Refine
Departments, institutes and facilities
- Institut für funktionale Gen-Analytik (IFGA) (584) (remove)
Document Type
- Article (493)
- Conference Object (56)
- Part of a Book (29)
- Contribution to a Periodical (2)
- Doctoral Thesis (2)
- Preprint (1)
- Working Paper (1)
Year of publication
Keywords
- ENaC (13)
- apoptosis (9)
- cytokine-induced killer cells (9)
- immunotherapy (7)
- DNA methylation (5)
- Organic aciduria (5)
- CD21 (4)
- Inborn error of metabolism (4)
- 5-Methylcytosine (3)
- Amiloride (3)
- Arthritis (3)
- Bcl-2 (3)
- DNA damage (3)
- DNA typing (3)
- K/BxN (3)
- Ketolysis (3)
- Ketone body (3)
- Metabolic acidosis (3)
- Na+/K+-ATPase (3)
- autophagy (3)
- cancer (3)
- cell death (3)
- cytokine-induced killer (CIK) cells (3)
- delta-subunit (3)
- evolution (3)
- extremophiles (3)
- shedding (3)
- unfolded protein response (3)
- 3-hydroxyisobutyrate dehydrogenase (2)
- 3-hydroxyisobutyric aciduria (2)
- Aminoacylase (2)
- B cell activation (2)
- CIK cells (2)
- Canavan disease (2)
- Capillary electrophoresis – laser-induced fluorescence (2)
- Chronic lymphocytic leukemia (2)
- Complement receptor (2)
- Complement receptor 2/CD21 (2)
- Content Module (2)
- DNA (2)
- DNA adducts (2)
- Enzyme activity (2)
- Epithelial Na+ channel (2)
- Epithelial sodium channel (2)
- Fatty acid metabolism (2)
- Fuzzy logic (2)
- GLYCTK (2)
- Glycine conjugation (2)
- H2S (2)
- HIBADH (2)
- HIBADH deficiency (2)
- Hyperammonemia (2)
- IRE1 (2)
- Isovaleric acidemia (2)
- Ketoacidosis (2)
- Ketogenesis (2)
- Ketone body utilization (2)
- Mars (2)
- Mass spectrometry (2)
- Mast cells (2)
- Membrane Transport (2)
- Metabolic decompensation (2)
- Metabolicdecompensation (2)
- Movement disorder (2)
- NF-κB (2)
- Original Story (2)
- Oxidative stress (2)
- PERK (2)
- Programmed cell death (2)
- Rheumatoid arthritis (2)
- SLC (2)
- Shedding (2)
- Short tandem repeat (STR) (2)
- Valproic acid (2)
- Whole genome amplification (2)
- acetylcholine (2)
- cystic fibrosis (2)
- d-Glycerate kinase deficiency (2)
- d-Glyceric aciduria (2)
- edutainment (2)
- endocytosis (2)
- endoplasmic reticulum stress (2)
- epithelial sodium channel (ENaC) (2)
- extraterrestrial analogue (2)
- extremophile (2)
- force generation (2)
- fungi (2)
- fuzzy logic (2)
- gasotransmitter (2)
- hydrogen sulfide (2)
- hypermedia (2)
- ketogenesis (2)
- ketolysis (2)
- life detection (2)
- lymphoma (2)
- melanin (2)
- mucociliary clearance (2)
- myosin (2)
- organic aciduria (2)
- sodium channel (2)
- sodium self-inhibition (2)
- sodium transport (2)
- transgenic mice (2)
- water-to-land transition (2)
- 16S rRNA gene sequencing (1)
- 2B4 (1)
- 3-hydroxy-n-butyric acid (1)
- 3-hydroxyisobutyrate dehydrogenase deficiency (1)
- 3-hydroxyisobutyric acid dehydrogenase deficiency (1)
- 3D shape (1)
- 5-HT (1)
- 5-Oxoprolinase (1)
- 5-oxoprolinuria (1)
- ACAT1 (1)
- ACacylcarnitines (1)
- ADA2 (1)
- ADP release (1)
- AMAtypical myopathy (1)
- AMT (1)
- APC superfamily (1)
- AR (1)
- ASIC (1)
- ASPA (1)
- ATB0,+ (1)
- ATF4 (1)
- ATF6 (1)
- ATPase cycle (1)
- Acute lymphoblastic leukemia (1)
- Acylpeptide hydrolase (1)
- Adaptation (1)
- Affinity proteomics (1)
- Airway surface liquid (1)
- Algorithms (1)
- Alkane (1)
- Allicin (1)
- Amino Acid Sequence (1)
- Aminoacylase 1 (1)
- Amylose stationary phases (1)
- Anionic surfactant (1)
- Ankle Joint (1)
- Ankle thickness (1)
- Antarctic Polar Plateau (1)
- Antarctic ice sheet (1)
- Antibodies* (1)
- Antibody Induced Arthritis (1)
- Antibody analysis (1)
- Antigen analysis (1)
- Antiphospholipid syndrome (APS) (1)
- Apheresis therapy (1)
- Articular Cartilage (1)
- Aspartoacylase (1)
- Assay development (1)
- Augmented reality (1)
- Autism (1)
- Autoantibody (1)
- Automated multiple development (1)
- Autophagy induction (1)
- B cells (1)
- B lymphocyte (1)
- B-cell lymphoma (1)
- BAD (1)
- BLAST (1)
- Bacillus (1)
- Background music (1)
- Bacteria, Anaerobic (1)
- Bactericidal effect (1)
- Basis set (1)
- BcL-2 family (1)
- Bcl-2 proteins (1)
- Behcet’s Disease (1)
- Benzyl alkyl ammonium chloride (1)
- Beta-ketothiolase (1)
- Beta-ketothiolase deficiency (1)
- Bicycle Simulator (1)
- Biomarkers stability (1)
- Biophysics (1)
- Biosignatures (1)
- Biotin (1)
- Block copolymer (1)
- Breast (1)
- CD146 (1)
- CD30+ cells (1)
- CD40 (1)
- CD40, CTLA-4 (1)
- CDH1 (1)
- CE-LIF (1)
- CFTR (1)
- CFTR inhibitors (1)
- CFTR mutations (1)
- CHRNA (1)
- CIBERSORT (1)
- CIK-Zellen (1)
- CLL (1)
- CO (1)
- CR2 (1)
- CREBBP (1)
- Calcium signaling (1)
- Calcium storage (1)
- Cancer (1)
- Capillary electrophoresis (1)
- Carbapenem (1)
- Carboxy-terminal fragments (1)
- Carcinogenic (1)
- Cartilage Destruction (1)
- Caspase (1)
- Cationic surfactant (1)
- Cell activation (1)
- Cellulose stationary phases (1)
- Ceramides (1)
- Cervical cancer screening (1)
- Cervicovaginal microbiome (1)
- Chaetocin (1)
- Chalcogenide glass sensor (1)
- Chiral stationary phases (1)
- Chloroquine (1)
- Cholesterol (1)
- Chromatogramm (1)
- Cislunar (1)
- Cognition (1)
- Collision induced dissociation (1)
- Color/Spot-Test (1)
- Colposcopy (1)
- Complement (1)
- Complement receptor 2 (1)
- Complement receptor 2 /CD21 (1)
- Comprehensive two-dimensional liquid chromatography (1)
- Computer Graphics (1)
- Confocal microscopy (1)
- Container Structure (1)
- Cross-sensitivity (1)
- Cytochrome c (1)
- Cytokine (1)
- Cytokine-induced killer (CIK) cells (1)
- DADA2 (1)
- DBSdried blot spots (1)
- DEG/ENaC family (1)
- DIDMOAD (1)
- DNA double- strand breaks (1)
- DNA extraction protocols (1)
- DNA profile (1)
- Daptomycin (1)
- Database Management Systems (1)
- Databases, Factual (1)
- Deficiency of ADA2 (1)
- Degraded DNA (1)
- Dehydrogenase (1)
- Delta-ENaC (1)
- Diaminphenylderivat (1)
- Digital Storytelling (1)
- Diselenide bridge (1)
- Docking (1)
- Dried serum spots (1)
- Drift tube (1)
- Drug resistance (1)
- Dystonia (1)
- E-cadherin (1)
- EEG (1)
- EPHB2 (1)
- ER stress (1)
- ER-mitochondria crosstalk (1)
- ERAD (1)
- ERO1α (1)
- ESKAPEE pathogens (1)
- Ectodomain shedding (1)
- Electronic tongue (1)
- Elephantiasis (1)
- Enantioselective gas chromatography (1)
- Endoplasmatic reticulum (1)
- Endoplasmic reticulum (1)
- Endosomes (1)
- Endothelial cells (1)
- Enhancer (1)
- Enzyme activity assays (1)
- Epigenomics (1)
- Epilepsy (1)
- Epithelial-mesenchymal transition (1)
- Epitope mapping: Epitope extraction (1)
- Eriodictyol (1)
- Esterquat (1)
- Evans blue (1)
- Ewing´s Sarcoma Family of Tumors (1)
- ExoMars (1)
- Exome sequencing (1)
- FGR (1)
- FOXA1 (1)
- FOXP3 (1)
- Fabry disease (1)
- Familial glioma (1)
- Fatty acids (1)
- Fatty alcohol alkoxylate (1)
- Fatty alcohol alkoxylates (1)
- Fe-ion radiation (1)
- Fibroblast-like synoviocytes (FLS) (1)
- Food allergy (1)
- Forensic genetics (1)
- Forensic genomics (1)
- Forkhead (1)
- Fructose (1)
- GC × GC (1)
- GC×GC (1)
- GC–MSgas chromatography–mass spectrometry (1)
- GSK-3b (1)
- Galactic Cosmic Rays (GCRs) (1)
- Garlic (1)
- Gas chromatography (1)
- Gelatin Zymography (1)
- Genomics/methods (1)
- Genregulation (1)
- Gesamt-Exom-Sequenzierung (1)
- Glutathione (1)
- Glutathione synthetase (1)
- Glycerate (1)
- Glyceric aciduria (1)
- Glycine N-Acyltransferase (GLYAT) (1)
- Glycine N-acyltransferase (1)
- Glycogen storage disease type (1)
- Glycopeptides (1)
- Golgi (1)
- HCI (1)
- HDAC inhibitor (1)
- HIF1α (1)
- HILIC (1)
- HMGCL (1)
- HPLC Optimierung (1)
- HPTLC (1)
- HPV diagnostic (1)
- HSD10 (1)
- HSP90 (1)
- Head-Mounted Displays (1)
- Health care policy (1)
- High hyperdiploidy (1)
- High performance liquid chromatography (1)
- Histamine (1)
- Histamine receptors (1)
- Humans (1)
- Hydrophobic interaction (1)
- Hydrophobicity (1)
- Hydroxychloroquine (1)
- Hypoglycemia (1)
- IR microspectroscopy (1)
- Ikaros (1)
- Illegal Wildlife Trade (1)
- Immersive Virtual Environments (1)
- Immersive Visualization Environment (1)
- Immune escape (1)
- Immunoadsorption (1)
- Immunology* (1)
- In silico epitope prediction (1)
- In silico modelling (1)
- Inborn errors of metabolism (1)
- Inherited metabolic disorders (1)
- Inhibitor (1)
- Intellectual disability (1)
- Interactive computer graphics (1)
- Intracellular Ca2+ (1)
- Involution (1)
- Ion mobility (1)
- Ion mobility spectrometer (1)
- Ionizing radiation (1)
- Isoleucine (1)
- Isoleucine degradation (1)
- Joint Destruction (1)
- Juvenile arthritis (JA) (1)
- K/BxN mouse model (1)
- K/B×N model (1)
- Ketoasidoz (1)
- Ketogenic diet (1)
- Ketone body synthesis (1)
- Kozak-sequence (1)
- Krebsforschung (1)
- Kriminaltechnik (1)
- LCxLC-MS (1)
- LEF1 (1)
- LET (1)
- LFA-1 (1)
- Laser-induced fluorescence (1)
- Leg (1)
- LeuT (1)
- Leucine (1)
- Leucine degradation (1)
- Ligand -Receptor Interactions* (1)
- Linezolid (1)
- Lipophilicity (1)
- Lipophilicity potential (1)
- Locomotion (1)
- Lymphedema (1)
- Lysosome (1)
- Lysosomes (1)
- MADDMultiple acyl-CoA dehydrogenase deficiency (1)
- MALDI QIT TOF MS (1)
- MCF-10A (1)
- MCT (1)
- MICA/B (1)
- MMP-9 (1)
- MOCS1 (1)
- MP2.5 (1)
- MPV17 monoclonal antibody (1)
- MRPP (1)
- MS/MS peptide sequencing (1)
- MYB (1)
- Macrophage (1)
- Macrophage migration inhibitory factor (1)
- Macrophages (1)
- Magnetic resonance imaging (MRI) (1)
- Mammary (1)
- Marbled crayfish (1)
- Mars environment (1)
- Mars exploration (1)
- Matrix metalloproteases (1)
- Mechanosensitive (1)
- Media in education (1)
- Memory (1)
- Metabolic stroke (-like event) (1)
- Methylation (1)
- Methylmalonic acidemia (1)
- Methylmalonic aciduria (1)
- Methylmalonyl-CoAmutase (1)
- Methyltransferase (1)
- Micromanipulation (1)
- Mitochondria (1)
- Mitochondria associated ER membranes (1)
- Mitochondrial DNA depletion syndrome (1)
- Mitochondrial apoptogens (1)
- Mitochondrial outer membrane permeabilization (MOMP) (1)
- Mitochondrial tRNA (1)
- Moco deficiency (1)
- Molecular Sequence Data (1)
- Molecular dynamics (1)
- Molecular modelling (1)
- Molecular rotation (1)
- Molecular surface (1)
- Molybdenum cofactor (1)
- Monocarboxylate transporter 1 (1)
- Motion tracking (1)
- Multi-component heavy metal solution (1)
- N-acetylaspartic acid (1)
- N-acylated amino acids (1)
- N-isovalerylglycine (1)
- NGS (1)
- NKG2D (1)
- NO (1)
- NSS family (1)
- Na+ absorption (1)
- Na+/K+ ATPase (1)
- Narration Module (1)
- Native mass spectrometry (1)
- Neugeborenenscreening (1)
- Neurometabolic disease (1)
- Neuropilin (1)
- Next Generation Sequencing (NGS) (1)
- Next generation sequencing (1)
- Nitrogruppe (1)
- Nitrosamine (1)
- Non-covalent interaction MS* (1)
- Nonketotic hyperglycinemia (1)
- OA, organic acids (1)
- OXCT1 (1)
- Occupational safety (1)
- Off-target effects (1)
- Oligodendroglioma (1)
- Orai1 (1)
- Organic acids (1)
- Organic compounds and Functional groups (1)
- Organische Säuren (1)
- Orion (1)
- PCR inhibitors (1)
- PD-1/CTLA-4 (1)
- PDI (1)
- PK-B/Akt (1)
- PLASM (1)
- Pain Reduction (1)
- Partikeltechnologie (1)
- Partition coefficients (1)
- Patient serum (1)
- Peroxisomes (1)
- Pervanadate (1)
- Pharmacogenetics (1)
- Phase II reaction (1)
- Physical exercising game platform (1)
- Polymorphism (1)
- Pre-punched filter paper discs (1)
- Pregnancy (1)
- Probabilistic methods (1)
- Prognosis (1)
- Propionic acidemia (1)
- Propionic aciduria (1)
- Propionyl-CoA carboxylase (1)
- Proteasome (1)
- Proteasome maturation (1)
- Protein Conformation (1)
- Protein Folding (1)
- Protein complex analysis (1)
- Protein folding (1)
- Protein homeostasis (1)
- Protein-protein interaction (1)
- Proteins/chemistry (1)
- Proteome analysis (1)
- Pulmonary epithelium (1)
- Pyroglutamic aciduria (1)
- Quantum mechanical methods (1)
- Quasi equilibrium conditions (1)
- R751L (1)
- RAID (1)
- RAS (1)
- RELA (1)
- RELA haploinsufficiency (1)
- RELA-associated inflammatory disease (1)
- Raman and FTIR spectroscopies (1)
- Random copolymer (1)
- Redox potential (1)
- Relapse (1)
- Relative Energies (1)
- Restorative Virtual Environments (1)
- RhoA GTPases (1)
- S-sulfocysteine (1)
- SAHA (1)
- SARS-COV-2 virus (1)
- SARS-CoV-2 (1)
- SCNN1D (1)
- SERS (1)
- SGN-35 (1)
- SLC6 (1)
- SLC6A14 (1)
- SNPSTR (1)
- SOS-LC (1)
- STARLIFE project (1)
- Scalable Vector Graphic (1)
- Schmauchspur (1)
- Schusswaffe (1)
- Seizures (1)
- Selektives Screening (1)
- Selenocysteine (1)
- Sequence Homology, Amino Acid (1)
- Serine (1)
- Sexual assault (1)
- Shear force (1)
- Silmitasertib (1)
- Single sperm cells (1)
- Skin (1)
- Soluble CD21 (1)
- Soluble CD23 (1)
- Space radiation (1)
- Splicing (1)
- Star Trek (1)
- Store-operated calcium entry (1)
- Story Element (1)
- Stratum corneum lipids (1)
- Stress Management (1)
- Submerge and dry protocol (1)
- Submucosal plexus (1)
- Sulfite oxidase (1)
- Surfactants (1)
- Survey (1)
- Synovial fluid (1)
- Systemic lupus erythomatosus (SLE) (1)
- TNF inhibitors (1)
- TP53 (1)
- Tandem-Massenspektrometrie (1)
- Targeted mass spectrometry (1)
- Telemedicine (1)
- Telogen hair (1)
- Tetramerisation (1)
- Therapeutic antibodies* (1)
- Thiol antioxidants (1)
- Time–kill methodology (1)
- Transcriptional enhancer (1)
- Transgenic mice (1)
- Triangle mesh (1)
- UI design (1)
- UPR signaling (1)
- UV-vis spectroscopy (1)
- Urea cycle defect (1)
- Urinary organic acids (1)
- Urine organic acid analysis (1)
- Urothione (1)
- User-Centered Approach (1)
- User-Computer Interface (1)
- VR (1)
- Vascular permeability (1)
- Virtual Environment (1)
- Virtual Memory Palace (1)
- Virtual Reality (1)
- Virtual reality (1)
- Vitamin A acetate isomers (1)
- Vitamin B12/adenosylcobalamin (1)
- Western blot (1)
- Whole-genome sequencing (1)
- Wild Type Mouse (1)
- Wildlife Forensics (1)
- Wnt/β-catenin (1)
- Wolframin (1)
- X-STR (1)
- XBP1 (1)
- Xenopus (1)
- Xenopus laevis (1)
- Xenopus oocyte (1)
- Y-STR (1)
- Yeast (1)
- Yersinia toxins (1)
- ZAP-70 (1)
- Zytokin-induzierte Killerzellen (1)
- accelerated iron ions (1)
- acetoacetic acid (1)
- acetone (1)
- actin (1)
- acute (1)
- acute respiratory distress syndrome (1)
- adaptive filters (1)
- adoptive cell transfer (1)
- affective computing (1)
- air-blood barrier (1)
- airway (1)
- airway rehydration (1)
- airway smooth muscle (1)
- albuminuria (1)
- alkaline phosphatase (1)
- allopurinol (1)
- allosteric communication (1)
- allosteric regulation (1)
- altered mitochondrial homeostasis (1)
- alveolar epithelium (1)
- alveolar fluid (1)
- alveolar fluid transport (1)
- alveoli (1)
- amino acid transport (1)
- amino acid transporter (1)
- amplicon sequencing (1)
- anaplastic lymphoma kinase (1)
- anorganische Schmauchspur (1)
- anti-TNF (1)
- antibody–drug conjugate (1)
- arthritis (1)
- astrobiology (1)
- atopy (1)
- autoimmune disease (1)
- autoimmunity (1)
- autoinflammation (1)
- autoinflammatory (1)
- autoinflammatory diseases (1)
- automated electrophysiology (1)
- automatic segmentation (1)
- automation of sample processing (1)
- autophagy signaling pathways (1)
- bacteria (1)
- bdelloid rotifer (1)
- biochemical fingerprinting (1)
- biochemistry (1)
- biofilm removal (1)
- biofilm-related infections (1)
- bioinformatics (1)
- biomarker (1)
- black fungi (1)
- blebbistatin (1)
- bone marrow failure (1)
- brain computer interfaces (1)
- brain tumor (1)
- branched-chain amino acids (1)
- breast cancer (1)
- breathing (1)
- bronchus (1)
- brush cells (1)
- built environment (1)
- cPMP (1)
- cancer progression (1)
- cancer treatment (1)
- cannabidiol, immunotherapy (1)
- carbohydrate metabolism (1)
- carbon monoxide (1)
- carbon monoxide-releasing molecule (1)
- caspase (1)
- caspase-3 (1)
- caspases (1)
- caveolin-1 (1)
- cell division (1)
- cell stress (1)
- chaetocin (1)
- chemical pathology (1)
- chemical sensors (1)
- chemosensory cells (1)
- childhood (1)
- childhood cancer syndrome (1)
- cholinergic (1)
- chromatin remodeling (1)
- chymotrypsin (1)
- ciclopirox olamine (1)
- clear cell renal cell carcinoma (1)
- clinical study (1)
- clinical trials (1)
- colorimetry (1)
- common variable immunodeficiency (1)
- compensation (1)
- complete basis set limit (1)
- computer vision (1)
- conformations (1)
- constitutional mismatch repair syndrome (1)
- contraction (1)
- cosmic rays (1)
- cyanide (1)
- cysticfibrosis (1)
- cytoskeleton (1)
- data base search (1)
- deficiency of adenosine deaminase 2 (1)
- degraded DNA (1)
- desert cyanobacteria (1)
- diagnosis and management (1)
- differentiation (1)
- digital storytelling (1)
- disabled people (1)
- distributed authoring (1)
- drug detoxification (1)
- drugs (1)
- duty ratio (1)
- dynamin (1)
- electrochemical sensor (1)
- electrolyte transport (1)
- electrophysiology (1)
- electroretinography (1)
- electrostatic potential (1)
- emotion computing (1)
- endoplasmic reticulum (ER) stress (1)
- enzyme activity (1)
- epilepsy (1)
- epithelial sodium channel (1)
- epithelial sodium channels (1)
- epithelial transport (1)
- epitope mapping (1)
- erbliche Krebssyndrome (1)
- ethacrynic acid (1)
- exon fusion (1)
- extra column band broadening (1)
- extraction-linked bias (1)
- familial Mediterranean fever (1)
- fatty acid metabolism (1)
- fish gill (1)
- flow cytometry (1)
- forensic (1)
- forensic genetics (1)
- four-ply (1)
- fuel (1)
- fungal and bacterial amplicon sequencing (1)
- furin (1)
- gas exchange (1)
- gene expression (1)
- genes (1)
- genetic testing (1)
- genetics (1)
- genetische Testung (1)
- genome sequencing (1)
- genomic data (1)
- genotype-phenotype correlations (1)
- glycerol (1)
- glycerophosphocholine (1)
- glycosylation (1)
- growth hormone (1)
- guidelines (1)
- habitability (1)
- healthcare-associated infections (HAI) (1)
- heat shock proteins (1)
- heat shock response (1)
- heavy ion particle (HZE) radations (1)
- heavy metal (1)
- hematopoietic stem cell transplantation (1)
- hepatocellular carcinoma (1)
- heterozygous ALPL mutation (1)
- high-performance liquid chromatography (1)
- high-throughput DNA sequencing (1)
- high-throughput sequencing (1)
- histamine receptor (1)
- histamine receptor antagonist (1)
- histidine decarboxylase (1)
- histone deacetylase inhibitors (1)
- hospital environment (1)
- hospital-acquired infections (1)
- human microbiome (1)
- hydrocarbon (1)
- hypermedia applications (1)
- hypertension (1)
- hypogammaglobulinemia (1)
- hypophosphatasia (1)
- hypoxia (1)
- immune checkpoint inhibition programmed cell death-1 (1)
- immunhistochemistry (1)
- immunodeficiency (1)
- immunology (1)
- infection prevention (1)
- inflammasome (1)
- inherited metabolic disease (1)
- inhibitor (1)
- inorganic pyrophosphate (1)
- insertion (1)
- interactive computer graphics (1)
- interferon γ (1)
- interleukin-1beta (1)
- intrinsic pathway (1)
- ion-selective electrodes (1)
- isoleucine (1)
- isoleucine metabolism (1)
- ketogenesis defects (1)
- ketogenez defektleri (1)
- ketoliz defektleri (1)
- ketolysis defects (1)
- keton bodies (1)
- ketone body synthesis (1)
- klarzelliges Nierenzellkarzinom (1)
- leucine (1)
- leucine degradation (1)
- leukemia (1)
- life on Mars (1)
- life-detection (1)
- linguistic variable (1)
- linguistic variables (1)
- lipid (1)
- lipid biosynthesis (1)
- liquid chromatography (1)
- local lipophilicity (1)
- long interspersed nuclear element-1 (1)
- loss-of-function variants (1)
- lung (1)
- lung cancer (1)
- lung liquid clearance (1)
- lymphocytic (1)
- lysophosphatidylcholine (1)
- mTOR (1)
- macrophages. (1)
- major histocompatibility complex class I polypeptide-related sequence A (MICA) (1)
- mammary gland (1)
- massive parallel sequencing (1)
- member D (NKG2D) (1)
- membrane trafficking (1)
- metabolic acidosis (1)
- metabolic effects (1)
- metabolic integration (1)
- metabolically active cells (1)
- methylmalonic acidaemia (1)
- methylmalonic acidemia (1)
- microbial community structure (1)
- microbial ecology (1)
- microbiome (1)
- microbiome analyses (1)
- microcephaly (1)
- microdialysis (1)
- micromanipulation (1)
- mitochondrial biogenesis (1)
- mitosis (1)
- mixed reality (1)
- mixed-mode chromatography (1)
- molecular docking (1)
- molecular dynamics simulations (1)
- molecular evolution (1)
- molecular motor (1)
- molecular surfaces (1)
- momentary frequency (1)
- monoclonal antibody (1)
- mouse model (1)
- mp2 (1)
- mucosal ulcers (1)
- multiple myeloma (1)
- multiple myeloma (MM) (1)
- muscarine (1)
- mutation (1)
- myogenesis (1)
- natural killer group 2 (1)
- next generation sequencing (1)
- nicotine and phosphocholine (1)
- nitric oxide (1)
- non-apoptotic roles (1)
- non-small cell lung cancer (1)
- nonlinear storytelling (1)
- nosocomial infections (1)
- nucleic acids (1)
- nutrient germinants (1)
- octane (1)
- optimized geometries (1)
- organic acid analysis (1)
- organische Schmauchspur (1)
- outer space (1)
- outside-out (1)
- pH (1)
- paediatric clinical genetics & dysmorphology (1)
- paediatric endocrinology (1)
- paediatric intensive & critical care (1)
- panspermia (1)
- patch clamp (1)
- patch-clamp (1)
- pathogen control (1)
- pathophysiology (1)
- peptide sequencing (1)
- pharmacokinetics (1)
- phenylketonuria (1)
- phosphoethanolamine (1)
- photometry (1)
- physiology (1)
- pigments (1)
- planetary protection (1)
- porphyria (1)
- power stroke (1)
- primary airway epithelial cells (1)
- probiotic cleaning (1)
- probiotic-based cleaning formulations (1)
- proliferation (1)
- propan-2-ol (1)
- propionic acidaemia (1)
- propionic acidemia (1)
- protease (1)
- protein microarray (1)
- protein secretion (1)
- proteomics (1)
- proximal tubule (1)
- pseudogene (1)
- pure red cell aplasia (1)
- pyridoxal phosphate (1)
- pyrin inflammasome (1)
- qPCR (1)
- quantum mechanics (1)
- radiation (1)
- radioresistance (1)
- real-time PCR (1)
- recurrent ketoacidotic episodes (1)
- renal cancer (1)
- renal cell carcinoma (1)
- renal tubular cells (1)
- resistance (1)
- retinal degeneration (1)
- rheumatoid arthritis (1)
- rodent (1)
- rodents (1)
- sCD21 (1)
- sFRP-4 (1)
- salt (1)
- screening (1)
- see-through display (1)
- selectivity tuning (1)
- sensitize (1)
- sequencing (1)
- serine-threonine kinase (1)
- serum and glucocorticoid-induced kinase 1 (1)
- sexual assault (1)
- short tandem repeat (1)
- short tandem repeat (STR) (1)
- single-cell RNA-seq (1)
- sirtuins (1)
- skin cancer (1)
- small molecule (1)
- sodium absorption (1)
- sodium/potassium-exchanging ATPase (1)
- solute carrier (1)
- space radiation environment (1)
- sperm cell (1)
- spore resistance (1)
- sporegermination (1)
- stationary phase (1)
- story authoring (1)
- structural biology (1)
- superficially porous particles (1)
- surface sanitization (1)
- surface shape (1)
- surface topography (1)
- surface topology (1)
- surrogate endpoint (1)
- survival (1)
- symbiosis (1)
- system optimization (1)
- tRNA processing (1)
- taste (1)
- temporomandibular joint (1)
- tetrapod (1)
- therapy (1)
- thermophoresis (1)
- three-ply (1)
- tiglyglycine (1)
- time series processing (1)
- transient kinetics (1)
- transient receptor potential vanilloid Type 2 (1)
- transporter (1)
- triiodothyronine (1)
- tumor microenvironment (1)
- tumor-infiltrating immune cells (1)
- two-electrode voltage clamp (1)
- ubiquitination (1)
- unfolded protein response (UPR) (1)
- urethra (1)
- urethral brush cells (1)
- valine catabolic pathway (1)
- valine degradation (1)
- van Deemter curve (1)
- vasculitis (1)
- voltage-independent Na+ channel (1)
- water dimer (1)
- whole genome amplification (WGA) (1)
- whole-exome sequencing (1)
- µCT (1)
- β-catenin (1)
- β-cells (1)
- γ-glutamyl cycle (1)
The gasotransmitter hydrogen sulphide decreases Na⁺ transport across pulmonary epithelial cells
(2012)
BACKGROUND AND PURPOSE The transepithelial absorption of Na(+) in the lungs is crucial for the maintenance of the volume and composition of epithelial lining fluid. The regulation of Na(+) transport is essential, because hypo- or hyperabsorption of Na(+) is associated with lung diseases such as pulmonary oedema or cystic fibrosis. This study investigated the effects of the gaseous signalling molecule hydrogen sulphide (H(2) S) on Na(+) absorption across pulmonary epithelial cells. EXPERIMENTAL APPROACH Ion transport processes were electrophysiologically assessed in Ussing chambers on H441 cells grown on permeable supports at air/liquid interface and on native tracheal preparations of pigs and mice. The effects of H(2)S were further investigated on Na(+) channels expressed in Xenopus oocytes and Na(+) /K(+)-ATPase activity in vitro. Membrane abundance of Na(+) /K(+)-ATPase was determined by surface biotinylation and Western blot. Cellular ATP concentrations were measured colorimetrically, and cytosolic Ca(2+) concentrations were measured with Fura-2. KEY RESULTS H(2)S rapidly and reversibly inhibited Na(+) transport in all the models employed. H(2)S had no effect on Na(+) channels, whereas it decreased Na(+) /K(+)-ATPase currents. H(2)S did not affect the membrane abundance of Na(+) /K(+)-ATPase, its metabolic or calcium-dependent regulation, or its direct activity. However, H(2)S inhibited basolateral calcium-dependent K(+) channels, which consequently decreased Na(+) absorption by H441 monolayers. CONCLUSIONS AND IMPLICATIONS H(2) S impairs pulmonary transepithelial Na(+) absorption, mainly by inhibiting basolateral Ca(2+)-dependent K(+) channels. These data suggest that the H(2)S signalling system might represent a novel pharmacological target for modifying pulmonary transepithelial Na(+) transport.
The vectorial transport of Na+ across epithelia is crucial for the maintenance of Na+ and water homeostasis in organs such as the kidneys, lung, or intestine. Dysregulated Na+ transport processes are associated with various human diseases such as hypertension, the salt-wasting syndrome pseudohypoaldosteronism type 1, pulmonary edema, cystic fibrosis, or intestinal disorders, which indicate that a precise regulation of epithelial Na+ transport is essential. Novel regulatory signaling molecules are gasotransmitters. There are currently three known gasotransmitters: nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S). These molecules are endogenously produced in mammalian cells by specific enzymes and have been shown to regulate various physiological processes. There is a growing body of evidence which indicates that gasotransmitters may also regulate Na+ transport across epithelia. This review will summarize the available data concerning NO, CO, and H2S dependent regulation of epithelial Na+ transport processes and will discuss whether or not these mediators can be considered as true physiological regulators of epithelial Na+ transport biology.
ENaC channels
(2023)
More than 25 years ago, it was a big surprise for physiologists that nitric oxide (NO) was identified as the endothelium derived relaxing factor which is responsible for endothelium-induced smooth muscle relaxation (Ignarro et al., 1987). Until then, small gaseous molecules were simply regarded as byproducts of cellular metabolism which were unlikely to be of any physiological relevance. The discovery that NO was synthesized by specific enzymes (NO-synthases), upon stimulation by specific, physiologically relevant stimuli (e.g., acetylcholine stimulation of endothelial cells), as well as the fact that it acted on specific cellular targets (e.g., soluble guanylate cyclase), set the course for numerous studies which investigated the physiological roles of gaseous signaling molecules—in other words, gasotransmitters (Wang, 2002).
The development of pulmonary edema can be considered as a combination of alveolar flooding via increased fluid filtration, impaired alveolar-capillary barrier integrity, and disturbed resolution due to decreased alveolar fluid clearance. An important mechanism regulating alveolar fluid clearance is sodium transport across the alveolar epithelium. Transepithelial sodium transport is largely dependent on the activity of sodium channels in alveolar epithelial cells. This paper describes how sodium channels contribute to alveolar fluid clearance under physiological conditions and how deregulation of sodium channel activity might contribute to the pathogenesis of lung diseases associated with pulmonary edema. Furthermore, sodium channels as putative molecular targets for the treatment of pulmonary edema are discussed.
Carbon Monoxide Rapidly Impairs Alveolar Fluid Clearance by Inhibiting Epithelial Sodium Channels
(2009)
Carbon monoxide (CO) is currently being evaluated as a therapeutic modality in the treatment of patients with acute lung injury and acute respiratory distress syndrome. No study has assessed the effects of CO on transepithelial ion transport and alveolar fluid reabsorption, two key aspects of alveolocapillary barrier function that are perturbed in acute lung injury/acute respiratory distress syndrome. Both CO gas (250 ppm) and CO donated by the CO donor, CO-releasing molecule (CORM)-3 (100 mu M in epithelial lining fluid), applied to healthy, isolated, ventilated, and perfused rabbit lungs, significantly blocked Na-22(+) clearance from the alveolar compartment, and blocked alveolar fluid reabsorption after fluid challenge. Apical application of two CO donors, CORM-3 or CORM-A1 (100 mu M), irreversibly inhibited amiloride-sensitive short-circuit currents in H441 human bronchiolar epithelial cells and primary rat alveolar type II cells by up to 40%. Using a nystatin permabilization approach, the CO effect was localized to amiloride-sensitive channels on the apical surface. This effect was abolished by hemoglobin, a scavenger of CO, and was not observed when inactive forms of CO donors were employed. The effects of CO were not blocked by 8-bromoguanosine-3',5'-cyclic guanosine monophosphate, soluble guanylate cyclase inhibitors (methylene blue and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one), or inhibitors of trafficking events (phalloidin oleate, MG-132, and brefeldin A), but the amiloride affinity of H441 cells was reduced after CO exposure. These data indicate that CO rapidly inhibits sodium absorption across the airway epithelium by cyclic guanosine monophosphate-and trafficking-independent mechanisms, which may rely on critical histidine residues in amiloride-sensitive channels or associated regulatory proteins on the apical surface of lung epithelial cells.
The epithelial sodium channel (ENaC) is a heterotrimeric ion channel that plays a key role in sodium and water homeostasis in tetrapod vertebrates. In the aldosterone-sensitive distal nephron, hormonally controlled ENaC expression matches dietary sodium intake to its excretion. Furthermore, ENaC mediates sodium absorption across the epithelia of the colon, sweat ducts, reproductive tract, and lung. ENaC is a constitutively active ion channel and its expression, membrane abundance, and open probability (PO) are controlled by multiple intracellular and extracellular mediators and mechanisms [9]. Aberrant ENaC regulation is associated with severe human diseases, including hypertension, cystic fibrosis, pulmonary edema, pseudohypoaldosteronism type 1, and nephrotic syndrome [9].
Nitric oxide (NO) is an important regulator of Na+ reabsorption by pulmonary epithelial cells and therefore of alveolar fluid clearance. The mechanisms by which NO affects epithelial ion transport are poorly understood and vary from model to model. In this study, the effects of NO on sodium reabsorption by H441 cell monolayers were studied in an Ussing chamber. Two NO donors, (Z)-1-[N-(3-aminopropyl)-N-(n-propyl) amino]diazen-1-ium-1,2-diolate and diethylammonium(Z)-1-(N, N-diethylamino) diazen-1-ium-1,2-diolate, rapidly, reversibly, and dose-dependently reduced amiloride-sensitive, short-circuit currents across H441 cell monolayers. This effect was neutralized by the NO scavenger hemoglobin and was not observed with inactive NO donors. The effects of NO were not blocked by 8-bromoguanosine-3',5'-cyclic monophosphate or by soluble guanylate cyclase inhibitors (methylene blue and 1H-[1,2,4] oxadiazolo[4,3-a]quinoxalin-1-one) and were therefore independent of soluble guanylate cyclase signaling. NO targeted apical, highly selective, amiloride-sensitive Na+ channels in basolaterally permeabilized H441 cell monolayers. NO had no effect on the activity of the human epithelial sodium channel heterologously expressed in Xenopus oocytes. NO decreased Na+/K+-ATPase activity in apically permeabilized H441 cell monolayers. The inhibition of Na+/K+-ATPase activity by NO was reversed by mercury and was mimicked by N-ethylmaleimide, which are agents that reverse and mimic, respectively, the reaction of NO with thiol groups. Consistent with these data, S-NO groups were detected on the Na+/K+-ATPase a subunit in response to NO-donor application, using a biotin-switch approach coupled to a Western blot. These data demonstrate that, in the H441 cell model, NO impairs Na+ reabsorption by interfering with the activity of highly selective Na+ channels and the Na+/K+-ATPase.
Once aberrantly activated, the Wnt/βcatenin pathway may result in uncontrolled proliferation and eventually cancer. Efforts to counter and inhibit this pathway are mainly directed against βcatenin, as it serves a role on the cytoplasm and the nucleus. In addition, speciallygenerated lymphocytes are recruited for the purpose of treating liver cancer. Peripheral blood mononuclear lymphocytes are expanded by the timely addition of interferon γ, interleukin (IL)1β, IL2 and anticluster of differentiation 3 antibody. The resulting cells are called cytokineinduced killer (CIK) cells. The present study utilised these cells and combine them with drugs inhibiting the Wnt pathway in order to examine whether this resulted in an improvement in the killing ability of CIK cells against liver cancer cells. Drugs including ethacrynic acid (EA) and ciclopirox olamine (CPX) were determined to be suitable candidates, as determined by previous studies. Drugs were administered on their own and combined with CIK cells and then a cell viability assay was performed. These results suggest that EAtreated cells demonstrated apoptosis and were significantly affected compared with untreated cells. Unlike EA, CPX killed normal and cancerous cells even at low concentrations. Subsequent to combining EA with CIK cells, the potency of killing was increased and a greater number of cells died, which proves a synergistic action. In summary, EA may be used as an antihepatocellular carcinoma drug, while CPX possesses a high toxicity to cancerous as well as to normal cells. It was proposed that EA should be integrated into present therapeutic methods for cancer.
RELA haploinsufficiency is a recently described autoinflammatory condition presenting with intermittent fevers and mucocutaneous ulcerations. The RELA gene encodes the p65 protein, one of five NF-κB family transcription factors. As RELA is an essential regulator of mucosal homeostasis, haploinsufficiency leads to decreased NF-κB signaling which promotes TNF-driven mucosal apoptosis with impaired epithelial recovery. Thus far, only eight cases have been reported in the literature. Here, we report four families with three novel and one previously described pathogenic variant in RELA. These four families included 23 affected individuals for which genetic testing was available in 16. Almost half of these patients had been previously diagnosed with more common rheumatologic entities (such as Behcet's Disease; BD) prior to the discovery of their pathogenic RELA variants. The most common clinical features were orogenital ulcers, rash, joint inflammation, and fever. The least common were conjunctivitis and recurrent infections. Clinical variability was remarkable even among familial cases, and incomplete penetrance was observed. Patients in our series were treated with a variety of medications, and benefit was observed with glucocorticoids, colchicine, and TNF inhibitors. Altogether, our work adds to the current literature and doubles the number of reported cases with RELA-Associated Inflammatory Disease (RAID). It reaffirms the central importance of the NF-κB pathway in immunity and inflammation, as well as the important regulatory role of RELA in mucosal homeostasis. RELA associated inflammatory disease should be considered in all patients with BD, particularly those with early onset and/or with a strong family history.
SLC6A14 (ATB0,+) is unique among SLC proteins in its ability to transport 18 of the 20 proteinogenic (dipolar and cationic) amino acids and naturally occurring and synthetic analogues (including anti-viral prodrugs and nitric oxide synthase (NOS) inhibitors). SLC6A14 mediates amino acid uptake in multiple cell types where increased expression is associated with pathophysiological conditions including some cancers. Here, we investigated how a key position within the core LeuT-fold structure of SLC6A14 influences substrate specificity. Homology modelling and sequence analysis identified the transmembrane domain 3 residue V128 as equivalent to a position known to influence substrate specificity in distantly related SLC36 and SLC38 amino acid transporters. SLC6A14, with and without V128 mutations, was heterologously expressed and function determined by radiotracer solute uptake and electrophysiological measurement of transporter-associated current. Substituting the amino acid residue occupying the SLC6A14 128 position modified the binding pocket environment and selectively disrupted transport of cationic (but not dipolar) amino acids and related NOS inhibitors. By understanding the molecular basis of amino acid transporter substrate specificity we can improve knowledge of how this multi-functional transporter can be targeted and how the LeuT-fold facilitates such diversity in function among the SLC6 family and other SLC amino acid transporters.
The human MPV17-related mitochondrial DNA depletion syndrome is an inherited autosomal recessive disease caused by mutations in the inner mitochondrial membrane protein MPV17. Although more than 30 MPV17 gene mutations were shown to be associated with mitochondrial DNA depletion syndrome, the function of MPV17 is still unknown. Mice deficient in Mpv17 show signs of premature aging. In the present study, we used electrophysiological measurements with recombinant MPV17 to reveal that this protein forms a non-selective channel with a pore diameter of 1.8 nm and located the channel's selectivity filter. The channel was weakly cation-selective and showed several subconductance states. Voltage-dependent gating of the channel was regulated by redox conditions and pH and was affected also in mutants mimicking a phosphorylated state. Likewise, the mitochondrial membrane potential (Δψm) and the cellular production of reactive oxygen species were higher in embryonic fibroblasts from Mpv17−/− mice. However, despite the elevated Δψm, the Mpv17-deficient mitochondria showed signs of accelerated fission. Together, these observations uncover the role of MPV17 as a Δψm-modulating channel that apparently contributes to mitochondrial homeostasis under different conditions.
Among the celestial bodies in the Solar System, Mars currently represents the main target for the search for life beyond Earth. However, its surface is constantly exposed to high doses of cosmic rays (CRs) that may pose a threat to any biological system. For this reason, investigations into the limits of resistance of life to space relevant radiation is fundamental to speculate on the chance of finding extraterrestrial organisms on Mars. In the present work, as part of the STARLIFE project, the responses of dried colonies of the black fungus Cryomyces antarcticus Culture Collection of Fungi from Extreme Environments (CCFEE) 515 to the exposure to accelerated iron (LET: 200 keV/μm) ions, which mimic part of CRs spectrum, were investigated. Samples were exposed to the iron ions up to 1000 Gy in the presence of Martian regolith analogues. Our results showed an extraordinary resistance of the fungus in terms of survival, recovery of metabolic activity and DNA integrity. These experiments give new insights into the survival probability of possible terrestrial-like life forms on the present or past Martian surface and shallow subsurface environments.
Evolutionary conservation of the antimicrobial function of mucus: a first defence against infection
(2018)
Mucus layers often provide a unique and multi-functional hydrogel interface between the epithelial cells of organisms and their external environment. Mucus has exceptional properties including elasticity, changeable rheology and an ability to self-repair by reannealing, and is therefore an ideal medium for trapping and immobilising pathogens and serving as a barrier to microbial infection. The ability to produce a functional surface mucosa was an important evolutionary step, which evolved first in the Cnidaria, which includes corals, and the Ctenophora. This allowed the exclusion of non-commensal microbes and the subsequent development of the mucus-lined digestive cavity seen in higher metazoans. The fundamental architecture of the constituent glycoprotein mucins is also evolutionarily conserved. Although an understanding of the biochemical interactions between bacteria and the mucus layer are important to the goal of developing new antimicrobial strategies, they remain relatively poorly understood. This review summarises the physicochemical properties and evolutionary importance of mucus, which make it so successful in the prevention of bacterial infection. In addition, the strategies developed by bacteria to counteract the mucus layer are also explored.
The deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessively inherited disease that has undergone extensive phenotypic expansion since being first described in patients with fevers, recurrent strokes, livedo racemosa, and polyarteritis nodosa in 2014. It is now recognized that patients may develop multisystem disease that spans multiple medical subspecialties. Here, we describe the findings from a large single center longitudinal cohort of 60 patients, the broad phenotypic presentation, as well as highlight the cohort's experience with hematopoietic cell transplantation and COVID-19. Disease manifestations could be separated into three major phenotypes: inflammatory/vascular, immune dysregulatory, and hematologic, however, most patients presented with significant overlap between these three phenotype groups. The cardinal features of the inflammatory/vascular group included cutaneous manifestations and stroke. Evidence of immune dysregulation was commonly observed, including hypogammaglobulinemia, absent to low class-switched memory B cells, and inadequate response to vaccination. Despite these findings, infectious complications were exceedingly rare in this cohort. Hematologic findings including pure red cell aplasia (PRCA), immune-mediated neutropenia, and pancytopenia were observed in half of patients. We significantly extended our experience using anti-TNF agents, with no strokes observed in 2026 patient months on TNF inhibitors. Meanwhile, hematologic and immune features had a more varied response to anti-TNF therapy. Six patients received a total of 10 allogeneic hematopoietic cell transplant (HCT) procedures, with secondary graft failure necessitating repeat HCTs in three patients, as well as unplanned donor cell infusions to avoid graft rejection. All transplanted patients had been on anti-TNF agents prior to HCT and received varying degrees of reduced-intensity or non-myeloablative conditioning. All transplanted patients are still alive and have discontinued anti-TNF therapy. The long-term follow up afforded by this large single-center study underscores the clinical heterogeneity of DADA2 and the potential for phenotypes to evolve in any individual patient.
Methylmalonic and propionic acidemia (MMA/PA) are inborn errors of metabolism characterized by accumulation of propionic acid and/or methylmalonic acid due to deficiency of methylmalonyl-CoA mutase (MUT) or propionyl-CoA carboxylase (PCC). MMA has an estimated incidence of ~ 1: 50,000 and PA of ~ 1:100'000 -150,000. Patients present either shortly after birth with acute deterioration, metabolic acidosis and hyperammonemia or later at any age with a more heterogeneous clinical picture, leading to early death or to severe neurological handicap in many survivors. Mental outcome tends to be worse in PA and late complications include chronic kidney disease almost exclusively in MMA and cardiomyopathy mainly in PA. Except for vitamin B12 responsive forms of MMA the outcome remains poor despite the existence of apparently effective therapy with a low protein diet and carnitine. This may be related to under recognition and delayed diagnosis due to nonspecific clinical presentation and insufficient awareness of health care professionals because of disease rarity.
Molybdenum cofactor deficiency (MoCD) is a rare inherited metabolic disorder characterized by severe and progressive neurological damage mainly caused by the loss of sulfite oxidase activity. Elevated urinary levels of sulfite, thiosulfate, and S-sulfocysteine (SSC) are hallmarks in the diagnosis of MoCD and sulfite oxidase deficiency (SOD). Recently, a first successful treatment of a human MoCD type A patient based on a substitution therapy with the molybdenum cofactor precursor cPMP has been reported, resulting in nearly complete normalization of MoCD biomarkers. Knowing the rapid progression of the disease symptoms in nontreated patients, an early diagnosis of MoCD as well as a sensitive method to monitor daily changes in SSC levels, a key marker of sulfite toxicity, is crucial for treatment outcome. Here, we describe a fast and sensitive method for the analysis of SSC in human urine samples using high performance liquid chromatography (HPLC). The analysis is based on precolumn derivatization with O-phthaldialdehyde (OPA) and separation on a C18 reverse phase column coupled to UV detection. The method was extended to human serum analysis and no interference with endogenous amino acids was found. Finally, SSC values from 45 pediatric urine, 75 adult urine, and 24 serum samples from control individuals as well as MoCD patients are reported. Our method represents a cost-effective technique for routine diagnosis of MoCD and SOD, and can be used also to monitor treatment efficiency in those sulfite toxicity disorders on a daily basis.
Dried serum spots that are well prepared can be attractive alternatives to frozen serum samples for shelving specimens in a medical or research center's biobank and mailing freshly prepared serum to specialized laboratories. During the pre-analytical phase, complications can arise which are often challenging to identify or are entirely overlooked. These complications can lead to reproducibility issues, which can be avoided in serum protein analysis by implementing optimized storage and transfer procedures. With a method that ensures accurate loading of filter paper discs with donor or patient serum, a gap in dried serum spot preparation and subsequent serum analysis shall be filled. Pre-punched filter paper discs with a 3 mm diameter are loaded within seconds in a highly reproducible fashion (approximately 10% standard deviation) when fully submerged in 10 μl of serum, named the "Submerge and Dry" protocol. Such prepared dried serum spots can store several hundred micrograms of proteins and other serum components. Serum-borne antigens and antibodies are reproducibly released in 20 μl elution buffer in high yields (approximately 90%). Dried serum spot-stored and eluted antigens kept their epitopes and antibodies their antigen binding abilities as was assessed by SDS-PAGE, 2D gel electrophoresis-based proteomics, and Western blot analysis, suggesting pre-punched filter paper discs as handy solution for serological tests.
Mitochondrial neurogastrointestinal encephalomyopathy is an autosomal recessive disorder in which a nuclear mutation of the thymidine phosphorylase gene leads to mitochondrial genomic dysfunction. Herein, we report a 29-year-old Iranian man with abdominal pain, diarrhea, hearing loss, ophthalmoplegia, sensorimotor axonal neuropathy, and elevated muscle enzymes. Magnetic resonance imaging showed leukoencephalopathic changes. Metabolite analysis revealed a very high thymidine concentration in the patient's urine consistent with the diagnosis of mitochondrial neurogastrointestinal encephalomyopathy.
ATM virtual studio services
(1996)
The term "virtual studio" refers to real-time 3D graphics systems used to render a virtual set in sync with live camera motion. As the camera pans and zooms, the virtual set is redrawn from the correct perspective. Using blue room techniques, actors in front of the real camera are then “placed in” the virtual set. Current virtual studio systems are centralized – the blue room, cameras, renderers etc. are located at a single site. However distributed configurations offer significant economies such as the sharing of expensive rendering equipment among many sites. This paper describes early expe- riences of the DVP1 project in the realization of a distributed virtual studio. In particular we de- scribe the first video production using a distributed virtual studio over ATM and make observations concerning network QOS requirements.
Amaç: Keton cisim oluşumu (ketogenez) bozuklukları; mitokondriyel 3-hidroksi-3metil glutaril CoA sentaz (Mhs) ve 3-hidroksi-3-metil glutaril CoA liyaz (HL) enzim eksiklikleri sonucu oluşur. Keton cisim yıkımı (ketoliz) bozuklukları ise suksinil CoA: 3 oksoasit CoA transferaz (SCOT) ve asetoasetil CoA thiolaz-beta ketotiolaz (MAT) enzim eksiklikleri sonucu oluşmaktadır. Keton metabolizma bozukluğu tanısıyla izlenen hastaların klinik ve laboratuvar bulguları ile değerlendirilmesi amaçlandı.
Yöntem: Keton metabolizması bozukluğu tanısıyla izlenen hasta verileri retrospektif olarak incelendi.
Bulgular: Dört hastada HL eksikliği, 3 hastada MAT eksikliği ve 2 hastada SCOT eksikliği tanısı mevcuttu. Hastaların ortanca yaşı 5 yıl (6 ay-15,5 yıl), ilk metabolik dekompanzasyon atak yaşı ortalama 7,7 ay (22 gün-19 ay) idi. MAT eksikliği olan bir hasta, kardeş taraması ile asemptomatik dönemde tanı aldı. İki hastada spastik tetraparezi gibi ağır nörolojik defisit gelişti. Dekompanzasyon ataklarının beslenememe, kusma ve gastroenterit gibi infeksiyon sonrası geliştiği görüldü.
Sonuç: Açıklanamayan metabolik asidoz atakları durumunda keton metabolizma bozuklukları akılda tutulmalıdır. Akut dekompanzasyon değişik yaşlarda ortaya çıkabilir, klinik şiddeti değişken olabilir. Erken tanı ve uygun tedavi mortalite ve morbidite açısından çok önemlidir.
A firm link between endoplasmic reticulum (ER) stress and tumors has been wildly reported. Endoplasmic reticulum oxidoreductase 1 alpha (ERO1α), an ER-resident thiol oxidoreductase, is confirmed to be highly upregulated in various cancer types and associated with a significantly worse prognosis. Of importance, under ER stress, the functional interplay of ERO1α/PDI axis plays a pivotal role to orchestrate proper protein folding and other key processes. Multiple lines of evidence propose ERO1α as an attractive potential target for cancer treatment. However, the unavailability of specific inhibitor for ERO1α, its molecular inter-relatedness with closely related paralog ERO1β and the tightly regulated processes with other members of flavoenzyme family of enzymes, raises several concerns about its clinical translation. Herein, we have provided a detailed description of ERO1α in human cancers and its vulnerability towards the aforementioned concerns. Besides, we have discussed a few key considerations that may improve our understanding about ERO1α in tumors.
PURPOSE
Cervical cancer (CC) is caused by a persistent high-risk human papillomavirus (hrHPV) infection. The cervico-vaginal microbiome may influence the development of (pre)cancer lesions. Aim of the study was (i) to evaluate the new CC screening program in Germany for the detection of high-grade CC precursor lesions, and (ii) to elucidate the role of the cervico-vaginal microbiome and its potential impact on cervical dysplasia.
METHODS
The microbiome of 310 patients referred to colposcopy was determined by amplicon sequencing and correlated with clinicopathological parameters.
RESULTS
Most patients were referred for colposcopy due to a positive hrHPV result in two consecutive years combined with a normal PAP smear. In 2.1% of these cases, a CIN III lesion was detected. There was a significant positive association between the PAP stage and Lactobacillus vaginalis colonization and between the severity of CC precursor lesions and Ureaplasma parvum.
CONCLUSION
In our cohort, the new cervical cancer screening program resulted in a low rate of additional CIN III detected. It is questionable whether these cases were only identified earlier with additional HPV testing before the appearance of cytological abnormalities, or the new screening program will truly increase the detection rate of CIN III in the long run. Colonization with U. parvum was associated with histological dysplastic lesions. Whether targeted therapy of this pathogen or optimization of the microbiome prevents dysplasia remains speculative.
It has become increasingly clear that caspases, far from being merely cell death effectors, have a much wider range of functions within the cell. These functions are as diverse as signal transduction and cytoskeletal remodeling, and caspases are now known to have an essential role in cell proliferation, migration, and differentiation. There is also evidence that apoptotic cells themselves can direct the behavior of nearby cells through the caspase-dependent secretion of paracrine signaling factors. In some processes, including the differentiation of skeletal muscle myoblasts, both caspase activation in differentiating cells as well as signaling from apoptotic cells has been reported. Here, we review the non-apoptotic outcomes of caspase activity in a range of different model systems and attempt to integrate this knowledge.
Reactive oxygen species and the bacteriostatic and bactericidal effects of isoconazole nitrate
(2013)
Intact Transition Epitope Mapping - Targeted High-Energy Rupture of Extracted Epitopes (ITEM-THREE)
(2019)
Epitope mapping, which is the identification of antigenic determinants, is essential for the design of novel antibody-based therapeutics and diagnostic tools. ITEM-THREE is a mass spectrometry-based epitope mapping method that can identify epitopes on antigens upon generating an immune complex in electrospray-compatible solutions by adding an antibody of interest to a mixture of peptides from which at least one holds the antibody's epitope. This mixture is nano-electrosprayed without purification. Identification of the epitope peptide is performed within a mass spectrometer that provides an ion mobility cell sandwiched in-between two collision cells and where this ion manipulation setup is flanked by a quadrupole mass analyzer on one side and a time-of-flight mass analyzer on the other side. In a stepwise fashion, immune-complex ions are separated from unbound peptide ions and dissociated to release epitope peptide ions. Immune complex-released peptide ions are separated from antibody ions and fragmented by collision induced dissociation. Epitope-containing peptide fragment ions are recorded, and mass lists are submitted to unsupervised data base search thereby retrieving both, the amino acid sequence of the epitope peptide and the originating antigen. ITEM-THREE was developed with antiTRIM21 and antiRA33 antibodies for which the epitopes were known, subjecting them to mixtures of synthetic peptides of which one contained the respective epitope. ITEM-THREE was then successfully tested with an enzymatic digest of His-tagged recombinant human β-actin and an antiHis-tag antibody, as well as with an enzymatic digest of recombinant human TNFα and an antiTNFα antibody whose epitope was previously unknown.
JNK1, but Not JNK2, Is Required in Two Mechanistically Distinct Models of Inflammatory Arthritis
(2011)
Impaired up-regulation of CD86 in B cells of "type A" common variable immunodeficiency patients
(2000)
Benches and CAVEs
(1997)
Benches and Caves
(1998)
Benches and Caves
(1998)
The AP-2 family of transcription factors consists of five different proteins in humans and mice: AP-2alpha, AP-2beta, AP-2gamma, AP-2delta and AP-2epsilon. Frogs and fish have known orthologs of some but not all of these proteins, and homologs of the family are also found in protochordates, insects and nematodes. The proteins have a characteristic helix-span-helix motif at the carboxyl terminus, which, together with a central basic region, mediates dimerization and DNA binding. The amino terminus contains the transactivation domain. AP-2 proteins are first expressed in primitive ectoderm of invertebrates and vertebrates; in vertebrates, they are also expressed in the emerging neural-crest cells, and AP-2alpha-/- animals have impairments in neural-crest-derived facial structures. AP-2beta is indispensable for kidney development and AP-2gamma is necessary for the formation of trophectoderm cells shortly after implantation; AP-2alpha and AP-2gamma levels are elevated in human mammary carcinoma and seminoma. The general functions of the family appear to be the cell-type-specific stimulation of proliferation and the suppression of terminal differentiation during embryonic development.
Hydrogen sulfide (H2S) is well known as a highly toxic environmental chemical threat. Prolonged exposure to H2S can lead to the formation of pulmonary edema. However, the mechanisms of how H2S facilitates edema formation are poorly understood. Since edema formation can be enhanced by an impaired clearance of electrolytes and, consequently, fluid across the alveolar epithelium, it was questioned whether H2S may interfere with transepithelial electrolyte absorption. Electrolyte absorption was electrophysiologically measured across native distal lung preparations (Xenopus laevis) in Ussing chambers. The exposure of lung epithelia to H2S decreased net transepithelial electrolyte absorption. This was due to an impairment of amiloride-sensitive sodium transport. H2S inhibited the activity of the Na+/K+-ATPase as well as lidocaine-sensitive potassium channels located in the basolateral membrane of the epithelium. Inhibition of these transport molecules diminishes the electrochemical gradient which is necessary for transepithelial sodium absorption. Since sodium absorption osmotically facilitates alveolar fluid clearance, interference of H2S with the epithelial transport machinery provides a mechanism which enhances edema formation in H2S-exposed lungs.
Brentuximab vedotin (SGN-35) is an antibody–drug conjugate with a high selectivity against CD30+ cell lines and more than 300-fold less activity against antigen-negative cells. In the last years, the results of many in vitro and in vivo studies have led to the fast approval of this drug to treat lymphoma patients. Another innovative method to treat tumor cells including lymphoma cells is the use cytokine-induced killer (CIK) cells, which have also been approved and proven to be a safe treatment with only minor adverse events. In this study, a possible additive effect when combining SGN-35 with CIK cells was investigated. The combinational treatment showed that it reduces the viability of CD30+ cell lines significantly in vitro. Additionally, the amount of lymphoma cells was significantly reduced when exposed to CIK cells as well as when exposed to SGN-35. A significant negative effect of SGN-35 on the function of CIK cells could be excluded. These results lead to the assumption that SGN-35 and CIK cells in combination might achieve better results in an in vitro setting compared to the single use of SGN-35 and CIK cells. Further investigations in in vivo models must be conducted to obtain a better understanding of the exact mechanisms of both treatments when applied in combination.
The motor protein myosin drives a wide range of cellular and muscular functions by generating directed movement and force, fueled through adenosine triphosphate (ATP) hydrolysis. Release of the hydrolysis product adenosine diphosphate (ADP) is a fundamental and regulatory process during force production. However, details about the molecular mechanism accompanying ADP release are scarce due to the lack of representative structures. Here we solved a novel blebbistatin-bound myosin conformation with critical structural elements in positions between the myosin pre-power stroke and rigor states. ADP in this structure is repositioned towards the surface by the phosphate-sensing P-loop, and stabilized in a partially unbound conformation via a salt-bridge between Arg131 and Glu187. A 5 Å rotation separates the mechanical converter in this conformation from the rigor position. The crystallized myosin structure thus resembles a conformation towards the end of the two-step power stroke, associated with ADP release. Computationally reconstructing ADP release from myosin by means of molecular dynamics simulations further supported the existence of an equivalent conformation along the power stroke that shows the same major characteristics in the myosin motor domain as the resolved blebbistatin-bound myosin-II·ADP crystal structure, and identified a communication hub centered on Arg232 that mediates chemomechanical energy transduction.
Cyanobacteria are gaining considerable interest as a method of supporting the long-term presence of humans on the Moon and settlements on Mars due to their ability to produce oxygen and their potential as bio-factories for space biotechnology/synthetic biology and other applications. Since many unknowns remain in our knowledge to bridge the gap and move cyanobacterial bioprocesses from Earth to space, we investigated cell division resumption on the rehydration of dried Chroococcidiopsis sp. CCMEE 029 accumulated DNA damage while exposed to space vacuum, Mars-like conditions, and Fe-ion radiation. Upon rehydration, the monitoring of the ftsZ gene showed that cell division was arrested until DNA damage was repaired, which took 48 h under laboratory conditions. During the recovery, a progressive DNA repair lasting 48 h of rehydration was revealed by PCR-stop assay. This was followed by overexpression of the ftsZ gene, ranging from 7.5- to 9-fold compared to the non-hydrated samples. Knowing the time required for DNA repair and cell division resumption is mandatory for deep-space experiments that are designed to unravel the effects of reduced/microgravity on this process. It is also necessary to meet mission requirements for dried-sample implementation and real-time monitoring upon recovery. Future experiments as part of the lunar exploration mission Artemis and the lunar gateway station will undoubtedly help to move cyanobacterial bioprocesses beyond low Earth orbit. From an astrobiological perspective, these experiments will further our understanding of microbial responses to deep-space conditions.
While many proteins are known clients of heat shock protein 90 (Hsp90), it is unclear whether the transcription factor, thyroid hormone receptor beta (TRb), interacts with Hsp90 to control hormonal perception and signaling. Higher Hsp90 expression in mouse fibroblasts was elicited by the addition of triiodothyronine (T3). T3 bound to Hsp90 and enhanced adenosine triphosphate (ATP) binding of Hsp90 due to a specific binding site for T3, as identified by molecular docking experiments. The binding of TRb to Hsp90 was prevented by T3 or by the thyroid mimetic sobetirome. Purified recombinant TRb trapped Hsp90 from cell lysate or purified Hsp90 in pull-down experiments. The affinity of Hsp90 for TRb was 124 nM. Furthermore, T3 induced the release of bound TRb from Hsp90, which was shown by streptavidin-conjugated quantum dot (SAv-QD) masking assay. The data indicate that the T3 interaction with TRb and Hsp90 may be an amplifier of the cellular stress response by blocking Hsp90 activity.
Microarray-based experiments revealed that thyroid hormone triiodothyronine (T3) enhanced the binding of Cy5-labeled ATP on heat shock protein 90 (Hsp90). By molecular docking experiments with T3 on Hsp90, we identified a T3 binding site (TBS) near the ATP binding site on Hsp90. A synthetic peptide encoding HHHHHHRIKEIVKKHSQFIGYPITLFVEKE derived from the TBS on Hsp90 showed, in MST experiments, the binding of T3 at an EC50 of 50 μM. The binding motif can influence the activity of Hsp90 by hindering ATP accessibility or the release of ADP.
The Virtual Memory Palace
(2006)
The intention of the Virtual Memory Palace is to help people memorize information by addressing their visual memory. The concept is based on the “Memory Palace” as an ancient Greek memorization technique, where symbols are placed in a certain way within an imaginative building in order to remember the original information whenever the mind goes through the vision of this building again. The goal of this work was to create such a Memory Palace in a virtual environment, so it requires less creative effort of the contemporary learner than was necessary in ancient Greece. The Virtual Memory Palace offers the possibility to freely explore a virtual 3d architectural model and to place icons at various locations within this model. Specific behaviors were assigned to these locations to make them more memorable. To test the benefit of this concept, an experiment with 15 subjects was conducted. The results show a higher remembrance rate of items learned in the Virtual Memory Palace compared to a wordlist. The observations made during the test showed that most of the subjects enjoyed the memorization environment and were astonished how well the Virtual Memory Palace worked for them.
Plant sap-feeding insects are widespread, having evolved to occupy diverse environmental niches despite exclusive feeding on an impoverished diet lacking in essential amino acids and vitamins. Success depends exquisitely on their symbiotic relationships with microbial symbionts housed within specialized eukaryotic bacteriocyte cells. Each bacteriocyte is packed with symbionts that are individually surrounded by a host-derived symbiosomal membrane representing the absolute host-symbiont interface. The symbiosomal membrane must be a dynamic and selectively permeable structure to enable bidirectional and differential movement of essential nutrients, metabolites, and biosynthetic intermediates, vital for growth and survival of host and symbiont. However, despite this crucial role, the molecular basis of membrane transport across the symbiosomal membrane remains unresolved in all bacteriocyte-containing insects. A transport protein was immuno-localized to the symbiosomal membrane separating the pea aphid Acyrthosiphon pisum from its intracellular symbiont Buchnera aphidicola. The transporter, A. pisum nonessential amino acid transporter 1, or ApNEAAT1 (gene: ACYPI008971), was characterized functionally following heterologous expression in Xenopus oocytes, and mediates both inward and outward transport of small dipolar amino acids (serine, proline, cysteine, alanine, glycine). Electroneutral ApNEAAT1 transport is driven by amino acid concentration gradients and is not coupled to transmembrane ion gradients. Previous metabolite profiling of hemolymph and bacteriocyte, alongside metabolic pathway analysis in host and symbiont, enable prediction of a physiological role for ApNEAAT1 in bidirectional host-symbiont amino acid transfer, supplying both host and symbiont with indispensable nutrients and biosynthetic precursors to facilitate metabolic complementarity.
Somatic Mutations in UBA1 Define a Distinct Subset of Relapsing Polychondritis Patients With VEXAS
(2021)
Imagine a person navigating on the trackball of a mouse - it would need full body control. In this article we describe the Virtual Balance, an input device for a responsive virtual environment. This device is driven by weight shift on a small platform and does neither require special training nor wearing uncomfortable equipment. The Virtual Balance aims at intuitive navigation through complex 3D space. It can be used to skate or fly like on a magic carpet through a virtual world. With shifts of body posture the navigator controls speed and direction of his/her movement in the model world, which is calculated from the changing pressure on three weight cells under the platform. Different fields of application are presented, showing scenarios already realized as well as a variety of possibilities for future use.
Isolated methylmalonic acidaemia (MMA) and propionic acidaemia (PA) are rare inherited metabolic diseases. Six years ago, a detailed evaluation of the available evidence on diagnosis and management of these disorders has been published for the first time. The article received considerable attention, illustrating the importance of an expert panel to evaluate and compile recommendations to guide rare disease patient care. Since that time, a growing body of evidence on transplant outcomes in MMA and PA patients and use of precursor free amino acid mixtures allows for updates of the guidelines. In this article, we aim to incorporate this newly published knowledge and provide a revised version of the guidelines. The analysis was performed by a panel of multidisciplinary health care experts, who followed an updated guideline development methodology (GRADE). Hence, the full body of evidence up until autumn 2019 was re‐evaluated, analysed and graded. As a result, 21 updated recommendations were compiled in a more concise paper with a focus on the existing evidence to enable well‐informed decisions in the context of MMA and PA patient care.