Response of Carcinogen-Altered Mouse Epidermal Cells to Phorbol Ester Tumor Promoters and Calcium

Primary cultures of mouse epidermal cells are induced to terminally differentiate when extracellular calcium levels are increased to more than 0.1mM After carcinogen treatment, cellular foci can be selected that resist this calcium signal to terminally differentiate Calcium causes these foci to stratify, however, in contrast to normal epidermis, DNA- synthesizing cells in these foci are found in the suprabasal cell layers as well as in basal cells Cell lines derived from these foci may be considered to be putative initiated cells Three of these cell lines, designated 308, D, and F, have been characterized for their response to calcium and phorbol ester tumor promoters. The formation of cornified cells and the activity of epidermal transglutaminase were utilized as markers of epidermal differentiation. Neither calcium nor the tumor promoter 12-O-tetradecanoylphorbol-13- acetate (TPA) increased transglutaminase activity or cornification of any of the 3 lines Proliferation was estimated by the [3H]thymidine labeling index, by incorporation of [3H]thymidine into DNA, and by a clonal growth assay. Unlike primary normal cultures, rising the calcium level of the medium did not markedly reduce the rate of proliferation of any of the 3 cell lines. in 2 of the lines, line 308 and line D, proliferation increased in response to TPA exposure. in line F, [3H]thymidine incorporation in confluent cultures was inhibited by TRA, while in cells plated at clonal densities, TPA was cytotoxic at doses of 5 ng/ml or higher. If these calcium-resistant epidermal cell lines correspond to initiated cells, their lack of sensitivity to the induction of terminal differentiation by TPA could account for their growth relative to normal cells. Those lines that also respond to stimulation of proliferation by TPA to a greater extent than normal cells would have a further growth advantage

Thank You to Space Weather Peer Reviewers

Space Weather Editors recognize contribution from peer reviewers.Key PointThank you to Space Weather 2017 reviewersPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144655/1/swe20690.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144655/2/swe20690_am.pd

Next generation magnetic field measurements from low-earth orbit satellites enable enhanced space weather operations

Large-scale current systems in the ionosphere and the magnetosphere are intimately controlled by the solar wind-magnetosphere interaction and the magnetosphere-ionosphere coupling. During space weather events, these currents reconfigure and intensify significantly in response to enhanced solar wind-magnetosphere interaction, facilitating explosive energy input from the magnetosphere into the ionosphere-thermosphere system and inducing electric current surges in electric power systems on the ground. Therefore, measurements of magnetic manifestations associated with the dynamic changes of the current systems are crucial for specifying the energy input into the ionosphere-thermosphere system, understanding energy dissipation mechanisms, and predicting the severity of their space weather impacts. We investigate the potential uses of high-quality magnetic field data for space weather operations and propose real-time data products from next generation constellation missions that enable improved space weather forecasting and mitigation. &nbsp;</p

Evaluation of vitamin D biosynthesis and pathway target genes reveals UGT2A1/2 and EGFR polymorphisms associated with epithelial ovarian cancer in African American Women.

An association between genetic variants in the vitamin D receptor (VDR) gene and epithelial ovarian cancer (EOC) was previously reported in women of African ancestry (AA). We sought to examine associations between genetic variants in VDR and additional genes from vitamin D biosynthesis and pathway targets (EGFR, UGT1A, UGT2A1/2, UGT2B, CYP3A4/5, CYP2R1, CYP27B1, CYP24A1, CYP11A1, and GC). Genotyping was performed using the custom-designed 533,631 SNP Illumina OncoArray with imputation to the 1,000 Genomes Phase 3 v5 reference set in 755 EOC cases, including 537 high-grade serous (HGSOC), and 1,235 controls. All subjects are of African ancestry (AA). Logistic regression was performed to estimate odds ratios (OR) and 95% confidence intervals (CI). We further evaluated statistical significance of selected SNPs using the Bayesian False Discovery Probability (BFDP). A significant association with EOC was identified in the UGT2A1/2 region for the SNP rs10017134 (per allele OR = 1.4, 95% CI = 1.2-1.7, P = 1.2 × 10-6 , BFDP = 0.02); and an association with HGSOC was identified in the EGFR region for the SNP rs114972508 (per allele OR = 2.3, 95% CI = 1.6-3.4, P = 1.6 × 10-5 , BFDP = 0.29) and in the UGT2A1/2 region again for rs1017134 (per allele OR = 1.4, 95% CI = 1.2-1.7, P = 2.3 × 10-5 , BFDP = 0.23). Genetic variants in the EGFR and UGT2A1/2 may increase susceptibility of EOC in AA women. Future studies to validate these findings are warranted. Alterations in EGFR and UGT2A1/2 could perturb enzyme efficacy, proliferation in ovaries, impact and mark susceptibility to EOC.Includes NIHR and CRUK

A Spatial Autocorrelation Approach for Examining the Effects of Urban Greenspace on Residential Property Values

Housing value, Urban greenspace, Hedonic pricing model, Spatial dependence,