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GR transcripts display a remarkable heterogeneity in their 5′ untranslated regions (5′UTRs). These variable 5′UTRs are encoded by a series of alternative 1st exons, and together with their associated promoters they maintain tissue-specific GR expression levels. In this study we over-expressed GR transcripts containing individual 1st exons, and assessed their effect on RNA stability, 3′-splicing, translation initiation and protein isoform production. We showed that these alternative 5′UTRs influence the predicted mRNA structure and free energy, and were associated with differential levels of functional spliced mRNA. However, the 5′UTR had little influence on the relative levels of the two principal 3′ splice transcripts, GR - α and - β . The overall mRNA length, the free energy of the transcript and the translational efficiency directly influenced total GR levels. However, individual N-terminal protein isoform levels appeared to depend upon elements within the 5′UTR. Membrane-GR specific labelling suggested that the mGR originates from transcripts containing exon 1D and possibly 1H, although the specific trafficking sequences or structures within these transcripts remain unidentified. The role of the alternative first exons and their associated 5′UTRs has now been expanded to translational control, influencing total GR levels, individual constituent isoform levels, as well as trafficking to the cell surface. [ABSTRACT FROM AUTHOR]

This research was conducted to determine the biogenic amine (BA) and ethyl carbamate (EC) concentrations in commercial Primitivo wine samples and the influence of the use of malolactic starter culture on concentrations of these potentially hazardous compounds in this wine. One hundred sixty bottles of wine from eight producers in the Apulia region of southern Italy were purchased at retail and analyzed. The most common BAs were histamine, 2-phenylethylamine, tyramine, cadaverine, putrescine, spermine, and spermidine. Putrescine (derived from ornithine) was the most abundant BA in all commercial Primitivo wines (5.41 to 9.51 mg/liter), 2-phenylethylamine was detected in only two commercial wines (at less than 2.12 mg/liter), and histamine was found at concentrations of 1.49 to 16.34 mg/liter. The concentration of EC in commercial Primitivo wine was 6.81 to 15.62 ppb, which is not considered dangerous for human health. Malolactic fermentation (MLF) affected the concentrations of BAs and EC differently. For EC, no significant differences were detected between samples of wine produced by spontaneous fermentation and wine that was inoculated malolactic starter. Mean EC concentrations were 12 and 14 ppb in two batches tested (always 18 ppb or less), regardless of whether the malolactic starter was added. Although present at trace levels in wine before the MLF, histamine accumulated during the MLF process, regardless of whether the malolactic starter was added. However, the increase in histamine was higher in wines without the malolactic starter. The concentrations of putrescine and cadaverine increased after MLF, especially in the wine that spontaneously fermented. The use of a selected malolactic starter resulted in reductions in BA concentrations in wine produced by this guided MLF compared with wine produced by spontaneous MLF. [ABSTRACT FROM AUTHOR]

We aimed to measure and validate differences in plasma concentrations of proteins that are associated with prognosis in children with idiopathic PAH and due to CHD to improve risk stratification. Pulmonary arterial hypertension (PAH) in children is a complex and heterogenous condition, mostly complicating congenital heart disease (CHD) and carrying an increased risk of mortality. Clinical management is difficult due to the scarcity of data to have an accurate assessment of risk in this subgroup of patients. In this observational cohort study, we enrolled 29 children (mean age: years 13.8±10.7, median: 10) with PAH, idiopathic and due to CHD. Blood samples were collected at routine clinical appointment visits. In the same day, all data for clinical status, biochemical and no-invasive tests were collected. Clinical data within 1 year of follow up have been recorded. We used an aptamer-based assay of 1000 plasma proteins, and patient clinical details were concealed to the technicians. We identified a panel of prognostic proteins, confirmed with alternative targeted assays, which we evaluated against multiparametric clinical assessment or natriuretic peptides. The primary endpoint was a combination of life threatening arrhythmias, rehospitalization and death. 3 proteins differentiated worse prognosis in 29 consecutive patients with PAH with 1 year of follow-up. 3 proteins were both prognostic independent of plasma NT-proBNP concentrations and confirmed by targeted assays. The functions of these proteins relate to inflammatory cascade and myocardial stress and coagulation. A combination of three circulating proteins identifies patients with PAH with a high risk of arrhythmia and hospitalization, independent of existing clinical assessments, and might have a use to stratify the risk in children. [ABSTRACT FROM AUTHOR]