CBP loss cooperates with PTEN haploinsufficiency to drive prostate cancer: implications for epigenetic therapy

Despite the high incidence and mortality of prostate cancer, the etiology of this disease is not fully understood. In this study, we develop functional evidence for CBP and PTEN interaction in prostate cancer based on findings of their correlate expression in the human disease. Cbppc−/−;Ptenpc+/− mice exhibited higher cell proliferation in the prostate and an early onset of high-grade prostatic intraepithelial neoplasia. Levels of EZH2 methyltransferase were increased along with its Thr350 phosphorylation in both mouse Cbp−/−;Pten+/− and human prostate cancer cells. CBP loss and PTEN deficiency cooperated to trigger a switch from K27-acetylated histone H3 to K27-trimethylated bulk histones, in a manner associated with decreased expression of the growth inhibitory EZH2 target genes DAB2IP, p27KIP1 and p21CIP1. Conversely, treatment with the histone deacetylase inhibitor panobinostat reversed this switch, in a manner associated with tumor suppression in Cbppc−/−;Ptenpc+/− mice. Our findings show how CBP and PTEN interact to mediate tumor suppression in the prostate, establishing a central role for histone modification in the etiology of prostate cancer and providing a rationale for clinical evaluation of epigenetic targeted therapy in prostate cancer patients

Identification of factors required for m6A mRNA methylation in Arabidopsis reveals a role for the conserved E3 ubiquitin ligase HAKAI

Peer reviewe

Monitoring Water and Energy Cycles at Climate Scale in the Third Pole Environment (CLIMATE-TPE)

A better understanding of the water and energy cycles at climate scale in the Third Pole Environment is essential for assessing and understanding the causes of changes in the cryosphere and hydrosphere in relation to changes of plateau atmosphere in the Asian monsoon system and for predicting the possible changes in water resources in South and East Asia. This paper reports the following results: (1) A platform of in situ observation stations is briefly described for quantifying the interactions in hydrosphere-pedosphere-atmosphere-cryosphere-biosphere over the Tibetan Plateau. (2) A multiyear in situ L-Band microwave radiometry of land surface processes is used to develop a new microwave radiative transfer modeling system. This new system improves the modeling of brightness temperature in both horizontal and vertical polarization. (3) A multiyear (2001–2018) monthly terrestrial actual evapotranspiration and its spatial distribution on the Tibetan Plateau is generated using the surface energy balance system (SEBS) forced by a combination of meteorological and satellite data. (4) A comparison of four large scale soil moisture products to in situ measurements is presented. (5) The trajectory of water vapor transport in the canyon area of Southeast Tibet in different seasons is analyzed, and (6) the vertical water vapor exchange between the upper troposphere and the lower stratosphere in different seasons is presented

Dark sectors 2016 Workshop: community report

This report, based on the Dark Sectors workshop at SLAC in April 2016, summarizes the scientific importance of searches for dark sector dark matter and forces at masses beneath the weak-scale, the status of this broad international field, the important milestones motivating future exploration, and promising experimental opportunities to reach these milestones over the next 5-10 years

Best Linear Unbiased Prediction of Genomic Breeding Values Using a Trait-Specific Marker-Derived Relationship Matrix

With the availability of high density whole-genome single nucleotide polymorphism chips, genomic selection has become a promising method to estimate genetic merit with potentially high accuracy for animal, plant and aquaculture species of economic importance. With markers covering the entire genome, genetic merit of genotyped individuals can be predicted directly within the framework of mixed model equations, by using a matrix of relationships among individuals that is derived from the markers. Here we extend that approach by deriving a marker-based relationship matrix specifically for the trait of interest