Updates in Psychosomatic Medicine: 2014.

BACKGROUND: The amount of literature published annually related to psychosomatic medicine is vast; this poses a challenge for practitioners to keep up-to-date in all but a small area of expertise. OBJECTIVES: To introduce how a group process using volunteer experts can be harnessed to provide clinicians with a manageable selection of important publications in psychosomatic medicine, organized by specialty area, for 2014. METHODS: We used quarterly annotated abstracts selected by experts from the Academy of Psychosomatic Medicine and the European Association of Psychosomatic Medicine in 15 subspecialties to create a list of important articles. RESULTS: In 2014, subspecialty experts selected 88 articles of interest for practitioners of psychosomatic medicine. For this review, 14 articles were chosen. CONCLUSIONS: A group process can be used to whittle down the vast literature in psychosomatic medicine and compile a list of important articles for individual practitioners. Such an approach is consistent with the idea of physicians as lifelong learners and educators.

Effects of zinc occupancy on human O6-alkylguanine-DNA alkyltransferase.

A recent crystallographic study of recombinant human O(6)-alkylguanine-DNA alkyltransferase (hAGT) revealed a previously unknown zinc atom [Daniels et al., (2000) EMBO J. 19, 1719-1730]. The effects of zinc on the properties of hAGT are reported here. In bacterial expression systems, recombinant hAGT was produced in increasingly larger quantities when growth media are supplemented with up to 0.1 mM ZnCl(2). Metal-enriched hAGT samples had a 5-fold increase in repair rate constant over conventionally purified protein samples and a 60-fold increase over metal-stripped hAGT. In addition, mutants of the zinc-binding residues had decreases in zinc occupancy that correlated with reductions in repair rate. Zinc modulation did not abolish the repair capacity of a fraction of the hAGT population, as evidenced by the stoichiometric reaction with an oligodeoxyribonucleotide substrate. Zinc occupancy had a similar effect on the rate of reaction with O(6)-benzylguanine, a free base substrate, as on the repair of methylated DNA. Differentially zinc-treated hAGTs showed the same affinity for binding to native DNA and substrate oligodeoxyribonucleotides. Metal content manipulations had little effect upon the CD spectrum of hAGT, but fluorescence studies revealed a small conformational change based upon metal binding, and zinc occupancy correlated with enhanced hAGT stability as evidenced by resistance to the denaturing effects of urea. These results indicate that the presence of zinc confers a mechanistic enhancement to repair activity that does not result from an increase in substrate binding affinity. Zinc also provides conformational stability to hAGT that may influence its regulation.