The epigenetic landscape of renal cancer

This is an accepted manuscript of an article published by Nature in Nature Reviews: Nephrology on 28/11/2016, available online: https://doi.org/10.1038/nrneph.2016.168 The accepted version of the publication may differ from the final published version.The majority of kidney cancers are associated with mutations in the von Hippel-Lindau gene and a small proportion are associated with infrequent mutations in other well characterized tumour-suppressor genes. In the past 15 years, efforts to uncover other key genes involved in renal cancer have identified many genes that are dysregulated or silenced via epigenetic mechanisms, mainly through methylation of promoter CpG islands or dysregulation of specific microRNAs. In addition, the advent of next-generation sequencing has led to the identification of several novel genes that are mutated in renal cancer, such as PBRM1, BAP1 and SETD2, which are all involved in histone modification and nucleosome and chromatin remodelling. In this Review, we discuss how altered DNA methylation, microRNA dysregulation and mutations in histone-modifying enzymes disrupt cellular pathways in renal cancers

Development of the Regional Arctic System Model (RASM): Near-Surface Atmospheric Climate Sensitivity

The near-surface climate, including the atmosphere, ocean, sea ice, and land state and fluxes, in the initial version of the Regional Arctic System Model (RASM) are presented. The sensitivity of the RASM near-surface climate to changes in atmosphere, ocean, and sea ice parameters and physics is evaluated in four simulations. The near-surface atmospheric circulation is well simulated in all four RASM simulations but biases in surface temperature are caused by biases in downward surface radiative fluxes. Errors in radiative fluxes are due to biases in simulated clouds with different versions of RASM simulating either too much or too little cloud radiative impact over open ocean regions and all versions simulating too little cloud radiative impact over land areas. Cold surface temperature biases in the central Arctic in winter are likely due to too few or too radiatively thin clouds. The precipitation simulated by RASM is sensitive to changes in evaporation that were linked to sea surface temperature biases. Future work will explore changes in model microphysics aimed at minimizing the cloud and radiation biases identified in this work.United States Department of Energy [DE-FG02-07ER64462, DE-SC0006178, DE-FG02-07ER64460, DE-SC0006856, DE-FG02-07ER64463, DE-SC0006693]; National Science Foundation [PLR-1107788, PLR-1417818]6 month embargo; Published Online: 29 June 2017This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]