The Pacific Centre for Isotopic and Geochemical Research (PCIGR) at the University of British Columbia has undertaken a systematic analysis of the isotopic (Sr, Nd, and Pb) compositions and concentrations of a broad compositional range of U.S. Geological Survey (USGS) reference materials, including basalt (BCR‐1, 2; BHVO‐1, 2), andesite (AGV‐1, 2), rhyolite (RGM‐1, 2), syenite (STM‐1, 2), granodiorite (GSP‐2), and granite (G‐2, 3). USGS rock reference materials are geochemically well characterized, but there is neither a systematic methodology nor a database for radiogenic isotopic compositions, even for the widely used BCR‐1. This investigation represents the first comprehensive, systematic analysis of the isotopic composition and concentration of USGS reference materials and provides an important database for the isotopic community. In addition, the range of equipment at the PCIGR, including a Nu Instruments Plasma MC‐ICP‐MS, a Thermo Finnigan Triton TIMS, and a Thermo Finnigan Element2 HR‐ICP‐MS, permits an assessment and comparison of the precision and accuracy of isotopic analyses determined by both the TIMS and MC‐ICP‐MS methods (e.g., Nd isotopic compositions). For each of the reference materials, 5 to 10 complete replicate analyses provide coherent isotopic results, all with external precision below 30 ppm (2 SD) for Sr and Nd isotopic compositions (27 and 24 ppm for TIMS and MC‐ICP‐MS, respectively). Our results also show that the first‐ and second‐generation USGS reference materials have homogeneous Sr and Nd isotopic compositions. Nd isotopic compositions by MC‐ICP‐MS and TIMS agree to within 15 ppm for all reference materials. Interlaboratory MC‐ICP‐MS comparisons show excellent agreement for Pb isotopic compositions; however, the reproducibility is not as good as for Sr and Nd. A careful, sequential leaching experiment of three first‐ and second‐generation reference materials (BCR, BHVO, AGV) indicates that the heterogeneity in Pb isotopic compositions, and concentrations, could be directly related to contamination by the steel (mortar/pestle) used to process the materials. Contamination also accounts for the high concentrations of certain other trace elements (e.g., Li, Mo, Cd, Sn, Sb, W) in various USGS reference materials.

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It has become standard practice to compare new amino-acid and nucleotide sequences with existing ones in the rapidly growing sequence databases. This has led to the recurring identification of certain sequence patterns, usually corresponding to less than 300 amino-acids in length. Many of these identifiable sequence regions have been shown to fold up to form a ‘domain’ structure; they are often called protein ‘modules’ (see definitions below). Proteins that contain such modules are widely distributed in biology, but they are particularly common in extracellular proteins.

Oncoprotein E6 is essential for oncogenesis induced by human papillomaviruses (HPVs). The solution structure of HPV16-E6 C-terminal domain reveals a zinc binding fold. A model of full-length E6 is proposed and analyzed in the context of HPV evolution. E6 appears as a chameleon protein combining a conserved structural scaffold with highly variable surfaces participating in generic or specialized HPV functions. We investigated surface residues involved in two specialized activities of high-risk genital HPV E6: p53 tumor suppressor degradation and nucleic acid binding. Screening of E6 surface mutants identified an in vivo p53 degradation-defective mutant that fails to recruit p53 to ubiquitin ligase E6AP and restores high p53 levels in cervical carcinoma cells by competing with endogeneous E6. We also mapped the nucleic acid binding surface of E6, the positive potential of which correlates with genital oncogenicity. E6 structure-function analysis provides new clues for understanding and counteracting the complex pathways of HPV-mediated pathogenesis.