Refine
Year of publication
Document Type
- Preprint (721)
- Article (618)
- Conference Proceeding (6)
- Working Paper (2)
- Part of a Book (1)
Has Fulltext
- yes (1348)
Is part of the Bibliography
- no (1348)
Keywords
- Heavy Ion Experiments (21)
- Hadron-Hadron Scattering (11)
- Hadron-Hadron scattering (experiments) (11)
- LHC (9)
- Heavy-ion collision (6)
- SARS-CoV-2 (5)
- ALICE experiment (4)
- COVID19-NMR (4)
- Collective Flow (4)
- Jets (4)
- Quark-Gluon Plasma (4)
- Solution NMR spectroscopy (4)
- 5′-UTR (3)
- ALICE (3)
- Elastic scattering (3)
- Heavy Ions (3)
- Heavy Quark Production (3)
- Jets and Jet Substructure (3)
- meningioma (3)
- neurodegeneration (3)
- pp collisions (3)
- Beauty production (2)
- COVID-19 (2)
- Cancer genomics (2)
- Charm physics (2)
- Clinical Trials and Observations (2)
- Collectivity (2)
- Correlation (2)
- Diffraction (2)
- Elliptic flow (2)
- Experimental nuclear physics (2)
- Experimental particle physics (2)
- Heavy-ion collisions (2)
- Lepton-Nucleon Scattering (experiments) (2)
- NR4A2 (2)
- PPARγ (2)
- Particle Correlations and Fluctuations (2)
- Particle and resonance production (2)
- Particle correlations and fluctuations (2)
- Pb–Pb collisions (2)
- Polarization (2)
- Pulmonary embolism (2)
- QCD (2)
- Quarkonium (2)
- RHIC (2)
- Relativistic heavy-ion collisions (2)
- SFAP (2)
- Shear viscosity (2)
- Single electrons (2)
- UAV (2)
- clinically important restrictions and symptoms (2)
- drug discovery (2)
- epilepsy (2)
- fragment screening (2)
- guidelines (2)
- hematopoietic stem cell transplantation (2)
- nuclear receptor (2)
- observational study (2)
- polypharmacology (2)
- rare disease (2)
- soil erosion (2)
- structural biology (2)
- transcription factor (2)
- 140Ce (1)
- 5'-UTR (1)
- 5_SL4 (1)
- 900 GeV (1)
- ABC transporters (1)
- ALICE detector (1)
- ARDS (1)
- ATAD2 (1)
- ATPases (1)
- Advanced biliary tract cancer (1)
- Alzheimer’s disease (1)
- Anti-nuclei (1)
- Antibiotic Resistance (1)
- Antibiotics (1)
- Atherosclerosis (1)
- B-slope (1)
- BET inhibitors (1)
- BRD2 (1)
- BRD4 (1)
- BROMO-10 (1)
- BTC (1)
- Bacillus (1)
- Bacterial pathogens (1)
- Baryonic resonances (1)
- Biochemistry and chemical biology (1)
- Biodiversity (1)
- Biogeography (1)
- Bipolar disorder (1)
- Boosted Jets (1)
- Brain metastasis (1)
- CD74 (1)
- COVID (1)
- Cancer (1)
- Cancer genetics (1)
- Cardiomyocyte signaling pathways (1)
- Cardioprotection (1)
- Cardiovascular disease (1)
- Cardiovascular diseases (1)
- Carrier-bound fibrin sealant (1)
- Centrality Class (1)
- Centrality Selection (1)
- Charge fluctuations (1)
- Charged-particle multiplicity (1)
- Charm quark spatial diffusion coefficient (1)
- Charmonia (1)
- Chemical tools (1)
- Circadian (1)
- Circulating MiRNA (1)
- Coalescence (1)
- Cold nuclear matter effects (1)
- Collagen hemostat (1)
- Collective Flow, (1)
- Comorbidities (1)
- Comparison with QCD (1)
- Conformational trapping (1)
- Coronary heart disease (1)
- Covid19-nmr (1)
- Critical care (1)
- Critical point (1)
- DIPSHIFT (1)
- Data management (1)
- Data sharing (1)
- Deuteron production (1)
- Di-hadron correlations (1)
- Diagnostic markers (1)
- Direct oral anticoagulation (1)
- Disease Activity (1)
- Drug safety (1)
- Drug screening (1)
- Drug targeting (1)
- E. colo (1)
- Early Rheumatoid Arthritis (1)
- Ecology (1)
- Ecophysiology (1)
- Ecosystems (1)
- Electromagnetic transitions (1)
- Electron-pion identification (1)
- Electroweak interaction (1)
- Endothelial permeability (1)
- Entomology (1)
- Environment (1)
- Experimental models of disease (1)
- Extracellular RNA (eRNA) (1)
- Femtoscopy (1)
- Fibre/foam sandwich radiator (1)
- Flow (1)
- Forschung (1)
- Freezeout (1)
- G protein-coupled receptor (GPCR) (1)
- G protein-coupled receptors (1)
- GVHD (1)
- Genomic instability (1)
- Germany (1)
- Glioblastoma survival (1)
- Groomed jet radius (1)
- HBT (1)
- HLA class II (1)
- HLA peptidome (1)
- HNO (1)
- Hadron production (1)
- Hadron-Hadron Scattering Heavy (1)
- Hadron-hadron interactions (1)
- Hals-Nasen-Ohren-Heilkunde (1)
- Hand-foot syndrome (1)
- Hard Scattering (1)
- Head and neck cancer (1)
- Health risk analysis (1)
- Heart regeneration (1)
- Heavy Ion Experiment (1)
- Heavy flavor production (1)
- Heavy flavour production (1)
- Heavy ions (1)
- Heavy-Ion Collision (1)
- Heavy-flavor decay electron (1)
- Heavy-flavour decay muons (1)
- Heavy-flavour production (1)
- Heavy-ion (1)
- Heavy-ion reactions (1)
- Hemostatics (1)
- HepG2 (1)
- Hif1α (1)
- High-throughput screening (1)
- Higher moments (1)
- HoLEP (1)
- Holmium laser enucleation (1)
- In vitro selection (1)
- Incidental prostate cancer (1)
- Inclusive spectra (1)
- Induced pluripotent stem cells (1)
- Intensity interferometry (1)
- Interference fragmentation function (1)
- Invariant Mass Distribution (1)
- Ionisation energy loss (1)
- Ischemia–reperfusion injury (1)
- Italy (1)
- J/ψ suppression (1)
- Jet Physics (1)
- Jet Substructure (1)
- Jet substructure (1)
- KCGS (1)
- KPS (1)
- LanI Protein (1)
- Lantibiotic (1)
- Lantibiotic Immunity (1)
- Lehre (1)
- Lipid metabolism (1)
- Lipoprotein (1)
- Liver Fibrosis (1)
- Liver resection (1)
- Low-molecular-weight heparin (1)
- Lymphocytes (1)
- Lymphoid Neoplasia (1)
- Lymphoid tissues (1)
- MACS (1)
- MODY (1)
- Malignant meningioma (1)
- Marine chemistry (1)
- Material budget (1)
- Medicinal chemistry (1)
- Membrane protein (1)
- Meningioma (1)
- Metabolic syndrome (1)
- MiR-29 (1)
- MicroRNAs (miRNAs) (1)
- Microbiome (1)
- Mid-rapidity (1)
- Minimum Bias (1)
- Mitochondria (1)
- Models & methods for nuclear reactions (1)
- Molecular medicine (1)
- Molecular modelling (1)
- Monte Carlo (1)
- Multi-Parton Interactions (1)
- Multi-strange baryons (1)
- Multi-wire proportional drift chamber (1)
- Multiple parton interactions (1)
- Myeloid Neoplasia (1)
- Myocardial infarction (1)
- N-acetylcysteine (1)
- NK cell (1)
- NK cell subset (1)
- NMR (1)
- NMR spectroscopy (1)
- NR4A3 (1)
- Nanobody (1)
- Neolithic (1)
- Neural network (1)
- Neuropilin (1)
- Neutron physics (1)
- Next-generation sequencing (1)
- Nonflow (1)
- Nuclear Magnetic Resonance (1)
- Nuclear modification factor (1)
- Nuclear reactions (1)
- ORL (1)
- Observation (1)
- Oncology (1)
- Orphan nuclear receptor (1)
- Otorhinolaryngology (1)
- Outcome (1)
- Outcomes research (1)
- PCV (1)
- PDGFRβ (1)
- PYTHIA (1)
- Palaeoceanography (1)
- Palaeoclimate (1)
- Parkinson’s disease (1)
- Particle and Resonance Production (1)
- Patterns of care (1)
- Pb–Pb (1)
- Periodontitis (1)
- Phage display (1)
- Phylogenomics (1)
- Population genetics (1)
- Preclinical research (1)
- Predictive markers (1)
- Production Cross Section (1)
- Prognostic markers (1)
- Prognostic models (1)
- Properties of Hadrons (1)
- Prostate cancer (1)
- Protein Structure (1)
- Proton-proton collisions (1)
- Proton–proton (1)
- Proton–proton collisions (1)
- Psychiatry (1)
- Pyogenic spondylodiscitis (1)
- QGP (1)
- Quark Deconfinement (1)
- Quark Gluon Plasma (1)
- Quark Production (1)
- Quark gluon plasma (1)
- RNA (1)
- RNA genome (1)
- RNASolution-state NMR (1)
- RXRα (1)
- Radiative capture (1)
- Radiotherapy (1)
- Randomized controlled trial (1)
- Rapidity Range (1)
- Relativistic heavy ion physics (1)
- Remote ischemic conditioning (1)
- Research (1)
- Residency (1)
- Resolution Parameter (1)
- Resonance reactions (1)
- Rheumatoid Arthritis (1)
- Ribosome display (1)
- Risk factor (1)
- Routine Medical Care (1)
- Rpo4/7 (1)
- SARS-CoV‑2 pandemic (1)
- SARS-CoV‑2-Pandemie (1)
- SCT (1)
- SKALE score (1)
- SL1 (1)
- SL5a (1)
- SL5b (1)
- SL5b + c (1)
- SL5c (1)
- STAMPE2 (1)
- STAR (1)
- Salivary gland carcinoma (1)
- Seasonal variation (1)
- Shannon index (1)
- Single muons (1)
- Socio-ecology (1)
- SoftDrop (1)
- Solar insolation (1)
- Sorafenib (1)
- SpaI (1)
- Specialist training (1)
- Spin alignment (1)
- Splitting function (1)
- Ste2p (1)
- Stroke (1)
- Structural biology and molecular biophysics (1)
- Subtilin (1)
- Suicide (1)
- Sunlight (1)
- Surgery (1)
- Sweden (1)
- Systematic Uncertainty (1)
- TIRADS (1)
- TR (1)
- TTW nodules (1)
- TUR-P (1)
- Target identification (1)
- Target validation (1)
- Taxonomy (1)
- Teaching (1)
- Teeth (1)
- Therapeutic anticoagulation (1)
- Thermal model (1)
- Thrombosis (1)
- Time Projection Chamber (1)
- Tools and ressources (1)
- Topology (1)
- Tracking (1)
- Transition radiation detector (1)
- Translational research (1)
- Transurethral resection of the prostate (1)
- Transverse momentum (1)
- Transversity (1)
- Treatment (1)
- Trigger (1)
- Tumor infiltrating lymphocytes (1)
- Unemployment (1)
- University hospitals (1)
- Universitätskliniken (1)
- VEGF (1)
- VEGF receptors (1)
- VEGFR-2 (1)
- VEGFR-3 (1)
- Vector Boson Production (1)
- Wealth Losses (1)
- Weiterbildung (1)
- X-ray crystallography (1)
- Xenon-based gas mixture (1)
- Zuckerkandl’s tubercle (1)
- accident (1)
- alleles (1)
- allostery (1)
- anaemia (1)
- androgen receptor (1)
- antibodies (1)
- anticonvulsants (1)
- autism spectrum disorder (1)
- autistic disorder (1)
- azacitidine (1)
- b-cell lymphomas (1)
- bendamustine (1)
- biogeographic legaciese (1)
- biomarker (1)
- bromodomain (1)
- bromodomain inhibitor (1)
- c-kit (1)
- capture (1)
- carbon and proton assignments (1)
- cardiocerebral resuscitation (1)
- cardiopulmonary resuscitation (1)
- castration-resistant prostate cancer (1)
- cell-free expression (1)
- cerium (1)
- charge transfer (1)
- chemogenomic set (1)
- chemotherapy (1)
- chemotherapy regimen (1)
- child (1)
- chimeric antigen receptor t-cell therapy (1)
- chimeric antigen receptors (1)
- chromatin (1)
- cirrhosis (1)
- clinical practice (1)
- cofactor recruitment (1)
- computational chemistry (1)
- copy number polymorphism (1)
- coronavirus (1)
- cross-section (1)
- cryo-EM (1)
- cytotoxicity (1)
- dE/dx (1)
- detector (1)
- dexamethasone (1)
- differential scanning fluorimetry (1)
- diffuse low-grade glioma (1)
- diffusion-weighted magnetic resonance imaging (1)
- domestication (1)
- double access (1)
- drug target (1)
- druggable genome (1)
- dynamics (1)
- ectosomes (1)
- elderly (1)
- epigenetic (1)
- everolimus (1)
- evolution (1)
- exercise (1)
- exosomes (1)
- experimental results (1)
- experiments (1)
- extracellular vesicles (1)
- fluorescence (1)
- follow-up (1)
- forest classification (1)
- forest functional similarity (1)
- fragment-based design (1)
- fragment-based drug design (1)
- freshwater ecosystems (1)
- gastric cancer (1)
- gastrointestinal stromal tumours (1)
- gene flow (1)
- genes (1)
- genetics (1)
- genome (1)
- genotype (1)
- genotype determination (1)
- glioblastoma (1)
- glioblastoma survival (1)
- glioma microenvironment (1)
- global change (1)
- habitat destruction (1)
- health (1)
- health-related quality of life (1)
- health-relatedquality of life (1)
- heavy ion experiments (1)
- hepatocyte nuclear factor 4α (1)
- hepatocyte transplantation (1)
- heterodimer (1)
- homodimer (1)
- homogeneous time-resolved FRET (HTRF) (1)
- hotspot loci (1)
- hypoxia (1)
- immune infiltration (1)
- immune reconstitution (1)
- injury (1)
- insect abundance (1)
- juvenile myelomonocytic leukemia (1)
- kinase inhibitor (1)
- land use (1)
- land-use change (1)
- leukapheresis (1)
- leukemia (1)
- lockdown (1)
- long-term research (1)
- lymphoma (1)
- magic angle spinning (1)
- membrane protein (1)
- membrane proteins (1)
- metabolic syndrome (1)
- metastatic renal cell carcinoma (1)
- miRNA (1)
- microdeletions (1)
- microparticles (1)
- microvesicles (1)
- minimal information requirements (1)
- molecular machines (1)
- monitoring (1)
- montelukast (1)
- multiple sclerosis (1)
- multiplexed immunofluorescence (1)
- multiscale (1)
- multitarget drugs (1)
- mutation (1)
- n_TOF (1)
- neoadjuvant chemoradiotherapy (1)
- neurodevelopmental (1)
- neutron (1)
- nuclear magnetic resonance (NMR) (1)
- nuclear receptor related-1 (1)
- nuclear receptor-related 1 (1)
- nucleosynthesis (1)
- object-based classification (1)
- oral cavity cancer (1)
- p+p collisions (1)
- pediatric intensive care (1)
- peritumoral edema (1)
- peritumoral edema zone (1)
- pharmacokinetics (1)
- pharmacophore model (1)
- phase IV (1)
- phenotype (1)
- phenotypic screening (1)
- photochemistry (1)
- photogrammetry (1)
- photolabile protecting groups (1)
- phylogenetic community distance (1)
- phylogeny (1)
- pole concept of goiter growth (1)
- portal hypertension (1)
- posterior horn (1)
- posteroinferior horn (1)
- pranlukast (1)
- predictive biomarker (1)
- primary active transporters (1)
- protein folding (1)
- protein kinase (1)
- pulmonary embolism (1)
- quark gluon plasma (1)
- recurrence pattern (1)
- red blood cells (1)
- remote sensing (1)
- renin-angiotensin system (1)
- reproducibility (1)
- retinoid X receptor (1)
- rigor (1)
- risk of malignancy (1)
- rituximab (1)
- s-process (1)
- sarcoma (1)
- second-line (1)
- secondary chemical shifts (1)
- seizures (1)
- sequence alignment (1)
- signature (1)
- single nucleotide polymorphism (1)
- small molecules (1)
- solid-state NMR (1)
- soluble epoxide hydrolase (1)
- spectra (1)
- speech reports (1)
- ssFLYA (1)
- standardization (1)
- stearic acid (1)
- taller-than-wide (1)
- temozolomide (1)
- tense (1)
- therapeutic anticoagulation (1)
- threats (1)
- transfusion (1)
- trauma (1)
- tropical forests (1)
- type 2 diabetes (1)
- tyrosine kinase inhibitors (1)
- understudied kinase (1)
- zafirlukast (1)
- √sN N = 2.76 TeV (1)
Institute
- Physik (1192)
- Frankfurt Institute for Advanced Studies (FIAS) (990)
- Informatik (921)
- Medizin (72)
- Biochemie, Chemie und Pharmazie (16)
- Biochemie und Chemie (9)
- Biowissenschaften (9)
- Geowissenschaften (8)
- Zentrum für Biomolekulare Magnetische Resonanz (BMRZ) (7)
- Pharmazie (5)
Microangiopathy with subsequent organ damage represents a major complication in several diseases. The mechanisms leading to microvascular occlusion include von Willebrand factor (VWF), notably the formation of ultra-large von Willebrand factor fibers (ULVWFs) and platelet aggregation. To date, the contribution of erythrocytes to vascular occlusion is incompletely clarified. We investigated the platelet-independent interaction between stressed erythrocytes and ULVWFs and its consequences for microcirculation and organ function under dynamic conditions. In response to shear stress, erythrocytes interacted strongly with VWF to initiate the formation of ULVWF/erythrocyte aggregates via the binding of Annexin V to the VWF A1 domain. VWF-erythrocyte adhesion was attenuated by heparin and the VWF-specific protease ADAMTS13. In an in vivo model of renal ischemia/reperfusion injury, erythrocytes adhered to capillaries of wild-type but not VWF-deficient mice and later resulted in less renal damage. In vivo imaging in mice confirmed the adhesion of stressed erythrocytes to the vessel wall. Moreover, enhanced eryptosis rates and increased VWF binding were detected in blood samples from patients with chronic renal failure. Our study demonstrates that stressed erythrocytes have a pronounced binding affinity to ULVWFs. The discovered mechanisms suggest that erythrocytes are essential for the pathogenesis of microangiopathies and renal damage by actively binding to ULVWFs.
The current pandemic situation caused by the Betacoronavirus SARS-CoV-2 (SCoV2) highlights the need for coordinated research to combat COVID-19. A particularly important aspect is the development of medication. In addition to viral proteins, structured RNA elements represent a potent alternative as drug targets. The search for drugs that target RNA requires their high-resolution structural characterization. Using nuclear magnetic resonance (NMR) spectroscopy, a worldwide consortium of NMR researchers aims to characterize potential RNA drug targets of SCoV2. Here, we report the characterization of 15 conserved RNA elements located at the 5′ end, the ribosomal frameshift segment and the 3′-untranslated region (3′-UTR) of the SCoV2 genome, their large-scale production and NMR-based secondary structure determination. The NMR data are corroborated with secondary structure probing by DMS footprinting experiments. The close agreement of NMR secondary structure determination of isolated RNA elements with DMS footprinting and NMR performed on larger RNA regions shows that the secondary structure elements fold independently. The NMR data reported here provide the basis for NMR investigations of RNA function, RNA interactions with viral and host proteins and screening campaigns to identify potential RNA binders for pharmaceutical intervention.
Background & aims: Current guidelines recommend immunosuppressive treatment (IT) in patients with primary sclerosing cholangitis (PSC) and elevated aminotransferase levels more than five times the upper limit of normal and elevated serum IgG-levels above twice the upper limit of normal. Since there is no evidence to support this recommendation, we aimed to assess the criteria that guided clinicians in clinical practice to initiate IT in patients with previously diagnosed PSC.
Methods: This is a retrospective analysis of 196 PSC patients from seven German hepatology centers, of whom 36 patients had received IT solely for their liver disease during the course of PSC. Analyses were carried out using methods for competing risks.
Results: A simplified autoimmune hepatitis (AIH) score >5 (HR of 36, p<0.0001) and a modified histological activity index (mHAI) greater than 3/18 points (HR 3.6, p = 0.0274) were associated with the initiation of IT during the course of PSC. Of note, PSC patients who subsequently received IT differed already at the time of PSC diagnosis from those patients, who did not receive IT during follow-up: they presented with increased levels of IgG (p = 0.004) and more frequently had clinical signs of cirrhosis (p = 0.0002).
Conclusions: This is the first study which investigates the parameters associated with IT in patients with PSC in clinical practice. A simplified AIH score >5 and a mHAI score >3, suggesting concomitant features of AIH, influenced the decision to introduce IT during the course of PSC. In German clinical practice, the cutoffs used to guide IT may be lower than recommended by current guidelines.
Androgen receptor deregulation drives bromodomain-mediated chromatin alterations in prostate cancer
(2017)
Global changes in chromatin accessibility may drive cancer progression by reprogramming transcription factor (TF) binding. In addition, histone acetylation readers such as bromodomain-containing protein 4 (BRD4) have been shown to associate with these TFs and contribute to aggressive cancers including prostate cancer (PC). Here, we show that chromatin accessibility defines castration-resistant prostate cancer (CRPC). We show that the deregulation of androgen receptor (AR) expression is a driver of chromatin relaxation and that AR/androgen-regulated bromodomain-containing proteins (BRDs) mediate this effect. We also report that BRDs are overexpressed in CRPCs and that ATAD2 and BRD2 have prognostic value. Finally, we developed gene stratification signature (BROMO-10) for bromodomain response and PC prognostication, to inform current and future trials with drugs targeting these processes. Our findings provide a compelling rational for combination therapy targeting bromodomains in selected patients in which BRD-mediated TF binding is enhanced or modified as cancer progresses.
Background: Glioblastoma (GBM) patients are at particularly high risk for thrombotic complications. In the event of a postoperative pulmonary embolism, therapeutic anticoagulation (tAC) is indispensable. The impact of therapeutic anticoagulation on recurrence pattern in GBM is currently unknown. Methods: We conducted a matched-pair cohort analysis of 57 GBM patients with or without tAC that were matched for age, sex, gross total resection and MGMT methylation status in a ratio of 1:2. Patients’ characteristics and clinical course were evaluated using medical charts. MRI characteristics were evaluated by two independent authors blinded to the AC status. Results: The morphologic MRI appearance in first GBM recurrence showed a significantly higher presence of multifocal, midline crossing and sharp demarcated GBM recurrence patterns in patients with therapeutic tAC compared to the matched control group. Although statistically non-significant, the therapeutic tAC cohort showed increased survival. Conclusion: Therapeutic anticoagulation induced significant morphologic changes in GBM recurrences. The underlying pathophysiology is discussed in this article but remains to be further elucidated.
Background: Even in the presence of oxygen, malignant cells often highly depend on glycolysis for energy generation, a phenomenon known as the Warburg effect. One strategy targeting this metabolic phenotype is glucose restriction by administration of a high-fat, low-carbohydrate (ketogenic) diet. Under these conditions, ketone bodies are generated serving as an important energy source at least for non-transformed cells. Methods: To investigate whether a ketogenic diet might selectively impair energy metabolism in tumor cells, we characterized in vitro effects of the principle ketone body 3-hydroxybutyrate in rat hippocampal neurons and five glioma cell lines. In vivo, a non-calorie-restricted ketogenic diet was examined in an orthotopic xenograft glioma mouse model. Results: The ketone body metabolizing enzymes 3-hydroxybutyrate dehydrogenase 1 and 2 (BDH1 and 2), 3-oxoacid-CoA transferase 1 (OXCT1) and acetyl-CoA acetyltransferase 1 (ACAT1) were expressed at the mRNA and protein level in all glioma cell lines. However, no activation of the hypoxia-inducible factor-1alpha (HIF-1alpha) pathway was observed in glioma cells, consistent with the absence of substantial 3-hydroxybutyrate metabolism and subsequent accumulation of succinate. Further, 3-hydroxybutyrate rescued hippocampal neurons from glucose withdrawal-induced cell death but did not protect glioma cell lines. In hypoxia, mRNA expression of OXCT1, ACAT1, BDH1 and 2 was downregulated. In vivo, the ketogenic diet led to a robust increase of blood 3-hydroxybutyrate, but did not alter blood glucose levels or improve survival. Conclusion: In summary, glioma cells are incapable of compensating for glucose restriction by metabolizing ketone bodies in vitro, suggesting a potential disadvantage of tumor cells compared to normal cells under a carbohydrate-restricted ketogenic diet. Further investigations are necessary to identify co-treatment modalities, e.g. glycolysis inhibitors or antiangiogenic agents that efficiently target non-oxidative pathways.
Folding of G-protein coupled receptors (GPCRs) according to the two-stage model (Popot, J. L., and Engelman, D. M. (1990) Biochemistry 29, 4031–4037) is postulated to proceed in 2 steps: partitioning of the polypeptide into the membrane followed by diffusion until native contacts are formed. Herein we investigate conformational preferences of fragments of the yeast Ste2p receptor using NMR. Constructs comprising the first, the first two, and the first three transmembrane (TM) segments, as well as a construct comprising TM1–TM2 covalently linked to TM7 were examined. We observed that the isolated TM1 does not form a stable helix nor does it integrate well into the micelle. TM1 is significantly stabilized upon interaction with TM2, forming a helical hairpin reported previously (Neumoin, A., Cohen, L. S., Arshava, B., Tantry, S., Becker, J. M., Zerbe, O., and Naider, F. (2009) Biophys. J. 96, 3187–3196), and in this case the protein integrates into the hydrophobic interior of the micelle. TM123 displays a strong tendency to oligomerize, but hydrogen exchange data reveal that the center of TM3 is solvent exposed. In all GPCRs so-far structurally characterized TM7 forms many contacts with TM1 and TM2. In our study TM127 integrates well into the hydrophobic environment, but TM7 does not stably pack against the remaining helices. Topology mapping in microsomal membranes also indicates that TM1 does not integrate in a membrane-spanning fashion, but that TM12, TM123, and TM127 adopt predominantly native-like topologies. The data from our study would be consistent with the retention of individual helices of incompletely synthesized GPCRs in the vicinity of the translocon until the complete receptor is released into the membrane interior.
Background: Transfusion of red blood cells (RBC) in patients undergoing major elective cranial surgery is associated with increased morbidity, mortality and prolonged hospital length of stay (LOS). This retrospective single center study aims to identify the impact of RBC transfusions on skull-base and non-skull-base meningioma patients including the identification of risk factors for RBC transfusion.
Methods: From October 2009 - October 2016 we retrospectively analyzed 423 primary meningioma patients undergoing surgery for primary meningioma resection our department.
Results: Of these 423 patients, 68 (16.1%) received RBC transfusion and 355 (83.9%) did not receive RBC units. Preoperative anaemia rate was significantly higher in transfused patients (17.7%) compared to patients without RBC transfusion (6.2%; p = 0.0015). In transfused patients, postoperative complications as well as hospital LOS was significantly higher (p < 00001) compared to non-transfused patients. After multivariate analyses, risk factors for RBC transfusion were preoperative American Society of Anesthesiologists (ASA) physical status score (p = 0.0247), tumor size (p = 0.0006), surgical time (p = 0.0018) and intraoperative blood loss (p < 0.001). Kaplan-Meier curves revealed significant influence on overall survival by preoperative anaemia, RBC transfusion, smoking, cardiovascular disease, preoperative KPS ≤ 60% and age (elderly ≥ 75 years).
Conclusion: We concluded that blood loss due to large tumors or localization near large vessels are the main triggers for RBC transfusion in meningioma patients paired with a potential preselection that masks the effect of preoperative anaemia in multivariate analysis. Further studies evaluating the impact of preoperative anaemia management for reduction of RBC transfusion are needed to improve clinical outcomes of meningioma patients.
Background: The extent of preoperative peritumoral edema in glioblastoma (GBM) has been negatively correlated with patient outcome. As several ongoing studies are investigating T-cell based immunotherapy in GBM, we conducted this study to assess whether peritumoral edema with potentially increased intracranial pressure, disrupted tissue homeostasis and reduced local blood flow has influence on immune infiltration and affects survival.
Methods: A volumetric analysis of preoperative imaging (gadolinium enhanced T1 weighted MRI sequences for tumor size and T2 weighted sequences for extent of edema (including the infiltrative zone, gliosis etc.) was conducted in 144 patients using the BrainlabÒ software. Immunohistochemical staining was analyzed for lymphocytic- (CD 3+) and myeloid (CD15+) tumor infiltration. A retrospective analysis of patient-, surgical-, and molecular characteristics was performed using medical records.
Results: The edema to tumor ratio was neither associated with progression-free nor overall survival (p=0.90, p=0.74). However, GBM patients displaying IDH-1 wildtype had significantly higher edema to tumor ratio than patients displaying an IDH-1 mutation (p=0.01). Immunohistopathological analysis did not show significant differences in lymphocytic or myeloid tumor infiltration (p=0.78, p=0.74) between these groups.
Conclusion: In our cohort, edema to tumor ratio had no significant correlation with immune infiltration and outcome. However, patients with an IDH-1wildtype GBM had a significantly higher edema to tumor ratio compared to their IDH-1 mutated peer group. Further studies are necessary to elucidate the underlying mechanisms.
Background: Glioblastoma (GBM) is a cancer type with high thrombogenic potential and GBM patients are therefore at a particularly high risk for thrombotic events. To date only limited data on anticoagulation management after pulmonary embolism (PE) in GBM is available and the sporadic use of DOACs remains off-label.
Methods: A retrospective cohort analysis of patients with GBM and postoperative, thoracic CT-scan confirmed, PE was performed. Clinical course, follow-up at 6 and 12 months and the overall survival (OS) were evaluated using medical charts and neuroradiological data.
Results: Out of 584 GBM patients, 8% suffered from postoperative PE. Out of theses, 30% received direct oral anticoagulants (DOACs) and 70% low-molecular-weight heparin (LMWH) for therapeutic anticoagulation. There was no significant difference in major intracranial hemorrhage (ICH), re-thrombosis or re-embolism between the two cohorts. Although statistically non-significant, a tendency to reduced mRS at 6- and 12 months was observed in the LMWH cohort. Furthermore, patients receiving DOACs had a statistical benefit in OS.
Conclusion: In our analysis DOACs showed a satisfactory safety profile in terms of major ICH, re-thrombosis and re-embolism compared to LMWH in GBM patients with postoperative PE. Prospective, randomized trials are urgent to evaluate DOACs for therapeutic anticoagulation in GBM patients with PE.