In an attempt to find the mechanism by which CpG islands remain free of methylation we have undertaken a detailed examination of the mouse adenine phosphoribosyhransferase (aprt) gene. This housekeeping gene has a CpG island that extends over the gene promoter and includes the first two exons. We show that the island is free of methylation at all CpGs, whereas the flanks are methyated. Detailed patterns of methylation beyond the boundaries of the CpG island vary between cells. In vivo footprinting across the island region shows that three GC boxes clustered at the 5' edge of the CpG island are occupied, most probably by Spl. No other footprints are detected within the island region. Deletion or mutagenesis of the Spl sites causes de novo methylation of the CpG island in a transgenic mouse assay. Thus, the peripherally located Spl sites are necessary to keep the aprt island methylation free.

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Background and Purpose-The characteristics of intracerebral hemorrhage (ICH) may vary by ICH location because of differences in the distribution of underlying cerebral small vessel diseases. Therefore, we investigated the incidence, characteristics, and outcome of lobar and nonlobar ICH. Methods-In a population-based, prospective inception cohort study of ICH, we used multiple overlapping sources of case ascertainment and follow-up to identify and validate ICH diagnoses in 2010 to 2011 in an adult population of 695 335. Results-There were 128 participants with first-ever primary ICH. The overall incidence of lobar ICH was similar to nonlobar ICH (9.

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Ecotourism is a form of tourism that is highly visible and growing rapidly. It is commonly presented and understood as very different from conventional mass tourism because it is especially responsible, and even beneficial, environmentally and socio‐culturally. However, such a view may be inaccurate. The favourable image of ecotourism is a consequence of viewing it in an ecotourist bubble, analogous to the idea of the tourist bubble. Within this ecotourist bubble, the destinations and experiences sold to tourists are abstracted from their contexts, thus inducing a distorted image of them and of ecotourism itself. Aspects of what the bubble excludes are illustrated through a consideration of two destinations in the Caribbean.