Refine
Year of publication
- 2018 (152) (remove)
Document Type
- Article (104)
- Doctoral Thesis (47)
- Report (1)
Language
- English (152) (remove)
Has Fulltext
- yes (152)
Is part of the Bibliography
- no (152)
Keywords
- - (87)
- climate change (4)
- dendrochronology (3)
- innate immunity (3)
- platelets (3)
- <i>Burkholderia pseudomallei</i> (2)
- Brain-derived neurotrophic factor (2)
- Bürgerkrieg (2)
- CASP model (2)
- China (2)
- Clinical guideline (2)
- Cystitis (2)
- Depression (2)
- Flavivirus (2)
- Fournier’s gangrene (2)
- GWAS (2)
- Germany (2)
- Hyperbaric oxygenation (2)
- Klimawandel (2)
- Morphologic changes (2)
- Necrotizing fasciitis (2)
- Necrotomy (2)
- Obesity (2)
- Plasmaphysik (2)
- Pyelonephritis (2)
- Sepsis (2)
- Sepsis score (2)
- Simulation (2)
- Small animal MRI (2)
- Soft tissue infection (2)
- Staphylococcus aureus (2)
- Streptococcus pneumoniae (2)
- Systematic review (2)
- Therapy (2)
- Urinary tract infection (2)
- Vitamin D (2)
- antibiotics (2)
- antimicrobial peptides (2)
- ascariasis (2)
- bias (2)
- biofilm (2)
- causal inference (2)
- dendroecology (2)
- environment (2)
- helminth (2)
- intestinal nematode (2)
- lectin (2)
- melioidosis (2)
- mendelian randomization (2)
- metabolomics (2)
- microbiota (2)
- phenotypic plasticity (2)
- proteomics (2)
- public awareness (2)
- statistical methods (2)
- tree-ring width (2)
- 1,2,3-benzotriazoles (1)
- 1,2,4-triazoles (1)
- 2,4-diamino-1,3,5-triazines (1)
- 2-imino-2<i>H</i>-chromen-3-yl-1,3,5-triazines (1)
- 2-imino-coumarins (1)
- 2<i>H</i>-chromen-3-yl-1,3,5-triazines (1)
- 2D PAGE (1)
- <i>Clostridiodes difficile</i> (1)
- <i>Hermite</i>-polynomials (1)
- <i>Kolmogorov</i>-backward-equation (1)
- <i>N</i>-acylhydrazones (1)
- <i>N</i>-sulfonylhydrazones (1)
- <i>S. aureus</i> (1)
- ACT-209905 (1)
- AFLP, microsatellite SSR, ITS, DNA isolation (1)
- ATP-binding cassette transporters (1)
- Adaptation (1)
- Africa (1)
- African swine fever virus (1)
- Afrikanische Schweinepest Virus (1)
- Alaska (1)
- Alfvén Waves (1)
- Animal behavior (1)
- Annual rings (1)
- Antioxidans (1)
- Anxiety sensitivity (1)
- Arbovirus (1)
- Asymmetric synthesis (1)
- Austria (1)
- B cell class switch (1)
- B1 B cells (1)
- Bathymodiolus (1)
- Bathymodiolus symbiosis (1)
- Baumgrenze (1)
- Bayley scales (1)
- Benign breast tumours (1)
- Beringung (1)
- Biochemie (1)
- Biomathematik , Bioinformatik (1)
- Blue Intensity (1)
- Bodentemperatur (1)
- Bronchopulmonary dysplasia (1)
- Buche (1)
- CA–Markov (1)
- CD40L (1)
- CFTR Cl (1)
- Cerebral Palsy Kinder (1)
- Cerebral cavernous malformations (1)
- Chemo-enzymatic synthesis (1)
- Chiral amines (1)
- Civil conflicts (1)
- Clade Annotation (1)
- Climate Change (1)
- Cochrane–Orcutt procedure (1)
- Collisions (1)
- Comparative Gene Finding (1)
- Comparative Genomics (1)
- CyberKnife robotic radiosurgery (1)
- Cybermobbing (1)
- Cytochrome P-450 (1)
- DHEAS (1)
- DISQOVER (1)
- DLX proteins (1)
- DNA-microarray (1)
- Deep-sea hydrothermal vents (1)
- Democracy (1)
- Demokratie (1)
- Dendrochronologie (1)
- Diagnosis (1)
- Dispersal (1)
- Doxorubicin (1)
- Dual Decomposition (1)
- EEG (1)
- EMSA (1)
- Ecosystem Dynamics (1)
- Elektrochemischer Sensor (1)
- Entwicklungszusammenarbeit (1)
- Environmental conditions (1)
- Epidemiology (1)
- Evolution (1)
- Evolutionsbiologie , Tierökologie , Sexuelle Selektion , Sexualverhalten (1)
- Fast Particles (1)
- Feldversuch (1)
- Fettsucht (1)
- Flight ability (1)
- Flug (1)
- Foreign aid (1)
- Fourier analysis (1)
- Friedensvertrag (1)
- GAPDH, ALDH (1)
- GHG emissions (1)
- GPU computing (1)
- Gastrointestinal oncology (1)
- Gastrointestinal stromal tumor (1)
- Gastrointestinal symptoms (1)
- Gastrointestinal tract (1)
- Gene Structure Prediction (1)
- Genetic counselling (1)
- Genetic diversity (1)
- Genome Annotation (1)
- Genotyping (1)
- Glazitektonik (1)
- Global South regional policy (1)
- Global change (1)
- Glutaredoxin (1)
- Glutaredoxine (1)
- Glutathion (1)
- Glutathione (1)
- Glycoprotein B (1)
- Graphen (1)
- Greifvögel (1)
- Gyro-kinetic Theory (1)
- HACA (1)
- HCMV (1)
- HCO (1)
- HEV (1)
- HIT (1)
- Hangzhou International Airport (1)
- Heat-flux (1)
- Hepatitis-E-Virus , Polymerase-Kettenreaktion , Microarray , West-Nil-Virus , Flaviviren , RNS-Viren , Genotypisierung (1)
- Herpesviren (1)
- Heterostrukturen (1)
- Himalayan Silver Fir (<i>Abies spectabilis</i>), Nepal Himalaya (1)
- Hirninfarkt (1)
- Hyperventilation (1)
- IDD in pregnant women (1)
- IL-10 (1)
- Ili River delta (1)
- Imaging features (1)
- Impfstoff (1)
- Individual phenotype (1)
- Integrins (1)
- Interoception (1)
- Interozeption (1)
- Intrastate conflicts (1)
- Intraventricular hemorrhage (1)
- Iodine (1)
- Iodine deficiency disorders (1)
- Ionthruster (1)
- Isopropylamine (1)
- JSNZ (1)
- Jahresring (1)
- Juniperus communis (1)
- Kinetic simulation (1)
- Komplexes Plasma (1)
- Konfliktregelung (1)
- Korrespondenzprinzip (1)
- LAVH (1)
- LPS (1)
- LUCC (1)
- Lagrangian Relaxation (1)
- Lake Balkhash (1)
- Landformanalyse (1)
- Landsat (1)
- Lemnaceae (1)
- LiDAR (1)
- Local adaptation (1)
- Lord's Resistance Army (1)
- Low temperature plasma (1)
- Lycaena tityrus (1)
- Lymphozyt (1)
- MTIP planning (1)
- Machtteilungsregierungen (1)
- Magnetismus (1)
- Master-Gleichung (1)
- Mathematik (1)
- Mediation (1)
- Medienbildung (1)
- Mediennutzungsethik (1)
- Membranfusion (1)
- Metastasis (1)
- Middle East (1)
- Mikrobiologie (1)
- Minimally invasive diagnostics (1)
- Mitochondrium (1)
- Mixed methods (1)
- Molecular biology (1)
- Molecular genetics (1)
- Molekularbiologie (1)
- Molekularbiologie, Genotypisierung, Genetische Diversität (1)
- Molybdenum (1)
- Molybdopterin (1)
- Monitoring IDD (1)
- Monte Carlo (1)
- Movement (1)
- NF-Y (1)
- Neurodevelopmental outcome (1)
- Neuroimmunologie (1)
- Nichtlineare Dynamik (1)
- OCT1 (1)
- Optomechanik (1)
- Oral health, Cerebral palsy, Children, Prevention (1)
- Orale Gesundheit (1)
- Osmoregulation (1)
- Outcomes research (1)
- Overview (1)
- Oxidativer Stress (1)
- Oxidoreduktase (1)
- P300 (1)
- PCLake (1)
- PD-L1 (1)
- PEI,PDADMA,PSS,surface forces,atomic force microscopy, colloidal probe (1)
- PF4 (1)
- Parkinson's disease (1)
- Partial migration (1)
- Pediatric (1)
- Permissive hypercapnia (1)
- Picea glauca (1)
- Plasma (1)
- Plasma , Plasmaphysik , Tokamak , Stellarator , Magnetohydrodynamik , Kinetische Theorie , Simulation , Alfvén-Welle , Energiereiches Teilchen (1)
- Plasma Physics (1)
- Plastizität (1)
- Political Economy (1)
- Politische Ökonomie (1)
- Polyphenole (1)
- Potamopyrgus antipodarum (1)
- Power-Sharing (1)
- Prevalence (1)
- Prevention (1)
- Profilbilanzierung (1)
- Protein engineering (1)
- Proteine (1)
- Proteomanalyse (1)
- Pt(II) complexes (1)
- Pterin (1)
- Quantenoptik (1)
- Quantenpunkt (1)
- RT-qPCR (1)
- Rabies (1)
- Rabies virus (1)
- Radikalfänger (1)
- Range shift (1)
- Reaktive Sauerstoffspezies (1)
- Recurrence (1)
- Relativistische Quantenmechanik (1)
- Rotbuche (1)
- S. aureus (1)
- SNP (1)
- STED microscopy (1)
- Salztoleranz (1)
- Schamethik (1)
- Schlaganfall induzierte Immunschwäche (1)
- Schmetterling (1)
- Schnecke (1)
- Schweinekrankheit (1)
- Sexting (1)
- Shrubs (1)
- Sinlge port (1)
- Sozialität (1)
- Sphingosine-1-Phosphate (1)
- Spinnen (1)
- Spintronik (1)
- Starch (1)
- Stark gekoppelte Systeme (1)
- Stellarator (1)
- Stickland reactions (1)
- Streutheorie (1)
- Stärke (1)
- T cell maturation (1)
- Teilzug (1)
- Theodoxus fluviatilis (1)
- Thiole (1)
- Thioredoxine (1)
- Third-party intervention (1)
- Thrombospondin (1)
- Tierphysiologie (1)
- Tierseuche (1)
- Tokamak (1)
- Tollwut (1)
- Tollwutvirus (1)
- Transaminases (1)
- Two component systems (1)
- Uganda (1)
- Uncoupling (1)
- VEEV (1)
- Vascular malformation (1)
- Vegetation Ecology (1)
- Verbreitung (1)
- Vietnam (1)
- Virologie (1)
- Virus (1)
- Virus evolution (1)
- Vogelzug (1)
- WNV (1)
- Waldgrenze (1)
- Waldökologie (1)
- Waldökosystem (1)
- Weichselvereisung (1)
- Weißfichte (1)
- Winter (1)
- Yeast (1)
- Zitterbewegung (1)
- Zoonose (1)
- [Fe-S] Cluster (1)
- absolute (1)
- adaptation (1)
- adaptive immunity (1)
- age (1)
- agroecosystems (1)
- airport cases (1)
- alanine scanning (1)
- alcohol risk drinking (1)
- alexithymia (1)
- amino acids (1)
- anaerobic metabolism (1)
- animal (1)
- anti-GD<sub>2</sub> immunotherapy (1)
- anticoagulants (1)
- anticonvulsants (1)
- antiseptic stewardship (1)
- aquaporins (1)
- aquatic plants (1)
- arable wild plants (1)
- arid river basins (1)
- arm (1)
- arm ability training (1)
- asymmetric synthesis (1)
- asymptotic expansion (1)
- atomic force microscopy (1)
- attention (1)
- autoimmunity (1)
- autoregressive conditional heteroskedasticity (1)
- averaging (1)
- bacterial meningitis (1)
- beech (1)
- big-fish-little-pond-effect (1)
- bile acids (1)
- binding force (1)
- binding land-use plan (1)
- biocide (1)
- biodiversity offsets (1)
- biomanipulation (1)
- blood–brain barrier (1)
- boreal forest (1)
- brain stimulation (1)
- brownfields (1)
- cancer therapy (1)
- carbon–carbon lyase (1)
- carboplatin (1)
- catalytic activity (1)
- ch14.18/CHO (1)
- chaperones (1)
- chromoplexy (1)
- chromosomal translocations (1)
- chromosome conformation capture (1)
- chronic pancreatitis (1)
- chronotypes (1)
- cisplatin (1)
- climate elasticity (1)
- climate regime (1)
- climate sensitivity (1)
- climate signal age effects (1)
- climate variability (1)
- climate warming (1)
- climate-growth relationships (1)
- climate–growth relationships (1)
- cloud removal (1)
- cognition (1)
- cognitive control (1)
- colonization (1)
- combination assay (1)
- comorbidity (1)
- complement dependent cytotoxicity (1)
- composite ridges (1)
- computational fluid dynamics (1)
- concussion (1)
- corridor development strategies (1)
- coumarins (1)
- counterfactual analysis (1)
- criterial (1)
- cross-reactivity (1)
- cross-resistance (1)
- cross-tolerance (1)
- crystallized intelligence (1)
- cutaneous T-cell lymphoma (1)
- cyberbullying (1)
- damage-associated molecular patterns (1)
- deep sequencing (1)
- dehydroepiandrosterone (1)
- dendritic cells (1)
- diffusion tensor imaging (1)
- diffusion tractography (1)
- diffusion weighted imaging (1)
- digital elevation models (1)
- dual task (1)
- duckweed (1)
- ductal closure (1)
- ductal epithelium (1)
- early competencies (1)
- echocardiography (1)
- ecology (1)
- ecosystem dynamics (1)
- education (1)
- embodied cognition (1)
- embodiment (1)
- empathy (1)
- entry (1)
- environmental offsets (1)
- epidemiology (1)
- epilepsy (1)
- epileptic encephalopathies (1)
- epithelial fluid secretion (1)
- ethics of media use (1)
- ethics of shame (1)
- eutrophication (1)
- experimental pancreatitis (1)
- experimental plant ecology (1)
- expression (1)
- fagus sylvatica (1)
- fatty acids (1)
- fetal and adult neurogenesis (1)
- fisheries (1)
- flow tank (1)
- fluid intelligence (1)
- forest ecology (1)
- forest understory vegetation (1)
- free amino acids (1)
- fusion loops (1)
- gH/gL complex (1)
- genetic adaptation (1)
- genomics (1)
- genotyping (1)
- geometric morphometrics (1)
- gestural-verbal association (1)
- glacier skiing (1)
- glacitectonics (1)
- glioblastoma multiforme (1)
- global production networks (1)
- glutaredoxins (1)
- gradient-design field experiment (1)
- granuloma (1)
- greenfields (1)
- gross tumor volume optimization (1)
- habituation (1)
- health risk behaviors (1)
- healthcare (1)
- heat-shock proteins (1)
- heparin- and antibody-induced thrombocytopenia (1)
- heparins (1)
- herpesvirus (1)
- high-ability tracked students (1)
- high-frequency heart rate variability (1)
- homoarginine (1)
- host-symbiont (1)
- humanized mice (1)
- hybrid molecules (1)
- hydrazones (1)
- hydrological regimes (1)
- ibuprofen (1)
- image reconstruction (1)
- imagery (1)
- immune evasion (1)
- immunogenicity (1)
- impact mitigation regulation (1)
- implied volatility surface (1)
- in vitro anticancer activity (1)
- in vitro antitumor activity (1)
- inactivity (1)
- incidence (1)
- individual academic self-concept (SESSKO) (1)
- individual based (1)
- indoleamine 2,3-dioxygenase (1)
- indomethacin (1)
- infants (1)
- infection (1)
- inflammation (1)
- infrastructure (1)
- inner urban development (1)
- insurance claims (1)
- interactions (1)
- invasive (1)
- iodine deficiency disorders (1)
- iron surrogates (1)
- isoprenoid degradation (1)
- jep Gene (1)
- katalytische Aktivität (1)
- knowledge-is-power (1)
- kynurenine pathway (1)
- lake restoration. nutrient load reduction (1)
- land conversion (1)
- land use change (1)
- landcover reconstruction (1)
- language disorders (1)
- language processing (1)
- levetiracetam (1)
- light-sheet imaging (1)
- linear discriminant analyses (1)
- lipoprotein (1)
- lipoprotein profiling (1)
- locus coeruleus (1)
- long-term infusion (1)
- longitudinal (1)
- luciferase reporter gene assay (1)
- lung metastases (1)
- lymphocyte trafficking (1)
- mTHPC (1)
- mass spectrometry (1)
- mast cell (1)
- matrix metalloproteinase (1)
- maximum latewood density (1)
- mechanism (1)
- media education (1)
- medical assistants (1)
- membrane fusion (1)
- mental representations (1)
- mental rotation (1)
- mental transformations (1)
- metabolic interactions (1)
- metabolism (1)
- methyltryptophan (1)
- micro-site (1)
- mineral soil (1)
- mixed model (1)
- mode comparison (1)
- monoterpene (1)
- mortality (1)
- mouse model (1)
- mucosal immunity (1)
- mucus (1)
- multiphoton imaging (1)
- multitasking (1)
- myeloid-derived suppressor cells (1)
- myxomycetes (1)
- near-hand space (1)
- neuroactive steroids (1)
- neuroblastoma (1)
- neuropsychiatric diseases (1)
- night shift work (1)
- no-net-loss (1)
- non-small cell lung cancer (1)
- norepinephrine (1)
- oil palm plantation (1)
- optical imaging analyses (1)
- osmoregulation (1)
- osmotolerance (1)
- overfishing (1)
- overweight (1)
- oxaliplatin (1)
- oxidoreductase (1)
- pain (1)
- palynology (1)
- pancreas (1)
- patent ductus arteriosus (1)
- pediatric thrombosis (1)
- peptidases (1)
- peptide sharing (1)
- peripersonal space (1)
- peritoneal B cells (1)
- photodynamic therapy (1)
- physiological responses (1)
- phytosterols (1)
- pig (1)
- plant traits (1)
- plasticity (1)
- poaching (1)
- podocyte nephropathy (1)
- pollen accumulation rates (1)
- pollen productivity estimates (1)
- poly(hydroxyalkanoates) (1)
- polycrystalline gold (1)
- population-based (1)
- post-translational modifications (1)
- pregnenolone sulfate (1)
- preterm infant (1)
- prevalence (1)
- principal component analyses (1)
- production-integrated compensation (1)
- promoter (1)
- protection (1)
- protein (1)
- protein synthesis (1)
- proteins (1)
- psychological refractory period (PRP) (1)
- pyramidal tract integrity (1)
- quinolines (1)
- radical polishing (1)
- radiometric interpolation (1)
- reactivation (1)
- recruitment curve steepness (1)
- redox regulation (1)
- regime shift (1)
- rehabilitation (1)
- ring-opening reactions (1)
- rubber plantation (1)
- rule changes (1)
- salinity (1)
- salivary alpha-amylase (1)
- secondary plantmetabolites (1)
- seizure (1)
- self assembled monolayer (1)
- serial block-face scanning electron microscopy (SBFSEM) (1)
- serious adverse reaction (1)
- sex (1)
- sexting (1)
- smoking (1)
- snail (1)
- snow cover manipulation (1)
- social (1)
- social cognition (1)
- social interaction (1)
- soil organic carbon stock (1)
- solute carriers (1)
- spatial analysis (1)
- spatial cognition (1)
- spectral matching (1)
- sphingosine-1-phosphate (S1P) (1)
- starvation (1)
- statistical analysis (1)
- stereotactic body radiation therapy (1)
- stream ecology (1)
- stroke (1)
- structure (1)
- structured illumination microscopy (1)
- subacute stroke (1)
- summer skiing (1)
- superresolution microscopy (1)
- surface forces (1)
- symbiosis (1)
- synergism (1)
- synthesis (1)
- tVNS (1)
- temporal dynamics (1)
- temporal fitting (1)
- terahertz emission spectroscopy (1)
- terahertz transmission spectroscopy (1)
- thrombosis (1)
- tiling, self-similarity, fractal, aperiodic, iterated function system (1)
- toxin formation (1)
- training (1)
- transfusion (1)
- tree growth–climate correlation (1)
- tree size (1)
- tree-growth patterns (1)
- treeline (1)
- treeline ecotone (1)
- tropical forest conversion (1)
- tuberculosis (1)
- ultrafast spincaloritronics (1)
- ultrafast spintronics (1)
- upper limb motor function (1)
- urine normalization (1)
- vagus nerve (1)
- vegetation history (1)
- venous thromboembolism (1)
- vent (1)
- viral diagnosis (1)
- viral infections (1)
- virulence (1)
- vocational education and training (1)
- volatility (1)
- voxel-based morphometry (1)
- white spruce (1)
- winter ecology (1)
- women’s’ health (1)
- wood anatomy (1)
- β-amino acid (1)
- β-phenylalanine ethyl ester (1)
- ω-transaminase (1)
Institute
- Institut für Botanik und Landschaftsökologie & Botanischer Garten (15)
- Institut für Physik (10)
- Kliniken und Polikliniken für Innere Medizin (8)
- Abteilung für Mikrobiologie und Molekularbiologie (7)
- Institut für Biochemie (7)
- Institut für Community Medicine (7)
- Institut für Pharmazie (7)
- Institut für Diagnostische Radiologie und Neuroradiologie (6)
- Institut für Psychologie (6)
- Klinik und Poliklinik für Neurologie (6)
Publisher
- Frontiers Media S.A. (37)
- MDPI (37)
- S. Karger AG (16)
- De Gruyter (5)
- BioMed Central (BMC) (4)
- Akadémiai Kiadó (1)
- Hindawi (1)
- IOP Publishing (1)
- Nature Publishing Group (1)
- SAGE Publications (1)
Two decades of research indicate that visual processing is typically enhanced for items that are in the space near the hands (near-hand space). Enhanced attention and cognitive control have been thought to be responsible for the observed effects, amongst others. As accumulating experimental evidence and recent theories of dual-tasking suggest an involvement of cognitive control and attentional processes during dual tasking, dual-task performance may be modulated in the near-hand space. Therefore, we performed a series of three experiments that aimed to test if the near-hand space affects the shift between task-component processing in two visual-manual tasks. We applied a Psychological Refractory Period Paradigm (PRP) with varying stimulus-onset asynchrony (SOA) and manipulated stimulus-hand proximity by placing hands either on the side of a computer screen (near-hand condition) or on the lap (far-hand condition). In Experiment 1, Task 1 was a number categorization task (odd vs. even) and Task 2 was a letter categorization task (vowel vs. consonant). Stimulus presentation was spatially segregated with Stimulus 1 presented on the right side of the screen, appearing first and then Stimulus 2, presented on the left side of the screen, appearing second. In Experiment 2, we replaced Task 2 with a color categorization task (orange vs. blue). In Experiment 3, Stimulus 1 and Stimulus 2 were centrally presented as a single bivalent stimulus. The classic PRP effect was shown in all three experiments, with Task 2 performance declining at short SOA while Task 1 performance being relatively unaffected by task-overlap. In none of the three experiments did stimulus-hand proximity affect the size of the PRP effect. Our results indicate that the switching operation between two tasks in the PRP paradigm is neither optimized nor disturbed by being processed in near-hand space.
Ductal Mucus Obstruction and Reduced Fluid Secretion Are Early Defects in Chronic Pancreatitis
(2018)
Objective: Defective mucus production in the pancreas may be an important factor in the initiation and progression of chronic pancreatitis (CP), therefore we aimed to (i) investigate the qualitative and quantitative changes of mucus both in human CP and in an experimental pancreatitis model and (ii) to correlate the mucus phenotype with epithelial ion transport function.
Design: Utilizing human tissue samples and a murine model of cerulein induced CP we measured pancreatic ductal mucus content by morphometric analysis and the relative expression of different mucins in health and disease. Pancreatic fluid secretion in CP model was measured in vivo by magnetic resonance cholangiopancreatography (MRCP) and in vitro on cultured pancreatic ducts. Time-changes of ductal secretory function were correlated to those of the mucin production.
Results: We demonstrate increased mucus content in the small pancreatic ducts in CP. Secretory mucins MUC6 and MUC5B were upregulated in human, Muc6 in mouse CP. In vivo and in vitro fluid secretion was decreased in cerulein-induced CP. Analysis of time-course changes showed that impaired ductal ion transport is paralleled by increased Muc6 expression.
Conclusion: Mucus accumulation in the small ducts is a combined effect of mucus hypersecretion and epithelial fluid secretion defect, which may lead to ductal obstruction. These results suggest that imbalance of mucus homeostasis may have an important role in the early-phase development of CP, which may have novel diagnostic and therapeutic implications.
Optomechanical (om) systems are characterized by their nonlinear light-matter interaction. This is responsible for unique dynamic properties and allows the detection of a variety of classical and quantum mechanical phenomena on a microscopic as well as on a macroscopic scale. In this work we have studied the dynamic behavior of two laser-driven om systems, the single om cell ("cavity optomechanics / membrane-in-the-middle setup") and a two-dimensional hexagonal array of these cells ("om graphene"). The first case was motivated by the possibility to detect the transition from quantum mechanics to classical mechanics directly on the basis of the dynamic behavior. For this we focus on multistability effects of the optical and mechanical degrees of freedom, that are modeled by harmonic oscillators. Our description is based on the quantum optical master equation, which takes into account the environmental interaction assuming a vanishing temperature. As a consequence of decoherence, the dynamics occur near the semiclassical limit, i.e. it is characterized by quantum fluctuations. The quantum-to-classical transition is realized formally by rescaling the equations of motion. In the classical limit, quantum fluctuations disappear and the mean field equations were evaluated by analytical and numerical methods. We found that classical multistability is characterized by stationary signatures on the route to chaos, as well as by the coexistence of single-periodic orbits for the mechanical degree of freedom. The latter point was extensively evaluated by means of a self-consistent approach. For the dynamics in the quantum regime quantum fluctuations cannot be neglected. For this purpose, the master equation was solved by means of a numerical implementation of the Quantum State Diffusion (QSD) method. Based on Wigner and autocorrelation functions, we were able to show that quantum multistability is a dynamic effect: chaotic dynamics is suppressed and there is a time-dependent distribution of the phase space volume on classical simple-periodic orbits. The results can be interpreted within a semiclassical picture, which makes use of the single QSD quantum trajectory. Accordingly, the quantum-classical transition is explained as a time-scale effect, which is determined by tunneling probabilities in an effective mean-field potential. The subject of the second part of the work is the transport of low-energy Dirac quasiparticles in om graphene, propagating as light and sound waves. For this purpose, we investigated the scattering of a plane light wave by laser-induced photon-phonon coupling planar and circular barriers. The starting point is the om Dirac equation, which results from the continuum approximation of the Hamiltonian description of the two-dimensional array near the semiclassical limit. This work was motivated by the rich and interesting relativistic transport and tunneling phenomena found for electrons in graphene, which now appear in a new way. The reason is the presence of the new spin degree of freedom, which distinguishes the optical and mechanical excitations. In this spin space, the om interaction can be understood as a potential, which in our analysis consists of a time-independent and a time-dependent sinusoidal part. For the first case of a static barrier, the transport is elastic and is characterized by stationary scattering signatures. After solving the scattering problem via continuity conditions we were able to identify different scattering regimes depending on scattering parameters. In addition to relativistic phenomena such as Klein tunneling, simple parameter variation allows to use the barrier as a resonant light-sound interconverter and angle-dependent emitter. For the oscillating barrier, the transport is inelastic and is characterized by dynamic scattering signatures. To solve the time-periodic scattering problem, we have applied the Floquet theory for an effective two-level system. As a result of the barrier oscillation, photons and phonons can get and give away energy portions in the form of integer multiples of the oscillation frequency. The interference of short (classical) and long-wave (quantum) components leads to mixing of the scattering regimes. This allows to use the barrier as a time-periodic light-sound interconverter with interesting radiation characteristics. In addition, we have argued that the oscillating barrier provides the necessary energetic conditions for detecting zitterbewegung.
: An enhanced indoleamine 2,3-dioxygenase 1 (IDO1) activity is associated with an increased
mortality risk in sepsis patients. Thus, the preventive inhibition of IDO1 activity may be
a promising strategy to attenuate the severity of septic shock. 1-methyltryptophan (1-MT)
is currently in the interest of research due to its potential inhibitory effects on IDO1 and
immunomodulatory properties. The present study aims to investigate the protective and
immunomodulatory effects of 1-methyltryptophan against endotoxin-induced shock in a porcine
in vivo model. Effects of 1-MT were determined on lipopolysaccharide (LPS)-induced tryptophan
(TRP) degradation, immune response and sickness behaviour. 1-MT increased TRP and its metabolite
kynurenic acid (KYNA) in plasma and tissues, suppressed the LPS-induced maturation of neutrophils
and increased inactivity of the animals. 1-MT did not inhibit the LPS-induced degradation of TRP
to kynurenine (KYN)—a marker for IDO1 activity—although the increase in KYNA indicates that
degradation to one branch of the KYN pathway is facilitated. In conclusion, our findings provide
no evidence for IDO1 inhibition but reveal the side effects of 1-MT that may result from the proven
interference of KYNA and 1-MT with aryl hydrocarbon receptor signalling. These effects should be
considered for therapeutic applications of 1-MT.
Recent research suggests that the P3b may be closely related to the activation of the locus coeruleus-norepinephrine (LC-NE) system. To further study the potential association, we applied a novel technique, the non-invasive transcutaneous vagus nerve stimulation (tVNS), which is speculated to increase noradrenaline levels. Using a within-subject cross-over design, 20 healthy participants received continuous tVNS and sham stimulation on two consecutive days (stimulation counterbalanced across participants) while performing a visual oddball task. During stimulation, oval non-targets (standard), normal-head (easy) and rotated-head (difficult) targets, as well as novel stimuli (scenes) were presented. As an indirect marker of noradrenergic activation we also collected salivary alpha-amylase (sAA) before and after stimulation. Results showed larger P3b amplitudes for target, relative to standard stimuli, irrespective of stimulation condition. Exploratory post hoc analyses, however, revealed that, in comparison to standard stimuli, easy (but not difficult) targets produced larger P3b (but not P3a) amplitudes during active tVNS, compared to sham stimulation. For sAA levels, although main analyses did not show differential effects of stimulation, direct testing revealed that tVNS (but not sham stimulation) increased sAA levels after stimulation. Additionally, larger differences between tVNS and sham stimulation in P3b magnitudes for easy targets were associated with larger increase in sAA levels after tVNS, but not after sham stimulation. Despite preliminary evidence for a modulatory influence of tVNS on the P3b, which may be partly mediated by activation of the noradrenergic system, additional research in this field is clearly warranted. Future studies need to clarify whether tVNS also facilitates other processes, such as learning and memory, and whether tVNS can be used as therapeutic tool.
Objective: To evaluate the efficacy and tolerability of brivaracetam (BRV) in a severely drug refractory cohort of patients with epileptic encephalopathies (EE).
Method: A multicenter, retrospective cohort study recruiting all patients treated with EE who began treatment with BRV in an enrolling epilepsy center between 2016 and 2017.
Results: Forty-four patients (27 male [61%], mean age 29 years, range 6 to 62) were treated with BRV. The retention rate was 65% at 3 months, 52% at 6 months and 41% at 12 months. A mean retention time of 5 months resulted in a cumulative exposure to BRV of 310 months. Three patients were seizure free during the baseline. At 3 months, 20 (45%, 20/44 as per intention-to-treat analysis considering all patients that started BRV including three who were seizure free during baseline) were either seizure free (n = 4; 9%, three of them already seizure-free at baseline) or reported at least 25% (n = 4; 9%) or 50% (n = 12; 27%) reduction in seizures. An increase in seizure frequency was reported in two (5%) patients, while there was no change in the seizure frequency of the other patients. A 50% long-term responder rate was apparent in 19 patients (43%), with two (5%) free from seizures for more than six months and in nine patients (20%, with one [2 %] free from seizures) for more than 12 months. Treatment-emergent adverse events were predominantly of psychobehavioural nature and were observed in 16%.
Significance: In this retrospective analysis the rate of patients with a 50% seizure reduction under BRV proofed to be similar to those seen in regulatory trials for focal epilepsies. BRV appears to be safe and relatively well tolerated in EE and might be considered in patients with psychobehavioral adverse events while on levetiracetam.
Iodine deficiency disorders (IDD) result from insufficient iodine intake, and may lead to many adverse effects on growth, development and thyroid diseases in humans.
Pakistan is a country with history of iodine deficiency.
Before reunification both parts of Germany were iodine deficient. In the Eastern part, however, due to mandatory iodine prophylaxis adaptation in 1983, the iodine status of the population improved from moderate to mild iodine deficiency. After the reunification of Germany in 1989 “voluntary principle” was adopted leading again to a decrease in iodine intake. Germany and Pakistan present different socioeconomics, cultural values and adaptations to the IDD eradication but have resemblance in history of iodine deficiency. In the recent years Germany has improved in IDD eradication more than Pakistan. The purpose of this research was to study the regional influence on iodine nutritional status of pregnant women in Pakistan and to monitor the effectiveness of the iodine fortification programme in the North-East German population.
Pregnant women data was obtained from randomly selected (public and private) prenatal clinics in five districts of the KPK province of Pakistan. Women visited there for their routine checkup between March and September 2012. Data were obtained from almost 250 pregnant women from each district reaching to a total of 1260 in all five districts.
The SHIP project consists of two population-based cohorts, for which only individuals with German citizenship and main residency in the study area were recruited. In the first SHIP cohort; SHIP-0, individuals aged 20-79 years were selected from population registries by a two-stage cluster sampling method. The net sample (without migrated or deceased persons) comprised 6265 eligible subjects, of which 4308 (response 68.8%) participated between 1997 and 2001. A separate stratified random sample of 8826 adults aged 20-79 years was drawn for SHIP-Trend, of which 4420 subjects participated between 2008 and 2012 (response 50.1%) in SHIP-Trend-0.
All the pregnant women were asked to complete a short interview questionnaire containing the information related to sources and reasons for intake and non-intake of iodized salt. The questionnaire also comprised questions related to knowledge of iodized salt nutrition. Information on the number of previous pregnancies and/or abortions (fetal loss due to various reasons, not including voluntary termination of pregnancy) was also obtained. The gestational age of the pregnant women was determined from the first day of the last regular menstrual period with gestational ages of ≤14.9, 28.9, and ≥29 weeks comprising the first, second, and third trimesters of pregnancy, respectively. For goiter assessment in pregnant women the WHO/UNICEF/IGN recommended palpation method was used. UIC was measured using a modification of the Sandell-Kolthoff reaction with spectrophotometric detection. Evaluation of group iodine status was based on median UIC categories defined by the WHO/IGN. These are: recommended – median 150-249 μg/L; mild iodine deficiency – median <150 μg/L.
For the analysis of monitoring trends of thyroid diseases in SHIP, diagnosed thyroid disorders were assessed by computer-assisted personal interviews. Medication data were obtained online using the IDOM program (online drug-database leaded medication assessment) and classified according to the Anatomical-Therapeutic-Chemical (ATC) classification system.In SHIP population goiter assessment was based on thyroid volume determined with ultrasonography. Goiter was defined as a thyroid volume exceeding 18 mL in women and 25 mL in men. Urinary iodine concentrations were measured from spot urine samples by a photometric procedure. Urinary creatinine concentrations were determined with the Jaffé method. Evaluation of group iodine status was based on median UIC categories defined by the WHO/IGN. The iodine/creatinine ratio was calculated by dividing urinary iodine by urinary creatinine concentrations. Serum TSH, fT3, fT4 levels in SHIP study were measured by an immunochemiluminescent procedure. A method comparison between the two TSH laboratory methods showed only negligible differences. High and low serum TSH levels were based on the reference range established from data for SHIP-0 (0.25 mIU/L - 2.12 mIU/L) and SHIP-TREND-0 (0.49 mIU/L - 3.29 mIU/L) respectively (21,22). Anti-TPO Abs were measured by an enzyme immunoassay in the whole SHIP study. The anti-TPO Abs status was defined as follows: normal < 60 IU/ml in men and < 100 IU/ml in women; increased > 60 IU/ml in men and > 100 IU/ml in women; positive: > 200 IU/ml in both sexes.
Thyroid ultrasonography was performed in SHIP-0 using an ultrasound VST-Gateway with a 5 MHz linear array transducer. In SHIP-Trend-0 ultrasonography was performed with a portable device using a 13-MHz linear array transducer. In both studies intra- and inter-observer reliabilities were assessed before the start of the study and semi-annually during the study. For thyroid volume all inter-observer and inter-device variabilities showed mean differences (±2 SD)of < 5% (<25%). Thyroid volume was calculated as length x width x depth x 0.479 (ml) for each lobe (26). The normal thyroid echo pattern was classified as homogeneous. A homogeneous echo pattern with reduced echogenicity was defined as hypoechogenic. Nodular changes exceeding 10 mm in diameter were defined as thyroid nodules.
Multivariable logistic regression analysis adjusting for age was used to regress the outcome measures (knowledge about IDD, iodized salt intake, UIC <150mIU/L and goiter prevalence) on regional influences (as exposure) in each specific district. These results are presented as odd ratios and their 95% confidence interval.
For the analysis in SHIP, all analyses were standardized by base-weights to account for different sampling probabilities. In SHIP-Trend-0, additionally, inverse probability weights for study participation were calculated, which were multiplied with the base-weights. Differences in median levels between SHIP-0 and SHIP-Trend-0 were tested by median regression models; prevalence differences between SHIP-0 and SHIP-Trend-0 were tested by Poisson regression models.
The majority of pregnant women (88.0%) had no knowledge about IDD. A very high (79%) percentage of pregnant women were not taking iodized salt, out of which 36.6% reported that iodized salt would negatively affect reproduction and for 17.0%, it was too expensive. Iodized salt intake in pregnant women was high in the big cities (Peshawar, Nowshehra) and in the urban areas (27.0%)
In 41.3% of the pregnant women, we observed a UIC of >150mIU/L. The median UIC level for the pregnant women was 131µg/L. The total goiter prevalence in pregnant women was 25.5%. The prevalence of UIC <150mIU/L in pregnant women did not differ between rural and urban areas. The results based on logistic regression analysis shows that the prevalence on knowledge about IDD, iodized salt intake, UIC <150mIU/L, and goiter did not differ in pregnant women between urban and rural areas. In district Lakki Marwat except, the pregnant women from urban residence had higher odds of having knowledge on IDD and iodized salt intake than their rural counterparts.
The prevalence of diagnosed thyroid disorders increased from 7.6% [CI 6.9-8.5] in SHIP-0 to 18.9% [CI 17.6-20.1] in SHIP-Trend-0. Likewise, the prevalence of thyroid medication intake increased from 6.2% [CI 5.5-7.0] to 11.1% [CI 10.1-12.2]. The median urinary iodine excretion levels decreased significantly, which was more pronounced in females than in males. The median iodine-to-creatinine ratio declined in all sex- and age-groups with stronger decrease in females than in males. The prevalence of median urinary iodine excretion levels <100µg/L increased between SHIP-0 and SHIP-Trend-0. Median serum TSH levels increased significantly between SHIP-0 and SHIP-Trend-0, resulting in a right shift of the serum TSH level distribution. The prevalence of high serum TSH levels remained almost stable between SHIP-0 and SHIP-Trend-0. Likewise, the prevalence of low TSH remained almost stable between SHIP-0 and SHIP-Trend-0. The prevalence of increased anti-TPO Abs and positive anti-TPO Abs decreased from SHIP-0 to SHIP-Trend-0 in the whole study population. The prevalence of hypoechogenic thyroid pattern decreased from SHIP-0 to SHIP-Trend-0. The median thyroid volume remained similar between SHIP-0 and SHIP-Trend-0 in the whole study population. Goiter prevalence decreased significantly; more pronounced in males than in females, while the prevalence of thyroid nodules increased between SHIP-0 and SHIP-Trend-0.
In pregnant women in Pakistan due to insufficient awareness campaigns and low literacy ratio in rural areas urinary iodine excretion levels indicate a stable iodine supply, which is still not sufficient. Our results show that rural/urban disparity is affecting the IDD prevention program in rural districts, but not in general. The SHIP data indicate that the improved iodine supply over the past two decades in Germany is paralleled by a reduction in prevalence of IDDs, while no increase was observed in markers of autoimmune thyroid disorders arguing for an optimal iodine supply of the general adult population in Northeast Germany. The increase in prevalence of diagnosed thyroid disorders and the intake of thyroid medication might be because of inappropriate therapeutical decisions which should be made with caution, based on regional TSH reference ranges, its prognostic value, and compliance with treatment.
The platinum(II) complexes carboplatin (CBDCA), cisplatin (CDDP) and oxaliplatin
(1-OHP) are used as anticancer drugs in a large number of tumour chemotherapy regimens.
Many attempts have been made to combine Pt(II)-based chemotherapy with alternative treatment
strategies. One such alternative anticancer approach is known as photodynamic therapy (PDT),
where a non-toxic photosensitizer (PS) produces oxidative stress via the formation of reactive
oxygen species (ROS) after local illumination of the affected tissue. A very promising PS is
5,10,15,20-tetra(m-hydroxyphenyl)chlorin (mTHPC, Temoporfin), which is approved for the treatment
of head and neck cancer in Europe. In the present study, a combination of mTHPC-mediated PDT
and either CBDCA, CDDP, or 1-OHP was applied to five human cancer cell lines from different
tumour origins. Cytotoxicity was determined by the MTT assay and synergistic effects on cytotoxicity
were evaluated by calculation of Combination Indices (CI). Synergy was identified in some of the
combinations, for example, with 1-OHP in three of the tested cell lines but antagonism was also
observed for a number of combinations in certain cell lines. In cases of synergy, elevated ROS levels
were observed after combination but apoptosis induction was not necessarily increased compared
to a treatment with a single compound. Cell cycle analysis revealed a formation of apoptotic
subG1 populations and S phase as well as G2/M phase arrests after combination. In conclusion,
pre-treatment with mTHPC-PDT has the potential to sensitize some types of tumour cells towards
Pt(II) complexes, in particular 1-OHP but synergy is highly dependent on the type of cancer.
Most animals live solitarily, but for some species the benefits of group living outweigh the costs and social communities have evolved. Truly social societies are characterized by cooperation in tasks like foraging, predator defense and brood care. In the most extreme cases, non-reproducing individuals act as helpers and provision offspring of reproducing individuals at the cost of their own reproductive success. This alloparental care is attributed to kin selection that provides the helpers with inclusive fitness benefits. However, how reproductive role is determined and in which ways virgin helpers in a group benefit the community is not always well understood.
Spiders are known to be generalist hunters, which in many cases do not shy away from cannibalism. Thus, most spiders live solitarily. However, in a few species a permanently social lifestyle has evolved in which individuals live together throughout their life, providing an intriguing case of social evolution. These spider communities are characterized by lack of premating dispersal leading to extreme inbreeding, by reproductive skew, in which only a proportion of females reproduce and by cooperative breeding of the reproducing females. It has been assumed that the large proportion of virgin females act as helpers not only in foraging and web maintenance but also during brood care. In the social spider Stegodyphus dumicola brood care involves the intensive task of regurgitation feeding, at which mothers regurgitate their own liquefied body tissue. At the end of brood care, the offspring sucks the mothers dry during matriphagy, leading to the death of brood caring females and a semelparous lifestyle. In the closely related solitarily breeding Stegodyphus lineatus virgin females do not provide brood care. The ability of virgin females in S. dumicola to care for offspring would thus depict an adaptation to sociality and cooperative breeding. I therefore aimed to clarify the role and significance of virgin females in colonies of social spiders and furthermore investigated a possible mechanism of how reproductive role within a colony is determined.
I investigated whether there is differential task participation in a non-reproductive task and the task of brood care among reproducing mothers and virgin females (helpers) in Stegodyphus dumicola. The study provides explicit evidence that brood care – including egg sac care, regurgitation feeding and matriphagy – is performed by mothers as well as by virgin helpers. Virgin females in a colony can thus rightfully be termed allomothers. However, the task participation differed between the reproductive states. While mothers engaged more often in brood care, virgin females were more active in foraging. However, the active provisioning of offspring by the virgin females decreases the motherly workload as is suggested by the extended brood care period in comparison to solitary breeders. The observations on virgin allomaternal care are supported by histological studies on the midgut tissue of brood caring females, which revealed that mothers and virgin helpers undergo comparable morphological changes in preparation of regurgitation feeding. The changes in virgin females correlate to ovarian development that might depict an internal maturation process which sets virgin females in the right state to provide care. The morphological changes in mothers and virgin helpers of S. dumicola are less comprehensive than in the solitarily breeding S. lineatus mothers. This indicates that cooperatively caring females are able to save on their resources, provision offspring for longer and thus are probably able to increase survival of the brood by an extended care period. A surprising consequence of cooperative brood care is the ability of mothers to produce a second viable egg sac, even when the first brood is successful. Mothers of the cooperative breeding S. dumicola can thus depart from the strictly semelparous lifestyle and instead invest part of their resources in a second clutch. This finding identified a new way of how cooperative breeding enhances breeding success of reproducers and thus inclusive fitness for helpers as well, thus adding to the benefits of allomaternal care.
Virgin females did not store significantly lower amounts of lipids in their midgut tissue than mothers, raising the question of how much reproductive role of females is determined by competition for resources during growth, as often assumed. Another possible determinant of female reproductive skew is the characteristic male scarcity in spider colonies, with only about 12 percent of spiders being male. Males are assumed to mature early within a few days and die early, thus leaving late maturing females unmated due to lack of mating partners. However, my studies provided evidence that male maturation is more skewed than expected and males might survive several months. Subadult females did not accelerate molting when an adult male was present, which could further indicate, that male presence is not a limiting factor on reproduction in males. Furthermore, males are able copulate with up to 16 females and did not show e preference for large females during mating trials. Males are thus able to fertilize all females, provided all females mature in time. I therefore suggest, that male scarcity is not major determinant of reproductive skew in females, especially in small and middle-sized colonies in which female maturation might only be moderately skewed.
My studies were able to demonstrate the meaning of the large proportion of unmated females in a colony of the social spider S. dumicola. Virgin helpers support mothers during brood care and thus do not only enhance the brood care period but facilitate mothers to produce multiple clutches. Virgin females are able to care as they undergo similar morphological changes as mothers’ do. This seems to be facilitated by an internal maturation process, indicated by ovarian development and oviposition by virgin females, both of which has never been observed in virgins of the subsocial species. How reproductive role is determined remains unclear, but I was able to exclude male scarcity as a major factor influencing reproductive skew.
Myxomycetes are protists belonging to the super-group Amoebozoa. The traditional taxonomic system, which is now largely outdated by molecular studies, recognizes five orders: Liceales, Trichiales, Physarales, Stemonitales and Echinosteliales. Molecular phylogenies revealed two basal clades: Physarales and Stemonitales (the so-called dark-spored myxomycetes) are the first; the other above-mentioned orders form the second (the bright-spored myxomycetes). However, except for Echinosteliales none of the traditional orders appears to be monophyletic in the traditionally used delimitation. The dark-spored myxomycetes encompass the majority of the described morphospecies. Due to the high genetic divergence in DNA sequences between the bright- and dark-spored myxomycetes, only the latter are considered in this dissertation. Historically myxomycetes have been described as fungi, due to their macroscopically visible fructifications which, though considerably smaller, resemble those of fungi. These fruit bodies provide enough morphological traits to support a morphological species concept with currently ca. 1000 species described. Therefore diversity studies of myxomycetes have been conducted for over 200 years and a substantial body of data on ecology and distribution of these fructifications exist. From these studies myxomycetes are known to form often distinct communities across terrestrial ecosystems with highly specific habitat requirements, such as snowbanks (nivicolous), herbivore dung (coprophilous) or decaying wood (xylophilous). However knowledge on the myxamoebae – the trophic life stage of the myxomycetes – is very scarce. Only recent advances in molecular techniques such as direct species identification based on DNA sequences from environmental samples (ePCR), have made studies of myxamoebae (and other microbes) possible. From these first molecular based studies myxomycetes are currently estimated to account for between 5 to almost 50% of all soil amoebae, and have been shown to be present in a wide variety of soils. To fully take advantage of these new methods, a molecular DNA marker needs to be established as well as a reference sequence database. The usability of a DNA marker gene depends on its ability to separate species by a distinction between intra- and interspecific divergence between sequences of the same and related species, the so-called ‘barcoding gap’.
The first part of this thesis (article I and II) deals with the subject of establishing such a DNA marker and database, and in doing so touches upon the subject of ‘what is a myxomycetes species?’
A total of 1 200 specimens were compiled into a reference database (the largest database to date of dark-spored myxomycetes). The genetic distance from sequence-to-sequence was used to assess genetic clade structures within morphospecies and putative biospecies (sexually isolated linages) were identified. The result was an estimate of hidden diversity, exceeding that of described morphospecies by 99%. The optimum sequence similarity threshold for OTU-picking (genetic species differentiation, denoted Operational Taxonomic Unit) with the used SSU marker was identified as 99.1% similarity.
The second part of this thesis (article III and IV) presents ecological studies conducted with NGS (ePCR) in which the established threshold and database are applied and are demonstrated to provide reliable and novel insights into the soil myxamoebae community. It is investigated whether the occurrence of fruit bodies reflects the distribution of soil myxamoebae, and the research questions ‘do myxomycetes show broader realized niches as soil amoebae than as fructifications?’ and ‘are myxamoebae distributions correlated to potential prey organisms (fungi and bacteria)?’ are investigated.
In the ecological study presented in article III parallel metabarcoding of bacteria, fungi and dark-spored myxomycete was used for the first time in a joint approach to analyze the communities from an elevational transect in the northern limestone German Alps (48 soil samples). Illumina sequencing of the soil samples revealed 1.68 Mio sequences of a section of the rRNA gene, which were assigned to 578 operational taxonomic units (OTU) from myxomycetes. These show a high similarity (>98%) to 42 different morphospecies (the respective figures for bacteria and fungi were 2.16/5710/215 and 3.68/6133/260, respectively). Multivariate analyses were carried out to disentangle microbial interplay and to identify the main environmental parameters determining the distribution of myxamoebae and thus setting the boundaries for their ecological niches. Potential interactions between the three target organisms were analysed by integrating community composition and phylogenetic diversity with environmental parameters. We identified niche differentiation for all three communities (bacteria, fungi and myxamoebae) which was strongly driven by the vegetation. Bacteria and fungi displayed similar community responses, driven by symbiont species and plant substrate quality. Myxamoebae showed a more patchy distribution, though still clearly stratified among genera, which seemed to be a response to both structural properties of the habitat and specific bacterial taxa. In addition we find an altitudinal species turn-over for all three communities, most likely explained by adaptation to harsh environmental conditions. Finally a high number of myxomycetes OTUs (associated with the genus Lamproderma) not currently represented in our reference database were found, representing potentially novel species. This study is the first to report niche differentiation between the guild of nivicolous (“snowbank”) myxomycetes and thus fine-scale niche differentiation among a predatory soil protist; identifying both potential food preferences and antagonistic interactions with specific bacterial taxa.
Finally, the second ecological study (article IV) focuses on comparing the distribution of myxamoebae revealed by ePCR of soil samples with fructifications collected from the same area (714 specimens determined to 30 morphospecies, which form 70 unique ribotypes that can be assigned to 45 ribotype clusters using a 99.1% similarity threshold). The study found a strong coherency between the two inventories, though with species specific relative differences in abundance, which can in part be attributed to the visibility of the fructifications. In addition, a year to year comparison of fructification records gives support to the hypothesis that the abundance of fructifications depends strongly on the onset of snowfall in the previous autumn and the soil temperature regime throughout the winter.
In the current era of anthropogenic climate change is the long-term survival of all organisms dependent on their ability to respond to changing environmental conditions either by (1) phenotypic plasticity, which allows species to tolerate novel conditions, (2) genetic adaptation, or (3) dispersal to more suitable habitats. The third option, dispersal, allows individuals to escape unfavorable conditions, the colonization of new areas (resulting in range shifts), and affects patterns of local adaptation. It is a complex process serving different functions and involving a variety of underlying mechanisms, but its multi-causality though has been fully appreciated in recent years only. Thus, the aim of this doctoral thesis was to disentangle the relative importance of the multiple factors relevant to dispersal in the copper butterfly Lycaena tityrus, including the individual condition (e.g. morphology, physiology, behavior) and the environmental context (e.g. habitat quality, weather). L. tityrus is a currently northward expanding species, which makes it particularly interesting to investigate traits underlying dispersal. In the first experiment, the influence of weather and sex on movement patterns under natural conditions was investigated. Using the Metatron, a unique experimental platform consisting of interconnected habitat patches, the second experiment aimed to examine the influence of environmental factors (resources, sun) on emigration propensity in experimental metapopulations. Human-induced global change (e.g. climate change, agricultural intensification) poses a substantial challenge to many herbivores due to a reduced availability or quality of feeding resources. Therefore, in the third experiment, the impact of larval and adult food stress on traits related to dispersal ability was investigated. Additionally, the effect of different ambient temperatures was tested. In the fourth experiment, core (Germany) and recently established edge (Estonia) populations were compared in order to explore variation in dispersal ability and life history traits indicative of local adaptation. Dispersal is often related to flight performance, and morphological and physiological traits, which was investigated in experiments 2-4. Butterflies were additionally subjected to behavioral experiments testing for the individual’s exploratory behavior (experiments 3 and 4).
Males and females differed substantially in morphology, with males showing traits typically associated with a better flight performance, which most likely result from selection on males for an increased flight ability to succeed in aerial combats with rivalling males and competition for females. This pattern could be verified by mobility measures under natural conditions and flight performance tests. Interestingly, although females showed traits associated with diminished flight performance, they had a higher emigration propensity than males (though in a context dependent manner). Reasons might be the capability of single mated females to found new populations, to spread their eggs over a wide range or to escape male harassment. Conditions indicative of poor habitat quality such as shade and a lack of resources promoted emigration propensity. The environmental context also affected condition and flight performance. The presence of resources increased the butterflies’ condition and flight performance. Larval and adult food stress in turn diminished flight performance, despite some reallocation of somatic resources in favor of dispersal-related traits. These detrimental effects seem to be mainly caused by reductions in body mass and storage reserves. A similar pattern was found for exploratory behavior. Furthermore, higher temperatures increased flight performance and mobility in the field, demonstrating the strong dependence of flight, and thus likely dispersal, on environmental conditions. Flight performance and exploratory behavior were positively correlated, probably indicating the existence of a dispersal syndrome. The population comparison revealed several differences between edge and core populations indicative of local adaptation and an enhanced dispersal ability in edge populations. For instance, edge populations were characterized by shorter development times, smaller size, and a higher sensitivity to high temperatures, which seem to reflect adaptations to the cooler Estonian climate and a shorter vegetation period. Moreover, Estonian individuals had an enhanced exploratory behavior, which can be advantageous in all steps of the dispersal process and may have facilitated the current range expansion.
In summary, these findings may have important implications for dispersal in natural environments, which should be considered when trying to forecast future species distributions. First, dispersal in this butterfly seems to be a highly plastic, context-dependent trait triggered largely by habitat quality rather than by individual condition. This suggests that dispersal in L. tityrus is not random, but an active process. Second, fast development and an enhanced exploratory behavior seem to facilitate the current range expansion. But third, while deteriorating habitat conditions are expected to promote dispersal, they may at the same time impair flight ability (as well as exploratory
behavior) and thereby likely dispersal rates. For a complete understanding of a complex process such as dispersal, further research is required.
Functional characterization of a novel protease isolated from a mouse-adapted S. aureus strain
(2018)
Background: The high incidence of methicillin-resistant Staphylococcus aureus
(MRSA) strengthens the need for new effective antibiotics and a protective vaccine. Up till now, mainly human-adapted Staphylococcus aureus strains were used to study S. aureus pathogenicity in mouse models. However, it is known that S. aureus is highly host-specific. Recently, a mouse-adapted S. aureus strain, JSNZ, was identified. This strain could be a promising tool in developing more appropriate infection models. JSNZ produces high amounts of a putative extracellular protease, named JSNZ extracellular protease (Jep). Since the jep gene was only detected in S. aureus isolates from laboratory mice and wild small rodents and shrews, we hypothesize that Jep is important for colonization and infection in mice. The jep deletion mutant previously created by our collaborators from the University of Auckland, New Zealand, intriguingly showed a reduced survival and growth fitness in murine serum and whole blood as compared to the JSNZ wild type (WT) strain.
Objective: To elucidate the role of Jep in the interaction between S. aureus and its
host by comparing the impact of JSNZ WT with a mutant and a complement strain on the murine immune system. In addition, the elucidation of possible genetic factors behind host-adaptation of S. aureus strains isolated from wild rodents and shrews.
Methods: A jep complemented strain was generated by chromosomal replacement.
JSNZ WT, the jep mutant and the complement strain were subjected to functional
assays (whole blood survival assay, coagulation assay). In addition, the genetic
background that might confer host specificity was tested by staph array genotyping.
Results: The mutant strain JSNZDjep was successfully complemented with the jep
gene using a chromosomal integration approach. The WT strain and the
complemented strain produced the Jep protein in comparable amounts.
Unexpectedly, the complemented strains did not behave like the WT strain but rather like the mutant in a series of in vitro assays. Firstly, the growth of both the deletion mutant and the complemented strains was slightly reduced in TSB as compared to the WT strain. Secondly, the jep knockout strain showed a strongly reduced survival in murine whole blood compared to its wild type counterpart, but so did the complemented strain. Finally, the coagulation of murine plasma was less pronounced for the jep deletion mutant and the complemented strain as compared to the JSNZ WT. To exclude a defect in jep gene expression, we compared the amount of Jep expressed during growth in TSB medium for the three strains. The complemented strain produced Jep in a manner similar to the WT strain in a growth-phase dependent manner, suggesting that Jep expression was not affected during the creation of the complemented strain.
The array data showed some differences in the genetic makeup between animal
isolated strains and matched human strains. For example, while all animal isolates of the CC88 lacked the resistance mecA gene it was found in some human isolates of the same strain.
Conclusion: In conclusion, our unidentified mutation created during the generation
of the jep knock-out strain rather than the jep gene itself manipulated the murine
immune response. The responsible gene and the underlying mechanisms remain to
be clarified. Genetic profiling of S. aureus strains allowed us to obtain some valuable information including data about CC49, the most frequently isolated lineage in wild rodents and shrews where compared to the human isolates the murine strains showed clear signs of host adaptation. However, the analysis had several limitations including the small sample size.
Class I and class II glutaredoxins (Grxs) are glutathione (GSH)-dependent proteins, that function as oxidoreductases (class I) or mediate cellular iron trafficking (class II). Some members of class I Grxs like human Grx2 are able to complex a [2Fe-2S] cluster and form a dimeric holo complex, which renders them catalytically inactive and is the basis for their function as redox sensors. Class II Grxs like human Grx5 also complex [2Fe-2S] clusters, however these proteins transfer the clusters to other proteins. Both functionally distinct classes share a similar thioredoxin fold and conserved interaction sites for the non-covalently binding of GSH, which is required to complex the [2Fe-2S] cluster. Furthermore, the proteins from both classes contain a highly nucleophilic active site cysteine that would allow both classes to catalyze GSH-dependent oxidoreduction reactions. Despite of these similar features, only class I Grxs are able to form a mixed disulfide with GSH and to reversibly transfer it to protein thiols (de-/glutathionylation). Interestingly, neither class I Grxs nor class II Grxs can effectively compensate the loss of an essential member of the other class. Even though some structural differences were described earlier, the basis for their different functions remained unknown. In particular, the lack of catalytic activity of class II Grxs as oxidoreductases could not be explained. Here, we demonstrate that the different conformations of a conserved lysyl side chain are the molecular determinant of the oxidoreductase or Fe-S transfer activity of class I and II Grxs, respectively. A specific loop structure that is conserved in all class II Grxs determines one lysyl conformation that prevents the formation of a mixed disulfide of the active site cysteinyl thiol with GSH. Using engineered mutants of hGrx2 and hGrx5, we demonstrated that the exchange of the distinct loop between the classes results in a loss of oxidoreductase function of class I hGrx2 and the gain of oxidoreductase activity of class II hGrx5. The altered GSH binding mode also profoundly changes the [2Fe-2S] cluster binding of the engineered mutants and thereby also influences stability of the holo complexes, a pre-determinant for [Fe-S] cluster transfer activity. With the minor shift of 2 Å in a conserved lysyl side chain orientation we were not only able to modify the catalytic activity of two small human mitochondrial proteins, but on a much larger scale also provided evidence for the previously unknown structural basis that determines the function of all class I and class II Grxs.
The oxidoreductase activity of hGrx2 was also analyzed in vivo in a model of doxorubicin cell toxicity. Applying a mass spectrometrical approach, we identified various mitochondrial proteins as targets for redox regulation. Furthermore, our results gave reason to reconsider some common assumptions regarding doxorubicin-induced apoptosis and the protective function of mitochondrial Grx2.
Background and Aims: Gastrointestinal stromal tumors (GISTs) are rare malignancies but the most common mesenchymal tumors of the digestive tract. Recent advances in diagnostic imaging and an increasing incidence will confront us more frequently with stromal tumors. This single center study aimed to characterize GIST patients in terms of tumor location, clinical presentation, metastasis formation, as well as associated secondary malignancies. Methods: In a retrospective study, 104 patients with a histologically confirmed diagnosis of GIST, collected between 1993 and 2011, were characterized for several clinical features. Results: The most common GIST location was the stomach (67.6%) followed by the small intestine (16.2%). Gastrointestinal bleeding (55.8%) and abdominal pain (38.5%) were the most frequently reported symptoms whereas about one-third of patients remained clinically asymptomatic (31.6%); 14.4% of patients had either synchronous or metachronous metastases and there was a significant prevalence also in the low risk group. The proportion of secondary malignant associated neoplasms was 31% in our GIST cohort, among which gastrointestinal, genitourinary tumors, and breast cancer were the most prevalent. Conclusion: There was a considerable risk for metastasis formation and the development of secondary neoplasias that should encourage discussion about the appropriate surveillance strategy after surgery for GIST.
Because Moringa is rich in secondary metabolites and phenolics, we faced a challenge in extracting a pure DNA required for AFLP (the first proposed genotyping method). Later, different DNA isolation methods were tested to overcome the obstacles caused by phenolics and sugars, an AFLP protocol that worked well with the cultivated seedlings at the botanical garden in Greifswald. The markers for the Internal Transcribed Spacer (ITS) were as well tested that showed a monomorphic structure between all samples. Finally, SSR (microsatellite) markers were established. To optimize DNA extraction, the method of Doyle and Doyle was modified and optimized. This is an ideal method for obtaining a non-fragmented DNA that could be used for AFLP. In addition, two other DNA extraction methods; (KingFisher Flex robot using Omega M1130 extraction Kits, and spin columns and 96-plates using Stratec kits). Although we achieved similar results for both Robot kits (Omega) and Stratec kits, the amplification for most of the samples extracted with Robot did not work, therefore the Stratec kit was the method of choice as it has also a lower cost, combined with a high quality of DNA. For ITS, no polymorphism was found for 28 samples of M. peregrina from Sinai (sequences submitted to GenBank). However, since microsatellite markers of M. peregrina were not known, it was a challenge to try a cross amplification from other species with well-known microsatellite primers. Cross-amplification of 16 primers known from the related species M. oleifera was tested, and three multiplex PCR reactions were established after testing different annealing temperatures and different primers concentrations. This included 13 primers out of the 16 investigated markers which gave a reliable band. All methods used for genetic assessments for the different Moringa species are compiled in a comparative review to look for connections between the different Moringa species. For Moringaceae, M. oleifera and M. peregrina are closely related to each other. Both species have slender trunks, with thick, tough bark and tough roots and bilaterally symmetrical flowers with a short hypanthium. All but one SSR markers used in this study are highly informative However, the degree of polymorphy varied considerably within the 13 markers used. The Probability of Identity (PI) for all loci was 2.6 x 10-9 with high resolution. The percentage of polymorphic loci for all populations was 88.5±2.2; figures for single populations were 92.3%, 84.6%, 84.6%, and 92.3% for the wadis WM, WA, WF, and WZ, respectively. The genotype accumulation curve as well demonstrated that 7–8 markers were necessary to discriminate between 100% of the multilocus genotypes. Significant departures from HWE were detected for eight loci (P < 0.001), probably due a high degree of inbreeding within population. The observed (HO) and expected (HE) heterozygosities ranged from 0 to 0.86 and from 0 to 0.81, respectively. However, for the pooled population, excluding the monomorphic locus MO41, HO and HE ranged from 0.069 to 0.742 and from 0.126 to 0.73 with averages of 0.423 and 0.469, respectively. The mean of FST was 0.133, indicating that, due to the long generation time of M. peregrina, there is still relatively little differentiation between the four remaining populations. An analysis of molecular variance (AMOVA) revealed that the old populations of M. peregrina are still genetically diverse where 75% of variance was recorded within individuals and 83% within populations. An analysis with STRUCTURE, varying the parameter K between 1 and 7, revealed the most pronounced genetic structure for K=3, thus uniting the populations from two neighboured wadis (W. Agala and W. Feiran). The three groups seem to be now genetically isolated. (They may be remainders of a formerly contiguous population, especially when considering the change towards a drier climate in Northern Africa within the last 6000 years). Six clones of each two individuals collected from the same wadi were found, pointing to vegetative dispersal via broken twigs, which may have rooted after flash floods. It may be an alternative mode of reproduction under harsh conditions. Our data reveal a low gene flow between three of the four wadis, suggesting that the trees are relictual populations. In general, conservation of populations from the three genetically most diverse wadis and cross-breeding of trees within a reforestation program is recommended as an effective strategy to ensure the survival of M. peregrina at Sinai, Egypt.