Multi-Omics of Tomato Glandular Trichomes Reveals Distinct Features of Central Carbon Metabolism Supporting High Productivity of Specialized Metabolites

Glandular trichomes are metabolic cell factories with the capacity to produce large quantities of secondary metabolites. Little is known about the connection between central carbon metabolism and metabolic productivity for secondary metabolites in glandular trichomes. To address this gap in our knowledge, we performed comparative metabolomics, transcriptomics, proteomics, and (13)C-labeling of type VI glandular trichomes and leaves from a cultivated (Solanum lycopersicum LA4024) and a wild (Solanum habrochaites LA1777) tomato accession. Specific features of glandular trichomes that drive the formation of secondary metabolites could be identified. Tomato type VI trichomes are photosynthetic but acquire their carbon essentially from leaf sucrose. The energy and reducing power from photosynthesis are used to support the biosynthesis of secondary metabolites, while the comparatively reduced Calvin-Benson-Bassham cycle activity may be involved in recycling metabolic CO2 Glandular trichomes cope with oxidative stress by producing high levels of polyunsaturated fatty acids, oxylipins, and glutathione. Finally, distinct mechanisms are present in glandular trichomes to increase the supply of precursors for the isoprenoid pathways. Particularly, the citrate-malate shuttle supplies cytosolic acetyl-CoA and plastidic glycolysis and malic enzyme support the formation of plastidic pyruvate. A model is proposed on how glandular trichomes achieve high metabolic productivity

Present criteria for prophylactic ICD implantation: Insights from the EU-CERT-ICD (Comparative Effectiveness Research to Assess the Use of Primary ProphylacTic Implantable Cardioverter Defibrillators in EUrope) project

BACKGROUND. The clinical effectiveness of primary prevention implantable cardioverter defibrillator (ICD) therapy is under debate. It is urgently needed to better identify patients who benefit from prophylactic ICD therapy. The EUropean Comparative Effectiveness Research to Assess the Use of Primary ProphylacTic Implantable Cardioverter Defibrillators (EU-CERT-ICD) completed in 2019 will assess this issue. SUMMARY. The EU-CERT-ICD is a prospective investigator-initiated non-randomized, controlled, multicenter observational cohort study done in 44 centers across 15 European countries. A total of 2327 patients with heart failure due to ischemic heart disease or dilated cardiomyopathy indicated for primary prophylactic ICD implantation were recruited between 2014 and 2018 (>1500 patients at first ICD implantation, >750 patients non-randomized non-ICD control group). The primary endpoint was all-cause mortality, first appropriate shock was co-primary endpoint. At baseline, all patients underwent 12-lead ECG and Holter-ECG analysis using multiple advanced methods for risk stratification as well as documentation of clinical characteristics and laboratory values. The EU-CERT-ICD data will provide much needed information on the survival benefit of preventive ICD therapy and expand on previous prospective risk stratification studies which showed very good applicability of clinical parameters and advanced risk stratifiers in order to define patient subgroups with above or below average ICD benefit. CONCLUSION. The EU-CERT-ICD study will provide new and current data about effectiveness of primary prophylactic ICD implantation. The study also aims for improved risk stratification and patient selection using clinical risk markers in general, and advanced ECG risk markers in particular.peerReviewe