Citrullinated histone H3, a marker of extracellular trap formation, is increased in blood of stable asthma patients

Background: Emerging data indicates that extracellular traps (ETs), structures formed by various immune cell types, may contribute to the pathology of noninfectious infammatory diseases. Histone hypercitrullination is an important step in ETs formation and citrullinated histone H3 (H3cit) is considered a novel and specifc biomarker of that process. In the present study we have evaluated circulating H3cit in stable asthmatics and investigated its relationship with asthma severity, pulmonary function and selected blood and bronchoalveolar lavage (BAL) biomarkers. Methods: In 60 white adult stable asthmatics and 50 well-matched controls we measured serum levels of H3cit. In asthmatics we also performed bronchoscopy with BAL. We analyzed blood and BAL biomarkers, including interleukin (IL)-4, IL-5, IL-6, IL-10, IL-12p70, IL-17A and interferon γ. For statistical analysis, Mann-Whitney U-test, χ2 test, one-way ANCOVA, ROC curve analysis and univariate linear regression were applied. Independent determinants of H3cit were established in a multiple linear regression model. Results: Asthma was characterized by elevated circulating H3cit (17.49 [11.25–22.58] vs. 13.66 [8.66–18.87] ng/ml, p=0.03). In asthmatics positive associations were demonstrated between serum H3cit and lung function variables, including total lung capacity (TLC) (β=0.37 [95% CI 0.24-0.50]) and residual volume (β=0.38 [95% CI 0.25–0.51]). H3cit was increased in asthma patients receiving systemic steroids (p=0.02), as well as in subjects with BAL eosino‑ philia above 144 cells/ml (p=0.02). In asthmatics, but not in controls, circulating H3cit correlated well with number of neutrophils (β=0.31 [95% CI 0.19–0.44]) and monocytes (β=0.42 [95% CI 0.29–0.55]) in peripheral blood. Further‑ more, BAL macrophages, BAL neutrophils, TLC, high-sensitivity C-reactive protein, Il-12p70 and bronchial obstruction degree were independent determinants of H3cit in a multivariate linear regression model. Conclusions: Asthma is characterized by increased circulating H3cit likely related to the enhanced lung ETs forma‑ tion. Inhibition of ETs might be a therapeutic option in selected asthma phenotypes, such as neutrophilic asthma

Increased oxidative stress in asthma - relation to inflammatory blood and lung biomarkers and airway remodeling indices

Airway inflammation in asthma is related to increased reactive oxygen species generation, potentially leading to tissue injury and subsequent airway remodeling. We evaluated oxidative stress in peripheral blood from asthmatic subjects (n = 74) and matched controls (n = 65), using recently developed real-time monitoring of the protein hydroperoxide (HP) formation by the coumarin boronic acid (CBA) assay. We also investigated the relation of the systemic oxidative stress response in asthma to disease severity, lung function, airway remodeling indices (lung computed tomography and histology), and blood and bronchoalveolar lavage fluid (BAL) inflammatory biomarkers. We documented enhanced systemic oxidative stress in asthma, reflected by 35% faster and 58% higher cumulative fluorescent product generation in the CBA assay (p < 0.001 for both). The dynamics of HP generation correlated inversely with lung function but not with asthma severity or histological measures of airway remodeling. HP generation was associated positively with inflammatory indices in the blood (e.g., C-reactive protein) and BAL (e.g., interleukin [IL]-6, IL-12p70, and neutrophil count). Bronchial obstruction, thicker airway walls, increased BAL IL-6, and citrullinated histone 3 in systemic circulation independently determined increased HP formation. In conclusion, a real-time CBA assay showed increased systemic HP generation in asthma. In addition, it was associated with inflammatory biomarkers, suggesting that proper disease control can also lead to a decrease in oxidative stress

Reticular basement membrane thickness is associated with growth : and fibrosis-promoting airway transcriptome profile-study in asthma patients

Airway remodeling in asthma is characterized by reticular basement membrane (RBM) thickening, likely related to epithelial structural and functional changes. Gene expression profiling of the airway epithelium might identify genes involved in bronchial structural alterations. We analyzed bronchial wall geometry (computed tomography (CT)), RBM thickness (histology), and the bronchial epithelium transcriptome profile (gene expression array) in moderate to severe persistent (n = 21) vs. no persistent (n = 19) airflow limitation asthmatics. RBM thickness was similar in the two studied subgroups. Among the genes associated with increased RBM thickness, the most essential were those engaged in cell activation, proliferation, and growth (e.g., CDK20, TACC2, ORC5, and NEK5) and inhibiting apoptosis (e.g., higher mRNA expression of RFN34, BIRC3, NAA16, and lower of RNF13, MRPL37, CACNA1G). Additionally, RBM thickness correlated with the expression of genes encoding extracellular matrix (ECM) components (LAMA3, USH2A), involved in ECM remodeling (LTBP1), neovascularization (FGD5, HPRT1), nerve functioning (TPH1, PCDHGC4), oxidative stress adaptation (RIT1, HSP90AB1), epigenetic modifications (OLMALINC, DNMT3A), and the innate immune response (STAP1, OAS2). Cluster analysis revealed that genes linked with RBM thickness were also related to thicker bronchial walls in CT. Our study suggests that the pro-fibrotic profile in the airway epithelial cell transcriptome is associated with a thicker RBM, and thus, may contribute to asthma airway remodeling

Experimental and theoretical studies of nanofluid thermal conductivity enhancement: a review

Nanofluids, i.e., well-dispersed (metallic) nanoparticles at low- volume fractions in liquids, may enhance the mixture's thermal conductivity, knf, over the base-fluid values. Thus, they are potentially useful for advanced cooling of micro-systems. Focusing mainly on dilute suspensions of well-dispersed spherical nanoparticles in water or ethylene glycol, recent experimental observations, associated measurement techniques, and new theories as well as useful correlations have been reviewed

CMS physics technical design report : Addendum on high density QCD with heavy ions

Peer reviewe

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

Dynamic Reducts as a Tool for Extracting Laws from Decisions Tables

. We apply rough set methods and boolean reasoning for knowledge discovery from decision tables. It is not always possible to extract general laws from experimental data by computing first all reducts [12] of a decision table and next decision rules on the basis of these reducts. We investigate a problem how information about the reduct set changes in a random sampling process of a given decision table could be used to generate these laws. The reducts stable in the process of decision table sampling are called dynamic reducts. Dynamic reducts define the set of attributes called the dynamic core. This is the set of attributes included in all dynamic reducts. The set of decision rules can be computed from the dynamic core or from the best dynamic reducts. We report the results of experiments with different data sets, e.g. market data, medical data, textures and handwritten digits. The results are showing that dynamic reducts can help to extract laws from decision tables. Key words: evol..