Search results for " Structure"
showing 10 items of 25475 documents
Identification of the Tetraspanin CD9 as an Interaction Partner of Organic Cation Transporters 1 and 2
2019
Organic cation transporters (OCTs) are membrane proteins with relevant physiological (because they accept neurotransmitters as substrate) and pharmacological (because of their interaction with drugs) roles. The human OCTs hOCT1 (SLC22A1/hOCT1) and hOCT2 (SLC22A2/hOCT2) are highly expressed in hepatic (hOCT1) and in renal and neuronal tissue (hOCT2), suggesting a possible role in modulating neurotransmitter activity in the liver, kidney, and brain, and their clearance from the blood. Even though there are several data demonstrating that OCTs are regulated under various patho-physiological conditions, it remains largely unknown which proteins directly interact with OCTs and thereby influence …
Dibutyl Phthalate (DBP)-Induced Apoptosis and Neurotoxicity are Mediated via the Aryl Hydrocarbon Receptor (AhR) but not by Estrogen Receptor Alpha (…
2016
Dibutyl phthalate (di-n-butyl phthalate, DBP) is one of the most commonly used phthalate esters. DBP is widely used as a plasticizer in a variety of household industries and consumer products. Because phthalates are not chemically bound to products, they can easily leak out to enter the environment. DBP can pass through the placental and blood–brain barriers due to its chemical structure, but little is known about its mechanism of action in neuronal cells. This study demonstrated the toxic and apoptotic effects of DBP in mouse neocortical neurons in primary cultures. DBP stimulated caspase-3 and LDH activities as well as ROS formation in a concentration (10 nM–100 µM) and time-dependent (3–…
2 H-1,2,3-Triazole-Based Dipeptidyl Nitriles: Potent, Selective, and Trypanocidal Rhodesain Inhibitors by Structure-Based Design.
2018
Macrocyclic inhibitors of rhodesain (RD), a parasitic cysteine protease and drug target for the treatment of human African trypanosomiasis, have shown low metabolic stability at the macrocyclic ether bridge. A series of acyclic dipeptidyl nitriles was developed using structure-based design (PDB ID: 6EX8). The selectivity against the closely related cysteine protease human cathepsin L (hCatL) was substantially improved, up to 507-fold. In the S2 pocket, 3,4-dichlorophenylalanine residues provided high trypanocidal activities. In the S3 pocket, aromatic residues provided enhanced selectivity against hCatL. RD inhibition (Ki values) and in vitro cell-growth of Trypanosoma brucei rhodesiense (I…
Development of novel 1,4-benzodiazepine-based Michael acceptors as antitrypanosomal agents
2016
Novel 1,4-benzodiazepines, endowed with a Michael acceptor moiety, were designed taking advantage of a computational prediction of their pharmacokinetic parameters. Among all the synthesized derivatives, we identified a new lead compound (i.e., 4a), bearing a vinyl ketone warhead and endowed with a promising antitrypanosomal activity against Trypanosoma brucei brucei (IC50 = 5.29 µM), coupled with a lack of cytotoxicity towards mammalian cells (TC50>100 µM).
2019
Purpose Myopia is increasing worldwide and possibly linked to education. In this study, we analyse the association of myopia and education in the U.S. and investigate its age-dependency. Methods We conducted a secondary data analysis using the public use files from the cross-sectional study National Health and Nutrition Examination Survey of the period from 1999 to 2008. 19,756 participants aged 20 to 85 years were included with data on education and ophthalmic parameters (distance visual acuity, objective refraction and keratometry). Spherical equivalent, astigmatism, corneal power and corneal astigmatism were evaluated for an association with education using linear regression analysis wit…
Actin Filaments Are Involved in the Coupling of V0-V1 Domains of Vacuolar H+-ATPase at the Golgi Complex*
2016
We previously reported that actin-depolymerizing agents promote the alkalization of the Golgi stack and the trans-Golgi network. The main determinant of acidic pH at the Golgi is the vacuolar-type H+-translocating ATPase (V-ATPase), whose V1 domain subunits B and C bind actin. We have generated a GFP-tagged subunit B2 construct (GFP-B2) that is incorporated into the V1 domain, which in turn is coupled to the V0 sector. GFP-B2 subunit is enriched at distal Golgi compartments in HeLa cells. Subcellular fractionation, immunoprecipitation, and inversal FRAP experiments show that the actin depolymerization promotes the dissociation of V1-V0 domains, which entails subunit B2 translocation from Go…
2018
Objectives: To evaluate the function of the oculomotor and vestibular systems and to correlate these findings with the clinical status of patients with Gaucher disease type 3 (GD3). The goal of this cross-sectional and longitudinal study was to find oculomotor biomarkers for future clinical trials. Methods: Twenty-six patients with GD3 were assessed for eligibility and 21 were able to perform at least one task. Horizontal and vertical reflexive saccades, smooth pursuit, gaze-holding, optokinetic nystagmus, and horizontal vestibulo-ocular reflex (VOR) were examined by video-oculography/video-head impulse test and compared concurrently with 33 healthy controls. The Scale for the Assessment an…
Seasonal recovery ofEdwardsiella piscicidafrom wild European eels and natural waters: Isolation methods, virulence and reservoirs
2018
A total of 127 wild eels caught in the L'Albufera Lake (Spain) and 24 samples of lagoon freshwater were analysed for 1-year period. Edwardsiella strains were isolated from liver/kidney on TSA-1 plates in 31.9% of total diseased specimens, and the edwardsiellosis prevalence in the fishery was of 11.8%. The use of double-strength Salmonella-Shigella (DSSS) broth and SS agar yielded Edwardsiella isolation from intestine in 100% of those edwardsiellosis-diseased eels, but also in 40.4% of other sick fish with vibriosis or aeromonosis and in 28.8% of healthy eels, as well as from freshwater in 8.3% of samples. Pure cultures were isolated on SS agar from the former, but motile Aeromonas, Plesiomo…
2019
Golgi α-mannosidase II (GMII) is a glycoside hydrolase playing a crucial role in the N-glycosylation pathway. In various tumour cell lines, the distribution of N-linked sugars on the cell surface is modified and correlates with the progression of tumour metastasis. GMII therefore is a possible molecular target for anticancer agents. Here, we describe the identification of a non-competitive GMII inhibitor using computer-aided drug design methods including identification of a possible allosteric binding site, pharmacophore search and virtual screening.
Primary vitrectomy for degenerative and tractional lamellar macular holes: A systematic review and meta-analysis
2021
Purpose To assess the efficacy of vitrectomy in degenerative and tractional lamellar macular holes (LMHs) by meta-analysis of published studies. Methods PubMed, Medline and Embase databases were searched up to May 2020. Included cohorts were divided into three groups: degenerative LMH group, lamellar hole associated epiretinal proliferation (LHEP) group and tractional LMH group. LHEP is likely to be associated with degenerative LMHs, but less commonly could be associated with mixed LMHs. To reduce risk of possible misclassification bias, eyes with LHEP which could not have been precisely classified by the authors, were included into the LHEP group. The primary outcome was to investigate th…