Inhaled glucocorticosteroids decrease hydrogen peroxide level in expired air condensate in asthmatic patients

AbstractH2O2is elevated in the exhaled air condensate in several inflammatory disorders of the lung, including bronchial asthma, and thus may reflect inflammatory processes in the airways. Exhaled H2O2may be used to guide the anti-inflammatory treatment of patients with asthma. Therefore in this study we analysed the effect of inhaled glucocorticosteroid beclomethasone for 4 weeks on H2O2level in the exhaled air condensate.Seventeen asthmatics and 10 healthy subjects were included to the study. Eleven patients were given inhaled beclomethasone and six were given placebo (3M Health Care). In all patients pulmonary function tests were performed. H2O2in the expired air condensate was measured spectrofluorimetically (homovanillic acid method).Inhaled beclomethasone significantly decreased H2O2in the expired air condensate in the active-treatment group, with a fall from baseline on day 1 which remained on day 43 (follow-up) (P<0·05). Exhaled H2O2in the active-treatment group was significantly lower than that in placebo group (P<0·05). A negative correlation between H2O2and forced expiratory volume in 1 sec (FEV1) on day 29 was observed.The decrease in exhaled H2O2in the active-treatment group was accompanied by an improvement in pulmonary function tests results.Inhaled glucocorticoids reduce the level of H2O2in the expired air condensate of asthmatic patients over a 4-week period and this may reflect their anti-inflammatory activity in lung diseases

3DLigandSite: Structure-based prediction of protein-ligand binding sites

3DLigandSite is a web tool for the prediction of ligand-binding sites in proteins. Here, we report a significant update since the first release of 3DLigandSite in 2010. The overall methodology remains the same, with candidate binding sites in proteins inferred using known binding sites in related protein structures as templates. However, the initial structural modelling step now uses the newly available structures from the AlphaFold database or alternatively Phyre2 when AlphaFold structures are not available. Further, a sequence-based search using HHSearch has been introduced to identify template structures with bound ligands that are used to infer the ligand-binding residues in the query protein. Finally, we introduced a machine learning element as the final prediction step, which improves the accuracy of predictions and provides a confidence score for each residue predicted to be part of a binding site. Validation of 3DLigandSite on a set of 6416 binding sites obtained 92% recall at 75% precision for non-metal binding sites and 52% recall at 75% precision for metal binding sites. 3DLigandSite is available at https://www.wass-michaelislab.org/3dligandsite. Users submit either a protein sequence or structure. Results are displayed in multiple formats including an interactive Mol* molecular visualization of the protein and the predicted binding sites

Structure of the yeast histone H3-ASF1 interaction: implications for chaperone mechanism, species-specific interactions, and epigenetics

BACKGROUND: The histone H3/H4 chaperone Asf1 (anti-silencing function 1) is required for the establishment and maintenance of proper chromatin structure, as well as for genome stability in eukaryotes. Asf1 participates in both DNA replication-coupled (RC) and replication-independent (RI) histone deposition reactions in vitro and interacts with complexes responsible for both pathways in vivo. Asf1 is known to directly bind histone H3, however, high-resolution structural information about the geometry of this interaction was previously unknown. RESULTS: Here we report the structure of a histone/histone chaperone interaction. We have solved the 2.2 Å crystal structure of the conserved N-terminal immunoglobulin fold domain of yeast Asf1 (residues 2–155) bound to the C-terminal helix of yeast histone H3 (residues 121–134). The structure defines a histone-binding patch on Asf1 consisting of both conserved and yeast-specific residues; mutation of these residues abrogates H3/H4 binding affinity. The geometry of the interaction indicates that Asf1 binds to histones H3/H4 in a manner that likely blocks sterically the H3/H3 interface of the nucleosomal four-helix bundle. CONCLUSION: These data clarify how Asf1 regulates histone stoichiometry to modulate epigenetic inheritance. The structure further suggests a physical model in which Asf1 contributes to interpretation of a "histone H3 barcode" for sorting H3 isoforms into different deposition pathways

Measuring and Assessing Sick Absence from Work: a European Cross‑sectional Study

This study analyses sickness absence in selected European countries. We suggested and applied three sick‑leave measures: global sickness absence rate, frequency rate, and absolute crude absence rate. To calculate the rates, open access data from Eurostat, the OECD, and the WHO were used. On the one hand, assessing sickness absence is a challenge in spite of accessible numbers of people and days of absence in public and employer registers. Simultaneously, a detailed understanding of sickness benefits and sick‑pay schemes is needed to elucidate cross‑country differences in sick‑leave rates. The long‑term dynamic trajectory (1970–2020) and regional differentiation effects on absenteeism among countries were considered. Using correlation coefficients and one‑way analysis of variance, a robustness check was performed, and the limitations of the proposed approach to measuring absenteeism were presented. The results evidence that the aforementioned indices present a unique and valid approximation to evaluate and monitor the state of sick absence and inequality in national policies

Abstract Competition

Articlehttp://deepblue.lib.umich.edu/bitstream/2027.42/97009/1/UMURJ-Issue09_2012-StudentAbstractCompetition.pd