The dynamic methylation of histone lysyl residues plays an important role in biology by regulating transcription, maintaining genomic integrity, and by contributing to epigenetic effects. Here we describe a variety of inhibitor scaffolds that inhibit the human 2-oxoglutarate-dependent JMJD2 subfamily of histone demethylases. Combined with structural data, these chemical starting points will be useful to generate small-molecule probes to analyze the physiological roles of these enzymes in epigenetic signaling.

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The incidence of dengue has grown dramatically in recent decades worldwide, especially in Southeast Asia and the Americas with substantial transmission in 2014–2015. Yet the mechanisms underlying the spatio-temporal circulation of dengue virus (DENV) serotypes at large geographical scales remain elusive. Here we investigate the co-circulation in Asia of DENV serotypes 1–3 from 1956 to 2015, using a statistical framework that jointly estimates migration history and quantifies potential predictors of viral spatial diffusion, including socio-economic, air transportation and maritime mobility data. We find that the spread of DENV-1, -2 and -3 lineages in Asia is significantly associated with air traffic. Our analyses suggest the network centrality of air traffic hubs such as Thailand and India contribute to seeding dengue epidemics, whilst China, Cambodia, Indonesia, and Singapore may establish viral diffusion links with multiple countries in Asia. Phylogeographic reconstructions help to explain how growing air transportation networks could influence the dynamics of DENV circulation.

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