Institutes
Refine
Year of publication
Document Type
- Article (320)
- Doctoral Thesis (179)
- Preprint (41)
Language
- English (540) (remove)
Has Fulltext
- yes (540)
Is part of the Bibliography
- no (540)
Keywords
- Podospora anserina (8)
- aging (8)
- SARS-CoV-2 (7)
- Cyanobacteria (5)
- Ecology (5)
- Membrane Proteins (5)
- Phylogeny (5)
- mitochondria (5)
- Acetogenesis (4)
- Biodiversity (4)
- Haloferax volcanii (4)
- Saccharomyces cerevisiae (4)
- Synechococcus (4)
- alternative splicing (4)
- bats (4)
- fungi (4)
- Acetogen (3)
- Bioenergetics (3)
- Biogeography (3)
- Biomarker (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)
- Transcriptomics (3)
- biodiversity (3)
- climate change (3)
- sleep (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)
- Biomarkers (2)
- Biosynthesis (2)
- Bleaching Herbicides (2)
- Climate change (2)
- Community ecology (2)
- Conservation biology (2)
- Covid19-NMR (2)
- Crustacea (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)
- Oxidative stress (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)
- 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)
- 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)
- migration (2)
- morphology (2)
- nuclear magnetic resonance (NMR) (2)
- one new species (2)
- oomycetes (2)
- peroxisomes (2)
- phylogeny (2)
- population genetics (2)
- population genomics (2)
- post-2020 biodiversity targets (2)
- pre-mRNA (2)
- predation (2)
- prefrontal cortex (2)
- prostate carcinoma cells (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)
- Behaviour (1)
- Benin (1)
- Benthic environment (1)
- Benthos (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)
- CLIP (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)
- Computational model (1)
- Conservation (1)
- Coronaries (1)
- Cortex (1)
- Cortical column (1)
- Costs (1)
- Crude oil (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)
- DIRAS2 (1)
- DNA Amplification Fingerprinting (1)
- DNA metabarcoding (1)
- DNA-Specific Labelling (1)
- Daboia russelii (1)
- Dark fermentation (1)
- Data standard (1)
- Data standards (1)
- Deep sea (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)
- Earthworms (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 disruptors (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 sciences (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)
- Europe (1)
- European Beech (1)
- European Union (1)
- Evolutionary biology (1)
- Evolutionary developmental biology (1)
- Evolutionary genetics (1)
- Excretion (1)
- Extinction (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)
- Human impact (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)
- Insularity (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 dark transition test (1)
- Light sheet-based fluorescence microscopy (1)
- Limnology (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)
- Maternal Immune Activation (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)
- Microplastics (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)
- Neurodevelopmental Psychiatric Disorders (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)
- Organophosphates (1)
- Orientation preference (1)
- Oxidation-Reduction (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)
- PURA (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)
- Pelagic (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)
- R-INLA (1)
- RBFOX1 (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)
- Shallow water (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)
- Species richness (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)
- Threatened species (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)
- Toxicity (1)
- Tragelaphus oryx (1)
- Transgenic organisms (1)
- Translational Psychiatry (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)
- Urgent actions (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)
- Zebrafish eleutheroembryo (1)
- aIF (1)
- abiotic factors (1)
- abundance (1)
- acetogen (1)
- acetogenic metabolism (1)
- acetyl-CoA (1)
- acoustic features (1)
- acoustic stream (1)
- acquisition strategy (1)
- active sensing (1)
- activity budgetx (1)
- adaptive transgenerational plasticity (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 behaviour (1)
- animal movement (1)
- animal welfare (1)
- annual plants (1)
- anomaly zone (1)
- antibiotic resistance (1)
- antibiotics (1)
- antimicrobial resistance (1)
- antipredator (1)
- apex bird species (1)
- aptamers (1)
- arabinose (1)
- archaea (1)
- arid climate (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)
- barrier (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)
- biotrophic parasites (1)
- birds (1)
- bitopic transmembrane α-helix (1)
- blood vessels (1)
- boundary patrolling (1)
- brain cancer (1)
- brain rhythms (1)
- brain waves (1)
- branching (1)
- breeding sites (1)
- cardiolipin (1)
- cardiovascular disease (1)
- carnivora (1)
- carnivores (1)
- carotenogenic pathways (1)
- carotenoid distribution (1)
- carotenoid pathway engineering (1)
- carotenoid structures (1)
- caudate (1)
- central place foraging (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)
- diatoms (1)
- differentially regulated orthologs (1)
- differentiation diversity (1)
- digital student lab (1)
- dimer interface formation (1)
- discrete choice modeling (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)
- ectrogella (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)
- fence (1)
- fitness (1)
- flowering (1)
- foliar pathogens (1)
- food contact materials (1)
- foraging (1)
- foraging site fidelity (1)
- foraging site switching (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)
- herbaria (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)
- inter- seasonal predictability (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)
- mPFC (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)
- memory (1)
- metabolic disruptors (1)
- metabolomics (1)
- metazoans (1)
- microRNA (1)
- microbiome (1)
- microplastics (1)
- microsatellite (1)
- miracula (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)
- movement (1)
- mt DNA (1)
- mtDNA haplotypes (1)
- multi-generation experiment (1)
- mushroom (1)
- mycorrhiza (1)
- myeloid angiogenic cells (1)
- natural behavior (1)
- natural products (1)
- naturalistic stimuli (1)
- nature connectedness (1)
- navigation (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)
- nomadism (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)
- oomycete (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)
- phenology (1)
- phosphoketolase (1)
- phosphotransacetylase (1)
- photocycle (1)
- phylogenetic informativeness (1)
- phylogenetic profiles (1)
- phylogenetic profiling (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)
- 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)
- root allocation strategy (1)
- root functional traits (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)
- search (1)
- sediment (1)
- selection gradients (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)
- spatial modelling (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)
- ungulate (1)
- universal (1)
- university students (1)
- unselected segregation (1)
- validity (1)
- vascular integrity (1)
- vegetation (1)
- venomous snakes (1)
- video action classification (1)
- video observation (1)
- viruses (1)
- vocalization (1)
- vocalization production; (1)
- volatile (1)
- warming (1)
- water security (1)
- white truffle (1)
- wing geometric morphometrics (1)
- wolf (1)
- wwtr1 (1)
- xenology (1)
- xylose (1)
- yap1 (1)
- yeast (1)
- zinc finger (1)
- zoo (1)
- zoo biology (1)
- zoo education (1)
- zoo elephants (1)
- µ-protein (1)
- β-Barrel Proteins (1)
- β-oxidation (1)
- ζ-Carotene (1)
Institute
- Biowissenschaften (540)
- Senckenbergische Naturforschende Gesellschaft (33)
- Medizin (17)
- Biodiversität und Klima Forschungszentrum (BiK-F) (15)
- Biochemie, Chemie und Pharmazie (13)
- Buchmann Institut für Molekulare Lebenswissenschaften (BMLS) (13)
- Zentrum für Biomolekulare Magnetische Resonanz (BMRZ) (13)
- Institut für Ökologie, Evolution und Diversität (11)
- MPI für Biophysik (8)
- Biochemie und Chemie (7)
Background: Capture and storage of the energy carrier hydrogen as well as of the greenhouse gas carbon dioxide are two major problems that mankind faces currently. Chemical catalysts have been developed, but only recently a group of anaerobic bacteria that convert hydrogen and carbon dioxide to acetate, formate, or biofuels such as ethanol has come into focus, the acetogenic bacteria. These biocatalysts produce the liquid organic hydrogen carrier formic acid from H2 + CO2 or even carbon monoxide with highest rates ever reported. The autotrophic, hydrogen-oxidizing, and CO2-reducing acetogens have in common a specialized metabolism to catalyze CO2 reduction, the Wood–Ljungdahl pathway (WLP). The WLP does not yield net ATP, but is hooked up to a membrane-bound respiratory chain that enables ATP synthesis coupled to CO2 fixation. The nature of the respiratory enzyme has been an enigma since the discovery of these bacteria and has been unraveled in this study.
Results: We have produced a His-tagged variant of the ferredoxin:NAD oxidoreductase (Rnf complex) from the model acetogen Acetobacterium woodii, solubilized the enzyme from the cytoplasmic membrane, and purified it by Ni2+–NTA affinity chromatography. The enzyme was incorporated into artificial liposomes and catalyzed Na+ transport coupled to ferredoxin-dependent NAD reduction. Our results using the purified enzyme do not only verify that the Rnf complex from A. woodii is Na+-dependent, they also demonstrate for the first time that this membrane-embedded molecular engine creates a Na+ gradient across the membrane of A. woodii which can be used for ATP synthesis.
Discussion: We present a protocol for homologous production and purification for an Rnf complex. The enzyme catalyzed electron-transfer driven Na+ export and, thus, our studies provided the long-awaited biochemical proof that the Rnf complex is a respiratory enzyme.
Following severe population decline and local extinction due to massive habitat destruction and persecution, wildcats have recently reappeared in several parts of Germany’s low mountain region. It remains unknown how this reemergence occurred, specifically if local populations have been overlooked at low densities or if the species has successfully spread across the highly fragmented anthropogenic landscape. In the central German Rhön Mountains, for instance, wildcats were believed to be extinct during most of the twentieth century, however, the species was recently detected and subsequent genetic monitoring found the presence of a sizeable population. In this study, we used microsatellite and SNP genotypes from 146 wildcat individuals from 2008 to 2017 across a ~ 15,000 km2 area in the central German low mountain region to understand the population re-establishment of wildcats in the region. Bayesian clustering and subsequent analyses revealed that animals in the Rhön Mountains appear to be a mix from the two adjacent populations in the North and South of the area, suggesting a recent range expansion from two different directions. Both populations meet in the Rhön Biosphere Reserve, leading to an admixture of the northern, autochthonous, and the southern reintroduced wildcat population. While we cannot completely exclude the possibility of undetected population persistence, the high genetic homogeneity in the central German wildcat population and the lack of any signatures of past population decline in the Rhön favor a scenario of natural expansion. Our findings thus suggest that wildcats are well capable of rapid range expansion across richly structured landscape mosaics consisting of open land, settlements, and forest patches and document the potential of massive non-invasive genetic sampling when aiming to reconstruct the complex population and range dynamics of wildlife.
In situ burning (ISB) is discussed to be one of the most suitable response strategies to combat oil spills in extreme conditions. After burning, a highly viscous and sticky residue is left and may over time pose a risk of exposing aquatic biota to toxic oil compounds. Scientific information about the impact of burn residues on the environment is scarce. In this context, a comprehensive ISB field experiment with approx. 1000L IFO 180 was conducted in a fjord in Greenland. The present study investigated the toxicity of collected ISB residues to early life stages of zebrafish (Danio rerio) as a model for potentially exposed pelagic organisms. The toxicity of ISB residues on zebrafish embryos was compared with the toxicity of the initial (unweathered) IFO 180 and chemically dispersed IFO 180. Morphological malformations, hatching success, swimming behavior, and biomarkers for exposure (CYP1A activity, AChE inhibition) were evaluated in order to cover the toxic response on different biological organization levels. Across all endpoints, ISB residues did not induce greater toxicity in zebrafish embryos compared with the initial oil. The application of a chemical dispersant increased the acute toxicity most likely due to a higher bioavailability of dissolved and particulate oil components. The results provide insight into the adverse effects of ISB residues on sensitive life stages of fish in comparison with chemical dispersant application.
Acetogenic bacteria such as Acetobacterium woodii use the Wood–Ljungdahl pathway (WLP) for fixation of CO2 and energy conservation. This pathway enables conversion of diverse substrates to the main product of acetogenesis, acetate. Methyl group containing substrates such as methanol or methylated compounds, derived from pectin, are abundant in the environment and a source for CO2. Methyl groups enter the WLP at the level of methyltetrahydrofolic acid (methyl-THF). For methyl transfer from methanol to THF a substrate-specific methyltransferase system is required. In this study, we used genetic methods to identify mtaBC2A (Awo_c22760-Awo_c22740) as the methanol-specific methyltransferase system of A. woodii. After methyl transfer, methyl-THF serves as carbon and/or electron source and the respiratory Rnf complex is required for redox homeostasis if methanol + CO2 is the substrate. Resting cells fed with methanol + CO2, indeed converted methanol to acetate in a 4:3 stoichiometry. When methanol was fed in combination with other electron sources such as H2 + CO2 or CO, methanol was converted Rnf-independently and the methyl group was condensed with CO to build acetate. When fed in combination with alternative electron sinks such as caffeate methanol was oxidized only and resulting electrons were used for non-acetogenic growth. These different pathways for the conversion of methyl-group containing substrates enable acetogens to adapt to various ecological niches and to syntrophic communities.
Tick-borne diseases are a major health problem worldwide and could become even more important in Europe in the future. Due to changing climatic conditions, ticks are assumed to be able to expand their ranges in Europe towards higher latitudes and altitudes, which could result in an increased occurrence of tick-borne diseases.
There is a great interest to identify potential (new) areas of distribution of vector species in order to assess the future infection risk with vector-borne diseases, improve surveillance, to develop more targeted monitoring program, and, if required, control measures.
Based on an ecological niche modelling approach we project the climatic suitability for the three tick species Ixodes ricinus, Dermacentor reticulatus and Dermacentor marginatus under current and future climatic conditions in Europe. These common tick species also feed on humans and livestock and are vector competent for a number of pathogens.
For niche modelling, we used a comprehensive occurrence data set based on several databases and publications and six bioclimatic variables in a maximum entropy approach. For projections, we used the most recent IPCC data on current and future climatic conditions including four different scenarios of socio-economic developments.
Our models clearly support the assumption that the three tick species will benefit from climate change with projected range expansions towards north-eastern Europe and wide areas in central Europe with projected potential co-occurrence.
A higher tick biodiversity and locally higher abundances might increase the risk of tick-borne diseases, although other factors such as pathogen prevalence and host abundances are also important.
tRNAs are L-shaped RNA molecules of ~ 80 nucleotides that are responsible for decoding the mRNA and for the incorporation of the correct amino acid into the growing peptidyl-chain at the ribosome. They occur in all kingdoms of life and both their functions, and their structure are highly conserved. The L-shaped tertiary structure is based on a cloverleaf-like secondary structure that consists of four base paired stems connected by three to four loops. The anticodon base triplet, which is complementary to the sequence of the mRNA, resides in the anticodon loop whereas the amino acid is attached to the sequence CCA at the 3′-terminus of the molecule. tRNAs exhibit very stable secondary and tertiary structures and contain up to 10% modified nucleotides. However, their structure and function can also be maintained in the absence of nucleotide modifications. Here, we present the assignments of nucleobase resonances of the non-modified 77 nt tRNAIle from the gram-negative bacterium Escherichia coli. We obtained assignments for all imino resonances visible in the spectra of the tRNA as well as for additional exchangeable and non-exchangeable protons and for heteronuclei of the nucleobases. Based on these assignments we could determine the chemical shift differences between modified and non-modified tRNAIle as a first step towards the analysis of the effect of nucleotide modifications on tRNA’s structure and dynamics.
Entoloma (Agaricales, Basidiomycota) is a species-rich genus with approximately 2000 species known worldwide. In Central America, however, information about the species of this genus is sparse, despite the generally high biodiversity in this region. Recently, 124 specimens of Entoloma were collected in Panama, Chiriquí Province. In the present publication, the morphology of 20 species represented by more than one specimen is described and depicted with photographs, line drawings, and scanning electron micrographs. Molecular phylograms based on ITS or concatenated ITS and partial nc LSU rDNA sequences are provided. The taxonomic status of these species is evaluated and 17 species of Entoloma are described as new to science. Only one species could be assigned to an already known species, viz. Entoloma belouvense. Nolanea albertinae, described from Brazil, appeared similar and is combined in E. belouvense on varietal level. The identifications of two further species are uncertain. At least 30 other species, including potentially new species, cannot formally be described due to insufficient material. A preliminary key to the species of the genus Entoloma in Panama is provided. The spatial shape of the polyhedroid basidiospores of Entoloma spp. is discussed based on literature and the micrographs generated for the present study. Our re-evaluations indicate that the type of polyhedroid basidiospore and the structure of its base are not reliable as diagnostic characters for the delimitation of subgenera in Entoloma.
NAD is a coenzyme central to metabolism that was also found to serve as a 5’-terminal cap of bacterial and eukaryotic RNA species. The presence and functionality of NAD-capped RNAs (NAD-RNAs) in the archaeal domain remain to be characterized in detail. Here, by combining LC-MS and NAD captureSeq methodology, we quantified the total levels of NAD-RNAs and determined the identity of NAD-RNAs in the two model archaea, Sulfolobus acidocaldarius and Haloferax volcanii. A complementary differential RNA-Seq (dRNA-Seq) analysis revealed that NAD transcription start sites (NAD-TSS) correlate with well-defined promoter regions and often overlap with primary transcription start sites (pTSS). The population of NAD-RNAs in the two archaeal organisms shows clear differences, with S. acidocaldarius possessing more capped small non-coding RNAs (sncRNAs) and leader sequences. The NAD-cap did not prevent 5’→3’ exonucleolytic activity by the RNase Saci-aCPSF2. To investigate enzymes that facilitate the removal of the NAD-cap, four Nudix proteins of S. acidocaldarius were screened. None of the recombinant proteins showed NAD decapping activity. Instead, the Nudix protein Saci_NudT5 showed activity after incubating NAD-RNAs at elevated temperatures. Hyperthermophilic environments promote the thermal degradation of NAD into the toxic product ADPR. Incorporating NAD into RNAs and the regulation of ADPR-RNA decapping by Saci_NudT5 is proposed to provide additional layers of maintaining stable NAD levels in archaeal cells.
Importance: This study reports the first characterization of 5’-terminally modified RNA molecules in Archaea and establishes that NAD-RNA modifications, previously only identified in the other two domains of life, are also prevalent in the archaeal model organisms Sulfolobus acidocaldarius and Haloferax volcanii. We screened for NUDIX hydrolases that could remove the NAD-RNA cap and showed that none of these enzymes removed NAD modifications, but we discovered an enzyme that hydrolyzes ADPR-RNA. We propose that these activities influence the stabilization of NAD and its thermal degradation to potentially toxic ADPR products at elevated growth temperatures.
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.
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.
Energy-conserving dimethyl sulfoxide reduction in the acetogenic bacterium Moorella thermoacetica
(2022)
Moorella thermoacetica is one of the well-studied thermophilic acetogenic bacteria. It grows by oxidation of organic substrates, CO or H2 coupled to CO2 reduction to acetate. Here, we describe that M. thermoacetica can also use dimethyl sulfoxide as terminal electron acceptor. Growth of M. thermoacetica on glucose or H2 + CO2 was stimulated by dimethyl sulfoxide (DMSO). Membranes showed a DMSO reductase activity, that was induced by growing cells in presence of DMSO. The enzyme used reduced anthraquinone-2,6-disulfonate, benzyl- and methyl viologen as electron donor, but not NAD(P)H. Activity was highest at pH 5 and 60°C, the Km for DMSO was 2.4 mM. Potential DMSO reductase subunits were identified by peptide mass fingerprinting; they are encoded in a genomic region that contains three potential dmsA genes, three dmsB genes and one dmsC gene. Transcriptome analysis revealed that two different dmsAB gene clusters were induced in the presence of DMSO. The function of these two and their predicted biochemical features are discussed. In addition, the data are in line with the hypothesis that M. thermoacetica can use DMSO alongside CO2 as electron acceptor and DMSO reduction is catalysed by an energy-conserving, membrane-bound electron transport chain with DMSO as final electron acceptor.
Thermoanaerobacter kivui is a thermophilic acetogen that can grow on carbon monoxide as sole carbon and energy source. To identify the gene(s) involved in CO oxidation, the genome sequence was analyzed. Two genes potentially encoding CO dehydrogenases were identified. One, cooS, potentially encodes a monofunctional CO dehydrogenase, whereas another, acsA, potentially encodes the CODH component of the CODH/ACS complex. Both genes were cloned, a His-tag encoding sequence was added, and the proteins were produced from a plasmid in T. kivui. His-AcsA copurified by affinity chromatography with AcsB, the acetyl-CoA synthase of the CO dehydrogenase/acetyl CoA synthase complex. His-CooS copurified with CooF1, a small iron-sulfur center containing protein likely involved in electron transport. Both protein complexes had CO:ferredoxin oxidoreductase as well as CO:methyl viologen oxidoreductase activity, but the activity of CooSF1 was 15-times and 231-times lower, respectively. To underline the importance of CooS, the gene was deleted in the CO-adapted strain. Interestingly, the ∆cooS deletion mutant did not grow on CO anymore. These experiments clearly demonstrated that CooS is essential for growth of T. kivui on CO. This is in line with the hypothesis that CooS is the CO-oxidizing enzyme in cells growing on CO.
Neuroligin-3 (Nlgn3), a neuronal adhesion protein implicated in autism spectrum disorder (ASD), is expressed at excitatory and inhibitory postsynapses and hence may regulate neuronal excitation/inhibition balance. To test this hypothesis, we recorded field excitatory postsynaptic potentials (fEPSPs) in the dentate gyrus of Nlgn3 knockout (KO) and wild-type mice. Synaptic transmission evoked by perforant path stimulation was reduced in KO mice, but coupling of the fEPSP to the population spike was increased, suggesting a compensatory change in granule cell excitability. These findings closely resemble those in neuroligin-1 (Nlgn1) KO mice and could be partially explained by the reduction in Nlgn1 levels we observed in hippocampal synaptosomes from Nlgn3 KO mice. However, unlike Nlgn1, Nlgn3 is not necessary for long-term potentiation. We conclude that while Nlgn1 and Nlgn3 have distinct functions, both are required for intact synaptic transmission in the mouse dentate gyrus. Our results indicate that interactions between neuroligins may play an important role in regulating synaptic transmission and that ASD-related neuroligin mutations may also affect the synaptic availability of other neuroligins.
Bei den meisten erwachsenen Säugetieren führt ein Herzinfarkt zu Fibrose und Verlust von funktionellem Herzgewebe. Einige Wirbeltiere, wie der Zebrabärbling, besitzen jedoch die bemerkenswerte Fähigkeit, nach einer Schädigung ihres Herzgewebes verlorenes Gewebe zu regenerieren und so schädliche Folgen zu verhindern. Die lokale Immunantwort auf eine Verletzung wird zunehmend als eine wichtige Determinante für das regenerative Potential eines Gewebes gesehen. Das Komplementsystem ist Teil des humoralen Immunsystems. Historisch ist es als eine Sammlung von Protein bekannt, den Komplementkomponenten, die in der Leber synthetisiert werden und im Blutkreislauf zirkulieren. Bei Exposition gegenüber einem Auslöser, wie z. B. einem Pathogen, wird eine Komplementkomponentproteinspaltungskaskade initiiert, die dazu führen kann, dass Immunzellen rekrutiert werden, und, dass die Phagozytose erleichtert, ggf. die Zielzelle lysiert wird. Studien legen nahe, dass das Komplementsystem an zellulären Prozessen beteiligt sei, die für Entwicklungs- und Krankheitsprozesse entscheidend sind, wie etwa Proliferation und Dedifferenzierung. Es gibt Hinweise, dass das Komplementsystem eine Rolle bei Krebserkrankungen und bei regenerativen Prozessen spielen könnte. In verschiedenen Arten wurde eine lokale verletzungsinduzierte Expression von komplementkomponentkodierenden Genen in regenerierendem Gewebe beobachtet.
Einzelne Studien legen nahe, dass Funktionsverlust einzelner Komplementkomponenten regenerative Prozesse beeinträchtigt.
Offene Fragen bleiben jedoch: Ist die lokale Expression von mehreren komplementkomponentkodierenden Genen ein Merkmal von regenerierendem Gewebe, das sie von Geweben unterscheidet, welchem die Fähigkeit zur Regeneration fehlt? Und welche Rolle könnte das Komplementsystem und seine Komponenten während des regenerativen Prozesses spielen? Um diesen Fragen nachzugehen, wurde eine Expressionsanalyse von Zebrabärblingsgewebe nach Verletzung mittels RT-qPCR und in situ Hybridisierung durchgeführt: kardiale Kryoverletzung, Larvenrumpfamputation und Schwanzflossenamputation. Ich beobachtete, dass mehrere komplementkomponentkodierende Gene in diesen Geweben nach Verletzung induziert wurden. Die Interpretation veröffentlichter single cell RNAseq Datensätze legt nahe, dass diese komplementkomponentenkodierenden Gene von verschiedenen Zelltypen exprimiert werden, darunter Immunzellen, Epikardzellen und Fibroblasten. Um transkriptionelle Unterschiede zwischen regenerierendem und nicht regenerierendem Gewebe zu identifizieren, verwendete ich ein nicht regeneratives Zebrabärblingmodell, die il11ra- Mutante. Dieser Mutante fehlt die Fähigkeit, verschiedene Organe zu regenerieren, das ist der Fall beim Herzen, dem larvalen Rumpf, und der Schwanzflosse. Ich stellte fest, dass die Mehrheit der verletzungsinduzierten komplementkomponentkodierenden Gene il11ra nachgeschaltet war. Darüber hinaus zeigten Experimente unter Verwendung chemischer Inhibitoren, dass speziell die Expression der komplementkomponentkodierenden Gene c3a.1,
c4b und c7a im Larvenrumpfamputationsmodell durch den Il11-Stat3-Signalweg moduliert wird.
Zur Klärung der Frage, ob das Komplementsystem und/ oder seine Komponenten eine Rolle während der Regeneration spielen, wurden verschiede Funktionsverlustmodelle generiert und im larvalen Rumpfamputationsmodell auf mögliche Aberrationen getestet. Zum einen generierte ich Überexpressionslinien von endogenen Inhibitoren der Komplementproteinspaltungskaskade. Überexpression eines etablierten Komplementsysteminhibitors rca2.1/ tecrem führte zu einer im Vergleich zu Wildtyp- Geschwistern verringerten Regeneration des larvalen Rumpfs. Zum anderen generierte ich Funktionsverlustmutanten von individuellen Komplementkomponenten durch CRISPR/Cas9 vermittelter Mutagenese, und zwar für masp1, masp2, cfd, c1s, c4b, c5 und c9. Die larvale Rumpfregeneration war in diesen Mutanten unauffällig. Allerdings zeigten c4b Mutanten eine verringerte Kardiomyozytenproliferation und eine differenzielle Expression von einigen Markergenen, einschließlich einer erhöhten Expression von inflammatorischen Zytokinen.
Meine Studien führten zu neuen Einblicken in das Komplementsystem im Kontext der Regeneration. Ich fand heraus, dass mehrere komplementkomponentenkodierenden Gene in regenerierendem Zebrabärblinggewebe exprimiert werden, und zwar im Herzgewebe, im larvalen Rumpf und in der adulten Flosse. Darüber hinaus zeige ich, dass die verletzungsinduzierte Expression von komplementkodierenden Genen in regenerierendem Gewebe dem Regenerationsmasterregulator il11ra nachgeschaltet ist. Speziell c3a.1, c4b und c7a wurden durch il11/ stat3 reguliert...
Bisphenols and phthalates, chemicals frequently used in plastic products, promote obesity in cell and animal models. However, these well-known metabolism-disrupting chemicals (MDCs) represent only a minute fraction of all compounds found in plastics. To gain a comprehensive understanding of plastics as a source of exposure to MDCs, we characterized the chemicals present in 34 everyday products using nontarget high-resolution mass spectrometry and analyzed their joint adipogenic activities by high-content imaging. We detected 55,300 chemical features and tentatively identified 629 unique compounds, including 11 known MDCs. Importantly, the chemicals extracted from one-third of the products caused murine 3T3-L1 preadipocytes to proliferate, and differentiate into adipocytes, which were larger and contained more triglycerides than those treated with the reference compound rosiglitazone. Because the majority of plastic extracts did not activate the peroxisome proliferator-activated receptor γ and the glucocorticoid receptor, the adipogenic effects are mediated via other mechanisms and, thus, likely to be caused by unknown MDCs. Our study demonstrates that daily-use plastics contain potent mixtures of MDCs and can, therefore, be a relevant yet underestimated environmental factor contributing to obesity.
Bisphenols and phthalates, chemicals frequently used in plastic products, promote obesity in cell and animal models. However, these well-known metabolism disrupting chemicals (MDCs) represent only a minute fraction of all compounds found in plastics. To gain a comprehensive understanding of plastics as a source of exposure to MDCs, we characterized all chemicals present in 34 everyday products using nontarget high-resolution mass spectrometry and analyzed their joint adipogenic activities by high-content imaging. We detected 55,300 chemical features and tentatively identified 629 unique compounds, including 11 known MDCs. Importantly, chemicals that induced proliferation, growth, and triglyceride accumulation in 3T3-L1 adipocytes were found in one third of the products. Since the majority did not target peroxisome proliferator-activated receptor γ, the effects are likely to be caused by unknown MDCs. Our study demonstrates that daily-use plastics contain potent mixtures of MDCs and can, therefore, be a relevant yet underestimated environmental factor contributing to obesity.
Teaser Plastics contain a potent mixture of chemicals promoting adipogenesis, a key process in developing obesity.
The toxicity of microplastics on Daphnia magna as 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 overall population density, 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 31–42% 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 risks 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 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.
Differential derepression of the genome of potato tuber cells can be initiated by slicing the tissue into disks. The consequence of this procedure on the cells of the wound surface is dedifferentiation and cell division followed by redifferentiation to a suberized phellem cell. The drift of glucose-, glucose-1-phosphate-, glucose-6-phosphate-, fructose-6-phosphate- and 6-phospho-gluconatelevels has been determined in the derepressed tissue. With the exception of 6-phospho-gluconate all intermediates so far investigated showed a rise in concentration after derepression.
This is interpreted as a consequence of altered enzymic activities which were estimated for phosphoglucomutase, hexokinase, phosphoglucoisomerase, gluco-6-phosphate- and 6-phosphogluconatedehydrogenase. The two dehydrogenases were activated after derepression, the activation represented a de-novo-synthesis, as was demonstrated with the inhibitors Actidione (translation) and p-Fluorophenyl-alanine (protein synthesis in general). Hexokinase and phosphoglucoisomerase were not severely affected by cutting the tissue. Phosphoglucomutase was degrated rapidly, the degradation being dependent on protein synthesis. The importance of an enhanced activity of the pentose phosphate shunt for the stressed cell is emphasized and the possibility of an alteration in the osmotic pressure within the cell and especially in the nucleus — a primary consequence of wounding — as a cause of derepression in potato tuber cells is discussed.
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.
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 particles 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 size 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.
Several clinically used drugs are derived from microorganisms that often produce them via non-ribosomal peptide synthetases (NRPS), giant megasynthases that activate and connect individual amino acids in an assembly line fashion. Since NRPS are not restricted to the incorporation of the 20 proteinogenic amino acids, their efficient manipulation would allow the biotechnological generation of several different peptides including linear, cyclic and further modified derivatives. Here we describe a detailed phylogenetic analysis of several bacterial NRPS that led to the identification of a new recombination breakpoint within the thiolation (T) domain important in natural NRPS evolution. From this an evolutionary-inspired eXchange Unit between T domains (XUT) approach was developed, which allows the assembly of NRPS fragments over a broad range of GC contents, protein similarities, and extender unit specificities, as was shown for the specific production of a proteasome inhibitor, designed and assembled from five different NRPS fragments.
Many clinically used drugs are derived from or inspired by bacterial natural products that often are biosynthesised via non-ribosomal peptide synthetases (NRPS), giant megasynthases that activate and join individual amino acids in an assembly line fashion. Since NRPS are not limited to the incorporation of the 20 proteinogenic amino acids, their efficient manipulation would allow the biotechnological generation of complex peptides including linear, cyclic and further modified natural product analogues, e.g. to optimise natural product leads. Here we describe a detailed phylogenetic analysis of several bacterial NRPS that led to the identification of a new recombination breakpoint within the thiolation (T) domain that is important for natural NRPS evolution. From this, an evolution-inspired eXchange Unit between T domains (XUT) approach was developed which allows the assembly of NRPS fragments over a broad range of GC contents, protein similarities, and extender unit specificities, as demonstrated for the specific production of a proteasome inhibitor designed and assembled from five different NRPS fragments.
Biosynthesis of butyrate from methanol and carbon monoxide by recombinant Acetobacterium woodii
(2022)
Methanol is one of the most widely produced organic substrates from syngas and can serve as a bio-feedstock to cultivate acetogenic bacteria which allows a major contribution to reducing greenhouse gas. Acetobacterium woodii is one of the very few acetogens that can utilize methanol to produce acetate as sole product. Since A. woodii is genetically tractable, it is an interesting candidate to introduce recombinant pathways for production of bio-commodities from methanol. In this study, we introduced the butyrate production operon from a related acetogen, Eubacterium callanderi KIST612, into A. woodii and show a stable production of butyrate from methanol. This study also reveals how butyrate production by recombinant A. woodii strains can be enhanced with addition of electrons in the form of carbon monoxide. Our results not only show a stable expression system of non-native enzymes in A. woodii but also increase in the product spectrum of A. woodii to compounds with higher economic value.
Thermoanaerobacter kivui is an acetogenic model organism that reduces CO2 with electrons derived from H2 or CO, or from organic substrates in the Wood–Ljugdahl pathway (WLP). For the calculation of ATP yields, it is necessary to know the electron carriers involved in coupling of the oxidative and reductive parts of metabolism. Analyses of key catabolic oxidoreductases in cell-free extract (CFE) or with purified enzymes revealed the physiological electron carriers involved. The glyceraldehyde-3-phosphate dehydrogenase (GA3P-DH) assayed in CFE was NAD+-specific, NADP+ was used with less than 4% and ferredoxin (Fd) was not used. The methylene-THF dehydrogenase was NADP+-specific, NAD+ or Fd were not used. A Nfn-type transhydrogenase that catalyzes reduced Fd-dependent reduction of NADP+ with NADH as electron donor was also identified in CFE. The electron carriers used by the potential electron-bifurcating hydrogenase (HydABC) could not be unambiguously determined in CFE for technical reasons. Therefore, the enzyme was produced homologously in T. kivui and purified by affinity chromatography. HydABC contained 33.9 ± 4.5 mol Fe/mol of protein and FMN; it reduced NADP+ but not NAD+. The methylene-THF reductase (MetFV) was also produced homologously in T. kivui and purified by affinity chromatography. MetFV contained 7.2 ± 0.4 mol Fe/mol of protein and FMN; the complex did neither use NADPH nor NADH as reductant but only reduced Fd. In sum, these analysis allowed us to propose a scheme for entire electron flow and bioenergetics in T. kivui.
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.
Exploring the power of moth samples to reveal community patterns along shallow ecological gradients
(2022)
1. Analysing the effects of environmental variation on species assemblages is a key topic in community ecology. However, the outcome may strongly depend on the focal species group. Moths have often been used as the target in ecological studies due to their fast response to environmental change. Yet, some moth subgroups might be more sensitive than others to reflect environmental differences, depending on their functional and physiological characteristics.
2. We investigated which moth subsets are especially suitable to mirror responses to subtle variation in vegetation. We analysed the susceptibility of different subsets to local weather conditions and inter-annual fluctuations. Finally, we checked for the importance of including abundance information. We analysed moth communities (392 species, 23.870 individuals) at 60 sites within two Mediterranean forest reserves and investigated relationships between community composition and environment of (1) all moths (with and without taking abundances into account), and of subsets comprising only (2) small-sized species, (3) host-plant specialists, (4) moss, lichen and detritus feeding species, (5) ‘microlepidoptera’, (6) ‘macro-moths’ and (7) random subsets of 50, 100 and 200 species.
3. Incidence data performed similarly to abundance data in matrix regression models. Host plant specialists responded especially sensitive to small-scaled variation in vegetation composition. Macro-moth samples in contrast were highly prone to local weather conditions and to inter-annual abundance fluctuations. Accordingly, a focus on host-specialists and micro-moths is the best way to analyse relationships between shallow environmental gradients and insect communities.
Riboswitches are regulatory RNA elements that undergo functionally important allosteric conformational switching upon binding of specific ligands. The here investigated guanidine-II riboswitch binds the small cation, guanidinium, and forms a kissing loop-loop interaction between its P1 and P2 hairpins. We investigated the structural changes to support previous studies regarding the binding mechanism. Using NMR spectroscopy, we confirmed the structure as observed in crystal structures and we characterized the kissing loop interaction upon addition of Mg2+ and ligand for the riboswitch aptamer from Escherichia coli. We further investigated closely related mutant constructs providing further insight into functional differences between the two (different) hairpins P1 and P2. Formation of intermolecular interactions were probed by small-angle X-ray scattering (SAXS) and NMR DOSY data. All data are consistent and show the formation of oligomeric states of the riboswitch induced by Mg2+ and ligand binding.
Identifying unexpected acoustic inputs, which allows to react appropriately to new situations, is of major importance for animals. Neural deviance detection describes a change of neural response strength to a stimulus solely caused by the stimulus' probability of occurrence. In the present study, we searched for correlates of deviance detection in auditory brainstem responses obtained in anaesthetised bats (Carollia perspicillata). In an oddball paradigm, we used two pure tone stimuli that represented the main frequencies used by the animal during echolocation (60 kHz) and communication (20 kHz). For both stimuli, we could demonstrate significant differences of response strength between deviant and standard response in slow and fast components of the auditory brainstem response. The data suggest the presence of correlates of deviance detection in brain stations below the inferior colliculus (IC), at the level of the cochlea nucleus and lateral lemniscus. Additionally, our results suggest that deviance detection is mainly driven by repetition suppression in the echolocation frequency band, while in the communication band, a deviant-related enhancement of the response plays a more important role. This finding suggests a contextual dependence of the mechanisms underlying subcortical deviance detection. The present study demonstrates the value of auditory brainstem responses for studying deviance detection and suggests that auditory specialists, such as bats, use different frequency-specific strategies to ensure an appropriate sensation of unexpected sounds.
1H, 13C and 15N chemical shift assignment of the stem-loops 5b + c from the 5′-UTR of SARS-CoV-2
(2022)
The ongoing pandemic of the respiratory disease COVID-19 is caused by the SARS-CoV-2 (SCoV2) virus. SCoV2 is a member of the Betacoronavirus genus. The 30 kb positive sense, single stranded RNA genome of SCoV2 features 5′- and 3′-genomic ends that are highly conserved among Betacoronaviruses. These genomic ends contain structured cis-acting RNA elements, which are involved in the regulation of viral replication and translation. Structural information about these potential antiviral drug targets supports the development of novel classes of therapeutics against COVID-19. The highly conserved branched stem-loop 5 (SL5) found within the 5′-untranslated region (5′-UTR) consists of a basal stem and three stem-loops, namely SL5a, SL5b and SL5c. Both, SL5a and SL5b feature a 5′-UUUCGU-3′ hexaloop that is also found among Alphacoronaviruses. Here, we report the extensive 1H, 13C and 15N resonance assignment of the 37 nucleotides (nts) long sequence spanning SL5b and SL5c (SL5b + c), as basis for further in-depth structural studies by solution NMR spectroscopy.
Background: Through the rapid development in DNA sequencing methods and tools, microbiome studies on a various number of species were performed during the last decade. This advance makes it possible to analyze hundreds of samples from different species at the same time in order to obtain a general overview of the microbiota. However, there is still uncertainty on the variability of the microbiota of different animal orders and on whether certain bacteria within a species are subject to greater fluctuations than others. This is largely due to the fact that the analysis in most extensive comparative studies is based on only a few samples per species or per study site. In our study, we aim to close this knowledge gap by analyzing multiple individual samples per species including two carnivore suborders Canoidea and Feloidea as well as the orders of herbivore Perissodactyla and Artiodactyla held in different zoos. To assess microbial diversity, 621 fecal samples from 31 species were characterized by sequencing the V3–V4 region of the 16S rRNA gene using Illumina MiSeq.
Results: We found significant differences in the consistency of microbiota composition and in fecal microbial diversity between carnivore and herbivore species. Whereas the microbiota of Carnivora is highly variable and inconsistent within and between species, Perissodactyla and Ruminantia show fewer differences across species boundaries. Furthermore, low-abundance bacterial families show higher fluctuations in the fecal microbiota than high-abundance ones.
Conclusions: Our data suggest that microbial diversity is significantly higher in herbivores than in carnivores, whereas the microbiota in carnivores, unlike in herbivores, varies widely even within species. This high variability has methodological implications and underlines the need to analyze a minimum amount of about 10 samples per species. In our study, we found considerable differences in the occurrence of different bacterial families when looking at just three and six samples. However, from a sample number of 10 onwards, these within-species fluctuations balanced out in most cases and led to constant and more reliable results.
Background: Efficient transfer of chemical signals is important for successful mating in many animal species. Multiple evolutionary lineages of animals evolved direct sex pheromone transmission during traumatic mating—the wounding of the partner with specialized devices—which helps to avoid signal loss to the environment. Although such direct transmission modes of so-called allohormone pheromones are well-documented in invertebrates, they are considered rare in vertebrates. Males of several species of the frog genus Plectrohyla (Hylidae, Anura) have elongated teeth and develop swollen lips during the breeding season. Here we investigated the possibility that these structures are used to scratch the females’ skin and apply allohormone pheromones during traumatic mating in several Plectrohyla species.
Results: Our behavioural observations revealed that males press their upper jaw onto the females’ dorsum during amplexus, leaving small skin scratches with their teeth. Histological examinations of the males’ lips identified specialized mucus glands, resembling known amphibian pheromone glands. Whole-transcriptome sequencing of these breeding glands showed high expression of sodefrin precursor-like factor (SPF) proteins, which are known to have a pheromone function in multiple amphibian species.
Conclusions: Our study suggests SPF delivery via traumatic mating in several anuran species: the males have specialized breeding glands in the lips for production and secretion and use their elongated teeth as wounding devices for application. We hypothesize that these SPF proteins end up in the females’ circulatory system, where understanding their exact function will require further molecular, physiological and behavioural testing.
Natural products have been proven to be important starting points for the development of new drugs. Bacteria in the genera Photorhabdus and Xenorhabdus produce antimicrobial compounds as secondary metabolites to compete with other organisms. Our study is the first comprehensive study screening the anti-protozoal activity of supernatants containing secondary metabolites produced by 5 Photorhabdus and 22 Xenorhabdus species against human parasitic protozoa, Acanthamoeba castellanii, Entamoeba histolytica, Trichomonas vaginalis, Leishmania tropica and Trypanosoma cruzi, and the identification of novel bioactive antiprotozoal compounds using the easyPACId approach (easy Promoter Activated Compound Identification) method. Though not in all species, both bacterial genera produce antiprotozoal compounds effective on human pathogenic protozoa. The promoter exchange mutants revealed that antiprotozoal bioactive compounds produced by Xenorhabdus bacteria were fabclavines, xenocoumacins, xenorhabdins and PAX peptides. Among the bacteria assessed, only P. namnaoensis appears to have acquired amoebicidal property which is effective on E. histolytica trophozoites. These discovered antiprotozoal compounds might serve as starting points for the development of alternative and novel pharmaceutical agents against human parasitic protozoa in the future.
Baleen whales (Mysticeti) are a clade of highly adapted carnivorous marine mammals that can reach extremely large body sizes and feature characteristic keratinaceous baleen plates used for obligate filter feeding. From a conservation perspective, nearly all baleen whale species were hunted extensively over a roughly 100 years lasting time period that depleted many of the respective whale stocks with so far unknown consequences for e.g. their molecular viability. From an evolutionary perspective, the lack of fossil records together with conflicting molecular patterns resulted in a still unclear and debated phylogeny of modern baleen whales, particularly in rorquals (Balaenopteridae). In this dissertation, I will demonstrate the application of baleen whale genomes to tackle these open questions by using modern approaches of conservation and evolutionary genomics.
Conservation genomic aspects of baleen whales were addressed in two projects, both using whole genome data of either an Icelandic fin whale (Balaenoptera physalus) population or multiple blue whale (Balaenoptera musculus) populations to evaluate the impact of the industrial whaling era on their molecular viability. The results suggest a substantial drop in effective population size of both species but also a lack of manifestation in genotypes of the fin whale population when compared to the blue whale populations. Especially the rare and short runs of homozygosity (ROH), usually indicative for inbreeding, suggest frequent outcrossing in fin whales while all analyzed blue whale populations featured long and frequent ROH. In addition to these analyses, genome data of blue whale populations was further used to evaluate if northern hemisphere blue whales diverged into different subspecies. Population genetic and gene flow analyses showed clearly separated and well isolated populations in accordance with their assumed geographical distance. In contrast, the genome-wide divergence between all blue whale populations was low compared to other cetacean populations and to the next closely related sei whale species. Because this includes the morphologically different and well recognized pygmy blue whale subspecies, a proposal was made to equally categorize the two northern-hemisphere blue whale populations as subspecies.
Evolutionary aspects were addressed in a third project, by constructing the genome of the pygmy right whale (Caperea marginata) and testing its potential in phylogenetics and cancer research. Phylogenomic analyses using fragments of a whole-genome alignment featuring nearly all extant baleen whales, allowed the revision of the complex evolutionary relationships of rorquals by quantifying and characterizing the amounts of conflicts in early diverging branches. These relationships were further used to identify phylogenetically independent pairs of baleen whales with a maximum of diverging body size differences to compare rates of positive selection between their genomes. The results suggest nearly evenly distributed frequencies of alternative topologies which supports the representation of the early divergence of rorquals as a hard polytomy with high amounts of introgression and incomplete lineage sorting. Within the set of available genomic data, three independent pairs of baleen whales with diverging body sizes were found and comparisons of positive selection rates resulted in many potentially body size and cancer related genes. The lack of conserved selection patterns, however, suggest a more convergent evolution of size and cancer resistance like previously discussed in paleontology.
In conclusion, the application of whole genome data using methods of conservation genetics allowed for a comprehensive estimation about the molecular viability of blue and fin whales as well as an assessment of the taxonomic status of northern-hemisphere blue whale populations. The rather different results between blue and fin whales underlines the importance of genomic monitoring of baleen whales because different species show rather different molecular consequences of their potentially varying depletions. Furthermore, as showcased for the northern-hemisphere blue whale, many important isolated populations of baleen whales may still be unknown to conservation management and genome-wide comparisons will most likely contribute to overcome this under-classification problem. The application of whole genome data in evolutionary research allowed the characterization of the complex patterns of molecular conflicts within baleen whales and especially rorquals that will contribute to the still rather unclear understanding of their evolution. The here found molecular support for the idea of convergent evolution of gigantism in whales will further guide the search for molecular patterns responsible for Peto’s paradox.
The brains of black 6 mice (Mus musculus) and Seba’s short-tailed bats (Carollia perspicillata) weigh roughly the same and share mammalian neocortical laminar architecture. Bats have highly developed sonar calls and social communication and are an excellent neuroethological animal model for auditory research. Mice are olfactory and somatosensory specialists, used frequently in auditory neuroscience for their advantage of standardization and wide genetic toolkit. This study presents an analytical approach to overcome the challenge of inter-species comparison with existing data. In both data sets, we recorded with linear multichannel electrodes down the depth of the primary auditory cortex (A1) while presenting repetitive stimuli trains at ~5 and ~40 Hz to awake bats and mice. We found that while there are similarities between cortical response profiles in both, there was a better signal to noise ratio in bats under these conditions, which allowed for a clearer following response to stimuli trains. Model fit analysis supported this, illustrating that bats had stronger response amplitude suppression to consecutive stimuli. Additionally, continuous wavelet transform revealed that bats had significantly stronger power and phase coherence during stimulus response and mice had stronger power in the background. Better signal to noise ratio and lower intertrial phase variability in bats could represent specialization for faster and more accurate temporal processing at lower metabolic costs. Our findings demonstrate a potentially different general auditory processing principle; investigating such differences may increase our understanding of how the ecological need of a species shapes the development and function of its nervous system.
Enhanced LTP of population spikes in the dentate gyrus of mice haploinsufficient for neurobeachin
(2020)
Deletion of the autism candidate molecule neurobeachin (Nbea), a large PH-BEACH-domain containing neuronal protein, has been shown to affect synaptic function by interfering with neurotransmitter receptor targeting and dendritic spine formation. Previous analysis of mice lacking one allele of the Nbea gene identified impaired spatial learning and memory in addition to altered autism-related behaviours. However, no functional data from living heterozygous Nbea mice (Nbea+/−) are available to corroborate the behavioural phenotype. Here, we explored the consequences of Nbea haploinsufficiency on excitation/inhibition balance and synaptic plasticity in the intact hippocampal dentate gyrus of Nbea+/− animals in vivo by electrophysiological recordings. Based on field potential recordings, we show that Nbea+/− mice display enhanced LTP of the granule cell population spike, but no differences in basal synaptic transmission, synapse numbers, short-term plasticity, or network inhibition. These data indicate that Nbea haploinsufficiency causes remarkably specific alterations to granule cell excitability in vivo, which may contribute to the behavioural abnormalities in Nbea+/− mice and to related symptoms in patients.
he most basic behavioural states of animals can be described as active or passive. While high-resolution observations of activity patterns can provide insights into the ecology of animal species, few methods are able to measure the activity of individuals of small taxa in their natural environment. We present a novel approach in which a combination of automatic radiotracking and machine learning is used to distinguish between active and passive behaviour in small vertebrates fitted with lightweight transmitters (<0.4 g).
We used a dataset containing >3 million signals from very-high-frequency (VHF) telemetry from two forest-dwelling bat species (Myotis bechsteinii [n = 52] and Nyctalus leisleri [n = 20]) to train and test a random forest model in assigning either active or passive behaviour to VHF-tagged individuals. The generalisability of the model was demonstrated by recording and classifying the behaviour of tagged birds and by simulating the effect of different activity levels with the help of humans carrying transmitters. The model successfully classified the activity states of bats as well as those of birds and humans, although the latter were not included in model training (F1 0.96–0.98).
We provide an ecological case-study demonstrating the potential of this automated monitoring tool. We used the trained models to compare differences in the daily activity patterns of two bat species. The analysis showed a pronounced bimodal activity distribution of N. leisleri over the course of the night while the night-time activity of M. bechsteinii was relatively constant. These results show that subtle differences in the timing of species' activity can be distinguished using our method.
Our approach can classify VHF-signal patterns into fundamental behavioural states with high precision and is applicable to different terrestrial and flying vertebrates. To encourage the broader use of our radiotracking method, we provide the trained random forest models together with an R package that includes all necessary data processing functionalities. In combination with state-of-the-art open-source automated radiotracking, this toolset can be used by the scientific community to investigate the activity patterns of small vertebrates with high temporal resolution, even in dense vegetation.
The most basic behavioural states of animals can be described as active or passive. However, while high-resolution observations of activity patterns can provide insights into the ecology of animal species, few methods are able to measure the activity of individuals of small taxa in their natural environment. We present a novel approach in which the automated VHF radio-tracking of small vertebrates fitted with lightweight transmitters (< 0.2 g) is used to distinguish between active and passive behavioural states.
A dataset containing > 3 million VHF signals was used to train and test a random forest model in the assignment of either active or passive behaviour to individuals from two forest-dwelling bat species (Myotis bechsteinii (n = 50) and Nyctalus leisleri (n = 20)). The applicability of the model to other taxonomic groups was demonstrated by recording and classifying the behaviour of a tagged bird and by simulating the effect of different types of vertebrate activity with the help of humans carrying transmitters. The random forest model successfully classified the activity states of bats as well as those of birds and humans, although the latter were not included in model training (F-score 0.96–0.98).
The utility of the model in tackling ecologically relevant questions was demonstrated in a study of the differences in the daily activity patterns of the two bat species. The analysis showed a pronounced bimodal activity distribution of N. leisleri over the course of the night while the night-time activity of M. bechsteinii was relatively constant. These results show that significant differences in the timing of species activity according to ecological preferences or seasonality can be distinguished using our method.
Our approach enables the assignment of VHF signal patterns to fundamental behavioural states with high precision and is applicable to different terrestrial and flying vertebrates. To encourage the broader use of our radio-tracking method, we provide the trained random forest models together with an R-package that includes all necessary data-processing functionalities. In combination with state-of-the-art open-source automated radio-tracking, this toolset can be used by the scientific community to investigate the activity patterns of small vertebrates with high temporal resolution, even in dense vegetation.
One of the earliest consequences of slicing plant storage organs such as potato tubers into thin disks is the formation of polysomes, which in potato slices is complete after 9 hours and is dependent on transcription. Fresh disks do not incorporate 32P, 3H-uridine or 14C-leucine into their ribosomes, whereas ribosomes and polysomes of aged disks use these precursors effectively. This development can be completely blocked by actinomycin D. Among the different RNAs synthesized during aging is 28S- and 16S—rRNA, 5S—RNA, tRNA, and a component sedimenting around 15—18S with a base-composition different from 16S—rRNA, 5S- and 4S—RNA and which supports peptide formation in an in vitro incorporation system.
It is suggested that this compound represents mRNA, which is not available immediately after slicing the tissue. These findings are consistent with the view of a derepression phenomenon in sliced storage tissue.
Whereas ribosome preparations of freshly sliced potato disks do not show appreciable activity in an in-vitro amino acid incorporation system, aging of the tissue leads to a greatly enhanced incorporation activity which reaches its maximum 24 hours after slicing. If ribosomes from freshly excised disks are provided with polyuridylic acid, their activity in the incorporation of phenylalanine is increased about 8 fold.
Moreover, an RNA-fraction can be dissociated by EDTA from ribosomes of aged potato tuber slices, which sediments at 15 —18S, has a base composition different from that of 16S — rRNA, 5S-and 4S —RNA, and is not present on ribosomes of fresh slices. Its appearance is inhibited by actinomycin D and therefore most probably dependent on transcription. This compound, purified from sucrose gradients, enhances in vitro leucine incorporation into peptide material by ribosomes of fresh potato slices.
The possibility is discussed that this fraction-among other factors-is responsible for the enhanced protein synthesis after slicing plant storage organs, and is indicative of a general derepression phenomenon in these tissues.
Macrophage infectivity potentiator (MIP) proteins are widespread in human pathogens including Legionella pneumophila, the causative agent of Legionnaires’ disease and protozoans such as Trypanosoma cruzi. All MIP proteins contain a FKBP (FK506 binding protein)-like prolyl-cis/trans-isomerase domain that hence presents an attractive drug target. Some MIPs such as the Legionella protein (LpMIP) have additional appendage domains of mostly unknown function. In full-length, homodimeric LpMIP, the N-terminal dimerization domain is linked to the FKBP-like domain via a long, free-standing stalk helix. Combining X-ray crystallography, NMR and EPR spectroscopy and SAXS, we elucidated the importance of the stalk helix for protein dynamics and inhibitor binding to the FKBP-like domain and bidirectional crosstalk between the different protein regions. The first comparison of a microbial MIP and a human FKBP in complex with the same synthetic inhibitor was made possible by high-resolution structures of LpMIP with a [4.3.1]-aza-bicyclic sulfonamide and provides a basis for designing pathogen-selective inhibitors. Through stereospecific methylation, the affinity of inhibitors to to L. pneumophila and T. cruzi MIP was greatly improved. The resulting X-ray inhibitor-complex structures of LpMIP and TcMIP at 1.49 and 1.34 Å, respectively, provide a starting point for developing potent inhibitors against MIPs from multiple pathogenic microorganisms.
The production of ribosomes is a complicated multistep, that is susceptible to changes occurring within the cell and its environment. The process itself requires many proteins, known as ribosome biogenesis factors (RBFs) and many non-coding RNAs like the small nucleolar RNAs (snoRNAs). While RBFs are required for the accurate processing of the pre-rRNA into mature rRNAs, the snoRNAs act to coordinate and guide enzymes for post-transcriptional modifications, chiefly 2´-O-ribose methylation and pseudouridylation. While ribosome biogenesis is mostly described in human and yeast model eucaryotes, similar detailed studies in the model plant Arabidopsis thaliana are far less explored and understood. Furthermore, for many experimentally confirmed modification sites the according snoRNAs and for many pre-rRNA processing steps the responsible RBFs are missing. Therefore, it is expected that a high number of snoRNAs and RBFs are not identified till yet. For this reason, RNA-deep sequencing was performed in order to identify novel snoRNAs and MS analysis data of nucleoli and nuclei of A. thaliana from a former PhD student were used in order to find new proteins involved in pre-rRNA processing.
In here, it is shown that with RNA deep-sequencing still new snoRNAs and snRNAs can be identified and that detection of predicted snoRNAs can be fulfilled with a) antisense oligonucleotides tagged with fluorescence dyes and b) with radioactive labeled antisense probes. Furthermore, a secondary structure map of the 60S and 40S subunit highlighting the predicted and moreover verified modification sites in 5.8S, 25S and 18S rRNA was created. Especially, the correlation between the modification sites and the guiding snoRNA is highlighted further shedding light on overview about current pre-rRNA modification sites and corresponding guiding snoRNAs. The next chapter reveals the complex and multi-layered existence of the 5.8S rRNA and its numerous precursors. The mutant prp24 (also known as seap1) encoding AtPRP24, is recognized as factor being important for splicing as it is promoting the recruitment of the U4 and U6 snRNAs to the spliceosome. In here, it was found that AtPRP24 is involved in processing of 5.8S rRNA precursors, recognizable by precursors that are over accumulating in the mutant. Moreover, it could be shown for the first time that the plant-specific precursor 5´-5.8S is exported to the cytoplasm, where final cleavage steps of 5.8S rRNA takes place. In the prp24.2 mutant, this precursor is exported at an increased rate to the cytoplasm, where it can be detected in the actively translating ribosomes (polysomes). A lower sensitivity of the mutant seeds to cycloheximide (CHX) suggests that due to the extension at the 5´-end of 5.8S, the structure of the 60S subunit has altered CHX binding. In conclusion, this work highlights the importance and complexity of 5.8S rRNA and its precursors for ribosome biogenesis and displays new insights into pre-rRNA processing in A. thaliana.
Xylose, an abundant sugar fraction of lignocellulosic biomass, is a five-carbon skeleton molecule. Since decades, utilization of this sugar has gained much attention and has been in particular focus as a substrate for production of biofuels like ethanol by microbial hosts, including Saccharomyces cerevisiae. In this yeast, xylose is naturally not used as a carbon source, but its utilization could be achieved by metabolic engineering either via the oxidoreductive route or through the isomerase pathway. Both pathways share xylulose as a common intermediate that must be phosphorylated before entering the endogenous metabolism via the non-oxidative pentose phosphate pathway (noxPPP). Besides this, in some bacteria a non-phosphorylating oxidative pathway for xylose degradation exists, known as Weimberg pathway, where a molecule of xylose is converted by a series of enzymes - xylose dehydrogenase (XylB), xylonate dehydratase (XylD), 3-keto-2-deoxy-xylonate dehydratase (XylX) and α-ketoglutarate semialdehyde dehydrogenase (KsaD) - to form α-ketoglutarate (AKG). Besides having several useful properties as a product, AKG could also be used for cell growth as an intermediate of the tricarboxylic acid (TCA) cycle. One target of the present study is to establish a functional Weimberg pathway in S. cerevisiae. Previous studies have shown that this task is not trivial, for instance due to the toxicity of xylonate (the first metabolite of the pathway) and the involvement of an iron-sulfur cluster dependent enzyme, the D-xylonate dehydratase. The assembly of iron-sulfur clusters on a heterologous protein in yeast is known to be challenging.
To establish the Weimberg pathway in yeast, the genes xylB, xylD, and xylX were obtained from Caulobacter cresentus and ksaD was from Corynebacterium glutamicum. In a variant, the dehydratase xylD was replaced with orf41 from Arthrobacter nicotinovorans, which is believed to be independent of iron-sulfur clusters. Growth of yeast cells on xylose as a sole carbon source was expected as an indicator of a functional Weimberg pathway. However, the heterologous expression of the codon optimized genes was not sufficient to reach this goal. Due to the complexity of the interactions of the heterologous pathway with the endogenous cellular processes, it was assumed that potential limitations could be overcome by adaptive laboratory evolution, using xylose as a sole source of carbon. Increasing selection pressure was applied on a strain with Weimberg pathway genes integrated into the genome over several generations. As a variant of the evolutionary engineering approach, mutator strains were generated. For this, RAD27 and MSH2 genes were deleted, which are involved in nucleotide excision and mismatch repair mechanisms, respectively. Some of the resulting strains PRY24, PRY25, PRY27 and PRY28 were able grow in xylose as a sole carbon source after evolutionary engineering. As a control, a non-mutator strain PRY19 was also included. Strikingly, only the mutator strains were able to consume xylose as a sole carbon source, which shows the feasibility of the approach.
In addition to the mutator strain strategy, a further approach employed in the present study was the simultaneous expression of the Weimberg pathway in the cytosol and mitochondria. This was based on the reasoning that the iron-sulfur cluster biogenesis on XylD may be improved in the organelle and that the AKG is an intermediate of the TCA cycle. In the strain AHY02, all enzymes of the pathway were tagged with mitochondrial targeting signals in addition to a full cytosolically localized pathway. The localization of the mitochondrial variants was confirmed by fluorescence microscopy. Together with AHY02, CEN.PK2-1C wild type strain was also included as a control for evolution. When a selection pressure on xylose was applied, both strains - AHY02 and CEN.PK2-1C - were able to grow in the course of evolution. Deletion of the xylulokinase (XKS1) gene was found to be detrimental for both evolved strains in xylose-containing media. This suggests that the evolution of the endogenous oxidoreductive and noxPPP genes is responsible for growth of the evolved cells. For the evolved strain AHY02, it could also be possible that the Weimberg pathway genes supported to growth in addition to the oxidoreductive route. To elucidate the underlying molecular mechanisms, genome sequencing and reverse engineering approaches would be necessary in future.
In addition to screening for growth on xylose as a sole carbon source, a less stringent screening system was created to examine even a minor flux of xylose towards AKG. For this, all genes necessary for conversion of isocitrate to AKG where deleted, yielding a glutamate auxotrophic strain. In this system, the cells can grow on other carbon sources, whereas xylose is only provided as a source of AKG for the synthesis of glutamate...
Identification of new natural products from nematode-associated bacteria using mass spectrometry
(2023)
This work aims to find unknown natural products produced by bacteria, that live in close association with nematodes and to elucidate their structure by using mass spectrometry.
The first chapter of this work is dedicated to the detection of hitherto unknown natural products by using a metabolomics approach and subsequent structure elucidation of said compounds. This chapter includes metabolomics analysis of Xenorhabdus szentirmaii wild type and knockout mutants, overproduction of the target compound, identification of derivatives from other strains and MS based structure elucidation.
The second and third chapters are about natural products that protect C. elegans from B. thuringiensis infections.
The second chapter deals with natural products that protect the nematode host without killing the pathogen. I deployed molecular biology methods to generate deletion and overproduction strains of a target compound, identified it via LC-MS/MS analysis and used LC-MS/MS and lipidomics to analyse the chemical properties of the active compound.
The third chapter aims at finding natural products, which are produced by Pseudomonas strains MYb11 and MYb12, respectively. These natural products display the ability to protect C. elegans by killing B. thuringiensis. I identified said compounds via fractionation and subsequent bioactivity testing. After identification, I generated production strains of the target compounds and elucidated the structure of the bioactive derivative.
The last chapter deals with the structure elucidation of peptides produced by an unusual GameXPeptide synthetase in Xenorhabdus miraniensis. I analysed producer strains of GameXPeptides using LC-MS and elucidated the structural differences between the known GameXPeptides, produced by P. luminescens TT01, and the unusual ones produced by X. miraniensis.
Bacterial biosynthetic assembly lines, such as non-ribosomal peptide synthetases (NRPS) and polyketide synthases, are often subject of synthetic biology – because they produce a variety of natural products invaluable for modern pharmacotherapy. Acquiring the ability to engineer these biosynthetic assembly lines allows the production of artificial non-ribosomal peptides (NRP), polyketides, and hybrids thereof with new or improved properties. However, traditional bioengineering approaches have suffered for decades from their very limited applicability and, unlike combinatorial chemistry, are stigmatized as inefficient because they cannot be linked to the high-throughput screening platforms of the pharmaceutical industry. Although combinatorial chemistry can generate new molecules cheaper, faster, and in greater numbers than traditional natural product discovery and bioengineering approaches, it does not meet current medical needs because it covers only a limited biologically relevant chemical space. Hence, methods for high-throughput generation of new natural product-like compound libraries could provide a new avenue towards the identification of new lead compounds. To this end, prior to this work, we introduced an artificial synthetic NRPS type, referred to as type S NRPS, to provide a first-of-its-kind bicombinatorial approach to parallelized high-throughput NRP library generation. However, a bottleneck of these first two generations of type S NRPS was a significant drop in production yields. To address this issue, we applied an iterative optimization process that enabled titer increases of up to 55-fold compared to the non-optimized equivalents, restoring them to wild-type levels and beyond.
Non-ribosomal peptide synthetases (NRPSs) are the origin of a wide range of natural products, including many clinically used drugs. Engineering of these often giant biosynthetic machineries to produce novel non-ribosomal peptides (NRPs) at high titre is an ongoing challenge. Here we describe a strategy to functionally combine NRPS fragments of Gram-negative and -positive origin, synthesising novel peptides at titres up to 290 mg l-1. Extending from the recently introduced definition of eXchange Units (XUs), we inserted synthetic zippers (SZs) to split single protein NRPSs into up to three independently expressed and translated polypeptide chains. These synthetic type of NRPS (type S) enables easier access to engineering, overcomes cloning limitations, and provides a simple and rapid approach to building peptide libraries via the combination of different NRPS subunits.
Adhesion to host cells is the first and most crucial step in infections with pathogenic Gram negative bacteria and is often mediated by trimeric autotransporter adhesins (TAAs). TAA-producing bacteria are the causative agent of many human diseases and TAA targeted anti-adhesive compounds might counteract such bacterial infections. The modularly structured Bartonella adhesin A (BadA) is one of the best characterised TAAs and serves as an attractive adhesin to study the domain-function relationship of TAAs during infection. BadA is a major virulence factor of B. henselae and is essential for the initial attachment to host cells via adhesion to extracellular matrix proteins. B. henselae is the causative agent of cat scratch disease and adheres to fibronectin using its long BadA fibres. The life cycle of this pathogen, with alternating host conditions, drives evolutionary and host-specific adaptations.
Human, feline, and laboratory adapted B. henselae isolates display genomic and phenotypic differences. By analysing the genomes of eight B. henselae strains using long-read sequencing, a variable genomic badA island with a diversified and highly repetitive badA gene flanked by badA pseudogenes was identified. Moreover, numerous conserved flanking genes were characterised, however, their influence on the regulation of badA expression and modification remains to be explored. It seems that B. henselae G 5436 is the evolutionary ancestor of the other B. henselae strains analysed in this work. The diversity of the badA island among the B. henselae strains indicates that the downstream badA-like domain region might be used as a ‘toolbox’ for rearrangements in the badA gene. Overall, it is suggested that badA-domain duplications, insertions, and/or deletions are the result of active phase variation via site-specific recombination and contribute to rapid host adaptation in the scope of pathogenicity, immune evasion, and/or enhanced long-term colonisation.
The model strain B. henselae Marseille expresses a badA gene that includes 30 repetitive neck/stalk domains, each consisting of several predicted structural motifs. To further elucidate the motif sequences that mediate fibronectin binding, various modified badA constructs were generated. Their ability to bind fibronectin was assessed via whole-cell ELISA and fluorescence microscopy. In conclusion, it is suggested that BadA adheres to fibronectin in a cumulative fashion with quick saturation via unpaired β-strands appearing in structural motifs present in BadA neck/stalk domains 19, 27, and other homologous domains. Furthermore, antibodies targeting a 15-mer amino acid sequence in the DALL motif of BadA neck/stalk domain 27 were able to reduce fibronectin binding of the B. henselae mutant strain S27. Moreover, this DALL motif sequence is conserved in the genome of all analysed B. henselae strains. The identification of common binding motifs between BadA and fibronectin supports the development of new anti-adhesive compounds that might inhibit the initial adherence of B. henselae and other TAA-producing pathogens during infection.
mRNA localization to subcellular compartments has been reported across all kingdoms of life and it is generally believed to promote asymmetric protein synthesis and localization. In striking contrast to previous observations, we show that in S. cerevisiae the B-type cyclin CLB2 mRNA is localized and translated in the yeast bud, while the Clb2 protein, a key regulator of mitosis progression, is concentrated in the mother nucleus. Using single-molecule RNA imaging in fixed (smFISH) and living cells (MS2 system), we show that the CLB2 mRNA is transported to the yeast bud by the She2-She3 complex, via an mRNA ZIP-code situated in the coding sequence. In CLB2 mRNA localization mutants, Clb2 protein synthesis in the bud is decreased resulting in changes in cell cycle distribution and genetic instability. Altogether, we propose that CLB2 mRNA localization acts as a sensor for bud development to couple cell growth and cell cycle progression, revealing a novel function for mRNA localization.
Deviance detection describes an increase of neural response strength caused by a stimulus with a low probability of occurrence. This ubiquitous phenomenon has been reported for multiple species, from subthalamic areas to auditory cortex. While cortical deviance detection has been well characterised by a range of studies covering neural activity at population level (mismatch negativity, MMN) as well as at cellular level (stimulus-specific adaptation, SSA), subcortical deviance detection has been studied mainly on cellular level in the form of SSA. Here, we aim to bridge this gap by using noninvasively recorded auditory brainstem responses (ABRs) to investigate deviance detection at population level in the lower stations of the auditory system of a hearing specialist: the bat Carollia perspicillata. Our present approach uses behaviourally relevant vocalisation stimuli that are closer to the animals' natural soundscape than artificial stimuli used in previous studies that focussed on subcortical areas. We show that deviance detection in ABRs is significantly stronger for echolocation pulses than for social communication calls or artificial sounds, indicating that subthalamic deviance detection depends on the behavioural meaning of a stimulus. Additionally, complex physical sound features like frequency- and amplitude-modulation affected the strength of deviance detection in the ABR. In summary, our results suggest that at population level, the bat brain can detect different types of deviants already in the brainstem. This shows that subthalamic brain structures exhibit more advanced forms of deviance detection than previously known.
As abundant carbohydrates in renewable feedstocks, such as pectin-rich and lignocellulosic hydrolysates, the pentoses arabinose and xylose are regarded as important substrates for production of biofuels and chemicals by engineered microbial hosts. Their efficient transport across the cellular membrane is a prerequisite for economically viable fermentation processes. Thus, there is a need for transporter variants exhibiting a high transport rate of pentoses, especially in the presence of glucose, another major constituent of biomass-based feedstocks. Here, we describe a variant of the galactose permease Gal2 from Saccharomyces cerevisiae (Gal2N376Y/M435I), which is fully insensitive to competitive inhibition by glucose, but, at the same time, exhibits an improved transport capacity for xylose compared to the wildtype protein. Due to this unique property, it significantly reduces the fermentation time of a diploid industrial yeast strain engineered for efficient xylose consumption in mixed glucose/xylose media. When the N376Y/M435I mutations are introduced into a Gal2 variant resistant to glucose-induced degradation, the time necessary for the complete consumption of xylose is reduced by approximately 40%. Moreover, Gal2N376Y/M435I confers improved growth of engineered yeast on arabinose. Therefore, it is a valuable addition to the toolbox necessary for valorization of complex carbohydrate mixtures.
Cyclophilins, or immunophilins, are proteins found in many organisms including bacteria, plants and humans. Most of them display peptidyl-prolyl cis-trans isomerase activity, and play roles as chaperones or in signal transduction. Here, we show that cyclophilin anaCyp40 from the cyanobacterium Anabaena sp. PCC 7120 is enzymatically active, and seems to be involved in general stress responses and in assembly of photosynthetic complexes. The protein is associated with the thylakoid membrane and interacts with phycobilisome and photosystem components. Knockdown of anacyp40 leads to growth defects under high-salt and high-light conditions, and reduced energy transfer from phycobilisomes to photosystems. Elucidation of the anaCyp40 crystal structure at 1.2-Å resolution reveals an N-terminal helical domain with similarity to PsbQ components of plant photosystem II, and a C-terminal cyclophilin domain with a substrate-binding site. The anaCyp40 structure is distinct from that of other multi-domain cyclophilins (such as Arabidopsis thaliana Cyp38), and presents features that are absent in single-domain cyclophilins.