Refine
Has Fulltext
- yes (100)
Is part of the Bibliography
- yes (100)
Year of publication
- 2016 (100) (remove)
Document Type
- Journal article (87)
- Doctoral Thesis (13)
Language
- English (100) (remove)
Keywords
- Drosophila (4)
- DNA methylation (3)
- Drosophila melanogaster (3)
- Taufliege (3)
- biodiversity (3)
- circadian rhythms (3)
- vision (3)
- DNA damage (2)
- Spermatogenesis (2)
- Staphylococcus aureus (2)
- Tagesrhythmus (2)
- Trypanosoma brucei (2)
- biological locomotion (2)
- breast cancer (2)
- circadian clock (2)
- cytotoxicity (2)
- database (2)
- gastric cancer (2)
- gene expression (2)
- genome (2)
- honey bees (2)
- host-pathogen interactions (2)
- insect brain (2)
- lung cancer (2)
- neurons (2)
- next generation sequencing (2)
- photoperiodism (2)
- phylogenetic trees (2)
- sexual selection (2)
- visualization (2)
- AP-1 (1)
- Action potentials (1)
- Acyrthosiphon pisum (1)
- Adultschlupfes (1)
- Agricultural intensification (1)
- Alvis (1)
- Alzheimers disease (1)
- Ameisenoogenese (1)
- Amphibians (1)
- Amyotrophic-lateral-sclerosis (1)
- Angiopoietin-2 (1)
- Angiopoietin-like 4 (1)
- Annotation (1)
- Anpassung (1)
- Antimikrobielle Peptide (1)
- Arabidopsis-thaliana (1)
- Arthropods (1)
- Aufmerksamkeit (1)
- Autism (1)
- Autism spectrum disorders (1)
- Axon degeneration (1)
- Axonal transport (1)
- Bacterial community analysis (1)
- Bacterial symbionts (1)
- Bauchspeicheldrüsenkrebs (1)
- Bee abundance (1)
- Biodiversity assessment (1)
- Biodiversität (1)
- Blochmannia floridanus (1)
- Bone disease (1)
- Camponotus floridanus (1)
- Cancer genetics (1)
- Candida albicans (1)
- Cervical cancer (1)
- ChIP-sequencing (1)
- Chromosomes (1)
- Chronobiologie (1)
- Cimex lectularius (1)
- Circadian clock (1)
- Cocalodinae (1)
- Coleoptera: Chrysomelidae (1)
- Colony growth (1)
- Context (1)
- Cytotoxic (1)
- DNA methylation dynamics (1)
- DNA-based species delimitation (1)
- DNS-Bindung (1)
- DNS-Sequenz (1)
- Danio-rerio (1)
- Darmflora (1)
- Densities (1)
- Dionaea-muscipula ellis (1)
- Down syndrome (1)
- Drosha (1)
- E3 ligase (1)
- Ecologically important traits (1)
- Endosymbiosen (1)
- Endothelial growth-factor (1)
- Environment (1)
- Epidermal growth-factor (1)
- Epigenetics (1)
- Epitope (1)
- Event (1)
- Exosome (1)
- FISH-CLEM (1)
- FOSL1 (1)
- FWGE (1)
- Fertilität (1)
- Fetal brain development (1)
- Fish Sex determination (1)
- Flabarin (1)
- Flow cytometry (1)
- Foragers (1)
- Frontal cortex (1)
- Geißel <Biologie> (1)
- Gene (1)
- Gene expression profiling (1)
- Gene-expression (1)
- Genetics research (1)
- Genom (1)
- Genome (1)
- Genome assembly (1)
- Genome comparison (1)
- Genomics data sets (1)
- Geschlechtsdifferenzierung (1)
- HKT transporter (1)
- HPV (1)
- Habitats (1)
- Horizontal transfer (1)
- Human prefrontal cortex (1)
- Hymenoptera (1)
- Immungene (1)
- Insect hosts (1)
- Insects (1)
- Interactive Tree Of Life (iTOL) (1)
- Intermediate filaments (1)
- Intracellular virulence (1)
- Jasmonate perception (1)
- Kernhülle (1)
- Kernproteine (1)
- Kristallstruktur (1)
- LASP1 (1)
- LINC complex (1)
- Lachsartige <Familie> (1)
- Lacking neurofilaments (1)
- Lepidoptera (1)
- Locomotor activity (1)
- Locus (1)
- Lynx lynx (1)
- MDSCs (1)
- MIZ1 (1)
- MRSA (1)
- MYC (1)
- MYCN (1)
- Male intromittent organ (1)
- Maus (1)
- Mechanisms (1)
- Meiosis (1)
- Melanom (1)
- Melanoma Maintenance (1)
- Mensch (1)
- Mesenchymal stem cells (1)
- Mesocestoides corti (1)
- Meta-barcoding (1)
- Metagenom (1)
- Methylome (1)
- Microorganisms (1)
- Microtubules (1)
- Missense mutation (1)
- Molekularbiologie (1)
- Molekulargenetik (1)
- Motoneuron disease (1)
- Mouse model (1)
- Mt. Kinabalu (1)
- Multiple myeloma (1)
- Mutations (1)
- Myc (1)
- NGS (1)
- NMD (1)
- NO (1)
- Nanda-Hamner (1)
- Nasonia courtship (1)
- Nesting resources (1)
- Neurofilament (1)
- Non-ribosomal peptide synthetase (1)
- Nurses (1)
- Oilseed rape (1)
- OmoMYC (1)
- Oogenese (1)
- Oogenesis (1)
- Opsins (1)
- Osteogenic precursor cells (1)
- PICD (1)
- Pain (1)
- Patterns (1)
- Peptidoglycan recognition (1)
- Plant utricularia-gibba (1)
- Podocarpus National Park (1)
- Poecilia reticulata (1)
- Polistine wasps (1)
- Polycistronic mRNA (1)
- Poor-prognosis (1)
- Primary endosymbiont (1)
- Programmed cell-death (1)
- Progressive motor neuronopathy (1)
- QTL analysis (1)
- RNA interference (1)
- RNA-SEQ data (1)
- RNAseq (1)
- Relapse (1)
- Reproduction (1)
- Reveals (1)
- Rhodopsins (1)
- Richness (1)
- SCD (1)
- SUN domain proteins (1)
- Saccharomyces cerevisiae (1)
- Schizophrenia (1)
- SdY (1)
- Selektive Wahrnehmung (1)
- Si-rhodamine (1)
- Single nucleotide change (1)
- Social entrainment (1)
- Spermatogenese (1)
- Spermienbildung (1)
- Spermiogenese (1)
- Stat3 (1)
- Stathmin (1)
- Stress responses (1)
- Symbiose (1)
- T lymphocytes (1)
- Temperature rhythms (1)
- Transcription (1)
- Transcriptome (1)
- Transgenic mice (1)
- Transkription <Genetik> (1)
- Transkriptionsfaktor (1)
- Transovarial transmission (1)
- Trinidadian guppy (1)
- Trypanosomes (1)
- USA300 (1)
- VACV (1)
- Vaccine (1)
- Venusfliegenfalle (1)
- Virulenz (1)
- Visueller Reiz (1)
- WDR5 (1)
- Wallemia ichthyophaga (1)
- Williamsia sp. ARP1 (1)
- Wirt (1)
- Wonderful plants (1)
- X. couchianus (1)
- X. hellerii (1)
- Xiphophorus (1)
- Xiphophorus fish (1)
- Yield (1)
- Zebrafish (1)
- achaete-scute homolog 1 (1)
- adaption (1)
- adipose (1)
- adipose tissue (1)
- adipose tissue dysfunction (1)
- adjuvant (1)
- agri-environment schemes (1)
- algorithm (1)
- anastomotic leakage (1)
- angiogenesis (1)
- angiogenic cytokines (1)
- animal behavior (1)
- animals (1)
- annotation (1)
- ant oogenesis (1)
- ant-mimicking spiders (1)
- anterior optic tubercle (1)
- anthropogenic activities (1)
- antimicrobial peptides (1)
- antimycotics (1)
- antioxidants (1)
- antitumor immune response (1)
- antiviral immunity (1)
- ants (1)
- apoptosis (1)
- arabidopsis (1)
- arabidopsis thaliana (1)
- army ants (1)
- artificial diet (1)
- assembly (1)
- astrocytes (1)
- attraction (1)
- autophagy (1)
- bed bug (1)
- bee community (1)
- bees (1)
- behavioral conditioning (1)
- benzoquinone (1)
- bevacizumab (1)
- biodiversity assessment (1)
- bioenergetics (1)
- biofuels (1)
- bioinformatics (1)
- biomarker (1)
- blood (1)
- body weight (1)
- brain-injury (1)
- breast-cancer (1)
- brefeldin-a (1)
- broodtranslocation (1)
- bug riptortus-pedestris (1)
- c-Fos (1)
- caenorhabditis elegans (1)
- calyx (1)
- camponotus ants (1)
- cancer biology (1)
- cancer cells (1)
- canopy spiders (1)
- capacitance (1)
- cell biology (1)
- cell compartmentation (1)
- cell cycle and cell division (1)
- cell cycle arrest (1)
- cell death (1)
- cell differentiation (1)
- cell membranes (1)
- cell motility (1)
- cell staining (1)
- cellular imaging (1)
- central complex (1)
- central nervous system (1)
- chemotherapy (1)
- chromatin (1)
- chronobiology (1)
- climate factors (1)
- cognition (1)
- cognitive functions (1)
- colony survival (1)
- color vision (1)
- colorectal cancer (1)
- community ecology (1)
- complication (1)
- computer-assisted (1)
- confocal laser microscopy (1)
- correlative light and electron microscopy (1)
- crop pollination (1)
- cytokines (1)
- cytokinins (1)
- cytosol (1)
- cytostatic (1)
- damped-oscillator-model of photoperiodic clock (1)
- data mining/methods (1)
- depreissia decipiens (1)
- deuterostomes (1)
- developmental biology (1)
- diapause (1)
- dichthadiigynes (1)
- direct stochasticoptical reconstruction microscopy (1)
- draft genome (1)
- drug-minded protein (1)
- early diagnosis (1)
- early secretory pathway (1)
- ecosystem services (1)
- ectotherms (1)
- endemism (1)
- endoplasmic-reticulum (1)
- endosomes (1)
- endosponge (1)
- endosymbiosis (1)
- enzyme regulation (1)
- epithelial cells (1)
- ethanol (1)
- excretory-secretory (1)
- exocrine glands (1)
- export (1)
- extracellular matrix (1)
- female choice (1)
- fertility (1)
- fetal brain development (1)
- field boundaries (1)
- finger protein 11 (1)
- fish model (1)
- flagella (1)
- flagellum (1)
- fluorescence recovery after photobleaching (1)
- fluorescent-probes (1)
- fluorophore (1)
- food consumption (1)
- foraging (1)
- forest edges (1)
- forest fragmentation (1)
- forest hedges (1)
- forest specialists (1)
- frontal cortex (1)
- fungicide (1)
- gap junction (1)
- gastrointestinal tract (1)
- gene-expression (1)
- genetic dissection (1)
- genetics (1)
- genome assembly (1)
- genotype (1)
- geographic biases (1)
- geographical variation (1)
- global dataset (1)
- gonad development (1)
- gut microbiota (1)
- halophilic fungus (1)
- heterozygosity (1)
- high resolution visualisation (1)
- high-osmolarity glycerol (HOG) (1)
- histone γH2AX (1)
- honeybee (1)
- host cells (1)
- hour-glass (1)
- hourglass clock (1)
- human (1)
- human ectoparasite (1)
- humans (1)
- hyperexpression techniques (1)
- hypothalamus (1)
- hypoxia-inducible factor 3A (1)
- iNOS (1)
- image data (1)
- image processing (1)
- immune genes (1)
- immune response (1)
- immunoreactive neurons (1)
- in-vitro (1)
- inflammation (1)
- inflammatory bowel disease (1)
- innate immune system (1)
- innexins (1)
- insects (1)
- insulin (1)
- insulin resistance (1)
- intensification (1)
- interaction (1)
- intracellular membranes (1)
- jumping spiders (1)
- junction proteins (1)
- land-use change (1)
- landscape compositionv (1)
- leaf beetle (1)
- learning (1)
- legionary ants (1)
- light-induced gene expression (1)
- light-trapping (1)
- lipid desaturation (1)
- lipidomics (1)
- liver metastasis (1)
- lncRNAs (1)
- localization micoscopy (1)
- locomotor activity (1)
- lungfish (1)
- lymphocytes (1)
- mRNA (1)
- macroecology (1)
- macrophages (1)
- marrow stromal cells (1)
- mathematical modeling (1)
- matrix metalloproteinases (1)
- melanoma (1)
- meliponines (1)
- membrane biophysics (1)
- membrane proteins (1)
- memory (1)
- memory formation (1)
- mesenchymal stem-cells (1)
- metabolism (1)
- metagenomics (1)
- miRNAs (1)
- mice (1)
- microRNA (1)
- microbiology (1)
- microglomeruli (1)
- microscopy (1)
- mitogen activated protein kinase (MAPK) (1)
- modeling (1)
- molecular biology (1)
- monoclonial gammopathy (1)
- monocytes (1)
- moths (1)
- mouse (1)
- mouse models (1)
- mouse-brain (1)
- multimodal (1)
- multiple sequence alignments (1)
- mushroom body (1)
- mutation detection (1)
- natural language processing (1)
- neoadjuvant (1)
- nervous-system (1)
- nervous-sytem (1)
- neural circuits (1)
- neural stem-cells (1)
- neurogenic locus notch homolog (1)
- neuroimaging (1)
- neuronal plasticity (1)
- neuropeptides (1)
- neutrophils (1)
- non-crop habitats (1)
- non-invasive biomarkers (1)
- nurses (1)
- obesity (1)
- olfaction (1)
- oncolytic virus therapy (1)
- oxidative stress (1)
- pacbio correction (1)
- parasitic cell cycles (1)
- parasitic diseases (1)
- parasitic life cycles (1)
- parasitology (1)
- peripheral-blood (1)
- phenotype (1)
- phosphorylation (1)
- photoactivation (1)
- photoperiodic time mesurement (1)
- phototransduction (1)
- phyllosphere (1)
- physiological traits (1)
- piRNA (1)
- pitcher-plant mosquito (1)
- plasticity (1)
- polarization vision (1)
- pollen analysis (1)
- potassium (1)
- precedes multiple-myeloma (1)
- prey selection (1)
- progenitors (1)
- promoter affinity (1)
- promoter invasion (1)
- prostate cancer (1)
- protein phosphorylation (1)
- protein-protein interaction (1)
- proteomes (1)
- proteomic analysis (1)
- protocadherin gamma cluster (1)
- protophormia terraenovae (1)
- pyramidal neurons (1)
- queens (1)
- radiation sensitivity (1)
- rainforest (1)
- reactive oxygen species (1)
- receptor tyrosine kinase (1)
- receptor tyrosine kinases (1)
- recombinat-human-erythropoietin (1)
- reconstruction (1)
- repeats (1)
- reproductive character displacement (1)
- reproductive diapause (1)
- resolution limit (1)
- resource availability (1)
- retinal dystrophies (1)
- retinoblastoma protein (1)
- rhythmic components (1)
- risk factor (1)
- salinity stress (1)
- salmonids (1)
- sampling bias (1)
- sampling method (1)
- sarcopterygian fish (1)
- semi-natural habitats (1)
- sequestration (1)
- serotonin transporter (1)
- sex pheromone (1)
- signal peptides (1)
- signaling (1)
- signaling pathway (1)
- single-molecule biophysics (1)
- sky-compass orientation (1)
- sleep (1)
- small RNA-sequencing (1)
- small cell lung cancer (1)
- sodium (1)
- software (1)
- speciation (1)
- species diversification (1)
- sperm head formation (1)
- spermiogenesis (1)
- spillover (1)
- stage specific regulation (1)
- stalking predators (1)
- structure (1)
- structured illumination microscopy (1)
- super-resolution imaging (1)
- super-resolution microscopy (1)
- survival (1)
- swimming (1)
- synaptic connections (1)
- synapticplasticity (1)
- systemic inflammatory response syndrome (1)
- targets (1)
- taxonomic biases (1)
- taxonomy (1)
- temperature (1)
- thermal adaptation (1)
- tool (1)
- trafficking (1)
- trans-splicing (1)
- transcriptional profiling (1)
- transcriptome (1)
- transcriptome analysis (1)
- transposable elements (1)
- trisomy 21 (1)
- tropical ecology (1)
- trypanosoma brucei gambiense (1)
- undetermined significance (1)
- urbanization (1)
- vertebrates (1)
- vesicles (1)
- viscosity (1)
- visuell (1)
- wasp-mimicking (1)
- whole genome duplications (1)
- whole genome sequencing (1)
- whole-genome shotgun sequencing (1)
- wild plant pollination (1)
- wyeomyia smithii (1)
- xylem loading (1)
Institute
- Theodor-Boveri-Institut für Biowissenschaften (100) (remove)
Sonstige beteiligte Institutionen
Chronobiological studies of individual activity rhythms in social insects can be constrained by the artificial isolation of individuals from their social context. We present a new experimental set-up that simultaneously measures the temperature rhythm in a queen-less but brood raising mini colony and the walking activity rhythms of singly kept honey bees that have indirect social contact with it. Our approach enables monitoring of individual bees in the social context of a mini colony under controlled laboratory conditions. In a pilot experiment, we show that social contact with the mini colony improves the survival of monitored young individuals and affects locomotor activity patterns of young and old bees. When exposed to conflicting Zeitgebers consisting of a light-dark (LD) cycle that is phase-delayed with respect to the mini colony rhythm, rhythms of young and old bees are socially synchronized with the mini colony rhythm, whereas isolated bees synchronize to the LD cycle. We conclude that the social environment is a stronger Zeitgeber than the LD cycle and that our new experimental set-up is well suited for studying the mechanisms of social entrainment in honey bees.
Although the concept of botanical carnivory has been known since Darwin's time, the molecular mechanisms that allow animal feeding remain unknown, primarily due to a complete lack of genomic information. Here, we show that the transcriptomic landscape of the Dionaea trap is dramatically shifted toward signal transduction and nutrient transport upon insect feeding, with touch hormone signaling and protein secretion prevailing. At the same time, a massive induction of general defense responses is accompanied by the repression of cell death-related genes/processes. We hypothesize that the carnivory syndrome of Dionaea evolved by exaptation of ancient defense pathways, replacing cell death with nutrient acquisition.
Unique features of a global human ectoparasite identified through sequencing of the bed bug genome
(2016)
The bed bug, Cimex lectularius, has re-established itself as a ubiquitous human ectoparasite throughout much of the world during the past two decades. This global resurgence is likely linked to increased international travel and commerce in addition to widespread insecticide resistance. Analyses of the C. lectularius sequenced genome (650 Mb) and 14,220 predicted protein-coding genes provide a comprehensive representation of genes that are linked to traumatic insemination, a reduced chemosensory repertoire of genes related to obligate hematophagy, host–symbiont interactions, and several mechanisms of insecticide resistance. In addition, we document the presence of multiple putative lateral gene transfer events. Genome sequencing and annotation establish a solid foundation for future research on mechanisms of insecticide resistance, human–bed bug and symbiont–bed bug associations, and unique features of bed bug biology that contribute to the unprecedented success of C. lectularius as a human ectoparasite.
Biochemical and molecular characterization of an original master sex determining gene in Salmonids
(2016)
Sexual development is a fundamental and versatile process that shapes animal morphology, physiology and behavior. The underlying developmental process is composed of the sex determination and the sex differentiation. Sex determination mechanisms are extremely labile among taxa. The initial triggers of the sex determination process are often genetics called sex determining genes. These genes are expressed in the bipotential gonad and tilt the balance to a developmental program allowing the differentiation of either a testis or an ovary. Fish represent a large and fascinating vertebrate group to study both sex determination and sex differentiation mechanisms. To date, among the known sex determining genes, three gene families namely sox, dmrt and TGF-β factors govern this developmental program. As exception to this rule, sdY “sexually dimorphic on the Y” does not belong to one of these families as it comes from the duplication / evolution of an ancestor gene related to immunity, i.e., the interferon related factor 9, irf9. sdY is the master sex determining gene in salmonids, a group of fishes that include species such as rainbow trout and Atlantic salmon. The present study was aimed to firstly characterize the features of SdY protein. Results indicate that SdY is predominantly localized in the cytoplasm tested in various fish and mammalian cell lines and confirmed by different methods. Predictive in silico analysis revealed that SdY is composed of a β-sandwich core surrounded by three α-helices as well specific characteristics conferring a putative protein-protein interaction site. Secondly, the study was aimed to understand how SdY could trigger testicular differentiation. SdY is a truncated divergent version of Irf9 that has a conserved protein-protein domain but lost the DNA interaction domain of its ancestor gene. It was then hypothesized that SdY could initiate testicular differentiation by protein-protein interactions. To evaluate this we first conducted a yeast-two-hybrid screen that revealed a high proportion of transcription factors including fox proteins. Using various biochemical and cellular methods we confirm an interaction between SdY and Foxl2, a major transcription factor involved in ovarian differentiation and identity maintenance. Interestingly, the interaction of SdY with Foxl2 leads to nuclear translocation of SdY from the cytoplasm. Furthermore, this SdY translocation mechanism was found to be specific to fish Foxl2 and to a lesser extend Foxl3 and not other Fox proteins or mammalian FoxL2. In addition, we found that this interaction allows the stabilization of SdY and prevents its degradation. Finally, to better decipher SdY action we used as a model a mutated version of SdY that was identified in XY females of Chinook salmon natural population. Results show that this mutation induces a local conformation defect obviously leading to a misfolded protein and a quick degradation. Moreover, the mutated version compromised the interaction with Foxl2 defining a minimal threshold to induce testicular differentiation. Altogether results from my thesis propose that SdY would trigger testicular differentiation in salmonids by preventing Foxl2 to promote ovarian differentiation. Further research should be now carried out on how this interaction of SdY and Foxl2 acts in-vivo.
Lungfish and coelacanths are the only living sarcopterygian fish. The phylogenetic relationship of lungfish to the last common ancestor of tetrapods and their close morphological similarity to their fossil ancestors make this species uniquely interesting. However their genome size, the largest among vertebrates, is hampering the generation of a whole genome sequence. To provide a partial solution to the problem, a high-coverage lungfish reference transcriptome was generated and assembled. The present findings indicate that lungfish, not coelacanths, are the closest relatives to land-adapted vertebrates. Whereas protein-coding genes evolve at a very slow rate, possibly reflecting a “living fossil” status, transposable elements appear to be active and show high diversity, suggesting a role for them in the remarkable expansion of the lungfish genome. Analyses of single genes and gene families documented changes connected to the water to land transition and demonstrated the value of the lungfish reference transcriptome for comparative studies of vertebrate evolution.
Staphylococcus aureus is a prevalent commensal bacterium which represents one of the leading causes in health care-associated bacterial infections worldwide and can cause a variety of different diseases ranging from simple abscesses to severe and life threatening infections including pneumonia, osteomyelitis and sepsis.
In recent times multi-resistant strains have emerged, causing severe problems in nosocomial as well as community-acquired (CA) infection settings, especially in the United States (USA). Therefore S. aureus has been termed as a superbug by the WHO, underlining the severe health risk originating from it. Today, infections in the USA are dominated by S. aureus genotypes which are classified as USA300 and USA400, respectively. Strains of genotype USA300 are responsible for about 70% of the CA infections.
The molecular mechanisms which render S. aureus such an effective pathogen are still not understood in its entirety. For decades S. aureus was thought to be a strictly extracellular pathogen relying on pore-forming toxins like α-hemolysin to damage human cells and tissue. Only recently it has been shown that S. aureus can enter non-professional phagocytes, using adhesins like the fibronectin-binding proteins which mediate an endocytotic uptake into the host cells. The bacteria are consequently localized to endosomes, where the degradation of enclosed bacterial cells through phagosome maturation would eventually occur.
S. aureus can avoid degradation, and translocate to the cellular cytoplasm, where it can replicate. The ability to cause this so-called phagosomal escape has mainly been attributed to a family of amphiphilic peptides called phenol soluble modulins (PSMs), but as studies have shown, they are not sufficient.
In this work I used a transposon mutant library in combination with automated fluorescence microscopy to screen for genes involved in the phagosomal escape process and intracellular survival of S. aureus. I thereby identified a number of genes, including a non-ribosomal peptide synthetase (NRPS). The NRPS, encoded by the genes ausA and ausB, produces two types of small peptides, phevalin and tyrvalin. Mutations in the ausAB genes lead to a drastic decrease in phagosomal escape rates in epithelial cells, which were readily restored by genetic complementation in trans as well as by supplementation of synthetic phevalin. In leukocytes, phevalin interferes with calcium fluxes and activation of neutrophils and promotes cytotoxicity of intracellular bacteria in both, macrophages and neutrophils. Further ausAB is involved in survival and virulence of the bacterium during mouse lung pneumoniae.
The here presented data demonstrates the contribution of the bacterial cyclic dipeptide phevalin to S. aureus virulence and suggests, that phevalin directly acts on a host cell target to promote cytotoxicity of intracellular bacteria.
Community-acquired (CA) Staphylococcus aureus cause various diseases even in healthy individuals. Enhanced virulence of CA-strains is partly attributed to increased production of toxins such as phenol-soluble modulins (PSM). The pathogen is internalized efficiently by mammalian host cells and intracellular S. aureus has recently been shown to contribute to disease. Upon internalization, cytotoxic S. aureus strains can disrupt phagosomal membranes and kill host cells in a PSM-dependent manner. However, PSM are not sufficient for these processes. Here we screened for factors required for intracellular S. aureus virulence. We infected escape reporter host cells with strains from an established transposon mutant library and detected phagosomal escape rates using automated microscopy. We thereby, among other factors, identified a non-ribosomal peptide synthetase (NRPS) to be required for efficient phagosomal escape and intracellular survival of S. aureus as well as induction of host cell death. By genetic complementation as well as supplementation with the synthetic NRPS product, the cyclic dipeptide phevalin, wild-type phenotypes were restored. We further demonstrate that the NRPS is contributing to virulence in a mouse pneumonia model. Together, our data illustrate a hitherto unrecognized function of the S. aureus NRPS and its dipeptide product during S. aureus infection.
Whole Genome Duplications Shaped the Receptor Tyrosine Kinase Repertoire of Jawed Vertebrates
(2016)
The receptor tyrosine kinase (RTK) gene family, involved primarily in cell growth and differentiation, comprises proteins with a common enzymatic tyrosine kinase intracellular domain adjacent to a transmembrane region. The amino-terminal portion of RTKs is extracellular and made of different domains, the combination of which characterizes each of the 20 RTK subfamilies among mammals. We analyzed a total of 7,376 RTK sequences among 143 vertebrate species to provide here the first comprehensive census of the jawed vertebrate repertoire. We ascertained the 58 genes previously described in the human and mouse genomes and established their phylogenetic relationships. We also identified five additional RTKs amounting to a total of 63 genes in jawed vertebrates. We found that the vertebrate RTK gene family has been shaped by the two successive rounds of whole genome duplications (WGD) called 1R and 2R (1R/2R) that occurred at the base of the vertebrates. In addition, the Vegfr and Ephrin receptor subfamilies were expanded by single gene duplications. In teleost fish, 23 additional RTK genes have been retained after another expansion through the fish-specific third round (3R) of WGD. Several lineage-specific gene losses were observed. For instance, birds have lost three RTKs, and different genes are missing in several fish sublineages. The RTK gene family presents an unusual high gene retention rate from the vertebrate WGDs (58.75% after 1R/2R, 64.4% after 3R), resulting in an expansion that might be correlated with the evolution of complexity of vertebrate cellular communication and intracellular signaling.
Purpose
Wilms tumor (WT) is the most common pediatric renal tumor. Treatment planning under International Society of Paediatric Oncology (SIOP) protocols is based on staging and histologic assessment of response to preoperative chemotherapy. Despite high overall survival (OS), many relapses occur in patients without specific risk factors, and many successfully treated patients are exposed to treatments with significant risks of late effects. To investigate whether molecular biomarkers could improve risk stratification, we assessed 1q status and other potential copy number biomarkers in a large WT series.
Materials and Methods
WT nephrectomy samples from 586 SIOP WT 2001 patients were analyzed using a multiplex ligation-dependent probe amplification (MLPA) assay that measured the copy number of 1q and other regions of interest.
Results
One hundred sixty-seven (28%) of 586 WTs had 1q gain. Five-year event-free survival (EFS) was 75.0% in patients with 1q gain (95% CI, 68.5% to 82.0%) and 88.2% in patients without gain (95% CI, 85.0% to 91.4%). OS was 88.4% with gain (95% CI, 83.5% to 93.6%) and 94.4% without gain (95% CI, 92.1% to 96.7%). In univariable analysis, 1q gain was associated with poorer EFS (P<.001; hazard ratio, 2.33) and OS (P=.01; hazard ratio, 2.16). The association of 1q gain with poorer EFS retained significance in multivariable analysis adjusted for 1p and 16q loss, sex, stage, age, and histologic risk group. Gain of 1q remained associated with poorer EFS in tumor subsets limited to either intermediate-risk localized disease or nonanaplastic localized disease. Other notable aberrations associated with poorer EFS included MYCN gain and TP53 loss.
Conclusion
Gain of 1q is a potentially valuable prognostic biomarker in WT, in addition to histologic response to preoperative chemotherapy and tumor stage.
Feeding and sleep are fundamental behaviours with significant interconnections and cross-modulations. The circadian system and peptidergic signals are important components of this modulation, but still little is known about the mechanisms and networks by which they interact to regulate feeding and sleep. We show that specific thermogenetic activation of peptidergic Allatostatin A (AstA)-expressing PLP neurons and enteroendocrine cells reduces feeding and promotes sleep in the fruit fly Drosophila. The effects of AstA cell activation are mediated by AstA peptides with receptors homolog to galanin receptors subserving similar and apparently conserved functions in vertebrates. We further identify the PLP neurons as a downstream target of the neuropeptide pigment-dispersing factor (PDF), an output factor of the circadian clock. PLP neurons are contacted by PDF-expressing clock neurons, and express a functional PDF receptor demonstrated by cAMP imaging. Silencing of AstA signalling and continuous input to AstA cells by tethered PDF changes the sleep/activity ratio in opposite directions but does not affect rhythmicity. Taken together, our results suggest that pleiotropic AstA signalling by a distinct neuronal and enteroendocrine AstA cell subset adapts the fly to a digestive energy-saving state which can be modulated by PDF.
Characterization of a novel putative factor involved in host adaptation in Trypanosoma brucei
(2016)
Trypanosomes are masters of adaptation to different host environments
during their complex life cycle. Large-scale proteomic approaches provide information on changes at
the cellular level in a systematic way. However, a detailed work on single components is necessary
to understand the adaptation mechanisms on a molecular level. Here we have performed a detailed
characterization of a bloodstream form (BSF) stage-specific putative flagellar host adaptation
factor (Tb927.11.2400) identified previously in a SILAC-based comparative proteome study.
Tb927.11.2400 shares 38% amino acid identity with TbFlabarin (Tb927.11.2410), a procyclic form
(PCF) stage specific flagellar BAR domain protein. We named Tb927.11.2400 TbFlabarin like
(TbFlabarinL) and demonstrate that it is a result of a gene duplication event, which occurred in
African trypanosomes. TbFlabarinL is not essential for growth of the parasites under cell culture
conditions and it is dispensable for developmental differentiation from BSF to the PCF in vitro. We
generated a TbFlabarinL-specific antibody and showed that it localizes in the flagellum. The
co-immunoprecipitation experiment together with a biochemical cell fractionation indicated a dual
association of TbFlabarinL with the flagellar
membrane and the components of the paraflagellar rod.
The microbial communities that live inside the human gastrointestinal tract -the human gut
microbiome- are important for host health and wellbeing. Characterizing this new “organ”,
made up of as many cells as the human body itself, has recently become possible through
technological advances. Metagenomics, the high-throughput sequencing of DNA directly from
microbial communities, enables us to take genomic snapshots of thousands of microbes living
together in this complex ecosystem, without the need for isolating and growing them.
Quantifying the composition of the human gut microbiome allows us to investigate its
properties and connect it to host physiology and disease. The wealth of such connections was
unexpected and is probably still underestimated. Due to the fact that most of our dietary as well
as medicinal intake affects the microbiome and that the microbiome itself interacts with our
immune system through a multitude of pathways, many mechanisms have been proposed to
explain the observed correlations, though most have yet to be understood in depth.
An obvious prerequisite to characterizing the microbiome and its interactions with the host is
the accurate quantification of its composition, i.e. determining which microbes are present and
in what numbers they occur. Historically, standard practices have existed for sample handling,
DNA extraction and data analysis for many years. However, these were generally developed for
single microbe cultures and it is not always feasible to implement them in large scale
metagenomic studies. Partly because of this and partly because of the excitement that new
technology brings about, the first metagenomic studies each took the liberty to define their own
approach and protocols. From early meta-analysis of these studies it became clear that the
differences in sample handling, as well as differences in computational approaches, made
comparisons across studies very difficult. This restricts our ability to cross-validate findings of
individual studies and to pool samples from larger cohorts. To address the pressing need for
standardization, we undertook an extensive comparison of 21 different DNA extraction methods
as well as a series of other sample manipulations that affect quantification. We developed a
number of criteria for determining the measurement quality in the absence of a mock
community and used these to propose best practices for sampling, DNA extraction and library
preparation. If these were to be accepted as standards in the field, it would greatly improve
comparability across studies, which would dramatically increase the power of our inferences
and our ability to draw general conclusions about the microbiome.
Most metagenomics studies involve comparisons between microbial communities, for example
between fecal samples from cases and controls. A multitude of approaches have been proposed
to calculate community dissimilarities (beta diversity) and they are often combined with
various preprocessing techniques. Direct metagenomics quantification usually counts
sequencing reads mapped to specific taxonomic units, which can be species, genera, etc. Due to
technology-inherent differences in sampling depth, normalizing counts is necessary, for
instance by dividing each count by the sum of all counts in a sample (i.e. total sum scaling), or by
subsampling. To derive a single value for community (dis-)similarity, multiple distance
measures have been proposed. Although it is theoretically difficult to benchmark these
approaches, we developed a biologically motivated framework in which distance measures can
be evaluated. This highlights the importance of data transformations and their impact on the
measured distances.
Building on our experience with accurate abundance estimation and data preprocessing
techniques, we can now try and understand some of the basic properties of microbial
communities. In 2011, it was proposed that the space of genus level variation of the human gut
microbial community is structured into three basic types, termed enterotypes. These were
described in a multi-country cohort, so as to be independent of geography, age and other host
properties. Operationally defined through a clustering approach, they are “densely populated
areas in a multidimensional space of community composition”(source) and were proposed as a
general stratifier for the human population. Later studies that applied this concept to other
datasets raised concerns about the optimum number of clusters and robustness of the
clustering approach. This heralded a long standing debate about the existence of structure and
the best ways to determine and capture it. Here, we reconsider the concept of enterotypes, in
the context of the vastly increased amounts of available data. We propose a refined framework
in which the different types should be thought of as weak attractors in compositional space and
we try to implement an approach to determining which attractor a sample is closest to. To this
end, we train a classifier on a reference dataset to assign membership to new samples. This way,
enterotypes assignment is no longer dataset dependent and effects due to biased sampling are
minimized. Using a model in which we assume the existence of three enterotypes characterized
by the same driver genera, as originally postulated, we show the relevance of this stratification
and propose it to be used in a clinical setting as a potential marker for disease development.
Moreover, we believe that these attractors underline different rules of community assembly and
we recommend they be accounted for when analyzing gut microbiome samples.
While enterotypes describe structure in the community at genus level, metagenomic sequencing
can in principle achieve single-nucleotide resolution, allowing us to identify single nucleotide
polymorphisms (SNPs) and other genomic variants in the gut microbiome. Analysis
methodology for this level of resolution has only recently been developed and little exploration
has been done to date. Assessing SNPs in a large, multinational cohort, we discovered that the
landscape of genomic variation seems highly structured even beyond species resolution,
indicating that clearly distinguishable subspecies are prevalent among gut microbes. In several
cases, these subspecies exhibit geo-stratification, with some subspecies only found in the
Chinese population. Generally however, they present only minor dispersion limitations and are
seen across most of our study populations. Within one individual, one subspecies is commonly
found to dominate and only rarely are several subspecies observed to co-occur in the same
ecosystem. Analysis of longitudinal data indicates that the dominant subspecies remains stable
over periods of more than three years. When interrogating their functional properties we find
many differences, with specific ones appearing relevant to the host. For example, we identify a
subspecies of E. rectale that is lacking the flagellum operon and find its presence to be
significantly associated with lower body mass index and lower insulin resistance of their hosts;
it also correlates with higher microbial community diversity. These associations could not be
seen at the species level (where multiple subspecies are convoluted), which illustrates the
importance of this increased resolution for a more comprehensive understanding of microbial
interactions within the microbiome and with the host.
Taken together, our results provide a rigorous basis for performing comparative metagenomics
of the human gut, encompassing recommendations for both experimental sample processing
and computational analysis. We furthermore refine the concept of community stratification into
enterotypes, develop a reference-based approach for enterotype assignment and provide
compelling evidence for their relevance. Lastly, by harnessing the full resolution of
metagenomics, we discover a highly structured genomic variation landscape below the
microbial species level and identify common subspecies of the human gut microbiome. By
developing these high-precision metagenomics analysis tools, we thus hope to contribute to a
greatly improved understanding of the properties and dynamics of the human gut microbiome.
Background
Spermatogenesis is a complex differentiation process that involves the successive and simultaneous execution of three different gene expression programs: mitotic proliferation of spermatogonia, meiosis, and spermiogenesis. Testicular cell heterogeneity has hindered its molecular analyses. Moreover, the characterization of short, poorly represented cell stages such as initial meiotic prophase ones (leptotene and zygotene) has remained elusive, despite their crucial importance for understanding the fundamentals of meiosis.
Results
We have developed a flow cytometry-based approach for obtaining highly pure stage-specific spermatogenic cell populations, including early meiotic prophase. Here we combined this methodology with next generation sequencing, which enabled the analysis of meiotic and postmeiotic gene expression signatures in mouse with unprecedented reliability. Interestingly, we found that a considerable number of genes involved in early as well as late meiotic processes are already on at early meiotic prophase, with a high proportion of them being expressed only for the short time lapse of lepto-zygotene stages. Besides, we observed a massive change in gene expression patterns during medium meiotic prophase (pachytene) when mostly genes related to spermiogenesis and sperm function are already turned on. This indicates that the transcriptional switch from meiosis to post-meiosis takes place very early, during meiotic prophase, thus disclosing a higher incidence of post-transcriptional regulation in spermatogenesis than previously reported. Moreover, we found that a good proportion of the differential gene expression in spermiogenesis corresponds to up-regulation of genes whose expression starts earlier, at pachytene stage; this includes transition protein-and protamine-coding genes, which have long been claimed to switch on during spermiogenesis. In addition, our results afford new insights concerning X chromosome meiotic inactivation and reactivation.
Conclusions
This work provides for the first time an overview of the time course for the massive onset and turning off of the meiotic and spermiogenic genetic programs. Importantly, our data represent a highly reliable information set about gene expression in pure testicular cell populations including early meiotic prophase, for further data mining towards the elucidation of the molecular bases of male reproduction in mammals.
Predicting bee community responses to land-use changes: Effects of geographic and taxonomic biases
(2016)
Land-use change and intensification threaten bee populations worldwide, imperilling pollination services. Global models are needed to better characterise, project, and mitigate bees' responses to these human impacts. The available data are, however, geographically and taxonomically unrepresentative; most data are from North America and Western Europe, overrepresenting bumblebees and raising concerns that model results may not be generalizable to other regions and taxa. To assess whether the geographic and taxonomic biases of data could undermine effectiveness of models for conservation policy, we have collated from the published literature a global dataset of bee diversity at sites facing land-use change and intensification, and assess whether bee responses to these pressures vary across 11 regions (Western, Northern, Eastern and Southern Europe; North, Central and South America; Australia and New Zealand; South East Asia; Middle and Southern Africa) and between bumblebees and other bees. Our analyses highlight strong regionally-based responses of total abundance, species richness and Simpson's diversity to land use, caused by variation in the sensitivity of species and potentially in the nature of threats. These results suggest that global extrapolation of models based on geographically and taxonomically restricted data may underestimate the true uncertainty, increasing the risk of ecological surprises.
Depreissia is a little known genus comprising two hymenopteran-mimicking species, one found in Central Africa and one in the north of Borneo. The male of D. decipiens is redescribed, the female is described for the first time. The carapace is elongated, dorsally flattened and rhombus-shaped, the rear of the thorax laterally depressed and transformed, with a pair of deep pits; the pedicel is almost as long as the abdomen. The male palp is unusual, characterized by the transverse deeply split membranous tegulum separating a ventral part which bears a sclerotized tegular apophysis and a large dagger-like retrodirected median apophysis. The female epigyne consists of one pair of large adjacent spermathecae and very long copulatory ducts arising posteriorly and rising laterally alongside the spermathecae continuing in several vertical and horizontal coils over the anterior surface. Relationships within the Salticidae are discussed and an affinity with the Cocalodinae is suggested. Arguments are provided for a hypothesis that D. decipiens is not ant-mimicking as was previously believed, but is a mimic of polistinine wasps. The species was found in the canopy in the Kinabalu area only, in primary and old secondary rainforest at 200–700 m.a.s.l. Overlap of canopy-dwelling spider species with those in the understorey are discussed and examples of species richness and endemism in the canopy are highlighted. Canopy fogging is a very efficient method of collecting for most arthropods. The canopy fauna adds an extra dimension to the known biodiversity of the tropical rainforest. In southeast Asia, canopy research has been neglected, inhibiting evaluation of comparative results of this canopy project with that from other regions. More use of fogging as a collecting method would greatly improve insight into the actual species richness and species distribution in general.
Developmental differentiation is a universal biological process that allows cells to adapt to different environments to perform specific functions. African trypanosomes progress through a tightly regulated life cycle in order to survive in different host environments when they shuttle between an insect vector and a vertebrate host. Transcriptomics has been useful to gain insight into RNA changes during stage transitions; however, RNA levels are only a moderate proxy for protein abundance in trypanosomes. We quantified 4270 protein groups during stage differentiation from the mammalian-infective to the insect form and provide classification for their expression profiles during development. Our label-free quantitative proteomics study revealed previously unknown components of the differentiation machinery that are involved in essential biological processes such as signaling, posttranslational protein modifications, trafficking and nuclear transport. Furthermore, guided by our proteomic survey, we identified the cause of the previously observed differentiation impairment in the histone methyltransferase DOT1B knock-out strain as it is required for accurate karyokinesis in the first cell division during differentiation. This epigenetic regulator is likely involved in essential chromatin restructuring during developmental differentiation, which might also be important for differentiation in higher eukaryotic cells. Our proteome dataset will serve as a resource for detailed investigations of cell differentiation to shed more light on the molecular mechanisms of this process in trypanosomes and other eukaryotes.
Quantitative Trait Locus Analysis of Mating Behavior and Male Sex Pheromones in Nasonia Wasps
(2016)
A major focus in speciation genetics is to identify the chromosomal regions and genes that reduce hybridization and gene flow. We investigated the genetic architecture of mating behavior in the parasitoid wasp species pair Nasonia giraulti and Nasonia oneida that exhibit strong prezygotic isolation. Behavioral analysis showed that N. oneida females had consistently higher latency times, and broke off the mating sequence more often in the mounting stage when confronted with N. giraulti males compared with males of their own species. N. oneida males produce a lower quantity of the long-range male sex pheromone (4R,5S)-5-hydroxy-4-decanolide (RS-HDL). Crosses between the two species yielded hybrid males with various pheromone quantities, and these males were used in mating trials with females of either species to measure female mate discrimination rates. A quantitative trait locus (QTL) analysis involving 475 recombinant hybrid males (F2), 2148 reciprocally backcrossed females (F3), and a linkage map of 52 equally spaced neutral single nucleotide polymorphism (SNP) markers plus SNPs in 40 candidate mating behavior genes revealed four QTL for male pheromone amount, depending on partner species. Our results demonstrate that the RS-HDL pheromone plays a role in the mating system of N. giraulti and N. oneida, but also that additional communication cues are involved in mate choice. No QTL were found for female mate discrimination, which points at a polygenic architecture of female choice with strong environmental influences.
Inhibition of Hsp90 can increase the radiosensitivity of tumor cells. However, inhibition of Hsp90 alone induces the anti-apoptotic Hsp70 and thereby decreases radiosensitivity. Therefore, preventing Hsp70 induction can be a promising strategy for radiosensitization. PI-103, an inhibitor of PI3K and mTOR, has previously been shown to suppress the up-regulation of Hsp70. Here, we explore the impact of combining PI-103 with the Hsp90 inhibitor NVP-AUY922 in irradiated glioblastoma and colon carcinoma cells. We analyzed the cellular response to drug-irradiation treatments by colony-forming assay, expression of several marker proteins, cell cycle progression and induction/repair of DNA damage. Although PI-103, given 24 h prior to irradiation, slightly suppressed the NVP-AUY922-mediated up-regulation of Hsp70, it did not cause radiosensitization and even diminished the radiosensitizing effect of NVP-AUY922. This result can be explained by the activation of PI3K and ERK pathways along with G1-arrest at the time of irradiation. In sharp contrast, PI-103 not only exerted a radiosensitizing effect but also strongly enhanced the radiosensitization by NVP-AUY922 when both inhibitors were added 3 h before irradiation and kept in culture for 24 h. Possible reasons for the observed radiosensitization under this drug-irradiation schedule may be a down-regulation of PI3K and ERK pathways during or directly after irradiation, increased residual DNA damage and strong G2/M arrest 24 h thereafter. We conclude that duration of drug treatment before irradiation plays a key role in the concomitant targeting of PI3K/mTOR and Hsp90 in tumor cells.
Physical interaction of skeletal precursors with multiple myeloma cells has been shown to suppress their osteogenic potential while favoring their tumor-promoting features. Although several transcriptome analyses of myeloma patient-derived mesenchymal stem cells have displayed differences compared to their healthy counterparts, these analyses insufficiently reflect the signatures mediated by tumor cell contact, vary due to different methodologies, and lack results in lineage-committed precursors. To determine tumor cell contact-mediated changes on skeletal precursors, we performed transcriptome analyses of mesenchymal stem cells and osteogenic precursor cells cultured in contact with the myeloma cell line INA-6. Comparative analyses confirmed dysregulation of genes which code for known disease-relevant factors and additionally revealed upregulation of genes that are associated with plasma cell homing, adhesion, osteoclastogenesis, and angiogenesis. Osteoclast-derived coupling factors, a dysregulated adipogenic potential, and an imbalance in favor of anti-anabolic factors may play a role in the hampered osteoblast differentiation potential of mesenchymal stem cells. Angiopoietin-Like 4 (ANGPTL4) was selected from a list of differentially expressed genes as a myeloma cell contact-dependent target in skeletal precursor cells which warranted further functional analyses. Adhesion assays with full-length ANGPTL4-coated plates revealed a potential role of this protein in INA6 cell attachment. This study expands knowledge of the myeloma cell contact-induced signature in the stromal compartment of myelomatous bones and thus offers potential targets that may allow detection and treatment of myeloma bone disease at an early stage.