Jagiellonian University

About: Jagiellonian University is a education organization based out in Krakow, Poland. It is known for research contribution in the topics: Population & Catalysis. The organization has 17438 authors who have published 44092 publications receiving 862633 citations. The organization is also known as: Academia Cracoviensis & Akademia Krakowska.

Proteolysis of human thrombin generates novel host defense peptides.

Abstract: The coagulation system is characterized by the sequential and highly localized activation of a series of serine proteases, culminating in the conversion of fibrinogen into fibrin, and formation of a fibrin clot. Here we show that C-terminal peptides of thrombin, a key enzyme in the coagulation cascade, constitute a novel class of host defense peptides, released upon proteolysis of thrombin in vitro, and detected in human wounds in vivo. Under physiological conditions, these peptides exert antimicrobial effects against Gram-positive and Gram-negative bacteria, mediated by membrane lysis, as well as immunomodulatory functions, by inhibiting macrophage responses to bacterial lipopolysaccharide. In mice, they are protective against P. aeruginosa sepsis, as well as lipopolysaccharide-induced shock. Moreover, the thrombin-derived peptides exhibit helical structures upon binding to lipopolysaccharide and can also permeabilize liposomes, features typical of "classical" helical antimicrobial peptides. These findings provide a novel link between the coagulation system and host-defense peptides, two fundamental biological systems activated in response to injury and microbial invasion.

Genomewide Association Study Using a High-Density Single Nucleotide Polymorphism Array and Case-Control Design Identifies a Novel Essential Hypertension Susceptibility Locus in the Promoter Region of Endothelial NO Synthase

Abstract: Essential hypertension is a multifactorial disorder and is the main risk factor for renal and cardiovascular complications. The research on the genetics of hypertension has been frustrated by the small predictive value of the discovered genetic variants. The HYPERGENES Project investigated associations between genetic variants and essential hypertension pursuing a 2-stage study by recruiting cases and controls from extensively characterized cohorts recruited over many years in different European regions. The discovery phase consisted of 1865 cases and 1750 controls genotyped with 1M Illumina array. Best hits were followed up in a validation panel of 1385 cases and 1246 controls that were genotyped with a custom array of 14 055 markers. We identified a new hypertension susceptibility locus (rs3918226) in the promoter region of the endothelial NO synthase gene (odds ratio: 1.54 [95% CI: 1.37-1.73]; combined P=2.58 · 10(-13)). A meta-analysis, using other in silico/de novo genotyping data for a total of 21 714 subjects, resulted in an overall odds ratio of 1.34 (95% CI: 1.25-1.44; P=1.032 · 10(-14)). The quantitative analysis on a population-based sample revealed an effect size of 1.91 (95% CI: 0.16-3.66) for systolic and 1.40 (95% CI: 0.25-2.55) for diastolic blood pressure. We identified in silico a potential binding site for ETS transcription factors directly next to rs3918226, suggesting a potential modulation of endothelial NO synthase expression. Biological evidence links endothelial NO synthase with hypertension, because it is a critical mediator of cardiovascular homeostasis and blood pressure control via vascular tone regulation. This finding supports the hypothesis that there may be a causal genetic variation at this locus.

A controlled study of 9α,11β-PGF2 (a prostaglandin D2 metabolite) in plasma and urine of patients with bronchial asthma and healthy controls after aspirin challenge

Abstract: Background: Prostaglandin D 2 (PGD 2 ) is the predominant cyclooxygenase product of mast cells, the number of which is increased in bronchial asthma. Release of PGD 2 might reflect mast cell activation and disordered function of the asthmatic lung. Objective: We sought to determine blood and urinary levels of 9α,11β-PGF 2 , a major stable PGD 2 metabolite in 2 well-defined phenotypes of asthma, aspirin-induced asthma (AIA) and aspirin-tolerant asthma (ATA), and in healthy control subjects and to study the effects of aspirin on PGD 2 release. Methods: Using gas chromatography/mass spectrometry, we determined plasma and urinary concentrations of 9α,11β-PGF 2 at baseline in 131 stable asthmatic patients, 65 of whom had AIA and 66 of whom had ATA. Fifty healthy nonatopic subjects served as the control group. The measurements were also performed after an aspirin challenge in 26 of 65 patients with AIA and in 24 of 50 control subjects. Results: At baseline, patients with AIA had significantly higher plasma levels of 9α,11β-PGF 2 than either patients with ATA or healthy subjects. A similar significant elevation of serum tryptase was observed in patients with AIA compared with patients with ATA and control subjects. Mean urinary 9α,11β-PGF 2 values did not differ among the 3 groups. In patients with AIA, as opposed to healthy subjects, aspirin challenge invariably precipitated a clinical reaction, accompanied in most patients by a further rise in plasma levels of PGD 2 metabolite and tryptase. Conclusions: In stable AIA, though not in ATA, there is a steady release of PGD 2 into the blood, accompanied by the release of tryptase. Aspirin enhances this reaction in most patients. Release of bronchoconstrictive PGD 2 might contribute to the severe clinical course of AIA.

Dialogue natural language inference

Abstract: Consistency is a long standing issue faced by dialogue models. In this paper, we frame the consistency of dialogue agents as natural language inference (NLI) and create a new natural language inference dataset called Dialogue NLI. We propose a method which demonstrates that a model trained on Dialogue NLI can be used to improve the consistency of a dialogue model, and evaluate the method with human evaluation and with automatic metrics on a suite of evaluation sets designed to measure a dialogue model’s consistency.

Search for resonances in diphoton events at √s=13 TeV with the ATLAS detector

Abstract: Searches for new resonances decaying into two photons in the ATLAS experiment at the CERN Large Hadron Collider are described. The analysis is based on protonproton collision data corresponding to ...