosphoribosyltransferase (1)
- Quinones (1)
- Qв Binding Protein (1)
- REM sleep (1)
- RMP1 (1)
- RNA Polymerase (1)
- RNA genome (1)
- RNA polymerase (1)
- RNA sequencing (1)
- RNA stability (1)
- RNA turnover (1)
- RNA-binding proteins (1)
- Radical Pair model (1)
- Radiotherapy (1)
- Range expansion (1)
- Recolonization (1)
- Regeneration (1)
- Regulation of D1 Protein (1)
- Reintroduction (1)
- Rep gene (1)
- Reproduction (1)
- Resilience (1)
- Respiration (1)
- Respiratory chain (1)
- Rheumatoid Arthritis (1)
- Rhodnius prolixus (1)
- Ribosomally synthesized and post-translationally modified peptides (1)
- Ribosomen, rRNA Prozessierung, snoRNA, Ribosomenbiogenesefaktoren (1)
- Rnf (1)
- Robert Koch Institute (1)
- Ross Sea (1)
- Russell´s Viper (1)
- S-azidoacyl-N-acetylcysteamine (1)
- S9 (1)
- SL1 (1)
- SL5b (1)
- SL5b + c (1)
- SL5c (1)
- SLAM-seq (1)
- SNF1 (1)
- SNP (1)
- SNP genotyping (1)
- SNPs (1)
- SPAD (1)
- SR proteins (1)
- SSA (1)
- Salinity (1)
- Scale-up (1)
- Schistosomiaisis (1)
- Schizokinen (1)
- Science–society interactions (1)
- Scrotifera (1)
- Sea water (1)
- Secondary metabolites (1)
- Secretin (1)
- Secretins (1)
- Secretion (1)
- Seed sowing experiment (1)
- Seedling establishment (1)
- Sensorimotor processing (1)
- Sensory processing (1)
- Sex Attractants (1)
- Shade Adaptation (1)
- Shores (1)
- Sign posts (1)
- Simuliidae (1)
- Smut fungi (1)
- Social sciences (1)
- Sodefrin precursor-like factor (1)
- Sodium Proton Exchange (1)
- Sodium Transport (1)
- Sodium transport (1)
- Solanum lycopersicum (1)
- Solid Supported Membrane (1)
- SpaI (1)
- Spatial navigation (1)
- Spectral clustering algorithm (1)
- Sporisorium reilianum (1)
- Ste2p (1)
- Stewardship (1)
- Stewardship and dissemination (1)
- Streams (1)
- Streptomyces hydrogenans (1)
- Structural protein (1)
- Structured Illumination Microscopy (1)
- Subjective Well-Being (1)
- Subtilin (1)
- Summer drought (1)
- Super resolution (1)
- Super resolution fluorescence microscopy (1)
- Supervised machine learning (1)
- Surface range (1)
- Sustainability research (1)
- Sustainable chemistry (1)
- Svetamycin (1)
- Swimming (1)
- Swimming behavior (1)
- Symbiont evolution (1)
- Symbiosis (1)
- Synaptosomal preparation (1)
- Synovial Fibroblast (1)
- Synthesis gas (1)
- Systematics (1)
- TWNK (1)
- Tabanidae (1)
- Tabanus (1)
- Temperature preference (1)
- Terbutryn (1)
- Terpenes (1)
- Terpenoid (1)
- Testosterone (1)
- Tetrad Analysis (1)
- Thalassiosira (1)
- Thermoanaerobacter kivui (1)
- Thermoascus aurantiacus (1)
- Thermophiles (1)
- Thermophilic acetogenic bacteria (1)
- Thermus thermophilus (1)
- Thin Layer Chromatography (1)
- Thioesterase (1)
- Three-Dimensional Structure (1)
- Thylakoid Membrane (1)
- Thymidylate Low Requirement (1)
- Thymidylate Sensitivity (1)
- Thymidylate Synthetase (1)
- Thymidylate Uptake (1)
- Thymine Dimers (1)
- Tick-borne diseases (1)
- Tie2 (1)
- Tigray (1)
- Tocochromanol (1)
- TolC (1)
- Tools and pipelines (1)
- Tooth Development (1)
- Topology (1)
- Tragelaphus oryx (1)
- Transgenic organisms (1)
- Transport (1)
- Traumatic mating (1)
- Tree rings (1)
- Triatominae (1)
- Trichoptera (1)
- Trimethylamine biosynthesis (1)
- Tropical forest restoration (1)
- Tropical montane forest (1)
- Truffle (1)
- Trypanosoma rangeli (1)
- Tuber magnatum (1)
- Tylosis (1)
- Type IV Pili (1)
- UV-B Effects (1)
- UV/V cones (1)
- Ultrastructure (1)
- University students (1)
- Uptake (1)
- Ustilaginales (1)
- Ustilaginomycotina (1)
- Ustilago maydis (1)
- Ustilagomaydis (1)
- V1 (1)
- VEGF (1)
- Variability (1)
- Vector-host-interaction (1)
- Viral infection (1)
- Visual cortex (1)
- Vitality monitoring (1)
- WL110547 (1)
- Water accommodated fractions (1)
- Weather conditions (1)
- West Africa (1)
- Western Kenya (1)
- Wood properties (1)
- X-ray crystallography (1)
- Xylem (1)
- Zea mays (1)
- aIF (1)
- abiotic factors (1)
- abundance (1)
- acetogen (1)
- acetogenic metabolism (1)
- acetyl-CoA (1)
- acoustic features (1)
- acoustic stream (1)
- active sensing (1)
- additive manufacturing (1)
- additives (1)
- adhesin (1)
- adipogenesis (1)
- alarm calls (1)
- algae (1)
- all-E Lycopene (1)
- alzheimer’s disease (1)
- amplicon sequencing (1)
- angipoietin (1)
- animal welfare (1)
- anomaly zone (1)
- antibiotic resistance (1)
- antibiotics (1)
- antimicrobial resistance (1)
- antipredator (1)
- apex bird species (1)
- aptamers (1)
- arabinose (1)
- archaea (1)
- articular chondrocytes (1)
- artificial docking domains (1)
- asgard group (1)
- assembly gaps (1)
- assisted migration (1)
- ataxia (1)
- attitudes towards species conservation (1)
- auditory cortex (1)
- automated radiotelemetry system (1)
- azido-fatty acids (1)
- bacillary angiomatosis (1)
- bacteria-host interaction (1)
- bacterial community (1)
- bacterial infection (1)
- behaviour (1)
- benchmarking (1)
- benthic fauna (1)
- bioacoustics (1)
- bioactivity testing (1)
- bioassays (1)
- biodiversity conservation (1)
- biodiversity in literature (1)
- bioenergetics (1)
- biofilm (1)
- bioinformatics (1)
- biological variables (1)
- biomarkers (1)
- biosonar (1)
- biotic factors (1)
- birds (1)
- bitopic transmembrane α-helix (1)
- blood vessels (1)
- brain cancer (1)
- brain rhythms (1)
- brain waves (1)
- branching (1)
- breeding sites (1)
- cardiolipin (1)
- cardiovascular disease (1)
- carnivora (1)
- carotenogenic pathways (1)
- carotenoid distribution (1)
- carotenoid pathway engineering (1)
- carotenoid structures (1)
- caudate (1)
- cerebellum (1)
- checklist (1)
- checkpoint inhibitors (1)
- chlorophyll fluorescence (1)
- chromosomes (1)
- click-chemistry (1)
- climatic variables (1)
- co-transcriptional regulation (1)
- coalescence (1)
- cobra (1)
- coevolution (1)
- communication (1)
- communication-mediating domains (1)
- community ecology (1)
- community mean (1)
- compass orientation (1)
- complete chloroplast genome (1)
- complexome profiling (1)
- computational literary studies (1)
- connection to nature (1)
- consortia (1)
- control theory (1)
- cooperation (1)
- cophylogeny (1)
- cospeciation (1)
- cotransformation (1)
- coupling (1)
- cpDNA (1)
- cross-species RNA-sequencing (1)
- crosslinking-mass spectrometry (1)
- crustacea (1)
- cryo-EM (1)
- cultural ecosystem services (1)
- custom (1)
- cyclooctyne (1)
- cytosolic free calcium (1)
- de novo Synthesis (1)
- de novo transcription (1)
- decomposition (1)
- deep learning (1)
- deep sea (1)
- deep-sea sediment (1)
- deletion mutant (1)
- demography (1)
- dendrite (1)
- dendritic branching (1)
- dendritic morphology (1)
- depth (1)
- dermosphere (1)
- diagnostics (1)
- differentially regulated orthologs (1)
- differentiation diversity (1)
- digital student lab (1)
- dimer interface formation (1)
- distribution (1)
- diurnal variation (1)
- docking domains (1)
- domain architecture evolution (1)
- downy mildew (1)
- drug design (1)
- easyPACId (1)
- ecological risk assessment (1)
- ecology and biodiversity (1)
- ecospat (1)
- ecosystem management (1)
- ecosystem services (1)
- ectomycorrhizal (1)
- effect monitoring (1)
- effectors (1)
- elapid snake (1)
- elephant (1)
- elevational gradient (1)
- endocrine disruption (1)
- endocrine-disrupting chemicals (1)
- endophytes (1)
- endothelium (1)
- energy (1)
- energy-converting hydrogenase (Ech) (1)
- engineering (1)
- envenoming (1)
- environmental DNA (1)
- environmental behavior (1)
- environmental factors (1)
- environmental gradients (1)
- environmental humanities (1)
- environmental knowledge (1)
- environmental pollution (1)
- eukaryotic biodiversity (1)
- evolution (1)
- evolutionary traceability (1)
- exon coalescence (1)
- exon concatenation (1)
- experiment (1)
- exposome (1)
- exposure (1)
- expression system (1)
- extracellular matrix (1)
- extreme frost (1)
- failure to diverge (1)
- fatty acid dependency (1)
- fatty acid desaturation (1)
- fatty acid metabolism (1)
- fitness (1)
- foliar pathogens (1)
- food contact materials (1)
- foraging (1)
- forest management (1)
- freshwater crayfish (1)
- functional group (1)
- functional traits (1)
- fungal effectors (1)
- fungal pathogens (1)
- fungal phylogeny (1)
- fungal traits (1)
- fuzzy clustering (1)
- gamma oscillations (1)
- gas exchange (1)
- gene conversion (1)
- gene families (1)
- gene models (1)
- generalised additive models (1)
- genetic engineering (1)
- genome architecture (1)
- genome assembly (1)
- genome assembly and annotation (1)
- genomic diversity (1)
- genotype (1)
- genotyping (1)
- geoecology (1)
- geographical origin (1)
- giraffe behavior (1)
- glidobactins (1)
- global biomes (1)
- glucocorticoid receptor (1)
- glucocorticoid response (1)
- graded structure (1)
- grasslands (1)
- gravity (1)
- growth promotion (1)
- guanidine riboswitch (1)
- guided zoo tours (1)
- habitat heterogeneity (1)
- hands-on elements (1)
- heat (1)
- heat and drought (1)
- heat-shock protein (1)
- heathlands (1)
- hematopoietic stem cell (1)
- herbivores (1)
- heteroplasmy (1)
- heterozygous cells (1)
- high temperature (1)
- high throughput screening (1)
- hippo (1)
- historical biodiversity (1)
- homeostasis (1)
- homologous gene expression (1)
- honey bee classification (1)
- honey bees (1)
- horizontal gene transfer (1)
- host specificity (1)
- host-switch (1)
- housing conditions (1)
- human footprint (1)
- human-wildlife conflict (1)
- hydroxamate (1)
- hyperparasitic fungi (1)
- hyperparasitism (1)
- hypoxia (1)
- in-vitro Assay (1)
- inbreeding (1)
- indel (1)
- individual interest (1)
- individuality (1)
- infectious diseases (1)
- infra-slow oscillation (1)
- integrate-and-fire (1)
- interaction networks (1)
- interest in nature (1)
- intersexuality (1)
- invasive mammals (1)
- iron starvation (1)
- krait (1)
- lab motivation scale (LMS) (1)
- land use (1)
- landscape fragmentation (1)
- lantibiotic (1)
- large subunit maturation (1)
- lateral line (1)
- latitudinal gradient (1)
- learning technology (1)
- left ventricular hypertrophy (1)
- leukodystrophy (1)
- light (1)
- light-harvesting (1)
- lipid metabolism (1)
- lipoprotein (1)
- livelihood (1)
- liver cancer (1)
- local field potentials (1)
- long noncoding RNA (1)
- long sequencing reads (1)
- long-term protection (1)
- long36 term protection (1)
- mPTP (1)
- mRNA (1)
- mTOR (1)
- machine learning (1)
- macroevolution (1)
- macrohabitat (1)
- magnetoreception (1)
- maladaptation (1)
- mathematical modeling (1)
- maturity (1)
- maximum likelihood (1)
- mean fruit body size (1)
- mechanics (1)
- medically relevant (1)
- meerkats (1)
- membrane protein (1)
- membrane trafficking (1)
- metabolic disruptors (1)
- metabolomics (1)
- metazoans (1)
- microRNA (1)
- microbiome (1)
- microplastics (1)
- microsatellite (1)
- migration (1)
- missing data (1)
- mitochondria localization (1)
- mitochondrial dysfunction (1)
- mitochondrial localization motif (1)
- mitohormesis (1)
- mitophagy (1)
- molecular phylogenetic analysis (1)
- monetary impacts (1)
- monocytes (1)
- morphology evaluation (1)
- moth indicator groups (1)
- mounting (1)
- mt DNA (1)
- mtDNA haplotypes (1)
- mushroom (1)
- mycorrhiza (1)
- myeloid angiogenic cells (1)
- natural behavior (1)
- natural products (1)
- naturalistic stimuli (1)
- nature connectedness (1)
- nematode diversity (1)
- network analysis (1)
- neural coding (1)
- neuro-vascular (1)
- neurobiology (1)
- neurodegeneration (1)
- neurodevelopment (1)
- neuroethology (1)
- neuromodulation (1)
- neuronal coherence (1)
- neurosimulation (1)
- nightly behavior (1)
- nisin binding (1)
- nocturnal activity (1)
- non-destructive sampling (1)
- non-material contribution (1)
- non-ribosomal peptide syntheses (1)
- non-ribosomal peptide synthetase (1)
- non-target chemical analysis (1)
- non-timber forest products (NTFPs) (1)
- nonsense-mediated mRNA decay (1)
- nontarget (1)
- northern giraffe (1)
- novel natural products (1)
- obesogens (1)
- obligate pathogens (1)
- octanoic acid (1)
- oncomodulation (1)
- one new species (1)
- oomycete (1)
- oomycetes (1)
- open-source 3D bioprinting (1)
- organoids (1)
- orientation behavior (1)
- orthogroup (1)
- orthology (1)
- orthology assignment (1)
- outdoor education (1)
- oxygenic photosynthesis (1)
- pH Regulation (1)
- paleobiology (1)
- parabolic flight (1)
- paralogy (1)
- parasitism (1)
- parasitoid (1)
- parathyroid hormone 2 (1)
- pathogenicity (1)
- pathway (1)
- pathway complexity (1)
- pathway evolution (1)
- peptide-antimicrobial-Xenorhabdus peptide (1)
- phosphoketolase (1)
- phosphotransacetylase (1)
- photocycle (1)
- phylogenetic informativeness (1)
- phylogenetic profiles (1)
- phylogenetic profiling (1)
- phylogeny (1)
- physiological stress (1)
- planning and design (1)
- plant regeneration (1)
- plasma (1)
- plasmid (1)
- plasmid copy number (1)
- playback experiment (1)
- policies (1)
- politics and governance (1)
- pollinator crisis (1)
- polymers (1)
- polyploidy (1)
- population structure (1)
- postglacial colonisation (1)
- posture estimation (1)
- power law (1)
- precipitation (1)
- predation (1)
- prediction error (1)
- priority natural areas (1)
- probe kit (1)
- propagating waves (1)
- proteasome inhibitors (1)
- protein folding (1)
- protein production (1)
- protein structure (1)
- proteobacteria (1)
- proteoliposomes, (1)
- proteomics (1)
- proton translocation (1)
- protoplast fusion (1)
- qH2 (1)
- quality control (1)
- quantitative disease resistance (1)
- quercus (1)
- raccoon dog (Nyctereutes procyonoides) (1)
- radical pair model (1)
- random forest (1)
- range boundary (1)
- range expansion (1)
- reaction mechanisms (1)
- receptor (1)
- regulation (1)
- reliability (1)
- repeat elements (1)
- repetition suppression (1)
- reptiles (1)
- resource losses (1)
- retrophylogenomics (1)
- ribosome (1)
- ribosomes, Arabiodpsis thaliana, pre-rRNA processing, snoRNA, (1)
- rock-climbing impact (1)
- roots (1)
- runs of homozygosity (1)
- sage downy mildew (1)
- saprobic and ectomycorrhizal basidiomycetes (1)
- saprotrophic (1)
- scale development (1)
- scale invariance (1)
- seafloor bathymetry (1)
- sediment (1)
- senescence (1)
- sensory (1)
- sensory acquisition (1)
- serine/arginine-rich proteins (1)
- shallow water (1)
- shroom (1)
- siderophore (1)
- siderophore-dependent iron uptake (1)
- signaling (1)
- silicate (1)
- simplified production (1)
- small angle x-ray scattering (1)
- small animals (1)
- small protein (1)
- small proteins (1)
- smut fungi (1)
- snake bite (1)
- social information (1)
- social isolation (1)
- socio-economic sectors (1)
- socio-economics (1)
- soil degradation (1)
- soil fungal communities (1)
- sound coding (1)
- spatial analysis (1)
- special needs students (1)
- speciation (1)
- species delimitation (1)
- species distribution model (1)
- species richness (1)
- splicing (1)
- splicing regulation (1)
- stairway plot (1)
- stereolithography (1)
- stimulus repetition (1)
- stingless bee (1)
- stochastic factors (1)
- strained promoted cycloadditon (1)
- sub-Saharan Africa (1)
- sugar uptake (1)
- sun exposure (1)
- suricates (1)
- surround suppression (1)
- survival rate (1)
- sustainability (1)
- symbiont association patterns (1)
- systems knowledge (1)
- tRNA (1)
- tRackIT (1)
- tafazzin (1)
- target knowledge (1)
- taxonomy (1)
- teaching tool (1)
- technology acceptance model (TAM) (1)
- temperate forest (1)
- temperature (1)
- terrestrial mammal (1)
- text mining (1)
- thermal-melanism hypothesis (1)
- thiolation domain (1)
- threatened cliff plant species (1)
- tight junctions (1)
- topology (1)
- trait evolution (1)
- traits (1)
- transcription (1)
- transcriptome (1)
- transcriptome analysis (1)
- transdisciplinarity (1)
- transformation knowledge (1)
- transglutaminase 2 (1)
- translation initiation (1)
- transplant experiment (1)
- trimeric autotransporter adhesin (1)
- trisporic acids (1)
- tritrophic interaction (1)
- trophic interactions (1)
- tumor model (1)
- tumor-associated macrophages (1)
- universal (1)
- university students (1)
- unselected segregation (1)
- validity (1)
- vascular integrity (1)
- vegetation (1)
- venomous snakes (1)
- video action classification (1)
- viruses (1)
- vocalization (1)
- vocalization production; (1)
- volatile (1)
- water security (1)
- white truffle (1)
- wing geometric morphometrics (1)
- wwtr1 (1)
- xenology (1)
- xylose (1)
- yap1 (1)
- yeast (1)
- zinc finger (1)
- zoo (1)
- zoo education (1)
- zoo elephants (1)
- µ-protein (1)
- β-Barrel Proteins (1)
- β-oxidation (1)
- ζ-Carotene (1)
Institute
- Biowissenschaften (521) (remove)
Highlights
• Three ecological groups were identified based on distributional patterns.
• Old assessments were confirmed with the latest occurrence data.
• For each group, we derived different population trends in times of global change.
• Global change elevates importance of vector-borne diseases.
• Our results serve as base for effective Simuliidae monitoring.
Abstract
The black fly genus Simulium includes medically and ecologically important species, characterized by a wide variation of ecological niches largely determining their distributional patterns. In a rapidly changing environment, species-specific niche characteristics determine whether a species benefits or not. With aquatic egg, larval and pupal stages followed by a terrestrial adult phase, their spatial arrangements depend upon the interplay of aquatic conditions and climatic-landscape parameters in the terrestrial realm. The aim of this study was to enhance the understanding of the distributional patterns among Simulium species and their ecological drivers. In an ecological niche modelling approach, we focused on 12 common black fly species with different ecological requirements. Our modelling was based on available distribution data along with five stream variables describing the climatic, land-cover, and topographic conditions of river catchments. The modelled freshwater habitat suitability was spatially interpolated to derive an estimate of the adult black flies' probability of occurrence. Based on similarities in the spatial patterns of modelled habitat suitability we were able to identify three biogeographical groups, which allows us to confirm old assessments with current occurrence data: (A) montane species, (B) broad range species and (C) lowland species. The five veterinary and human medical relevant species Simulium equinum, S. erythrocephalum, S. lineatum, S. ornatum and S. reptans are mainly classified in the lowland species group. In the course of climatic changes, it is expected that biocoenosis will slightly shift towards upstream regions, so that the lowland group will presumably emerge as the winner. This is mainly explained by wider ecological niches, including a higher temperature tolerance and tolerance to various pollutants. In conclusion, these findings have significant implications for human and animal health. As exposure to relevant Simulium species increases, it becomes imperative to remain vigilant, particularly in investigating the potential transmission of pathogens.
Trait-dependent effects of biotic and abiotic filters on plant regeneration in Southern Ecuador
(2024)
Tropical forests have always fascinated scientists due to their unique biodiversity. However, our understanding of ecological processes shaping the complexity of tropical rainforests is still relatively poor. Plant regeneration is one of the processes that remain understudied in the tropics although this is a key process defining the structure, diversity and assembly of tropical plant communities. In my dissertation, I combine experimental, observational and trait-based approaches to identify processes shaping the assembly of seedling communities and compare associations between environmental conditions and plant traits across plant life stages. By working along a steep environmental gradient in the tropical mountains of Southern Ecuador, I was able to investigate how processes of plant regeneration vary in response to biotic and abiotic factors in tropical montane forests.
My dissertation comprises three complementary chapters, each addressing an individual research question. First, I studied how trait composition in plant communities varies in relation to the broad- and local-scale environmental conditions and across the plant life cycle. I measured key traits reflecting different ecological strategies of plants that correspond to three stages of the plant life cycle (i.e., adult trees, seed rain and recruiting seedlings). I worked on 81 subplots along an elevational gradient covering a large climatic gradient at three different elevations (1000, 2000 and 3000 m a.s.l.). In addition, I measured soil and light conditions at the local spatial scale within each subplot. My findings show that the trait composition of leaves, seeds and seedlings changed similarly across the elevational gradient, but that the different life stages responded differently to the local gradients in soil nutrients and light availability. Consequently, my findings highlight that trait-environment associations in plant communities differ between large and small spatial scales and across plant life stages.
Second, I investigated how seed size affects seedling recruitment in natural forests and in pastures in relation to abiotic and biotic factors. I set up a seed sowing experiment in both habitat types and sowed over 8,000 seeds belonging to seven tree species differing in seed size. I found that large-seeded species had higher proportions of recruitment in the forests compared to small-seeded species. However, small-seeded species tended to recruit better in pastures compared to large-seeded species. I showed that high surface temperature was the main driver of differences in seedling recruitment between habitats, because it limited seedling recruitment of large-seeded species. The results from this experiment show that pasture restoration requires seed addition of large-seeded species and active protection of recruiting seedlings in order to mitigate harmful conditions associated with high temperatures in deforested areas.
Third, I examined the associations between seedling beta-diversity and different abiotic and biotic factors between and within elevations. I applied beta-diversity partitioning to obtain two components of beta-diversity: species turnover and species richness differences. I associated these components of beta-diversity with biotic pressures by herbivores and fungal pathogens and environmental heterogeneity in light and soil conditions. I found that species turnover in seedling communities was positively associated with the dissimilarity in biotic pressures within elevations and with environmental heterogeneity between elevations. Further, I found that species richness differences increased primarily with increasing environmental heterogeneity within elevations. My findings show that the associations between beta-diversity of seedling communities and abiotic and biotic factors are scale-dependent, most likely due to differences in species sorting in response to biotic pressures and species coexistence in response to environmental heterogeneity.
My dissertation reveals that studying processes of community assembly at different plant life stages and spatial scales can yield new insights into patterns and processes of plant regeneration in tropical forests. I investigated how community assembly processes are governed by abiotic and biotic filtering across and within elevations. I also experimentally explored how the process of seedling recruitment depends on seed size-dependent interactions, and verified how these effects are associated with abiotic and biotic filtering. Identifying such processes is crucial to inform predictive models of environmental change on plant regeneration and successful forest restoration. Further exploration of plant functional traits and their associations with local-scale environmental conditions could effectively support local conservation efforts needed to enhance forest cover in the future and halt the accelerating loss of biodiversity.
EF-P and its paralog EfpL (YeiP) differentially control translation of proline containing sequences
(2024)
Polyproline sequences (XPPX) stall ribosomes, thus being deleterious for all living organisms. In bacteria, translation elongation factor P (EF-P) plays a crucial role in overcoming such arrests. 12% of eubacteria possess an EF-P paralog – YeiP (EfpL) of unknown function. Here, we functionally and structurally characterize EfpL from Escherichia coli and demonstrate its yet unrecognized role in the translational stress response. Through ribosome profiling, we analyzed the EfpL arrest motif spectrum and discovered additional stalls beyond the canonical XPPX motifs at single-proline sequences (XPX), that both EF-P and EfpL can resolve. Notably, the two factors can also induce pauses. We further report that, contrary to the housekeeping EF-P, EfpL can sense the metabolic state of the cell, via lysine acylation. Together, our work uncovers a new player in ribosome rescue at proline-containing sequences, and provides evidence that co-occurrence of EF-P and EfpL is an evolutionary driver for higher bacterial growth rates.
Zinc finger (ZnF) domains appear in a pool of structural contexts and despite their small size achieve varying target specificities, covering single-stranded and double-stranded DNA and RNA as well as proteins. Combined with other RNA-binding domains, ZnFs enhance affinity and specificity of RNA-binding proteins (RBPs). The ZnF-containing immunoregulatory RBP Roquin initiates mRNA decay, thereby controlling the adaptive immune system. Its unique ROQ domain shape-specifically recognizes stem-looped cis-elements in mRNA 3’-untranslated regions (UTR). The N-terminus of Roquin contains a RING domain for protein-protein interactions and a ZnF, which was suggested to play an essential role in RNA decay by Roquin. The ZnF domain boundaries, its RNA motif preference and its interplay with the ROQ domain have remained elusive, also driven by the lack of high-resolution data of the challenging protein. We provide the solution structure of the Roquin-1 ZnF and use an RBNS-NMR pipeline to show that the ZnF recognizes AU-rich elements (ARE). We systematically refine the contributions of adenines in a poly(U)-background to specific complex formation. With the simultaneous binding of ROQ and ZnF to a natural target transcript of Roquin, our study for the first time suggests how Roquin integrates RNA shape and sequence specificity through the ROQ-ZnF tandem.
Highlights
• Seed size mediates seedling recruitment in tropical forests and pastures.
• Large-seeded species recruited better than small-seeded species in the forest.
• Recruitment of large-seeded species in pastures was limited by surface temperature.
• Large-seeded species should be protected against drought in regenerating pastures.
Abstract
Seedling recruitment is a key process of plant regeneration that often depends on plant functional traits, such as seed size. To optimize forest restoration efforts, we need to better understand how seedling recruitment of different seed sizes varies along environmental gradients with strong variation in abiotic and biotic factors. To understand these interacting effects, we conducted a sowing experiment with different-sized seeds in forests and pastures in the tropical mountains of southern Ecuador. We quantified seedling recruitment in relation to temperature, soil moisture and biotic pressures. We sowed seeds of five tree species of varying seed size at three elevations (1000, 2000 and 3000 m a.s.l.) in primary forest and pastures. We tested (1) how habitat type influences the recruitment of seedlings belonging to three small- and two large-seeded species, and (2) how abiotic and biotic factors limit seedling recruitment of species with different seed sizes. We found that seedlings of the two large-seeded species recruited better than seedlings of the three small-seeded species, but only in the forest habitat. Seedling recruitment of large seeds was primarily limited by high surface temperature, which explains lower recruitment of large seeds in pastures compared to forests. Our study shows that seed size can be a key trait mediating variability in seedling recruitment in tropical ecosystems. We conclude that restoration measures should aim to mitigate extreme temperatures in tropical pastures to aid the natural regeneration of large-seeded tree species.
Establishing and maintaining protected areas (PAs) is a key action in delivering post-2020 biodiversity targets. PAs often need to meet multiple objectives, ranging from biodiversity protection to ecosystem service provision and climate change mitigation, but available land and conservation funding is limited. Therefore, optimizing resources by selecting the most beneficial PAs is vital. Here, we advocate for a flexible and transparent approach to selecting PAs based on multiple objectives, and illustrate this with a decision support tool on a global scale. The tool allows weighting and prioritization of different conservation objectives according to user-specified preferences as well as real-time comparison of the outcome. Applying the tool across 1,346 terrestrial PAs, we demonstrate that decision makers frequently face trade-offs among conflicting objectives, e.g., between species protection and ecosystem integrity. Nevertheless, we show that transparent decision support tools can reveal synergies and trade-offs associated with PA selection, thereby helping to illuminate and resolve land-use conflicts embedded in divergent societal and political demands and values.
The capacity of pathogenic bacteria to adhere to host cells and to avoid subsequent clearance by the host´s immune response is the initial and most decisive step leading to infections. Human pathogenic bacteria circulating in the bloodstream need to find ways to interact with endothelial cells (ECs) lining the blood vessels to infect and colonise the host. The extracellular matrix (ECM) of ECs might represent an attractive initial target for bacterial interaction, as many bacterial adhesins have reported affinities to ECM proteins, particularly fibronectin (Fn). Trimeric autotransporter adhesins (TAA) have been described as important pathogenicity factors of Gram-negative bacteria. The TAA from human pathogenic Bartonella henselae, Bartonella adhesin A (BadA), is one of the longest and best characterised adhesin and represents a prototypic TAA due to its domain architecture. B. henselae, the causative agent of cat scratch disease, endocarditis, and bacillary angiomatosis, adheres to ECs and ECM proteins via BadA interaction.
In this research, it was determined that the interaction between BadA and Fn is essential for B. henselae host cell adhesion. BadA interactions were identified within the heparin-binding domains of Fn, and the exact binding sites were revealed by mass spectrometry analysis of chemically crosslinked whole-cell bacteria and Fn. It turned out that specific BadA interactions with defined Fn regions represent the molecular basis for bacterial adhesion to ECs. These data were confirmed by using BadA-deficient bacteria and CRISPR-Cas FN1 knockout ECs. It was also identified that BadA binds to Fn from both cellular and plasma origin, suggesting that B. henselae binding to Fn might possibly take part in other infection processes apart from bacterial adherence, e.g. evasion from the host cell immune system.
Interactions between TAAs and Fn represent a key step for adherence of B. henselae to ECs. Still, Fn-mediated binding is of more significant importance for pathogenic bacteria than broadly recognised. Fn removal from the ECM environment of ECs, also reduced adherence of Staphylococcus aureus, Borrelia burgdorferi, and Acinetobacter baumannii to host cells Interactions between adhesins and Fn might therefore represent a crucial step for the adhesion of human-pathogenic Gram-negative and Gram-positive bacteria targeting the ECs as a niche of infection or as means for persistence.
This research demonstrated that combining large-scale analysis approaches to describe protein-protein interactions with supportive functional readouts (binding assays) allows for the discrimination of crucial interactions involved in bacterial adhesion to the host. The herein-described experimental approaches and tools might guide future research for other pathogenic bacteria and represent an initial point for the future generation of anti-virulence strategies to inhibit bacterial binding to host cells.
Brain development is a complex and highly organized process that relies on the coordinated interaction between neurons and vessels. These cell systems form a neurovascular link that involves the exchange of oxygen, ions, and other physiological components necessary for proper neuronal and vascular function. This physiologically coupled process is executed through analogous structural and molecular signaling mechanisms shared by both cell types. At the neurovascular interface, the cellular crosstalk via these shared signaling mechanisms allows for the synchronized expansion and integration of neurons and vessels into complex cellular networks. This study investigated the role of VEGFR2, a receptor for vascular endothelial growth factor (VEGF), during postnatal neuronal development in the mouse hippocampus. Prior studies have revealed physiological roles of VEGF, a pro-angiogenic morphogen, in nervous system development. However, it was unclear if VEGF signaling had a direct effect on neuronal physiology and function through neuronal-expressing receptors. In this investigative work, we identified a previously unknown function of VEGFR2, whereby VEGF-induced signaling coordinates the development and circuitry integration of CA3 pyramidal neurons in the early postnatal mouse hippocampus. Mechanistically, we found that VEGFR2 signaling requires receptor endocytosis, a process mediated by ephrinB2. We also found that VEGF-induced cooperative signaling between VEGFR2 and ephrinB2 is functionally required for the dendritic arborization and spine maturation of developing CA3 neurons during the first few postnatal weeks. Moreover, in a collaborative effort with the research group of Carmen Ruiz de Almodovar, formerly at the University of Heidelberg, we simultaneously studied VEGF-induced VEGFR2 signaling in CA3 axonal development. Together, we aimed to gain a comprehensive understanding of the complex interplay between VEGF and VEGFR2 signaling during the early postnatal development of CA3 neurons. Ruiz de Almodovar’s research group found that, unlike the branch and spine development of CA3 dendrites, VEGF-VEGFR2 signaling promotes axonal development through mechanisms that are independent of ephrinB2 function. Our findings on CA3 dendritic development are reported in the published manuscript, Harde et al. (2019), and the complementary work on CA3 axonal development from Ruiz de Almodovar's group is presented in the co-published manuscript, Luck et al. (2019). Although the totality of Ruiz de Almodovar's group's work on CA3 axons is not fully discussed here, it is referenced where noted to provide biological context for our findings on CA3 dendritic development.
VEGFR2 signaling within neurovascular niches is known to play a role in the neurogenesis of neural progenitor cells during embryonic development and within the adult brain. However, the precise localization of neuronal VEGFR2 expression and functional role within the nervous system during postnatal brain development was unknown. To investigate this, we used immunohistochemistry to identify the spatial expression of VEGFR2 within the mouse hippocampus during the first few weeks after birth. Our results showed that VEGFR2 was predominantly expressed within the hippocampal vasculature, consistent with prior studies. However, we also observed localized VEGFR2 expression in pyramidal cell neurons of the hippocampal CA3 region by postnatal day 10 (P10). This spatially restricted postnatal expression of VEGFR2 in CA3 neurons suggested a potential role in the development of these neurons during this developmental stage.
The first two weeks after birth in the mouse hippocampus is a critical period for the development of neuronal circuits, as neurons undergo extensive dendritic arborization and spine formation. To explore the role of VEGFR2 in the postnatal nervous system, we used a Nes-cre VEGFR2lox/- mouse line to target the deletion of VEGFR2 expression within the nervous system while preserving normal receptor expression in all other cell types. We also generated corresponding control mice that were negative for Nes-cre. By breeding these mice with Thy1-GFP reporter mice, we could analyze the functional consequences of VEGFR2 by assessing the morphologies of CA3 dendritic trees and spine density and maturation at P10 and P15, respectively. Our analysis showed that CA3 neurons in Nes-cre VEGFR2lox/- mice had less complex dendritic arbors compared to control mice. There were significant reductions in total length and branch points, particularly in areas located 100-250 μm from the cell soma within the stratum radiatum layer. Additionally, Nes-cre VEGFR2lox/- mice exhibited a significant decrease in spine density accompanied by an increased proportion of immature spines. These findings suggest that VEGFR2 plays a crucial role in the proper development of CA3 dendrites and spines during the early postnatal weeks.
In view of a growing world population and the finite nature of fossil resources, the development of eco-friendly production processes is essential for the transition towards a sustainable industry. Methanol, which can be produced both petrochemically and from renewable resources, offers itself as bridging technology and attractive alternative raw material for biotechnological processes. This work describes developments for the progress of the well-studied methylotrophic α proteobacterium Methylorubrum extorquens AM1 towards an efficient methylotrophic cell factory. Although many homologous and heterologous production routes have already been described and realized for M. extorquens in a laboratory scale, no industrial process has yet been realized. Three major reasons can be identified for this: (1) A limited choice of tools for genetic modifications, (2) a lack of understanding of carbon fluxes and side reactions occurring in modified strains, such as product reimports, and (3) the lack of tailored production strains for profitable target products and optimized bioprocessing protocols. The aim of the present work was to achieve developments for the mentioned areas. As a model application, the high-level production of chiral dicarboxylic acids from the substrate methanol was chosen. Enantiomerically pure chiral compounds are of great interest, e.g., as building blocks for chiral drugs. The ethylmalonyl CoA metabolic pathway (EMCP) which is part of the primary metabolism of M. extorquens, harbors unique chiral CoA-ester intermediates. Their acid derivatives can be released by cleavage of the CoA-moiety using heterologous enzymes. The dicarboxylic acids 2 methylsuccinic acid and mesaconic acid were produced in a previous study by introducing the heterologous thioesterase YciA into M. extorquens. In the said study, a combined product titer of 0.65 g/L was obtained in shake flask experiments. These results serve as the basis for the developments in the present work.
First, the previously described reuptake of products was thoroughly investigated and dctA2, a gene encoding for an acid transporter, was identified as target for reducing the product reuptake. In addition, reuptake of mesaconic acid was prevented by converting it to (S)-citramalic acid, a product not metabolizable by M. extorquens, by the introduction of a heterologous mesaconase. Together with 2-methylsuccinic acid, for which a high enantiomeric excess of (S)-2-methylsuccinic acid was determined, a second chiral molecule was thus added to the product spectrum. For the release of dicarboxylic acid products, YciA, a broad-range thioesterase that accepts a variety of CoA-esters with different chain lengths as substrates, was chosen. The enzyme should theoretically be able to hydrolyze all CoA-esters of interest present in the EMCP. However, in culture supernatants of M. extorquens strains that were overexpressing the corresponding yciA gene, only mesaconic acid and 2 methylsuccinic acid could be detected. To expand the substrate spectrum of YciA thioesterase with respect to other EMCP intermediates, semi-rational enzyme engineering was attempted. Screening of the corresponding strains carrying the respective YciA variants did not result in strains capable of producing new dicarboxylic acid products. However, the experiments revealed an amino acid position that strongly affected the production of mesaconic acid and 2-methylsuccinic acid in vivo. By substituting the according amino acid in YciA, the maximum titers of mesaconic acid and 2-methylsuccinic acid could be increased substantially. Application of an improved thioesterase variant in a second E. coli-based process confirmed the enhanced activity of the enzyme. The desired extension of the product spectrum by another chiral molecule (2-hydroxy-3-methylsuccinic acid, presumably the (2S,3R)-form) was finally achieved by using an alternative thioesterase. Tailored fermentation strategies were developed for the high-level production of the above-mentioned products.
As second part of the work, two novel genetic tools for M. extorquens were developed and characterized. The pBBR1-derived plasmid pMis1_1B was shown to be stably maintained in M. extorquens cells. In addition, its suitability for co-transformations with other plasmids was demonstrated. The second tool, the cumate-inducible promoter Ps6, is tailored for expression of pathways with toxic products, as the transcription of genes controlled by Ps6 is strongly repressed in the absence of an inducer.
Overall, the present work demonstrates the enormous potential of using M. extorquens as a methylotrophic cell factory. In the applications shown, the biotechnological production of high-priced chiral molecules is combined with the use of an attractive alternative substrate. In addition, new achievements and approaches are presented to facilitate the development of future M. extorquens production strains.
Seed dispersal is a key ecosystem function for plant regeneration, as it involves the movement of seeds away from the parental plants to particular habitats where they can germinate and transition to seedlings and ultimately adult plants. Seed dispersal is shaped by a diversity of abiotic and biotic factors, particularly by associations between plants and climate and between plants and other species. Due to the ongoing loss of biodiversity and changing global conditions, such interactions are prone to change and pose a severe threat to plant regeneration. One way to address this challenge is to study associations between plant traits and abiotic and biotic factors to understand the potential impacts of global change on plant regeneration. Plant communities have long been analyzed through the lens of vegetative traits, mainly ignoring how other traits interact and respond to the environment. For instance, while associations between vegetative traits (e.g., specific leaf area, leaf nitrogen content) and climate are well studied, there are few case studies of reproductive traits in relation to trait-environment associations in the context of global change.
Thus, the overarching aim of this dissertation is to explore how trait-environment associations, with a special focus on reproductive traits, can improve our understanding of the effect that global change may have on seed dispersal, and ultimately on plant regeneration. To this end, my research focuses on studying associations between plant traits and abiotic and biotic factors along an elevational gradient in both forests and deforested areas of tropical mountains. This dissertation addresses three principal research objectives.
First, I investigate the extent to which reproductive (seed and fruit traits) and vegetative traits (leaf traits) are related to abiotic and biotic factors for communities of fleshy-fruited plants in the Ecuadorian Andes. I used multivariate analyses to test associations between four (a)biotic factors and seven reproductive traits and five vegetative traits measured on 18 and 33 fleshy fruited plant species respectively. My analyses demonstrate that climate and soil conditions are strongly associated with the distribution of both reproductive and vegetative traits in tropical tree communities. The production of “costly” vs. “cheap” seeds, fruits and leaves, i.e., the production of few rewarding fruits and acquisitive leaves versus the production of many less-rewarding fruits and conservative leaves, is primarily limited by temperature, whereas the size of plant organs is more related to variation in precipitation and soil conditions. My findings suggest that associations between reproductive and vegetative traits and the abiotic environment follow similar principles in tropical tree communities.
Second, I assess how climate and microhabitat conditions affect the prevalence of endozoochorous plant species in the seed rain of tropical montane forests in southern Ecuador. I analyzed seed rain data for an entire year from 162 traps located across an elevational gradient spanning of 2000 m. I documented the microhabitat conditions (leaf area index and soil moisture next to each seed trap) at small spatial scale as well as the climatic conditions (mean annual temperature and rainfall in each plot) at large spatial scale. After a one-year of sampling, I counted 331,838 seeds of 323 species/morphospecies. My analyses demonstrate that the prevalence of endozoochorous plant species in the seed rain increases with temperature across elevations and with leaf area index within elevations. These results show that the prevalence of endozoochory is shaped by the interplay of both abiotic and biotic factors at large and small spatial scales.
Third, I examine the potential of seed rain to restore deforested tropical areas along an elevational gradient in southern Ecuador. For this chapter, I collected seed rain using 324 seed traps installed in 18 1-ha plots in forests (nine forest plots) and in pastures (nine deforested plots) along an elevational gradient of 2000 m. After a sampling period of three months, I collected a total of 123,039 seeds of 255 species/morphospecies from both forests and pastures along the elevational gradient. I did not find a consistent decrease in the amount and richness of seed rain between forests and pastures, but I detected a systematic change in the type of dispersed seeds, as heavier seeds and a higher proportion of endozoochorous species were found in forests compared to pastures at all elevations. This finding suggests that deforestation acts as a strong filter selecting seed traits that are vital for plant regeneration.
Understanding the role that trait-environment associations play in how plant communities regenerate today could serve as a basis for predicting changes in regeneration processes of plant communities under changing global conditions in the near future. Here, I show how informative the measurement of reproductive traits and trait environment associations are in facilitating the conservation of forest habitats and the restoration of deforested areas in the context of global change.
Subject of this thesis was the investigation of the actin-interacting and glucocorticoid-sensitive Protein DRR1 (or Fam107a) and its role in promoting stress resilience in the murine hippocampus.
We proposed the hypothesis that DRR1 through its actin-binding properties specifically modulates neuronal actin dynamics and promotes resilience through synaptic plasticity leading to subsequently improvement of cognitive performance and social behavior. The accompanied AMPA-receptor transport could create an efficient way regulating neural function and complex behavior during stress episodes.
By utilizing fluorescent immunohistochemistry, we showed basal expression of DRR1 primarily in the murine cerebellum and hippocampal CA3 and CA1 area. Co-staining with different cell marker proteins showed DRR1 expression in neurons, microglia and especially in astrocytic end-feet, which create contact to the brain vasculature.
To test whether DRR1 and AMPA receptor function correlate to modulate stress-associated consequences, primary hippocampal neuron cultures were transduced with adeno-associated virus (AAV) for overexpression or suppression of the protein. Western Blot analysis showed a positive correlation between the AMPA-receptor subunit GluR2 and DRR1 amounts. Further the application of the proximity ligation assay (PLA) in untreated neural cultures indicated interaction between DRR1 and the AMPA receptor subunit GluR2. To address whether DRR1 even affects AMPAR trafficking we performed the “newly inserted assay” after AAV-treatment of primary hippocampal neuron cultures. Suppression of DRR1 revealed less newly inserted GluR2 subunits as compared to controls. Inconclusive were the results upon DRR1 overexpression, however they point to no changes.
In the second part we correlated behavioral phenotypes originating from in vivo overexpression and suppression of DRR1 in the murine hippocampus with potential alterations in neuronal morphology. Therefore, in vitro analysis was performed utilizing AAV transduced primary hippocampal cultures overexpressing or suppressing DRR1. Synchronously the viral vector included a green fluorescent protein (GFP) being expressed throughout the complete neural cell. GFP staining was used to verify successful transfection and for reconstruction of dendritic arbors and dendritic stretches for spine classification. DRR1 suppression showed reduced total spine numbers especially evoked by reduced numbers of immature spine classes – namely long thin spines and filopodia. Whereas mature mushroom spines and stubby spines were unaffected. By overexpressing DRR1, tendencies inclined against higher total dendritic lengths, branch points and increased dendritic arbors in comparison to controls. In regard of spines, total numbers were unaffected. However, mature mushroom spines were significantly declined in numbers, but compensated by increased numbers of immature long thin spines and filopodia.
Chronic social defeat stress (CSDS) is widely used in mouse models to study the effects of stress and resilience. We exposed C57Bl/6J mice expressing GFP under the Thy1 promoter CSDS and categorized them into resilient (R+/-), susceptible (R-/-) and non-learning (R+/+) mice following a modified social interaction test (MSIT). We found alterations in CA1 spine compositions with resilient animals resembling the untreated phenotype. Stress susceptible and non-learning animals displayed reduced numbers in stubby spines with simultaneous increases in mature mushroom spines. In addition, we could detect a tendency towards more immature spines in susceptible animals and non-learners, mirroring our in vitro results.
Finally, we present a different investigative approach in this thesis. Sequenced acute stress was previously found to compromise cognition including spine loss.
We aimed to investigate the implication of acute stress on DRR1 levels and its occurrence in diverse cell types of the brain. We subjected one group of C57Bl/6J mice to acute stress and injected another group with the artificial glucocorticoid DEX. Six hours post stress, animals were perfused and brains were subsequently immunobiologically analyzed. We found DRR1 protein levels elevated in the hippocampus of stressed and DEX-treated animals compared to controls. Interestingly, DRR1 seemed was especially elevated in endothelial cells. This coincides with our investigations finding DRR1 present in astrocytic end-feet under basal conditions and might claim a participation of DRR1 in the blood-brain-barrier integrity.
Our results show DRR1 as actin-interacting and glucocorticoid-sensitive gene affecting structural plasticity of hippocampal spines. Moreover, DRR1 directly interacts with AMPA glutamate receptors and presumably is involved in AMPA trafficking to the postsynaptic membrane. In addition, this study could demonstrate that DRR1 is expressed by other cell types of the brain. Of special interest is DRR1’s occurrence in astrocytic end-feet and endothelial cells suggesting a role as integrator of cell-cell communication and to this end also acting as modifier of stress-induced consequences at the neurovascular unit.
In vivo data of chronically stressed mice displayed no phenotypic differences in hippocampal pyramidal neurons of resilient animals as compared to unstressed mice. Morphological alterations of spine structures were particularly visible in stress susceptible and non-learning animals. Integrating our findings with existing behavioral data, we can conclude that DRR1 plays a role in stress resilience whereby it needs to be expressed in a tightly managed homeostatic equilibrium.
The functional and molecular role of transglutaminase 2 in hematopoietic stem and progenitor cells
(2023)
Long-term repopulating hematopoietic stem cells (LT-HSCs) that reside in the bone marrow (BM) give rise to all blood cell types including erythrocytes, leukocytes and platelets. LT-HSCs are mainly quiescent during steady state hematopoiesis. LT-HSCs can process self-renewal to expand and maintain stemness, or commit to differentiation into short-term (ST) repopulating HSC and multipotent progenitors (MPPs). MPPs differentiate into oligopotent lineagerestricted progenitors which eventually produce all mature blood cell lineages, and thereby regenerate hematopoietic system.
Previous studies have shown in transcription profiles and quantitative PCR (qPCR) analysis that transglutaminase 2 (Tgm2) is one of the most upregulated genes in quiescent LT-HSCs in comparison to active HSCs, mobilized HSCs, ST-HSCs, MPPs, as well as leukemic stem cells (LSC). However, the reason why Tgm2 is strongly upregulated in dormant mouse LTHSCs and what the role of Tgm2 is in LT-HSCs has not been investigated yet.
Tgm2, encoded by the Tgm2 gene, is a multi-functional protein within the transglutaminase family. It has been found to be widely expressed inside and outside the cells. It consists of four domains and two functionally exclusive forms that are regulated by the Ca2+ and GTP concentration. Besides the most well-known transglutaminase enzymatic activity for transamidation, deamidation and crosslinking, Tgm2 acts also as a GTPase/ATPase, kinase, adhesion/scaffold protein, as well as disulfide isomerase. The role of Tgm2 in hematopoiesis remains elusive. Accordingly, the aim of this dissertation is to investigate the role of Tgm2 in murine hematopoiesis, especially in murine LT-HSCs.
Firstly, the expression of Tgm2 was analyzed in highly purified murine hematopoietic stem and progenitor cell (HSPC) populations. Low input label-free mass spectrometric proteomics and WES protein analysis confirmed the highly specific expression of Tgm2 in LT-HSCs at protein level. Already at the state of MPPs, Tgm2 protein was almost absent with further decline towards oligopotent progenitors. These results indicated Tgm2 as a specific protein marker for LT-HSCs, justifying the future generation of a fluorescent reporter mouse line based on endogenous Tgm2 tagging.
To delineate the functional and molecular role of Tgm2 in LT-HSCs, a conditional Tgm2 knockout mouse model was generated using the Mx1-Cre/loxP system, with the loxP sites flanking the coding exons of the catalytic domain of Tgm2. After PolyIC-mediated induction, a more than 95% knockout efficiency was observed in purified LT-HSCs and the protein expression of Tgm2 was confirmed to be vanished in the purified LT-HSCs from conditional Tgm2-KO mice. Conditional knockout mice are viable and show no aberrant organ functions.
In steady state condition, the distribution of mature blood cell lineages and immunophenotypically-defined HSPC populations within the BM, the mitochondrial potential of HSPCs reflected by the non-invasive cationic dye JC-1, as well as the cell cycle status of HSPCs mirrored by the intracellular Ki67 staining did not show any significant variations upon loss of Tgm2. However, the in vitro continuous observation of prospectivly isolated LT-HSCs by time-lapse microscopy-based cell tracking revealed a delayed entry into cell cycle with a two fold increased apoptosis rate after knocking out Tgm2, indicating Tgm2 expression might be essential for survival of LT-HSCs. Moreover, while the absence of Tgm2 in LT-HSCs did not influence differentiation and lineage choice in vitro, overexpression of Tgm2 in LT-HSCs resulted in an increase of the most immature subpopulation upon cultivation. All these features were not observed in Tgm2-deleted MPPs, suggesting Tgm2 playing a specific function at the level of LT-HSCs. Upon stress hematopoiesis, induced by the administration of 5-fluorouracil (5-FU), there was a trend towards delayed recovery of LT-HSCs lacking Tgm2. Although Tgm2 express specificly in LT-HSCs, two rounds of competitive BM serial transplantation displayed an equal overall engraftment and multi-lineage reconstitution of LT-HSCs from Tgm2-WT and Tgm2-KO mice in peripheral blood (PB), BM and spleens. Interestingly, LT-HSCs from Tgm2-KO mice reconstituted to more myeloid cells and fewer B cells in the first four weeks after primary transplantation, which disappeared at later time points.
Gene expression profiling and simultaneous single cell proteo-genomic profiling indicated that HSPCs and LT-HSCs from Tgm2-KO mice were transcriptionally more active. A heterogeneity of Tgm2 expression within Tgm2-WT LT-HSCs was revealed by single cell data. Commonly up-regulated genes in Tgm2-KO LT-HSCs and MPPs were significantly involved in regulation of transcription from RNA polymerase II promoter in response to stress, positive regulation of cell death as well as negative regulation of mitogen-activated protein kinase (MAPK) signaling pathways. In Tgm2-KO LT-HSCs, 136 up-regulated genes demonstrated an enrichment of genes involved in apoptosis, as well as negative regulation of MAPK signaling pathway.
Taken together, this dissertation shows that Tgm2 protein is highly specifically expressed in LT-HSCs, but not in subsequent progenitor populations. However, Tgm2 is not essential for differentiation and maturation of myeloid lineages, the proliferation and the long-term multilineage reconstitution potential of LT-HSCs after transplantation. Tgm2 might be involved in accurate stress response of LT-HSCs and the transition from LT-HSCs into MPPs, meaning that the absence of Tgm2 results in poor survival, myeloid bias upon transplantation, as well as slower recovery upon chemotherapeutic treatment.
Sphingolipids are not only structural components of cell membranes but can also act as signalling molecules in different pathways. Sphingolipid precursors, Ceramides (Cer), are synthesized de novo by six different synthases (CerS1-6) which generate Cer of different chain lengths. Cer can be further synthesized to glycosphingolipids and sphingomyelin. Cell membrane parts that are enriched in glycosphingolipids are so-called lipid rafts and can function as signalling platforms for different receptors, such like the T cell receptor (TCR). CD4+ T cells play a crucial role in the development of ulcerative colitis, a chronic inflammatory disease of the colon. As CerS3 expression was increased in the white blood cells of human colitis patients, the role of CerS3 in the TCR signalling and colitis was investigated in this dissertation. By lenti-viral transduction of a CerS3-shRNA into a CD4+ Jurkat cell line, it was shown that CerS3 has an impact on activated T cells. A decrease of different sphingolipids after T cell activation via CD2/3/28 activation beads and IL2 treatment was observed that was accompanied by an inhibition of Zap70 phosphorylation, an important protein of the TCR signalling. The impaired TCR signalling led to a diminished NFAT1 translocation into the nucleus which subsequently led to a reduced NFAT1- dependent TNFα release. Downregulation of CerS3 in primary CD4+ T cells, obtained from the blood of healthy volunteers, also showed a reduced release of pro-inflammatory cytokines after activation. This dissertation demonstrates a pivotal role for CerS3 in T cell function and highlights CerS3 as potential new target for T cell driven colitis.
For thousands of years, S. cerevisiae has been employed by humans in brewing and baking. Nowadays, this budding yeast is more than that: it is a well investigated model organism and an established workhorse in biotechnology. S. cerevisiae serves as a production host for various applications such as i) bioethanol production ii) the biosynthesis of hormones including insulin or iii) cannabinoid biosynthesis. Hereby, the robustness of S. cerevisiae and its high tolerances regarding pH and salt concentrations qualifies it for a wide range of industrial applications. Moreover, products of S. cerevisiae are generally recognised as safe (GRAS), enabling diverse biotechnological applications. Various mechanisms for genetic engineering of S. cerevisiae are applicable and the engineering process itself is straightforward since methods are established and widely known. Due to the wide range of industrial applications of S. cerevisiae, this organism is an ideal candidate for applied research and implementation of the recombinant biosynthesis of tocochromanols in this study.
Tocochromanols encompass tocotrienols and tocopherols, which are lipid-soluble compounds that are commonly associated with vitamin E activity. Hereby, α-tocopherol is the most prevalent form, as it is an essential nutrient in the diet of humans and animals. Naturally, tocochromanols are almost exclusively synthesised by photoautotrophic organisms such as plants or cyanobacteria. They consist of an aromatic head group and a polyprenyl side chain which is saturated in tocopherols and 3-fold unsaturated in tocotrienols. The methylation status of the chromanol ring distinguishes α-, β-, γ- and δ-tocochromanol. All forms of tocochromanols represent a group of powerful antioxidants, scavenging reactive oxygen species (ROS) and preventing the propagation of lipid oxidation in lipophilic environments. Recently, attention has been drawn to tocotrienols, due to their benefits in neuroprotection as well as cholesterol-lowering and anti-cancer properties. Consequently, tocochromanols are valuable additives in the food, feed, cosmetic and pharmaceutical industries.
The metabolic engineering strategy of S. cerevisiae to enable tocochromanol biosynthesis was started in a preceding master thesis with the provision of the aromatic moiety, homogentisic acid (HGA), from the aromatic amino acid biosynthesis. Hereby, the upregulation and redirection of the native pathway was essential. Therefore, a strain with an engineered aromatic amino acid pathway for improved 4 hydroxyphenylpyruvate (HPP) production (MRY33) was utilised from Reifenrath and Boles (2018). Furthermore, a heterologous hydroxyphenylpyruvate dioxygenase (HPPD) was required to convert HPP into HGA. Thus, several heterologous HPPDs were expressed and characterised regarding their HGA production within the previous study. The best variant originated from Yarrowia lipolytica, YlHPPD, and was integrated into the genome of MRY33. The resulting strain JBY2, produced 435 mg/L HGA in a shake flask fermentation.
This work was started with the genetically highly modified strain JBY2, whose genome already contained a large number of genes artificially expressed behind strong promoters. For further strain development, it was advantageous to maintain a high degree of sequence variability in order to prevent genomic instabilities due to sequence homologies. Thus, 17 artificial promoters (AP1-AP17) were characterised regarding their strength of expression by the yellow fluorescent protein (YFP). These sequences were also part of a patent that was filed during this work (WO2023094429A1).
The key point of this study was the development of a metabolic engineering strategy for the strain JBY2. First, the sufficient supply of the second precursor, the polyprenyl side chain, was investigated. Natively, S. cerevisiae produces the precursor, geranylgeranyl diphosphate (GGPP), from the isopentenyl diphosphate pathway. However, without further engineering, GGPP was barely detectable in JBY2 (< 0.1 mg/L). Thus, engineering of the isopentenyl diphosphate biosynthesis was necessary. The limiting enzyme of the mevalonate pathway was the 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), which is encoded by HMG1. Therefore, a truncation for feedback-resistance and its overexpression by a promoter exchange was performed. Furthermore, the promoter of the gene for the squalene synthase (pERG9) was exchanged by the ergosterol sensitive promoter pERG1 to limit the metabolic flux of the mevalonate pathway into the ergosterol pathway. The native GGPP synthase (BTS1) was another limitation that was observed throughout this study. To overcome this bottleneck, plasmid-based and integrative overexpression of the native BTS1 and a codon optimised BTS1 were investigated. Other strategies to improve GGPP production were the deletion of the gene for the diacylglycerol pyrophosphate phosphatase (DPP1) to prevent excessive dephosphorylation of GGPP to geranylgeraniol (GGOH), and the overexpression of the farnesyl pyrophosphate synthetase, encoded by ERG20. However, the best improvements of the GGPP biosynthesis, inferred through GGOH measurements, were achieved from the screening of several heterologous GGPP synthases in S. cerevisiae. The best performing strain was JBY61 (JBY2, hmg1Δ::pTDH3-HMG1tr[1573–3165], pERG9Δ::pERG1, ChrIV-49293-49345Δ::pTDH3-XdcrtE-tSSA1_LEU2), bearing the heterologous GGPP synthase crtE of Xanthophyllomyces dendrorhous and produced 64.23 mg/L GGOH. Consequently, this engineering strategy improved the GGOH production by a factor of 642 compared to the parent strain JBY2.
Methylorubrum extorquens is an important model methylotroph and has enormous potential for the development of C1-based microbial cell factories. During strain construction, regulated promoters with a low background expression level are important genetic tools for expression of potentially toxic genes. Here we present an accordingly optimised promoter, which can be used for that purpose. During construction and testing of terpene production strains harbouring a recombinant mevalonate pathway, strong growth defects were observed which made strain development impossible. After isolation and characterisation of suppressor mutants, we discovered a variant of the cumate-inducible promoter PQ2148 used in this approach. Deletion of 28 nucleotides resulted in an extremely low background expression level, but also reduced the maximal expression strength to about 30% of the original promoter. This tightly repressed promoter version is a powerful module for controlled expression of potentially toxic genes in M. extorquens.
The toxicity of microplastics on Daphnia magna as a key model for freshwater zooplankton is well described. While several studies predict population-level effects based on short-term, individual-level responses, only very few have validated these predictions experimentally. Thus, we exposed D. magna populations to irregular polystyrene microplastics and diatomite as natural particle (both ≤ 63 μm) over 50 days. We used mixtures of both particle types at fixed particle concentrations (50,000 mL-1) and recorded the effects on overall population size and structure, the size of the individual animals, and resting egg production. Particle exposure adversely affected the population density and structure, and induced resting egg production. The terminal population size was 28–42% lower in exposed compared to control populations. Interestingly, mixtures containing diatomite induced stronger effects than microplastics alone, highlighting that natural particles are not per se less toxic than microplastics. Our results demonstrate that an exposure to synthetic and natural particles has negative population-level effects on zooplankton. Understanding the mixture toxicity of microplastics and natural particles is important given that aquatic organisms will experience exposure to both. Just as for chemical pollutants, better knowledge of such joint effects is essential to fully understand the environmental impacts of complex particle mixtures.
Environmental Implications While microplastics are commonly considered hazardous based on individual-level effects, there is a dearth of information on how they affect populations. Since the latter is key for understanding the environmental impacts of microplastics, we investigated how particle exposures affect the population size and structure of Daphnia magna. In addition, we used mixtures of microplastics and natural particles because neither occurs alone in nature and joint effects can be expected in an environmentally realistic scenario. We show that such mixtures adversely affect daphnid populations and highlight that population-level and mixture-toxicity designs are one important step towards more environmental realism in microplastics research.
Gravitropism is a fundamental process in plants that allows shoots to grow upward and roots to grow downward. Protein phosphorylation has been postulated to participate in the intricate signaling cascade of gravitropism. In order to elucidate the underlying mechanisms governing the gravitropic signaling and unearth novel protein constituents, an exhaustive investigation employing microgravity-induced phosphoproteomics was undertaken. The significantly phosphorylated proteins unraveled in this study can be effectively divided into two groups through clustering analysis. Furthermore, the elucidation of Gene Ontology (GO) enrichment analysis disclosed the conspicuous overrepresentation of these clustered phosphoproteins in cytoskeletal organization and in hormone-mediated responses intimately intertwined with the intricate phenomenon of gravitropism. Motif enrichment analysis unveiled the overrepresentation of [-pS-P-] and [-R-x-x-pS-] motifs. Notably, the [-pS-P-] motif has been suggested as the substrate for the Casein kinase II (CK II) and Cyclin-dependent kinase (CDK). Kinase-inhibitor assays confirmed the pivotal role played by CK II and CDK in root gravitropism. Mutant gravitropism assays validated the functional significance of identified phosphoproteins, with some mutants exhibiting altered bending kinetics using a custom-developed platform. The study also compared phosphoproteomics data from different platforms, revealing variations in the detected phosphopeptides and highlighting the impact of treatment differences. Furthermore, the involvement of TOR signaling in microgravity-induced phosphorylation changes was uncovered, expanding the understanding of plant gravitropism responses.
To fulfill the large-scale verification of interesting candidates from the phosphoproteomics study, a novel root and hypocotyl gravitropism phenotyping platform was developed. This platform integrated cost-effective hardware, including Raspberry Pi, a high-quality camera, an Arduino board, a rotation stage (obtained from Prof. Dr. Maik Böhmer), and programmable green light (modified by Sven Plath). In addition, through collaboration with a software developer, machine-learning-based software was developed for data analysis. This platform tested the gravitropic response of candidate mutants identified in the phosphoproteomics study. Furthermore, the capabilities of this platform were expanded to investigate tropisms in other species and organs. To find novel proteins that might act as partners of a key protein that is involved in gravitropism signaling, ALTERED RESPONSE TO GRAVITY 1 (ARG1), immunoprecipitation coupled with Mass Spectrometry (IP-MS) was performed and identified ARG1-LIKE1 (ARL1) as a potential interacting protein with ARG1. This interaction was further confirmed through in vivo pull-down assays and bimolecular fluorescence complementation assays. In addition, the interaction between ARG1 and HSP70-1 was also validated.
Overall, this thesis sheds light on the molecular components and signaling events involved in plant gravitropism. It contributes to existing knowledge and opens up new ways to investigate this fascinating area of plant biology.
Branching allows neurons to make synaptic contacts with large numbers of other neurons, facilitating the high connectivity of nervous systems. Neuronal arbors have geometric properties such as branch lengths and diameters that are optimal in that they maximize signaling speeds while minimizing construction costs. In this work, we asked whether neuronal arbors have topological properties that may also optimize their growth or function. We discovered that for a wide range of invertebrate and vertebrate neurons the distributions of their subtree sizes follow power laws, implying that they are scale invariant. The power-law exponent distinguishes different neuronal cell types. Postsynaptic spines and branchlets perturb scale invariance. Through simulations, we show that the subtree-size distribution depends on the symmetry of the branching rules governing arbor growth and that optimal morphologies are scale invariant. Thus, the subtree-size distribution is a topological property that recapitulates the functional morphology of dendrites.
The establishment and maintenance of protected areas (PAs) is viewed as a key action in delivering post-2020 biodiversity targets. PAs often need to meet multiple objectives, ranging from biodiversity protection to ecosystem service provision and climate change mitigation, but available land and conservation funding is limited. Therefore, optimizing resources by selecting the most beneficial PAs is vital. Here, we advocate for a flexible and transparent approach to selecting protected areas based on multiple objectives, and illustrate this with a decision support tool on a global scale. The tool allows weighting and prioritization of different conservation objectives according to user-specified preferences, as well as real-time comparison of the selected areas that result from such different priorities. We apply the tool across 1347 terrestrial PAs and highlight frequent trade-offs among different objectives, e.g., between species protection and ecosystem integrity. Outputs indicate that decision makers frequently face trade-offs among conflicting objectives. Nevertheless, we show that transparent decision-support tools can reveal synergies and trade-offs associated with PA selection, thereby helping to illuminate and resolve land-use conflicts embedded in divergent societal and political demands and values.