Regulation of manganese superoxide dismutase in glomerular epithelial cells: Mechanisms for interleukin 1 induction

Regulation of manganese superoxide dismutase in glomerular epithelial cells: Mechanisms for interleukin 1 induction. Reactive oxygen species have been implicated as mediators of tissue injury in glomerular inflammation. The expression of the antioxidant enzyme, manganese superoxide dismutase (MnSOD), was examined in primary cultures of rat glomerularepithelial cells (GEC) in response to inflammatory mediators. The results demonstrate that GEC respond to interleukin-1 (IL-1) and bacterial lipopolysaccharride (LPS) with an increase in MnSOD steady-state mRNA levels. The IL-1α-mediated induction of MnSOD mRNA levels was both time- and dose-dependent. Maximal levels, approximately 40-fold above controls, were observed at 12 hours with 2 ng/ml of IL-1α. MnSOD protein levels were also markedly elevated by IL-1α. The induction of MnSOD mRNA by IL-1α required de novo transcription as well as some degree of protein synthesis. To elucidate the potential intracellular signal that mediates IL-1α-dependent MnSOD expression, three classical signaling pathways were examined. We found no evidence that MnSOD induction by IL-lα is mediated by either the cyclooxygenase or lipoxygenase pathway or via activation of protein kinase C. Based on the presence of IL-lα in several forms of glomerular inflammation, the observed increase in MnSOD expression by this immunoregulatory cytokine must have an important role in the antioxidant defense of glomerular epithelial cells

Chalcogenide glass planar MIR couplers for future chip based Bracewell interferometers

Photonic integrated circuits are established as the technique of choice for a number of astronomical processing functions due to their compactness, high level of integration, low losses, and stability. Temperature control, mechanical vibration and acoustic noise become controllable for such a device enabling much more complex processing than can realistically be considered with bulk optics. To date the benefits have mainly been at wavelengths around 1550 nm but in the important Mid-Infrared region, standard photonic chips absorb light strongly. Chalcogenide glasses are well known for their transparency to beyond 10000 nm, and the first results from coupler devices intended for use in an interferometric nuller for exoplanetary observation in the Mid-Infrared L band (3800-4200 nm) are presented here showing that suitable performance can be obtained both theoretically and experimentally for the first fabricated devices operating at 4000 nm.Comment: in Proc. SPIE 9907, Optical and Infrared Interferometry and Imaging V, 990730 (August 4, 2016

Induction of Group IVC Phospholipase A2 in Allergic Asthma: Transcriptional Regulation by TNF-α in Bronchoepithelial Cells

Airway inflammation in allergen-induced asthma is associated with eicosanoid release. These bioactive lipids exhibit anti- and pro-inflammatory activities with relevance to pulmonary pathophysiology. We hypothesized that sensitization/challenge using an extract from the ubiquitous fungus, Aspergillus fumigatus (Af), in a mouse model of allergic asthma would result in altered phospholipase gene expression, thus modulating the downstream eicosanoid pathway. We observed the most significant induction in the group IVC phospholipase A2 (cPLA2γ or PLA2G4C). Our results infer that Af extract can induce cPLA2γ levels directly in eosinophils while induction in lung epithelial cells is most likely a consequence of TNF-α secretion by Af-activated macrophages. The mechanism of TNF-α-dependent induction of cPLA2γ gene expression was elucidated through a combination of promoter deletions, ChIP and overexpression studies in human bronchoepithelial cells, leading to the identification of functionally relevant CRE, NF-κB and E-box promoter elements. ChIP analysis demonstrated that RNA polymerase II, c-Jun/ATF-2, p65/p65 and USF1/USF2 complexes are recruited to the cPLA2γ enhancer/promoter in response to TNF-α with overexpression and dominant negative studies implying a strong level of cooperation and interplay between these factors. Overall, our data link cytokine-mediated alterations in cPLA2γ gene expression with allergic asthma and outline a complex regulatory mechanism

FuelCell2010-33214 Evaluating Methods for Infiltration of LSCF Cathodes with Mixed Electric/Ionic Conductors for Improved Oxygen Exchange

ABSTRACT Infiltration methods for improving lanthanum strontium cobalt ferrite (LSCF) cathode performance through catalyst surface modification were evaluated at the U.S. Department of Energy, National Energy Technology Laboratory. Infiltration of mixed conductors into LSCF cathodes of solid oxide fuel cells promises a low cost method of improving oxygen exchange and performance in these materials at lower temperatures. LSCF cathodes on Nickel-Yttria Stabilized Zirconia (Ni-YSZ) anode supported cells were infiltrated with strontium-doped lanthanum zirconate (LSZ) pyrochlores using two methods. An aqueous solution of nitrate salts was vacuum infiltrated into the cathodes of anode supported button cells, and the cells were heated to form the pyrochlore phase in-situ. This was compared to the efficacy of infiltrating a suspension of pyrochlore nanoparticles. Different dispersants were used to prepare the nanoparticle suspensions at varying concentrations and pH levels, and the results are compared. INTRODUCTION Solid oxide fuel cells have shown promise in power generation both in stand-alone applications and as the enabling component in high efficiency coal-based power with reduced emissions

Low-dose CT measurements of airway dimensions and emphysema associated with airflow limitation in heavy smokers:a cross sectional study

Background: Increased airway wall thickness (AWT) and parenchymal lung destruction both contribute to airflow limitation. Advances in computed tomography (CT) post-processing imaging allow to quantify these features. The aim of this Dutch population study is to assess the relationships between AWT, lung function, emphysema and respiratory symptoms.Methods: AWT and emphysema were assessed by low-dose CT in 500 male heavy smokers, randomly selected from a lung cancer screening population. AWT was measured in each lung lobe in cross-sectionally reformatted images with an automated imaging program at locations with an internal diameter of 3.5 mm, and validated in smaller cohorts of patients. The 15th percentile method (Perc15) was used to assess the severity of emphysema. Information about respiratory symptoms and smoking behavior was collected by questionnaires and lung function by spirometry.Results: Median AWT in airways with an internal diameter of 3.5 mm (AWT(3.5)) was 0.57 (0.44 - 0.74) mm. Median AWT in subjects without symptoms was 0.52 (0.41-0.66) and in those with dyspnea and/or wheezing 0.65 (0.52-0.81) mm (pConclusions: Post processing standardization of airway wall measurements provides a reliable and useful method to assess airway wall thickness. Increased airway wall thickness contributes more to airflow limitation than emphysema in a smoking male population even after adjustment for smoking behavior.</p

The Vehicle, Spring 1970, Vol. 12 no. 2

Vol. 12, No. 2 Table of Contents Prose short storyCarol Jean Baumgartepage 5 essayDan Franklinpage 8 short storyMary Yarbroughpage 21 Poetry Sara Brinkerhoffpage 20 Nick Dagerpage 18 E.S.page 17 Harry Fordpage 20 Melinda Gimbutpage 19 Ann Graffpage 20 Heather Hoebelpage 7 Becky McIntoshpage 20 John Metcalfpage 17 Mary Pipekpage 19 Cynthia C. Yohopage 17 Photography Dennis Hoaglundpages 5, 10, 21 Dale Huberpage 23 Scott Redfieldpages 7, 19 Tribute to the Ordinary Studentpage 11artMike DorseystoryNick Dagerhttps://thekeep.eiu.edu/vehicle/1022/thumbnail.jp

Genetic Determinants of Circulating Sphingolipid Concentrations in European Populations

Sphingolipids have essential roles as structural components of cell membranes and in cell signalling, and disruption of their metabolism causes several diseases, with diverse neurological, psychiatric, and metabolic consequences. Increasingly, variants within a few of the genes that encode enzymes involved in sphingolipid metabolism are being associated with complex disease phenotypes. Direct experimental evidence supports a role of specific sphingolipid species in several common complex chronic disease processes including atherosclerotic plaque formation, myocardial infarction (MI), cardiomyopathy, pancreatic beta-cell failure, insulin resistance, and type 2 diabetes mellitus. Therefore, sphingolipids represent novel and important intermediate phenotypes for genetic analysis, yet little is known about the major genetic variants that influence their circulating levels in the general population. We performed a genome-wide association study (GWAS) between 318,237 single-nucleotide polymorphisms (SNPs) and levels of circulating sphingomyelin (SM), dihydrosphingomyelin (Dih-SM), ceramide (Cer), and glucosylceramide (GluCer) single lipid species (33 traits); and 43 matched metabolite ratios measured in 4,400 subjects from five diverse European populations. Associated variants (32) in five genomic regions were identified with genome-wide significant corrected p-values ranging down to 9.08 x 10(-66). The strongest associations were observed in or near 7 genes functionally involved in ceramide biosynthesis and trafficking: SPTLC3, LASS4, SGPP1, ATP10D, and FADS1-3. Variants in 3 loci (ATP10D, FADS3, and SPTLC3) associate with MI in a series of three German MI studies. An additional 70 variants across 23 candidate genes involved in sphingolipid-metabolizing pathways also demonstrate association (p = 10(-4) or less). Circulating concentrations of several key components in sphingolipid metabolism are thus under strong genetic control, and variants in these loci can be tested for a role in the development of common cardiovascular, metabolic, neurological, and psychiatric diseases

Circulating Monocyte Chemoattractant Protein-1 and Risk of Stroke: A Meta-Analysis of Population-Based Studies Involving 17,180 Individuals.

RATIONALE: Pro-inflammatory cytokines have been identified as potential targets for lowering vascular risk. Experimental evidence and Mendelian randomization suggest a role of monocyte-chemoattractant protein-1 (MCP-1) in atherosclerosis and stroke. However, data from large-scale observational studies are lacking. OBJECTIVE: To determine whether circulating levels of MCP-1 are associated with risk of incident stroke in the general population. METHODS AND RESULTS: We used previously unpublished data on 17,180 stroke-free individuals (mean age 56.7{plus minus}8.1 years; 48.8% males) from six population-based prospective cohort studies and explored associations between baseline circulating MCP-1 levels and risk of any stroke, ischemic stroke, and hemorrhagic stroke over a mean follow-up interval of 16.3 years (280,522 person-years at risk; 1,435 incident stroke events). We applied Cox proportional hazard models and pooled hazard ratios (HR) using random-effects meta-analyses. Following adjustments for age, sex, race, and vascular risk factors, higher MCP-1 levels were associated with increased risk of any stroke (HR per 1 SD increment in ln-transformed MCP-1: 1.07, 95%CI: 1.01-1.14). Focusing on stroke subtypes, we found a significant association between baseline MCP-1 levels and higher risk of ischemic stroke (HR: 1.11, [1.02-1.21]), but not hemorrhagic stroke (HR: 1.02, [0.82-1.29]). The results followed a dose-response pattern with a higher risk of ischemic stroke among individuals in the upper quartiles of MCP-1 levels as compared to the 1st quartile (HRs: 2nd quartile: 1.19 [1.00-1.42]; 3rd quartile: 1.35, [1.14-1.59]; 4th quartile: 1.38, [1.07-1.77]). There was no indication for heterogeneity across studies and in a sub-sample of four studies (12,516 individuals) the risk estimates were stable after additional adjustments for circulating levels of interleukin-6 and high-sensitivity C-reactive protein. CONCLUSIONS: Higher circulating levels of MCP-1 are associated with increased long-term risk of stroke. Our findings along with genetic and experimental evidence suggest that MCP-1-signaling might represent a therapeutic target to lower stroke risk.M. Georgakis is funded by scholarships from the German Academic Exchange Service (DAAD) and Onassis Foundation. The ARIC study has been funded in whole or in part with Federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, under Contract nos. (HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700005I, HHSN268201700004I). The DHS study was funded by a grant from the Donald W. Reynolds Foundation. The EPIC-Norfolk study is funded by grants from the Medical Research Council UK (G9502233, G0401527) and Cancer Research UK (C864/A8257, C864/A2883). FHS is supported by the National Heart, Lung and Blood Institute’s Framingham Heart Study (Contract No. N01-HC-25195 and No. HHSN268201500001I and 75N92019D00031), received funding by grants from the National Institute of Aging (R01s AG054076, AG049607, AG059421, U01-AG049505, AG058589 and AG052409) and the National Institute of Neurological Disorders and Stroke (R01 NS017950, UH2 NS100605), as well as grants for the MCP-1 measurements by NIH (1RO1 HL64753, R01 HL076784, 1 R01 AG028321). The KORA study was initiated and financed by the Helmholtz Zentrum München – German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria. Furthermore, KORA research was supported within the Munich Center of Health Sciences (MC-Health), Ludwig-Maximilians-Universität, as part of LMUinnovativ. The MDCS-CV study has been supported with funding from the Swedish Research Council, Swedish Heart and Lung Foundations, and the Swedish Foundation for Strategic Research. This project has received funding from the European Union’s Horizon 2020 research and innovation programme (No 666881), SVDs@target (to M. Dichgans) and No 667375, CoSTREAM (to M. Dichgans); the DFG as part of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy – ID 390857198) and the CRC 1123 (B3) (to M. Dichgans); the Corona Foundation (to M. Dichgans); the Fondation Leducq (Transatlantic Network of Excellence on the Pathogenesis of Small Vessel Disease of the Brain)(to M. Dichgans); the e:Med program (e:AtheroSysMed) (to M. Dichgans) and the FP7/2007-2103 European Union project CVgenes@target (grant agreement number Health-F2-2013-601456) (to M. Dichgans)