Crystal structure of the human papillomavirus type 18 E2 activation domain.

The papillomavirus E2 protein regulates viral transcription and DNA replication through interactions with cellular and viral proteins. The amino-terminal activation domain, which represents a protein class whose structural themes are poorly understood, contains key residues that mediate these functional contacts. The crystal structure of a protease-resistant core of the human papillomavirus type 18 E2 activation domain reveals a novel fold creating a cashew-shaped form with a glutamine-rich alpha helix packed against a beta-sheet framework. The protein surface shows extensive overlap of determinants for replication and transcription. The structure broadens the concept of activators to include proteins with potentially malleable, but certainly ordered, structures.

Pancreaticoduodenectomy for peri-ampullary neoplasia leads to specific micronutrient deficiencies.

BACKGROUND/AIMS: After pancreaticoduodenectomy (PD) patients may be deficient in essential micronutrients. This study was designed to determine if this is a consequence of surgery. METHODS: Long-term survivors (>6 months) of PD for peri-ampullary neoplasia and healthy controls (patients' spouse/partner) were enrolled in the study. Specific clinical parameters were recorded, serum micronutrient levels were measured and subjects completed 7-day food diaries. RESULTS: Thirty-seven patients were studied, 25 with paired controls. All were well nourished, as defined by body mass index and food diary analysis. Patients with paired controls were representative of all patients studied. Patients had raised transferrin (median 2.60 vs. 2.16 g/l, p = 0.001) and low ferritin levels (34.9 vs. 119.0 g/l, p < 0.001) indicating relative iron deficiency. Patients also demonstrated lower levels of the anti-oxidants selenium (0.77 vs. 0.93 micromol/l, p < 0.001) and vitamin E (23.2 vs. 35.7 micromol/l, p < 0.001) with 57% of patients having frank selenium deficiencies. Patients had lower levels of vitamin D than controls (15.7 vs. 19.6 micromol/l, p = 0.001) and 30% of patients had a raised parathyroid hormone level, suggesting compensatory mechanisms operate to maintain normocalcaemia. CONCLUSIONS: Long-term survivors of PD are relatively deficient in several micronutrients compared to non-operated controls taking the same diet. We recommend that micronutrient status should be regularly checked in these patients and treated where necessary.