Increased expression of the gene encoding the enzyme glucose-6-phosphatase (G6Pase) contributes to the increased production of glucose by the liver that occurs in individuals with diabetes. Puigserver et al. show that the transcription factor FOXO1 and the transcriptional co-activator PGC-1alpha act synergistically to stimulate the expression of genes in the gluconeogenesis pathway and propose that PGC-1alpha acts, in part, directly through FOXO1. Here we show that FOXO1 is neither required nor sufficient for the stimulation of G6Pase-luciferase fusion gene expression by PGC-1alpha. Our results indicate that the transcriptional interaction between FOXO1 and PGC-1alpha is indirect.

CD4+ T cells developing towards a T helper 2 (Th2) fate express IL-4, IL-5, and IL-13 while inhibiting production of cytokines associated with other T helper types, such as the Th1 cytokine IFN- γ. IL-4-producing Th2 effector cells give rise to a long-lived memory population committed to re-activation of the Th2 cytokine gene expression program. However, re-activation of these effector-derived cells under Th1-skewing conditions leads to production of IFN-γ along with IL-4 in the same cell. We now show that this flexibility (“plasticity”) of cytokine expression is preceded by a loss of the repressive DNA methylation of the Ifng promoter acquired during Th2 polarization yet requires STAT4 along with T-bet. Surprisingly, loss of either STAT4 or T-bet increased Ifng promoter CpG methylation in both effector and memory Th2 cells. Taken together, our data suggest a model in which the expression of IFN-γ by Th2-derived memory cells involves attenuation of epigenetic repression in memory Th2 cells, combined with Th1-polarizing signals after their recall activation.

Abstract

Long-term exposure to ultraviolet (UV) rays has been attributed to irreversible health defects at the cellular level. Most importantly, damage to DNA by UVA and UVB rays can result in uncontrolled cellular growth, leading to skin cancer. As a result, topical treatments have been developed over time to protect the skin from UVA and UVB rays. The active ingredients in sunscreens or sun creams are sometimes unsaturated, aromatic organic compounds capable of absorbing harmful UV photons at a great range of wavelengths. Absorption capabilities of these species depend on their degree of conjugation and their molar absorptivity. With this knowledge, two cinnamaldehyde derivatives were synthesized into five potential organic UV filters by the aldol condensation reaction. The products were identified using nuclear magnetic resonance (NMR) and attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopies, and ultraviolet-visible (UV-vis) spectroscopy was used to determine the UV absorption range and intensity of absorption for each compound. Since the compounds would hypothetically be utilized in topical ointments to aide in skin protection, these compounds were assessed in the presence of Pseudomonas aeruginosa, a representative bacterium of the skin’s natural flora. A time-course assay was conducted to detect growth effects of P. aeruginosa in the presence of the organic compounds. According to the spectroscopic and bacterial analyses of these UV-blocking compounds, three compounds were determined to be potential UV filters that cover UVA region while demonstrating no apparent harm to the natural skin bacteria P. aeruginosa, while the other two likely diminished bacterial growth by simple niche inhibition.

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