The MYST family of histone acetyltransferases and their intimate links to cancer.

The histone acetyltransferases (HATs) of the MYST family are highly conserved in eukaryotes and carry out a significant proportion of all nuclear acetylation. These enzymes function exclusively in multisubunit protein complexes whose composition is also evolutionarily conserved. MYST HATs are involved in a number of key nuclear processes and play critical roles in gene-specific transcription regulation, DNA damage response and repair, as well as DNA replication. This suggests that anomalous activity of these HATs or their associated complexes can easily lead to severe cellular malfunction, resulting in cell death or uncontrolled growth and malignancy. Indeed, the MYST family HATs have been implicated in several forms of human cancer. This review summarizes the current understanding of these enzymes and their normal function, as well as their established and putative links to oncogenesis.

Comprehensive sequence analysis of the E1A proteins of human and simian adenoviruses.

Despite extensive study of human adenovirus type 5 E1A, surprisingly little is known about the E1A proteins of other adenoviruses. We report here a comprehensive analysis of the sequences of 34 E1A proteins. These represent all six primate adenovirus subgroups and include all human representatives of subgroups A, C, E, and F, eight from subgroup B, nine from subgroup D, and seven simian adenovirus E1A sequences. We observed that many, but not all, functional domains identified in human adenovirus type 5 E1A are recognizably present in the other E1A proteins. Importantly, we identified highly conserved sequences without known activities or binding partners, suggesting that previously unrecognized determinants of E1A function remain to be uncovered. Overall, our analysis forms a solid foundation for future study of the activities and features of the E1A proteins of different serotypes and identifies new avenues for investigating E1A function.

Operational characteristics of a prototype x-ray needle device.

A prototype x-ray needle, which emits 62.5 kVp x-rays at the tip of a 20 cm long, 4 mm diameter steel needle, has been developed by Titan Pulse Sciences Incorporated (PSI) (Albuquerque, NM) and was tested for its suitability in brachytherapy applications in comparison with a similar device by the Photoelectron Corporation. The depth dose profiles were also compared with those of two common brachytherapy sources (125I and 192Ir). The depth dose characteristics of the radiation were comparable with the two brachytherapy sources with a slightly reduced attenuation gradient. The dose rate from the x-ray needle tip was relatively isotropic at the needle tip and was continuously adjustable over the range of 0 cGy min(-1) to upwards of 62 cGy min(-1) at a reference distance of 1 cm in air. We detected a significant proportion of x-rays generated along the needle shaft, and not at the needle tip, as intended. The energy spectrum emitted from this device had a peak intensity at 21 keV and an average energy of 28 keV. The beam was attenuated in both aluminium (the first half-value layer being less than 0.1 mm) and in water (50% dose at approximately 2 mm). These studies confirm that although there is potential for a system similar to this one for clinical applications, the simplistic electron guidance used in this particular prototype device limits it to research applications. Further optimization is required in focusing and steering the electron beam to the target, improving x-ray production efficiency and using x-ray target cooling to achieve higher dose rates.