Refine
Has Fulltext
- yes (122) (remove)
Is part of the Bibliography
- yes (122) (remove)
Year of publication
- 2014 (122) (remove)
Document Type
- Journal article (75)
- Doctoral Thesis (47)
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)
- 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)
- 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)
- 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 (122) (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)
Background: Teleost fish present a high diversity of sex determination systems, with possible frequent evolutionary turnover of sex chromosomes and sex-determining genes. In order to identify genes involved in male sex determination and differentiation in the platyfish Xiphophorus maculatus, bacterial artificial chromosome contigs from the sex-determining region differentiating the Y from the X chromosome have been assembled and analyzed.
Results: A novel three-copy gene called teximY (for testis-expressed in Xiphophorus maculatus on the Y) was identified on the Y but not on the X chromosome. A highly related sequence called texim1, probably at the origin of the Y-linked genes, as well as three more divergent texim genes were detected in (pseudo) autosomal regions of the platyfish genome. Texim genes, for which no functional data are available so far in any organism, encode predicted esterases/lipases with a SGNH hydrolase domain. Texim proteins are related to proteins from very different origins, including proteins encoded by animal CR1 retrotransposons, animal platelet-activating factor acetylhydrolases (PAFah) and bacterial hydrolases. Texim gene distribution is patchy in animals. Texim sequences were detected in several fish species including killifish, medaka, pufferfish, sea bass, cod and gar, but not in zebrafish. Texim-like genes are also present in Oikopleura (urochordate), Amphioxus (cephalochordate) and sea urchin (echinoderm) but absent from mammals and other tetrapods. Interestingly, texim genes are associated with a Helitron transposon in different fish species but not in urochordates, cephalochordates and echinoderms, suggesting capture and mobilization of an ancestral texim gene in the bony fish lineage. RT-qPCR analyses showed that Y-linked teximY genes are preferentially expressed in testis, with expression at late stages of spermatogenesis (late spermatids and spermatozeugmata).
Conclusions: These observations suggest either that TeximY proteins play a role in Helitron transposition in the male germ line in fish, or that texim genes are spermatogenesis genes mobilized and spread by transposable elements in fish genomes.
In contrast to c-Myc, a deregulated expression of the MYCN gene is restricted to human neuroendocrine tumours. In most cases, the excessive activity of N-Myc results from a MYCN amplification. In neuroblastoma, amplification of MYCN is a predictor of poor prognosis and resistance to therapy. The inability to target the N-Myc protein directly necessitates the search for alternative targets. This project aimed at identifying genes specifically required for growth and survival of cells that express high levels of N-Myc using high-throughput shRNA screening combined with next generation sequencing. The identification and analysis of these genes will shed light on functional interaction partners of N-Myc.
We screened a shRNA library containing 18,327 shRNAs and identified 148 shRNAs, which were selectively depleted in the presence of active N-Myc. In addition, shRNAs targeting genes that are involved in p53 and ARF turnover and apoptosis were depleted in the cell population during the screen. These processes are known to affect N-Myc-mediated apoptosis. Consequently, these results biologically validated the screen. The 148 shRNAs that showed a significant synthetic lethal interaction with high levels of N-Myc expression were further analysed using the bioinformatics program DAVID. We found an enrichment of shRNAs that target genes involved in specific biological processes. For example, we validated synthetic lethal interactions for genes such as, THOC1, NUP153 and LARP7, which play an important role in the process of RNA polymerase II-mediated transcription elongation. We also validated genes that are involved in the neddylation pathway.
In the screen we identified Cullin 3, which is a component of the BTB-CUL3-Rbx1 ubiquitin ligase that is involved in the turnover of Cyclin E. Depletion of cullin 3 and activation of N-Myc was found to synergistically increase Cyclin E expression to supraphysiological levels, inducing S-phase arrest and a strong DNA damage response.
Together with results from a proteomics analysis of N-Myc associated proteins, our results lead us to the following hypothesis: In a neuroblastoma cell, the high levels of N-Myc result in a conflict between RNA polymerase II and the replication machinery during S-phase. The newly identified interaction partners of N- Myc are required to solve this conflict. Consequently, loss of the interaction leads to a massive DNA damage and the induction of apoptosis. In addition, inhibition or depletion of the essential components of the neddylation pathway also results in an unresolvable problem during S-phase.