Mediator is a multiprotein complex that connects regulation mediated by transcription factors with RNA polymerase II transcriptional machinery and integrates signals from the cell regulatory cascades with gene expression. One of the Mediator subunits, Mediator complex subunit 28 (MED28), has a dual nuclear and cytoplasmic localization and function. In the nucleus, MED28 functions as part of Mediator and in the cytoplasm, it interacts with cytoskeletal proteins and is part of the regulatory
cascades including that of Grb2. MED28 thus has the potential to bring cytoplasmic regulatory interactions towards the centre of gene expression regulation. In this study, we identified MDT-28, the nematode orthologue of MED28, as a likely target of lysine acetylation using bioinformatic prediction of post-translational modifications. Lysine acetylation was experimentally confirmed using anti-acetyl lysine antibody on immunoprecipitated GFP::MDT-28 ex-pressed in synchronized C. elegans. Valproic acid (VPA), a known inhibitor of lysine deacetylases, enhanced the lysine acetylation of GFP::MDT-28. At the subcellular level, VPA decreased the nuclear localization of GFP::MDT-28 detected by fluorescence-lifetime imaging microscopy (FLIM). This indicates that the nuclear pool of MDT-28 is regulated by a mechanism sensitive to VPA and provides an indirect support for a variable relative proportion of MED28 orthologues with other Mediator subunits. and Corresponding author: Markéta Kostrouchová
This study investigated the value of oxygen (O2) pulse curves obtained during cardiopulmonary exercise testing (CPET) for the diagnosis of coronary artery disease (CAD). Forty patients with known coronary anatomy (35.0 % normal, 27.0 % single-vessel and 38.0 % multivessel CAD) underwent CPET with radiotracer injection at peak exercise, followed by myocardial scintigraphy. O2 pulse curves were classified as: A-normal, B-probably normal (normal slope with low peak value); C-probably abnormal (flat, with low peak value); or D- definitely abnormal (descending slope). Sensitivity, specificity, positive and negative predictive values of the O2 pulse curve pattern (A or B vs. C or D) for the diagnosis of CAD were, respectively, 38.5 %, 81.3 %, 76.9 %, and 44.8 %. The concordance rate between the abnormal O2 pulse curve pattern and ischemia in myocardial scintigraphy was 38.1 %. Age and the extent of scintigraphic perfusion defect, but not the abnormal O2 pulse curve patterns (B or C or both combined) were independently associated with CAD. In conclusion, the O2 pulse curve pattern has low diagnostic performance for the diagnosis of obstructive CAD, and the abnormal curve pattern was not associated with myocardial ischemia defined by scintigraphy., A. De Lorenzo, C. L. Da Silva, F. C. Castro Souza, R. De Souza Leão Lima., and Obsahuje bibliografii