Refine
Has Fulltext
- yes (168)
Is part of the Bibliography
- yes (168)
Year of publication
- 2021 (168) (remove)
Document Type
- Journal article (132)
- Doctoral Thesis (33)
- Preprint (2)
- Working Paper (1)
Language
- English (168) (remove)
Keywords
- climate change (5)
- Apis mellifera (4)
- Trypanosoma brucei (4)
- insects (4)
- Neisseria gonorrhoeae (3)
- SARS-CoV-2 (3)
- Staphylococcus aureus (3)
- biodiversity (3)
- cancer (3)
- deadwood (3)
- distribution (3)
- meiosis (3)
- metabolism (3)
- neuropeptides (3)
- super-resolution microscopy (3)
- Bordetella pertussis (2)
- COVID-19 (2)
- CSF (2)
- Cataglyphis (2)
- Fluoreszenzmikroskopie (2)
- Formicidae (2)
- Kinetoplastida (2)
- LC/MS (2)
- MYCN (2)
- Melanom (2)
- Parkinson's disease (2)
- abscisic acid (ABA) (2)
- active zone (2)
- adaptation (2)
- antennal lobe (2)
- apoptosis (2)
- behavior (2)
- beta diversity (2)
- biological techniques (2)
- biomarker (2)
- caloric restriction (2)
- central complex (2)
- cerebrospinal fluid (2)
- circadian clock (2)
- cosmology (2)
- dSTORM (2)
- ecology (2)
- endocytosis (2)
- evolution (2)
- fluorescence spectroscopy (2)
- forensic neuropathology (2)
- forensic neurotraumatology (2)
- forest management (2)
- functional diversity (2)
- genome (2)
- genomics (2)
- global change (2)
- habitat (2)
- honeybee (2)
- host-pathogen interaction (2)
- imaging (2)
- infection (2)
- isothermal titration calorimetry (2)
- land use (2)
- loop quantum gravity (2)
- mass spectrometry (2)
- methionine restriction (2)
- nature conservation (2)
- neuroanatomy (2)
- neuromodulation (2)
- nutrients (2)
- nutrition (2)
- p53 (2)
- plasticity (2)
- proboscis extension response (2)
- proteins (2)
- time series (2)
- transcriptomics (2)
- trypanosoma (2)
- tsetse fly (2)
- 3D reconstruction (1)
- A2a-R receptor (1)
- ALPH (1)
- ALPH1 (1)
- ATP-DnaA complex (1)
- African agriculture (1)
- African trypanosome (1)
- African trypanosomes (1)
- Agrarumweltmaßnahmen (1)
- Agro-ecology (1)
- Antagonismus (1)
- Antioxidantien (1)
- ApaH (1)
- ApaH like phosphatase (1)
- Artenvielfalt (1)
- Arthropod (1)
- Aspergillus (1)
- Aspergillus fumigatus (1)
- Aureobasidium (1)
- Aurora-A (1)
- B-cell (1)
- BM (1)
- Basal Ganglia (1)
- Basalganglien (1)
- BayPass (1)
- Biene <Gattung> (1)
- Bienen (1)
- Biodiversität (1)
- Bombus terrestris (1)
- Brain-derived neurotrophic factor (1)
- Bruchpilot (1)
- CA2+ channels (1)
- CA3 pyrimidal cells (1)
- CCR7 (1)
- CD28 (1)
- CETCH cycle (1)
- CO2-sequestration (1)
- COI (1)
- CRC (1)
- CRISPR-Cas9 (1)
- Cadherin-13 (CDH13) (1)
- Caenorhabditis elegans (1)
- Caenorhabditis elegans (C. elegans) (1)
- Calciumkanal (1)
- Carabidae (1)
- Cardiomyocyte (1)
- Cdu1 (1)
- Chimpanzee (1)
- ChlaDUB1 (1)
- Chlamydia (1)
- Chlamydia trachomatis (1)
- Chromatin (1)
- Chronobiologie (1)
- Chrysomelidae (1)
- Click-Chemie (1)
- Comoé National Park (1)
- Cortico-striatal projection neurons (1)
- Cryptic species (1)
- Curculionidae (1)
- Cystein (1)
- DNA damage (1)
- DNA nanotechnology (1)
- DNA repair (1)
- DNA replication initiation (1)
- DNA-PK (1)
- DOT1 (1)
- DOT1B (1)
- DUB inhibitor (1)
- DeepSqueak (1)
- Dopaminergic PAM cluster neurons (1)
- Drosophila (1)
- ERG (1)
- ERK-Kaskade (1)
- ERK-cascade (1)
- Ecosystem services (1)
- Einzelmolekül-Lokalisationsmikroskopie (1)
- Elektronenmikroskopie (1)
- Emotional behavior (1)
- European beech (1)
- Evolution (1)
- Expansionsmikroskopie (1)
- FBXW7 (1)
- FIB-SEM (1)
- Fluorescence spectroscopy (1)
- Fluoreszenzspektroskopie (1)
- Fungal traits (1)
- GABA-A receptor (1)
- GDNF5 (1)
- GPI-anchor (1)
- GWAS (1)
- Genexpression (1)
- Genotype-phenotype relationship (1)
- Genregulation (1)
- Glutathion (1)
- Golgi (1)
- HHV-6 (1)
- HIV (1)
- Halictidae (1)
- HeLa cells (1)
- Heart development (1)
- Hepatitis B Virus (1)
- Herpesvirus (1)
- Herzhypertrophie (1)
- Herzmuskelzelle (1)
- Heterogenität (1)
- Hill numbers (1)
- Hippo pathway (1)
- Histon-Methyltransferase (1)
- Histone gamma H2AX (1)
- Hochaufgelöste Fluoreszenzmikroskopie (1)
- Hurwitz-Theorem (1)
- IL2 branching (1)
- In-silico Modell (1)
- IncuCyte\(^®\)S3 (1)
- Insect pests (1)
- Insektenstaaten (1)
- Interaktion (1)
- Ips typographus (1)
- JUN (1)
- Ki67 (1)
- Kinetoplastea (1)
- Klimaerwärmung (1)
- Klimawandel (1)
- Klimaänderung (1)
- Kosmologie (1)
- Krebsforschung (1)
- L929 (1)
- Landnutzung (1)
- Landscape ecology (1)
- Lebensraum (1)
- Legume crops (1)
- Leishmania (1)
- Lepidoptera (1)
- Lichtheimia (1)
- Life expectancy (1)
- LysR-type (1)
- MALDI imaging (1)
- MAX (1)
- MHC I (1)
- MHC II (1)
- MSCI (1)
- MYC (1)
- Mauerbiene (1)
- Mbt (1)
- Medium spiny neurons (1)
- Membrane receptor (1)
- Membranrezeptor (1)
- Motilität (1)
- Motor learning (1)
- Motorisches Lernen (1)
- Mutualismus (1)
- Myatrophische Lateralsklerose (1)
- Myb-MuvB complex (1)
- NRF2 (1)
- Negative geotaxis (1)
- Neisseria (1)
- Neuroanatomie (1)
- Neuroblastom (1)
- Neuroethologie (1)
- Neuropeptide (1)
- Non-coding RNA (1)
- Nuclear export control (1)
- Nuclear periphery granules (1)
- Olea (1)
- Oxidativer Stress (1)
- PAK4 (1)
- PER (1)
- Pacific Ocean (1)
- Pangenom (1)
- Parasit (1)
- Parasitoid (1)
- Parc National de la Comoé (1)
- Parkinson Krankheit (1)
- Persistence (1)
- Pflanzen (1)
- Phenotypic switch (1)
- Phänologie (1)
- PknB (1)
- Plant-insect interactions (1)
- Plastizität (1)
- Pollen (1)
- Pollination (1)
- Pseudotsuga menziesii (1)
- Quantenschleifen-Gravitation (1)
- Qubits (1)
- R-loop (1)
- RET6 (1)
- RIM-binding protein (1)
- RNA (1)
- RNA granules (1)
- RNA polymerase II (1)
- RNAseq (1)
- RRID: AB_2315425 (1)
- RRID: AB_2337244 (1)
- Rab (1)
- Radiation sensitivity (1)
- Ribonuclease H2 (1)
- Rnsstoffwechsel (1)
- SCC (1)
- SIM (1)
- SMART (1)
- SMART version 9 (1)
- SPRED (1)
- SPRED2 (1)
- Schimpanse (1)
- Sentinel-2 (1)
- Sleep fragmentation (1)
- Small-holder agriculture (1)
- Sphingosinanaloga (1)
- Sphingosinkinase (1)
- Spider Silk (1)
- Spinnenseide (1)
- Stammvielfalt (1)
- Staphylococcal infection (1)
- Stp (1)
- Striatum (1)
- Super-resolution microscopy (1)
- Superagonistic antibody (1)
- Synapse (1)
- Synaptic plasticity (1)
- Synaptonemaler Komplex (1)
- Synchronisation (1)
- Systembiologie (1)
- T-cell (1)
- TERB1-TERB2-MAJIN (1)
- Tanzania (1)
- Terminal domains (1)
- Terminale Domaine (1)
- Th1 cells (1)
- Tp63 (1)
- Triple co-culture (1)
- Triton X 100 (1)
- TrkB (1)
- Tropical agriculture (1)
- Trypanosomen (1)
- Trypanosomes (1)
- Tsetsefliege (1)
- USP25 (1)
- USP28 (1)
- Verhalten (1)
- Verschränkung (1)
- Wald (1)
- Waldstruktur (1)
- Wespen (1)
- Wilms tumor (1)
- Zellzyklus (1)
- Zentriolen (1)
- abandonment (1)
- abiotic (1)
- acid sphingomyelinase (1)
- actin (1)
- acute appendicitis (1)
- acute myeloid leukaemia (1)
- adaptive traits (1)
- adenylate cyclase toxin (1)
- adrenal tumors (1)
- adrenocortical carcinoma (1)
- agricultural soils (1)
- agriculture (1)
- airway epithelia (1)
- allatostatin‐A (1)
- altitudinal gradient (1)
- alveolar fibrosis (1)
- alveolar regeneration (1)
- alzheimer's disease (1)
- ambrosia beetle (1)
- ambrosia fungi (1)
- amino acid (1)
- amino acid analogues (1)
- amphids (1)
- amphimixis (1)
- ant brain (1)
- antenna (1)
- anthropogenic drivers (1)
- antibiotics (1)
- anticancer activity (1)
- antigenic variation (1)
- antimicrobials (1)
- antiproliferative (1)
- aphids (1)
- apomixis (1)
- approved drugs (1)
- arginine metabolism (1)
- artificial rearing (1)
- automixis (1)
- autophagosomes (1)
- bacteriology (1)
- barcoding (1)
- bark and ambrosia beetles (1)
- bee pollinator (1)
- bees (1)
- behaviour (1)
- biodiversity response (1)
- biofluid (1)
- biofuel (1)
- biogenic amines (1)
- biological fluorescence (1)
- biology (1)
- biomanufacturing (1)
- biomimetic 3D tissue model (1)
- bioreactor culture (1)
- biospecies (1)
- birds (1)
- black yeast (1)
- bodies (1)
- body size (1)
- bohemian forest ecosystem (1)
- brain (1)
- brain metastases (1)
- breed predisposition (1)
- bumblebee*s (1)
- butterflies (1)
- c-MYC (1)
- calcium (1)
- calcofluor white staining (1)
- cancer genomics (1)
- cancer predisposition syndromes (1)
- cancer therapy (1)
- cancers (1)
- canine (1)
- carboxylation (1)
- cardiac hypertrophy (1)
- cell biology (1)
- cell surface (1)
- cell surface proteome (1)
- cellular signalling networks (1)
- ceramides (1)
- cerebral metastases (1)
- chaperones (1)
- chemical similarity (1)
- chemokine receptor (1)
- chemotypes (1)
- chlamydia (1)
- chordotonal organ (1)
- chromatin structure (1)
- chromosomes telomere-led movement (1)
- ciliostasis (1)
- circadian rhythms (1)
- clathrin (1)
- click-chemistry (1)
- clinical malformations (1)
- collections (1)
- color lightness (1)
- colorectal cancer (1)
- colour patterns (1)
- combinatorial drug predictions (1)
- compaction (1)
- compatible solutes and other metabolites (1)
- computational (1)
- computational biology and bioinformatics (1)
- conformational restriction (1)
- connectomics (1)
- corazonin (1)
- crop management (1)
- cross pollination (1)
- cryptochrome (1)
- crystallization (1)
- cuticular chemistry (1)
- cuticular hydrocarbons (1)
- cyanine dyes (1)
- cysteine restriction (1)
- cysteine synthase inhibitor (1)
- cytokine release (1)
- cytokinin kinetin (1)
- cytoskeleton (1)
- cytotoxicity (1)
- data pool (1)
- date palm (1)
- dauer (1)
- deadwood enrichment (1)
- decay (1)
- decoherence (1)
- deep learning–artificial neural network (DL-ANN) (1)
- design (1)
- detoxification (1)
- development (1)
- developmental biology (1)
- developmental differentiation (1)
- diet (1)
- disturbance gradient (1)
- disturbed humid area (1)
- diversity gradients (1)
- division of labor (1)
- docking (1)
- drug delivery (1)
- drug repurposing (1)
- dry-mounted samples (1)
- ecological intensification (1)
- ecological stoichiometry (1)
- ecosystem services (1)
- electron cryo microscopy (1)
- electron cryo-microscopy (1)
- element translocation (1)
- elementary modes (1)
- elevation (1)
- elevation gradient (1)
- elevational gradient (1)
- encapsulation (1)
- endosomes (1)
- engineering (1)
- entanglement (1)
- enteric glial cells (1)
- enteric nervous system (1)
- entomology (1)
- envelopment (1)
- environmental association analysis (1)
- environmental impact (1)
- environmental justice (1)
- environmental variability (1)
- enzyme (1)
- epithelial cells (1)
- epitope mapping (1)
- ethanol (1)
- evolutionary genetics (1)
- exocytosis (1)
- exotic species (1)
- expansion microscopy (1)
- experiment (1)
- extinction risk (1)
- female reproductive tract (1)
- fertility (1)
- flagellar pocket (1)
- flagellar pocket collar (1)
- flg22 (1)
- flight characteristics (1)
- flooding (1)
- fluid collectives (1)
- fluorescence imaging (1)
- fluorescent dyes (1)
- fluorescent recombinant vaccinia virus (1)
- flux balance analysis (1)
- flux measurements (1)
- focused ion-beam scanning electron microscopy (1)
- foraging (1)
- foraging activities (1)
- forest biodiversity (1)
- forest ecosystem science (1)
- forestry (1)
- fuel wood (1)
- fullerene (1)
- functional traits (1)
- fungal infection model (1)
- fungal rhodopsins (1)
- fusion and fission (1)
- gametogenesis (1)
- gene prediction (1)
- genetic code expansion (1)
- genetic diversity (1)
- genetic markers (1)
- genomic integrity (1)
- genomic traits (1)
- genus Aspergillus (1)
- germination speed (1)
- glioblastoma (1)
- global biomes (1)
- glycophyte Arabidopsis (1)
- glycosphingolipids (1)
- graviception (1)
- grazing (1)
- greenhouse gases (1)
- guard cell (1)
- guard cells (1)
- gut barrier (1)
- gynogenesis (1)
- habitat availability (1)
- halophyte Thellungiella/Eutrema (1)
- hemiptera (1)
- hepatitis B core protein (1)
- hepatitis B virus (1)
- herbivorous beetles (1)
- herbivory (1)
- heterogeneous background (1)
- high-resolution imaging (1)
- hippocampal (1)
- homeostasis (1)
- homocysteine (1)
- honey bee (1)
- honey bees and native bees (1)
- honeybee*s (1)
- hook complex (1)
- host cells (1)
- host specificity (1)
- host–parasitoid interaction (1)
- human airway mucosa tissue models (1)
- human genomics (1)
- human induced pluripotent stem cell (hiPSC) (1)
- human nasal epithelial cells (1)
- human pathogenic fungi (1)
- human tracheo-bronchial epithelial cells (1)
- hybridogenesis (1)
- imaging the immune system (1)
- immune epitope mapping (1)
- immune genes (1)
- immune organs (1)
- immune system (1)
- immunotherapies (1)
- immunotherapy (1)
- in vitro (1)
- in vivo toxicity (1)
- in-silico model (1)
- infection spread (1)
- infectious diseases (1)
- inflammation (1)
- inflammatory bowel disease (1)
- insect (1)
- insect brain (1)
- insect decline (1)
- insect standard brain atlas (1)
- insect tracking (1)
- insights (1)
- interactome (1)
- intercellular junctions (1)
- interferon γ (1)
- intestinal epithelial barrier (1)
- intracellular (1)
- intracellular bacterial pathogens (1)
- intracellular pathogens (1)
- invasiveness (1)
- ion signaling (1)
- ion transport (1)
- island biogeography (1)
- iterative shape averaging (1)
- juvenile hormone (1)
- kinetics (1)
- land use intensification (1)
- landscape heterogeneity (1)
- laparoscopic appendectomy (1)
- latency (1)
- latitudinal gradient (1)
- learning and memory (1)
- lethality rate (1)
- life cycle (1)
- ligand-gated ion channels (1)
- light stimuli (1)
- limiting dilution cloning (1)
- liquid chromatography/mass spectrometry (1)
- lncRNAs (1)
- local adaptation (1)
- long non-coding RNA (1)
- low-secretion phenotype mutants (1)
- lung cancer (1)
- lysosomal recruitment (1)
- m7G cap (1)
- mRNA (1)
- mRNA cap (1)
- mRNA decapping (1)
- macro moths (1)
- macro- and micro-elements (1)
- magnetic compass (1)
- malignant tumors (1)
- maturation signal (1)
- mean fruit body size (1)
- measles (1)
- mechanisms of persister formation (1)
- mechanistic model (1)
- medaka (1)
- median and dorsal raphe (1)
- meiotic prophase (1)
- melanoma (1)
- melanoma dedifferentiation (1)
- membrane fission (1)
- membrane recycling (1)
- membrane trafficking (1)
- menstrual cycles (1)
- meta-analysis (1)
- metabolic adaptation (1)
- metabolic modeling (1)
- metabolome (1)
- metabolomic profiling (1)
- metabolomics (1)
- metagenomics (1)
- methylation (1)
- miR-30 (1)
- miRNA processing (1)
- mice (1)
- microbes (1)
- microbial community abundance and compositions (1)
- microbial ecology and evolution (1)
- microbial rhodopsins (1)
- microbiology (1)
- microbiology techniques (1)
- microbiome (1)
- microbiome metabarcoding (1)
- microhabitats (1)
- microscopy (1)
- microswimming (1)
- microtubule cytoskeleton (1)
- mikrobielle Ökologie und Evolution (1)
- mitochondria (1)
- mixed-species forestry (1)
- model (1)
- modular tumor tissue models (1)
- modulation (1)
- modulatory effects (1)
- molecular biology (1)
- molecular conformation (1)
- molecular dynamics simulation (1)
- molecular evolution (1)
- molecular modeling (1)
- molecular neuroscience (1)
- monoclonal stable cell (1)
- monolayer (1)
- moon (1)
- more-individuals hypothesis (1)
- morphometry (1)
- mossy fiber synapses (1)
- motile behaviour (1)
- motility (1)
- mouse model (1)
- movement ecology (1)
- multisensory integration (1)
- multispecies studies (1)
- mushroom bodies (1)
- mushroom body (1)
- mushroom body calyx (1)
- mutation screening (1)
- mutualism (1)
- nanocarrier (1)
- nanotube formation (1)
- nanovesicle formation (1)
- natural enemies (1)
- natural enemy (1)
- natural environment (1)
- naturalized species (1)
- navigation (1)
- ncuCyte\(^®\)S3 (1)
- nephroblastoma (1)
- nephroblastomatosis (1)
- nesting ecology (1)
- network biology (1)
- neural networks (1)
- neuroblast growth (1)
- neuroblastoma (1)
- neuroethology (1)
- neuropeptidomics (1)
- neuropils (1)
- neuropsychiatric disorders (1)
- neuroscience (1)
- neurospheres (1)
- neurotransmitter (1)
- neurotrophic factors (1)
- neutral theory (1)
- neutrophil transmigration (1)
- niche partitioning (1)
- non-small cell lung cancer (1)
- novel disturbance (1)
- nucleolus (1)
- nursing (1)
- octopamine (1)
- oil bees (1)
- olfactory learning (1)
- olive (1)
- open appendectomy (1)
- optic lobes (1)
- optogenetics (1)
- organic amendment (1)
- organoid (1)
- organoids (1)
- outcome (1)
- overstory (1)
- pH (1)
- painted nest preference (1)
- pangenome (1)
- parabiosis (1)
- parallel evolution (1)
- parasite evolution (1)
- parasite genetics (1)
- parthenogenesis (1)
- pathogenicity (1)
- patient-derived organoid (PDOs) (1)
- patient-derived tumor organoid (PDTO) (1)
- pediatric adrenocortical adenoma (1)
- pediatric adrenocortical cancer (1)
- pediatric adrenocortical tumor (1)
- peptide inhibitor of envelopment (1)
- peptide microarray (1)
- perception (1)
- perfusion-based bioreactor system (1)
- period (1)
- persistence (1)
- pests (1)
- phenological escape (1)
- phenology (1)
- phosphorylation (1)
- photodynamic therapy (1)
- photoperiodism (1)
- photoreceptor (1)
- photorespiration (1)
- phototaxis (1)
- phylogenetic analysis (1)
- phylogenetic inertia (1)
- phylogenetische Trägheit (1)
- phytophagous beetles (1)
- plant ecology (1)
- plant functional traits (1)
- plant growth (1)
- plant invasion (1)
- plant–pollinator interaction (1)
- plaque assay (1)
- plaque isolation (1)
- platform (1)
- pocket factor (1)
- policy (1)
- pollen (1)
- pollen limitation (1)
- pollen metabarcoding (1)
- pollen tube (1)
- pollinator (1)
- polyethism (1)
- polymorphism (1)
- population coverage (1)
- population divergence (1)
- positive selection (1)
- post-disturbance logging (1)
- pregnancy (1)
- presynaptic plasticity (1)
- primate (1)
- pro-oxidant (1)
- prognostic factors (1)
- proliferation (1)
- prolonged survival (1)
- protein crowding (1)
- protein domain architectures (1)
- protein domains (1)
- proton channel (1)
- protozoan (1)
- pyrazolo[3,4-d]pyrimidine (1)
- quantum computing (1)
- qubit (1)
- rapid evolution (1)
- real-time (1)
- reception (1)
- recombination (1)
- reconstruction (1)
- red lists (1)
- regime shift (1)
- regulation (1)
- regulation of gene expression (1)
- release (1)
- remote sensing (1)
- remote sensing‐enabled essential biodiversity variables (1)
- reproductive health (1)
- retinoic acid (1)
- retrotransposons (1)
- reveals (1)
- ribosome biogenesis (1)
- riboswitch (1)
- risk management (1)
- rocus sieberi (1)
- salinity (1)
- salt stress (1)
- saprobic and ectomycorrhizal basidiomycetes (1)
- saproxylic beetles (1)
- scaffold search (1)
- secondary site infection (1)
- serotonin-specific neurons (1)
- sex determination (1)
- shoot–root interaction (1)
- short‐rotation coppice (1)
- shrub‐cover (1)
- signaling pathway (1)
- silkworm (1)
- single molecule localization microscopy (1)
- single strand blocking (1)
- single-molecule biophysics (1)
- single-molecule fluorescence spectroscopy (1)
- sky compass (1)
- sleeping sickness (1)
- social insect (1)
- social insects (1)
- soil (1)
- soil characteristics (1)
- spanlastic (1)
- specialists (1)
- specialization (1)
- species as individuals (1)
- species as natural kinds (1)
- species coexistence mechanism (1)
- species concept (1)
- species diversity (1)
- species problem (1)
- species richness (1)
- spermatogenesis (1)
- spermatogenic cell sorting (1)
- sphingolipids (1)
- sphingomyelinase (1)
- sphingomyelinase release (1)
- sphingosine (1)
- sphingosine 1-phosphate (1)
- squamous (1)
- standing variation (1)
- staphylococcal alpha-toxin (1)
- stomata (1)
- stomatal conductance (1)
- strain diversity (1)
- stress conditions (1)
- structural biology (1)
- structural synaptic plasticity (1)
- sturgeon (1)
- subungual (1)
- sucrose responsiveness (1)
- sulfate (1)
- super-resolution (1)
- super-resolution array tomography (1)
- super-resolution microscopy (SRM) (1)
- sustainable intensification (1)
- symbiont selection (1)
- synapse formation (1)
- synaptic complexes (1)
- synaptic plasticity (1)
- synthetic pathways (1)
- systematic review (1)
- systems biology (1)
- tachykinin (1)
- temperature (1)
- temporal development (1)
- temporal mismatch (1)
- therapy (1)
- tight junction (1)
- time lapse cameras (1)
- tissue model (1)
- toe (1)
- tool (1)
- tool-use (1)
- total internal reflection microscopy (1)
- tracheal cytotoxin (1)
- trachomatis (1)
- trade‐offs (1)
- transcriptional regulation (1)
- transcriptome (1)
- transmission (1)
- transposable elements (1)
- triglycerides (1)
- trypanosome (1)
- tumor (1)
- tumor disease (1)
- tumor surveillance (1)
- tumour immunology (1)
- type I interferon (1)
- tyramine (1)
- ultrasound vocalizations (1)
- understory (1)
- urban greening (1)
- variant surface glycoproteins (1)
- vascular plants (1)
- vector-parasite interaction (1)
- vertical mismatch (1)
- vesicles (1)
- virus reactivation (1)
- visual system (1)
- wasps (1)
- water quality (1)
- wheat yield (1)
- whole-genome analysis (1)
- wind compass (1)
- yvcK/glmR operon (1)
- Ökologie (1)
- Ökosystemdienstleistung (1)
- ΔNp63 (1)
Institute
- Theodor-Boveri-Institut für Biowissenschaften (168) (remove)
Sonstige beteiligte Institutionen
High attrition-rates entailed by drug testing in 2D cell culture and animal models stress the need for improved modeling of human tumor tissues. In previous studies our 3D models on a decellularized tissue matrix have shown better predictivity and higher chemoresistance. A single porcine intestine yields material for 150 3D models of breast, lung, colorectal cancer (CRC) or leukemia. The uniquely preserved structure of the basement membrane enables physiological anchorage of endothelial cells and epithelial-derived carcinoma cells. The matrix provides different niches for cell growth: on top as monolayer, in crypts as aggregates and within deeper layers. Dynamic culture in bioreactors enhances cell growth. Comparing gene expression between 2D and 3D cultures, we observed changes related to proliferation, apoptosis and stemness. For drug target predictions, we utilize tumor-specific sequencing data in our in silico model finding an additive effect of metformin and gefitinib treatment for lung cancer in silico, validated in vitro. To analyze mode-of-action, immune therapies such as trispecific T-cell engagers in leukemia, as well as toxicity on non-cancer cells, the model can be modularly enriched with human endothelial cells (hECs), immune cells and fibroblasts. Upon addition of hECs, transmigration of immune cells through the endothelial barrier can be investigated. In an allogenic CRC model we observe a lower basic apoptosis rate after applying PBMCs in 3D compared to 2D, which offers new options to mirror antigen-specific immunotherapies in vitro. In conclusion, we present modular human 3D tumor models with tissue-like features for preclinical testing to reduce animal experiments.
Single mRNA molecules are frequently detected by single molecule fluorescence in situ hybridization (smFISH) using branched DNA technology. While providing strong and background-reduced signals, the method is inefficient in detecting mRNAs within dense structures, in monitoring mRNA compactness and in quantifying abundant mRNAs. To overcome these limitations, we have hybridized slices of high pressure frozen, freeze-substituted and LR White embedded cells (LR White smFISH). mRNA detection is physically restricted to the surface of the resin. This enables single molecule detection of RNAs with accuracy comparable to RNA sequencing, irrespective of their abundance, while at the same time providing spatial information on RNA localization that can be complemented with immunofluorescence and electron microscopy, as well as array tomography. Moreover, LR White embedding restricts the number of available probe pair recognition sites for each mRNA to a small subset. As a consequence, differences in signal intensities between RNA populations reflect differences in RNA structures, and we show that the method can be employed to determine mRNA compactness. We apply the method to answer some outstanding questions related to trans-splicing, RNA granules and mitochondrial RNA editing in single-cellular trypanosomes and we show an example of differential gene expression in the metazoan Caenorhabditis elegans.
The nuclear envelope serves as important mRNA surveillance system. In yeast and humans, several control mechanisms act in parallel to prevent nuclear export of unprocessed mRNAs. However, trypanosomes lack homologues to most of the proteins involved. In addition, gene expression in trypanosomes relies almost completely on post-transcriptional regulation as they transcribe mRNAs as long polycistrons, which are subsequently processed into individual mRNA molecules by trans-splicing. As trans-splicing is not error-free, unspliced mRNAs may be recognized and prevented from reaching the cytoplasm by a yet unknown mechanism.
When trans-splicing is inhibited in trypanosomes, the formation of a novel RNA granule type at the cytoplasmic periphery of the nucleus, so called nuclear periphery granules (NPGs) was previously observed. To identify potential regulators of nuclear export control, changes in protein localization which occur when trans-splicing is inhibited, were globally analyzed during this work. For this, trypanosome nuclei were purified under conditions maintaining NPG attachment to the nucleus, in the absence and presence of trans-splicing. Mass spectrometry analyses identified 128 proteins which are specifically enriched in nuclear preparations of cells inhibited for trans-splicing. Amongst them are proteins, which change their localization to the nucleus or to the nuclear pores as well as many proteins that move into NPGs. Some of these proteins are promising candidates for nuclear export control proteins, as the changes in localization (to the nucleus or nuclear pores) were specific to the accumulation of unspliced mRNAs. The NPG proteome almost exclusively contains proteins involved in mRNA metabolism, mostly unique to trypanosomes, notably major translation initiation factors were absent. These data indicate that NPGs are RNP complexes which have started or completed nuclear export, but not yet entered translation. As a byproduct of these proteomic studies, a high-quality dataset of the yet unknown T. brucei nuclear proteome is provided, closing an important gap in knowledge to study trypanosome biology, in particular nuclear related processes.
NPGs were characterized in more detail by microscopy. The granules are cytoplasmic and present in at least two different trypanosome life cycle stages. There are at least two distinct granule subsets, with differences in protein composition. A closer analysis of NPGs by electron microscopy revealed that the granules are electron dense structures, which are connected to nuclear pores by string-like structures.
In order to approach the function of NPGs, on the one hand, the hypothesis that NPGs might be related to perinuclear germ granules of adult gonads of C. elegans was tested: we found no relation between the two granule types. On the other hand, initial single molecule mRNA FISH experiments performed in trypanosomes showed no accumulation of unspliced transcripts in NPGs, arguing against an involvement of the granules in mRNA quality control.
The transcription factor NRF2 is considered as the master regulator of cytoprotective and ROS-detoxifying gene expression. Due to their vulnerability to accumulating reactive oxygen species, melanomas are dependent on an efficient oxidative stress response, but to what extent melanomas rely on NRF2 is only scarcely investigated so far. In tumor entities harboring activating mutations of NRF2, such as lung adenocarcinoma, NRF2 activation is closely connected to therapy resistance. In melanoma, activating mutations are rare and triggers and effectors of NRF2 are less well characterized.
This work revealed that NRF2 is activated by oncogenic signaling, cytokines and pro-oxidant triggers, released cell-autonomously or by the tumor microenvironment. Moreover, silencing of NRF2 significantly reduced melanoma cell proliferation and repressed well-known NRF2 target genes, indicating basal transcriptional activity of NRF2 in melanoma. Transcriptomic analysis showed a large set of deregulated gene sets, besides the well-known antioxidant effectors. NRF2 suppressed the activity of MITF, a marker for the melanocyte lineage, and induced expression of epidermal growth factor receptor (EGFR), thereby stabilizing the dedifferentiated melanoma phenotype and limiting pigmentation markers and melanoma-associated antigens. In general, the dedifferentiated melanoma phenotype is associated with a reduced tumor immunogenicity. Furthermore, stress-inducible cyclooxygenase 2 (COX2) expression, a crucial immune-modulating gene, was regulated by NRF2 in an ATF4-dependent manner. Only in presence of both transcription factors was COX2 robustly induced by H2O2 or TNFα. COX2 catalyzes the first step of the prostaglandin E2 (PGE2) synthesis, which was described to be associated with tumor immune evasion and reduction of the innate immune response.
In accordance with these potentially immune-suppressive features, immunocompetent mice injected with NRF2 knockout melanoma cells had a strikingly longer tumor-free survival compared to NRF2-proficient cells. In line with the in vitro data, NRF2-deficient tumors showed suppression of COX2 and induction of MITF. Furthermore, transcriptomic analyses of available tumors revealed a strong induction of genes belonging to the innate immune response, such as RSAD2 and IFIH1. The expression of these genes strongly correlated with immune evasion parameters in human melanoma datasets and NRF2 activation or PGE2 supplementation limited the innate immune response in vitro.
In summary, the stress dependent NRF2 activation stabilizes the dedifferentiated melanoma phenotype and facilitates the synthesis of PGE2. As a result, NRF2 reduces gene expression of the innate immune response and promotes the generation of an immune-cold tumor microenvironment. Therefore, NRF2 not only elevated the ROS resilience, but also strongly contributed to tumor growth, maintenance, and immune control in cutaneous melanoma.
Nutrition facts of pollen: nutritional quality and how it affects reception and perception in bees
(2021)
Nutrients belong to the key elements enabling life and influencing an organism’s fitness. The intake of nutrients in the right amounts and ratios can increase fitness; strong deviations from the optimal intake target can decrease fitness. Hence, the ability to assess the nutritional profile of food would benefit animals. To achieve this, they need the according nutrient receptors, the ability to interpret the receptor information via perceptive mechanisms, and the ability to adjust their foraging behavior accordingly. Additionally, eventually existing correlations between the nutrient groups and single nutrient compounds in food could help them to achieve this adjustment. A prominent interaction between food and consumer is the interaction between flowering plants (angiosperms) and animal pollinators. Usually both of the interacting partners benefit from this mutualistic interaction. Plants are pollinated while pollinators get a (most of the times) nutritional reward in form of nectar and/or pollen. As similar interactions between plants and animals seem to have existed even before the emergence of angiosperms, these interactions between insects and angiosperms very likely have co-evolved right from their evolutionary origin. Therefore, insect pollinators with the ability to assess the nutritional profile may have shaped the nutritional profile of plant species depending on them for their reproduction via selection pressure. In Chapter I of this thesis the pollen nutritional profile of many plant species was analyzed in the context of their phylogeny and their dependence on insect pollinators. In addition, correlations between the nutrients were investigated. While the impact of phylogeny on the pollen protein content was little, the mutual outcome of both of the studies included in this chapter is that protein content of pollen is mostly influenced by the plant’s dependence on insect pollinators. Several correlations found between nutrients within and between the nutrient groups could additionally help the pollinators to assess the nutrient profile of pollen. An important prerequisite for this assessment would be that the pollinators are able to differentiate between pollen of different plant species. Therefore, in Chapter II it was investigated whether bees have this ability. Specifically, it was investigated whether honeybees are able to differentiate between pollen of two different, but closely related plant species and whether bumblebees prefer one out of three pollen mixes, when they were fed with only one of them as larvae. Honeybees indeed were able to differentiate between the pollen species and bumblebees preferred one of the pollen mixes to the pollen mix they were fed as larvae, possibly due to its nutritional content. Therefore, the basis for pollen nutrient assessment is given in bees. However, there also was a slight preference for the pollen fed as larvae compared to another non-preferred pollen mix, at least hinting at the retention of larval memory in adult bumblebees. Chapter III looks into nutrient perception of bumblebees more in detail. Here it was shown that they are principally able to perceive amino acids and differentiate between them as well as different concentrations of the same amino acid. However, they do not seem to be able to assess the amino acid content in pollen or do not focus on it, but instead seem to focus on fatty acids, for which they could not only perceive concentration differences, but also were able to differentiate between. These findings were supported by feeding experiments in which the bumblebees did not prefer any of the pollen diets containing less or more amino acids but preferred pollen with less fatty acids. In no choice feeding experiments, bumblebees receiving a diet with high fatty acid content accepted undereating other nutrients instead of overeating fat, leading to increased mortality and the inability to reproduce. Hence, the importance of fat in pollen needs to be looked into further. In conclusion, this thesis shows that the co-evolution of flowering plants and pollinating insects could be even more pronounced than thought before. Insects do not only pressure the plants to produce high quality nectar, but also pressure those plants depending on insect pollination to produce high quality pollen. The reason could be the insects’ ability to receive and perceive certain nutrients, which enables them to forage selectively leading to a higher reproductive success of plants with a pollinator-suitable nutritional pollen profile.
The human pathogen Chlamydia trachomatis is the main cause of sexually transmitted infections worldwide. The obligate intracellular bacteria are the causative agent of several diseases that reach from conjunctivitis causing trachoma and blindness as well as salpingitis and urethritis which can lead to infertility if left untreated.
In order to gain genetically engineered Chlamydia that inducible knock down specific gene expression, the CRISPRi system was established in C. trachomatis. In a proof of principle experiment it was shown that C. trachomatis pCRISPRi:gCdu1III target ChlaDUB1 expression and reduce the protein amount up to 50 %. Knock-down of the DUB did not influence protein levels of anti-apoptotic Mcl-1 and did not make cells susceptible for apoptosis. However, reduced dCas9 protein size, bacterial growth impairment and off target effects interfering with the GFP signal, form obstacles in CRISPRi system in Chlamydia. For routinely use of the CRISPRi method in C. trachomatis further investigation is needed.
Since the bacterial life cycle includes two morphological and functional distinct forms, it is essential for chlamydial spread to complete the development cycle and form infectious progeny. Therefore, Chlamydia has evolved strategies to evade the host immune system in order to stay undetected throughout the developmental cycle. The bacteria prevent host cell apoptosis via stabilization of anti-apoptotic proteins like Mcl-1, Survivin and HIF-1α and activate pro-survival pathways, inhibiting invasion of immune cells to the site of infection. The host cell itself can destroy intruders via cell specific defense systems that involve autophagy and recruitment of professional immune cells. In this thesis the role of the chlamydial deubiuqitinase ChlaDUB1 upon immune evasion was elucidated. With the mutant strain Ctr Tn-cdu1 that encodes for a truncated DUB due to transposon insertion, it was possible to identify ChlaDUB1 as a potent opponent of the autophagic system. Mutant inclusions were targeted by K48 and K63 chain ubiquitination. Subsequently the inclusion was recognized by autophagic receptors like p62, NBR1 and NDP52 that was reversed again by complementation with the active DUB. Xenophagy was promoted so far as LC3 positive phagosomes formed around the inclusion of Ctr Tn-cdu1, which did not fuse with the lysosome. The detected growth defect in human primary cells of Chlamydia missing the active DUB was not traced back to autophagy, but was due to impaired development and replication. It was possible to identify Ankib1, the E3 ligase, that ubiquitinates the chlamydial inclusion in a siRNA based screen. The activating enzyme Ube1 and the conjugating enzyme Ube2L3 are also essential in this process. Chlamydia have a reduced genome and depend on lipids and nutrients that are translocated from the host cell to the inclusion to proliferate. Recruitment of fragmented Golgi stacks to the inclusion surface was prevented when ChlaDUB1 was inactive, probably causing diminished bacterial growth. Additionally, the modification of the inclusion by Ankib1 and subsequent decoration by autophagic markers was not only present in human but also murine cells. Comparison of other Chlamydia strains and species revealed Ankib1 to be located at the proximity of the inclusion in C. trachomatis strains only but not in C. muridarum or C. pneumoniae, indicating that Ankib1 is specifically the E3 ligase of C. trachomatis. Moreover, the role of ChlaDUB1 in infected tissue was of interest, since ChlaDUB1 protein was also found in early EB stage and so might get in contact with invading immune cells after cell lysis. While bacteria spread and infect new host cells, Chlamydia can also infect immune cells. Infection of human neutrophils with Ctr Tn-cdu1 shows less bacterial survival and affirms the importance of the DUB for bacterial fitness in these cells.
ERK1/2 are known key players in the pathophysiology of heart failure, but the members of the ERK cascade, in particular Raf1, can also protect the heart from cell death and ischemic injury. An additional autophosphorylation (ERK1 at Thr208, ERK2 at Thr188) empowers ERK1/2 translocation to the nucleus and phosphorylation of nuclear targets which take part in the development of cardiac hypertrophy. Thereby, targeting this additional phosphorylation is a promising pharmacological approach.
In this thesis, an in silico model of ERK cascade in the cardiomyocyte is introduced. The model is a semi-quantitive model and its behavior was tested with different softwares (SQUAD and CellNetAnalyzer). Different phosphorylation states of ERK1/2 as well as different stimuli can be reproduced. The different types of stimuli include hypertrophic as well as non-hypertrophic stimuli. With the introduced in-silico model time courses and synergistic as well as antagonistic receptor stimuli combinations can be predicted. The simulated time courses were experimentally validated. SQUAD was mainly used to make predictions about time courses and thresholds, whereas CNA was used to analyze steady states and feedback loops.
Furthermore, new targets of ERK1/2 which partially contribute, also in the formation of cardiac hypertrophy, were identified and the most promising of them were illuminated. Important further targets are Caspase 8, GAB2, Mxi-2, SMAD2, FHL2 and SPIN90.
Cardiomyocyte gene expression data sets were analyzed to verify involved components and to find further significantly altered genes after induced hypertrophy with TAC (transverse aortic constriction). Changes in the ultrastructure of the cardiomyocyte are the final result of induced hypertrophy.
Bark beetles (sensu lato) colonize woody tissues like phloem or xylem and are associated with a broad range of micro-organisms. Specific fungi in the ascomycete orders Hypocreales, Microascales and Ophistomatales as well as the basidiomycete Russulales have been found to be of high importance for successful tree colonization and reproduction in many species. While fungal mutualisms are facultative for most phloem-colonizing bark beetles (sensu stricto), xylem-colonizing ambrosia beetles are long known to obligatorily depend on mutualistic fungi for nutrition of adults and larvae. Recently, a defensive role of fungal mutualists for their ambrosia beetle hosts was revealed: Few tested mutualists outcompeted other beetle-antagonistic fungi by their ability to produce, detoxify and metabolize ethanol, which is naturally occurring in stressed and/or dying trees that many ambrosia beetle species preferentially colonize. Here, we aim to test (i) how widespread beneficial effects of ethanol are among the independently evolved lineages of ambrosia beetle fungal mutualists and (ii) whether it is also present in common fungal symbionts of two bark beetle species (Ips typographus, Dendroctonus ponderosae) and some general fungal antagonists of bark and ambrosia beetle species. The majority of mutualistic ambrosia beetle fungi tested benefited (or at least were not harmed) by the presence of ethanol in terms of growth parameters (e.g., biomass), whereas fungal antagonists were inhibited. This confirms the competitive advantage of nutritional mutualists in the beetle’s preferred, ethanol-containing host material. Even though most bark beetle fungi are found in the same phylogenetic lineages and ancestral to the ambrosia beetle (sensu stricto) fungi, most of them were highly negatively affected by ethanol and only a nutritional mutualist of Dendroctonus ponderosae benefited, however. This suggests that ethanol tolerance is a derived trait in nutritional fungal mutualists, particularly in ambrosia beetles that show cooperative farming of their fungi.
Sex determination (SD) is a highly diverse and complex mechanism. In vertebrates, one of the first morphological differences between the sexes is the timing of initiation of the first meiosis, where its initiation occurs first in female and later in male. Thus, SD is intimately related to the responsiveness of the germ cells to undergo meiosis in a sex-specific manner. In some vertebrates, it has been reported that the timing for meiosis entry would be under control of retinoic acid (RA), through activation of Stra8. In this study, we used a fish model species for sex determination and lacking the stra8 gene, the Japanese medaka (Oryzias latipes), to investigate the connection between RA and the sex determination pathway. Exogenous RA treatments act as a stress factor inhibiting germ cell differentiation probably by activation of dmrt1a and amh. Disruption of the RA degrading enzyme gene cyp26a1 induced precocious meiosis and oogenesis in embryos/hatchlings of female and even some males. Transcriptome analyzes of cyp26a1–/–adult gonads revealed upregulation of genes related to germ cell differentiation and meiosis, in both ovaries and testes. Our findings show that germ cells respond to RA in a stra8 independent model species. The responsiveness to RA is conferred by sex-related genes, restricting its action to the sex differentiation period in both sexes.
Activity of Tracheal Cytotoxin of Bordetella pertussis in a Human Tracheobronchial 3D Tissue Model
(2021)
Bordetella pertussis is a highly contagious pathogen which causes whooping cough in humans. A major pathophysiology of infection is the extrusion of ciliated cells and subsequent disruption of the respiratory mucosa. Tracheal cytotoxin (TCT) is the only virulence factor produced by B. pertussis that has been able to recapitulate this pathology in animal models. This pathophysiology is well characterized in a hamster tracheal model, but human data are lacking due to scarcity of donor material. We assessed the impact of TCT and lipopolysaccharide (LPS) on the functional integrity of the human airway mucosa by using in vitro airway mucosa models developed by co-culturing human tracheobronchial epithelial cells and human tracheobronchial fibroblasts on porcine small intestinal submucosa scaffold under airlift conditions. TCT and LPS either alone and in combination induced blebbing and necrosis of the ciliated epithelia. TCT and LPS induced loss of ciliated epithelial cells and hyper-mucus production which interfered with mucociliary clearance. In addition, the toxins had a disruptive effect on the tight junction organization, significantly reduced transepithelial electrical resistance and increased FITC-Dextran permeability after toxin incubation. In summary, the results indicate that TCT collaborates with LPS to induce the disruption of the human airway mucosa as reported for the hamster tracheal model.