Adipocyte PU.1 knockout promotes insulin sensitivity in HFD-fed obese mice.

Insulin resistance is a key feature of obesity and type 2 diabetes. PU.1 is a master transcription factor predominantly expressed in macrophages but after HFD feeding PU.1 expression is also significantly increased in adipocytes. We generated adipocyte specific PU.1 knockout mice using adiponectin cre to investigate the role of PU.1 in adipocyte biology, insulin and glucose homeostasis. In HFD-fed obese mice systemic glucose tolerance and insulin sensitivity were improved in PU.1 AKO mice and clamp studies indicated improvements in both adipose and liver insulin sensitivity. At the level of adipose tissue, macrophage infiltration and inflammation was decreased and glucose uptake was increased in PU.1 AKO mice compared with controls. While PU.1 deletion in adipocytes did not affect the gene expression of PPARg itself, we observed increased expression of PPARg target genes in eWAT from HFD fed PU.1 AKO mice compared with controls. Furthermore, we observed decreased phosphorylation at serine 273 in PU.1 AKO mice compared with fl/fl controls, indicating that PPARg is more active when PU.1 expression is reduced in adipocytes. Therefore, in obesity the increased expression of PU.1 in adipocytes modifies the adipocyte PPARg cistrome resulting in impaired glucose tolerance and insulin sensitivity

Knockdown of Ant2 Reduces Adipocyte Hypoxia And Improves Insulin Resistance in Obesity.

Decreased adipose tissue oxygen tension and increased HIF-1α expression can trigger adipose tissue inflammation and dysfunction in obesity. Our current understanding of obesity-associated decreased adipose tissue oxygen tension is mainly focused on changes in oxygen supply and angiogenesis. Here, we demonstrate that increased adipocyte O2 demand, mediated by ANT2 activity, is the dominant cause of adipocyte hypoxia. Deletion of adipocyte Ant2 improves obesity-induced intracellular adipocyte hypoxia by decreasing obesity-induced adipocyte oxygen demand, without effects on mitochondrial number or mass, or oligomycin-sensitive respiration. This led to decreased adipose tissue HIF-1α expression and inflammation with improved glucose tolerance and insulin resistance in both a preventative or therapeutic setting. Our results suggest that ANT2 may be a target for the development of insulin sensitizing drugs and that ANT2 inhibition might have clinical utility

The Chemical Compositions of Very Metal-Poor Stars HD 122563 and HD 140283; A View From the Infrared

From high resolution (R = 45,000), high signal-to-noise (S/N > 400) spectra gathered with the Immersion Grating Infrared Spectrograph (IGRINS) in the H and K photometric bands, we have derived elemental abundances of two bright, well-known metal-poor halo stars: the red giant HD 122563 and the subgiant HD 140283. Since these stars have metallicities approaching [Fe/H] = -3, their absorption features are generally very weak. Neutral-species lines of Mg, Si, S and Ca are detectable, as well as those of the light odd-Z elements Na and Al. The derived IR-based abundances agree with those obtained from optical-wavelength spectra. For Mg and Si the abundances from the infrared transitions are improvements to those derived from shorter wavelength data. Many useful OH and CO lines can be detected in the IGRINS HD 122563 spectrum, from which derived O and C abundances are consistent to those obtained from the traditional [O I] and CH features. IGRINS high resolutions H- and K-band spectroscopy offers promising ways to determine more reliable abundances for additional metal-poor stars whose optical features are either not detectable, or too weak, or are based on lines with analytical difficulties.Comment: Accepted for publication in ApJ (28 pages, 4 tables, 6 figures

Variants of the Distinguished Point Method for Cryptanalytic Time Memory Trade-offs (Full version)

The time memory trade-off (TMTO) algorithm, first introduced by Hellman, is a method for quickly inverting a one-way function, using pre-computed tables. The distinguished point method (DP) is a technique that reduces the number of table lookups performed by Hellman\u27s algorithm. In this paper we propose a new variant of the DP technique, named variable DP (VDP), having properties very different from DP. It has an effect on the amount of memory required to store the pre-computed tables. We also show how to combine variable chain length techniques like DP and VDP with a more recent trade-off algorithm called the rainbow table method

Simple Quantification of Pentosidine in Human Urine and Plasma by High-Performance Liquid Chromatography

Pentosidine is an advanced glycation end-product (AGE) and fluorescent cross-link compound. A simple high-performance liquid chromatographic (HPLC) method was developed for the detection and quantification of pentosidine in human urine and plasma. The mobile phase used a gradient system to improve separation of pentosidine from endogenous peaks, and chromatograms were monitored by fluorescent detector set at excitation and emission wavelengths of 328 and 378 nm, respectively. The retention time for pentosidine was 24.3 min and the lower limits of quantification (LLOQ) in human urine and plasma were 1 nM. The intraday assay precisions (coefficients of variation) were generally low and found to be in the range of 5.19–7.49% and 4.96–8.78% for human urine and plasma, respectively. The corresponding values of the interday assay precisions were 9.45% and 4.27%. Accuracies (relative errors) ranged from 87.9% to 115%. Pentosidine was stable in a range of pH solutions, human urine, and plasma. In summary, this HPLC method can be applied in future preclinical and clinical evaluation of pentosidine in the diabetic patients

Efficacy and Safety of a Dexamethasone Implant in Patients with Diabetic Macular Edema at Tertiary Centers in Korea

Purpose. To evaluate the real-world efficacy and safety of the dexamethasone implant (DEX implant) in patients with diabetic macular edema (DME). Methods. Retrospective, multicenter, and noncomparative study of DME patients who were treated with at least one DEX implant. A total of 186 eyes from 165 patients were included. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), complications, and number of retreatments were collected. Data at baseline and monthly for 6 months were analyzed. Results. The average baseline BCVA and CRT were 0.60 LogMAR and 491.6 μm, respectively. The mean BCVA improved until 3 months and then decreased up to 6 months of follow-up (0.53, 0.49, and 0.55 LogMAR at 1, 3, and 6 months; p=0.001, <0.001, and 0.044, resp.). The change of mean CRT was similar to BCVA (345.0, 357.7, and 412.5 μm at 1, 3, and 6 months, p<0.001, <0.001, and <0.001, resp.). 91 eyes (48.9%) received additional treatment with anti-VEGF or DEX implant. The average treatment-free interval was 4.4 months. In group analyses, the DEX implant was more effective in pseudophakic eyes, DME with subretinal fluid (SRF), or diffuse type. Conclusions. Intravitreal dexamethasone implants are an effective treatment for patients with DME, most notably in pseudophakic eyes, DME with SRF, or diffuse type. A half of these patients require additional treatment within 6 months

Atopic Dermatitis-Like Skin Lesions Reduced by Topical Application and Intraperitoneal Injection of Hirsutenone in NC/Nga Mice

Atopic dermatitis (AD) is a common inflammatory skin disease. The increasing prevalence and severity of AD have prompted the developments of safer, more effective drugs. Although topical corticosteroids have been used as first line therapy for AD, their potential side effects limit their clinical applications. To investigate the effect of hirsutenone (HIR), a diarylheptanoid compound, on AD-like skin lesions and other factors related to immune response is the aim of this paper Th2-related cytokines (IL-4, IL-5, IL-13), eosinophil, IgE inflammatory factors (COX-2, iNOS) levels were reduced in blood, lymphocytes, and tissue after HIR treatment. These results suggest that HIR might be an effective treatment for AD

IGRINS Spectral Library

We present a library of high-resolution (R $\equiv$ $\lambda$/$\Delta$$\lambda$ $\sim$ 45,000) and high signal-to-noise ratio (S/N $\geq$ 200) near-infrared spectra for stars of a wide range of spectral types and luminosity classes. The spectra were obtained with the Immersion GRating INfrared Spectrograph (IGRINS) covering the full range of the H (1.496-1.780 $\mu$m) and K (2.080-2.460 $\mu$m) atmospheric windows. The targets were primarily selected for being MK standard stars covering a wide range of effective temperatures and surface gravities with metallicities close to the Solar value. Currently, the library includes flux-calibrated and telluric-absorption-corrected spectra of 84 stars, with prospects for expansion to provide denser coverage of the parametric space. Throughout the H and K atmospheric windows, we identified spectral lines that are sensitive to $T_\mathrm{eff}$ or $\log g$ and defined corresponding spectral indices. We also provide their equivalent widths. For those indices, we derive empirical relations between the measured equivalent widths and the stellar atmospheric parameters. Therefore, the derived empirical equations can be used to calculate $T_\mathrm{eff}$ and $\log g$ of a star without requiring stellar atmospheric models.Comment: 65 pages, 27 figures, 8 tables, accepted for publication in ApJ