Refine
Is part of the Bibliography
- yes (123) (remove)
Year of publication
- 2014 (123) (remove)
Document Type
- Journal article (75)
- Doctoral Thesis (48)
Keywords
- gene expression (5)
- Epigenetik (4)
- Maus (4)
- Bioinformatik (3)
- Genexpression (3)
- antibodies (3)
- ants (3)
- biodiversity (3)
- cancer (3)
- cytoskeleton (3)
- dSTORM (3)
- diversity (3)
- ecology (3)
- evolution (3)
- expression (3)
- metabolism (3)
- phosphorylation (3)
- proliferation (3)
- Bestäuber (2)
- Biodiversität (2)
- Chromatin (2)
- Echinococcus (2)
- Fluoreszenzmikroskopie (2)
- Hochauflösendes Verfahren (2)
- Hochauflösung (2)
- Hämatopoese (2)
- Kilimandscharo (2)
- Kilimanjaro (2)
- MAP-Kinase (2)
- Mikroskopie (2)
- Myc (2)
- Neisseria gonorrhoeae (2)
- PALM (2)
- Regulation (2)
- Signaltransduktion (2)
- Taufliege (2)
- Trypanosoma brucei (2)
- Zellzyklus (2)
- apis mellifera (2)
- bacteria (2)
- bees (2)
- binding (2)
- culture (2)
- drosophila melanogaster (2)
- foraging (2)
- fungal structure (2)
- fungi (2)
- immunoprecipitation (2)
- meiosis (2)
- membrane proteins (2)
- miRNA (2)
- pollination (2)
- protein (2)
- reveals (2)
- sequence alignment (2)
- super-resolution (2)
- telomeres (2)
- "-omics" (1)
- 3D (1)
- 3D microscopy (1)
- ANP (1)
- ARF tumor-suppressor induced lymphomagenes (1)
- Aberration (1)
- Ackerrandstreifen (1)
- African Trypanosomes (1)
- Alignment <Biochemie> (1)
- Alkaline phosphatase (1)
- Ameisen (1)
- Angiogenese (1)
- Angiotensin II (1)
- Anticoagulants (1)
- Antigen CD8 (1)
- Apoptosis (1)
- Argonaute (1)
- Arten-Energy-Theory (1)
- Arteriogenese (1)
- Atriales natriuretisches Hormon (1)
- Atriales natriuretisches Peptid (1)
- B cell receptors (1)
- BBL (1)
- BCL-X-L P53 (1)
- BDNF (1)
- BYL-719 (1)
- Bandscheibenerkrankung (1)
- Bandscheibenkrankheit (1)
- Berger-Parker (1)
- Bestäubungsökologie (1)
- Bienen <Überfamilie> (1)
- Bildauflösung (1)
- Bilderkennnung (1)
- Bilderkennung (1)
- Bioinformatics (1)
- Biologische Uhr (1)
- Biomarker (1)
- Blattschneiderameisen (1)
- Bombus (1)
- Bombus Spp. Hymenoptera (1)
- Bone regeneration (1)
- Bortezomib (1)
- Bos taurus (1)
- Botanischer Garten (1)
- Brain (1)
- Bumblebee (1)
- Butterfly (1)
- C-MYC (1)
- C-MYC PUMA (1)
- CCDC79 (1)
- CK2 (1)
- CLAVATA3 (1)
- Carfilzomib (1)
- Cestoda (1)
- Cestode (1)
- Chirurgie (1)
- Chlamydia (1)
- Chlamydia trachomatis (1)
- Chlamydia-trachomatis-Infektion (1)
- Chromosomal Passenger Complex (1)
- Circadian Rhythms (1)
- Click-Chemie (1)
- Climate Change (1)
- Coagulation factor IX (1)
- Coexpression (1)
- Colonkrebs (1)
- Cord blood-derived hematopoietic stem and progenitor cells (1)
- Coumarin (1)
- Cross-species analyses (1)
- Cytoskeleton Chromosomal Passenger Complex Interaction GAR Domain (1)
- DM-domain gene (1)
- DNA-Methylierung (1)
- DNA-binding domain (1)
- DNA-damage checkpoint (1)
- DNS (1)
- DNS-Schädigung (1)
- DOT1 methyltransferase (1)
- Demethylierung (1)
- Deregulierung (1)
- Deutschland (1)
- Differenzierung (1)
- Dimension 3 (1)
- Diversity (1)
- Domäne <Biochemie> (1)
- Drosophila (1)
- Drosophila melanogaster (1)
- Drought (1)
- Dysplasie (1)
- ERK (1)
- Echinococcosis (1)
- Ectopic bone formation (1)
- Einfluss (1)
- Einzelmolekülmikroskopie (1)
- Embryonale Stammzelle (1)
- Embryonale Stammzellen (1)
- Epigenetic (1)
- Escherichia coli-derived recombinant human bone morphogenetic protein-2 (1)
- Evaluation (1)
- Evolution (1)
- Explorative analyses (1)
- Extrakorporale Befruchtung (1)
- FLS2 receptor (1)
- Fbw7 (1)
- Feature-Selection (1)
- Fisher-Score (1)
- Fluoreszenzlöschung (1)
- Foldamere (1)
- Foldamers (1)
- Forest management (1)
- French-Canadian patients (1)
- GAS2L3 (1)
- GC-A (1)
- Gamet (1)
- Gen notch (1)
- Gen-Knockout (1)
- Gene regulation (1)
- Gene sets (1)
- Genregulation (1)
- Germinative cell (1)
- Geschlechtsbestimmung (1)
- Glutamatrezeptor (1)
- Gonadenentwicklung (1)
- Grasses (1)
- Guanylatzyklase (1)
- Guanylylcyclase (1)
- H-Dimerbildung (1)
- HIV (1)
- HIV-1 protease (1)
- HPA Axis (1)
- HUWE1 (1)
- HeLa cells (1)
- Hearing loss (1)
- Hematopoietic stem cell ex-vivo expansion (1)
- Herbivory (1)
- Hey Proteine (1)
- Hey proteins (1)
- Hidden-Markov-Modell (1)
- Hill's powers (1)
- Histon-Demethylase UTX (1)
- Histon-Methyltransferase (1)
- Histone (1)
- Honeybee (1)
- Host-parasite interaction (1)
- Huwe1 (1)
- Hydra <Polyp> (1)
- Hypopharyngeal glands (1)
- Hypophysen-Zwischenhirn-System (1)
- Hypothalamisch-hypophysäre Achse (1)
- Höhengradient (1)
- Hörverlust (1)
- I-tasser (1)
- ITS2 (1)
- Il 4 (1)
- Immunohistochemistry (1)
- Implantat (1)
- Implantatmatrices (1)
- Improved survival (1)
- Innere Uhr (1)
- Insects (1)
- Insulin (1)
- Isoform (1)
- Isomer (1)
- Japankärpfling (1)
- KSR1 (1)
- Kenyon cells (1)
- Kernporen-Komplex (1)
- Kidney cancer (1)
- Kinase inhibitor (1)
- Knochenmark (1)
- Knock-Out (1)
- Knockout <Molekulargenetik> (1)
- Knockout mouse (1)
- Knorpelzelle (1)
- Kollagen (1)
- Kolonkarzinom (1)
- Konstruktive Didaktik (1)
- Korrelative Mikroskopie (1)
- Kreuzvalidierung (1)
- Käfer (1)
- LCK (1)
- LIN9 (1)
- Labial glands (1)
- Landnutzungsgradient (1)
- Leaves (1)
- Legumes (1)
- Lenalidomid (1)
- Lernort (1)
- Lokalisationsmikroskopie (1)
- Lymphozyten (1)
- Lymphozyten mediierter Angriff auf Neurone (1)
- MAP Kinase Signaling (1)
- MAPK (1)
- MAPK signaling cascades (1)
- MIZ1 (1)
- MRT (1)
- MSOT (1)
- MYC (1)
- Makrophage (1)
- Malaria (1)
- Massentrachten (1)
- Mausmodell (1)
- Mbm (1)
- Meiose (1)
- Melanin (1)
- Melphalan (1)
- Mensch (1)
- Mesenchymzelle (1)
- Metabolic Modelling (1)
- Metabolischen Modellierung (1)
- Methylene blue (1)
- Mexican coffee plantations (1)
- Mitose (1)
- Modellierung (1)
- Modifizierung (1)
- Molekularbiologie (1)
- Molekulargenetik (1)
- Mucin (1)
- Multiples Myelom (1)
- Mushroom bodies (1)
- Mutagenese (1)
- N-Myc (1)
- NF-KAPPA-B (1)
- Nanos (1)
- Neoblast (1)
- Nervendegeneration (1)
- Nestbau (1)
- Neuroblast (1)
- Neuroblastom (1)
- Neuropeptide (1)
- Northeastern Costa Rica (1)
- Notch Signalweg (1)
- Notch signalling (1)
- Onkolyse (1)
- Oocytes (1)
- Oozyte (1)
- Oozyten (1)
- Osmoregulation (1)
- Out-of-school learning settings (1)
- PEG chemical modification (1)
- PI3K (1)
- PPD (1)
- PRC2 (1)
- Pharmakogenetik (1)
- Phosphatidylinositolkinase <Phosphatidylinositol-3-Kinase> (1)
- Phospho-Akt (1)
- Phosphoproteine (1)
- Photoinduzierter Elektronentransfer (1)
- Phytoplankton (1)
- Plant-herbivore interactions (1)
- Plasmozytom (1)
- Pollination (1)
- Polylactide-co-glycolide (1)
- Pomalidomid (1)
- Profiling (1)
- Prognose (1)
- Prognosis (1)
- Protein p53 (1)
- Protein-Protein-Wechselwirkung (1)
- Proteindomänen (1)
- Proteindynamiken (1)
- PyMOL (1)
- RAS (1)
- RCC (1)
- RNA extraction (1)
- RNA sequence (1)
- RNA splicing (1)
- RNA-SEQ (1)
- RNA-SEQ data (1)
- RNS-Interferenz (1)
- RNS-Spleißen (1)
- Raps (1)
- Receptor kinase (1)
- Rectal cancer (1)
- Regularisierung (1)
- Regulatory Volume Decrease (1)
- Renal cell carcinoma (1)
- Renin Angiotensin System (1)
- Renin-Angiotensin-Aldosteron-System (1)
- Renin-Angiotensin-System (1)
- Repression <Genetik> (1)
- Reprogramming (1)
- Rescorla-Wagner model (1)
- Rind (1)
- SGNH hydrolase (1)
- SH3-Domäne (1)
- SPR-Spektroskopie (1)
- SPRED2 (1)
- SREC-I (1)
- SUN1 (1)
- Salmonella-containing vacuole (SCV) (1)
- Saproxylic beetles (1)
- Saproxylophage (1)
- Schwebfliegen (1)
- Sex determination (1)
- Sexual development (1)
- Sonnenblumen (1)
- Spectral Data Analysis (1)
- Spinnenseide (1)
- Spred Protein (1)
- Spred-Proteine (1)
- Spumaviren (1)
- Stammzelle (1)
- Stationenarbeit (1)
- Stem cell (1)
- Stickstoffmonoxid (1)
- Stoffwechsel (1)
- Support-Vektor-Maschine (1)
- Synaptinemal-Komplex (1)
- Säugetiere (1)
- T-Lymphozyt (1)
- TERB1 (1)
- TLR4 (1)
- TME (1)
- Tanzania (1)
- Tapeworm (1)
- Taxonomie (1)
- Teamwork (1)
- Termiten (1)
- Thrombozyt (1)
- Toll-like-Rezeptoren (1)
- Transkriptionsfaktor (1)
- Transporter SLC5A3 (1)
- Transporter SLC6A6 (1)
- Transposon (1)
- Tumour markers (1)
- Tyrosinase (1)
- Ubiquitin (1)
- VKORC1 (1)
- Vaccinia Virus (1)
- Venlafaxin (1)
- Viabilität (1)
- Virulenzfaktor (1)
- Vitamin K epoxide reductase (1)
- Volumenregulation (1)
- Vorläuferzellen (1)
- Wald (1)
- Warfarin (1)
- WebLogo (1)
- Werk (1)
- Wirkmechanismus (1)
- Y chromosome (1)
- Zelle (1)
- Zellmarker (1)
- Zellmarkierung (1)
- Zellskelett (1)
- Zellteilung (1)
- Zellvolumen (1)
- Zellüberleben (1)
- Zutokin (1)
- Zwei-Poren Domänen Kaliumkanäle (1)
- aberration (1)
- abundance (1)
- acetyltransferase RTT109 (1)
- acoustic signals (1)
- activity rhythm (1)
- adaptive plasticity (1)
- african trypanosomes (1)
- age polyethism (1)
- agroecosystems (1)
- albinaria (1)
- alpha-helical structure (1)
- ambystoma opacum (1)
- amphibian metamorphosis (1)
- amyotrophic-lateral-sclerosis (1)
- analysis of variance (1)
- ant (1)
- antigenetic variation (1)
- antigenic variation (1)
- apoptosis (1)
- arbuscular mycorrhizal fungi (1)
- arginine (1)
- arthropods (1)
- aspergillus fumigatus (1)
- auxin (1)
- background odor (1)
- bee pollinators (1)
- behavior (1)
- beta-oxidation (1)
- binding protein (1)
- biodiversity index (1)
- biodiversity measure (1)
- biogenesis (1)
- bioinformatic (1)
- biological locomotion (1)
- biological sciences (1)
- biominarlization proteins (1)
- bird species richness (1)
- birth rates (1)
- botanical gardens (1)
- brain (1)
- breast-cancer cells (1)
- bumblebee nest density (1)
- butterfly euphydryas-aurinia (1)
- cGMP (1)
- camponotus aethiops (1)
- cancer cell (1)
- cancer treatment (1)
- capacitance (1)
- carcinomas (1)
- carriage (1)
- cations (1)
- cell binding (1)
- cell biology (1)
- cell cultures (1)
- cell death (1)
- cell growth (1)
- cell membranes (1)
- cell-cycle arrest cancer therapy (1)
- chemical diversity (1)
- chemische Modifizierung (1)
- chemotherapy resistance (1)
- chi square tests (1)
- chlamydia trachomatis (1)
- chondrocytes (1)
- chromatin assembly factors (1)
- circadian oscillators (1)
- circadian rhythms (1)
- circular-dichroism (1)
- classical conditioning (1)
- clausiliidae (1)
- clumping factor-B (1)
- cohesin SMC1-Beta (1)
- colonies (1)
- colony (1)
- colorectal cancer (1)
- comb (1)
- commercial grades (1)
- communication (1)
- community structures (1)
- complex (1)
- complex-III (1)
- components (1)
- compound eye (1)
- concept maps (1)
- conceptual change (1)
- conifers (1)
- conservation (1)
- constraints (1)
- copy-number alteration (1)
- cotton rats (1)
- crop yield (1)
- crops (1)
- crosstalk (1)
- cul3 ring ligase (1)
- cycle regulation (1)
- cytokinesis (1)
- cytokinin (1)
- cytokinins (1)
- data sharing (1)
- data-bank (1)
- death rates (1)
- declines (1)
- denritic cells (1)
- density (1)
- dentichasmias busseolae (1)
- deprivation (1)
- determinant (1)
- developing country (1)
- developmental biology (1)
- developmental plasticity (1)
- developmental reprogramming (1)
- diagnosis (1)
- differentiation (1)
- digestive system (1)
- disc deseases (1)
- discrimination (1)
- dominant optic atrophy (1)
- drug discovery (1)
- dung beetle coleoptera (1)
- dye stains-all (1)
- dynamics (1)
- e1071 (1)
- economy services (1)
- ecosystem service (1)
- ecosystem services (1)
- ecosystemservices (1)
- elevational gradient (1)
- embryos (1)
- enhance (1)
- envelope (1)
- environmental cues (1)
- enzyme-linked immunoassays (1)
- epithelial cells (1)
- essential genes (1)
- evolutionary mutant model (1)
- expression site attenuation (1)
- extinction risk (1)
- factor acetylhydrolase activity (1)
- fish (1)
- fish model (1)
- fission yeast (1)
- flow cytometry (1)
- flowers (1)
- fluorescence (1)
- fluorescence microscopy (1)
- fluorescence quenching (1)
- foraging behavior (1)
- forecasting (1)
- forests (1)
- formica cunicularia (1)
- fragmented landscapes (1)
- fruit set (1)
- fruit-quality (1)
- fungal diseases (1)
- fungal pathogens (1)
- gene regulation (1)
- generalization (1)
- generation (1)
- genes and chromosomes (1)
- genome (1)
- geometric mean (1)
- global change (1)
- grasslands (1)
- growth (1)
- guanylyl cylcase A (1)
- habitat destruction (1)
- habitat patch (1)
- habitat quality (1)
- habitats (1)
- helitron (1)
- herbivores (1)
- hippocampal neurons (1)
- hive (1)
- homologous chromosomes (1)
- homology modeling (1)
- honey (1)
- honey bees (1)
- honeybee (1)
- host cells (1)
- host-cells (1)
- human impact (1)
- human mineralocorticoid receptor (1)
- humidity (1)
- hypotonic (1)
- iPS Reprogrammierung (1)
- identification (1)
- idiopathic inflammatory myopathies (1)
- image correlation spectroscopy (1)
- immune receptors (1)
- immune response (1)
- in vitro kinase assay (1)
- in-vitro (1)
- in-vivo (1)
- in-vivo expression (1)
- inducible factor-I (1)
- infections (1)
- inhibitors (1)
- insects (1)
- instensively managed farmland (1)
- interaction networks (1)
- invertebrate herbivory (1)
- isotonic (1)
- katydids orthoptera (1)
- kidneys (1)
- konditioneller Knockout (1)
- lactate dehydrogenase (1)
- lactic acid bacteria (1)
- lactobacillus (1)
- land use (1)
- land-use (1)
- land-use change (1)
- language (1)
- larval density (1)
- leaf-cutting ant (1)
- learning at workstations (1)
- learning curve (1)
- lepidoptera (1)
- life history (1)
- life stage (1)
- linguistic morphology (1)
- lipid bilayer (1)
- lipogenesis (1)
- live-cell (1)
- living cells (1)
- local enhancement (1)
- localization microscopy (1)
- location behavior (1)
- macrophage (1)
- major histocompatibility complex (1)
- malaria (1)
- mammalian septins (1)
- management (1)
- mass-flowering crops (1)
- mechanics (1)
- mechanisms (1)
- medaka (1)
- media geométrica (1)
- medical and biological imaging (1)
- medida de la biodiversidad (1)
- meiotic chromosome dynamics (1)
- melanoma (1)
- membrane characteristics (1)
- membrane organization (1)
- membrane potential (1)
- membrane structures (1)
- memory (1)
- menschlicher Einfluss (1)
- mesenchymal stem cells (1)
- messenger RNA (1)
- metapopulation (1)
- metastasis (1)
- miR-126 (1)
- miR-21 (1)
- miRNS (1)
- microvilli (1)
- mitofilin (1)
- mobility (1)
- model (1)
- modulating (1)
- mole crickets (1)
- molecular biology (1)
- molecular diversity (1)
- molecular mass (1)
- molecular-dynamics simulations (1)
- monoallelic expression (1)
- morphology (1)
- mosquito (1)
- mutation (1)
- nacreous layer formation (1)
- native pollinators (1)
- natural enemies (1)
- natural variation (1)
- naturnahe Habitate (1)
- nervous system (1)
- nest building (1)
- neurone (1)
- neurons (1)
- nonhost plant (1)
- nuclear import (1)
- nuclear-pore complexes (1)
- nympahlidae (1)
- oaks (1)
- odor marks (1)
- oilseed rape (1)
- olfaction (1)
- olyelectrolyte domains (1)
- oncogenic transformation (1)
- oncolytic viruses (1)
- organization (1)
- oryzias-latipes (1)
- p110alpha (1)
- parasite (1)
- patterns (1)
- perception (1)
- pharmacology (1)
- phenotypic plasticity (1)
- phosphorylation sites (1)
- phylogenetic trees (1)
- physical properties (1)
- pi3kinase (1)
- pines (1)
- plant community composition (1)
- plant diversity (1)
- plant hormones (1)
- plantago lanceolata (1)
- platelet activation factor (1)
- platyfish (1)
- pollinators (1)
- polyelectrolyte domains (1)
- population (1)
- populations (1)
- post-harvest quality (1)
- predation (1)
- predation risk (1)
- predictive factors (1)
- presynapse (1)
- prey growth rate (1)
- primary biliary-cirrhosis (1)
- proboscis extension response (PER) (1)
- procambarus-clarkii (1)
- product specificity (1)
- profile distances (1)
- prolactin (1)
- protease (1)
- protein domains (1)
- protein dynamics (1)
- protein-protein interactions (1)
- proteins (1)
- psycholinguistics (1)
- pulmonata (1)
- pupae (1)
- quality (1)
- rana temporaria populations (1)
- reconstruction (1)
- recruitment (1)
- red blood cells (1)
- regression analysis (1)
- regulation (1)
- renal cancer (1)
- renal cell carcinoma (1)
- replicative stress (1)
- resistance (1)
- resource use (1)
- rhythms (1)
- ribosome biogenesis (1)
- riesgo de extinción (1)
- rolling-circle transposons (1)
- saccharomyces cerevisiae (1)
- saccharomyes cerevisiae (1)
- saproxylic Coleoptera (1)
- scanning electron microscopy (1)
- scavender receptor (1)
- scientific computing (1)
- secondary structure (1)
- secreted effector protein (1)
- selection (1)
- self-organization (1)
- semi-natural habitats (1)
- sequence databases (1)
- sequential introduction (1)
- sex chromosomes (1)
- sex determination (1)
- sex-determining region (1)
- shannon index (1)
- shelf life (1)
- signaling (1)
- simpson's index (1)
- single molecule microscopy (1)
- single-trial learning (1)
- small organic osmolytes (1)
- socioeconomic (1)
- sound production (1)
- species diversity (1)
- species gastropoda (1)
- species richness (1)
- species-energy-theory (1)
- spermatocytes (1)
- spiders (1)
- spliceosomes (1)
- splicing factors (1)
- squalius alburnoides (1)
- stable-isotope (1)
- stem cell niche (1)
- strawberry (1)
- structure prediction (1)
- sucrose responsiveness (1)
- sucrose sensitivity (1)
- sunflowers (1)
- super-resolution microscopy (1)
- superresolution (1)
- surface proteins (1)
- surface water (1)
- surgical and invasive medical procedures (1)
- surgical oncology (1)
- symbiotic fungus (1)
- synapse structure (1)
- synapsis (1)
- synaptic localization (1)
- synergistische Effekte (1)
- synthetic lethality (1)
- synthetische Letalität (1)
- systematics (1)
- systemic sclerosis (1)
- systems biology (1)
- teichoic acids (1)
- telomere attachment (1)
- temperate forests (1)
- temporal spillover (1)
- termites (1)
- testis (1)
- tettigoniidae (1)
- therapy (1)
- thermoregulation (1)
- three-dimensional microscopy (1)
- tool (1)
- tousled-like kinases (1)
- toxins (1)
- transcription (1)
- transcription factor MIZ-1 (1)
- transfer RNA-synthetases (1)
- transgenic mice (1)
- transplantation (1)
- transposition (1)
- transposon mutagenesis (1)
- tree plantations (1)
- trees (1)
- triglyceride accumulation (1)
- tropical ecology (1)
- tropische Ökologie (1)
- tumor (1)
- two-color microscopy (1)
- two-pore domain potassium channels (1)
- tyrosine phosphorylation (1)
- ubiquitination (1)
- unstructured proteins (1)
- urban-rural gradient (1)
- vaccinia virus (1)
- variant detection (1)
- variant surface glycoprotein (VSG) (1)
- vibration (1)
- viral entry (1)
- viral replication (1)
- viral transmission and infection (1)
- virulence (1)
- virulence factors (1)
- visual cues (1)
- visual learning (1)
- vocabulary (1)
- volatiles (1)
- waggle dance (1)
- wild (1)
- wild bees (1)
- xanthurenic acid (1)
- xiphophorus maculatus (1)
- zebrafish (1)
- zeitlicher Spillover (1)
- Ökosystem (1)
- Überexpression (1)
- índice de biodiversidad (1)
Institute
- Theodor-Boveri-Institut für Biowissenschaften (123) (remove)
Sonstige beteiligte Institutionen
- DNA Analytics Core Facility, Biocenter, University of Würzburg, Würzburg, Germany (1)
- Department of Animal Ecology and Tropical Biology, University of Würzburg, Würzburg, Germany (1)
- Forschungsstation Fabrikschleichach (1)
- Institut für Tierökologie und Tropenbiologie (1)
- Interdisziplinäres Zentrum für Klinische Forschung (ZIKF), Würzburg (1)
- Klinische Mikrobiologie am Universitätsklinikum Erlangen (1)
- Technische Hochschule Wildau (1)
All organisms have to adapt to acute as well as to regularly occurring changes in the environment. To deal with these major challenges organisms evolved two fundamental mechanisms: the p38 mitogen-activated protein kinase (MAPK) pathway, a major stress pathway for signaling stressful events, and circadian clocks to prepare for the daily environmental changes. Both systems respond sensitively to light. Recent studies in vertebrates and fungi indicate that p38 is involved in light-signaling to the circadian clock providing an interesting link between stress-induced and regularly rhythmic adaptations of animals to the environment, but the molecular and cellular mechanisms remained largely unknown. Here, we demonstrate by immunocytochemical means that p38 is expressed in Drosophila melanogaster's clock neurons and that it is activated in a clock-dependent manner. Surprisingly, we found that p38 is most active under darkness and, besides its circadian activation, additionally gets inactivated by light. Moreover, locomotor activity recordings revealed that p38 is essential for a wild-type timing of evening activity and for maintaining ∼ 24 h behavioral rhythms under constant darkness: flies with reduced p38 activity in clock neurons, delayed evening activity and lengthened the period of their free-running rhythms. Furthermore, nuclear translocation of the clock protein Period was significantly delayed on the expression of a dominant-negative form of p38b in Drosophila's most important clock neurons. Western Blots revealed that p38 affects the phosphorylation degree of Period, what is likely the reason for its effects on nuclear entry of Period. In vitro kinase assays confirmed our Western Blot results and point to p38 as a potential "clock kinase" phosphorylating Period. Taken together, our findings indicate that the p38 MAP Kinase is an integral component of the core circadian clock of Drosophila in addition to playing a role in stress-input pathways.
Virotherapy on the basis of oncolytic vaccinia virus (VACV) infection is a promising approach for cancer therapy. In this study we describe the establishment of a new preclinical model of feline mammary carcinoma (FMC) using a recently established cancer cell line, DT09/06. In addition, we evaluated a recombinant vaccinia virus strain, GLV-5b451, expressing the anti-vascular endothelial growth factor (VEGF) single-chain antibody (scAb) GLAF-2 as an oncolytic agent against FMC. Cell culture data demonstrate that GLV-5b451 virus efficiently infected, replicated in and destroyed DT09/06 cancer cells. In the selected xenografts of FMC, a single systemic administration of GLV-5b451 led to significant inhibition of tumor growth in comparison to untreated tumor-bearing mice. Furthermore, tumor-specific virus infection led to overproduction of functional scAb GLAF-2, which caused drastic reduction of intratumoral VEGF levels and inhibition of angiogenesis.
In summary, here we have shown, for the first time, that the vaccinia virus strains and especially GLV-5b451 have great potential for effective treatment of FMC in animal model.
Bacterial symbionts of insects have received increasing attention due to their prominent role in nutrient acquisition and defense. In social bees, symbiotic bacteria can maintain colony homeostasis and fitness, and the loss or alteration of the bacterial community may be associated with the ongoing bee decline observed worldwide. However, analyses of microbiota associated with bees have been largely confined to the social honeybees (Apis mellifera) and bumblebees (Bombus spec.), revealing – among other taxa – host-specific lactic acid bacteria (LAB, genus Lactobacillus) that are not found in solitary bees. Here, we characterized the microbiota of three Australian stingless bee species (Apidae: Meliponini) of two phylogenetically distant genera (Tetragonula and Austroplebeia). Besides common plant bacteria, we find LAB in all three species, showing that LAB are shared by honeybees, bumblebees and stingless bees across geographical regions. However, while LAB of the honeybee-associated Firm4–5 clusters were present in Tetragonula, they were lacking in Austroplebeia. Instead, we found a novel clade of likely host-specific LAB in all three Australian stingless bee species which forms a sister clade to a large cluster of Halictidae-associated lactobacilli. Our findings indicate both a phylogenetic and geographical signal of host-specific LAB in stingless bees and highlight stingless bees as an interesting group to investigate the evolutionary history of the bee-LAB association.
Intricate mechanisms discriminate between friends and foes in plants. Plant organs deploy overlapping and distinct protection strategies. Despite vulnerability to a plethora of pathogens, the growing tips of plants grow bacteria free. The shoot apical meristem (SAM) is among three stem cells niches, a self-renewable reservoir for the future organogenesis of leaf, stem, and flowers. How plants safeguard this high value growth target from infections was not known until now. Recent reports find the stem cell secreted 12-amino acid peptide CLV3p (CLAVATA3 peptide) is perceived by FLS2 (FLAGELLIN SENSING 2) receptor and activates the transcription of immunity and defense marker genes. No infection in the SAM of wild type plants and bacterial infection in clv3 and fls2 mutants illustrate this natural protection against infections. Cytokinins (CKs) are enriched in the SAM and regulate meristem activities by their involvement in stem cell signaling networks. Auxin mediates plant susceptibility to pathogen infections while CKs boost plant immunity. Here, in addition to the stem-cell-triggered immunity we also highlight a potential link between CK signaling and CLV3p mediated immune response in the SAM.
Fbw7, the substrate recognition subunit of SCF(Fbw7) ubiquitin ligase, mediates the turnover of multiple proto-oncoproteins and promotes its own degradation. Fbw7-dependent substrate ubiquitination is antagonized by the Usp28 deubiquitinase. Here, we show that Usp28 preferentially antagonizes autocatalytic ubiquitination and stabilizes Fbw7, resulting in dose-dependent effects in Usp28 knockout mice. Monoallelic deletion of Usp28 maintains stable Fbw7 but drives Fbw7 substrate degradation. In contrast, complete knockout triggers Fbw7 degradation and leads to the accumulation of Fbw7 substrates in several tissues and embryonic fibroblasts. On the other hand, overexpression of Usp28 stabilizes both Fbw7 and its substrates. Consequently, both complete loss and ectopic expression of Usp28 promote Ras-driven oncogenic transformation. We propose that dual regulation of Fbw7 activity by Usp28 is a safeguard mechanism for maintaining physiological levels of proto-oncogenic Fbw7 substrates, which is equivalently disrupted by loss or overexpression of Usp28.
Depressive Erkrankungen verursachen sowohl das persönliche Leid der erkrankten Individuen als auch volkswirtschaftlichen Schaden durch krankheitsbedingten Arbeitsausfall und Belastung der Gesundheitsversorgungssysteme. Therapeutische Konzepte wie die Anwendung pharmakotherapeutischer Intervention sind in unterschiedlichem Maß von Erfolg gekrönt.
Zahlreiche somatische Faktoren wurden mit der Ätiologie depressiver Störungen in Verbindung gebracht. Die primär verfolgten pharmakologischen Ansätze basieren nach wie vor auf Erkenntnissen aus der Mitte des vergangenen Jahrhunderts. In erster Linie setzt die Pharmakotherapie Substanzen ein, die die Wiederaufnahme monoaminerger Neurotransmitter (Serotonin, Noradrenalin, zum Teil auch Dopamin) aus dem synaptischen Spalt inhibieren und nach einer allerdings meist mehrwöchigen, regelmäßigen Einnahme des Präparates zu einem Rückgang der depressiven Symptomatik führen. Andererseits kann jedoch bei zahlreichen Erkrankten auch nach fortgesetzter Therapie mit verschiedenen Behandlungsansätzen keine Remission verzeichnet werden und es stellt sich die Frage nach der Ursache dieser Diskrepanz.
Im Fokus der vorliegenden Arbeit stand der als Antidepressivum eingesetzte selektive Serotonin- / Noradrenalin-Wiederaufnahme-Inhibitor Venlafaxin. Durch Blockade des präsynaptischen Serotonin- und Noradrenalin-Transporters führt Venlafaxin initial zu einer intensivierten Neurotransmission. Die Zielstrukturen von Venlafaxin sind der präsynaptische Serotonin- und der Noradrenalin-Transporter, wobei aufgrund unterschiedlicher Affinität eine geringe Dosis beziehungsweise Konzentration als rein serotonerg betrachtet wird und bei einer hohen Dosis beziehungsweise Konzentration sowohl die Wiederaufnahme von Serotonin als auch Noradrenalin inhibiert wird.
Es wurden in dieser Arbeit zwei Ziele verfolgt. Im ersten Teil wurde mittels Gen-expressionsuntersuchungen nach potentiellen Effektoren von Venlafaxin gesucht, um prinzipielle Mechanismen der antidepressiven Wirkung zu identifizieren und auf ihrer Basis die Entwicklung spezifischerer Intervention zu ermöglichen.
Der zweite Teil beinhaltet eine pharmakogenetische Untersuchung am Menschen. Ziel war zu evaluieren, inwieweit die Expressionsaktivität von SLC6A2 und SLC6A4 und damit die präsynaptische Transportkapazität in Kombination mit der Serumkonzentration aktiver Substanz als Prädiktor des therapeutischen Effektes dienen kann. Die Kenntnis dieser Zusammenhänge würde bei Vorliegen eines bestimmten Genotyps eine gezieltere Titration der individuell benötigten Konzentration ermöglichen und könnte die Effektivität der Therapie steigern.
Für die Genexpressionsuntersuchungen erhielten DBA/2-Mäuse über einen Zeitraum von 30 Tagen Venlafaxin in verschiedenen Dosierungen über das Trinkwasser. Anschließend wurden die Hippokampi der Tiere mittels genomweiter Microarray-Analyse hypothesenfrei auf zwischen den Dosisgruppen differentiell exprimierte Gene hin untersucht. Der Hippokampus wird als zentrales Element der Steuerung, Ausbildung und Veränderung von Verhaltensmustern gesehen. Signifikant differentiell exprimierte Gene, die in vorherigen Studien mit depressiver Erkrankung beziehungsweise einem Effekt psychiatrischer Medikation assoziiert worden waren, wurden mittels qRT-PCR-Analyse validiert. Im Anschluss an die Analyse im Tier wurden als differentiell exprimiert bestätigte Gene per qRT-PCR analog in humanen Leukozyten untersucht. Die Blutproben waren in einem klinisch-naturalistischen Design während der ersten und der fünften Woche einer Venlafaxin-Pharmakotherapie von Patienten der Klinik für Psychiatrie, Psychosomatik und Psychotherapie des Universitätsklinikums Würzburg gewonnen worden, das heißt vor und nach potentiellem Eintreten der antidepressiven Wirkung. Trotz der unterschiedlichen Herkunft der analysierten Gewebe könnten auf diesem Weg Hinweise auf Vorgänge im menschlichen Gehirn gefunden werden, wie in vergleichenden post mortem Untersuchungen zwischen peripherem und zentralem humanem Material erkannt worden war.
Die in der Tierstudie identifizierten Gene kodieren für Transkriptionsfaktoren sowie Proteine die als Teil von second messenger-Kaskaden bekannt sind. Von statistischer Signifikanz erwies sich in der Analyse der humanen Leukozyten die Expressionsreduktion der mRNA der Transkriptionsfaktor-Untereinheit Fos.
Befunde zu einer Funktion von Fos, die eine Interpretation im Bezug auf den antidepressiven Effekt von Venlafaxin ermöglichen, liegen lediglich aus Tierstudien vor. Fos-ko im Hippo-kampus von Mäusen wurde mit reduziertem Angstverhalten und höherer Exzitabilität von hippokampalen Neuronen assoziiert. Auch wurde eine Assoziation mit Vorgängen bei synaptischer Plastizität und damit potentiell bei Lernvorgängen gefunden. Auf der anderen Seite wurde depressions-ähnliches Verhalten bei Ratten mit niedriger hippokampaler Fos-Expression und dessen erfolgreiche pharmakologische "Therapie" mit einer Induktion der Fos-Expression assoziiert. Es scheinen also bereits zwischen nicht-menschlichen Spezies ausgeprägte Unterschiede der Rolle von Fos beziehungsweise Fos zu bestehen.
Aufgrund der unterschiedlichen Spezies und Gewebe in den hier durchgeführten Untersuchungen sowie den uneinheitlichen Befunden bezüglich der Rolle von Fos beziehungsweise Fos in vorangegangenen Studien kann abschließend lediglich konstatiert werden, dass Fos vermutlich an der Entstehung depressionsbegünstigender Physiologie beteiligt ist und auch, dass eine antidepressive Pharmakotherapie mit Venlafaxin ihre Wirkung vermutlich unter Beteiligung von Fos entfaltet.
Die Entwicklung innovativer Antidepressiva die unter Umgehung der monoaminergen Transmissionssysteme durch gezielte Reduktion der Fos-Abundanz das therapeutische Ziel erreichen lassen, könnte auf Basis der vorliegenden Studie angedacht werden, scheint allerdings aufgrund der ubiquitären Mediatorentätigkeit des Proteins und insbesondere aufgrund seiner nicht endgültig definierten Rolle bei der Entstehung von Krebs nicht praktikabel. Zukünftige Untersuchungen sollten daher auf andere im Microarray differentiell exprimiert gefundene Gene fokussieren.
In die Untersuchung der Expressionsaktivität der für die primären Zielstrukturen von Venlafaxin (Serotonin- beziehungsweise Noradrenalin-Transporter) kodierenden Gene (SLC6A4 beziehungsweise SLC6A2) und der Serumkonzentration an aktiver Substanz nach Venlafaxin-Applikation im Hinblick auf deren Prädiktivität des therapeutischen Effektes, wurden in einem klinisch-naturalistischen Design Patienten der Klinik für Psychiatrie, Psychosomatik und Psychotherapie des Universitätsklinikums Würzburg eingeschlossen. Genotypisiert wurden für SLC6A2 der SNP rs28386840 und für SLC6A4 der Polymorphismus 5-HTTLPR. Die Genotypen wurden jeweils in niedrig- und hoch-exprimierend unterteilt und damit auf die phänotypische Transportkapazität der präsynaptischen Membran Bezug genommen. Der therapeutische Erfolg wurde anhand der CGI-I-Skala evaluiert und für die Analysen in "gutes Ansprechen" und "schlechtes Ansprechen" dichotomisiert.
Der SLC6A2-Polymorphismus zeigte sich als nicht mit dem therapeutischen Effekt assoziiert. Der hochexprimierende SLC6A4-Genotyp wurde signifikant mit einem schlechteren Ansprechen assoziiert. Dies war in den nach Serumkonzentration aktiver Substanz stratifizierten Unterkollektiven insbesondere in dem Bereich zwischen 200 und 400 ng / ml zu erkennen, wohingegen unter- und oberhalb dieses Bereiches keine Assoziation zu finden war.
Aus diesen Resultaten kann gefolgert werden, dass sich aus der Genotypisierung von rs28386840 keine therapeutischen Instruktionen ableiten lassen. Bei Kenntnis des 5-HTTLPR-Genotyps könnte für den klinischen Alltag die Empfehlung ergehen, falls Venlafaxin als sSNRI bei Patienten mit hochexprimierendem Genotyp eingesetzt werden soll, eine Serumsummenkonzentration jenseits des durch die AGNP empfohlenen Bereiches (100 - 400 ng / ml) anzustreben.
Da hier jedoch lediglich eine Stichprobe von 56 Patienten untersucht und insbesondere, da zahlreiche potentielle Kofaktoren des therapeutischen Effektes nicht in die Analyse einbezogen werden konnten, ist die Assoziation vor Anwendung in der Therapiesteuerung anhand umfassenderer prospektiver kontrollierter Studien zu validieren.
Neisseria gonorrhoeae is a human-specific pathogen that causes gonorrhea. It is defined as a super bacterium by the WHO due to the emergence of gonococci that are resistant to a variety of antibiotics and a rapidly increasing infection incidence. Genome-wide investigation of neisserial gene essentiality and novel virulence factors is urgently required in order to identify new targets for anti-neisserial therapeutics. To identify essential genes and new virulence factors, a high-density mutant library in N. gonorrhoeae MS11 was generated by in vitro transposon mutagenesis. The transposon library harbors more than 100,000 individual mutants, a density that is unprecedented in gonococcal research. Essential genes in N. gonorrhoeae were determined by enumerating frequencies of transposon insertion sites (TIS) with Illumina deep sequencing (Tn-seq). Tn-seq indicated an average distance between adjacent TIS of 25 bp. Statistical analysis unequivocally demonstrated 781 genes that were significantly depleted in TIS and thus are essential for Neisseria survival. A subset of the genes was experimentally verified to comprise essential genes and thus support the outcome of the study. The hereby identified candidate essential genes thus may constitute excellent targets for the development of new antibiotics or vaccines.
In a second study, the transposon mutant library was applied in a genome-scale “negative-selection strategy” to identify genes that are involved in low phosphate-dependent invasion (LPDI). LPDI is dependent on the Neisseria porin subtype PorBIA which acts as an epithelial cell invasin in absence of phosphate and is associated with severe pathogenicity in disseminated gonococcal infections (DGI). Tn-seq demonstrated 98 genes, which were involved in adherence to host cells and 43 genes involved in host cell invasion. E.g. the hypothetical protein NGFG_00506, an ABC transporter ATP-binding protein NGFG_01643, as well as NGFG_04218 encoding a homolog of mafI in N. gonorrhoeae FA1090 were experimentally verified as new invasive factors in LPDI. NGFG_01605, a predicted protease, was identified to be a common factor involved in PorBIA, Opa50 and Opa57-mediated neisserial engulfment by the epithelial cells. Thus, this first systematic Tn-seq application in N. gonorrhoeae identified a set of previously unknown N. gonorrhoeae invasive factors which demonstrate molecular mechanisms of DGI.
Obligate intracellular bacteria depend entirely on nutrients from the host cell for their reproduction. Here, we show that obligate intracellular Chlamydia downregulate the central tumor suppressor p53 in human cells. This reduction of p53 levels is mediated by the PI3K-Akt signaling pathway, activation of HDM2, and subsequent proteasomal degradation of p53. The stabilization of p53 in human cells severely impaired chlamydial development and caused the loss of infectious particle formation. DNA-damage-induced p53 interfered with chlamydial development through downregulation of the pentose phosphate pathway (PPP). Increased expression of the PPP key enzyme glucose-6-phosphate dehydrogenase rescued the inhibition of chlamydial growth induced by DNA damage or stabilized p53. Thus, downregulation of p53 is a key event in the chlamydial life cycle that reprograms the host cell to create a metabolic environment supportive of chlamydial growth.
Deregulated expression of MYC is a driver of colorectal carcinogenesis, necessitating novel strategies to inhibit MYC function. The ubiquitin ligase HUWE1 (HECTH9, ARF-BP1, MULE) associates with both MYC and the MYC-associated protein MIZ1. We show here that HUWE1 is required for growth of colorectal cancer cells in culture and in orthotopic xenograft models. Using high-throughput screening, we identify small molecule inhibitors of HUWE1, which inhibit MYC-dependent transactivation in colorectal cancer cells, but not in stem and normal colon epithelial cells. Inhibition of HUWE1 stabilizes MIZ1. MIZ1 globally accumulates on MYC target genes and contributes to repression of MYC-activated target genes upon HUWE1 inhibition. Our data show that transcriptional activation by MYC in colon cancer cells requires the continuous degradation of MIZ1 and identify a novel principle that allows for inhibition of MYC function in tumor cells.
For social insects, colony performance is largely dependent on the quantity and quality of food intake and thus on the efficiency of its foragers. In addition to innate preferences and previous experience, foragers can use social information to decide when and where to forage. In some stingless bee (Meliponini) species, individual foraging decisions are shown to be influenced by the presence of social information at resource sites. In dual choice tests, we studied whether visual and/or olfactory cues affect individual decision-making in rigona corvina Cockerell and if this information is species-specific. We found that T. corvina foragers possess local enhancement: they are attracted by olfactory and visual cues released by conspecifics but avoid feeders associated with heterospecific individuals of the species Tetragona ziegleri (Friese). Overall, olfactory cues seem to be more important than visual cues, but information by visual cues alone is sufficient for discrimination.