Search results for "COU"
showing 10 items of 14566 documents
The expression and prognostic relevance of programmed cell death protein 1 in tongue squamous cell carcinoma
2020
Background Programmed cell death protein 1 (PD‐1) is an immune checkpoint receptor which plays an important role in a patient´s immune responses to microbial and cancer antigens. It is expressed in tumor infiltrating lymphocytes (TILs) with many different malignancies. The aim of the study was to evaluate PD‐1 expression and its prognostic value in tongue cancer. Methods The data of tongue squamous cell carcinoma (TSCC) patients (N=81) treated in Tampere University Hospital between 1999‐2013 was used. Control data consisted of patients with non‐malignant tongue mucous membrane lesions (N=48). The formalin‐fixed paraffin‐embedded samples were stained immunohistochemically and scanned via dig…
The Crystal Structure of Gurmarin, a Sweet Taste–Suppressing Protein: Identification of the Amino Acid Residues Essential for Inhibition
2018
International audience; Gurmarin is a highly specific sweet-taste suppressing protein in rodents that is isolated from the Indian plant Gymnemasylvestre. Gurmarin consists of 35 amino acid residues containing three intramolecular disulfide bridges that form a cystine knot. Here, we report the crystal structure of gurmarin at a 1.45 Å resolution and compare it with previously reported NMR solution structures. The atomic structure at this resolution allowed us to identify a very flexible region consisting of hydrophobic residues. Some of these amino acid residues had been identified as a putative binding site for the rat sweet taste receptor in a previous study. By combining alanine-scanning …
Evaluating the stability of pharmacophore features using molecular dynamics simulations.
2016
Abstract Molecular dynamics simulations of twelve protein—ligand systems were used to derive a single, structure based pharmacophore model for each system. These merged models combine the information from the initial experimental structure and from all snapshots saved during the simulation. We compared the merged pharmacophore models with the corresponding PDB pharmacophore models, i.e., the static models generated from an experimental structure in the usual manner. The frequency of individual features, of feature types and the occurrence of features not present in the static model derived from the experimental structure were analyzed. We observed both pharmacophore features not visible in …
Biomarkers in Anderson–Fabry Disease
2020
Fabry disease is a rare lysosomal storage disorder caused by a deficiency of α-galactosidase A, resulting in multisystemic involvement. Lyso-Gb3 (globotriaosylsphingosine), the deacylated form of Gb3, is currently measured in plasma as a biomarker of classic Fabry disease. Intensive research of biomarkers has been conducted over the years, in order to detect novel markers that may potentially be used in clinical practice as a screening tool, in the context of the diagnostic process and as an indicator of response to treatment. An interesting field of application of such biomarkers is the management of female heterozygotes who present difficulty in predictable clinical progression. This revi…
Cell Type-Specific Tandem Affinity Purification of the Mouse Hippocampal CB1 Receptor-Associated Proteome
2016
G protein coupled receptors (GPCRs) exert their effects through multiprotein signaling complexes. The cannabinoid receptor type 1 (CB1) is among the most abundant GPCRs in the mammalian brain and involved in a plethora of physiological functions. We used a combination of viral-mediated cell type-specific expression of a tagged CB1 fusion protein (CB1-SF), tandem affinity purification (TAP) and proteomics on hippocampal mouse tissue to analyze the composition and differences of CB1 protein complexes in glutamatergic neurons and in GABAergic interneurons. Purified proteins underwent tryptic digestion and were identified using deep-coverage data-independent acquisition with ion mobility separa…
The Small Heat Shock Protein α-Crystallin B Shows Neuroprotective Properties in a Glaucoma Animal Model
2017
Glaucoma is a neurodegenerative disease that leads to irreversible retinal ganglion cell (RGC) loss and is one of the main causes of blindness worldwide. The pathogenesis of glaucoma remains unclear, and novel approaches for neuroprotective treatments are urgently needed. Previous studies have revealed significant down-regulation of α-crystallin B as an initial reaction to elevated intraocular pressure (IOP), followed by a clear but delayed up-regulation, suggesting that this small heat-shock protein plays a pathophysiological role in the disease. This study analyzed the neuroprotective effect of α-crystallin B in an experimental animal model of glaucoma. Significant IOP elevation induced b…
Impact of COVID-19 on global HCV elimination efforts.
2021
Background & Aims COVID-19 has placed significant strain on national healthcare systems at a critical moment in the context of hepatitis elimination. Mathematical models can be used to evaluate the possible impact of programmatic delays on hepatitis disease burden. The objective of this analysis was to evaluate the incremental change in hepatitis C liver-related deaths and liver cancer, following a 3-month, 6-month, or 1-year hiatus in hepatitis elimination program progress. Methods Previously developed models were adapted for 110 countries to include a status quo or “no delay” scenario and a “1-year delay” scenario assuming significant disruption in interventions (screening, diagnosis and …
HLA-E-Restricted CD8+ T Lymphocytes Efficiently Control Mycobacterium tuberculosis and HIV-1 Co-Infection
2020
We investigated the contribution of human leukocyte antigen A2 (HLA-A2) and HLA-E-restricted CD8+ T cells in patients with Mycobacterium tuberculosis and human immunodeficiency virus 1 (HIV-1) coinfection. HIV-1 downregulates HLA-A, -B, and -C molecules in infected cells, thus influencing recognition by HLA class I-restricted CD8+ T cells but not by HLA-E-restricted CD8+ T cells, owing to the inability of the virus to downmodulate their expression. Therefore, antigen-specific HLA-E-restricted CD8+ T cells could play a protective role in Mycobacterium tuberculosis and HIV-1 coinfection. HLA-E- and HLA-A2-restricted Mycobacterium tuberculosis-specific CD8+ T cells were tested in vitro for cyt…
Physical fitness assessment in Goalball: A scoping review of the literature
2020
Background Goalball is a Paralympic sport for visually impaired athletes. Although it is widely practiced, a great variety of tests are adopted to evaluate athletes' physical fitness. Therefore, the objective was to identify the physical fitness tests adopted in this sport to find the common aspects between them and, eventually, to propose a standard operating procedure. Methods The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines were adopted. The studies were extracted from PubMed, Web of Science, and Scopus. A selection process by title, abstract, and full-text, according to the inclusion and exclusion criteria, was …
New Approach of Controlling Cardiac Alternans
2018
The alternans of the cardiac action potential duration is a pathological rhythm. It is considered to be relating to the onset of ventricular fibrillation and sudden cardiac death. It is well known that, the predictive control is among the control methods that use the chaos to stabilize the unstable fixed point. Firstly, we show that alternans (or period-2 orbit) can be suppressed temporally by the predictive control of the periodic state of the system. Secondly, we determine an estimation of the size of a restricted attraction's basin of the unstable equilibrium point representing the unstable regular rhythm stabilized by the control. This result allows the application of predictive control…