Refine
Year of publication
- 2018 (250) (remove)
Document Type
- Doctoral Thesis (141)
- Article (108)
- Report (1)
Language
- English (152)
- German (97)
- Multiple languages (1)
Has Fulltext
- yes (250)
Is part of the Bibliography
- no (250)
Keywords
- - (90)
- Staphylococcus aureus (5)
- Depression (4)
- climate change (4)
- Mecklenburg-Vorpommern (3)
- SHIP (3)
- Sepsis (3)
- Simulation (3)
- Study of Health in Pomerania (3)
- 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)
- Digitale Volumentomographie (2)
- Epidemiologie (2)
- Fettsucht (2)
- Flavivirus (2)
- Fournier’s gangrene (2)
- GWAS (2)
- Germany (2)
- Hyperbaric oxygenation (2)
- Kernspintomografie (2)
- Klimawandel (2)
- Magen (2)
- Morphologic changes (2)
- Necrotizing fasciitis (2)
- Necrotomy (2)
- Obesity (2)
- Oxidoreduktase (2)
- Plasma (2)
- Plasmaphysik (2)
- Proteine (2)
- Pyelonephritis (2)
- Sepsis score (2)
- Small animal MRI (2)
- Soft tissue infection (2)
- Spiroergometrie (2)
- Streptococcus pneumoniae (2)
- Systematic review (2)
- Therapy (2)
- Tollwut (2)
- Urinary tract infection (2)
- Uterus (2)
- Verhalten (2)
- Vitamin D (2)
- Wirkstofffreisetzung (2)
- Wundheilung (2)
- antibiotics (2)
- antimicrobial peptides (2)
- ascariasis (2)
- bias (2)
- biofilm (2)
- causal inference (2)
- dendroecology (2)
- environment (2)
- epidemiology (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)
- 1999-2009 (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)
- 3D-Druck (1)
- 4015016-1 (1)
- 4042270-7 (1)
- 4042278-1 (1)
- 4049722-7 (1)
- 4121138-8 (1)
- 4121944-2 (1)
- 4137913-5 (1)
- 4165547-3 (1)
- 4175999-0 (1)
- 4185874-8 (1)
- 4188802-9 (1)
- 4216345-6 (1)
- 4251573-7 (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)
- AMC DCBA (1)
- AQT90 FLEX (1)
- ATP-binding cassette transporters (1)
- Acne inversa (1)
- Adaptation (1)
- Adenosarkom (1)
- Aerobe Leistungsfähigkeit (1)
- Africa (1)
- African swine fever virus (1)
- Afrikanische Schweinepest Virus (1)
- Afrikanisches Schweinepest-Virus (1)
- Aggravation (1)
- Akne inversa (1)
- Alaska (1)
- Alfvén Waves (1)
- Allgemeinbevölkerung (1)
- Alpha-Winkel (1)
- Amymetacresol (1)
- Anatomie (1)
- Angiogenese (1)
- Angiopoietine (1)
- Angiotensin-(1-7) (1)
- Animal behavior (1)
- Annual rings (1)
- Anthropometrie (1)
- Antibiotika (1)
- Antibiotikum (1)
- Antioxidans (1)
- Antisense-Transkription (1)
- Anxiety sensitivity (1)
- Aorta (1)
- Aortenwanddicke (1)
- Apolipoprotein E (1)
- Arbovirus (1)
- Architektur (1)
- Arsen (1)
- Arzneistofftransporter (1)
- Asymmetric synthesis (1)
- Atherosklerose (1)
- Aufbereitung (1)
- Aufbissschiene (1)
- Austria (1)
- B cell class switch (1)
- B1 B cells (1)
- Bathymodiolus (1)
- Bathymodiolus symbiosis (1)
- Bauchspeicheldrüse (1)
- Bauleitplanung (1)
- Baumgrenze (1)
- Baurecht (1)
- Bayley scales (1)
- Befragung (1)
- Belastungshypertonus (1)
- Benign breast tumours (1)
- Beringung (1)
- Berufsausbildung (1)
- Bicyclomycin (1)
- Bildqualität (1)
- Biochemie (1)
- Biodiesel (1)
- Biokatalyse , Organische Synthese , Enzym , Prozessoptimierung (1)
- Biomathematik , Bioinformatik (1)
- Biopharmazie (1)
- Biorelevante Wirkstofffreisetzung (1)
- Biosphärenreservat (1)
- Blue Intensity (1)
- Bodentemperatur (1)
- Bronchialkarzinom (1)
- Bronchopulmonary dysplasia (1)
- Brust MRT (1)
- Buche (1)
- CA–Markov (1)
- CCD-Winkel (1)
- CD40L (1)
- CD8+ T-Zellantwort (1)
- CFTR Cl (1)
- CKD (1)
- CM-Wire (1)
- CPET (1)
- CRMP2 (1)
- Canalis (1)
- Canalis nasolacrimalis (1)
- Candida albicans (1)
- Capillary blood glucose; Diabetes mellitus; Glucose concentration measurement; Impaired glucose tolerance; Oral glucose tolerance test; OGTT; Point-of-care-testing; POCT; Plasma-referenced blood glucose; Unit use (1)
- Cardiopulmonary bypass (1)
- Center-Edge Winkel (1)
- Cerebral Palsy Kinder (1)
- Cerebral cavernous malformations (1)
- Chemo-enzymatic synthesis (1)
- Chinin (1)
- Chiral amines (1)
- Civil conflicts (1)
- Clade Annotation (1)
- Claudicatio spinalis (1)
- Climate Change (1)
- ClinROM, Clinician reported outcome measures (1)
- Clusteranalyse (1)
- Cochlea-Implantat (1)
- Cochrane–Orcutt procedure (1)
- Cold Atmospheric Pressure Plasma (1)
- Collisions (1)
- Comparative Gene Finding (1)
- Comparative Genomics (1)
- Cowpox virus (1)
- Craniomandibuläre Dysfunktion (1)
- Cronbach's alpha (1)
- CyberKnife robotic radiosurgery (1)
- Cybermobbing (1)
- Cystatin C (1)
- Cytochrome P-450 (1)
- DHEAS (1)
- DIN-Norm (1)
- DISQOVER (1)
- DLX proteins (1)
- DNA-microarray (1)
- Dach1 (1)
- Dark Blood Sequenz (1)
- Darm (1)
- Darstellung (1)
- Deep-sea hydrothermal vents (1)
- Democracy (1)
- Demokratie (1)
- Dendrochronologie (1)
- Depressivität (1)
- Dermatochirurgie (1)
- Desinfektion (1)
- Deutschland (1)
- Deutschland <DDR> (1)
- Diabetes mellitus , Blutzucker , Messgerät , Kapillarblut , Messgenauigkeit (1)
- Diagnosis (1)
- Diastolische Dysfunktion (1)
- Differenzierung (1)
- Dispersal (1)
- Diversität (1)
- Doppelkronen (1)
- Doxorubicin (1)
- Drug recall (1)
- Drygala (1)
- Dual Decomposition (1)
- Dysfunktionale Kognitionen (1)
- EBERA (1)
- ECAP (1)
- EEG (1)
- EMSA (1)
- Ecosystem Dynamics (1)
- Efflux (1)
- Einstellung (1)
- Einzelhandel (1)
- Elektrochemischer Sensor (1)
- Empfindlichkeit (1)
- Endometriumkarzinom (1)
- Endothel (1)
- Entdifferenzierung (1)
- Entropium (1)
- Entwicklungszusammenarbeit (1)
- Environmental conditions (1)
- Epidemiology (1)
- Epigenetik (1)
- Erwartungsbilder (1)
- Evolution (1)
- Evolutionsbiologie , Tierökologie , Sexuelle Selektion , Sexualverhalten (1)
- Exosomen (1)
- FMD (1)
- FRET (1)
- FRS (1)
- Facettengelenksinjektion (1)
- Facettensyndrom (1)
- Fachkräfte akquirieren (1)
- False-Belief-Test (1)
- Fast Particles (1)
- Faszikularisgruppe (1)
- Feldversuch (1)
- Femurkopfdurchmesser (1)
- Feste Arzneiform (1)
- Fettfreie Masse (1)
- Fettstoffwechsel (1)
- Flight ability (1)
- Flug (1)
- Fluoreszenz-Resonanz-Energie-Transfer (1)
- Folgekosten (1)
- Foreign aid (1)
- Fossa pterygopalatina (1)
- Fourier analysis (1)
- Friedensvertrag (1)
- Frühkindliche Lebensereignisse (1)
- Full Anticoagulation (1)
- Funktionsfragebogen Hannover-Rückenschmerz (1)
- Fusarium solani (1)
- Fused Deposition Modeling (1)
- Förster-Resonanzenergietransfer (1)
- G-Quadruplex (1)
- GAPDH, ALDH (1)
- GHG emissions (1)
- GPU computing (1)
- Gastrointestinal oncology (1)
- Gastrointestinal stromal tumor (1)
- Gastrointestinal symptoms (1)
- Gastrointestinal tract (1)
- Gastroretentive Arzneiform (1)
- Gefäßstenose (1)
- Gehstrecke (1)
- Gender Mainstreaming (1)
- Gene Structure Prediction (1)
- Genetic counselling (1)
- Genetic diversity (1)
- Genome Annotation (1)
- Genotyping (1)
- Geräuschreduktion (1)
- Gesamtüberleben (1)
- Geschichte (1)
- Geschlechterforschung (1)
- Gesunde (1)
- Gewaltopfer, Gewaltambulanz, Unfallchirurgie, Dokumentationsqualität (1)
- Glazitektonik (1)
- Global South regional policy (1)
- Global change (1)
- Glomeruläre Filtrationsrate (1)
- Glutaredoxin (1)
- Glutaredoxine (1)
- Glutathion (1)
- Glutathione (1)
- Glycoprotein B (1)
- Gorilla (1)
- Graphen (1)
- Greifvögel (1)
- Gyro-kinetic Theory (1)
- Güstrow Parchim (1)
- HACA (1)
- HCMV (1)
- HCO (1)
- HEV (1)
- HFpEF (1)
- HIT (1)
- HSP27 (1)
- Halsschmerz (1)
- Hangzhou International Airport (1)
- Harris Hip Score (1)
- Haupttestgütekriterien von Assessments (1)
- Heart failure (1)
- Heat-flux (1)
- Henipavirus-ähnliche Partikel (1)
- Hepatitis-E-Virus , Polymerase-Kettenreaktion , Microarray , West-Nil-Virus , Flaviviren , RNS-Viren , Genotypisierung (1)
- Hermeneutik (1)
- Herpesviren (1)
- Herpesvirus suis (1)
- Herz-Lungen-Maschine (1)
- Herzchirurgie (1)
- Herzinsuffizienz (1)
- Heterostrukturen (1)
- Himalayan Silver Fir (<i>Abies spectabilis</i>), Nepal Himalaya (1)
- Hirninfarkt (1)
- Histon-Demethylase (1)
- Hitzeschockprotein (1)
- Hominidae (1)
- Homo sapiens (1)
- Homöopathie (1)
- Humanmedizin (1)
- Humanphysiologie (1)
- Hydrozephalus (1)
- Hyperspectral Imaging (1)
- Hyperventilation (1)
- Hüft- und Knie-Totalendoprothese (TEP) (1)
- Hüftgelenk (1)
- IDD in pregnant women (1)
- IL-10 (1)
- Ili River delta (1)
- Imaging features (1)
- Immunologie (1)
- Immuntoxizität (1)
- Impfeinstellung (1)
- Impfen (1)
- Impfstoff (1)
- Impfverhalten (1)
- Implantate (1)
- In vitro (1)
- In vitro-Freisetzungsmodell (1)
- In vivo (1)
- Individual phenotype (1)
- Indolochinolin (1)
- Insulin-like Growth Factor (1)
- Integrins (1)
- Intelligenzstörung (1)
- Interoception (1)
- Interozeption (1)
- Intrastate conflicts (1)
- Intraventricular hemorrhage (1)
- Iodine (1)
- Iodine deficiency disorders (1)
- Ionthruster (1)
- Isopropylamine (1)
- Isothermale Titrationskalorimetrie (1)
- JSNZ (1)
- Jahresring (1)
- Japanische (1)
- Japanische Makaken (1)
- Juniperus communis (1)
- Jurkat (1)
- Kaltplasma (1)
- Kardiopulmonale Fitness (1)
- Kardiorespiratorische Fitness (1)
- Kartografie (1)
- Kartographiegeschichte (1)
- Karzinom (1)
- Karzinosarkom (1)
- Kephalometrie (1)
- Kephalometrische Analyse (1)
- Keratin 15 (1)
- Ketamin (1)
- Kieferorthopädie (1)
- Kindergarten (1)
- Kindesalter (1)
- Kinetic simulation (1)
- Klinische Studie (1)
- Knee Society Score (1)
- Knochendicke (1)
- Kohärenzgefühl (1)
- Kolonkarzinom (1)
- Komplexes Plasma (1)
- Komplikationen (1)
- Konfliktregelung (1)
- Kontaktlinsen (1)
- Kontaktlinsendesinfektion (1)
- Kontaktlinsenreinigung (1)
- Konuskronenprothesen (1)
- Korrespondenzprinzip (1)
- Kosten (1)
- Kreatinin (1)
- Kritische Lebensereignisse (1)
- Kuhpockenvirus (1)
- Kupffer-Zellen (1)
- Kupfferzellen (1)
- Körperzellmasse (1)
- Körperzusammensetzung (1)
- LAVH (1)
- LED (1)
- LIGHT (1)
- LPS (1)
- LUCC (1)
- Lagrangian Relaxation (1)
- Lake Balkhash (1)
- Landformanalyse (1)
- Landolt-Ring (1)
- Landsat (1)
- Lebensereignis (1)
- Leber (1)
- Lebermetastasen (1)
- Leistungsphysiologie (1)
- Lemnaceae (1)
- LiDAR (1)
- Ligand-DNA-Interaktion (1)
- Lipide (1)
- Liposomen (1)
- Local adaptation (1)
- Lord's Resistance Army (1)
- Low temperature plasma (1)
- Lumbale Fusionsoperationen (1)
- Lumbale Spinalkanalstenose (1)
- Lungentumor (1)
- Lycaena tityrus (1)
- Lymphknotensilikose (1)
- Lymphozyt (1)
- M-Wire (1)
- MTIP planning (1)
- Macaca (1)
- Macaca fuscata (1)
- Machtteilungsregierungen (1)
- Magenmotilität (1)
- Magnetfeld (1)
- Magnetfeldinduktion (1)
- Magnetismus (1)
- Makaken (1)
- Makrophagen (1)
- Makrophagendepletion (1)
- Maligner Müller Mischtumor (1)
- Mantelgas (1)
- Manuelle Muskelkrafttestung (1)
- Mas-Rezeptor (1)
- Master-Gleichung (1)
- Mathematik (1)
- Maximale Sauerstoffaufnahme (1)
- Mediation (1)
- Medienbildung (1)
- Mediennutzungsethik (1)
- Medikamentenkonsum (1)
- Medizin (1)
- Membranfusion (1)
- Mensch (1)
- Mentale Retardierung (1)
- Metastasis (1)
- Methoden der Philosophie (1)
- Middle East (1)
- Migration (1)
- Mikrobiologie (1)
- Minimally invasive diagnostics (1)
- Mitochondrium (1)
- Mixed methods (1)
- Modellverbindungen (1)
- Molarenwurzel (1)
- Molecular biology (1)
- Molecular genetics (1)
- Molekularbiologie (1)
- Molekularbiologie, Genotypisierung, Genetische Diversität (1)
- Molybdenum (1)
- Molybdopterin (1)
- Molybdän-Cofaktor (1)
- Molybdän-Cofaktor-Defizienz (1)
- Monitoring IDD (1)
- Monte Carlo (1)
- Motivation (1)
- Movement (1)
- NF-Y (1)
- NUTS2-Regionen (1)
- Naturstoff (1)
- NeT (1)
- Nerve Root Sedimentation Sign (1)
- Neurodevelopmental Disorders (1)
- Neurodevelopmental outcome (1)
- Neuroimmunologie (1)
- Neurologie (1)
- Neuronale Differenzierung (1)
- Neuronale Plastizität (1)
- Neurowissenschaften (1)
- Neutral-Null-Methode (1)
- Nichtlineare Dynamik (1)
- Nickel-Titan-Systeme (1)
- Nickel-titanium (1)
- Nierenfunktionsparameter (1)
- Nipahvirus (1)
- OATP2B1 (1)
- OCT1 (1)
- Olga Maria Drygala (1)
- Online Befragung (1)
- Optomechanik (1)
- Oral health, Cerebral palsy, Children, Prevention (1)
- Orale Gesundheit (1)
- Orang-Utan (1)
- Organo-Anionen-Transporter (1)
- Organo-Anionen-Transporter 2B1 (1)
- Osmoregulation (1)
- Osteocalcin (1)
- Osteoporose (1)
- Osteosarkom (1)
- Outcomes research (1)
- Ovarialkarzinom (1)
- Overview (1)
- Oxidativer Stress (1)
- P300 (1)
- PCLake (1)
- PD-L1 (1)
- PEI,PDADMA,PSS,surface forces,atomic force microscopy, colloidal probe (1)
- PF4 (1)
- POCT (1)
- PP2 (1)
- PROM, Patient reported outcome measures (1)
- Pantoprazol (1)
- Parietale Epithelzellen (1)
- Parkinson's disease (1)
- Partial migration (1)
- Pathogenität (1)
- Patientennahe Sofortdiagnostik (1)
- Pearson Korrelation (1)
- Pediatric (1)
- Permissive hypercapnia (1)
- Pflege (1)
- Pflegepraktikum (1)
- Pharmakokinetik (1)
- Pharmakologie (1)
- Pharmazeutische Technologie (1)
- Physiotherapie (1)
- Picea glauca (1)
- Plasma , Plasmaphysik , Tokamak , Stellarator , Magnetohydrodynamik , Kinetische Theorie , Simulation , Alfvén-Welle , Energiereiches Teilchen (1)
- Plasma Physics (1)
- Plasmamedizin (1)
- Plastizität (1)
- Podocyte (1)
- Political Economy (1)
- Politische Ökonomie (1)
- Polymere (1)
- Polyneuropathie (1)
- Polyphenole (1)
- Pongiden (1)
- Postoperatives Schmerzempfinden nach Wirbelsäulenoperationen (1)
- Potamopyrgus antipodarum (1)
- Potentiale (1)
- Power-Sharing (1)
- Prevalence (1)
- Prevention (1)
- Primaten (1)
- Printmedien (1)
- Profilbilanzierung (1)
- Proliferation (1)
- Protease-aktivierter Rezeptor-2 (1)
- Protein engineering (1)
- Proteom (1)
- Proteomanalyse (1)
- Prädikate (1)
- Prädikatoren (1)
- Prävention (1)
- Pseudomonas aeruginosa (1)
- Psychiatrie (1)
- Psychopathologie (1)
- Psychosomatik (1)
- Pt(II) complexes (1)
- Pterin (1)
- Pulswelle (1)
- Pulswellenanalyse (1)
- Pädiater (1)
- Qualitätsmanagement Akutschmerz (1)
- Quantenoptik (1)
- Quantenpunkt (1)
- Quantifizierung (1)
- Quarz (1)
- Querschnittserhebung (1)
- RT-qPCR (1)
- Rabies (1)
- Rabies virus (1)
- Radikalfänger (1)
- Radiologische Diagnostik (1)
- Radon (1)
- Range shift (1)
- Rapsanbau (1)
- Raumbedeutsamkeit (1)
- Raumordnung (1)
- Raumordnungsrecht (1)
- Reaktive Sauerstoffspezies (1)
- Recurrence (1)
- Redoxplasmid (1)
- Referenzwerte (1)
- Relativismus (1)
- Relativistische Quantenmechanik (1)
- RenBP (1)
- Renin (1)
- Renin Binding Protein (1)
- Reservoirwirt (1)
- Rezidivfreies Intervall (1)
- Risk Assessment (1)
- Rocker switch (1)
- Rotbuche (1)
- S. aureus (1)
- SFC-MS (1)
- SHIP- Studie (1)
- SIRT2 (1)
- SLCO2B1 (1)
- SNP (1)
- STED microscopy (1)
- SaeRS (1)
- Salztoleranz (1)
- Sarkom (1)
- Sarkomatös entdifferenziertes Endometriumkarzinom (1)
- Schamethik (1)
- Scheindissense (1)
- Scherstress (1)
- Schimpanse (1)
- Schlaganfall (1)
- Schlaganfall induzierte Immunschwäche (1)
- Schmetterling (1)
- Schnecke (1)
- Schwangerschaft (1)
- Schweinekrankheit (1)
- Schweineleberesterase (1)
- SedSign (1)
- Sekretion (1)
- Selbstmanagement (1)
- Serratia marcescens (1)
- Sexting (1)
- Short Form 36 Health Questionnaire (SF-36) (1)
- Shrubs (1)
- Shunt (1)
- Silikose (1)
- Sinlge port (1)
- Sinus maxillaris (1)
- Sirt2 (1)
- Sirtuin (1)
- Solute Carrier (1)
- Sonographie (1)
- Sonography (1)
- Sowjetisch-Deutsche Aktiengesellschaft Wismut (1)
- Soziale Unterstützung (1)
- Sozialität (1)
- Sphingosine-1-Phosphate (1)
- Spinalkanalstenose (1)
- Spinnen (1)
- Spintronik (1)
- Splitomicin (1)
- SrGAP3 (1)
- Src Tyrosinkinase (1)
- Stadtentwicklung (1)
- Staffelstein-Score Version Hüfte und Knie (1)
- Starch (1)
- Stark gekoppelte Systeme (1)
- Statine (1)
- Stellarator (1)
- Stelligkeitserhöhung (1)
- Sterilisation (1)
- Stickland reactions (1)
- Stickstoffdüngung (1)
- Stimmungen (1)
- Streutheorie (1)
- Study of Healt in Pomerania (1)
- Stumpfes Bauchtrauma (1)
- Stärke (1)
- T cell maturation (1)
- THP-1 (1)
- TRPC (1)
- Tabletten (1)
- Teilzug (1)
- Tetrahydroindolon (1)
- Tetrazol (1)
- Theodoxus fluviatilis (1)
- Theory of Mind (1)
- Thiole (1)
- Thioredoxine (1)
- Third-party intervention (1)
- Thorakale Periduralanästhesie (1)
- Thrombospondin (1)
- Tierphysiologie (1)
- Tierseuche (1)
- Tigecyclin (1)
- Tokamak (1)
- Tollwutvirus (1)
- Topografie (1)
- Touristische Karten der DDR (1)
- Toxizität (1)
- Transaminases (1)
- Transfektion (1)
- Transkriptionstermination (1)
- Transporter (1)
- Treibhausgasemissionen (1)
- Triangulärer Index (1)
- Troponin (1)
- Tumor (1)
- Two component systems (1)
- Tyrosinkinase-Rezeptor 2 (1)
- UNESCO (1)
- UV-Strahlung (1)
- UVC-Bestrahlung (1)
- Uganda (1)
- Ultraschalldiagnostik (1)
- Umwelt (1)
- Uncoupling (1)
- VEEV (1)
- Vagusnerv (1)
- Validierung (1)
- Vascular malformation (1)
- Vegetation Ecology (1)
- Verbreitung (1)
- Verlag (1)
- Verlagsgeschichte (1)
- Videodefiziteffekt (1)
- Vietnam (1)
- Virologie (1)
- Virus (1)
- Virus evolution (1)
- Virusinfektion (1)
- Visustest (1)
- Vogelzug (1)
- Vollheparinisierung (1)
- Vorpommern (1)
- WNV (1)
- WOMAC® (1)
- Wachstum (1)
- Waldgrenze (1)
- Waldökologie (1)
- Waldökosystem (1)
- Weichselvereisung (1)
- Weißfichte (1)
- Windenergieanlagen (1)
- Winter (1)
- Wirbelsäulendeformität (1)
- Wohnungsbau (1)
- Wound Healing (1)
- Wurzelkanalmodelle (1)
- Wurzellänge (1)
- Yeast (1)
- Zahnentwicklung (1)
- Zahnkeimvolumina (1)
- Zahnwurzel (1)
- Zellkultur (1)
- Zitterbewegung (1)
- Zoonose (1)
- Zufriedenheit (1)
- Zukunftspläne (1)
- Zweikomponentensystem (1)
- Zytoskelett (1)
- Zytosolisches Renin (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)
- ambulante muskuloskeletale Rehabilitation (1)
- amino acids (1)
- anaerobic metabolism (1)
- animal (1)
- anthropometrics (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)
- berufliche Entwicklung (1)
- berufliche Spezialisierung (1)
- berufliche Ziele (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)
- biorelevant dissolution (1)
- blood–brain barrier (1)
- body cell mass (1)
- body composition (1)
- boreal forest (1)
- brain stimulation (1)
- brownfields (1)
- cancer therapy (1)
- carbon–carbon lyase (1)
- carboplatin (1)
- cardiac surgery (1)
- cardiac troponin (1)
- cardiopulmonary fitness (1)
- cardiorespiratory exercise capacity (1)
- catalytic activity (1)
- caudal epidural morphin (1)
- ch14.18/CHO (1)
- chaperones (1)
- child development (1)
- chromoplexy (1)
- chromosomal translocations (1)
- chromosome conformation capture (1)
- chronic pancreatitis (1)
- chronotypes (1)
- cine SSFP- Sequenz (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)
- clinical wound healing (1)
- cloud removal (1)
- clustering (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)
- cone beam computed tomography (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)
- cytosolic Renin (1)
- damage-associated molecular patterns (1)
- deep sequencing (1)
- dehydroepiandrosterone (1)
- dendritic cells (1)
- deutschlandweit (1)
- developmental screening (1)
- diffusion tensor imaging (1)
- diffusion tractography (1)
- diffusion weighted imaging (1)
- digital elevation models (1)
- digitale Volumentomographie (1)
- dreidimenional (1)
- dreidimensional (1)
- dual task (1)
- duckweed (1)
- ductal closure (1)
- ductal epithelium (1)
- early competencies (1)
- echocardiography (1)
- ecology (1)
- ecosystem dynamics (1)
- education (1)
- elektrische Stimulation (1)
- embodied cognition (1)
- embodiment (1)
- empathy (1)
- endothelfunktion (1)
- entry (1)
- environmental offsets (1)
- epilepsy (1)
- epileptic encephalopathies (1)
- epithelial fluid secretion (1)
- ethics of media use (1)
- ethics of shame (1)
- eutrophication (1)
- evozierte Potentiale (1)
- exercise (1)
- exercise physiology (1)
- experimental pancreatitis (1)
- experimental plant ecology (1)
- expression (1)
- fagus sylvatica (1)
- fat-free mass (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)
- fuscata (1)
- fusion loops (1)
- gH/gL complex (1)
- gastroretentive dosage form (1)
- genetic adaptation (1)
- genomics (1)
- genotyping (1)
- geometric morphometrics (1)
- gestural-verbal association (1)
- gewebeverträgliches Plasma (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)
- gutachterlich (1)
- habituation (1)
- health risk behaviors (1)
- healthcare (1)
- heat-shock proteins (1)
- heparin- and antibody-induced thrombocytopenia (1)
- heparins (1)
- herpesvirus (1)
- high thoracic peridural anaesthesie (1)
- high-ability tracked students (1)
- high-frequency heart rate variability (1)
- homoarginine (1)
- host-symbiont (1)
- human (1)
- humanized mice (1)
- hybrid molecules (1)
- hydrazones (1)
- hydrological regimes (1)
- hypertension (1)
- häusliche Gewalt (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)
- industrielle Biokatalyse (1)
- infants (1)
- infection (1)
- inflammation (1)
- infrastructure (1)
- inner urban development (1)
- insurance claims (1)
- interactions (1)
- intrakraniell (1)
- invasive (1)
- iodine deficiency disorders (1)
- iron surrogates (1)
- isoprenoid degradation (1)
- jep Gene (1)
- junge Erwachsene (1)
- kINPenMed (1)
- kaltes Atmosphärendruck-Argon-Plasma (1)
- kardiopulmonale Belastbarkeit (1)
- kardiovaskuläre Risikofaktoren (1)
- katalytische Aktivität (1)
- kephalometrisch (1)
- knowledge-is-power (1)
- kognitive Entwicklungspsychologie (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)
- maligner Mischtumor (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)
- mikrobielle Reinigung (1)
- mineral soil (1)
- mixed model (1)
- mode comparison (1)
- monoterpene (1)
- mortality (1)
- motility (1)
- mouse model (1)
- mucosal immunity (1)
- mucus (1)
- multiphoton imaging (1)
- multitasking (1)
- myeloid-derived suppressor cells (1)
- myxomycetes (1)
- nasolacrimalis (1)
- near-hand space (1)
- neuroactive steroids (1)
- neuroblastoma (1)
- neuroendokrin (1)
- neuropsychiatric diseases (1)
- night shift work (1)
- no-net-loss (1)
- noXrayceph® (1)
- non-small cell lung cancer (1)
- norepinephrine (1)
- objektive Diagnostik (1)
- objektivierter Sehschärfevalidierungstest (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)
- patientennahe und klinische Erhebungsverfahren (1)
- peak oxygen uptake (1)
- pediatric thrombosis (1)
- peptidases (1)
- peptide sharing (1)
- peripersonal space (1)
- peritoneal B cells (1)
- photodynamic therapy (1)
- phylogenetic (1)
- physiological responses (1)
- phytosterols (1)
- pig (1)
- plant traits (1)
- plasticity (1)
- poaching (1)
- podocyte nephropathy (1)
- point-of-care testing (1)
- pollen accumulation rates (1)
- pollen productivity estimates (1)
- poly(hydroxyalkanoates) (1)
- polycrystalline gold (1)
- population-based (1)
- population-based study (1)
- post-translational modifications (1)
- postnatales Wachstum (1)
- pregnenolone sulfate (1)
- preschool (1)
- preterm infant (1)
- prevalence (1)
- prevention (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)
- pterygopalatine fossa (1)
- pyramidal tract integrity (1)
- quinolines (1)
- rabies (1)
- radical polishing (1)
- radiometric interpolation (1)
- raumbedeutsam (1)
- re-epithelialization (1)
- reactivation (1)
- recruitment curve steepness (1)
- redox regulation (1)
- regime shift (1)
- rehabilitation (1)
- ring-opening reactions (1)
- rotary (1)
- rubber plantation (1)
- rule changes (1)
- röntgenfrei (1)
- s-förmig (1)
- s-shaped (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)
- sex differences (1)
- sexting (1)
- shaping ability (1)
- simulated (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)
- stomach (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)
- topography (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)
- turbulente Verdünnungsströmung (1)
- turbulenzarme Verdrängungsströmung (1)
- uACR (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)
- vertebrobasiläre Stenosen (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)
- wound healing (1)
- zellautonome Immunität (1)
- Änderungssensitivität (1)
- Ärzte (1)
- Überblähung (1)
- β-amino acid (1)
- β-phenylalanine ethyl ester (1)
- ω-transaminase (1)
Institute
- Institut für Botanik und Landschaftsökologie & Botanischer Garten (16)
- Kliniken und Polikliniken für Innere Medizin (15)
- Institut für Community Medicine (13)
- Institut für Pharmazie (13)
- Abteilung für Mikrobiologie und Molekularbiologie (11)
- Institut für Biochemie (10)
- Institut für Physik (10)
- Institut für Diagnostische Radiologie und Neuroradiologie (9)
- Klinik und Poliklinik für Neurologie (8)
- Institut für Pharmakologie (7)
Publisher
- Frontiers Media S.A. (37)
- MDPI (37)
- S. Karger AG (17)
- De Gruyter (8)
- BioMed Central (BMC) (4)
- Akadémiai Kiadó (1)
- Hindawi (1)
- IOP Publishing (1)
- Nature Publishing Group (1)
- SAGE Publications (1)
Die vorliegende Untersuchung legt nahe, dass für den interindividuellen Vergleich der kardiopulmonalen Leistungsfähigkeit die Normalisierung der maximalen Sauerstoffaufnahme auf die Körperzellmasse anderen Normalisierungen vorzuziehen ist, weil die
Körperzellmasse die Summe aller aktiv am Stoffwechsel beteiligten Zellen definiert und daher ein körpermassenunabhängiges Maß darstellt. Nach unseren Analysen scheint die fettfreie Masse aufgrund der hohen Korrelation mit der maximalen Sauerstoffaufnahme bei gleichzeitig niedriger Regressionskonstante die zweitbeste Normalisierungsvariable
zu sein. Die Normalisierung der maximalen Sauerstoffaufnahme auf
das Gesamtkörpergewicht geht mit starken Limitationen einher und kann zu Fehleinschätzungen der kardiopulmonalen Leistungsfähigkeit führen, da verschiedene Körperbestandteile wie die Körperzellmasse, fettfreie Masse und Körperfett im Gesamtkörpergewicht nicht berücksichtigt werden. Insbesondere bei Adipösen kann die kardiopulmonale
Leistungsfähigkeit durch diese Normalisierung systematisch unterschätzt werden. Demnach können körpergewichtsbasierte Indizes, wie zum Beispiel der gebräuchliche BMI, für die Einschätzung der kardiopulmonalen Leistungsfähigkeit nur bedingt genutzt werden. Weiterhin erwiesen sich die Fettmasse und die Körperhöhe
als ungeeignete Normalisierungsvariablen für die kardiopulmonale Leistungsfähigkeit. Zusammenfassend sollte für den interindividuellen Vergleich der kardiopulmonalen Leistungsfähigkeit die Normalisierung der maximalen Sauerstoffaufnahme mit der Körperzellmasse
oder fettfreien Masse erfolgen, anstatt das Gesamtkörpergewicht zu nutzen.
Ein notwendiger nächster Schritt wäre die Untersuchung der klinisch prognostischen Wertigkeit von verschiedenen Normalisierungen in longitudinalen Studien mit klinischen Endpunkten.
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.
Background: We aimed to update the 2010 evidence- and consensus-based national clinical guideline on the diagnosis and management of uncomplicated urinary tract infections (UTIs) in adult patients. Results are published in 2 parts. Part 1 covers methods, the definition of patient groups, and diagnostics. This second publication focuses on treatment of acute episodes of cystitis and pyelonephritis as well as on prophylaxis of recurrent UTIs. Materials and Methods: An interdisciplinary group consisting of 17 representatives of 12 medical societies and a patient representative was formed. Systematic literature searches were conducted in MEDLINE, EMBASE, and the Cochrane Library to identify literature published in 2010–2015. Results: For the treatment of acute uncomplicated cystitis (AUC), fosfomycin-trometamol, nitrofurantoin, nitroxoline, pivmecillinam, and trimethoprim (depending on the local rate of resistance) are all equally recommended. Cotrimoxazole, fluoroquinolones, and cephalosporins are not recommended as antibiotics of first choice, for concern of an unfavorable impact on the microbiome. Mild to moderate uncomplicated pyelonephritis should be treated with oral cefpodoxime, ceftibuten, ciprofloxacin, or levofloxacin. For AUC with mild to moderate symptoms, instead of antibiotics symptomatic treatment alone may be considered depending on patient preference after discussing adverse events and outcomes. Primarily non-antibiotic options are recommended for prophylaxis of recurrent urinary tract infection. Conclusion: In accordance with the global antibiotic stewardship initiative and considering new insights in scientific research, we updated our German clinical UTI guideline to promote a responsible antibiotic use and to give clear hands-on recommendations for the diagnosis and management of UTIs in adults in Germany for healthcare providers and patients.
Significance of Hyperbaric Oxygenation in the Treatment of Fournier’s Gangrene: A Comparative Study
(2018)
Introduction: Hyperbaric oxygenation (HBO), in addition to anti-infective and surgical therapy, seems to be a key treatment point for Fournier’s gangrene. The aim of this study was to investigate the influence of HBO therapy on the outcome and prognosis of Fournier’s gangrene. Patients and Methods: In the present multicenter, retrospective observational study, we evaluated the data of approximately 62 patients diagnosed with Fournier’s gangrene between 2007 and 2017. For comparison, 2 groups were distinguished: patients without HBO therapy (group A, n = 45) and patients with HBO therapy (group B, n = 17). The analysis included sex, age, comorbidities, clinical symptoms, laboratory and microbiological data, debridement frequency, wound dressing, antibiotic use, outcome and prognosis. The statistical analysis was performed with GraphPad Prism 7® (GraphPad Software, Inc., La Jolla, USA). Results: Demographic data showed no significant differences. The laboratory parameters C-reactive protein and urea were significantly higher in group B (group B: 301.7 vs. 140.6 mg/dL; group A: 124.8 vs. 54.7 mg/dL). Sepsis criteria were fulfilled in 77.8 and 100% of the patients in groups A and B respectively. Treatment in the intensive care unit (ICU) was therefore indicated in 69% of the patients in group A and 100% of the patients in group B. The mean ICU stay was 9 and 32 days for patients in groups A and B respectively. The wound debridement frequency and hospitalization stay were significantly greater in group B (13 vs. 5 debridement and 40 vs. 22 days). Initial antibiosis was test validated in 80% of the patients in group A and 76.5% of the patients in group B. Mortality was 0% in group B and 4.4% in the group A. Conclusion: The positive influence of HBO on the treatment of Fournier’s gangrene can be estimated only from the available data. Despite poorer baseline findings with comparable risk factors, mortality was 0% in the HBO group. The analysis of a larger patient cohort is desirable to increase the significance of the results.
Staphylococcus aureus ist ein Gram-positives pathogenes Bakterium, welches bei ca. 30 % der gesunden Bevölkerung zur kommensalen Flora der Nasenschleimhaut gehört. Jedoch zählt S. aureus auch zu den häufigsten Erregern bakterieller Infektionen beim Menschen. Aus diesem Grund wurden S. aureus-Stämme in zahlreichen Studien untersucht, um die Pathophysiologie und Virulenz der Bakterien sowie die zugrundeliegenden Regulationsmechanismen zu verstehen. Die Expression von Virulenzfaktoren wird direkt oder indirekt durch verschiedene Regulatoren beeinflusst. Zu diesen zählen beispielsweise das Quorum-Sensing-System Agr, der alternative Sigma-Faktor SigB und das Zweikomponentensystem SaeRS. Bei der Regulation der Genexpression spielt neben Mechanismen, die die Transkriptionsinitiation beeinflussen, auch die Transkriptions-termination eine Rolle. Bei Bakterien unterscheidet man zwischen der Rho-unabhängigen und der Rho-abhängigen Transkriptionstermination. In bisherigen Studien wurde die Rolle des Transkriptionsterminationsfaktors Rho in Escherichia coli, Bacillus subtilis und Mycobacterium tuberculosis untersucht. Hierzu zählt unter anderem das Silencing von horizontal erworbenen Genen, die Verhinderung von DNA-Doppelstrangbrüchen und die Unterdrückung der persistierenden Antisense-Transkripten. Besonders die erhöhte Antisense-Transkription konnte auch in einer Tiling Array-Studie des S. aureus Wildtypstammes HG001 und einer isogenen Δrho-Mutante ST1258 festgestellt werden. In dieser Transkriptom-Analyse wurden die S. aureus-Stämme in RPMI- und TSB-Medium in der exponentiellen und stationären Wachstumsphase untersucht. Es konnten insgesamt 416 chromosomale Regionen identifiziert werden, deren Transkriptmenge in einer der vier Bedingungen in der Δrho-Mutante im Vergleich zum Wildtyp wenigstens 4-fach erhöht waren. Von diesen Regionen ließen sich nur 11 % annotierten Genen zuordnen, während eine massive Erhöhung der Menge solcher Transkripte festgestellt wurde, die vom Gegenstrang kodierender Gene stammen.
Ausgehend von diesen Befunden wurde in dieser Studie das zelluläre und extrazelluläre Proteom des S. aureus Wildtyps HG001 und der Δrho-Mutante ST1258 verglichen, um die Auswirkungen der Abwesenheit von Rho auf das Proteom zu untersuchen. Dabei lag die Mehrheit der relativ quantifizierten Proteine in erhöhten Mengen in der Δrho-Mutante im Vergleich zum Wildtyp vor. Viele dieser Proteine konnten dem SaeRS-Zweikomponentensystem von S. aureus zugeordnet werden. In der Proteomanalyse konnten 34 von 39 Proteinen, die durch SaeR reguliert werden, quantifiziert werden. Von diesen wiesen 29 erhöhte Proteinmengen in der Δrho-Mutante auf. Durch das Sae-System werden Gene reguliert, von denen die meisten für Virulenzfaktoren, wie Adhäsine, Toxine und immune evasion-Proteine, kodieren. Die Daten der Proteomanalyse zeigen, dass in S. aureus-Zellen, denen die Aktivität von Rho fehlt, das Sae-System aktiviert wird und dadurch die Induktion des SaeR-Regulons zu beobachten ist.
Die Relevanz dieser Ergebnisse wurde durch ein in vivo-Infektionsexperiment untersucht. In einem Bakteriämie-Modell führte die Inaktivierung von Rho zu einer signifikant erhöhten Virulenz von S. aureus, welche sich in einer signifikant reduzierten Überlebensrate der Mäuse äußerte. Zwischen dem Wildtyp und dem Komplementationsstamm konnte kein signifikanter Unterschied in der Überlebensrate der infizierten Mäuse gezeigt werden.
Es ist bekannt, dass SaeRS-abhängige Virulenzfaktoren auch für die Invasion in Epithel- und Endothelzellen entscheidend sind. Anhand der Zahl der internalisierten S. aureus-Bakterien nach Infektion von humanen Lungenepithelzellen konnten in dieser Arbeit keine Unterschiede zwischen dem Wildtyp HG001 und ∆rho-Mutante ST1258 im zeitlichen Verlauf festgestellt werden. Dabei konnten weder Unterschiede im Überleben in 16HBE14o- Zellen noch in der Internalisierungsrate in A549-Zellen zwischen den beiden Stämmen gezeigt werden.
Das Antibiotikum Bicyclomycin ist ein spezifischer Inhibitor des Transkriptionsterminationsfaktors Rho und wird in Studien zur Rho-abhängigen Transkriptionstermination in Gram-negativen Bakterien eingesetzt, da in diesen Rho ein essentielles Protein ist. In Transkriptom- und Proteomanalysen konnten vergleichbare Effekte durch die Behandlung des Wildtyps mit Bicyclomycin wie in der ∆rho-Mutante hervorgerufen werden. Die Antisense-Transkription und die Expression SaeRS-abhängigen Gene waren im Wildtyp nach Gabe von Bicyclomycin deutlich erhöht. Es konnte gezeigt werden, dass die Aktivierung des Sae-Systems unter Rho-defizienten Bedingungen direkt mit der Transkriptionsterminationsaktivität von Rho verbunden ist und eine neue Verbindung zwischen antibiotischer Wirkung und schädlicher Virulenzgenexpression in S. aureus herstellt werden konnte. In anderen Studien konnten Effekte von Antibiotika auf die Expression von Virulenzfaktoren in S. aureus gezeigt werden, jedoch wurden in diesen Studien die Effekte von Anti-Staphylokokken-Wirkstoffen untersucht. Im Gegensatz dazu ist im Fall von Bicyclomycin ein Antibiotikum verwendet worden, das gegen Gram-negative Bakterien wirksam ist und dennoch die Expression von Virulenzfaktoren in S. aureus beeinflusst. Diese Untersuchungen haben damit auch klinische Relevanz, nicht nur für Patienten, die an gemischten Infektionen mit verschiedenen Bakterienarten leiden, sondern auch für Patienten mit einer Gram-negativen bakteriellen Infektion, die jedoch Träger von S. aureus sind.
Rabies virus (RABV) is an ancient, highly neurotropic rhabdovirus that causes lethal encephalitis. Most RABV pathogenesis determinants have been identified with laboratory-adapted or attenuated RABVs, but details of natural RABV pathogenesis and attenuation mechanisms are still poorly understood. To provide a deeper insight in the cellular mechanism of pathogenies of field RABV, this work was performed to assess virus strain specific differences in intra-neuronal virus transport, to identify cell culture adaptive mutations in recombinant field viruses and to explore shRNA-expressing RABVs as research tools for targeted host manipulation in infected cells.
Comparison of chimeric RABVs with glycoprotein (G) ecto-domains of different lyssaviruses, together with field RABVs from dog and fox in dorsal root ganglion (DRG) neurons revealed no detectable differences in the axonal accumulation of the viruses. This indicates that previously described G-dependent transport of newly formed RABV in axons can occur both in laboratory-adapted and field RABV. Moreover, partial overlap of nucleoprotein (N) and G protein particles in field virus infected DRG axons supported the hypothesis of the “separate model” for anterograde RABV transport.
Serial passages of recombinant dog and fox field clones in different cell lines led to the identification of general (D266N) and cell line specific (K444N) adaptive mutations in the G ecto-domain of both viruses. In BHK cells, synergistic effects of D226N, K444N and A417T on field dog virus G protein surface localization led to the loss of endoplasmic reticulum (ER) retention of G and increased virus titers in the supernatant, indicating that limited virus release by ER retention is a major bottleneck in cell culture adaptation. In addition, selection of mutations within the C-terminus of the RABV phosphoprotein (P) (R293H and R293C in fox and dog viruses, respectively) led to the hypothesis of altered binding affinities to nucleoprotein and RNP complexes. Identification of the above mentioned amino acid substitutions together with alterations in a suboptimal transcription stop signal in the P/M gene border indicated that adaptation to cell culture replication occurs on both levels, RNA transcription/replication and virus release.
To evaluate the possibility of an expression of a functional microRNA-adapted short-hairpin RNAs (miR-shRNA) expressing RABV, recombinant RABVs encoding miR-shRNAs against cellular Dynein Light Chain 1 (DYNLL1) and Acidic Nuclear Phosphoprotein 32 family member B (ANP32B) were generated. In spite of cytoplasmic transcription of the respective mRNAs, downregulation of DYNLL1 and ANP32B mRNA and respective protein levels in infected cells revealed correct processing to functional shRNAs. Specific downregulation of the cellular genes at 2, 3 and 4 days post infection further demonstrated feasibility of the approach in standard cell lines. However, it remained open whether miR-shRNA expressing RABV can be used to study neuro-infection in vivo. Since first attempts in primary rat neuron cultures failed, it has to be clarified in further experiments whether this strategy can be used in mature, non-dividing neurons or whether breakdown of the nucleus in the course of cell division is a requirement for the processing of cytoplasmically expressed miR-RNA by nuclear RNases.
By providing novel insights in axonal RABV transport and cell culture adaptive mutations this work extends the current understanding of RABV pathogenesis in natural and non-natural cell environments. Moreover, it provides a basis for further pathogenicity studies in which the impact of cell culture adaptation through increased virus release on RABV virulence can be investigated. With successful expression of functional miR-shRNAs from RABV vectors, this work also provides a tool for RABV gene targeting in infected cell lines and thus may contribute to the further investigation of RABV-host-cell-interactions.
Streptococcus pneumoniae is a commensal of the human upper respiratory tract and
the etiological agent of several life-threatening diseases. This pathogen is the model bacterium
for natural competence. Furthermore, the pneumococci played an important role in the
identification of DNA as the main molecule involved in bacterial transformation. As a result,
studies on the pneumococcal genome provided an initial overview of the genetic potential of
this pathogen. The pneumococcus is a highly versatile bacterium possessing a high rate of
uptake and recombination of exogenous DNA from neighboring bacteria. As such, a significant
diversity in the genome content among the different pneumococcal strains has been reported.
The capsular polysaccharide, an important pneumococcal virulence factor, is the best example
on the pneumococcal diversity. There are over 98 serotypes characterized to date presenting
differences in their capsule (cps) locus. Additional to the cps locus, the pneumococcus also
presents 13 genomic islets annotated as regions of diversity (RD) encoded in the auxiliary
genome. Remarkably, 8 of the pneumococcal RD studied so far have been associated with
virulence. Furthermore, the ongoing sequencing of over 4000 pneumococcal genomes have
shed light on the conservation level of well-known pneumococcal virulence factors.
Interestingly, important pneumococcal virulence determinants show variations in the gene and
protein sequence among the different strains. Prototypes are for example the pneumococcal
surface protein C (PspC) and pneumococcal adherence and virulence factor B (PavB).
Conversely, gene regulation in S. pneumoniae is carried out by highly conserved and genome-
wide distributed transcriptional factors. Overall, the pneumococci interplays with its
environment with 4 major regulatory systems: quorum sensing (QS), stand-alone
transcriptional regulators, small RNAs (sRNAs) and two-component regulatory systems (TCS).
Some of these systems are multifaceted and share more than one feature. Furthermore, there
is crosstalk among the different systems, requiring the activation of a signaling cascade to
function properly.
A comprehensive analysis of the distribution and conservation of pneumococcal
virulence factors and TCS was obtained in this study. The results are summarized as a
simplified variome in which 25 pneumococcal strains with a complete sequenced genome were
analyzed. Interestingly, the genes encoding the glycolytic protein enolase and the toxin
pneumolysin were the most conserved virulence determinants. Additionally, the high level of
conservation was confirmed for the pneumococcal TCS regulators, especially for WalKR,
CiaRH and TCS08.
The main focus of this study was on the regulatory functions of pneumococcal TCS.
With this in mind, an extensive and detailed systematic review of the 13 pneumococcal TCS
and its orphan RR was undertaken. For this purpose, every pneumococcal TCS was analyzed
for its reported functional and structural information along with its contribution to the main
pathophysiology of the pneumococci. In brief, S. pneumoniae can utilize its TCS for the
regulation of important cellular processes and the sensing of detectable signals in the
environment. Additionally, the role of TCS in pneumococcal processes and signal sensing can
be divided further. In the first place, pneumococcal TCS regulate competence and fratricide,
the production of bacteriocins and host-pathogen interaction processes, while the detectable
signals include cell-wall perturbations, environmental stress, and nutrients. As a conclusion
from this section, it is possible to analyze the pneumococcal TCS in a comprehensive manner.
There is a complex network among the different pneumococcal regulators and the TCS play
an important role. Moreover, these systems are highly conserved and essential for the proper
functioning of the pneumococcus as a pathogen.
Following up on pneumococcal TCS, this study focused especially on the TCS08.
Interestingly, the pneumococcal TCS08 has been previously associated with the regulation of the cellobiose metabolism. Furthermore, this system has also been reported to regulate the
expression of genes encoded in the RD4 (Pilus-1). Remarkably, the pneumococcal TCS08
was shown to be highly homologous to the SaeRS system of Staphylococcus aureus. Initially,
mutant strains lacking a single (Δrr08 or Δhk08) or both components (Δtcs08) of the TCS08
were generated in pneumococcal D39 and TIGR4 strains. Transcriptomics and functional
assays showed a downregulation of the PI-1 in the absence of the complete tcs08, while PavB
presented an upregulation in the Δhk08 knockout. Moreover, an important number of genes
coding for intermediary metabolism proteins were also found to be differentially expressed by
microarray analysis. As such, the TIGR4Δhk08 strain presented a downregulation for the
cellobiose operon (cel). In contrast, an upregulation was reported for the fatty acid biosynthesis
(fab) and arginine catabolism (arc) operons. Conversely, a decrease in gene expression was
seen in the TIGR4Δrr08 strain for the arc operon. Finally, in vivo murine pneumonia and sepsis
models highlighted an involvement of TCS08 in pneumococcal virulence. Remarkably, the
different TCS08 mutants presented a strain dependent effect on their virulence severity. The
TIGR4Δrr08, and all TCS08 mutants in D39 showed a decrease in virulence in the pneumonia
model, with no changes in sepsis. Conversely, the absence of HK08 in TIGR4 presented a
highly virulent phenotype in both pneumonia and sepsis models. To sum up, the pneumococcal
TCS08 influenced the expression of genes involved in fitness and colonization. Specifically,
those coding for the adhesins PavB and PI-1 and fitness proteins from the cel, arc and fab
operons. Remarkably, the highest changes in expression were observed in the strains lacking
the HK08. Additionally, TCS08 has a strain dependent impact on pneumococcal virulence as
showed by murine pneumonia and sepsis models when comparing the effects in D39 and
TIGR4.