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Background By means of a structured nutritional support intervention, EFFORT showed a risk reduction for adverse events in medical in-patients. We were interested in the prognostic and therapeutic potential of an untargeted proteomics approach to understand response to nutritional support, risk of 30-day mortality, and distinct patterns in severity of malnutrition risk as assessed by the Nutritional Risk screening (NRS 2002), respectively. Methods From 2,088 patients, we randomly took 120 blood samples drawn before treatment initiation on day 1 after hospital admission. Cases were selected by treatment allocation (nutritional support vs. usual nutrition), NRS 2002, and mortality at 30 days, but not on disease type. We measured proteins by untargeted liquid chromatography mass spectrometry (LC-MS/MS). Results We found 242 distinct proteins in 120 patients of which 81 (67.5%) survived until day 30. Between group analysis revealed a slight difference between the treatment groups in patients with a NRS 3, but not in those with a higher NRS. C-statistic between non-survivors and survivors at day 30 ranged from 0.60 (95% confidence interval 0.34–0.78) for a combination of 3 proteins/predictors to 0.65 (95% CI 0.53–0.78) for a combination of 32 proteins/predictors. In nutritional support non-survivors, pathway analysis found significant enrichment in pathways for signal transduction, platelet function, immune system regulation, extracellular matrix organization, and integrin cell surface interactions compared to survivors. Conclusion Within this pilot study using an untargeted proteomics approach, there was only little prognostic and therapeutic potential of proteomics for phenotyping the risk of malnutrition and response to nutritional therapy. The small sample size and high heterogeneity of our population regarding comorbidity burden calls for more targeted approaches in more homogenous populations to understand the true potential of proteomics for individualizing nutritional care. Trial registration This is a pre-planned secondary analysis of the EFFORT trial (ClinicalTrials.gov NCT02517476)., Clinical Nutrition ESPEN, 48, ISSN:2405-4577

In order to unravel the functions of ASR (Abscisic acid, Stress, Ripening-induced) proteins in the nucleus, we created a new model of genetically transformed grape embryogenic cells by RNAi-knockdown of grape ASR (VvMSA). Nuclear proteomes of wild-type and VvMSA-RNAi grape cell lines were analyzed by quantitative isobaric tagging (iTRAQ 8-plex). The most significantly up-or down-regulated nuclear proteins were involved in epigenetic regulation, DNA replication/repair, transcription, mRNA splicing/stability/editing, rRNA processing/biogenesis, metabolism, cell division/differentiation and stress responses. The spectacular up-regulation in VvMSA-silenced cells was that of the stress response protein VvLEA D-29 (Late Embryogenesis Abundant). Both VvMSA and VvLEA D-29 genes displayed strong and contrasted responsiveness to auxin depletion, repression of VvMSA and induction of VvLEA D-29. In silico analysis of VvMSA and VvLEA D-29 proteins highlighted their intrinsically disordered nature and possible compensatory relationship. Semi-quantitative evaluation by medium-throughput immunoblotting of eighteen post-translational modifications of histones H3 and H4 in VvMSA-knockdown cells showed significant enrichment/depletion of the histone marks H3K4me1, H3K4me3, H3K9me1, H3K9me2, H3K36me2, H3K36me3 and H4K16ac. We demonstrate that grape ASR repression differentially affects members of complex nucleoprotein structures and may not only act as molecular chaperone/transcription factor, but also participates in plant responses to developmental and environmental cues through epigenetic mechanisms., International Journal of Molecular Sciences, 23 (3), ISSN:1422-0067