PPM1A Controls Diabetic Gene Programming through Directly Dephosphorylating PPAR?? at Ser273

Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a master regulator of adipose tissue biology. In obesity, phosphorylation of PPAR gamma at Ser273 (pSer273) by cyclin-dependent kinase 5 (CDK5)/extracellular signal-regulated kinase (ERK) orchestrates diabetic gene reprogramming via dysregulation of specific gene expression. Although many recent studies have focused on the development of non-classical agonist drugs that inhibit the phosphorylation of PPAR gamma at Ser273, the molecular mechanism of PPAR gamma dephosphorylation at Ser273 is not well characterized. Here, we report that protein phosphatase Mg2+/Mn2+-dependent 1A (PPM1A) is a novel PPAR gamma phosphatase that directly dephosphorylates Ser273 and restores diabetic gene expression which is dysregulated by pSer273. The expression of PPM1A significantly decreases in two models of insulin resistance: diet-induced obese (DIO) mice and db/db mice, in which it negatively correlates with pSer273. Transcriptomic analysis using microarray and genotype-tissue expression (GTEx) data in humans shows positive correlations between PPM1A and most of the genes that are dysregulated by pSer273. These findings suggest that PPM1A dephosphorylates PPAR gamma at Ser273 and represents a potential target for the treatment of obesity-linked metabolic disorders

Thermoelectric properties of nanoporous three-dimensional graphene networks

We propose three dimensional-graphene nanonetworks (3D-GN) with pores in the range of 10 similar to 20 nm as a potential candidate for thermoelectric materials. The 3D-GN has a low thermal conductivity of 0.90 W/mK @773 K and a maximum electrical conductivity of 6660 S/m @773 K. Our results suggest a straightforward way to individually control two interdependent parameters, sigma and kappa, in the nanoporous graphene structures to ultimately improve the figure of merit value.open

Short Term Effect and Safety of Antidiuretic Hormone in the Patients with Nocturia

Purpose To investigate the short-term safety of antidiuretic hormone in elderly patients with nocturnal polyuria, focus on hyponatremia and others electrolytes disturbances and to assess short-term effects on nocturnal urine output and number of nocturnal voids. Methods Between June 2005 and August 2006, a total of 34 patients with nocturnal polyuria were orally administered 0.2 mg desmopressin tablet at bedtime for two weeks. Serum sodium, others electrolytes, urine sodium and urine osmolarity were assessed in the third days, one week and two weeks after treatment with desmopressin and compared adult group (<65 years of age) with elderly group (≥65 years of age). We assessed the effect of desmopressin using a frequency-volume charts and analysed. Results In total 34 patients (20 adult, 14 elderly) were analyzed. Desmopressin treatment did not significantly change serum and urine electrolytes include soduim concentration in elderly patients comparied with adult patients. Serum sodium concentration below normal range was recorded in 2 patients in elderly group, but no serious adverse events occurred and recovered without sequelae. The mean number of nocturnal voids decresed (54% reduction) and nocturnal urine output decreased (57% reduction) after using desmopressin. Conclusions Desmopressin was well tolerated and effective in elderly patients with nocturnal polyuria without clinically significant hyponatremia

Enhancing photoluminescence quantum efficiency of metal halide perovskites by examining luminescence-limiting factors

Metal halide perovskites (MHPs) show superior optoelectronic properties, which give them the great potential for use in next generation light-emitting diodes (LEDs). In particular, their narrow emission linewidths can achieve ultrahigh color purity. However, the reported luminescence efficiency (LE) values are not high enough to be commercialized in displays and solid-state lightings. Moreover, the operational stability of LEDs associated with the overshooting of luminance and the high relative standard deviation of reported external quantum efficiencies are still problematic. In this perspective, we review photophysical factors that limit the photoluminescence quantum efficiency of perovskite-based LEDs. These factors are categorized into (i) weak exciton binding, (ii) nonradiative recombinations, (iii) slow cooling of long-lived hot carriers, (iv) deep-level defects, and (v) interband transition rates. We then present various physicochemical methods to effectively overcome these luminescence-limiting factors. We finally suggest some useful research directions to further improve the LE of MHP emitters as core components in displays and solid-state lightings.

Broussonetia papyrifera Root Bark Extract Exhibits Anti-inflammatory Effects on Adipose Tissue and Improves Insulin Sensitivity Potentially Via AMPK Activation

The chronic low-grade inflammation in adipose tissue plays a causal role in obesity-induced insulin resistance and its associated pathophysiological consequences. In this study, we investigated the effects of extracts of Broussonetia papyrifera root bark (PRE) and its bioactive components on inflammation and insulin sensitivity. PRE inhibited TNF-alpha-induced NF-kappa B transcriptional activity in the NF-kappa B luciferase assay and pro-inflammatory genes&apos; expression by blocking phosphorylation of I kappa B and NF-kappa B in 3T3-L1 adipocytes, which were mediated by activating AMPK. Ten-week-high fat diet (HFD)-fed C57BL6 male mice treated with PRE had improved glucose intolerance and decreased inflammation in adipose tissue, as indicated by reductions in NF-kappa B phosphorylation and pro-inflammatory genes&apos; expression. Furthermore, PRE activated AMP-activated protein kinase (AMPK) and reduced lipogenic genes&apos; expression in both adipose tissue and liver. Finally, we identified broussoflavonol B (BF) and kazinol J (KJ) as bioactive constituents to suppress pro-inflammatory responses via activating AMPK in 3T3-L1 adipocytes. Taken together, these results indicate the therapeutic potential of PRE, especially BF or KJ, in metabolic diseases such as obesity and type 2 diabetes

Characteristics of the aberrant pyramidal tract in comparison with the pyramidal tract in the human brain

<p>Abstract</p> <p>Background</p> <p>The aberrant pyramidal tract (APT) refers to the collateral pathway of the pyramidal tract (PT) through the medial lemniscus in the midbrain and pons. Using diffusion tensor tractography (DTT), we investigated the characteristics of the APT in comparison with the PT in the normal human brain.</p> <p>Results</p> <p>In thirty-four (18.3%, right hemisphere: 20, left hemisphere: 14) of the 186 hemispheres, the APTs separated from the PT at the upper midbrain level, descended through the medial lemniscus from the midbrain to the pons, and then rejoined with the PT at the upper medulla. Nine (26.5%) of the 34 APTs were found to originate from the primary somatosensory cortex without a primary motor cortex origin. Values of fractional anisotropy (FA) and tract volume of the APT were lower than those of the PT (<it>P </it>< 0.05); however, no difference in mean diffusivity (MD) value was observed (<it>P ></it>0.05).</p> <p>Conclusion</p> <p>We found that the APT has different characteristics, including less directionality, fewer neural fibers, and less origin from the primary motor cortex than the PT.</p

The Protein Kinase C Inhibitor Aeb071 (Sotrastaurin) Modulates Migration and Superoxide Anion Production by Human Neutrophils In Vitro

We examined the effect of the protein kinase C-selective inhibitor AEB071 (sotrastaurin) on neutrophil functions in vitro. Pre-incubation with AEB071 at concentrations similar to those reached during in vivo therapy significantly reduced cell capacity to migrate toward three different chemo-attractants and to produce superoxide anions (O2) in response to phorbol myristate acetate (PMA) or to iV-formyl-methionyl-leucyl-phenylalanine (fMLP). AEB071 also significantly inhibited the O−2 "overproduction induced by fMLP in neutrophils primed with tumor necrosis factor alpha (TNF-α) or granulocyte/macrophage-colony stimulating factor (GM-CSF). This inhibition was not linked to fMLP-receptor down-regulation since the drug had no effect on either fMLP-receptors or fMLP-induced CD11b membrane expression. When the activity of AEB071 was compared to that of the conventional protein kinase C (PKC) inhibitor Gö6850 (which, like sotrastaurin, inhibits classical and novel PKC isoforms), Gö6976 (an inhibitor of α and β PKC isoforms) and rottlerin (a prevailing δ PKC isoform inhibitor), AEB071 at an equimolar concentration of 3 μM (close to the maximum drug concentration reached in patients treated with AEB071) caused significantly more inhibition on both chemotactic response and superoxide production. These in vitro findings suggest that neutrophils may offer a cellular target for AEB071 activity in vivo

Floristic study of Cheondeungsan Mountain in Korea

AbstractThe distribution of native plants of Cheondeungsan Mountain (807 m, N 37°05'00“–37°05'30”, E 128°00'0“–128°02'0”) in Chungcheongbuk-do was determined and the major flora were identified. During field investigations carried out from May 2011 to October 2011, 87 families, 254 genera, and 369 taxonomic groups (327 species, 4 subspecies, 33 varieties, and 5 forms) were confirmed, and the distribution of 219 taxonomic groups was discovered for the first time. The distribution of four endemic plants of Korea, including Ajuga spectabilis Nakai and Salvia chanryoenica Nakai, and that of Penthorum chinense Pursh, a Grade V specific plant species, was found. There were 20 taxa of naturalized plants at Cheondeungsan; the growth and development of plants that are harmful to the ecosystem, such as Ambrosia artemisiifolia L., Ambrosia trifida L., Eupatorium rugosum Houtt., and Aster pilosus Willd., was observed around the forest paths and lowlands

Synergistic Effects of Simvastatin and Irinotecan against Colon Cancer Cells with or without Irinotecan Resistance

Aims. We here investigated whether the combination of simvastatin and irinotecan could induce the synergistic effect on colon cancer cells with or without resistance to irinotecan. Methods. We investigated cell proliferation assay and assessed cell death detection ELISA and caspase-3 activity assay of various concentrations of simvastatin and irinotecan to evaluate the efficacy of drug combination on colon cancer cells with or without irinotecan resistance. Results. The IC50 values of simvastatin alone and irinotecan alone were 115.4±0.14 μM (r=0.98) and 62.5±0.18 μM (r=0.98) in HT-29 cells without resistance to irinotecan. The IC50 values of these two drugs were 221.9±0.22 μM (r=0.98) and 195.9±0.16 μM (r=0.99), respectively, in HT-29 cell with resistance to irinotecan. The results of combinations of the various concentrations of two drugs showed that combined treatment with irinotecan and simvastatin more efficiently suppressed cell proliferation of HT-29 cells even with resistance to irinotecan as well as without resistance. Furthermore, the combination of simvastatin and irinotecan at 2:1 molar ratio showed the best synergistic interaction. Conclusion. Simvastatin could act synergistically with irinotecan to overcome irinotecan resistance of colon cancer