Refine
Year of publication
- 2019 (53) (remove)
Document Type
- Article (53)
Language
- English (53)
Has Fulltext
- yes (53)
Is part of the Bibliography
- no (53)
Keywords
- - (48)
- proteomics (4)
- <i>Staphylococcus aureus</i> (3)
- <i>Bacillus subtilis</i> (2)
- <i>Streptococcus pyogenes</i> (2)
- Araneae (2)
- aerogel (2)
- antares (2)
- antimicrobial photodynamic therapy (2)
- apoptosis (2)
- autocorrelation (2)
- bolaform amphiphilic lipids (2)
- bolalipids (2)
- central blood pressure (2)
- chorioallantoic membrane model (2)
- drug delivery system (2)
- group A streptococcus (2)
- hydrogel (2)
- immune responses (2)
- immunomodulatory proteases (2)
- invasive (2)
- metabolomics (2)
- microbiome (2)
- mitochondria (2)
- necrotizing soft tissue infections (2)
- order pattern (2)
- permutation entropy (2)
- pore-forming toxins (2)
- pulse wave analysis (2)
- self-assembly (2)
- sepsis (2)
- signal processing (2)
- single nucleotide polymorphism (2)
- skin infections (2)
- superantigens (2)
- time series (2)
- validation (2)
- 1,4-naphthoquinones (1)
- 3D (1)
- 90-day mortality (1)
- <i>Argiope bruennichi</i> (1)
- <i>S. aureus</i> (1)
- <i>lpxM</i> (<i>msbB</i>) (1)
- BDNF (1)
- CTLA-4 (1)
- GPR68 (1)
- GastroDuo (1)
- Henrik Ibsen (1)
- Influenza A virus (1)
- OGR1 (1)
- PAβN (1)
- RNAlater (1)
- Rosmersholm (1)
- S-thioallylation (1)
- Sigmund Freud (1)
- TREM-1 (1)
- Tenericutes (1)
- Warburg effect (1)
- adenine nucleotide translocase 1 (1)
- age (1)
- airway epithelial cells (1)
- allicin (1)
- alpha-toxin (1)
- annually laminated lake sediments (1)
- antibacterial activity (1)
- antibiotics (1)
- antibody (1)
- antimicrobial (1)
- antimicrobial activity (1)
- antiseptic stewardship (1)
- atmospheric pressure (1)
- autophagy (1)
- bacillithiol (1)
- biocide (1)
- bioinformatics (1)
- biorelevant in vitro model (1)
- bovine soft palate (1)
- carbon catabolite repression (1)
- cardioprotection (1)
- cardiorespiratory exercise capacity (1)
- cardiorespiratory fitness (1)
- career trajectories (1)
- castration-resistant prostate cancer (1)
- cell cycle (1)
- cell physiology (1)
- cell signaling (1)
- chiral resolution (1)
- chiral stationary phase (1)
- cisplatin (1)
- clinical classifications (1)
- clinical study (1)
- coated (1)
- codon (1)
- cold argon plasma (1)
- complex plasmas (1)
- computer vision (1)
- crop production (1)
- cross-resistance (1)
- cross-tolerance (1)
- dating (1)
- decontamination (1)
- deforestation and forest degradation (1)
- depression (1)
- developing countries (1)
- diallyl polysulfane (1)
- dissolution method (1)
- dissolution methods (1)
- drug release (1)
- drying–rewetting (1)
- dusty plasmas (1)
- ecosystem service valuation (1)
- educational decisions (1)
- efflux pump inhibitor (1)
- eicosanoids (1)
- endosymbiont (1)
- evidence-based practice (1)
- exercise (1)
- external evidence (1)
- flash freezing (1)
- food geographies (1)
- foot-and-mouth disease virus (FMDV) (1)
- gender (1)
- gender inequality (1)
- gene expression (1)
- gene library (1)
- globalization (1)
- haplotypes (1)
- head and neck squamous cell carcinoma (1)
- heart failure with preserved ejection fraction (1)
- heat shock protein 27 (1)
- human (1)
- human kidneys (1)
- hyperspectral image processing (1)
- immobilized (1)
- immunohistochemistry (1)
- inductively-limited discharge (1)
- infection (1)
- inhibition (1)
- innate immune system (1)
- interferon-stimulated genes (ISG) (1)
- internal evidence (1)
- intravaginal ring (1)
- invertebrate host (1)
- ion chromatography (1)
- keratinocytes (1)
- ketamine (1)
- labour market attachment (1)
- land use and land cover change (1)
- lipid mediator (1)
- lipid metabolism (1)
- lipids (1)
- liver disease (1)
- mTHPC (1)
- mast (1)
- membrane transporters (1)
- metabolites (1)
- metagenomics (1)
- metaproteomics (1)
- microbial diversity (1)
- microbial function (1)
- microbiota (1)
- microwave (1)
- modernisation (1)
- morphology (1)
- multiview geometry (1)
- myocardial infarction (1)
- nasopharynx (1)
- necrosis (1)
- nephrotoxicity (1)
- neuroendocrine (1)
- nitrate (1)
- nitrite (1)
- non-thermal plasma (1)
- organic cation transporter 2 (1)
- overflow metabolites (1)
- oxidative stress (1)
- parental leave (1)
- parotid gland (1)
- particle tracking (1)
- penta-acylated lipid A (1)
- perfusion measurements (1)
- permeabilizer (1)
- pharmacological chaperone (1)
- photodynamic therapy (1)
- pig (1)
- plasma diagnostic (1)
- plasma medicine (1)
- plasma-treated water (1)
- pollen analysis (1)
- practice-based evidence (1)
- predictors (1)
- protein abundance (1)
- protein engineering (1)
- protein expression (1)
- pyruvate (1)
- pyruvate kinase (1)
- random mutagenesis (1)
- randomization (1)
- range expansion (1)
- remote sensing (1)
- saliva (1)
- salivary tracer technique (1)
- sample storage (1)
- secularisation (1)
- semantic network (1)
- single nucleotide polymorphisms (1)
- snoD mutant (1)
- social evidence (1)
- soil proteins (1)
- sphingomyelin (1)
- spiders (1)
- stereoscopy (1)
- structure-activity (1)
- sub-ambient temperature (1)
- subcritical fluid chromatography (1)
- substituent (1)
- supercritical CO<sub>2</sub> (1)
- survival (1)
- survival analysis (1)
- symbiosis (1)
- synthesis (1)
- systematics (1)
- tPMP resistance (1)
- tap water (1)
- taxonomy (1)
- toll-like receptor 4 (1)
- trajectory analysis (1)
- transcriptomics (1)
- transmission (1)
- transporters (1)
- tree-rings (1)
- trinucleotide building block (1)
- tropical forests (1)
- tumours (1)
- value chains (1)
- variant of unknown significance (1)
- varves (1)
- virus-host interaction (1)
Institute
- Institut für Pharmazie (8)
- Institut für Pharmakologie (6)
- Abteilung für Mikrobiologie und Molekularbiologie (5)
- Kliniken und Polikliniken für Innere Medizin (4)
- Institut für Biochemie (3)
- Institut für Hygiene und Umweltmedizin (3)
- Institut für Mikrobiologie - Abteilung für Genetik & Biochemie (3)
- Zoologisches Institut und Museum (3)
- Institut für Botanik und Landschaftsökologie & Botanischer Garten (2)
- Institut für Geographie und Geologie (2)
- Institut für Mathematik und Informatik (2)
- Institut für Med. Biochemie u. Molekularbiologie (2)
- Interfakultäres Institut für Genetik und Funktionelle Genomforschung (MNF) (2)
- Institut für Erziehungswissenschaft (1)
- Institut für Fennistik und Skandinavistik (1)
- Institut für Pathologie (1)
- Institut für Physik (1)
- Institut für Politik- und Kommunikationswissenschaft (1)
- Klinik und Poliklinik für Hautkrankheiten (1)
- Klinik und Poliklinik für Mund-, Kiefer- und Gesichtschirurgie/Plastische Operationen (1)
- Universitätsmedizin (1)
Publisher
- MDPI (53) (remove)
Determination of the Pathological Features of NPC1 Variants in a Cellular Complementation Test
(2019)
Niemann-Pick Type C (NP-C) is a rare disorder of lipid metabolism caused by mutations
within the NPC1 and NPC2 genes. NP-C is a neurovisceral disease leading to a heterogeneous,
multisystemic spectrum of symptoms in those affected. Until now, there is no investigative tool to
demonstrate the significance of single variants within the NPC genes. Hence, the aim of the study
was to establish a test that allows for an objective assessment of the pathological potential of NPC1
gene variants. Chinese hamster ovary cells defective in the NPC1 gene accumulate cholesterol in
lysosomal storage organelles. The cells were transfected with NPC1-GFP plasmid vectors carrying
distinct sequence variants. Filipin staining was used to test for complementation of the phenotype.
The known variant p.Ile1061Thr showed a significantly impaired cholesterol clearance after 12 and
24 h compared to the wild type. Among the investigated variants, p.Ser954Leu and p.Glu1273Lys
showed decelerated cholesterol clearance as well. The remaining variants p.Gln60His, p.Val494Met,
and p.Ile787Val showed a cholesterol clearance indistinguishable from wild type. Further, p.Ile1061Thr
acquired an enhanced clearance ability upon 25-hydroxycholesterol treatment. We conclude that the
variants that caused an abnormal clearance phenotype are highly likely to be of clinical relevance.
Moreover, we present a system that can be utilized to screen for new drugs.
GPR68 (OGR1) belongs to the proton-sensing G protein-coupled receptors that are involved
in cellular adaptations to pH changes during tumour development. Although expression of GPR68
has been described in many tumour cell lines, little is known about its presence in human tumour
entities. We characterised the novel rabbit monoclonal anti-human GPR68 antibody 16H23L16
using various cell lines and tissue specimens. The antibody was then applied to a large series of
formalin-fixed, paraffin-embedded normal and neoplastic human tissue samples. Antibody specificity
was demonstrated in a Western blot analysis of GPR68-expressing cells using specific siRNAs.
Immunocytochemical experiments revealed pH-dependent changes in subcellular localisation of the
receptor and internalisation after stimulation with lorazepam. In normal tissue, GPR68 was present in
glucagon-producing islet cells, neuroendocrine cells of the intestinal tract, gastric glands, granulocytes,
macrophages, muscle layers of arteries and arterioles, and capillaries. GPR68 was also expressed
in neuroendocrine tumours, where it may be a positive prognostic factor, in pheochromocytomas,
cervical adenocarcinomas, and endometrial cancer, as well as in paragangliomas, medullary thyroid
carcinomas, gastrointestinal stromal tumours, and pancreatic adenocarcinomas. Often, tumour
capillaries were also strongly GPR68-positive. The novel antibody 16H23L16 will be a valuable tool for
basic research and for identifying GPR68-expressing tumours during histopathological examinations.
Renal drug transporters such as the organic cation transporters (OCTs), organic anion
transporters (OATs) and multidrug resistance proteins (MRPs) play an important role in the tubular
secretion of many drugs influencing their efficacy and safety. However, only little is known about
the distinct protein abundance of these transporters in human kidneys, and about the impact of
age and gender as potential factors of inter-subject variability in their expression and function.
The aim of this study was to determine the protein abundance of MDR1, MRP1-4, BCRP, OAT1-3,
OCT2-3, MATE1, PEPT1/2, and ORCTL2 by liquid chromatography-tandem mass spectrometry-based
targeted proteomics in a set of 36 human cortex kidney samples (20 males, 16 females; median age
53 and 55 years, respectively). OAT1 and 3, OCT2 and ORCTL2 were found to be most abundant
renal SLC transporters while MDR1, MRP1 and MRP4 were the dominating ABC transporters.
Only the expression levels of MDR1 and ORCTL2 were significantly higher abundant in older donors.
Moreover, we found several significant correlations between different transporters, which may
indicate their functional interplay in renal vectorial transport processes. Our data may contribute to
a better understanding of the molecular processes determining renal excretion of drugs.
Salivary glands provide secretory functions, including secretion of xenobiotics and among
them drugs. However, there is no published information about protein abundance of drug transporters
measured using reliable protein quantification methods. Therefore, mRNA expression and absolute
protein content of clinically relevant ABC (n = 6) and SLC (n = 15) family member transporters in the
human parotid gland, using the qRT-PCR and liquid chromatography-tandem mass spectrometry
(LC−MS/MS) method, were studied. The abundance of nearly all measured proteins ranged between
0.04 and 0.45 pmol/mg (OCT3 > MRP1 > PEPT2 > MRP4 > MATE1 > BCRP). mRNAs of ABCB1,
ABCC2, ABCC3, SLC10A1, SLC10A2, SLC22A1, SLC22A5, SLC22A6, SLC22A7, SLC22A8, SLCO1A2,
SLCO1B1, SLCO1B3 and SLCO2B1 were not detected. The present study provides, for the first time,
information about the protein abundance of membrane transporters in the human parotid gland,
which could further be used to define salivary bidirectional transport (absorption and secretion)
mechanisms of endogenous compounds and xenobiotics.