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Abstract: The preparation, structure and magnetic properties of two mono-N-substituted ethylenediammonium copper chloride salts are reported. Both [(MEDA)Cl]2CuCl4 and [(EEDA)Cl]2CuCl4 assume monoclinic layered perovskite A2CuCl4 type structures (here MEDA2+ is the N-methylethylenediammonium dication and EEDA2+ is the N-ethylethylenediammonium dication). In these structures, planar ions are linked together into layers of corner-sharing distorted octahedra via semi-coordinate Cu⋯Cl bonds. The magnetic studies reveal the presence of dominant ferromagnetic coupling in both compounds and analysis of the higher temperature data yielded J/k =19.29(1)K and 19.0(4)K for the methyl and ethyl derivatives, respectively. Further ac susceptibility studies reveal the onset of ferromagnetic ordering below 9.0K for both compounds. The ferromagnetic ordering is further confirmed by the presence of hysteresis loops with rapid saturation in both compounds. [Copyright &y& Elsevier]

Purpose: Excessive formation of tumor necrosis factor-α (TNF-α), a pro-inflammatory cytokine, has been implicated in the development of insulin resistance in obesity and type-2 diabetes. In skeletal muscle, chronic exposure to TNF-α impairs insulin-stimulated glucose uptake and insulin signaling. The aim of this study is to investigate the effects of enzymatic egg white hydrolysate (EWH) and its responsible peptide, IRW, on TNF-α-induced insulin resistance and the underlying molecular mechanisms using rat skeletal muscle cells (L6 cells). Methods: Insulin resistance was induced by treating L6 cells with 5 ng/ml TNF-α for 24 h. Effects of EWH and IRW on glucose uptake were detected by glucose uptake assay, glucose transporter 4 (GLUT4) translocation by immunofluorescence, and western blot, while insulin-signaling pathway and mitogen-activated protein kinase (MAPK) pathway were investigated using western blot. Results: Adding both EWH and IRW significantly improved glucose uptake in TNF-α-treated cells, increased activation of insulin receptor substrate (IRS-1) tyrosine residue and protein kinase B (Akt), whereas decreased activation of IRS-1 serine residue. In addition, TNF-α-induced activation of p38-mitogen-activated protein kinase (p38) and c-Jun N-terminal kinases (JNK) 1/2 were decreased by either EWH or IRW treatment. Conclusion: EWH and IRW improve impaired insulin sensitivity by down-regulating the activation of p38 and JNK1/2 in TNF-α-treated skeletal muscle cells. [ABSTRACT FROM AUTHOR]

Sixty Duroc × Large White × Landrace pigs with an average initial body weight (BW) of 77.1 ± 1.3 kg were selected to investigate the effects of dietary supplementation with arginine (Arg) and/or glutamic acid (Glu) on free amino acid (FAA) profiles, expression of AA transporters, and growth-related genes in skeletal muscle. The animals were randomly assigned to one of five treatment groups (basic diet, iso-nitrogenous, Arg, Glu, and Arg + Glu groups). The results showed that plasma Glu concentration was lowest in the Arg + Glu group and highest in the Glu group (P < 0.05). In the longissimus dorsi (LD) muscle, the concentrations of histidine, Arg, and taurine in the Arg + Glu group were higher, and the concentrations of 3-methylhistidine was lower, than in the basic diet group (P < 0.05). The mRNA levels of ASC amino acid transporter-2 (ASCT2), L-type AA transporter 1, and sodium-coupled neutral amino acid transporter 2 in the LD muscle, as well as the mRNA levels of ASCT2 and proton-assisted amino acid transporter in the biceps femoris (BF) muscle, were higher in the Arg + Glu group compared to the basic diet group (P < 0.05). The mRNA levels of the muscle-specific RING finger-1 and muscle atrophy F-box genes in the LD muscle were downregulated in the Glu and Arg + Glu groups compared to the basic diet group (P < 0.05). Collectively, these findings suggest that dietary supplementation with both Arg and Glu increases intramuscular FAA concentrations and decreases the mRNA levels of genes involved in protein degradation in skeletal muscle. [ABSTRACT FROM AUTHOR]

Atonal homolog 1 (Atoh1) is a basic helix-loop-helix 9 (bHLH) transcription factor acting downstream of Notch and is required for the differentiation of sensory hair cells in the inner ear and the specification of secretory cells during the intestinal crypt cell regeneration. Motivated by the observations that the upregulation of Atoh1 gene expression, through genetic manipulation or pharmacological inhibition of Notch signaling (e.g. γ-secretase inhibitors, GSIs), induces ectopic hair cell growth in the cochlea of the inner ear and partially restores hearing after injuries in experimental models, we decided to identify small molecule modulators of the Notch-Atoh1 pathway, which could potentially regenerate hair cells. However, the lack of cellular models of the inner ear has precluded the screening and characterization of such modulators. Here we report using a colon cancer cell line LS-174T, which displays Notch inhibition-dependent Atoh1 expression as a surrogate cellular model to screen for inducers of Atoh1 expression. We designed an Atoh1 promoter-driven luciferase assay to screen a target-annotated library of ~6000 compounds. We further developed a medium throughput, real-time quantitative RT-PCR assay measuring the endogenous Atoh1 gene expression to confirm the hits and eliminate false positives from the reporter-based screen. This strategy allowed us to successfully recover GSIs of known chemotypes. This LS-174T cell-based assay directly measures Atoh1 gene expression induced through Notch-Hes1 inhibition, and therefore offers an opportunity to identify novel cellular modulators along the Notch-Atoh1 pathway. [ABSTRACT FROM AUTHOR]