Refine
Has Fulltext
- yes (131) (remove)
Is part of the Bibliography
- yes (131)
Year of publication
- 2020 (131) (remove)
Document Type
- Journal article (99)
- Doctoral Thesis (32)
Keywords
- biodiversity (5)
- autophagy (4)
- Apis mellifera (3)
- Drosophila melanogaster (3)
- Staphylococcus aureus (3)
- cell death (3)
- colorectal cancer (3)
- diversity (3)
- evolution (3)
- foraging (3)
- forest management (3)
- mutualism (3)
- nutrition (3)
- Acromyrmex fracticornis (2)
- Chlamydia trachomatis (2)
- Chrysididae (2)
- Einzelmolekülmikroskopie (2)
- Entwicklung (2)
- Epichloë (2)
- Expansion microscopy (2)
- High throughput screening (2)
- Hill numbers (2)
- Lolium perenne (2)
- Mikroskopie (2)
- Plasmozytom (2)
- Signaltransduktion (2)
- Surgery (2)
- Taufliege (2)
- bee decline (2)
- bees (2)
- body size (2)
- circadian clock (2)
- climate change (2)
- cool-season grass species (2)
- deadwood enrichment (2)
- dispersal (2)
- ecological intensification (2)
- ecosystem services (2)
- endophyte (2)
- exome sequencing (2)
- honey bees (2)
- identification (2)
- infection rates (2)
- kardiale Hypertrophie (2)
- leaf-cutting ants (2)
- molecular docking (2)
- mortality (2)
- natural disturbance (2)
- plant-insect interactions (2)
- pollinator friendly plants (2)
- saproxylic beetles (2)
- self-organization (2)
- solitary bee (2)
- symbiosis (2)
- toxicity (2)
- wild bees (2)
- wood-inhabiting fungi (2)
- 28 (1)
- 3D reconstruction (1)
- 3D tissue models (1)
- 6-benzylaminopurine (1)
- ATP-adenosine triphosphate (1)
- Acipenser baerii (1)
- Adaptive Optics (1)
- Adaptive Optik (1)
- Adipozytäre mesenchymale Stammzelle (1)
- Alkaloide (1)
- Alzheimerkrankheit (1)
- Amelogenese (1)
- Amplicon Sequencing (1)
- Amyotrophic Lateral Sclerosis (1)
- Anthropocene (1)
- Artensterben (1)
- Aspergillus medium (1)
- Aufmerksamkeitsdefizit-Syndrom (1)
- Automated analysis (1)
- Axl tyrosine kinase (1)
- BRAF mutation (1)
- Bacillus (1)
- Bembix (1)
- Biene (1)
- Bienenverhalten (1)
- Bilharziose (1)
- Bio-artifizieller Tubulus (1)
- Biologie (1)
- Biologische Schädlingsbekämpfung (1)
- Biologische Uhr (1)
- Boolesches Netz (1)
- Brain-Computer Interface (1)
- C-Typ natriuretisches Peptid (1)
- C. elegans (1)
- CCL3 (1)
- CCL4 (1)
- CCL5 (1)
- CCl\(_4\) (1)
- CDC14A (1)
- CLV3p (1)
- COVID-19 (1)
- COX2 expression (1)
- Cadherin-13 (1)
- Calcineurin (1)
- Cataglyphis-Wüstenameisen (1)
- Cdu1 (1)
- Chagas diagnosis (1)
- Chagas disease (1)
- Chagas monitoring (1)
- Chagas real time PCR (1)
- ChlaDUB1 (1)
- Complex medium (1)
- Correlative microscopy (1)
- Costa Rica (1)
- Cuticular hydrocarbons (1)
- DFNB32 (1)
- DNA barcoding (1)
- DNA double-strand breaks (1)
- DNA metabarcoding (1)
- DNS-Reparatur (1)
- DUB (1)
- Deutsches Weidelgras (1)
- Drosophila (1)
- Education (1)
- Elektroencephalographie (1)
- Endophytische Pilze (1)
- Endothelzelle (1)
- Epichloe endophytes (1)
- Epichloë spp. (1)
- Fagus orientalis (1)
- Fagus sylvatica (1)
- Fanconi-Anämie (1)
- Fitness (1)
- Fluoreszenzmikroskopie (1)
- Fourthcorner analysis (1)
- Gehirn (1)
- Gehirn-Computer-Schnittstelle (1)
- Gehirnentwicklung (1)
- Gene expression vectors (1)
- Genexpression (1)
- Genpanel (1)
- Genregulation (1)
- Glucosetransporter Typ3 (1)
- Glutamatrezeptor (1)
- Golgi (1)
- Guanylylcyclase B Rezeptor (1)
- HGF (1)
- HIV-1 (1)
- HNSCC (1)
- HPLC-MS (1)
- HPLC/UPLC methods (1)
- Herzinsuffizienz (1)
- High-throughput data (1)
- Himmelskompass (1)
- Hochaufgelöste Fluoreszenzmikroskopie (1)
- Hochauflösende Mikroskopie (1)
- Hohlfaserreaktor (1)
- Honigbienen (1)
- Hörstörungen (1)
- ICP27 (1)
- IGF1R (1)
- Image-Scanning Microscope (1)
- ImageJ plugin (1)
- Immunbiologie (1)
- Inoculum production (1)
- Insect symbiois (1)
- Insektennavigation (1)
- Ionizing radiation (1)
- Jena Experiment (1)
- Kardiomyopathie (1)
- Kenyon cells (1)
- Kleine GTP-bindende Proteine (1)
- Knochenmark (1)
- Ko-Kultur (1)
- Landwirtschaft (1)
- Langzeitgedächtnis (1)
- Luftfeuchtigkeit (1)
- Magnetkompass (1)
- Maus (1)
- Meiose (1)
- Meiosis (1)
- Membranproteine (1)
- Mensch (1)
- Mesenchymale Stammzelldifferenzierung (1)
- Met (1)
- Microarray analysis (1)
- Microscopy (1)
- Mitochondria (1)
- Moleküle (1)
- Multiple Myeloma (1)
- Multiples Myelom (1)
- Multivariate analysis (1)
- Muskelzelle (1)
- Mutationsanalyse (1)
- Myatrophische Lateralsklerose (1)
- Myc (1)
- NOTCH (1)
- NRF2 (1)
- Naturschutz (1)
- Netzwerkrekonstruktion (1)
- Netzwerksimulation (1)
- Neuroblast (1)
- Neuroblastenproliferation (1)
- Neurodegeneration (1)
- Neuromuskuläre Synapse (1)
- Next generation sequencing (1)
- Nicotinischer Acetylcholinrezeptor (1)
- Oligomerisation (1)
- Open-source tool (1)
- Ordination methods (1)
- Osmia bicornis (1)
- PALM stoichiometry (1)
- PER (1)
- Paenibacillus (1)
- Pakistan (1)
- Parasit (1)
- Peptide (1)
- Pflanzen-Bienen-Netzwerke (1)
- Photoschädigung (1)
- Plant growth promotion (1)
- Plant root endophyte (1)
- Polymerase chain reaction (1)
- Quantitative Mikroskopie (1)
- RAL (1)
- RFID (1)
- RLQ analysis (1)
- RNA-Seq analysis (1)
- Radiation biology (1)
- Radiochemotherapy (1)
- Real-time PCR (1)
- Receptor-Tyrosine Kinases (1)
- Rectal cancer (1)
- Renaturierung <Ökologie> (1)
- Rezeptor-Tyrosinkinasen (1)
- Rollstuhl (1)
- SARS-CoV-2 (1)
- SLAC/SLAH (1)
- Sandminen (1)
- Sanger sequencing (1)
- Savanna–Forest mosaic (1)
- Schistosomiasis (1)
- Seahorse XF (1)
- Sequenzdaten (1)
- Serendipita indica (1)
- Shotgun method (1)
- Small RNA (1)
- Sporosarcina (1)
- Stammzelle (1)
- Sunitinib (1)
- Super-resolution microscopy (1)
- Superresolution microscopy (1)
- Synthetic biology (1)
- Systembiologie (1)
- T cell receptor (1)
- Tageslänge (1)
- Tansania (1)
- Temperatur (1)
- Tetrazin (1)
- Time interval (1)
- Transcriptomics (1)
- TreMs (1)
- Trematoden (1)
- Trypanosoma brucei (1)
- Trypanosoma cruzi (1)
- Tyrosine kinase inhibition (1)
- Universität Würzburg. Lehrstuhl für Bioinformatik (1)
- VSG (1)
- Varroa destructor (1)
- Vegetable juice (1)
- Vernachlässigte Tropenkrankheiten (1)
- Virtual sequencing (1)
- Visualisierung (1)
- Visualization (1)
- Weidegräser (1)
- Wheelchair Navigation (1)
- Wildbienen (1)
- Wirtszelle (1)
- Zahnentwicklung (1)
- Zelldifferenzierung (1)
- Zellen (1)
- Zelltod (1)
- Zellüberleben (1)
- acipenserid minisatellite (1)
- activity rhythm (1)
- activity-based probes (1)
- acylcarnitine (1)
- adipose tissue-derived MSCs (1)
- adult bees (1)
- affinity (1)
- agriculture (1)
- alkaloid concentrations (1)
- alkaloid detection methods (1)
- alkaloids (1)
- altitudinal gradient (1)
- ambrosia beetles (1)
- amino acids (1)
- amyotrophic lateral sclerosis (1)
- angiogenesis (1)
- annotation (1)
- ant brain (1)
- antagonists (1)
- antennal lobes (1)
- anthropogenic food subsidies (1)
- anti-cancer drug-like molecules (1)
- antigenic variation (1)
- antimicrobial (1)
- ants (1)
- aposematism (1)
- architecture (1)
- assembly mechanisms (1)
- autosomal recessive hearing loss (1)
- autotoxicity (1)
- bacterial infection (1)
- bacterial spread (1)
- bacterial transmission (1)
- baited traps (1)
- bark beetle (1)
- bark beetles (1)
- bark-peeling (1)
- bee conservation (1)
- beech forest (1)
- beetle (1)
- behavioral plasticity (1)
- behavioural plasticity (1)
- bestäuberfreundliche Pflanzen (1)
- bet-hedging (1)
- beta-diversity (1)
- binding (1)
- binding protein (1)
- biodiversity threats (1)
- bioinformatics (1)
- biological macromolecules (1)
- biological pest control (1)
- biosecurity (1)
- bird communities (1)
- birds (1)
- blood brain barrier (1)
- blood stream (1)
- bombus terrestris (1)
- bottom‐up and top‐down control (1)
- brain development (1)
- breeding season (1)
- broadleaf tree species (1)
- bryophytes (1)
- building behavior (1)
- bypass (1)
- c-type natriuretic peptide (1)
- calcium signaling pathway (1)
- cancer (1)
- cancer metabolism (1)
- canine adipose-derived mesenchymal stem cells (cAdMSCs) (1)
- canine cancer cell lines (1)
- canine cancer therapy (1)
- canine soft tissue sarcoma (CSTS) (1)
- capture (1)
- carbohydrates (1)
- cardiac hypertrophy (1)
- carrion ecology (1)
- cascade (1)
- caspases (1)
- cathepsin (1)
- ceiba pentandra (1)
- cell cycle (1)
- central complex (1)
- cereals (1)
- cerebEND cells (1)
- checkered beetles (1)
- chemical mimicry (1)
- chimpanzee (1)
- circadian rhythms (1)
- click chemistry (1)
- collective building (1)
- collective pattern (1)
- common garden experiment (1)
- community composition (1)
- community data (1)
- community‐weighted mean (1)
- complex behavior (1)
- complications (1)
- comportement des travailleurs (1)
- connectance (1)
- consanguinity (1)
- conservation (1)
- cooperative breeding (1)
- corticosteroids (1)
- cristae (1)
- cross-link repair (1)
- cuticular hydrocarbons (1)
- cycle (1)
- cytokinins (1)
- dSTORM (1)
- database (1)
- deadwood (1)
- deadwood experiments (1)
- defense signaling (1)
- definition (1)
- dendritic specializations (1)
- development (1)
- developmental biology (1)
- diapause (1)
- differentiation (1)
- direct drivers (1)
- discharge definition (1)
- dispersal ability (1)
- dispersal timing (1)
- distance gradient (1)
- domain (1)
- drosophila (1)
- ecological network (1)
- ecological niche (1)
- electron tomography (1)
- elevational diversity (1)
- elevational gradients (1)
- endocytosis (1)
- environmental filtering (1)
- eugenol (1)
- evolutionary (1)
- exit (1)
- exotic plants (1)
- exotische Pflanzen (1)
- expression (1)
- extracellular vesicle (1)
- facultatively intracellular pathogens (1)
- feeding (1)
- feeding experiment (1)
- feeding guilds (1)
- fire (1)
- flagellar pocket (1)
- flight behaviour (1)
- flippase (1)
- floral display (1)
- floral resources (1)
- flower-visiting insects (1)
- fluorescence microscopy (1)
- flupyradifurone (1)
- folliculin (1)
- forest (1)
- forest conservation (1)
- forest degradation (1)
- forest pests (1)
- forest physiognomy (1)
- forest succession (1)
- frameshift (1)
- functional network analysis (1)
- functional traits (1)
- fungi (1)
- fungus community (1)
- fungus-farming (1)
- fused in sarcoma (1)
- gamma H2AX-foci (1)
- gene duplications (1)
- gene expression (1)
- generalization (1)
- genetic diagnosis (1)
- genome-wide linkage analysis (1)
- genregulatorisches Netzwerk (1)
- global change (1)
- gonococcal invasion (1)
- gradients (1)
- grass endophytes (1)
- grasslands (1)
- ground‐dwelling predators (1)
- guanylyl cyclase B receptor (1)
- habitat filter (1)
- habitat heterogeneity (1)
- harvesting (1)
- head and neck cancer (1)
- hearing loss (1)
- heat shock response (1)
- hepatic fibrosis (1)
- high-risk Prostate Cancer (1)
- histology (1)
- honey bee (1)
- honeybee (1)
- honeybees (1)
- horses (1)
- host cell (1)
- human (1)
- hyphae (1)
- hypoxia (1)
- hypthesis (1)
- immunology (1)
- impact (1)
- in silico simulation (1)
- individual based model (1)
- individual-based simulation (1)
- infected-cell protein (1)
- inflammation (1)
- insect (1)
- insect agriculture (1)
- insect fungal interactions (1)
- insect nutrition (1)
- insect vision (1)
- insecticide (1)
- insects (1)
- integrase (1)
- interaction map (1)
- interactome (1)
- interspecies comparison (1)
- intoxication risk (1)
- invasion (1)
- invasive species (1)
- isosteviol sodium (1)
- isothiocyanates (1)
- jewel beetles (1)
- kinetic mechanism (1)
- land-use change (1)
- land-use intensity (1)
- landscape structure (1)
- lantana canescens (1)
- learning and behaviour (1)
- lentic inland water bodies (1)
- lipid asymmetry (1)
- lipid metabolism (1)
- livestock (1)
- long‐term monitoring (1)
- low fidelity (1)
- lowland rainforest (1)
- lung fibrosis (1)
- lysosome (1)
- management (1)
- material composition (1)
- melanoma malignancy (1)
- membrane occupation (1)
- memory enhancement (1)
- mesenchymal stem cell differentiation (1)
- messenger RNA (1)
- meta-transcriptome (1)
- metabarcoding (1)
- metabolic adaptation (1)
- metabolomics (1)
- metapopulation (1)
- miR (1)
- microRNA (1)
- microRNA-221 (1)
- microbiome (1)
- microglomeruli (1)
- microstructure (1)
- migration (1)
- mimicry rings (1)
- mitochondria (1)
- mitochondrial activity (1)
- modularity (1)
- molecular cloning (1)
- molecular dynamics (1)
- molecular modelling (1)
- monitoring (1)
- monoallelic expression (1)
- mortality rate (1)
- mouse (1)
- multi-modal stimuli (1)
- mushroom bodies (1)
- mushroom body (1)
- mushroom body miniature (1)
- mustard oil bomb (1)
- mutualistic interactions (1)
- mycotoxins (1)
- nanoscale imaging (1)
- natural disturbances (1)
- natural killer cell (1)
- naturally occurring polymorphisms (1)
- nature conservation (1)
- necrobiome (1)
- negative density dependence (1)
- neotropical region (1)
- network (1)
- network reconstruction (1)
- network simulation (1)
- network specialization index (H2′) (1)
- neuroblast proliferation (1)
- neuroenhancement (1)
- neuromuscular junction (1)
- neuronal network (1)
- neuroprotection (1)
- neutral processes (1)
- neutral sphingomyelinase-2 (1)
- nicotinic acetylcholine receptor (1)
- non-sense mediated mRNA decay (1)
- non‐native plants (1)
- number of interactions (1)
- nutrients (1)
- nutritional adaptations (1)
- oil palm plantations (1)
- olfaction (1)
- oncolytic virus (1)
- optical tracts (1)
- oxidative phosphorylation (1)
- pancreatectomy (1)
- pantanal wetland (1)
- paralogs (1)
- parasitoids (1)
- passes (1)
- pathogen (1)
- perennial ryegrass (1)
- pest control (1)
- pest species (1)
- phagocytosis (1)
- phenology (1)
- phosphatidylethanolamine (1)
- phosphatidylserine (1)
- phosphatidylserine transport (1)
- plant bacteria (1)
- plant composition (1)
- plant fresh/dry weight (1)
- plant-bee visitation networks (1)
- plant–bee visitation networks (1)
- platelet (1)
- polarized cell culture (1)
- polarized epithelium (1)
- pollen (1)
- pollen and nectar resources (1)
- pollen provisions (1)
- pollen quality (1)
- pollination (1)
- pollinator attraction (1)
- polyploidy (1)
- primeval forest (1)
- productivity hypothesis (1)
- projection neurons (1)
- protein synthesis (1)
- proteome (1)
- proteomics (1)
- public outreach (1)
- quantitative stigmergy (1)
- radiofrequency identification (1)
- rational drug design (1)
- reactive electrophilic species (1)
- recognition nexus domain (1)
- rectal cancer (1)
- rectal resection (1)
- redox homeostasis (1)
- regional species pool (1)
- release (1)
- reliability (1)
- replication (1)
- reproductive performance (1)
- resource use (1)
- resources (1)
- restoration strategy (1)
- reveals (1)
- robustness (1)
- salvage logging (1)
- sand mine (1)
- saproxylic species (1)
- satellite DNA (1)
- seasonal phenology (1)
- seasonality (1)
- secondary invader (1)
- secondary site infection (1)
- self-renewal (1)
- semi‐natural habitats (1)
- senescence (1)
- sequence (1)
- shoot apical meristem (1)
- signal transduction (1)
- signaling (1)
- social (1)
- social behavior (1)
- sociality (1)
- solution scattering (1)
- spatial variation (1)
- specialization (1)
- species energy theory (1)
- species richness (1)
- species traits (1)
- species turnover (1)
- sphingolipid expansion microscopy (1)
- sphingolipids (1)
- sphingosine (1)
- sphingosine kinases (1)
- spiders (1)
- splicing (1)
- sporidia (1)
- squamous cell carcinoma (1)
- stem cell transplantation (1)
- stem-cell-triggered immunity (1)
- stratification (1)
- structural synaptic plasticity (1)
- structured illumination microscope (1)
- stumpy development (1)
- sturgeon (1)
- sturgeon karyotype (1)
- successional trajectory (1)
- sucrose responsiveness (1)
- sulforaphane (1)
- sun exposure (1)
- superior (1)
- surgical care (1)
- surveillance (1)
- survival (1)
- sustainable (1)
- sustainable farming (1)
- system inference (1)
- tandem repeats (1)
- target (1)
- targeted therapy (1)
- temperature (1)
- temperature-speciation hypothesis (1)
- temporal variation (1)
- température (1)
- theta (1)
- thin sections (1)
- time series (1)
- transcriptional regulation (1)
- transcriptome (1)
- translation (1)
- translation initiation (1)
- trophic levels (1)
- trophic position (1)
- trypanosoma brucei (1)
- tryptophan (1)
- tumor-associated macrophage (1)
- type 1 (1)
- ultrastructure (1)
- uper-resolution array tomography (1)
- vaccinia virus (1)
- vascular plants (1)
- vertebrate scavenger (1)
- vision (1)
- wasps (1)
- water beetles (1)
- whole genome duplication (1)
- whole-genome duplication (1)
- wildlife management (1)
- windthrow (1)
- woody plant richness (1)
- wood‐inhabiting fungi (1)
- worker behavior (1)
- xenophagy (1)
- Öffentlichkeitsarbeit (1)
- Ökologische Intensivierung (1)
- Ökosystemdienstleistungen (1)
- β-diversity (1)
- ∆Np63 (1)
Institute
- Theodor-Boveri-Institut für Biowissenschaften (131) (remove)
Sonstige beteiligte Institutionen
- Core Unit Systemmedizin (1)
- Interdisciplinary Center for Clinical Research (1)
- Lehrstuhl für Translationale Onkologie (1)
- Technische Hochschule Nürnberg Georg Simon Ohm (1)
- Zentrum für Innere Medizin I, Städtisches Klinikum Brandenburg GmbH, Hochschulklinikum der MHB Theodor Fontane (1)
- eXcorLab GmbH (1)
EU-Project number / Contract (GA) number
- 311781 (1)
- 765937 (1)
- CoG 721016–HERPES (1)
The fruit fly Drosophila is a prime model in circadian research, but still little is known about its circadian regulation of metabolism. Daily rhythmicity in levels of several metabolites has been found, but knowledge about hydrophobic metabolites is limited. We here compared metabolite levels including lipids between period\(^{01}\) (per\(^{01}\)) clock mutants and Canton-S wildtype (WT\(_{CS}\)) flies in an isogenic and non-isogenic background using LC–MS. In the non-isogenic background, metabo-lites with differing levels comprised essential amino acids, kynurenines, pterinates, glycero(phospho)lipids, and fatty acid esters. Notably, detectable diacylglycerols (DAG) and acylcarnitines (AC), involved in lipid metabolism, showed lower levels in per\(^{01}\) mutants. Most of these differences disappeared in the isogenic background, yet the level differences for AC as well as DAG were consistent for fly bodies. AC levels were dependent on the time of day in WTCS in phase with food consumption under LD conditions, while DAGs showed weak daily oscillations. Two short-chain ACs continued to cycle even in constant darkness. per\(^{01}\) mutants in LD showed no or very weak diel AC oscillations out of phase with feeding activity. The low levels of DAGs and ACs in per\(^{01}\) did not correlate with lower total food consumption, body mass or weight. Clock mutant flies showed higher sensitivity to starvation independent of their background-dependent activity level. Our results suggest that neither feeding, energy storage nor mobilisation is significantly affected in per\(^{01}\) mutants, but point towards impaired mitochondrial activity, supported by upregulation of the mitochondrial stress marker 4EBP in the clock mutants
Bees need food of appropriate nutritional quality to maintain their metabolic functions. They largely obtain all required nutrients from floral resources, i.e., pollen and nectar. However, the diversity, composition and nutritional quality of floral resources varies with the surrounding environment and can be strongly altered in human-impacted habitats. We investigated whether differences in plant species richness as found in the surrounding environment correlated with variation in the floral diversity and nutritional quality of larval provisions (i.e., mixtures of pollen, nectar and salivary secretions) composed by the mass-provisioning stingless bee Tetragonula carbonaria (Apidae: Meliponini). We found that the floral diversity of larval provisions increased with increasing plant species richness. The sucrose and fat (total fatty acid) content and the proportion and concentration of the omega-6 fatty acid linoleic acid decreased, whereas the proportion of the omega-3 fatty acid linolenic acid increased with increasing plant species richness. Protein (total amino acid) content and amino acid composition did not change. The protein to fat (P:F) ratio, known to affect bee foraging, increased on average by more than 40% from plantations to forests and gardens, while the omega-6:3 ratio, known to negatively affect cognitive performance, decreased with increasing plant species richness. Our results suggest that plant species richness may support T. carbonaria colonies by providing not only a continuous resource supply (as shown in a previous study), but also floral resources of high nutritional quality.
The opportunistic human pathogen Staphylococcus aureus causes serious infectious diseases that range from superficial skin and soft tissue infections to necrotizing pneumonia and sepsis. While classically regarded as an extracellular pathogen, S. aureus is able to invade and survive within human cells. Host cell exit is associated with cell death, tissue destruction, and the spread of infection. The exact molecular mechanism employed by S. aureus to escape the host cell is still unclear. In this study, we performed a genome-wide small hairpin RNA (shRNA) screen and identified the calcium signaling pathway as being involved in intracellular infection. S. aureus induced a massive cytosolic Ca\(^{2+}\) increase in epithelial host cells after invasion and intracellular replication of the pathogen. This was paralleled by a decrease in endoplasmic reticulum Ca\(^{2+}\) concentration. Additionally, calcium ions from the extracellular space contributed to the cytosolic Ca2+ increase. As a consequence, we observed that the cytoplasmic Ca\(^{2+}\) rise led to an increase in mitochondrial Ca\(^{2+}\) concentration, the activation of calpains and caspases, and eventually to cell lysis of S. aureus-infected cells. Our study therefore suggests that intracellular S. aureus disturbs the host cell Ca\(^{2+}\) homeostasis and induces cytoplasmic Ca\(^{2+}\) overload, which results in both apoptotic and necrotic cell death in parallel or succession.
IMPORTANCE Despite being regarded as an extracellular bacterium, the pathogen Staphylococcus aureus can invade and survive within human cells. The intracellular niche is considered a hideout from the host immune system and antibiotic treatment and allows bacterial proliferation. Subsequently, the intracellular bacterium induces host cell death, which may facilitate the spread of infection and tissue destruction. So far, host cell factors exploited by intracellular S. aureus to promote cell death are only poorly characterized. We performed a genome-wide screen and found the calcium signaling pathway to play a role in S. aureus invasion and cytotoxicity. The intracellular bacterium induces a cytoplasmic and mitochondrial Ca\(^{2+}\) overload, which results in host cell death. Thus, this study first showed how an intracellular bacterium perturbs the host cell Ca\(^{2+}\) homeostasis."
Rational drug design of Axl tyrosine kinase type I inhibitors as promising candidates against cancer
(2020)
The high level of Axl tyrosine kinase expression in various cancer cell lines makes it an attractive target for the development of anti-cancer drugs. In this study, we carried out several sets of in silico screening for the ATP-competitive Axl kinase inhibitors based on different molecular docking protocols. The best drug-like candidates were identified, after parental structure modifications, by their highest affinity to the target protein. We found that our newly designed compound R5, a derivative of the R428 patented analog, is the most promising inhibitor of the Axl kinase according to the three molecular docking algorithms applied in the study. The molecular docking results are in agreement with the molecular dynamics simulations using the MM-PBSA/GBSA implicit solvation models, which confirm the high affinity of R5 toward the protein receptor. Additionally, the selectivity test against other kinases also reveals a high affinity of R5 toward ABL1 and Tyro3 kinases, emphasizing its promising potential for the treatment of malignant tumors.
Ants build complex nest structures by reacting to simple, local stimuli. While underground nests result from the space generated by digging, some leaf- and grass-cutting ants also construct conspicuous aboveground turrets around nest openings. We investigated whether the selection of specific building materials occurs during turret construction in Acromyrmex fracticornis grass-cutting ants, and asked whether single building decisions at the beginning can modify the final turret architecture. To quantify workers' material selection, the original nest turret was removed and a choice between two artificial building materials, thin and thick sticks, was offered for rebuilding. Workers preferred thick sticks at the very beginning of turret construction, showed varying preferences thereafter, and changed to prefer thin sticks for the upper, final part of the turret, indicating that they selected different building materials over time to create a stable structure. The impact of a single building choice on turret architecture was evaluated by placing artificial beams that divided a colony's nest entrance at the beginning of turret rebuilding. Splitting the nest entrance led to the self-organized construction of turrets with branched galleries ending in multiple openings, showing that the spatial location of a single building material can strongly influence turret morphology.
The amyotrophic lateral sclerosis (ALS) neurodegenerative disorder has been associated with multiple genetic lesions, including mutations in the gene for fused in sarcoma (FUS), a nuclear-localized RNA/DNA-binding protein. Neuronal expression of the pathological form of FUS proteins in Caenorhabditis elegans results in mislocalization and aggregation of FUS in the cytoplasm, and leads to impairment of motility. However, the mechanisms by which the mutant FUS disrupts neuronal health and function remain unclear. Here we investigated the impact of ALS-associated FUS on motor neuron health using correlative light and electron microscopy, electron tomography, and electrophysiology. We show that ectopic expression of wild-type or ALS-associated human FUS impairs synaptic vesicle docking at neuromuscular junctions. ALS-associated FUS led to the emergence of a population of large, electron-dense, and filament-filled endosomes. Electrophysiological recording revealed reduced transmission from motor neurons to muscles. Together, these results suggest a pathological effect of ALS-causing FUS at synaptic structure and function organization.
Ischemic stroke is one of the leading causes of death worldwide. It damages neurons and other supporting cellular elements in the brain. However, the impairment is not only confined to the region of assault but the surrounding area as well. Besides, it also brings about damage to the blood-brain barrier (BBB) which in turn leads to microvascular failure and edema. Hence, this necessitates an on-going, continuous search for intervention strategies and effective treatment. Of late, the natural sweetener stevioside proved to exhibit neuroprotective effects and therapeutic benefits against cerebral ischemia-induced injury. Its injectable formulation, isosteviol sodium (STVNA) also demonstrated favorable results. Nonetheless, its effects on the BBB have not yet been investigated to date. As such, this present study was designed to assess the effects of STVNA in our in vitro stroke model of the BBB.The integrity and permeability of the BBB are governed and maintained by tight junction proteins (TJPs) such as claudin-5 and occludin. Our data show increased claudin-5 and occludin expression in oxygen and glucose (OGD)-deprived murine brain capillary cerebellar endothelial cells (cerebEND) after STVNa treatment. Likewise, the upregulation of the transmembrane protein integrin-αv was also observed. Finally, cell volume was reduced with the simultaneous administration of STVNA and OGD in cerebEND cells. In neuropathologies such as stroke, the failure of cell volume control is a major feature leading to loss of cells in the penumbra as well as adverse outcomes. Our initial findings, therefore, point to the neuroprotective effects of STVNA at the BBB in vitro, which warrant further investigation for a possible future clinical intervention.
Background
Phosphorylated histone H2AX, also known as gamma H2AX, forms mu m-sized nuclear foci at the sites of DNA double-strand breaks (DSBs) induced by ionizing radiation and other agents. Due to their specificity and sensitivity, gamma H2AX immunoassays have become the gold standard for studying DSB induction and repair. One of these assays relies on the immunofluorescent staining of gamma H2AX followed by microscopic imaging and foci counting. During the last years, semi- and fully automated image analysis, capable of fast detection and quantification of gamma H2AX foci in large datasets of fluorescence images, are gradually replacing the traditional method of manual foci counting. A major drawback of the non-commercial software for foci counting (available so far) is that they are restricted to 2D-image data. In practice, these algorithms are useful for counting the foci located close to the midsection plane of the nucleus, while the out-of-plane foci are neglected.
Results
To overcome the limitations of 2D foci counting, we present a freely available ImageJ-based plugin (FocAn) for automated 3D analysis of gamma H2AX foci in z-image stacks acquired by confocal fluorescence microscopy. The image-stack processing algorithm implemented in FocAn is capable of automatic 3D recognition of individual cell nuclei and gamma H2AX foci, as well as evaluation of the total foci number per cell nucleus. The FocAn algorithm consists of two parts: nucleus identification and foci detection, each employing specific sequences of auto local thresholding in combination with watershed segmentation techniques. We validated the FocAn algorithm using fluorescence-labeled gamma H2AX in two glioblastoma cell lines, irradiated with 2 Gy and given up to 24 h post-irradiation for repair. We found that the data obtained with FocAn agreed well with those obtained with an already available software (FoCo) and manual counting. Moreover, FocAn was capable of identifying overlapping foci in 3D space, which ensured accurate foci counting even at high DSB density of up to similar to 200 DSB/nucleus.
Conclusions
FocAn is freely available an open-source 3D foci analyzer. The user-friendly algorithm FocAn requires little supervision and can automatically count the amount of DNA-DSBs, i.e. fluorescence-labeled gamma H2AX foci, in 3D image stacks acquired by laser-scanning microscopes without additional nuclei staining.
Resource availability in agricultural landscapes has been disturbed for many organisms, including pollinator species. Abundance and diversity in flower availability benefit bee populations; however, little is known about which of protein or carbohydrate resources may limit their growth and reproductive performance. Here, we test the hypothesis of complementary resource limitation using a supplemental feeding approach. We applied this assumption with bumble bees (Bombus terrestris), assuming that colony growth and reproductive performance should depend on the continuous supply of carbohydrates and proteins, through the foraging for nectar and pollen, respectively. We placed wild‐caught bumble bee colonies along a landscape gradient of seminatural habitats, and monitored the colonies’ weight, foraging activity, and reproductive performance during the whole colony cycle. We performed supplemental feeding as an indicator of landscape resource limitation, using a factorial design consisting of the addition of sugar water (carbohydrate, supplemented or not) crossed by pollen (protein, supplemented or not). Bumble bee colony dynamics showed a clear seasonal pattern with a period of growth followed by a period of stagnation. Higher abundance of seminatural habitats resulted in reducing the proportion of pollen foragers relative to all foragers in both periods, and in improving the reproductive performance of bumble bees. Interestingly, the supplemental feeding of sugar water positively affected the colony weight during the stagnation period, and the supplemental feeding of pollen mitigated the landscape effect on pollen collection investment. Single and combined supplementation of sugar water and pollen increased the positive effect of seminatural habitats on reproductive performance. This study reveals a potential colimitation in pollen and nectar resources affecting foraging behavior and reproductive performance in bumble bees, and indicates that even in mixed agricultural landscapes with higher proportions of seminatural habitats, bumble bee populations face resource limitations. We conclude that the seasonal management of floral resources must be considered in conservation to support bumble bee populations and pollination services in farmlands.
Post-embryonic Development of the Circadian Clock Seems to Correlate With Social Life Style in Bees
(2020)
Social life style can influence many aspects of an animal’s daily life, but it has not yet been clarified, whether development of the circadian clock in social and solitary living bees differs. In a comparative study, with the social honey bee, Apis mellifera, and the solitary mason bee, Osmia bicornis, we now found indications for a differentially timed clock development in social and solitary bees. Newly emerged solitary bees showed rhythmic locomotion right away and the number of neurons in the brain that produce the clock component pigment-dispersing factor (PDF) did not change during aging of the adult solitary bee. Honey bees on the other hand, showed no circadian locomotion directly after emergence and the neuronal clock network continued to grow after emergence. Social bees appear to emerge at an early developmental stage at which the circadian clock is still immature, but bees are already able to fulfill in-hive tasks.