Epigenetic modulation of Fgf21 in the perinatal mouse liver ameliorates diet-induced obesity in adulthood

The nutritional environment to which animals are exposed in early life can lead to epigenetic changes in the genome that influence the risk of obesity in later life. Here, we demonstrate that the fibroblast growth factor-21 gene (Fgf21) is subject to peroxisome proliferator-activated receptor (PPAR) α–dependent DNA demethylation in the liver during the postnatal period. Reductions in Fgf21 methylation can be enhanced via pharmacologic activation of PPARα during the suckling period. We also reveal that the DNA methylation status of Fgf21, once established in early life, is relatively stable and persists into adulthood. Reduced DNA methylation is associated with enhanced induction of hepatic FGF21 expression after PPARα activation, which may partly explain the attenuation of diet-induced obesity in adulthood. We propose that Fgf21 methylation represents a form of epigenetic memory that persists into adulthood, and it may have a role in the developmental programming of obesity

Torus Constraints in ANEPD-CXO245: A Compton-thick AGN with Double-peaked Narrow Lines

We report on the torus constraints of the Compton-thick active galactic nucleus (AGN) with double-peaked optical narrow-line region emission lines, ANEPD-CXO245, at z = 0.449 in the AKARI NEP Deep Field. The unique infrared data on this field, including those from the nine-band photometry over 2–24 μm with the AKARI Infrared Camera, and the X-ray spectrum from Chandra allow us to constrain torus parameters such as the torus optical depth, X-ray absorbing column, torus angular width (σ), and viewing angle (i). We analyze the X-ray spectrum as well as the UV–optical–infrared spectral energy distribution (UOI-SED) with clumpy torus models in X-ray (XCLUMPY) and infrared (CLUMPY), respectively. From our current data, the constraints on σ–i from both X-rays and UOI show that the line of sight crosses the torus as expected for a type 2 AGN. We obtain a small X-ray scattering fraction (NH from the X-ray spectrum, we find that the gas-to-dust ratio is <4 times larger than the Galactic value

Small Molecules with Similar Structures Exhibit Agonist, Neutral Antagonist or Inverse Agonist Activity toward Angiotensin II Type 1 Receptor

Small differences in the chemical structures of ligands can be responsible for agonism, neutral antagonism or inverse agonism toward a G-protein-coupled receptor (GPCR). Although each ligand may stabilize the receptor conformation in a different way, little is known about the precise conformational differences. We synthesized the angiotensin II type 1 receptor blocker (ARB) olmesartan, R239470 and R794847, which induced inverse agonism, antagonism and agonism, respectively, and then investigated the ligand-specific changes in the receptor conformation with respect to stabilization around transmembrane (TM)3. The results of substituted cysteine accessibility mapping studies support the novel concept that ligand-induced changes in the conformation of TM3 play a role in stabilizing GPCR. Although the agonist-, neutral antagonist and inverse agonist-binding sites in the AT1 receptor are similar, each ligand induced specific conformational changes in TM3. In addition, all of the experimental data were obtained with functional receptors in a native membrane environment (in situ)

Determination of ¹⁰⁷Pd in Pd Recovered by Laser-Induced Photoreduction with Inductively Coupled Plasma Mass Spectrometry

Safety evaluation of a radioactive waste repository requires credible activity estimates confirmed by actual measurements. A long-lived radionuclide, ¹⁰⁷Pd, which can be found in radioactive wastes, is one of the difficult-to-measure nuclides and results in a deficit in experimentally determined contents. In this study, a precipitation-based separation method has been developed for the determination of ¹⁰⁷Pd with inductively coupled plasma mass spectrometry. The photoreduction induced by pulsed laser irradiation at 355 nm provides short-time and one-step recovery of Pd. The proposed method was verified by applying it to a spent nuclear fuel sample. To recover Pd efficiently, a natural Pd standard was employed as the Pd carrier. Taking advantage of the absence of ¹⁰²Pd in spent nuclear fuel, ¹⁰²Pd in the Pd carrier was utilized as the internal standard. The chemical yield of Pd was about 90% with virtually no impurities, allowing accurate quantification of ¹⁰⁷Pd. The amount of ¹⁰⁷Pd in the Pd precipitate was 17.3 ± 0.7 ng, equivalent to 239 ± 9 ng per mg of ²³⁸U in the sample