The Effects of Dexamethasone on Mitogen Activated Protein Kinase-14 Signaling in Diffuse Intrinsic Pontine Glioma (DIPG) Cells

Objective: Determine the effects of dexamethasone (DEX) on diffuse intrinsic pontine glioma (DIPG) cell behavior. Background: Patients with DIPG routinely receive DEX to treat vasogenic edema, but the direct effects on tumor growth and sensitivity to other therapies are unknown. Previous studies on glioblastoma cell lines have suggested that DEX interferes with nuclear translocation of p38α mitogen activated protein kinase-14 (MAPK-14), which may be required for cytokine production, cell mobility, and invasion, in addition to a metabolic shift from glycolysis to the pentose phosphate pathway. We tested the hypothesis that DEX prevents nuclear translocation of MAPK-14 in DIPG, resulting in metabolic reprogramming and decreased cell survival, migration, and colony formation. Design/Methods: We used immunocytochemistry to measure the nuclear translocation of total and phosphorylated MAPK-14 in cultured SU-DIPG-IV cells following treatment with DEX or vehicle. We also treated cells with DEX, with or without the clinically relevant chemotherapies panobinostat and imatinib on logarithmic dose curves, and measured proliferation rate, viability and apoptosis with combined assays of trypan blue exclusion and caspase 3/7 activation. Results: Treatment with DEX reduced nuclear localization of phosphorylated MAPK-14 in DIPG cells, but did not affect basal or chemotherapy-inhibited rates of cell proliferation, viability or apoptosis. Conclusions: DEX, a commonly prescribed medication for DIPG patients, decreased nuclear localization of phosphorylated MAPK-14 but had no apparent effects on basal or chemotherapy-inhibited rates of cell proliferation, viability or apoptosis. We are currently exploring the effects of DEX and MAPK-14 signaling on cell metabolism, migration, and colony formation

The Effects of Dexamethasone on Mitogen Activated Protein Kinase-14 Signaling in Diffuse Intrinsic Pontine Glioma (DIPG) Cells

Objective: Determine the effects of dexamethasone (DEX) on diffuse intrinsic pontine glioma (DIPG) cell behavior. Background: Patients with DIPG routinely receive DEX to treat vasogenic edema, but the direct effects on tumor growth and sensitivity to other therapies are unknown. Previous studies on glioblastoma cell lines have suggested that DEX interferes with nuclear translocation of p38α mitogen activated protein kinase-14 (MAPK-14), which may be required for cytokine production, cell mobility, and invasion, in addition to a metabolic shift from glycolysis to the pentose phosphate pathway. We tested the hypothesis that DEX prevents nuclear translocation of MAPK-14 in DIPG, resulting in metabolic reprogramming and decreased cell survival, migration, and colony formation. Design/Methods: We used immunocytochemistry to measure the nuclear translocation of total and phosphorylated MAPK-14 in cultured SU-DIPG-IV cells following treatment with DEX or vehicle. We also treated cells with DEX, with or without the clinically relevant chemotherapies panobinostat and imatinib on logarithmic dose curves, and measured proliferation rate, viability and apoptosis with combined assays of trypan blue exclusion and caspase 3/7 activation. Results: Treatment with DEX reduced nuclear localization of phosphorylated MAPK-14 in DIPG cells, but did not affect basal or chemotherapy-inhibited rates of cell proliferation, viability or apoptosis. Conclusions: DEX, a commonly prescribed medication for DIPG patients, decreased nuclear localization of phosphorylated MAPK-14 but had no apparent effects on basal or chemotherapy-inhibited rates of cell proliferation, viability or apoptosis. We are currently exploring the effects of DEX and MAPK-14 signaling on cell metabolism, migration, and colony formation

Re-activated adult epicardial progenitor cells are a heterogeneous population molecularly distinct from their embryonic counterparts.

Cardiovascular disease remains the major cause of mortality, and cardiac cell therapy has recently emerged as a paradigm for heart repair. The epicardium is a layer of mesothelial cells covering the heart that during development contributes to different cardiovascular lineages, including cardiomyocytes, but which becomes quiescent after birth. We previously revealed that the peptide thymosin beta 4 (Tβ4) can reactivate adult epicardium-derived cells (EPDCs) after myocardial infarction (MI), to proliferate, and differentiate into cardiovascular derivatives. The aim of this study was to provide a lineage characterization of the adult EPDCs relative to the embryonic epicardial lineage and to determine prospective cell fate biases within the activated adult population during cardiovascular repair. Wt1(GFPCre/+) mice were primed with Tβ4 and MI induced by ligation of the left anterior descending coronary artery. Adult WT1(+) GFP(+) EPDCs were fluorescence-activated cell sorted (FACS) at 2, 4, and 7 days after MI. Embryonic WT1(+) GFP(+) EPDCs were isolated from embryonic hearts (E12.5) by FACS, and sorted cells were characterized by real-time quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR) and immunostaining. Adult WT1(+) GFP(+) EPDCs were highly heterogeneous, expressing cardiac progenitor and mesenchymal stem markers. Based on the expression of stem cell antigen-1 (Sca-1), CD44, and CD90, we identified different subpopulations of EPDCs of varying cardiovascular potential, according to marker gene profiles, with a molecular phenotype distinct from the source embryonic epicardial cells at E12.5. Thus, adult WT1(+) GFP(+) cells are a heterogeneous population that when activated can restore an embryonic gene programme, but do not revert entirely to adopt an embryonic phenotype. Potential biases in cardiovascular cell fate suggest that discrete subpopulations of EPDCs might be clinically relevant for regenerative therapy

Coronal Heating as Determined by the Solar Flare Frequency Distribution Obtained by Aggregating Case Studies

Flare frequency distributions represent a key approach to addressing one of the largest problems in solar and stellar physics: determining the mechanism that counter-intuitively heats coronae to temperatures that are orders of magnitude hotter than the corresponding photospheres. It is widely accepted that the magnetic field is responsible for the heating, but there are two competing mechanisms that could explain it: nanoflares or Alfv\'en waves. To date, neither can be directly observed. Nanoflares are, by definition, extremely small, but their aggregate energy release could represent a substantial heating mechanism, presuming they are sufficiently abundant. One way to test this presumption is via the flare frequency distribution, which describes how often flares of various energies occur. If the slope of the power law fitting the flare frequency distribution is above a critical threshold, $\alpha=2$ as established in prior literature, then there should be a sufficient abundance of nanoflares to explain coronal heating. We performed $>$600 case studies of solar flares, made possible by an unprecedented number of data analysts via three semesters of an undergraduate physics laboratory course. This allowed us to include two crucial, but nontrivial, analysis methods: pre-flare baseline subtraction and computation of the flare energy, which requires determining flare start and stop times. We aggregated the results of these analyses into a statistical study to determine that $\alpha = 1.63 \pm 0.03$. This is below the critical threshold, suggesting that Alfv\'en waves are an important driver of coronal heating.Comment: 1,002 authors, 14 pages, 4 figures, 3 tables, published by The Astrophysical Journal on 2023-05-09, volume 948, page 7