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
In this paper, I investigate the scalar semantics of evaluative adjective in general, and of good in particular. Lassiter (2017) has argued that good, when taking propositions as arguments, has an interval scale. I argue that there’s evidence in support of the view that good, when taking individuals as argument, has a scale that is stronger than interval, but weaker than ratio. In particular, I propose that individual-level good has a “round” ratio scale, which allows a broader set of ratio transformations than standard ratio scales. This conclusion is consistent with the fact that good admits round ratio modifiers (twice as good), but eschews precise ones (# 1.38x as good). An important consequence of this view is that the scales of individual and propositional-level good are severed.