Refine
Has Fulltext
- yes (173)
Is part of the Bibliography
- yes (173)
Year of publication
- 2021 (173) (remove)
Document Type
- Journal article (133)
- Doctoral Thesis (37)
- Preprint (2)
- Working Paper (1)
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)
- Einzelmolekülspektroskopie (2)
- Fluoreszenzmikroskopie (2)
- Fluoreszenzspektroskopie (2)
- Formicidae (2)
- Genregulation (2)
- Kinetoplastida (2)
- Klimawandel (2)
- LC/MS (2)
- MYCN (2)
- Melanom (2)
- Parkinson's disease (2)
- Photoinduzierter Elektronentransfer (2)
- Proteinsynthese (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)
- neuroanatomy (2)
- neuromodulation (2)
- nutrients (2)
- nutrition (2)
- p53 (2)
- photoinduced electron transfer (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)
- Abbe-Limit (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)
- CXCR4 (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)
- Fluoreszenzkorrelationsspektroskopie (1)
- Fluoreszenzsonden (1)
- Fungal traits (1)
- GABA-A receptor (1)
- GDNF5 (1)
- GPI-anchor (1)
- GWAS (1)
- Gallium-68 Pentixafor (1)
- Genexpression (1)
- Genotype-phenotype relationship (1)
- Glutamatrezeptor (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)
- High-End-Mikroskopie (1)
- Hill numbers (1)
- Hippo pathway (1)
- Histon-Methyltransferase (1)
- Histone gamma H2AX (1)
- Hitzeschock-Proteine (1)
- Hochaufgelöste Fluoreszenzmikroskopie (1)
- Hsp90 (1)
- Hurwitz-Theorem (1)
- IL2 branching (1)
- In vitro (1)
- In-silico Modell (1)
- IncuCyte\(^®\)S3 (1)
- Insect pests (1)
- Insektenstaaten (1)
- Interaktion (1)
- Ionotrope Glutamatrezeptoren (1)
- Ips typographus (1)
- JUN (1)
- Ki67 (1)
- Kinetoplastea (1)
- Klimaerwärmung (1)
- Klimaneutralität (1)
- Klimapflanzen (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)
- Ligandenbindedomäne (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)
- Modul (1)
- Module search (1)
- Modulsuche (1)
- Motilität (1)
- Motor learning (1)
- Motorisches Lernen (1)
- Multiples Myelom (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)
- Pilze (1)
- PknB (1)
- Plant-insect interactions (1)
- Plasmozytom (1)
- Plastizität (1)
- Pollen (1)
- Pollination (1)
- Promotor <Genetik> (1)
- Proteinmarkierungen (1)
- Pseudotsuga menziesii (1)
- Quantenschleifen-Gravitation (1)
- Qubits (1)
- R-loop (1)
- RET6 (1)
- RIM-binding protein (1)
- RNA (1)
- RNA Motivsuche (1)
- RNA granules (1)
- RNA motiv serach (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)
- 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)
- Theranostik (1)
- Tp63 (1)
- Transkriptionsfaktor (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)
- 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)
- black yeast (1)
- bodies (1)
- body size (1)
- bohemian forest ecosystem (1)
- brain (1)
- brain metastases (1)
- breed predisposition (1)
- bumblebee*s (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)
- ionotropic glutamate receptors (1)
- island biogeography (1)
- iterative shape averaging (1)
- juvenile hormone (1)
- kinetics (1)
- landscape heterogeneity (1)
- laparoscopic appendectomy (1)
- latency (1)
- latitudinal gradient (1)
- learning and memory (1)
- lethality rate (1)
- life cycle (1)
- ligand binding domain (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)
- mikroskopische Untersuchung (1)
- mitochondria (1)
- mixed-species forestry (1)
- model (1)
- modular tumor tissue models (1)
- modulation (1)
- modulatory effects (1)
- module search (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)
- nature conservation (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)
- 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)
- 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 (173) (remove)
Sonstige beteiligte Institutionen
Im Zuge der Bemühungen um neue, tumorspezifische Therapieansätze für die Myelomerkrankung hat sich der C-X-C-Chemokinrezeptor 4 (CXCR4) aufgrund seiner zentralen Rolle in der Tumorgenese als vielversprechender Angriffspunkt hervorgetan. Im Sinne eines theranostischen Konzepts wird der Rezeptor mithilfe eines radioaktiv markierten Liganden quantifiziert und anschließend von rezeptorspezifischen Radiotherapeutika als Zielstruktur genutzt. Die CXCR4-Expression ist allerdings ein höchst dynamischer Prozess mit großer inter- und intraindividueller Heterogenität, der u.a. durch eine begleitende Chemotherapie beeinflusst werden kann. Ob sich therapieinduzierte Veränderungen der Rezeptorexpression gezielt nutzen lassen, um die CXCR4-Expression zu optimieren und so die Effektivität der CXCR4-gerichteten Strategien zu steigern, wurde bislang nicht untersucht.
Vor diesem Hintergrund wurden in der vorliegenden Arbeit verschiedene, in der Myelomtherapie etablierte Substanzen sowohl einzeln als auch in Kombination hinsichtlich ihres Einflusses auf die CXCR4-Expression von MM-Zelllinien und primären MM-Zellen unter in vitro Bedingungen analysiert.
In den durchgeführten Experimenten zeigte sich eine hohe Variabilität der CXCR4-Expression der MM-Zellen nach Therapieinduktion, die sich als substanz-, dosis- und zeitabhängig herausstellte. Die Ergebnisse bestätigten das große Potenzial der therapieinduzierten Modulation der CXCR4-Expression. Im weiteren Verlauf sind translationale Forschungsansätze gerechtfertigt, die die Übertragbarkeit der in vitro gewonnenen Ergebnisse auf die komplexen Vorgänge im lebenden Organismus überprüfen. Langfristiges Ziel ist der Entwurf eines patientenzentrierten, multimodalen Therapiekonzepts, welches das CXCR4-gerichtete theranostische Konzept mit einer individuell angepassten, medikamentösen MM-Therapie kombiniert.
Background: ApaH like phosphatases (ALPHs) originate from the bacterial ApaH protein and are present in eukaryotes of all eukaryotic super-groups; still, only two proteins have been functionally characterised. One is ALPH1 from the Kinetoplastid Trypanosoma brucei that we recently found to be the mRNA decapping enzyme of the parasite. mRNA decapping by ALPHs is unprecedented in eukaryotes, which usually use nudix hydrolases, but the bacterial ancestor protein ApaH was recently found to decap non-conventional caps of bacterial mRNAs. These findings prompted us to explore whether mRNA decapping by ALPHs is restricted to Kinetoplastida or more widespread among eukaryotes.
Results: We screened 824 eukaryotic proteomes with a newly developed Python-based algorithm for the presence of ALPHs and used the data to refine phylogenetic distribution, conserved features, additional domains and predicted intracellular localisation of ALPHs. We found that most eukaryotes have either no ALPH (500/824) or very short ALPHs, consisting almost exclusively of the catalytic domain. These ALPHs had mostly predicted non-cytoplasmic localisations, often supported by the presence of transmembrane helices and signal peptides and in two cases (one in this study) by experimental data. The only exceptions were ALPH1 homologues from Kinetoplastida, that all have unique C-terminal and mostly unique N-terminal extension, and at least the T. brucei enzyme localises to the cytoplasm. Surprisingly, despite of these non-cytoplasmic localisations, ALPHs from all eukaryotic super-groups had in vitro mRNA decapping activity.
Conclusions: ALPH was present in the last common ancestor of eukaryotes, but most eukaryotes have either lost the enzyme since, or use it exclusively outside the cytoplasm in organelles in a version consisting of the catalytic domain only. While our data provide no evidence for the presence of further mRNA decapping enzymes among eukaryotic ALPHs, the broad substrate range of ALPHs that includes mRNA caps provides an explanation for the selection against the presence of a cytoplasmic ALPH protein as a mean to protect mRNAs from unregulated degradation. Kinetoplastida succeeded to exploit ALPH as their mRNA decapping enzyme, likely using the Kinetoplastida-unique N- and C-terminal extensions for regulation.
Healthy functioning of the female reproductive tract (FRT) depends on balanced and dynamic regulation by hormones during the menstrual cycle, pregnancy and childbirth. The mucosal epithelial lining of different regions of the FRT—ovaries, fallopian tubes, uterus, cervix and vagina—facilitates the selective transport of gametes and successful transfer of the zygote to the uterus where it implants and pregnancy takes place. It also prevents pathogen entry. Recent developments in three-dimensional (3D) organoid systems from the FRT now provide crucial experimental models that recapitulate the cellular heterogeneity and physiological, anatomical and functional properties of the organ in vitro. In this review, we summarise the state of the art on organoids generated from different regions of the FRT. We discuss the potential applications of these powerful in vitro models to study normal physiology, fertility, infections, diseases, drug discovery and personalised medicine.
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.
Circadian clocks prepare the organism to cyclic environmental changes in light, temperature, or food availability. Here, we characterized the master clock in the brain of a strongly photoperiodic insect, the aphid Acyrthosiphon pisum, immunohistochemically with antibodies against A. pisum Period (PER), Drosophila melanogaster Cryptochrome (CRY1), and crab Pigment-Dispersing Hormone (PDH). The latter antibody detects all so far known PDHs and PDFs (Pigment-Dispersing Factors), which play a dominant role in the circadian system of many arthropods. We found that, under long days, PER and CRY are expressed in a rhythmic manner in three regions of the brain: the dorsal and lateral protocerebrum and the lamina. No staining was detected with anti-PDH, suggesting that aphids lack PDF. All the CRY1-positive cells co-expressed PER and showed daily PER/CRY1 oscillations of high amplitude, while the PER oscillations of the CRY1-negative PER neurons were of considerable lower amplitude. The CRY1 oscillations were highly synchronous in all neurons, suggesting that aphid CRY1, similarly to Drosophila CRY1, is light sensitive and its oscillations are synchronized by light-dark cycles. Nevertheless, in contrast to Drosophila CRY1, aphid CRY1 was not degraded by light, but steadily increased during the day and decreased during the night. PER was always located in the nuclei of the clock neurons, while CRY was predominantly cytoplasmic and revealed the projections of the PER/CRY1-positive neurons. We traced the PER/CRY1-positive neurons through the aphid protocerebrum discovering striking similarities with the circadian clock of D. melanogaster: The CRY1 fibers innervate the dorsal and lateral protocerebrum and putatively connect the different PER-positive neurons with each other. They also run toward the pars intercerebralis, which controls hormone release via the neurohemal organ, the corpora cardiaca. In contrast to Drosophila, the CRY1-positive fibers additionally travel directly toward the corpora cardiaca and the close-by endocrine gland, corpora allata. This suggests a direct link between the circadian clock and the photoperiodic control of hormone release that can be studied in the future.
L-type voltage-gated calcium channels (LTCC) are heteromultimeric membrane proteins that allow Ca2+ entry into the cell upon plasma membrane depolarization. The β subunit of voltage-dependent calcium channels (Cavβ) binds to the α-interaction domain in the pore-forming α1 subunit and regulates the trafficking and biophysical properties of these channels. Of the four Cavβ isoforms, Cavβ2 is predominantly expressed in cardiomyocytes. This subunit associates with diverse proteins besides LTCC, but the molecular composition of the Cavβ2 nanoenvironments in cardiomyocytes is yet unresolved. Here, we used a protein-labeling technique in living cells based on an engineered ascorbate peroxidase 2 (APEX2). In this strategy, Cavβ2b was fused to APEX2 and expressed in adult rat cardiomyocytes using an adenovirus system. Nearby proteins covalently labeled with biotin-phenol were purified using streptavidin-coated beads and identified by mass spectrometry (MS). Analysis of the in situ APEX2-based biotin labeling by MS revealed 61 proteins located in the nanoenvironments of Cavβ2b, with a high specificity and consistency in all the replicates. These proteins are involved in diverse cellular functions such as cellular trafficking, sarcomere organization and excitation-contraction coupling. Among these proteins, we demonstrated an interaction between the ryanodine receptor 2 (RyR2) and Cavβ2b, probably coupling LTCC and the RyR2 into a supramolecular complex at the dyads. This interaction is mediated by the Src homology 3 (SH3) domain of Cavβ2b and is necessary for an effective pacing frequency‐dependent increase in Ca2+-induced Ca2+ release in cardiomyocytes.
One of the fascinating features of meiotic prophase I, is the highly conserved
vigorous movements of homologous chromosomes. These movements are
critical for the success of essential events as homologs alignment, synapsis and
recombination. Several organisms studied so far, including mammals, worms,
yeast and plants achieve these movements by anchoring the chromosome ends
to specialized sites in the nuclear envelope (NE). This attachment requires
telomere adaptor proteins which have to date been identified in fission yeast
and mice.
The mouse meiosis-specific telomere adaptor proteins TERB1, TERB2, and
MAJIN are involved in the attachment of ubiquitous shelterin telomere to the
LINC complex, in an analogous mechanism as those described in fission yeast.
Despite the essential role of meiosis-specific telomere adaptor proteins, the
precise mechanism of anchorage of telomeres to the nuclear envelope, as well
as their evolutionary history, are still not well understood. Therefore, the main
aim of this thesis is to investigate the organization of the mouse meiosis-specific
telomere adaptor complex TERB1-TERB2-MAJIN and its evolutionary history.
In the first part of this thesis high-resolution Structured Illumination Microscopy
(SIM), indirect immunofluorescence and Telo-FISH on mouse spermatocytes
were used to determine precisely how the telomere complex proteins are
localized with relation to the shelterin telomeric TRF1 protein and telomeric
DNA. During zygotene and pachytene stages staining patterns revealed
extensively overlapping of meiotic telomere complex proteins distributions in
which TERB2 organization is more heterogeneous than TERB1 and MAJIN at
the chromosome ends. Further, TRF1 localization was shown at the side of
lateral elements (LEs) ends with grasp-like distribution surrounding the TERB1
and MAJIN signals in zygotene and pachytene stages. Interestingly, telomeric
DNA was shown to be laterally distributed and partially overlapping with the
more central distribution displayed by meiotic telomere complex proteins of LEs
ends. The combination of these results allowed to describe an alternative model
of the telomere attachment to the NE during meiotic prophase I. The second part of this thesis, analyses mouse TERB1, TERB2, and MAJIN
evolutionary history. The lack of similarity between mouse and fission yeast
meiotic-specific telomere adaptor proteins has raised the question about the
origin of this specific complex through evolution. To identify mouse TERB1,
TERB2, and MAJIN putative orthologues, computational approaches and
phylogenetic analyses were performed. Besides, to test their potential function
during meiosis, expression studies were conducted. From these analyses, it was
revealed that mouse meiosis-specific telomere complex is ancient, as it
originated as early as eumetazoans pointing to a single origin. The absence of
any homologs in Nematoda and only a few candidates detected in Arthropoda
for meiosis-specific telomere complex, seemed, that these proteins have been
lost/replaced or highly diversified in these lineages. Remarkably, TERB1, TERB2,
and MAJIN protein domains involved in the formation of the complex as well as
those required for the interaction with the telomere shelterin protein and the
LINC complexes revealed high sequence similarity across all clades. Finally,
gene expression in the cnidarian Hydra Vulgaris provided evidence that the
TERB1-TERB2-MAJIN complex is selectively expressed in the germline
suggesting conservation of meiotic functions across metazoan evolution.
In summary, this thesis provides significant insights into the meiosis-specific
telomere complex mechanism to engage telomeres to the nuclear envelope and
the elucidation of its origin in metazoans.
Our universe may have started by Qubit decoherence:
In quantum computers, qubits have all their states undefined during calculation and become defined as output (“decoherence”). We study the transition from an uncontrolled, chaotic quantum vacuum (“before”) to a clearly interacting “real world”. In such a cosmology, the Big Bang singularity is replaced by a condensation event of interacting strings. This triggers a crystallization process. This avoids inflation, not fitting current observations: increasing long-range interactions limit growth and crystal symmetries ensure the same laws of nature and basic symmetries over the whole crystal. Tiny mis-arrangements provide nuclei of superclusters and galaxies and crystal structure allows arrangement of dark (halo regions) and normal matter (galaxy nuclei) for galaxy formation. Crystals come and go: an evolutionary cosmology is explored: entropic forces from the quantum soup “outside” of the crystal try to dissolve it. This corresponds to dark energy and leads to a “big rip” in 70 Gigayears. Selection for best growth and condensation events over generations of crystals favors multiple self-organizing processes within the crystal including life or even conscious observers in our universe. Philosophically this theory shows harmony with nature and replaces absurd perspectives of current cosmology.
Independent of cosmology, we suggest that a “real world” (so our everyday macroscopic world) happens only inside a crystal. “Outside” there is wild quantum foam and superposition of all possibilities. In our crystallized world the vacuum no longer boils but is cooled down by the crystallization event, space-time exists and general relativity holds. Vacuum energy becomes 10**20 smaller, exactly as observed in our everyday world. We live in a “solid” state, within a crystal, the n quanta which build our world have all their different m states nicely separated. There are only nm states available for this local “multiverse”. The arrow of entropy for each edge of the crystal forms one fate, one world-line or clear development of our world, while layers of the crystal are different system states. Mathematical leads from loop quantum gravity (LQG) point to required interactions and potentials. Interaction potentials for strings or loop quanta of any dimension allow a solid, decoherent state of quanta challenging to calculate. However, if we introduce here the heuristic that any type of physical interaction of strings corresponds just to a type of calculation, there is already since 1898 the Hurwitz theorem showing that then only 1D, 2D, 4D and 8D (octonions) allow complex or hypercomplex number calculations. No other hypercomplex numbers and hence dimensions or symmetries are possible to allow calculations without yielding divisions by zero. However, the richest solution allowed by the Hurwitz theorem, octonions, is actually the observed symmetry of our universe, E8. Standard physics such as condensation, crystallization and magnetization but also solid-state physics and quantum computing allow us to show an initial mathematical treatment of our new theory by LQG to describe the cosmological state transformations by equations, and, most importantly, point out routes to parametrization of free parameters looking at testable phenomena, experiments and formulas that describe processes of crystallization, protein folding, magnetization, solid-state physics and quantum computing. This is presented here for LQG, for string theory it would be more elegant but was too demanding to be shown here.
Note: While my previous Opus server preprint “A new cosmology of a crystallization process (decoherence) from the surrounding quantum soup provides heuristics to unify general relativity and quantum physics by solid state physics” (https://doi.org/10.25972/OPUS-23076) deals with the same topics and basic formulas, this new version is improved: clearer in title, better introduction, more stringent in its mathematics and improved discussion of the implications including quantum computing, hints for parametrization and connections to LQG and other current cosmological efforts.
This 5th of June 2021 version is again an OPUS preprint, but this will next be edited for Archives https://arxiv.org.
We explore a cosmology where the Big Bang singularity is replaced by a condensation event of interacting strings. We study the transition from an uncontrolled, chaotic soup (“before”) to a clearly interacting “real world”. Cosmological inflation scenarios do not fit current observations and are avoided. Instead, long-range interactions inside this crystallization event limit growth and crystal symmetries ensure the same laws of nature and basic symmetries over our domain. Tiny mis-arrangements present nuclei of superclusters and galaxies and crystal structure leads to the arrangement of dark (halo regions) and normal matter (galaxy nuclei) so convenient for galaxy formation. Crystals come and go, allowing an evolutionary cosmology where entropic forces from the quantum soup “outside” of the crystal try to dissolve it. These would correspond to dark energy and leads to a big rip scenario in 70 Gy. Preference of crystals with optimal growth and most condensation nuclei for the next generation of crystals may select for multiple self-organizing processes within the crystal, explaining “fine-tuning” of the local “laws of nature” (the symmetry relations formed within the crystal, its “unit cell”) to be particular favorable for self-organizing processes including life or even conscious observers in our universe.
Independent of cosmology, a crystallization event may explain quantum-decoherence in general: The fact, that in our macroscopic everyday world we only see one reality. This contrasts strongly with the quantum world where you have coherence, a superposition of all quantum states. We suggest that a “real world” (so our everyday macroscopic world) happens only in our domain, i.e. inside a crystal. “Outside” of our domain and our observable universe there is the quantum soup of boiling quantum foam and superposition of all possibilities. In our crystallized world the vacuum no longer boils but is cooled down by the crystallization event and hence is 10**20 smaller, exactly as observed in our everyday world. As we live in a “solid” state, within a crystal, the different quanta which build our world have all their different states nicely separated. This theory postulates there are only n quanta and m states available for them (there is no Everett-like ever splitting multiverse after each decision). In the solid state we live in, there is decoherence, the states are nicely separated. The arrow of entropy for each edge of the crystal forms one fate, one worldline or clear development of a world, while the layers of the crystal are different system states.
Some mathematical leads from loop quantum gravity point to required interactions and potentials. A complete mathematical treatment of this unified theory is far too demanding currently. Interaction potentials for strings or membranes of any dimension allow a solid state of quanta, so allowing decoherence in our observed world are challenging to calculate. However, if we introduce here the heuristic that any type of physical interaction of strings corresponds just to a type of calculation, there is already since 1898 the Hurwitz theorem showing that then only 1D, 2D, 4D and 8D (octonions) allow complex or hypercomplex number calculations. No other hypercomplex numbers and hence dimensions or symmetries are possible to allow calculations without yielding divisions by zero. However, the richest solution allowed by the Hurwitz theorem, octonions, is actually the observed symmetry of our universe, E8.
Climate plants are critical to prevent global warming as all efforts to save carbon dioxide are too slow and climate disasters on the rise. For best carbon dioxide harvesting we compare algae, trees and crop plants and use metagenomic analysis of environmental samples. We compare different pathways, carbon harvesting potentials of different plants as well as synthetic modifications including carbon dioxide flux balance analysis. For implementation, agriculture and modern forestry are important.
Endogenous clocks enable organisms to adapt cellular processes, physiology, and behavior to daily variation in environmental conditions. Metabolic processes in cyanobacteria to humans are under the influence of the circadian clock, and dysregulation of the circadian clock causes metabolic disorders. In mouse and Drosophila, the circadian clock influences translation of factors involved in ribosome biogenesis and synchronizes protein synthesis. Notably, nutrition signals are mediated by the insulin receptor/target of rapamycin (InR/TOR) pathways to regulate cellular metabolism and growth. However, the role of the circadian clock in Drosophila brain development and the potential impact of clock impairment on neural circuit formation and function is less understood. Here we demonstrate that changes in light stimuli or disruption of the molecular circadian clock cause a defect in neural stem cell growth and proliferation. Moreover, we show that disturbed cell growth and proliferation are accompanied by reduced nucleolar size indicative of impaired ribosomal biogenesis. Further, we define that light and clock independently affect the InR/TOR growth regulatory pathway due to the effect on regulators of protein biosynthesis. Altogether, these data suggest that alterations in InR/TOR signaling induced by changes in light conditions or disruption of the molecular clock have an impact on growth and proliferation properties of neural stem cells in the developing Drosophila brain.
Background: Radiotherapy is routinely used to combat glioblastoma (GBM). However, the treatment efficacy is often limited by the radioresistance of GBM cells.
Methods: Two GBM lines MO59K and MO59J, differing in intrinsic radiosensitivity and mutational status of DNA-PK and ATM, were analyzed regarding their response to DNA-PK/PI3K/mTOR inhibition by PI-103 in combination with radiation. To this end we assessed colony-forming ability, induction and repair of DNA damage by gamma H2AX and 53BP1, expression of marker proteins, including those belonging to NHEJ and HR repair pathways, degree of apoptosis, autophagy, and cell cycle alterations.
Results: We found that PI-103 radiosensitized MO59K cells but, surprisingly, it induced radiation resistance in MO59J cells. Treatment of MO59K cells with PI-103 lead to protraction of the DNA damage repair as compared to drug-free irradiated cells. In PI-103-treated and irradiated MO59J cells the foci numbers of both proteins was higher than in the drug-free samples, but a large portion of DNA damage was quickly repaired. Another cell line-specific difference includes diminished expression of p53 in MO59J cells, which was further reduced by PI-103. Additionally, PI-103-treated MO59K cells exhibited an increased expression of the apoptosis marker cleaved PARP and increased subG1 fraction. Moreover, irradiation induced a strong G2 arrest in MO59J cells (similar to 80% vs. similar to 50% in MO59K), which was, however, partially reduced in the presence of PI-103. In contrast, treatment with PI-103 increased the G2 fraction in irradiated MO59K cells.
Conclusions: The triple-target inhibitor PI-103 exerted radiosensitization on MO59K cells, but, unexpectedly, caused radioresistance in the MO59J line, lacking DNA-PK. The difference is most likely due to low expression of the DNA-PK substrate p53 in MO59J cells, which was further reduced by PI-103. This led to less apoptosis as compared to drug-free MO59J cells and enhanced survival via partially abolished cell-cycle arrest. The findings suggest that the lack of DNA-PK-dependent NHEJ in MO59J line might be compensated by DNA-PK independent DSB repair via a yet unknown mechanism.
Physiological responses of date palm (Phoenix dactylifera) seedlings to seawater and flooding
(2021)
In their natural environment along coast lines, date palms are exposed to seawater inundation and, hence, combined stress by salinity and flooding.
To elucidate the consequences of this combined stress on foliar gas exchange and metabolite abundances in leaves and roots, date palm seedlings were exposed to flooding with seawater and its major constituents under controlled conditions.
Seawater flooding significantly reduced CO\(_{2}\) assimilation, transpiration and stomatal conductance, but did not affect isoprene emission. A similar effect was observed upon NaCl exposure. By contrast, flooding with distilled water or MgSO\(_{4}\) did not affect CO\(_{2}\)/H\(_{2}\)O gas exchange or stomatal conductance significantly, indicating that neither flooding itself, nor seawater sulfate, contributed greatly to stomatal closure. Seawater exposure increased Na and Cl contents in leaves and roots, but did not affect sulfate contents significantly. Metabolite analyses revealed reduced abundances of foliar compatible solutes, such as sugars and sugar alcohols, whereas nitrogen compounds accumulated in roots.
Reduced transpiration upon seawater exposure may contribute to controlling the movement of toxic ions to leaves and, therefore, can be seen as a mechanism to cope with salinity. The present results indicate that date palm seedlings are tolerant towards seawater exposure to some extent, and highly tolerant to flooding.
Exposure of plants to environmental stressors can modify their metabolism, interactions with other organisms and reproductive success. Tropospheric ozone is a source of plant stress. We investigated how an acute exposure to ozone at different times of plant development affects reproductive performance, as well as the flowering patterns and the interactions with pollinators and herbivores, of wild mustard plants. The number of open flowers was higher on plants exposed to ozone at earlier ages than on the respective controls, while plants exposed at later ages showed a tendency for decreased number of open flowers. The changes in the number of flowers provided a good explanation for the ozone-induced effects on reproductive performance and on pollinator visitation. Ozone exposure at earlier ages also led to either earlier or extended flowering periods. Moreover, ozone tended to increase herbivore abundance, with responses depending on herbivore taxa and the plant age at the time of ozone exposure. These results suggest that the effects of ozone exposure depend on the developmental stage of the plant, affecting the flowering patterns in different directions, with consequences for pollination and reproduction of annual crops and wild species.
Plasma membrane receptors are the most crucial and most commonly studied components of cells, since they not only ensure communication between the extracellular space and cells, but are also responsible for the regulation of cell cycle and cell division. The composition of the surface receptors, the so-called "Receptome", differs and is characteristic for certain cell types. Due to their significance, receptors have been important target structures for diagnostic and therapy in cancer medicine and often show aberrant expression patterns in various cancers compared to healthy cells. However, these aberrations can also be exploited and targeted by different medical approaches, as in the case of personalized immunotherapy. In addition, advances in modern fluorescence microscopy by so-called single molecule techniques allow for unprecedented sensitive visualization and quantification of molecules with an attainable spatial resolution of 10-20 nm, allowing for the detection of both stoichiometric and expression density differences.
In this work, the single molecule sensitive method dSTORM was applied to quantify the receptor composition of various cell lines as well as in primary samples obtained from patients with hematologic malignancies. The focus of this work lies on artefact free quantification, stoichiometric analyses of oligomerization states and co localization analyses of membrane receptors.
Basic requirements for the quantification of receptors are dyes with good photoswitching properties and labels that specifically mark the target structure without generating background through non-specific binding. To ensure this, antibodies with a predefined DOL (degree of labeling) were used, which are also standard in flow cytometry. First background reduction protocols were established on cell lines prior analyses in primary patient samples. Quantitative analyses showed clear expression differences between the cell lines and the patient cells, but also between individual patients.
An important component of this work is the ability to detect the oligomerization states of receptors, which enables a more accurate quantification of membrane receptor densities compared to standard flow cytometry. It also provides information about the activation of a certain receptor, for example of FLT3, a tyrosine kinase, dimerizing upon activation. For this purpose, different well-known monomers and dimers were compared to distinguish the typical localization statistics of single bound antibodies from two or more antibodies that are in proximity. Further experiments as well as co localization analyses proved that antibodies can bind to closely adjacent epitopes despite their size.
These analytical methods were subsequently applied for quantification and visualization of receptors in two clinically relevant examples. Firstly, various therapeutically relevant receptors such as CD38, BCMA and SLAMF7 for multiple myeloma, a malignant disease of plasma cells, were analyzed and quantified on patient cells. Furthermore, the influence of TP53 and KRAS mutations on receptor expression levels was investigated using the multiple myeloma cell lines OPM2 and AMO1, showing clear differences in certain receptor quantities.
Secondly, FLT3 which is a therapeutic target receptor for acute myeloid leukemia, was quantified and stoichiometrically analyzed on both cell lines and patient cells. In addition, cells that have developed resistance against midostaurin were compared with cells that still respond to this type I tyrosine-kinase-inhibitor for their FLT3 receptor expression and oligomerization state.
Cyanine dyes are exceptionally useful probes for a range of fluorescence-based applications, but their photon output can be limited by trans-to-cis photoisomerization. We recently demonstrated that appending a ring system to the pentamethine cyanine ring system improves the quantum yield and extends the fluorescence lifetime. Here, we report an optimized synthesis of persulfonated variants that enable efficient labeling of nucleic acids and proteins. We demonstrate that a bifunctional sulfonated tertiary amide significantly improves the optical properties of the resulting bioconjugates. These new conformationally restricted cyanines are compared to the parent cyanine derivatives in a range of contexts. These include their use in the plasmonic hotspot of a DNA-nanoantenna, in single-molecule Förster-resonance energy transfer (FRET) applications, far-red fluorescence-lifetime imaging microscopy (FLIM), and single-molecule localization microscopy (SMLM). These efforts define contexts in which eliminating cyanine isomerization provides meaningful benefits to imaging performance.
The family of trypanosomatid parasites, including the human pathogens Trypanosoma brucei and Leishmania, has evolved sophisticated strategies to survive in harmful host environments. While Leishmania generate a safe niche inside the host’s macrophages, Trypanosoma brucei lives extracellularly in the mammalian bloodstream, where it is constantly exposed to the attack of the immune system. Trypanosoma brucei ensures its survival by periodically changing its protective surface coat in a process known as antigenic variation. The surface coat is composed of one species of ‘variant surface glycoprotein’ (VSG). Even though the genome possesses a large repertoire of different VSG isoforms, only one is ever expressed at a time from one out of the 15 specialized subtelomeric ‘expression sites’ (ES). Switching the coat can be accomplished either by a recombination-based exchange of the actively-expressed VSG with a silent VSG, or by a transcriptional switch to a previously silent ES.
The conserved histone methyltransferase DOT1B methylates histone H3 on lysine 76 and is involved in ES regulation in T. brucei. DOT1B ensures accurate transcriptional silencing of the inactive ES VSGs and influences the kinetics of a transcriptional switch. The molecular machinery that enables DOT1B to execute these regulatory functions at the ES is still elusive, however. To learn more about DOT1B-mediated regulatory processes, I wanted to identify DOT1B-associated proteins.
Using two complementary approaches, specifically affinity purification and proximity-dependent biotin identification (BioID), I identified several novel DOT1B-interacting candidates. To validate these data, I carried out reciprocal co-immunoprecipitations with the most promising candidates. An interaction of DOT1B with the Ribonuclease H2 protein complex, which has never been described before in any other organism, was confirmed. Trypanosomal Ribonuclease H2 maintains genome integrity by resolving RNA-DNA hybrids, structures that if not properly processed might initiate antigenic variation. I then investigated DOT1B’s contribution to this novel route to antigenic variation. Remarkably, DOT1B depletion caused an increased RNA-DNA hybrid abundance, accumulation of DNA damage, and increased VSG switching. Deregulation of VSGs from throughout the silent repertoire was observed, indicating that recombination-based switching events occurred. Encouragingly, the pattern of deregulated VSGs was similar to that seen in Ribonuclease H2-depleted cells. Together these data support the hypothesis that both proteins act together in modulating RNA-DNA hybrids to contribute to the tightly-regulated process of antigenic variation.
The transmission of trypanosomatid parasites to mammalian hosts is facilitated by insect vectors. Parasites need to adapt to the extremely different environments encountered during transmission. To ensure their survival, they differentiate into various specialized forms adapted to each tissue microenvironment. Besides antigenic variation, DOT1B additionally affects the developmental differentiation from the mammalian-infective to the insect stage of Trypanosoma brucei. However, substantially less is known about the influence of chromatin-associated proteins such as DOT1B on survival and adaptation strategies of related Leishmania parasites. To elucidate whether DOT1B’s functions are conserved in Leishmania, phenotypes after gene deletion were analyzed. As in Trypanosoma brucei, generation of a gene deletion mutant demonstrated that DOT1B is not essential for the cell viability in vitro. DOT1B deletion was accompanied with a loss of histone H3 lysine 73 trimethylation (the lysine homologous to trypanosomal H3K76), indicating that Leishmania DOT1B is also solely responsible for catalyzing this post-translational modification. As in T. brucei, dimethylation could only be observed during mitosis/cytokinesis, while trimethylation was detectable throughout the cell cycle in wild-type cells. In contrast to the trypanosome DOT1B, LmxDOT1B was not essential for differentiation in vitro. However, preliminary data indicate that the enzyme is required for effective macrophage infection.
In conclusion, this study demonstrated that the identification of protein networks and the characterization of protein functions of orthologous proteins from related parasites are effective tools to improve our understanding of the parasite survival strategies. Such insights are a necessary step on the road to developing better treatments for the devastating diseases they cause.
The parasite Trypanosoma brucei periodically changes the expression of protective variant surface glycoproteins (VSGs) to evade its host's immune sys-tem in a process known as antigenic variation. One route to change VSG expres-sion is the transcriptional activation of a previously silent VSG expression site (ES), a subtelomeric region containing the VSG genes. Homologous recombination of a different VSG from a large reservoir into the active ES represents another route. The conserved histone methyltransferase DOT1B is involved in transcriptional silencing of inactive ES and influences ES switching kinetics. The molecular machin-ery that enables DOT1B to execute these regulatory functions remains elusive, however. To better understand DOT1B-mediated regulatory processes, we purified DOT1B-associated proteins using complementary biochemical approaches. We iden-tified several novel DOT1B interactors. One of these was the RNase H2 complex, previously shown to resolve RNA-DNA hybrids, maintain genome integrity, and play a role in antigenic variation. Our study revealed that DOT1B depletion results in an increase in RNA-DNA hybrids, accumulation of DNA damage, and ES switch-ing events. Surprisingly, a similar pattern of VSG deregulation was observed in RNase H2 mutants. We propose that both proteins act together in resolving R-loops to ensure genome integrity and contribute to the tightly regulated process of anti-genic variation.
Persistence has evolved as a potent survival strategy to overcome adverse environmental conditions. This capability is common to almost all bacteria, including all human bacterial pathogens and likely connected to chronic infections caused by some of these pathogens. Although the majority of a bacterial cell population will be killed by the particular stressors, like antibiotics, oxygen and nitrogen radicals, nutrient starvation and others, a varying subpopulation (termed persisters) will withstand the stress situation and will be able to revive once the stress is removed. Several factors and pathways have been identified in the past that apparently favor the formation of persistence, such as various toxin/antitoxin modules or stringent response together with the alarmone (p)ppGpp. However, persistence can occur stochastically in few cells even of stress-free bacterial populations. Growth of these cells could then be induced by the stress conditions. In this review, we focus on the persister formation of human intracellular bacterial pathogens, some of which belong to the most successful persister producers but lack some or even all of the assumed persistence-triggering factors and pathways. We propose a mechanism for the persister formation of these bacterial pathogens which is based on their specific intracellular bipartite metabolism. We postulate that this mode of metabolism ultimately leads, under certain starvation conditions, to the stalling of DNA replication initiation which may be causative for the persister state.
The flowers of plants of the genus Ludwigia are an important source of food for several species of bees. In the current study, we conducted an experiment with the aim to describe the reproductive biology and phenology of L. nervosa; to identify the species of visiting bees; analyze the foraging behavior of bees; and to investigate whether the reproductive success of the species is related to the foraging activity of bees. We found that the flowers received visits from several native bee species (n = 7), in addition of the exotic honey bees which came to be the dominant species. During visits the majority of the bees foraged in both resources, pollen and nectar. The significantly higher production of fruits in open pollinated pollination experiment compared to artificial cross pollination, suggests honey bees as effective pollinator of this plant species in the study site. Pollen deposition occurs efficiently, given the absence of pollen limitation. Despite massive visitation of honey bees, Ludwigianervosa is attractive to native bees, and therefore it may help to sustain population of both native and exotic pollinators in fragmented humid areas.