Refine
Has Fulltext
- yes (61)
Is part of the Bibliography
- yes (61)
Year of publication
- 2017 (61) (remove)
Document Type
- Journal article (61) (remove)
Language
- English (61)
Keywords
- biology (8)
- Trypanosoma (4)
- ants (4)
- social systems (4)
- Apis mellifera (3)
- Drosophila melanogaster (3)
- animal sociality (3)
- fungi (3)
- Biology (2)
- DNA methylation (2)
- Drosophila (2)
- carbon dioxide (2)
- cell differentiation (2)
- chemotherapy (2)
- comparative genomics (2)
- foraging (2)
- genetic variation (2)
- humidity (2)
- learning (2)
- memory (2)
- methylation (2)
- mushroom bodies (2)
- nesting habits (2)
- symbiosis (2)
- 5-fluorouracil (1)
- Acyrthosiphon pisum (1)
- Aspergillus fumigatus (1)
- B cell receptors (1)
- B cells (1)
- BMP (1)
- Burkina Faso (1)
- Caenorhabditis elegans (1)
- Cell surface proteomics (1)
- Chlamydia trachomatis (1)
- Circadian rhythms and sleep (1)
- CoA (1)
- Computer software (1)
- DNA damage (1)
- Dunce isoforms (1)
- EZH2 (1)
- Enzyme Regulation (1)
- Enzyme kinetics (1)
- Enzyme metabolism (1)
- Enzyme regulation (1)
- Enzymes (1)
- Epicardium-derived cells (1)
- Genetics (1)
- HECT Ligase (1)
- HUWE1 (1)
- Human atrial stromal cells (1)
- Latrophilin (1)
- MITE (1)
- Mcl-1 (1)
- Medicine (1)
- Megalobrama amblycephala (1)
- Megaponera analis (1)
- Meliponini (1)
- Metabolic pathways (1)
- Molecular Biophysics (1)
- N-terminal domain (1)
- NAD (1)
- NFATc1 (1)
- Neisseria (1)
- Neisseria meningitidis (1)
- Neuromuscular junctions (1)
- P14ARF (1)
- PDE4d (1)
- PER (1)
- Predictive toxicology (1)
- RNA in situ hybridization (1)
- RNA interference (1)
- Saccharomyces cerevisiae (1)
- Septins (1)
- Structural Biology (1)
- Synapses (1)
- Synaptic vesicles (1)
- T cells (1)
- T-cadherin (1)
- TP53 (1)
- Toxicity (1)
- Transcriptional control (1)
- Trypanosoma brucei (1)
- Ubiquitin (1)
- Vesicles (1)
- Wilms tumour (1)
- X-Ray Chrystallography (1)
- Zebrafish (1)
- acute myeloid leukaemia (1)
- adhesion GPCR (1)
- agroecology (1)
- alcohol tolerance (1)
- alu elements (1)
- anaplasia (1)
- antimicrobials (1)
- bees (1)
- behavior (1)
- behavioural ecology (1)
- biogenic amines (1)
- bioinformatics (1)
- biomarker (1)
- biomaterials (1)
- biophysics (1)
- blood (1)
- blood platelets (1)
- bone (1)
- brain (1)
- brain development (1)
- breast cancer (1)
- cadherin-13 (CDH13) (1)
- cancer treatment (1)
- cash crops (1)
- catabolism (1)
- cell binding (1)
- cell cycle (1)
- cell cycle and cell division (1)
- cell proliferation (1)
- cell-autonomous defense (1)
- cellular stress (1)
- central clocks (1)
- central complex (1)
- ceramide (1)
- ceramide analogs (1)
- cholera (1)
- chronobiology (1)
- circadian clock (1)
- circadian mechanisms (1)
- clinical genetics (1)
- cloning (1)
- cognition (1)
- colorectal carcinoma (1)
- compound conditioning (1)
- confocal laser scanning microscopy (1)
- confocal-microscopy based automated quantification (1)
- cotton (1)
- crotonase (1)
- cryptic (1)
- cytokines (1)
- cytokinesis (1)
- cytotoxic T cells (1)
- dCIRL (1)
- damped circadian clock (1)
- decision-making (1)
- deformed wing virus (1)
- dehydrogenase (1)
- desert ants (1)
- deubiquitinase (1)
- differential olfactory conditioning (1)
- division of labor (1)
- dorsal raphe (1)
- dunce (1)
- eEF1A1 (1)
- eclosion (1)
- ecosystem services (1)
- epigenetics (1)
- eukaryota (1)
- evolutionary response (1)
- fetal cord blood (1)
- fetal programming (1)
- fibroblasts (1)
- floral resource distribution (1)
- fluorescence imaging (1)
- forager (1)
- foraging behaviour (1)
- functional complementarity (1)
- functional redundancy (1)
- fungal infection (1)
- fungal physiology (1)
- fungal structure (1)
- gambiense (1)
- gene expression (1)
- gene regulation (1)
- genetic loci (1)
- genome collection (1)
- genome integrity (1)
- genome sequencing (1)
- genomic libraries (1)
- genomic sequence (1)
- genomics research (1)
- gestational diabetes mellitus (1)
- glioblastoma multiforme (1)
- glycoprotein Ib (1)
- gut microflora (1)
- habitat information (1)
- hangover (1)
- herbivorous diet (1)
- herpes virus (1)
- high-throughput screening (1)
- histones (1)
- honey bees (1)
- honeybees (1)
- hyperexpression techniques (1)
- image analysis (1)
- imaging the immune system (1)
- immune cells (1)
- immune evasion (1)
- infectious diseases (1)
- infectious-disease diagnostics (1)
- infrared radiation (1)
- insect (1)
- insulin treatment (1)
- intermuscular bone (1)
- kinesin (1)
- landscape ecology (1)
- leaves (1)
- light pulses (1)
- lipids (1)
- look-back behavior (1)
- lung cancer (1)
- lymphocyte activation (1)
- mass spectrometry (1)
- mating success (1)
- mechanobiology (1)
- mechanotransduction (1)
- megakaryocytes (1)
- membrane receptor signaling (1)
- messenger RNA (1)
- metabolism (1)
- metabotropic signalling (1)
- metagenomics (1)
- microRNAs (1)
- microRNA–target interaction (1)
- microbiome (1)
- microswimmer (1)
- migration (1)
- mitochondria (1)
- molecular neuroscience (1)
- molting (1)
- morphometry (1)
- multiple myeloma (1)
- mushroom body (1)
- natural killer cells (1)
- neisseria meningitidis (1)
- nephroblastoma (1)
- nesting habit (1)
- networks (1)
- neuroanatomy (1)
- neurodevelopment (1)
- neuronal development (1)
- neuropeptide pathway (1)
- none (1)
- nurse bee (1)
- nutrition (1)
- nutritional ecology (1)
- octopamine (1)
- optogenetics (1)
- orientation (1)
- osteocytes (1)
- oxaliplatin (1)
- parasitic cell cycles (1)
- parasitic diseases (1)
- pattern recognition receptors (1)
- perception (1)
- peripheral clocks (1)
- plant-insect interactions (1)
- plant–insect interactions (1)
- pollen (1)
- pollination (1)
- pollinator decline (1)
- population structure (1)
- prefrontal cortex (1)
- proGenomes (1)
- proboscis extension reflex (1)
- prokaryotic clade (1)
- prokaryotic subspecies (1)
- protein structure (1)
- proteomes (1)
- psychiatric disorders (1)
- radial glia (1)
- reactivating p53 and inducing tumor apoptosis (RITA) (1)
- recruitment (1)
- regulation (1)
- regulatory T cells (1)
- regulatory circuit downstream (1)
- relA (1)
- replication (1)
- reproductive asynchrony (1)
- rescue behavior (1)
- resin (1)
- retinal development (1)
- sacbrood virus (1)
- season (1)
- sensory physiology (1)
- sept3 (1)
- sept5a (1)
- sept5b (1)
- septin (1)
- sequence assembly tools (1)
- serotonin (1)
- sesame (1)
- sex-specific mortality (1)
- sexual dimorphism in timing (1)
- signal transduction (1)
- signaling (1)
- sky-compass pathway (1)
- sleeping sickness (1)
- small interfering RNAs (1)
- social immunity (1)
- spider (1)
- spidroin (1)
- stringent response (1)
- structural biology (1)
- substrate channeling (1)
- super-resolution microscopy (1)
- systems biology (1)
- taxonomic description (1)
- tetracyclines (1)
- therapeutic strategy (1)
- throat (1)
- toxins (1)
- transcriptome (1)
- treatment (1)
- tsetse fly (1)
- tumour heterogeneity (1)
- vector navigation (1)
- video recording (1)
- virulenceregulatory evolution (1)
- visual orientation (1)
- whole genome (1)
- yellow fluorescent protein (1)
Institute
- Theodor-Boveri-Institut für Biowissenschaften (61) (remove)
Immature or semi-mature dendritic cells (DCs) represent tolerogenic maturation stages that can convert naive T cells into Foxp3\(^{+}\) induced regulatory T cells (iTreg). Here we found that murine bone marrow-derived DCs (BM-DCs) treated with cholera toxin (CT) matured by up-regulating MHC-II and costimulatory molecules using either high or low doses of CT (CT\(^{hi}\), CT\(^{lo}\)) or with cAMP, a known mediator CT signals. However, all three conditions also induced mRNA of both isoforms of the tolerogenic molecule cytotoxic T lymphocyte antigen 2 (CTLA-2α and CTLA-2β). Only DCs matured under CT\(^{hi}\) conditions secreted IL-1β, IL-6 and IL-23 leading to the instruction of Th17 cell polarization. In contrast, CT\(^{lo}\)- or cAMP-DCs resembled semi-mature DCs and enhanced TGF-β-dependent Foxp3\(^{+}\) iTreg conversion. iTreg conversion could be reduced using siRNA blocking of CTLA-2 and reversely, addition of recombinant CTLA-2α increased iTreg conversion in vitro. Injection of CT\(^{lo}\)- or cAMP-DCs exerted MOG peptide-specific protective effects in experimental autoimmune encephalomyelitis (EAE) by inducing Foxp3\(^{+}\) Tregs and reducing Th17 responses. Together, we identified CTLA-2 production by DCs as a novel tolerogenic mediator of TGF-β-mediated iTreg induction in vitro and in vivo. The CT-induced and cAMP-mediated up-regulation of CTLA-2 also may point to a novel immune evasion mechanism of Vibrio cholerae.
Animal circadian clocks consist of central and peripheral pacemakers, which are coordinated to produce daily rhythms in physiology and behaviour. Despite its importance for optimal performance and health, the mechanism of clock coordination is poorly understood. Here we dissect the pathway through which the circadian clock of Drosophila imposes daily rhythmicity to the pattern of adult emergence. Rhythmicity depends on the coupling between the brain clock and a peripheral clock in the prothoracic gland (PG), which produces the steroid hormone, ecdysone. Time information from the central clock is transmitted via the neuropeptide, sNPF, to non-clock neurons that produce the neuropeptide, PTTH. These secretory neurons then forward time information to the PG clock. We also show that the central clock exerts a dominant role on the peripheral clock. This use of two coupled clocks could serve as a paradigm to understand how daily steroid hormone rhythms are generated in animals.
Multiple myeloma (MM) represents a haematological cancer characterized by the pathological hyper proliferation of antibody-producing B-lymphocytes. Patients typically suffer from kidney malfunction and skeletal disorders. In the context of MM, the transforming growth factor β (TGFβ) member Activin A was recently identified as a promoter of both accompanying symptoms. Because studies have shown that bone morphogenetic protein (BMP)-2-mediated activities are counteracted by Activin A, we analysed whether BMP2, which also binds to the Activin A receptors ActRII and ActRIIB but activates the alternative SMAD-1/5/8 pathway, can be used to antagonize Activin A activities, such as in the context of MM. Therefore three BMP2 derivatives were generated with modified binding activities for the type II (ActRIIB) and/or type I receptor (BMPRIA) showing either increased or decreased BMP2 activity. In the context of MM these BMP2 muteins show two functionalities since they act as a) an anti-proliferative/apoptotic agent against neoplastic B-cells, b) as a bone-formation promoting growth factor. The molecular basis of both activities was shown in two different cellular models to clearly rely on the properties of the investigated BMP2 muteins to compete for the binding of Activin A to the Activin type II receptors. The experimental outcome suggests new therapeutic strategies using BMP2 variants in the treatment of MM-related pathologies.
The highly motile and versatile protozoan pathogen Trypanosoma brucei undergoes a complex life cycle in the tsetse fly. Here we introduce the host insect as an expedient model environment for microswimmer research, as it allows examination of microbial motion within a diversified, secluded and yet microscopically tractable space. During their week-long journey through the different microenvironments of the fly´s interior organs, the incessantly swimming trypanosomes cross various barriers and confined surroundings, with concurrently occurring major changes of parasite cell architecture. Multicolour light sheet fluorescence microscopy provided information about tsetse tissue topology with unprecedented resolution and allowed the first 3D analysis of the infection process. High-speed fluorescence microscopy illuminated the versatile behaviour of trypanosome developmental stages, ranging from solitary motion and near-wall swimming to collective motility in synchronised swarms and in confinement. We correlate the microenvironments and trypanosome morphologies to high-speed motility data, which paves the way for cross-disciplinary microswimmer research in a naturally evolved environment.
Adhesion-type G protein-coupled receptors (aGPCRs), a large molecule family with over 30 members in humans, operate in organ development, brain function and govern immunological responses. Correspondingly, this receptor family is linked to a multitude of diverse human diseases. aGPCRs have been suggested to possess mechanosensory properties, though their mechanism of action is fully unknown. Here we show that the Drosophila aGPCR Latrophilin/dCIRL acts in mechanosensory neurons by modulating ionotropic receptor currents, the initiating step of cellular mechanosensation. This process depends on the length of the extended ectodomain and the tethered agonist of the receptor, but not on its autoproteolysis, a characteristic biochemical feature of the aGPCR family. Intracellularly, dCIRL quenches cAMP levels upon mechanical activation thereby specifically increasing the mechanosensitivity of neurons. These results provide direct evidence that the aGPCR dCIRL acts as a molecular sensor and signal transducer that detects and converts mechanical stimuli into a metabotropic response.
Division of labor is a hallmark of social insects. In the honeybee (Apis mellifera) each sterile female worker performs a series of social tasks. The most drastic changes in behavior occur when a nurse bee, who takes care of the brood and the queen in the hive, transitions to foraging behavior. Foragers provision the colony with pollen, nectar or water. Nurse bees and foragers differ in numerous behaviors, including responsiveness to gustatory stimuli. Differences in gustatory responsiveness, in turn, might be involved in regulating division of labor through differential sensory response thresholds. Biogenic amines are important modulators of behavior. Tyramine and octopamine have been shown to increase gustatory responsiveness in honeybees when injected into the thorax, thereby possibly triggering social organization. So far, most of the experiments investigating the role of amines on gustatory responsiveness have focused on the brain. The potential role of the fat body in regulating sensory responsiveness and division of labor has large been neglected. We here investigated the role of the fat body in modulating gustatory responsiveness through tyramine signaling in different social roles of honeybees. We quantified levels of tyramine, tyramine receptor gene expression and the effect of elevating fat body tyramine titers on gustatory responsiveness in both nurse bees and foragers. Our data suggest that elevating the tyramine titer in the fat body pharmacologically increases gustatory responsiveness in foragers, but not in nurse bees. This differential effect of tyramine on gustatory responsiveness correlates with a higher natural gustatory responsiveness of foragers, with a higher tyramine receptor (Amtar1) mRNA expression in fat bodies of foragers and with lower baseline tyramine titers in fat bodies of foragers compared to those of nurse bees. We suggest that differential tyramine signaling in the fat body has an important role in the plasticity of division of labor through changing gustatory responsiveness.
Alterations to the gene encoding the EZH2 (KMT6A) methyltransferase, including both gain-of-function and loss-of-function, have been linked to a variety of haematological malignancies and solid tumours, suggesting a complex, context-dependent role of this methyltransferase. The successful implementation of molecularly targeted therapies against EZH2 requires a greater understanding of the potential mechanisms by which EZH2 contributes to cancer. One aspect of this effort is the mapping of EZH2 partner proteins and cellular targets. To this end we performed affinity-purification mass spectrometry in the FAB-M2 HL-60 acute myeloid leukaemia (AML) cell line before and after all-trans retinoic acid-induced differentiation. These studies identified new EZH2 interaction partners and potential non-histone substrates for EZH2-mediated methylation. Our results suggest that EZH2 is involved in the regulation of translation through interactions with a number of RNA binding proteins and by methylating key components of protein synthesis such as eEF1A1. Given that deregulated mRNA translation is a frequent feature of cancer and that eEF1A1 is highly expressed in many human tumours, these findings present new possibilities for the therapeutic targeting of EZH2 in AML.
The human ubiquitin ligase HUWE1 has key roles in tumorigenesis, yet it is unkown how its activity is regulated. We present the crystal structure of a C-terminal part of HUWE1, including the catalytic domain, and reveal an asymmetric auto-inhibited dimer. We show that HUWE1 dimerizes in solution and self-associates in cells, and that both occurs through the crystallographic dimer interface. We demonstrate that HUWE1 is inhibited in cells and that it can be activated by disruption of the dimer interface. We identify a conserved segment in HUWE1 that counteracts dimer formation by associating with the dimerization region intramolecularly. Our studies reveal, intriguingly, that the tumor suppressor p14ARF binds to this segment and may thus shift the conformational equilibrium of HUWE1 toward the inactive state. We propose a model, in which the activity of HUWE1 underlies conformational control in response to physiological cues—a mechanism that may be exploited for cancer therapy.
A recent study by Peng and Yang in Scientific Reports using confocal-microscopy based automated quantification of anti-synapsin labeled microglomeruli in the mushroom bodies of honeybee brains reports potentially incorrect numbers of microglomerular densities. Whereas several previous studies using visually supervised or automated counts from confocal images and analyses of serial 3D electron-microscopy data reported consistent numbers of synaptic complexes per volume, Peng and Yang revealed extremely low numbers differing by a factor of 18 or more from those obtained in visually supervised counts, and by a factor 22–180 from numbers in two other studies using automated counts. This extreme discrepancy is especially disturbing as close comparison of raw confocal images of anti-synapsin labeled whole-mount brain preparations are highly similar across these studies. We conclude that these discrepancies may reside in potential misapplication of confocal imaging followed by erroneous use of automated image analysis software. Consequently, the reported microglomerular densities during maturation and after manipulation by insecticides require validation by application of appropriate confocal imaging methods and analyses tools that rely on skilled observers. We suggest several improvements towards more reliable or standardized automated or semi-automated synapse counts in whole mount preparations of insect brains.
Defense against biotic or abiotic stresses is one of the benefits of living in symbiosis. Leaf-cutting ants, which live in an obligate mutualism with a fungus, attenuate thermal and desiccation stress of their partner through behavioral responses, by choosing suitable places for fungus-rearing across the soil profile. The underground environment also presents hypoxic (low oxygen) and hypercapnic (high carbon dioxide) conditions, which can negatively influence the symbiont. Here, we investigated whether workers of the leaf-cutting ant Acromyrmex lundii use the CO\(_{2}\) concentration as an orientation cue when selecting a place to locate their fungus garden, and whether they show preferences for specific CO\(_{2}\) concentrations. We also evaluated whether levels preferred by workers for fungus-rearing differ from those selected for themselves. In the laboratory, CO\(_{2}\) preferences were assessed in binary choices between chambers with different CO\(_{2}\) concentrations, by quantifying number of workers in each chamber and amount of relocated fungus. Leaf-cutting ants used the CO\(_{2}\) concentration as a spatial cue when selecting places for fungus-rearing. A. lundii preferred intermediate CO\(_{2}\) levels, between 1 and 3%, as they would encounter at soil depths where their nest chambers are located. In addition, workers avoided both atmospheric and high CO\(_{2}\) levels as they would occur outside the nest and at deeper soil layers, respectively. In order to prevent fungus desiccation, however, workers relocated fungus to high CO\(_{2}\) levels, which were otherwise avoided. Workers’ CO\(_{2}\) preferences for themselves showed no clear-cut pattern. We suggest that workers avoid both atmospheric and high CO\(_{2}\) concentrations not because they are detrimental for themselves, but because of their consequences for the symbiotic partner. Whether the preferred CO\(_{2}\) concentrations are beneficial for symbiont growth remains to be investigated, as well as whether the observed preferences for fungus-rearing influences the ants’ decisions where to excavate new chambers across the soil profile.