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Carbohydrate active enzymes (CAZymes) are a large class of enzymes, which build and breakdown the complex carbohydrates of the cell. On the basis of their amino acid sequences they are classified in families and clans that show conserved catalytic mechanism, structure, and active site residues, but may vary in substrate specificity. We report here the identification and the detailed molecular characterization of a novel glycoside hydrolase encoded from the gene sso1353 of the hyperthermophilic archaeon Sulfolobus solfataricus. This enzyme hydrolyzes aryl ␤-gluco-and ␤-xylosides and the observation of transxylosylation reactions products demonstrates that SSO1353 operates via a retaining reaction mechanism. The catalytic nucleophile (Glu-335) was identified through trapping of the 2-deoxy-2-fluoroglucosyl enzyme intermediate and subsequent peptide mapping, while the general acid/base was identified as Asp-462 through detailed mechanistic analysis of a mutant at that position, including azide rescue experiments. SSO1353 has detectable homologs of unknown specificity among Archaea, Bacteria, and Eukarya and shows distant similarity to the non-lysosomal bile acid ␤-glucosidase GBA2 also known as glucocerebrosidase. On the basis of our findings we propose that SSO1353 and its homologs are classified in a new CAZy family, named GH116, which so far includes ␤-glucosidases (EC 3.2.1.21), ␤-xylosidases (EC 3.2.1.37), and glucocerebrosidases (EC 3.2

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The human papilloma virus (HPV) vaccine is a new and expensive vaccine potentially effective in the prevention of a cancer. We reviewed the economic evaluations (EEs) on the vaccine in the EU to assess their potential contribution to public decision-making in a fairly homogeneous setting where HPV vaccination has been widely adopted. A literature search on PubMed selected EEs on HPV vaccines in the EU for the period 2007-2010 using the terms "HPV vaccines" and "Costs and cost analysis." Fifteen articles were eventually selected. All studies were based on modelling techniques, either "cohort" or "dynamic transmission": three were cost utility, three cost-effectiveness, and the remainder included both. The ten studies explicitly assessing one of the two vaccines were all sponsored by their manufacturer, while the five studies unrelated to the vaccine type were funded by public agencies. Apart from two studies, utility estimates were always obtained from three US sources. Direct costs were always vaccination, diagnosis and treatment of related pathologies. Incremental cost-effectiveness ratio (ICER) results were less favourable when life years gained were valued rather than quality-adjusted life years, genital warts were excluded, and booster doses and extension of vaccination to men were included in the base-case analysis. All but one of the sponsored EEs recommend in favour of the vaccination strategy, which is dominant in one English study. The ICER results were very sensitive to discount rates, followed by duration of protection and vaccine price. At such an early stage, when the vaccines' efficacy have been demonstrated by well-designed studies, it is not possible (and not even reasonable) to wait for several years to measure their effectiveness; public decision-makers might benefit more from EEs designed to indicate sustainable prices using realistic estimates of crucial variables like coverage rates, rather than referring to a large number of assumptions in order to show acceptable cost-effectiveness.

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