AMPK suppresses Th2 cell responses by repressing mTORC2

Allergic inflammation is a T helper 2 (Th2) cell-driven pathophysiological phenomenon, but the mechanism by which the metabolic cascade affects Th2 cell differentiation remains unclear. In this study, we investigated the roles of AMP-activated protein kinase (AMPK) and intracellular energy sensors in Th2 cell differentiation and the pathogenesis of allergic inflammation. Accordingly, T-cell-specific AMPK or Sirtuin 1 (Sirt1)-knockout mice were subjected to allergic inflammation, and their Th2 cell responses were investigated. The results demonstrated that inducing allergic inflammation in AMPK- and Sirt1-knockout mice increased Th2 cell responses and exacerbated allergic phenotypes. Furthermore, treatment with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), an activator of AMPK, ameliorated allergic inflammation in mice. Mechanistically, our findings revealed that AMPK repressed mechanistic target of rapamycin complex 2 (mTORC2), which downregulated the expression of suppressor of cytokine signaling 5 (SOCS5) in CD4⁺ T cells. In addition, the loss of AMPK signaling reduced SOCS5 expression and increased interleukin-4-STAT6–GATA3 axis-mediated Th2 cell differentiation. Finally, the T-cell-specific deletion of Rictor, a member of mTORC2, in Sirt1^T-KO mice led to the reversal of allergic exacerbation to the level in control mice. Overall, our findings suggest that AMPK in CD4⁺ T cells inhibits the differentiation of Th2 cells by repressing mTORC2 and thus serves as a potential target for Th2 cell-associated diseases.Subject terms: Lymphocytes, Inflammation     

Pim1 promotes IFN-β production by interacting with IRF3

The Pim (proviral integration site for Moloney murine leukemia virus) proteins compose a serine threonine kinase family whose members regulate cell proliferation, migration and cell survival. However, whether Pim kinases participate in innate immune responses is unclear. Here, we show for the first time that Pim1 plays an essential role in the production of interferon (IFN)-β by macrophages after their Toll-like receptor (TLR) pathway is activated by pathogen-associated molecular patterns (PAMPs). Specifically, Pim1 was quickly upregulated in an NF-κB-dependent manner after TLR stimulation with PAMPs. Pim1 deficiency reduced TLR3- or TLR4-stimulated IFN-β and IFN-stimulated gene (ISG) expression but not proinflammatory cytokine expression in macrophages. Mechanistically, Pim1 specifically upregulates IRF3 phosphorylation and nuclear translocation. However, this role is not dependent on Pim1 kinase activity. Rather, Pim1 appears to promote IRF3 phosphorylation by enhancing the formation of IFN-β signaling complexes composed of TRIF, TRAF3, TBK1, and IRF3. Poly (I:C)-treated Pim1^−/− mice produced less serum IFN-β and were less likely to survive than wild-type mice. These findings show for the first time that Pim1 participates in TLR-mediated IFN-β production, thus revealing a novel target for controlling antiviral innate immune responses.Subject terms: Toll-like receptors, Phagocytes     

Development of a Quantitative Method for Detection of Multiclass Veterinary Drugs in Feed Using Modified QuPPe Extraction and LC–MS/MS

A method was developed for the rapid and quantitative analysis of 30 veterinary drugs belonging to 17 classes (amphenicols (1), anthelmintics (1), cephalosporins (4), coccidiostats (1), lincosamides (1), macrolide (1), nitroimidazole (1), penicillins (3), phenylhydrazines (1), polypeptides (1), pyrethrins (1), quinolones (5), sulfonamides (3), tetracycline (3), neuroleptic agents (1), triazene trypanocidal agents (1), other. (1)) in feeds. The proposed method with a modified Quick Polar Pesticides (QuPPe) sample preparation was validated for the determination of 30 veterinary drugs in feed samples by liquid chromatography triple-quadrupole mass spectrometry (LC–MS/MS). The sample was extracted with methanol containing 1% acetic acid and purified by dispersive solid-phase extraction (d-SPE) with C18. Good linearity (r² ≥ 0.98) was observed, and the LOQ values ranged from 10 to 200 µg/kg. Average recoveries ranged from 70.8 to 118.4%, and the relative standard deviation was ≤ 18.7%. This validated method was used in the determination of 30 veterinary drugs in 142 feed samples obtained from South Korea. The results show that lincomycin was present in only one of the tested feed samples, although it was detected at a value lower than the LOQ. In conclusion, this multi-residue method can be used for screening through the detection and quantitation of residual multiclass veterinary drugs in feed samples.     

Performance Improvement of Acid Pretreated 3D-printing Composite for the Heavy Metal Ions Analysis

The performance enhancement of 3D-printed electrode comprised of polylactic acid (PLA) and graphite (Gr) doped with graphene oxide (GO) was studied to detect five heavy metal ions in trace level. The pretreatment of PLA/Gr/GO electrode with potential cycling in H₂SO₄ solution achieved the most sensitive response. The characteristics of the composite electrodes were verified using XPS, FE-SEM, EDXS, Raman, and impedance spectroscopy. The experimental variables affecting the response current were optimized with respect to pH, deposition time, ratio of PLA/Gr/GO, and supporting electrolytes. The pretreated 3D-PLA/Gr/GO electrode showed a wide dynamic range from 0.5 ppb to 1.0 ppm with low detection limits of 0.039–0.13 ppb. The reliability of the PLA/Gr/GO electrode was evaluated by analyzing the reference samples of European Reference Materials.     

Effect of gamma irradiation on polypropylene yarns under air and water

Journal of Radioanalytical and Nuclear Chemistry - Polypropylene (PP) filters are used for the treatment of radioactive liquid waste containing gamma nuclides such as Co-60, and filter physical and...     

Investigation on the magnetic and Mössbauer spectroscopy of 57Fe doped LiMnPO4

Journal of Radioanalytical and Nuclear Chemistry - The 57Fe doped LiMnPO4 cathode with potential applications in Li-ion batteries was prepared by solid-state reaction. The magnetic susceptibility...     

Pretilt angle generation by UV exposure during imidization of polyimide

We investigated pretilt angle generation and liquid crystal (LC) alignment by ultraviolet exposure during the imidization of polyimide (PI). The generated pretilt angle of a nematic (N) LC using an in situ photo-alignment method is smaller than that using a conventional photo-alignment method on a surface of PI having side chains. The NLC pretilt angles using an in situ photo-alignment method injected at isotropic phase increased with annealing were observed.     

Determination of PF‐04620110, a novel inhibitor of diacylglycerol acyltransferase‐1, in rat plasma using liquid chromatography–tandem mass spectrometry and its application in pharmacokinetic studies

In this study, we developed a method for the determination of PF‐04620110 (2‐{(1r,4r)‐4‐[4‐(4‐amino‐5‐oxo‐7,8‐dihydropyrimido[5,4‐f][1,4]oxazepin‐6(5H)‐yl)phenyl]cyclohexyl}acetic acid), a novel diacylglycerol acyltransferase 1 (DGAT‐1) inhibitor, in rat plasma and validated it using liquid chromatography–tandem mass spectrometry (LC‐MS/MS). Rat plasma samples were processed following a protein precipitation method by using acetonitrile and were then injected into an LC‐MS/MS system for quantification. PF‐04620110 and imipramine (internal standard) were separated using a Hypersil Gold C₁₈ column, with a mixture of acetonitrile and 10 mm ammonium formate (90:10, v/v) as the mobile phase. The ion transitions monitored in positive‐ion mode [M + H]⁺ of multiple‐reaction monitoring were m/z 397.0 → 260.2 for PF‐04620110 and m/z 280.8 → 86.0 for imipramine. The detector response was specific and linear for PF‐04620110 at concentrations within the range 0.05–50 µg/mL and the signal‐to‐noise ratios for the samples were ≥10. The intra‐ and inter‐day precision and accuracy of the method matched the acceptance criteria for assay validation. PF‐04620110 was stable under various processing and/or handling conditions. PF‐04620110 concentrations in the rat plasma samples could be measured up to 24 h after intravenous or oral administration of PF‐04620110, suggesting that the assay is useful for pharmacokinetic studies in rats. Copyright © 2013 John Wiley & Sons, Ltd.