2,821 research outputs found

    Additional file 1 of The Golgi stacking protein GRASP55 is targeted by the natural compound prodigiosin

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    Additional file 1: Figure S1. Schematic representation of the thermal proteome profiling temperature range (TPP-TR) workflow. HeLa wt cells were treated with 100 nM prodigiosin or DMSO for 6 h. After the incubation, cells were harvested, washed and aliquots of the cell suspensions were exposed to short (3 min) treatments at different temperatures in the range between 36.5 °C and 67 °C. Cells were lysed and the non-denatured protein fraction was recovered after centrifugation. Quantitative protein analysis was performed by immunoblotting (CETSA) or MS (TPP). For MS, proteins underwent tryptic digest and the resulting peptides were labeled using TMT 10plex. The samples were combined such that prodigiosin treated and corresponding control samples belonging to the same temperature were analyzed within the same TMT set (similarly as described before for RTSA), allowing for studying not only thermal stability but also abundance effects upon prodigiosin treatment

    Ammonia reduction by trees (ART). Summary report

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    The aim of Ammonia Reduction by Trees (ART) project was to provide new scientific evidence on tree planting for reducing the impact of ammonia emissions from farming to inform better advice, guidance and incentives for farmers on ammonia mitigation through treebelt planting

    Premorbid frailty predicts short- and long-term outcomes of reperfusion treatment in acute stroke

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    Background: Frailty is the most important short- and long-term predictor of disability in the elderly and, thus, might influence the clinical outcome of acute treatment of stroke. Objective: To evaluate whether frailty predicts short- and long-term all-cause mortality and neurological recovery in elderly patients who underwent reperfusion acute treatment of stroke. Methods: The study included consecutive patients older than 65 years who underwent reperfusion treatment in a single stroke unit from 2015 to 2016. Predictors of stroke outcomes were assessed including demographics, baseline NIHSS, time to needle, treatment and medical complications. Premorbid frailty was assessed with a comprehensive geriatric assessment including functional, nutritional, cognitive, social and comorbidities status. At three and twelve months, all-cause death and clinical recovery (using modified Rankin scale, mRS) were evaluated. Results: One-hundred and two patients who underwent acute reperfusion treatment for stroke entered the study (mean age 77.5, 65–94 years). Frailty was diagnosed in 32 out of 102 patients and associated with older age (p = 0.001) but no differences in baseline NIHSS score, vascular risk profile or treatment management strategy. Frailty status was associated with worse improvement at 24 h and higher in-hospital mortality. At follow-up, frail patients showed poorer survival at 3 (25% vs 3%, p = 0.008) and 12 (38% vs 7%, p = 0.001) months. Frailty was the best predictor of neurological recovery at one year follow-up (mRS 3.2 ± 1.9 vs 1.9 ± 1.9). Discussion: Frailty is an important predictor of efficacy of acute treatment of stroke beyond classical predictors of stroke outcomes. Larger longitudinal studies are, thus, warranted to evaluate the risk–benefit of reperfusion treatment in the growing elderly frail population

    Increased serum miR-193a-5p during non-alcoholic fatty liver disease progression: Diagnostic and mechanistic relevance

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    Background & Aims: Serum microRNA (miRNA) levels are known to change in non-alcoholic fatty liver disease (NAFLD) and may serve as useful biomarkers. This study aimed to profile miRNAs comprehensively at all NAFLD stages. Methods: We profiled 2,083 serum miRNAs in a discovery cohort (183 cases with NAFLD representing the complete NAFLD spectrum and 10 population controls). miRNA libraries generated by HTG EdgeSeq were sequenced by Illumina NextSeq. Selected serum miRNAs were profiled in 372 additional cases with NAFLD and 15 population controls by quantitative reverse transcriptase PCR. Results: Levels of 275 miRNAs differed between cases and population controls. Fewer differences were seen within individual NAFLD stages, but miR-193a-5p consistently showed increased levels in all comparisons. Relative to NAFL/non-alcoholic steatohepatitis (NASH) with mild fibrosis (stage 0/1), 3 miRNAs (miR-193a-5p, miR-378d, and miR378d) were increased in cases with NASH and clinically significant fibrosis (stages 2–4), 7 (miR193a-5p, miR-378d, miR-378e, miR-320b, miR-320c, miR-320d, and miR-320e) increased in cases with NAFLD activity score (NAS) 5–8 compared with lower NAS, and 3 (miR-193a-5p, miR-378d, and miR-378e) increased but 1 (miR-19b-3p) decreased in steatosis, activity, and fibrosis (SAF) activity score 2–4 compared with lower SAF activity. The significant findings for miR-193a-5p were replicated in the additional cohort with NAFLD. Studies in Hep G2 cells showed that following palmitic acid treatment, miR-193a-5p expression decreased significantly. Gene targets for miR-193a-5p were investigated in liver RNAseq data for a case subgroup (n = 80); liver GPX8 levels correlated positively with serum miR-193a-5p. Conclusions: Serum miR-193a-5p levels correlate strongly with NAFLD activity grade and fibrosis stage. MiR-193a-5p may have a role in the hepatic response to oxidative stress and is a potential clinically tractable circulating biomarker for progressive NAFLD. Lay summary: MicroRNAs (miRNAs) are small pieces of nucleic acid that may turn expression of genes on or off. These molecules can be detected in the blood circulation, and their levels in blood may change in liver disease including non-alcoholic fatty liver disease (NAFLD). To see if we could detect specific miRNA associated with advanced stages of NAFLD, we carried out miRNA sequencing in a group of 183 patients with NAFLD of varying severity together with 10 population controls. We found that a number of miRNAs showed changes, mainly increases, in serum levels but that 1 particular miRNA miR-193a-5p consistently increased. We confirmed this increase in a second group of cases with NAFLD. Measuring this miRNA in a blood sample may be a useful way to determine whether a patient has advanced NAFLD without an invasive liver biopsy

    Targeted reduction of airborne viral transmission risk in long-term residential aged care

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    COVID-19 has demonstrated the devastating consequences of the rapid spread of an airborne virus in residential aged care. We report the use of CO2-based ventilation assessment to empirically identify potential ‘super-spreader’ zones within an aged care facility, and determine the efficacy of rapidly implemented, inexpensive, risk reduction measures

    Ammonia reduction by trees (ART). Field case studies for monitoring ammonia reduction by treebelts

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    The ART project's aim was to build further the evidence base for understanding the reduction effect and techniques in the field which are used to qualitatively and quantitatively understand the process of ammonia capture by trees. Ammonia concentrations were measured at five case study farms in Cumbria with existing woodland planting in the vicinity of livestock housing. The aim of this study is to provide field measurement data to contribute towards assessing how effective treebelts are at reducing ammonia concentrations downwind of a variety of agricultural livestock housing and to provide datasets for current and future model verification
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