A PRMT5-ZNF326 axis mediates innate immune activation upon replication stress.

DNA replication stress (RS) is a widespread phenomenon in carcinogenesis, causing genomic instability and extensive chromatin alterations. DNA damage leads to activation of innate immune signaling, but little is known about transcriptional regulators mediating such signaling upon RS. Using a chemical screen, we identified protein arginine methyltransferase 5 (PRMT5) as a key mediator of RS-dependent induction of interferon-stimulated genes (ISGs).

LINE-1 promotes tumorigenicity and exacerbates tumor progression via stimulating metabolism reprogramming in non-small cell lung cancer.

Background: Long Interspersed Nuclear Element-1 (LINE-1, L1) is increasingly regarded as a genetic risk for lung cancer. Transcriptionally active LINE-1 forms a L1-gene chimeric transcript (LCTs), through somatic L1 retrotransposition (LRT) or L1 antisense promoter (L1-ASP) activation, to play an oncogenic role in cancer progression.

Methods: Here, we developed Retrotransposon-gene fusion estimation program (ReFuse), to identify and quantify LCTs in RNA sequencing data from TCGA lung cancer cohort (n = 1146) and a single cell RNA sequencing dataset then further validated those LCTs in an independent cohort (n = 134).

GWAS in Mice Maps Susceptibility to HIV-Associated Nephropathy to the Locus.

Background: To gain insight into the pathogenesis of collapsing glomerulopathy, a rare form of FSGS that often arises in the setting of viral infections, we performed a genome-wide association study (GWAS) among inbred mouse strains using a murine model of HIV-1 associated nephropathy (HIVAN).

Methods: We first generated F1 hybrids between HIV-1 transgenic mice on the FVB/NJ background and 20 inbred laboratory strains. Analysis of histology, BUN, and urinary NGAL demonstrated marked phenotypic variation among the transgenic F1 hybrids, providing strong evidence for host genetic factors in the predisposition to nephropathy.

Estimating greenhouse gas emissions from direct land use change due to crop production in multiple countries.

Greenhouse gas (GHG) emissions from direct land use change (LUC) in GHG footprint studies of crops are often estimated using national land use change statistics, as in many cases the exact location of crop cultivation and land use history is unknown. As such, these studies neglect spatial variability in land use change (amount and configuration) at the sub-national level as well as spatial variability in natural carbon stocks. For this reason, a spatial approach that enables consistent implementation of LUC emissions of crop production at different locations is developed and applied in this study.

Greenhouse gas footprints of palm oil production in Indonesia over space and time.

Palm oil, the most widely used vegetable oil, is one of the largest drivers of greenhouse gas (GHG) emissions from global land use and land cover change. Here, we provide fine-resolution (100 m × 100 m) estimates of GHG footprints of current (2015) and potential future scenarios (2030) of crude palm oil (CPO) production in Indonesia. The current estimated average GHG footprint excluding production on Java is 5.

Diagnostic Utility of Exome Sequencing for Kidney Disease.

Background: Exome sequencing is emerging as a first-line diagnostic method in some clinical disciplines, but its usefulness has yet to be examined for most constitutional disorders in adults, including chronic kidney disease, which affects more than 1 in 10 persons globally.

Methods: We conducted exome sequencing and diagnostic analysis in two cohorts totaling 3315 patients with chronic kidney disease. We assessed the diagnostic yield and, among the patients for whom detailed clinical data were available, the clinical implications of diagnostic and other medically relevant findings.

Variability of Greenhouse Gas Footprints of Field Tomatoes Grown for Processing: Interyear and Intercountry Assessment.

Our study provides an integrated analysis of the variability of greenhouse gas (GHG) footprints of field-grown tomatoes for processing. The global farm-specific data set of 890 observations across 14 countries over a three-year period (2013-2015) was obtained from farms grown under Unilever's sustainable agricultural code. It represents on average 3% of the annual global production of processing tomatoes: insights can be used to help inform corporate sourcing strategies and certification schemes.