Prostate cancer reactivates developmental epigenomic programs during metastatic progression.

Epigenetic processes govern prostate cancer (PCa) biology, as evidenced by the dependency of PCa cells on the androgen receptor (AR), a prostate master transcription factor. We generated 268 epigenomic datasets spanning two state transitions-from normal prostate epithelium to localized PCa to metastases-in specimens derived from human tissue. We discovered that reprogrammed AR sites in metastatic PCa are not created de novo; rather, they are prepopulated by the transcription factors FOXA1 and HOXB13 in normal prostate epithelium.

The androgen receptor cistrome is extensively reprogrammed in human prostate tumorigenesis.

Master transcription factors interact with DNA to establish cell type identity and to regulate gene expression in mammalian cells. The genome-wide map of these transcription factor binding sites has been termed the cistrome. Here we show that the androgen receptor (AR) cistrome undergoes extensive reprogramming during prostate epithelial transformation in man.

CAUSEL: an epigenome- and genome-editing pipeline for establishing function of noncoding GWAS variants.

The vast majority of disease-associated single-nucleotide polymorphisms (SNPs) mapped by genome-wide association studies (GWASs) are located in the non-protein-coding genome, but establishing the functional and mechanistic roles of these sequence variants has proven challenging. Here we describe a general pipeline in which candidate functional SNPs are first evaluated by fine mapping, epigenomic profiling, and epigenome editing, and then interrogated for causal function by using genome editing to create isogenic cell lines followed by phenotypic characterization. To validate this approach, we analyzed the 6q22.

Reappearance and treatment of penicillin-susceptible Staphylococcus aureus in a tertiary medical centre.

Objectives: The purpose of this study was to describe trends in the prevalence and treatment patterns of penicillin-susceptible Staphylococcus aureus (SA) infections.

Methods: This was a cross-sectional study of MSSA isolates from blood cultures at a tertiary-care centre between 1 January 2003 and 31 December 2012. All blood cultures positive for MSSA drawn during the study period were used to calculate the prevalence of penicillin-susceptible SA.

Whole-exome sequencing of circulating tumor cells provides a window into metastatic prostate cancer.

Comprehensive analyses of cancer genomes promise to inform prognoses and precise cancer treatments. A major barrier, however, is inaccessibility of metastatic tissue. A potential solution is to characterize circulating tumor cells (CTCs), but this requires overcoming the challenges of isolating rare cells and sequencing low-input material.

ATR-FTIR studies on the nature of surface complexes and desorption efficiency of p-arsanilic acid on iron (oxyhydr)oxides.

The fate of organoarsenicals introduced to the environment through the application of arsenic-contaminated manure has attracted considerable attention after the recent implementation of the latest maximum contaminant level (MCL) of total arsenic in drinking water by the U.S. Environmental Protection Agency (EPA).