The circulating level of the inflammatory cytokine interleukin (IL)-6 is elevated in various insulin-resistant states including type 2 diabetes, obesity, cancer, and HIV-associated lipodystrophy. To determine the role of IL-6 in the development of insulin resistance, we examined the effects of IL-6 treatment on whole-body insulin action and glucose metabolism in vivo during hyperinsulinemic-euglycemic clamps in awake mice. Pretreatment of IL-6 blunted insulin's ability to suppress hepatic glucose production and insulin-stimulated insulin receptor substrate (IRS)-2-associated phosphatidylinositol (PI) 3-kinase activity in liver. Acute IL-6 treatment also reduced insulin-stimulated glucose uptake in skeletal muscle, and this was associated with defects in insulin-stimulated IRS-1-associated PI 3-kinase activity and increases in fatty acyl-CoA levels in skeletal muscle. In contrast, we found that co-treatment of IL-10, a predominantly anti-inflammatory cytokine, prevented IL-6 -induced defects in hepatic insulin action and signaling activity. Additionally, IL-10 co-treatment protected skeletal muscle from IL-6 and lipidinduced defects in insulin action and signaling activity, and these effects were associated with decreases in intramuscular fatty acyl-CoA levels. This is the first study to demonstrate that inflammatory cytokines IL-6 and IL-10 alter hepatic and skeletal muscle insulin action in vivo, and the mechanism may involve cytokineinduced alteration in intracellular fat contents. These findings implicate an important role of inflammatory cytokines in the pathogenesis of insulin resistance.

OBJECTIVEInsulin resistance is a major characteristic of type 2 diabetes and is causally associated with obesity. Inflammation plays an important role in obesity-associated insulin resistance, but the underlying mechanism remains unclear. Interleukin (IL)-10 is an anti-inflammatory cytokine with lower circulating levels in obese subjects, and acute treatment with IL-10 prevents lipid-induced insulin resistance. We examined the role of IL-10 in glucose homeostasis using transgenic mice with muscle-specific overexpression of IL-10 (MCK-IL10).RESEARCH DESIGN AND METHODSMCK-IL10 and wild-type mice were fed a high-fat diet (HFD) for 3 weeks, and insulin sensitivity was determined using hyperinsulinemic-euglycemic clamps in conscious mice. Biochemical and molecular analyses were performed in muscle to assess glucose metabolism, insulin signaling, and inflammatory responses.RESULTSMCK-IL10 mice developed with no obvious anomaly and showed increased whole-body insulin sensitivity. After 3 weeks of HFD, MCK-IL10 mice developed comparable obesity to wild-type littermates but remained insulin sensitive in skeletal muscle. This was mostly due to significant increases in glucose metabolism, insulin receptor substrate-1, and Akt activity in muscle. HFD increased macrophage-specific CD68 and F4/80 levels in wild-type muscle that was associated with marked increases in tumor necrosis factor-α, IL-6, and C-C motif chemokine receptor-2 levels. In contrast, MCK-IL10 mice were protected from diet-induced inflammatory response in muscle.CONCLUSIONSThese results demonstrate that IL-10 increases insulin sensitivity and protects skeletal muscle from obesity-associated macrophage infiltration, increases in inflammatory cytokines, and their deleterious effects on insulin signaling and glucose metabolism. Our findings provide novel insights into the role of anti-inflammatory cytokine in the treatment of type 2 diabetes.

Rapid translation of genome sequences into meaningful biological information hinges on the integration of multiple experimental and informatics methods into a cohesive platform. Despite the explosion in the number of genome sequences available, such a platform does not exist for filamentous fungi. Here we present the development and application of a functional genomics and informatics platform for a model plant pathogenic fungus, Magnaporthe oryzae. In total, we produced 21,070 mutants through large-scale insertional mutagenesis using Agrobacterium tumefaciens-mediated transformation. We used a high-throughput phenotype screening pipeline to detect disruption of seven phenotypes encompassing the fungal life cycle and identified the mutated gene and the nature of mutation for each mutant. Comparative analysis of phenotypes and genotypes of the mutants uncovered 202 new pathogenicity loci. Our findings demonstrate the effectiveness of our platform and provide new insights on the molecular basis of fungal pathogenesis. Our approach promises comprehensive functional genomics in filamentous fungi and beyond.

[Purpose] The purpose of this study was to investigate the use of smartphones by university students in selected areas, their musculoskeletal symptoms, and the associated hazard ratio. [Subjects and Methods] This involved the completion of a self-administered questionnaire by dental hygiene students in Seoul, Gyeonggido, and Gyeongsangbukdo. The 292 completed copies of the questionnaire were then analyzed. [Results] The most painful body regions after the use of smartphones were found to be the shoulders and neck. In the musculoskeletal system, back pain was found to have a positive correlation with the size of the smartphone’s liquid crystal display (LCD) screen, and pain in legs and feet were found to have a negative correlation with the length of time that the smartphone was used. As a result, it was revealed that the use of a smartphone was correlated with musculoskeletal symptoms. [Conclusion] Therefore, in today’s environment, where the use of smartphones is on the rise, it is necessary to improve the ways that they are used and to develop a preventive program to alleviate the symptoms of musculoskeletal damage.

SummaryNeurospora crassa is a heterothallic filamentous fungus with two mating types, mat a and mat A . Its mating involves differentiation of female reproductive structures (protoperithecia) and chemotropic growth of female-specific hyphae (trichogynes) towards a cell of the opposite mating type in a pheromone-mediated process. In this study, we characterize the pre-1 gene, encoding a predicted G-protein-coupled receptor with sequence similarity to fungal pheromone receptors. pre-1 is most highly expressed in mat A strains under mating conditions, but low levels can also be detected in mat a strains. Analysis of pre-1 deletion mutants showed that loss of pre- D pre-1 mat A mutant could not be complemented by constitutive activation of gna-1 , suggesting additional layers of regulation. We propose that PRE-1 is a pheromone receptor coupled to GNA-1 that is essential for the mating of mat A strains as females, consistent with a role in launching the pheromone response pathway in N. crassa .

The protein tyrosine phosphatase SHP-1 is a well-known inhibitor of activation-promoting signaling cascades in hematopoietic cells but its potential role in insulin target tissues is unknown. Here we show that Ptpn6(me-v/me-v) (also known as viable motheaten) mice bearing a functionally deficient SHP-1 protein are markedly glucose tolerant and insulin sensitive as compared to wild-type littermates, as a result of enhanced insulin receptor signaling to IRS-PI3K-Akt in liver and muscle. Downregulation of SHP-1 activity in liver of normal mice by adenoviral expression of a catalytically inert mutant of SHP-1, or after small hairpin RNA-mediated SHP-1 silencing, further confirmed this phenotype. Tyrosine phosphorylation of CEACAM1, a modulator of hepatic insulin clearance, and clearance of serum [125I]-insulin were markedly increased in SHP-1-deficient mice or SHP-1-deficient hepatic cells in vitro. These findings show a novel role for SHP-1 in the regulation of glucose homeostasis through modulation of insulin signaling in liver and muscle as well as hepatic insulin clearance.

We report the effect of chemical and physical treatments on the structural stability of DNA origami nanostructures. Our result shows that DNA nanostructure maintains its shape under harsh processing conditions, including thermal annealing up to 200°C for 10 min, immersing in a wide range of organic solvents for up to 24 h, brief exposure to alkaline aqueous solutions, and 5 min exposure to UV/ O 3 . Our result suggests that the application window of DNA nanostructure is significantly wider than previously believed. ■ INTRODUCTIONThe past decade has witnessed an explosive growth in the design and synthesis of DNA nanostructures. Through careful design of sequences, almost any desired 2D and 3D shapes can be constructed with nanometer scale precision and accuracy. Examples of such structures include individual 2D and 3D objects, 1−6 1D nanowires and nanotubes, 7,8 2D lattices, 9 and 3D crystals. 10 Many of the applications of DNA nanostructures take advantage of their precise and highly configurable geometries. DNA nanostructures have been used as templates to pattern and direct the assembly of various biomolecular, organic, and inorganic materials, including metal nanoparticles, 8,11−19 proteins, 11,12,20,21 carbon nanotubes, 22,23 and quantum dots. 24 In addition, efforts have also been made to use DNA as a template to directly or indirectly pattern graphene and inorganic oxide substrates. 25−29 For example, Becerril et al. used aligned DNA molecule as a shadow mask for angled metal vapor deposition. 25 A spatial resolution in the sub-10 nm range was demonstrated. Deng et al. reported the metal evaporation onto DNA nanostructures deposited on a mica substrate followed by lift-off to create metal replicas of DNA. 26 Recently we demonstrated the use of DNA nanostructures as a mask for the etching of SiO 2 and chemical vapor deposition of inorganic oxides; in both cases, both positive tone and negative tone pattern transfers were obtained through a careful control of the reaction conditions. 28,29 Although significant progress has been made, using DNA nanostructures in the bottom-up fabrication still faces significant challenges. In particular, many bottom-up fabrications involve very harsh processing conditions such as high temperatures and corrosive chemicals. However, DNA is a soft, chemically labile material that has limited thermal and chemical stability. In fact, even widely used solution phase processes could pose a significant risk, since deposited DNA nanostructures could be easily lifted-off from the substrate. 13,17 Because of this reason, the success of a DNA-mediated bottom-up fabrication is often limited and constrained by the stability of DNA nanostructures themselves. Therefore, understanding their structural stability under various chemical and physical environments is critical to the advance of this field of research.In aqueous solution, the kinetics and thermodynamics of DNA hybridization are well understood. Several groups have recently investigated the stability of DNA nanostructure in buff...

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