Proteomic profile of cystic fibrosis sputum cells in adults chronically infected with Pseudomonas aeruginosa.

Lung disease is the main cause of morbidity and mortality in cystic fibrosis (CF), and involves chronic infection and perturbed immune responses. Tissue damage is mediated mostly by extracellular proteases, but other cellular proteins may also contribute to damage through their effect on cell activities and/or release into sputum fluid by means of active secretion or cell death.We employed MudPIT (multidimensional protein identification technology) to identify sputum cellular proteins with consistently altered abundance in adults with CF, chronically infected with Pseudomonas aeruginosa, compared with healthy controls. Ingenuity Pathway Analysis, Gene Ontology, protein abundance and correlation with lung function were used to infer their potential clinical significance.Differentially abundant proteins relate to Rho family small GTPase activity, immune cell movement/activation, generation of reactive oxygen species, and dysregulation of cell death and proliferation. Compositional breakdown identified high abundance of proteins previously associated with neutrophil extracellular traps. Furthermore, negative correlations with lung function were detected for 17 proteins, many of which have previously been associated with lung injury.These findings expand our current understanding of the mechanisms driving CF lung disease and identify sputum cellular proteins with potential for use as indicators of disease status/prognosis, stratification determinants for treatment prescription or therapeutic targets.

Social competence in children and young people treated for a brain tumour.

PURPOSE: The purposes of this study were to provide a multi-informant assessment of social competence in 8-16-year olds treated for a brain tumour (BT) and then to compare these assessment outcomes to peers. METHOD: A cross-sectional, mixed (within and between group) design was used to compare a paediatric BT survivor group (n = 33) with an age-matched control group (n = 34) on two multi-informant (self-report, parent, teacher) social competence questionnaires: Social Skills Improvement System (SSIS) and Social Responsiveness Scale (SRS). Demographic factors (age, gender, social economic status (SES), intellectual ability and emotional/behavioural difficulties were investigated as potential non-insult-related risk factors. RESULTS: Compared to controls, the BT group was reported to have difficulties in social adjustment, interactions and information processing, on both social competence questionnaire measures by parents and teachers, but not self-report. Social competence scores for the BT group were broadly distributed within the normal-severe clinical range, with 40 % of BT survivors scoring in the clinical range for social competence difficulties on the SRS. Lower intellectual ability and emotional/behavioural difficulties accounted for some of the group differences in social competence, but group effects remained once estimated IQ and emotional/behavioural difficulties were controlled for. CONCLUSIONS: Paediatric BT survivors were reported by parents and teachers to have significant difficulties at all three levels of social competence: adjustment, interaction and information processing. The results highlight the importance of routine assessment in clinic settings for social competence and emotional/behavioural difficulties in BT survivors, to promote early identification and to ensure that survivors are referred for appropriate services and intervention as part of their multi-disciplinary care package.

A tool to evaluate correspondence between extraction ion chromatographic peaks and peptide-spectrum matches in shotgun proteomics experiments.

Chromatographed peptide signals form the basis of further data processing that eventually results in functional information derived from data-dependent bottom-up proteomics assays. We seek to rank LC/MS parent ions by the quality of their extracted ion chromatograms. Ranked extracted ion chromatograms act as an intuitive physical/chemical preselection filter to improve the quality of MS/MS fragment scans submitted for database search. We identify more than 4900 proteins when considering detector shifts of less than 7 ppm. High quality parent ions for which the database search yields no hits become candidates for subsequent unrestricted analysis for PTMs. Following this rational approach, we prioritize identification of more than 5000 spectrum matches from modified peptides and confirmed the presence of acetylaldehyde-modified His/Lys. We present a logical workflow that scores data-dependent selected ion chromatograms and leverage information about semianalytical LC/LC dimension prior to MS. Our method can be successfully used to identify unexpected modifications in peptides with excellent chromatography characteristics, independent of fragmentation pattern and activation methods. We illustrate analysis of ion chromatograms detected in two different modes by RF linear ion trap and electrostatic field orbitrap.