Structure/Function Analysis of Recurrent Mutations in SETD2 Protein Reveals a Critical and Conserved Role for a SET Domain Residue in Maintaining Protein Stability and Histone H3 Lys-36 Trimethylation

The yeast Set2 histone methyltransferase is a critical enzyme that plays a number of key roles in gene transcription and DNA repair. Recently, the human homologue, SETD2, was found to be recurrently mutated in a significant percentage of renal cell carcinomas, raising the possibility that the activity of SETD2 is tumor-suppressive. Using budding yeast and human cell line model systems, we examined the functional significance of two evolutionarily conserved residues in SETD2 that are recurrently mutated in human cancers. Whereas one of these mutations (R2510H), located in the Set2 Rpb1 interaction domain, did not result in an observable defect in SETD2 enzymatic function, a second mutation in the catalytic domain of this enzyme (R1625C) resulted in a complete loss of histone H3 Lys-36 trimethylation (H3K36me3). This mutant showed unchanged thermal stability as compared with the wild type protein but diminished binding to the histone H3 tail. Surprisingly, mutation of the conserved residue in Set2 (R195C) similarly resulted in a complete loss of H3K36me3 but did not affect dimethylated histone H3 Lys-36 (H3K36me2) or functions associated with H3K36me2 in yeast. Collectively, these data imply a critical role for Arg-1625 in maintaining the protein interaction with H3 and specific H3K36me3 function of this enzyme, which is conserved from yeast to humans. They also may provide a refined biochemical explanation for how H3K36me3 loss leads to genomic instability and cancer

Teaching in Educational Leadership Using Web 2.0 Applications: Perspectives on What Works

To prepare 21st Century school leaders, educational leadership professors need to learn and teach the utilization of increasingly sophisticated technologies in their courses. The co-authors, a professor and an educational specialist degree candidate, describe how the use of advanced technologies — such as Wikis, Google Docs, Wimba Classroom, and Discussion Board — have served as a catalyst for learning among educational leadership students. Details regarding how technology has been used in one course are described, demonstrating how various apps and software applications can easily be applied in other courses

ECONOMY, ECOLOGY, ORGANIZATION OF FOUNDRY PRODUCTION BY LOST FOAM CASTING

The process of receipt of castings by Lost Foam Casting Process (LFCP) from the point of view of economic efficiency and possibilities of receipt of the high-fidelity and high quality castings with the forecast properties. Indexes of hazardous substances emissions at LFCP are defined, measures to purify are worked out and ecological safety of process is shown

REGULATING OF CAST CONSTRUCTIONS PROPERTIES BY INTENSIFYING HEAT EXCHANGE IN MOLD WITH GASIFIED PATTERN

The paper discusses ways to intensify the heat exchange of the casting in the mold of particulate filler. These methods include the supply of refrigerant to the mold, the dynamic and aerodynamic movement of the refractory filler around the casting. The examples of application of these methods to increase the local properties of cast iron cylinder block body are shown. Application of aerodynamic movement of molding material for aluminum castings has allowed to increase their mechanical properties in 1,3–1,6 times

APPLICATION OF POLYSTYRENE FOAM CORE FUSIBLE PATTERNS IN PRODUCTION OF GAS TURBINES’ CAST PARTS

The task of replacing the LVM dissolves polystyrene molding on models is at the present time, technologically, economically and environmentally promising from the point of view of industrial applications for gas turbine plants in Ukraine. The authors proposed and tested manufacturing process of casting ceramic molds way to remove the polystyrene model of the dissolution of her organic solvents. Kinetic parameters of the process of dissolving and removing patterns of degradation products the polystyrene in the group of solvents depending on the type and amount of polystyrene were identified. The absence of surface defects of castings, reduction of roughness, increased their accuracy class in comparison to accepted technological regulations of the process of production, which reduced the cost of machined parts and increased utilization of expensive heat-resistant alloys were produced

THE PRODUCTION OF COMPLEX PROFILE DETAILS BY COMBINED METHOD OF LOST-WAX CASTING AND OF CONSUMABLE PATTERN MODELS

The technological process of receiving figurine castings of a heat resisting alloy HN57KTVYuMBL brand developed and tested by authors a combined method of oflost-wax casting (pouring gate system) and of consumable expanded polystyrene pattern in shell forms kompleks modify ceramics promotes decrease in crack formation of forms at the expense of correctly picked up temperature and time mode of annealing of a form with model. Besides this method allows to receive figurine castings with minimization of an allowance for machining of details, to increase their geometrical accuracy and to lower a roughness