31 research outputs found

    Activator protein transcription factors coordinate human IL-33 expression from noncanonical promoters in chronic airway disease

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    IL-33 is a cytokine central to type 2 immune pathology in chronic airway disease. This cytokine is abundantly expressed in the respiratory epithelium and increased in disease, but how expression is regulated is undefined. Here we show that increased IL33 expression occurs from multiple noncanonical promoters in human chronic obstructive pulmonary disease (COPD), and it facilitates production of alternatively spliced isoforms in airway cells. We found that phorbol 12-myristate 13-acetate (PMA) can activate IL33 promoters through protein kinase C in primary airway cells and lines. Transcription factor (TF) binding arrays combined with RNA interference identified activator protein (AP) TFs as regulators of baseline and induced IL33 promoter activity. ATAC-Seq and ChIP-PCR identified chromatin accessibility and differential TF binding as additional control points for transcription from noncanonical promoters. In support of a role for these TFs in COPD pathogenesis, we found that AP-2 (TFAP2A, TFAP2C) and AP-1 (FOS and JUN) family members are upregulated in human COPD specimens. This study implicates integrative and pioneer TFs in regulating IL33 promoters and alternative splicing in human airway basal cells. Our work reveals a potentially novel approach for targeting IL-33 in development of therapeutics for COPD

    Non-Rigid Structure from Locally-Rigid Motion

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    We introduce locally-rigid motion, a general framework for solving the M-point, N-view structure-from-motion problem for unknown bodies deforming under orthography. The key idea is to first solve many local 3-point, N-view rigid problems independently, providing a “soup ” of specific, plausibly rigid, 3D triangles. The main advantage here is that the extraction of 3D triangles requires only very weak assumptions: (1) deformations can be locally approximated by near-rigid motion of three points (i.e., stretching not dominant) and (2) local motions involve some generic rotation in depth. Triangles from this soup are then grouped into bodies, and their depth flips and instantaneous relative depths are determined. Results on several sequences, both our own and from related work, suggest these conditions apply in diverse settings—including very challenging ones (e.g., multiple deforming bodies). Our starting point is a novel linear solution to 3-point structure from motion, a problem for which no general algorithms currently exist. 1

    Effect of Active Metal Supported on SiO2 for Selective Hydrogen Production from the Glycerol Steam Reforming Reaction

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    The performance of nickel, cobalt, and copper supported on silica as catalysts was evaluated for the glycerol steam reforming (GSR) reaction. The samples were characterized by nitrogen-porosimetry according to Brunauer-Emmett-Teller (BET) method, X-ray diffraction (XRD), and inductively coupled plasma atomic emission spectroscopy (ICP-AES), while the deposited carbon on the catalytic surface was measured with a CHN-analyzer. Catalysts were studied in order to investigate the effect of the reaction temperature on (i) glycerol total conversion, (ii) glycerol conversion to gaseous products, (iii) hydrogen selectivity and yield, (iv) selectivity of gaseous products, and (v) selectivity of liquid products. The results showed that the Ni based on silica (Ni/Si) catalyst was more active and produced less liquid effluents than the catalysts that used an active metal such as Co or Cu. Moreover, the H2 yield from the Ni/Si catalyst was very close to the theoretical maximum predicted by thermodynamics, and the CO2 production was favoured in comparison to CO production, which is important for use in fuel cells

    Oral Calcium Supplementation Ambulatory Blood Pressure and Relation to Changes in Intracellular Ions and Sodium-Hydrogen Exchange

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    BACKGROUND Calcium (Ca2+) supplementation has been shown paradoxically to reduce intracellular Ca2+ and induce vascular relaxation. The aim of the study was to assess 24-h blood pressure (BP) change after Ca2+ supplementation and to investigate its relation to changes in intracellular ions and the activity of the first isoform of sodium-hydrogen exchange (NHE-1) in subjects with hypertension and type 2 diabetes. METHODS This parallel, randomized controlled, single-blinded trial, consisted of 31 patients with type 2 diabetes, and hypertension who were allocated to receive 1,500 mg of Ca2+ per day (n = 15) or no treatment (n = 16) for 8 weeks. RESULTS In the Ca2+ group a decrease of 1.7 +/- 2.7 mm Hg (mean +/- SE) P = 0.52 for mean 24-h systolic BP (SBP) and 2.1 +/- 1.5 mm Hg, P = 0.19 for mean 24-h diastolic BP (DBP) was recorded. Whereas in the control group an increase of 1.4 +/- 2.7 mm Hg, P = 0.59 for mean 24-h SBP and 1.2 +/- 2.8 mm Hg, P = 0.83 for mean 24-h DBP was observed. Intraplatelet Ca2+ decreased whereas intraplatelet magnesium (Mg2+) and erythrocyte K+ increased in the intervention group. Change in mean 24-h SBP in the pooled group correlated with both change in intraplatelet Ca2+ (r = 0.49, P < 0.05) and NHE-1 activity (r = 0.6, P < 0.001). The contribution of intraplatelet Ca2+ was attenuated when both parameters were entered in a multivariate regression model. CONCLUSIONS The present study shows a weak, statistically nonsignificant trend towards association of Ca2+ supplementation on 24-h BP in hypertensive subjects with type 2 diabetes. However, our results indicated an interrelation of [Ca2+], levels and NHE-1 activity on BP in patients with hypertension and type 2 diabetes
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