Med5(Nut1) and Med17(Srb4) Are Direct Targets of Mediator Histone H4 Tail Interactions

The Mediator complex transmits activation signals from DNA bound transcription factors to the core transcription machinery. In addition to its canonical role in transcriptional activation, recent studies have demonstrated that S. cerevisiae Mediator can interact directly with nucleosomes, and their histone tails. Mutations in Mediator subunits have shown that Mediator and certain chromatin structures mutually impact each other structurally and functionally in vivo. We have taken a UV photo cross-linking approach to further delineate the molecular basis of Mediator chromatin interactions and help determine whether the impact of certain Mediator mutants on chromatin is direct. Specifically, by using histone tail peptides substituted with an amino acid analog that is a UV activatible crosslinker, we have identified specific subunits within Mediator that participate in histone tail interactions. Using Mediator purified from mutant yeast strains we have evaluated the impact of these subunits on histone tail binding. This analysis has identified the Med5 subunit of Mediator as a target for histone tail interactions and suggests that the previously observed effect of med5 mutations on telomeric heterochromatin and silencing is direct

Feasibility study for SOFC-GT hybrid locomotive power part II. System packaging and operating route simulation

This work assesses the feasibility of Solid Oxide Fuel Cell-Gas Turbine (SOFC-GT) hybrid power systems for use as the prime mover in freight locomotives. The available space in a diesel engine-powered locomotive is compared to that required for an SOFC-GT system, inclusive of fuel processing systems necessary for the SOFC-GT. The SOFC-GT space requirement is found to be similar to current diesel engines, without consideration of the electrical balance of plant. Preliminary design of the system layout within the locomotive is carried out for illustration. Recent advances in SOFC technology and implications of future improvements are discussed as well. A previously-developed FORTRAN model of an SOFC-GT system is then augmented to simulate the kinematics and power notching of a train and its locomotives. The operation of the SOFC-GT-powered train is investigated along a representative route in Southern California, with simulations presented for diesel reformate as well as natural gas reformate and hydrogen as fuels. Operational parameters and difficulties are explored as are comparisons of expected system performance to modern diesel engines. It is found that even in the diesel case, the SOFC-GT system provides significant savings in fuel and CO 2 emissions, making it an attractive option for the rail industry. © 2012 Elsevier B.V. All rights reserved

Distinct roles for Mediator Cdk8 module subunits in Drosophila development

Mediator (MED) is a conserved multisubunit complex bridging transcriptional activators and repressors to the general RNA polymerase II initiation machinery. In yeast, MED is organized in three core modules and a separable ‘Cdk8 module' consisting of the cyclin-dependent kinase Cdk8, its partner CycC, Med12 and Med13. This regulatory module, specifically required for cellular adaptation to environmental cues, is thought to act through the Cdk8 kinase activity. Here we have investigated the functions of the four Cdk8 module subunits in the metazoan model Drosophila. Physical interactions detected among the four fly subunits provide support for a structurally conserved Cdk8 module. We analyzed the in vivo functions of this module using null mutants for Cdk8, CycC, Med12 and Med13. Each gene is required for the viability of the organism but not of the cell. Cdk8–CycC and Med12–Med13 act as pairs, which share some functions but also have distinct roles in developmental gene regulation. These data reveal functional attributes of the Cdk8 module, apart from its regulated kinase activity, that may contribute to the diversification of genetic programs