Cheilanthane sesterterpenes, protein kinase inhibitors, from a marine sponge of the genus Ircinia

Four cheilanthane sesterterpenoids, 25-hydroxy-13(24), 15, 17-cheilanthatrien- 19,25-olide (1), 13,16-epoxya5-hydroxy- 17-cheilanthen- 19,25-olide (2), 25-hydroxy-13(24), 17-cheilanthadien-16,19-olide (3), and 16,25-dihydroxy-13(24),17-cheilanthadien 19,25-olide (4), were isolated from the marine sponge Ircinia sp. Compounds 1, 3, and 4 are new natural products. The four compounds inhibit MSK1 (mitogen and stress activated kinase) and MAPKAPK-2 (mitogen activated protein kinase activated protein kinase), two protein kinases involved in mitogen and stress signal transduction

Positional cloning of a quantitative trait locus on chromosome 13q14 that influences immunoglobulin E levels and asthma

Atopic or immunoglobulin E (IgE)-mediated diseases include the common disorders of asthma, atopic dermatitis and allergic rhinitis1. Chromosome 13q14 shows consistent linkage to atopy and the total serum IgE concentration2,3,4,5,6. We previously identified association between total serum IgE levels and a novel 13q14 microsatellite (USAT24G1; ref. 7) and have now localized the underlying quantitative-trait locus (QTL) in a comprehensive single-nucleotide polymorphism (SNP) map. We found replicated association to IgE levels that was attributed to several alleles in a single gene, PHF11. We also found association with these variants to severe clinical asthma. The gene product (PHF11) contains two PHD zinc fingers and probably regulates transcription. Distinctive splice variants were expressed in immune tissues and cells