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Sample records for enac mediates elastase

  1. Macrophage elastase (MMP-12: a pro-inflammatory mediator?

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    Soazig Nénan

    2005-03-01

    Full Text Available As many metalloproteinases (MMPs, macrophage elastase (MMP-12 is able to degrade extracellular matrix components such as elastin and is involved in tissue remodeling processes. Studies using animal models of acute and chronic pulmonary inflammatory diseases, such as pulmonary fibrosis and chronic obstrutive pulmonary disease (COPD, have given evidences that MMP-12 is an important mediator of the pathogenesis of these diseases. However, as very few data regarding the direct involvement of MMP-12 in inflammatory process in the airways were available, we have instilled a recombinant form of human MMP-12 (rhMMP-12 in mouse airways. Hence, we have demonstrated that this instillation induced a severe inflammatory cell recruitment characterized by an early accumulation of neutrophils correlated with an increase in proinflammatory cytokines and in gelatinases and then by a relatively stable recruitment of macrophages in the lungs over a period of ten days. Another recent study suggests that resident alveolar macrophages and recruited neutrophils are not involved in the delayed macrophage recruitment. However, epithelial cells could be one of the main targets of rhMMP-12 in our model. We have also reported that a corticoid, dexamethasone, phosphodiesterase 4 inhibitor, rolipram and a non-selective MMP inhibitor, marimastat could reverse some of these inflammatory events. These data indicate that our rhMMP-12 model could mimic some of the inflammatory features observed in COPD patients and could be used for the pharmacological evaluation of new anti-inflammatory treatment. In this review, data demonstrating the involvement of MMP-12 in the pathogenesis of pulmonary fibrosis and COPD as well as our data showing a pro-inflammatory role for MMP-12 in mouse airways will be summarized.

  2. Neutrophil elastase-mediated increase in airway temperature during inflammation

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    Schmidt, Annika; Belaaouaj, Azzaq; Bissinger, Rosi

    2014-01-01

    in the exhaled air of cystic fibrosis (CF) patients. To further test our hypothesis, a pouch inflammatory model using neutrophil elastase-deficient mice was employed. Next, the impact of temperature changes on the dominant CF pathogen Pseudomonas aeruginosa growth was tested by plating method and RNAseq. Results...

  3. Neutrophil elastase processing of Gelatinase A is mediated by extracellular matrix

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    Rice, A.; Banda, M.J. [Univ. of California, San Franciso, CA (United States)

    1995-07-18

    Gelatinase A (72-kDa type IV collagenase) is a metalloproteinase that is expressed by many cells in culture and is overexpressed by some tumor cells. It has been suggested that the serine proteinase neutrophil elastase might play a role iii the posttranslational processing of gelatinase A and that noncatalytic interactions between gelatinase A and components of the extracellular matrix might alter potential processing pathways. These questions were addressed with the use of gelatin substrate zymography, gelatinolytic activity assays, and amino acid sequence analysis. We found that neutrophil elastase does proteolytically modify gelatinase A by cleaving at a number of sites within gelatinase A. Sequential treatment of gelatinase A with 4-aminophenylmercuric acetate (APMA) and neutrophil elastase yielded an active gelatinase with a 4-fold increase in gelatinolytic activity. The increased gelatinolytic activity correlated with that of a 40-kDa fragment of gelatinase A. Matrix components altered the proteolytic modifications in gelatinase A that were mediated by neutrophil elastase. In the absence of gelatin, neutrophil elastase destructively degraded gelatinase A by hydrolyzing at least two bonds within the fibronectin-like gelatin-binding domain of gelatinase A. In the presence of gelatin, these two inactivating cleavage sites were protected, and cleavage at a site within the hemopexin-like carboxyl-terminal domain resulted in a truncated yet active gelatinase. The results suggest a regulatory role for extracellular matrix molecules in stabilizing gelatinase A fragments and in altering the availability of sites susceptible to destructive proteolysis by neutrophil elastase. 32 refs., 10 figs.

  4. Increased renal alpha-epithelial sodium channel (ENAC) protein and increased ENAC activity in normal pregnancy.

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    West, Crystal; Zhang, Zheng; Ecker, Geoffrey; Masilamani, Shyama M E

    2010-11-01

    Pregnancy-mediated sodium (Na) retention is required to provide an increase in plasma volume for the growing fetus. The mechanisms responsible for this Na retention are not clear. We first used a targeted proteomics approach and found that there were no changes in the protein abundance compared with virgin rats of the β or γ ENaC, type 3 Na(+)/H(+) exchanger (NHE3), bumetanide-sensitive cotransporter (NKCC2), or NaCl cotransporter (NCC) in mid- or late pregnancy. In contrast, we observed marked increases in the abundance of the α-ENaC subunit. The plasma volume increased progressively during pregnancy with the greatest plasma volume being evident in late pregnancy. ENaC inhibition abolished the difference in plasma volume status between virgin and pregnant rats. To determine the in vivo activity of ENaC, we conducted in vivo studies of rats in late pregnancy (days 18-20) and virgin rats to measure the natriuretic response to ENaC blockade (with benzamil). The in vivo activity of ENaC (U(Na)V postbenzamil-U(Na)V postvehicle) was markedly increased in late pregnancy, and this difference was abolished by pretreatment with the mineralocorticoid receptor antagonist, eplerenone. These findings demonstrate that the increased α-ENaC subunit of pregnancy is associated with an mineralocorticoid-dependent increase in ENaC activity. Further, we show that ENaC activity is a major contributor of plasma volume status in late pregnancy. These changes are likely to contribute to the renal sodium retention and plasma volume expansion required for an optimal pregnancy.

  5. Neutrophil elastase-induced elastin degradation mediates macrophage influx and lung injury in 60% O2-exposed neonatal rats.

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    Masood, Azhar; Yi, Man; Belcastro, Rosetta; Li, Jun; Lopez, Lianet; Kantores, Crystal; Jankov, Robert P; Tanswell, A Keith

    2015-07-01

    Neutrophil (PMNL) influx precedes lung macrophage (LM) influx into the lung following exposure of newborn pups to 60% O2. We hypothesized that PMNL were responsible for the signals leading to LM influx. This was confirmed when inhibition of PMNL influx with a CXC chemokine receptor-2 antagonist, SB-265610, also prevented the 60% O2-dependent LM influx, LM-derived nitrotyrosine formation, and pruning of small arterioles. Exposure to 60% O2 was associated with increased lung contents of neutrophil elastase and α-elastin, a marker of denatured elastin, and a decrease in elastin fiber density. This led us to speculate that neutrophil elastase-induced elastin fragments were the chemokines that led to a LM influx into the 60% O2-exposed lung. Inhibition of neutrophil elastase with sivelestat or elafin attenuated the LM influx. Sivelestat also attenuated the 60% O2-induced decrease in elastin fiber density. Daily injections of pups with an antibody to α-elastin prevented the 60% O2-dependent LM influx, impaired alveologenesis, and impaired small vessel formation. This suggests that neutrophil elastase inhibitors may protect against neonatal lung injury not only by preventing structural elastin degradation, but also by blocking elastin fragment-induced LM influx, thus preventing tissue injury from LM-derived peroxynitrite formation. Copyright © 2015 the American Physiological Society.

  6. The LasB Elastase of Pseudomonas aeruginosa Acts in Concert with Alkaline Protease AprA To Prevent Flagellin-Mediated Immune Recognition.

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    Casilag, Fiordiligie; Lorenz, Anne; Krueger, Jonas; Klawonn, Frank; Weiss, Siegfried; Häussler, Susanne

    2016-01-01

    The opportunistic pathogen Pseudomonas aeruginosa is capable of establishing severe and persistent infections in various eukaryotic hosts. It encodes a wide array of virulence factors and employs several strategies to evade immune detection. In the present study, we screened the Harvard Medical School transposon mutant library of P. aeruginosa PA14 for bacterial factors that modulate interleukin-8 responses in A549 human airway epithelial cells. We found that in addition to the previously identified alkaline protease AprA, the elastase LasB is capable of degrading exogenous flagellin under calcium-replete conditions and prevents flagellin-mediated immune recognition. Our results indicate that the production of two proteases with anti-flagellin activity provides a failsafe mechanism for P. aeruginosa to ensure the maintenance of protease-dependent immune-modulating functions. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  7. Involvement of ENaC in the development of salt-sensitive hypertension.

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    Pavlov, Tengis S; Staruschenko, Alexander

    2017-08-01

    Salt-sensitive hypertension is associated with renal and vascular dysfunctions, which lead to impaired fluid excretion, increased cardiac output, and total peripheral resistance. It is commonly accepted that increased renal sodium handling and plasma volume expansion are necessary factors for the development of salt-induced hypertension. The epithelial sodium channel (ENaC) is a trimeric ion channel expressed in the distal nephron that plays a critical role in the regulation of sodium reabsorption in both normal and pathological conditions. In this mini-review, we summarize recent studies investigating the role of ENaC in the development of salt-sensitive hypertension. On the basis of experimental data obtained from the Dahl salt-sensitive rats, we and others have demonstrated that abnormal ENaC activation in response to a dietary NaCl load contributes to the development of high blood pressure in this model. The role of different humoral factors, such as the components of the renin-angiotensin-aldosterone system, members of the epidermal growth factors family, arginine vasopressin, and oxidative stress mediating the effects of dietary salt on ENaC are discussed in this review to highlight future research directions and to determine potential molecular targets for drug development. Copyright © 2017 the American Physiological Society.

  8. Optimization of Microbial Elastase Production

    International Nuclear Information System (INIS)

    Abd EI-Aziz, A.B.; Hassan, A.A.

    2010-01-01

    The extra cellular proteases (caseinase, gelatinase and elastase) and hemolytic activities of the tested microorganisms on agar plates were detected, using different substrates (gelatin, casein, hemoglobin and elastin).The proteolytic activities were detected only from Pseudomonas aeruginosa, Prevotella bivius, Bacillus subtilis and Micrococcus luteus. The production of elastase by Bacillus subtilis (has low hemolysins activity) at various temperatures (30 degree C - 37 degree C) and at exposure to different doses of gamma irradiation (0.25-1.0 kGy) was investigated in shake flask. The results indicated that the incubation temperature 37 degree C was the optimum for cell growth at earlier stage; while maximum elastase activity was obtained when the cells were cultivated at 30 degree C and irradiation dose level of 0.75 kGy. The effects of temperature, substrate content, elastase concentration, ph and different metals ions on elastolysis were investigated as well the elastase amino acids composition was detected by using amino acids analyzer

  9. Effect of dietary salt intake on epithelial Na+ channels (ENaC) in vasopressin magnocellular neurosecretory neurons in the rat supraoptic nucleus.

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    Sharma, Kaustubh; Haque, Masudul; Guidry, Richard; Ueta, Yoichi; Teruyama, Ryoichi

    2017-09-01

    A growing body of evidence suggests that epithelial Na + channels (ENaCs) in the brain play a significant role in the regulation of blood pressure; however, the brain structures that mediate the effect are not well understood. Because vasopressin (VP) neurons play a pivotal role in coordinating neuroendocrine and autonomic responses to maintain cardiovascular homeostasis, a basic understanding of the regulation and activity of ENaC in VP neurons is of great interest. We show that high dietary salt intake caused an increase in the expression and activity of ENaC which resulted in the steady state depolarization of VP neurons. The results help us understand one of the mechanisms underlying how dietary salt intake affects the activity of VP neurons via ENaC activity. All three epithelial Na + channel (ENaC) subunits (α, β and γ) are located in vasopressin (VP) magnocellular neurons in the hypothalamic supraoptic (SON) and paraventricular nuclei. Our previous study demonstrated that ENaC mediates a Na + leak current that affects the steady state membrane potential in VP neurons. In the present study, we evaluated the effect of dietary salt intake on ENaC regulation and activity in VP neurons. High dietary salt intake for 7 days caused an increase in expression of β- and γENaC subunits in the SON and the translocation of αENaC immunoreactivity towards the plasma membrane. Patch clamp experiments on hypothalamic slices showed that the mean amplitude of the putative ENaC currents was significantly greater in VP neurons from animals that were fed a high salt diet compared with controls. The enhanced ENaC current contributed to the more depolarized basal membrane potential observed in VP neurons in the high salt diet group. These findings indicate that high dietary NaCl intake enhances the expression and activity of ENaCs, which augments synaptic drive by depolarizing the basal membrane potential close to the action potential threshold during hormonal demand. However

  10. Detection of extracellular neutrophil elastase in hamster lungs after intratracheal instillation of E. coli lipopolysaccharide using a fluorogenic, elastase-specific, synthetic substrate.

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    Rudolphus, A.; Stolk, J.; van Twisk, C.; van Noorden, C. J.; Dijkman, J. H.; Kramps, J. A.

    1992-01-01

    Repeated intratracheal instillations of E. coli lipopolysaccharide (LPS) in hamster lungs cause an influx of polymorphonuclear leukocytes (PMNs) into the alveolar walls, with concomitant development of severe emphysema. It has been suggested that elastase, released by these PMNs, is involved in the development of emphysema. This study demonstrates the release of elastase from recruited PMNs in cryostat sections of hamster lungs, after being treated once, twice, or thrice with LPS, intratracheally. Elastase activity was visualized using two elastase-specific synthetic substrates, to which a methoxynaphthylamine (MNA) group had been bound covalently. Liberated MNA, when made insoluble by coupling with 5-nitrosalicylaldehyde, fluoresces strongly. The authors observed that the interval between start of incubation and appearance of fluorescence and the intensity of fluorescence correlated with the number of LPS administrations. Fluorescence was observed to be located in or in close vicinity to alveolar walls. No fluorescence was observed in sections of untreated hamsters. Liberation of MNA from synthetic substrates was delayed strongly by the addition of a recombinant secretory leukocyte proteinase inhibitor or a substituted cephalosporin neutrophil elastase inhibitor. The authors conclude that LPS-mediated PMN influx into the lung is accompanied by release of elastase from these cells and speculate that this PMN-elastase is involved in the development of LPS-mediated emphysema. Images Figure 1 Figure 2 Figure 3 PMID:1632460

  11. Hydration status regulates sodium flux and inflammatory pathways through epithelial sodium channel (ENaC) in the skin.

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    Xu, Wei; Hong, Seok Jong; Zeitchek, Michael; Cooper, Garry; Jia, Shengxian; Xie, Ping; Qureshi, Hannan A; Zhong, Aimei; Porterfield, Marshall D; Galiano, Robert D; Surmeier, D James; Mustoe, Thomas A

    2015-03-01

    Although it is known that the inflammatory response that results from disruption of epithelial barrier function after injury results in excessive scarring, the upstream signals remain unknown. It has also been observed that epithelial disruption results in reduced hydration status and that the use of occlusive dressings that prevent water loss from wounds decreases scar formation. We hypothesized that hydration status changes sodium homeostasis and induces sodium flux in keratinocytes, which result in activation of pathways responsible for keratinocyte-fibroblast signaling and ultimately lead to activation of fibroblasts. Here, we demonstrate that perturbations in epithelial barrier function lead to increased sodium flux in keratinocytes. We identified that sodium flux in keratinocytes is mediated by epithelial sodium channels (ENaCs) and causes increased secretion of proinflammatory cytokines, which activate fibroblast via the cyclooxygenase 2 (COX-2)/prostaglandin E2 (PGE2) pathway. Similar changes in signal transduction and sodium flux occur by increased sodium concentration, which simulates reduced hydration, in the media in epithelial cultures or human ex vivo skin cultures. Blockade of ENaC, prostaglandin synthesis, or PGE2 receptors all reduce markers of fibroblast activation and collagen synthesis. In addition, employing a validated in vivo excessive scar model in the rabbit ear, we demonstrate that utilization of either an ENaC blocker or a COX-2 inhibitor results in a marked reduction in scarring. Other experiments demonstrate that the activation of COX-2 in response to increased sodium flux is mediated through the PIK3/Akt pathway. Our results indicate that ENaC responds to small changes in sodium concentration with inflammatory mediators and suggest that the ENaC pathway is a potential target for a strategy to prevent fibrosis.

  12. Elastase-induced emphysema in guinea pigs

    International Nuclear Information System (INIS)

    Loscutoff, S.M.

    1979-01-01

    Pulmonary function changes measured in guinea pigs 4 to 5 wk following intratracheal instillation of crystalline porcine pancreatic elastase resembled comparable changes in humans with moderately severe pulmonary emphysema. Compared with saline-treated controls, elastase-treated animals had increased values for all divisions of lung volume, increased static compliance and prolonged time constants. Since humans with emphysema are especially sensitive to air pollutants, elastase-treated animals may be useful as sensitive animal models in inhalatio toxicology

  13. Effects of elastase on fatty liver

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    Ogura, Kazuo; Shimizu, Yoshikazu; Hihara, Masafumi; Ando, Hideki; Nishiyama, Masateru; Tano, Hironobu

    1984-01-01

    Elastase (Elaszym 6T) was administered, in addition to the dietary instruction, to three patients with fatty liver. CT scanning revealed marked improvement in fatty liver. Transaminase levels returned to normal, total cholesterol levels tended to decrease, and HDL-cholesterol levels tended to increase. These results suggest that elastase is effective in the treatment of fatty liver. (Namekawa, K.)

  14. Effective silencing of ENaC by siRNA delivered with epithelial-targeted nanocomplexes in human cystic fibrosis cells and in mouse lung.

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    Tagalakis, Aristides D; Munye, Mustafa M; Ivanova, Rositsa; Chen, Hanpeng; Smith, Claire M; Aldossary, Ahmad M; Rosa, Luca Z; Moulding, Dale; Barnes, Josephine L; Kafetzis, Konstantinos N; Jones, Stuart A; Baines, Deborah L; Moss, Guy W J; O'Callaghan, Christopher; McAnulty, Robin J; Hart, Stephen L

    2018-05-10

    Loss of the cystic fibrosis transmembrane conductance regulator in cystic fibrosis (CF) leads to hyperabsorption of sodium and fluid from the airway due to upregulation of the epithelial sodium channel (ENaC). Thickened mucus and depleted airway surface liquid (ASL) then lead to impaired mucociliary clearance. ENaC regulation is thus a promising target for CF therapy. Our aim was to develop siRNA nanocomplexes that mediate effective silencing of airway epithelial ENaC in vitro and in vivo with functional correction of epithelial ion and fluid transport. We investigated translocation of nanocomplexes through mucus and their transfection efficiency in primary CF epithelial cells grown at air-liquid interface (ALI).Short interfering RNA (SiRNA)-mediated silencing was examined by quantitative RT-PCR and western analysis of ENaC. Transepithelial potential (V t ), short circuit current (I sc ), ASL depth and ciliary beat frequency (CBF) were measured for functional analysis. Inflammation was analysed by histological analysis of normal mouse lung tissue sections. Nanocomplexes translocated more rapidly than siRNA alone through mucus. Transfections of primary CF epithelial cells with nanocomplexes targeting αENaC siRNA, reduced αENaC and βENaC mRNA by 30%. Transfections reduced V t , the amiloride-sensitive I sc and mucus protein concentration while increasing ASL depth and CBF to normal levels. A single dose of siRNA in mouse lung silenced ENaC by approximately 30%, which persisted for at least 7 days. Three doses of siRNA increased silencing to approximately 50%. Nanoparticle-mediated delivery of ENaCsiRNA to ALI cultures corrected aspects of the mucociliary defect in human CF cells and offers effective delivery and silencing in vivo. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  15. Rab27a regulates epithelial sodium channel (ENaC) activity through synaptotagmin-like protein (SLP-5) and Munc13-4 effector mechanism

    International Nuclear Information System (INIS)

    Saxena, Sunil K.; Horiuchi, Hisanori; Fukuda, Mitsunori

    2006-01-01

    Liddle's syndrome (excessive absorption of sodium ions) and PHA-1 (pseudohypoaldosteronism type 1) with decreased sodium absorption are caused by the mutations in the amiloride-sensitive epithelial sodium channel ENaC. Rab proteins are small GTPases involved in vesicle transport, docking, and fusion. Earlier, we reported that Rab27a inhibits ENaC-mediated currents through protein-protein interaction in HT-29 cells. We hereby report that Rab27a-dependent inhibition is associated with the GTP/GDP status as constitutively active or GTPase-deficient mutant Q78L inhibits amiloride-sensitive currents whereas GDP-locked inactive mutant T23N showed no effect. In order to further explore the molecular mechanism of this regulation, we performed competitive assays with two Rab27a-binding proteins: synaptotagmin-like protein (SLP-5) and Munc13-4 (a putative priming factor for exocytosis). Both proteins eliminate negative modulation of Rab27a on ENaC function. The SLP-5 reversal of Rab27a effect was restricted to C-terminal C2A/C2B domains assigned for putative phospholipids-binding function while the Rab27a-binding SHD motif imparted higher inhibition. The ENaC-mediated currents remain unaffected by Rab27a though SLP-5 appears to strongly bind it. The immunoprecipitation experiments suggest that in the presence of excessive Munc13-4 and SLP-5 proteins, Rab27a interaction with ENaC is diminished. Munc13-4 and SLP-5 limit the Rab27a availability to ENaC, thus minimizing its effect on channel function. These observations decisively prove that Rab27a inhibits ENaC function through a complex mechanism that involves GTP/GDP status, and protein-protein interactions involving Munc13-4 and SLP-5 effector proteins

  16. Regulation of ENaC in mice lacking renal insulin receptors in the collecting duct

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    Pavlov, Tengis S.; Ilatovskaya, Daria V.; Levchenko, Vladislav; Li, Lijun; Ecelbarger, Carolyn M.; Staruschenko, Alexander

    2013-01-01

    The epithelial sodium channel (ENaC) is one of the central effectors involved in regulation of salt and water homeostasis in the kidney. To study mechanisms of ENaC regulation, we generated knockout mice lacking the insulin receptor (InsR KO) specifically in the collecting duct principal cells. Single-channel analysis in freshly isolated split-open tubules demonstrated that the InsR-KO mice have significantly lower ENaC activity compared to their wild-type (C57BL/6J) littermates when animals were fed either normal or sodium-deficient diets. Immunohistochemical and Western blot assays demonstrated no significant changes in expression of ENaC subunits in InsR-KO mice compared to wild-type littermates. Insulin treatment caused greater ENaC activity in split-open tubules isolated from wild-type mice but did not have this effect in the InsR-KO mice. Thus, these results suggest that insulin increases ENaC activity via its own receptor affecting the channel open probability. To further determine the mechanism of the action of insulin on ENaC, we used mouse mpkCCDc14 principal cells. Insulin significantly augmented amiloride-sensitive transepithelial flux in these cells. Pretreatment of the mpkCCDc14 cells with phosphatidylinositol 3-kinase (LY294002; 10 μM) or mTOR (PP242; 100 nM) inhibitors precluded this effect. This study provides new information about the importance of insulin receptors expressed in collecting duct principal cells for ENaC activity.—Pavlov, T. S., Ilatovskaya, D. V., Levchenko, V., Li, L., Ecelbarger, C. M., Staruschenko, A. Regulation of ENaC in mice lacking renal insulin receptors in the collecting duct. PMID:23558339

  17. Pancreatic elastase in human serum. Determination by radioimmunoassay

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    Geokas, M.C. (Univ. of California, Davis); Brodrick, J.W.; Johnson, J.H.; Largman, C.

    1977-01-10

    This study demonstrates that a serine endopeptidase of pancreatic origin (elastase 2) circulates in human blood. A specific and highly sensitive radioimmunoassay has been developed for pancreatic elastase 2 in human serum. The inactivation of elastase 2 employed as radioiodinated tracer with an active site-specific reagent (phenylmethanesulfonyl fluoride) was necessary to prevent its binding by serum ..cap alpha../sub 1/-antitrypsin and ..cap alpha../sub 2/-macroglobulin while maintaining its immunoreactivity. The assay is based upon competition of standard human pancreatic elastase 2 with /sup 125/I-labeled phenylmethanesulfonyl elastase 2 for specific antibody binding sites, after which a second antibody precipitation step is used to separate bound from free /sup 125/I-labeled phenylmethanesulfonyl elastase 2. The minimum detectable concentration of elastase 2 was 0.9 ng/ml. The average normal fasting serum level determined was 71 ng/ml, approximately 80-fold greater than the minimum detectable amount.

  18. Targeting an Oncolytic Influenza A Virus to Tumor Tissue by Elastase

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    Irina Kuznetsova

    2017-12-01

    Full Text Available Oncolytic viruses are currently established as a novel type of immunotherapy. The challenge is to safely target oncolytic viruses to tumors. Previously, we have generated influenza A viruses (IAVs containing deletions in the viral interferon antagonist. Those deletions have attenuated the virus in normal tissue but allowed replication in tumor cells. IAV entry is mediated by hemagglutinin (HA, which needs to be activated by a serine protease, for example, through trypsin. To further target the IAV to tumors, we have changed the trypsin cleavage site to an elastase cleavage site. We chose this cleavage site because elastase is expressed in the tumor microenvironment. Moreover, the exchange of the cleavage site previously has been shown to attenuate viral growth in lungs. Newly generated elastase-activated influenza viruses (AE viruses grew to similar titers in tumor cells as the trypsin-activated counterparts (AT viruses. Intratumoral injection of AE viruses into syngeneic B16f1 melanoma-derived tumors in mice reduced tumor growth similar to AT viruses and had a better therapeutic effect in heterologous human PANC-1-derived tumors. Therefore, the introduction of the attenuation marker “elastase cleavage site” in viral HA allows for safe, effective oncolytic virus therapy.

  19. BACILLUS THURINGIENSIS ELASTASES WITH INSECTICIDE ACTIVITY

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    E. V. Matseliukh

    2015-10-01

    Full Text Available The purpose of the research was a screening of proteases with elastase activity among Bacillus thuringiensis strains, their isolation, partially purification, study of physicochemical properties and insecticide activity in relation to the larvae of the Colorado beetle. The objects of the investigation were 18 strains of B. thuringiensis, isolated from different sources: sea water, dry biological product "Bitoksibatsillin" and also from natural populations of Colorado beetles of the Crimea, Kherson, Odesa, Mykolaiv and Zaporizhiia regions of Ukraine. Purification of enzymes with elastase activity isolated from above mentioned strains was performed by gel-chromatography and insecticide activity was studied on the 3–4 larvae instar of Colorado beetle. The ability of a number of B. thuringiensis strains to synthesize the proteases with elastase activity has been established. The most active were enzymes obtained from strains IMV B-7465, IMV B-7324 isolated from sea water, and strains 9, 902, Bt-H and 0-239 isolated from Colorado beetles. The study of the physicochemical properties of the partially purified proteases of these strains showed that they belonged to enzymes of the serine type. Peptidases of a number of B. thuringiensis strains (IMV B-7324, IMV B-7465, 902, 0-239, 9 are metal-dependent enzymes. Optimal conditions of action of all tested enzymes are the neutral and alkaline рН values and the temperatures of 30–40 °С. The studies of influence of the complex enzyme preparations and partially purified ones of B. thuringiensis strains on the larvae instar of Colorado beetles indicated that enzymes with elastase activity could be responsible for insecticide action of the tested strains.

  20. The Plant-Derived Bauhinia bauhinioides Kallikrein Proteinase Inhibitor (rBbKI Attenuates Elastase-Induced Emphysema in Mice

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    Bruno Tadeu Martins-Olivera

    2016-01-01

    Full Text Available Background. Elastase mediates important oxidative actions during the development of chronic obstructive pulmonary disease (COPD. However, few resources for the inhibition of elastase have been investigated. Our study evaluated the ability of the recombinant plant derived Bauhinia bauhinioides Kallikrein proteinase Inhibitor (rBbKI to modulate elastase-induced pulmonary inflammation. Methods. C57Bl/6 mice were given intratracheal elastase (ELA group or saline (SAL group and were treated intraperitoneally with rBbKI (ELA-rBbKI and SAL-rBbKI groups. At day 28, the following analyses were performed: (I lung mechanics, (II exhaled nitric oxide (ENO, (III bronchoalveolar lavage fluid (BALF, and (IV lung immunohistochemical staining. Results. In addition to decreasing mechanical alterations and alveolar septum disruption, rBbKI reduced the number of cells in the BALF and decreased the cellular expression of TNF-α, MMP-9, MMP-12, TIMP-1, eNOS, and iNOS in airways and alveolar walls compared with the ELA group. rBbKI decreased the volume proportion of 8-iso-PGF2α, collagen, and elastic fibers in the airways and alveolar walls compared with the ELA group. A reduction in the number of MUC-5-positive cells in the airway walls was also observed. Conclusion. rBbKI reduced elastase-induced pulmonary inflammation and extracellular matrix remodeling. rBbKI may be a potential pharmacological tool for COPD treatment.

  1. Sodium 4-phenylbutyrate upregulates ENaC and sodium absorption in T84 cells.

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    Iordache, Claudiu; Duszyk, Marek

    2007-01-15

    Butyrate and other short-chain fatty acids (SCFA), produced by colonic bacterial flora, affect numerous epithelial cell functions. To better understand how SCFA regulate ion transport, we investigated the effects of 4-phenylbutyrate (4-PBA) on Na(+) absorption in T84 cells. Under standard cell culture conditions, the short circuit current did not display any amiloride-sensitive Na(+) absorption and was wholly representative of Cl(-) secretion. However, when T84 cells were grown in the presence of 5 mM 4-PBA, a gradual appearance of amiloride-sensitive Na(+) channel (ENaC) activity was observed that reached a plateau after 24 h. Quantitative RT-PCR and Western blot studies of ENaC subunit expression indicated that 4-PBA stimulated alpha and gamma subunits. Trichostatin A, an inhibitor of histone deacetylase, mimicked the effects of 4-PBA, suggesting that 4-PBA affects ENaC expression by inhibiting deacetylases. 4-PBA had no effect on ENaC expression in airway epithelial cells indicating tissue-specific effect. We conclude that butyrate plays an important role in regulating colonic Na(+) absorption by increasing ENaC transcription and activity.

  2. Inhaled ENaC antisense oligonucleotide ameliorates cystic fibrosis-like lung disease in mice.

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    Crosby, Jeff R; Zhao, Chenguang; Jiang, Chong; Bai, Dong; Katz, Melanie; Greenlee, Sarah; Kawabe, Hiroshi; McCaleb, Michael; Rotin, Daniela; Guo, Shuling; Monia, Brett P

    2017-11-01

    Epithelial sodium channel (ENaC, Scnn1) hyperactivity in the lung leads to airway surface dehydration and mucus accumulation in cystic fibrosis (CF) patients and in mice with CF-like lung disease. We identified several potent ENaC specific antisense oligonucleotides (ASOs) and tested them by inhalation in mouse models of CF-like lung disease. The inhaled ASOs distributed into lung airway epithelial cells and decreased ENaC expression by inducing RNase H1-dependent degradation of the targeted Scnn1a mRNA. Aerosol delivered ENaC ASO down-regulated mucus marker expression and ameliorated goblet cell metaplasia, inflammation, and airway hyper-responsiveness. Lack of systemic activity of ASOs delivered via the aerosol route ensures the safety of this approach. Our results demonstrate that antisense inhibition of ENaC in airway epithelial cells could be an effective and safe approach for the prevention and reversal of lung symptoms in CF and potentially other inflammatory diseases of the lung. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  3. Effects of brachytherapy on gene expressions of elastin and elastase

    International Nuclear Information System (INIS)

    Li Junming; Zhou Jingqun; Hu Bin; Li Shuguo

    2004-01-01

    Objective: To study the effects of brachytherapy on the gene expressions of elastin and elastase in cultured rat vascular smooth muscle cells (VSMCs). Methods: Rat VSMCs cultured in DMEM containing 10% FBS were irradiated by 60 Co γ-rays at 0, 7, 14, 28 Gy respectively. Then mRNA levels of elastin and elastase were determined by reverse transcription competitive PCR(RT-PCR). Results: Brachytherapy inhibited the expressions of elastase. Elastase mRNA decreased 25.3% and 50.1% in VSMC irradiated with 14, 28 Gy, respectively (P<0.05). The elastin mRNA level increased 80.7% and 102.3% in VSMC irradiated with 14, 25 Gy, respectively (P<0.05). Conclusion: Brachytherapy inhabits the expressions of elastase and increased elastin in VSMC cells

  4. Urinary serine proteases and activation of ENaC in kidney

    DEFF Research Database (Denmark)

    Svenningsen, Per; Andersen, Henrik; Nielsen, Lise Hald

    2015-01-01

    with albuminuria compatible with impaired renal Na(+) excretion: hypertension and volume retention is secondary to proteinuria in, e.g., preeclampsia and nephrotic syndrome; plasma concentrations of renin, angiotensin II, and aldosterone are frequently suppressed in proteinuric conditions, e.g., preeclampsia......Serine proteases, both soluble and cell-attached, can activate the epithelial sodium channel (ENaC) proteolytically through release of a putative 43-mer inhibitory tract from the ectodomain of the γ-subunit. ENaC controls renal Na(+) excretion and loss-of-function mutations lead to low blood...... pressure, while gain-of-function mutations lead to impaired Na(+) excretion, hypertension, and hypokalemia. We review an emerging pathophysiological concept that aberrant glomerular filtration of plasma proteases, e.g., plasmin, prostasin, and kallikrein, contributes to proteolytic activation of ENaC, both...

  5. Enacs Survey of Southern Galaxies Indicates Open Universe

    Science.gov (United States)

    1996-02-01

    candidate clusters. Such observations are crucial, as they not only prove the existence of a cluster, but also determine its distance and provide information about the motion of the individual galaxies within the cluster. The ESO Nearby Abell Cluster Survey (ENACS) Until recently, there existed no large cluster sample with extensive and uniform data on the motions of the individual galaxies. But now, in the context of an ESO Key-Programme known as the ESO Nearby Abell Cluster Survey or ENACS , the team of European astronomers has collected spectroscopic and photometric data for a substantial sample of more than one-hundred, rich and relatively nearby southern clusters from the Abell catalogue [2]. The extensive observations were carried out with the OPTOPUS multi-fibre spectrograph attached to the ESO 3.6-metre telescope at the La Silla Observatory, during 35 nights in the period from September 1989 to October 1993. With this very efficient spectrograph, the spectra of about 50 galaxies could be recorded simultaneously, dramatically reducing the necessary observing time. In total, the programme has yielded reliable radial velocities for more than 5600 galaxies in the direction of about 100 rich clusters. The velocities were derived from a comparison of the observed wavelengths of absorption and emission lines with their rest wavelengths (the galaxy `redshifts'). Assuming a particular value of the `Hubble constant' (the proportionality factor between the velocity of a galaxy and its distance, due to the general expansion of the Universe), the distances of the galaxies can then be derived directly from the measured velocities. The new observations approximately double the amount of data available for rich clusters of galaxies. In combination with earlier data, the ENACS has produced a `complete' sample of 128 rich Abell clusters in a region centered near the south galactic pole (the direction which is perpendicular to the main plane of the Milky Way galaxy), and comprising

  6. Modulation of the epithelial sodium channel (ENaC by bacterial metalloproteases and protease inhibitors.

    Directory of Open Access Journals (Sweden)

    Michael B Butterworth

    Full Text Available The serralysin family of metalloproteases is associated with the virulence of multiple gram-negative human pathogens, including Pseudomonas aeruginosa and Serratia marcescens. The serralysin proteases share highly conserved catalytic domains and show evolutionary similarity to the mammalian matrix metalloproteases. Our previous studies demonstrated that alkaline protease (AP from Pseudomonas aeruginosa is capable of activating the epithelial sodium channel (ENaC, leading to an increase in sodium absorption in airway epithelia. The serralysin proteases are often co-expressed with endogenous, intracellular or periplasmic inhibitors, which putatively protect the bacterium from unwanted or unregulated protease activities. To evaluate the potential use of these small protein inhibitors in regulating the serralysin induced activation of ENaC, proteases from Pseudomonas aeruginosa and Serratia marcescens were purified for characterization along with a high affinity inhibitor from Pseudomonas. Both proteases showed activity against in vitro substrates and could be blocked by near stoichiometric concentrations of the inhibitor. In addition, both proteases were capable of activating ENaC when added to the apical surfaces of multiple epithelial cells with similar slow activation kinetics. The high-affinity periplasmic inhibitor from Pseudomonas effectively blocked this activation. These data suggest that multiple metalloproteases are capable of activating ENaC. Further, the endogenous, periplasmic bacterial inhibitors may be useful for modulating the downstream effects of the serralysin virulence factors under physiological conditions.

  7. Urinary plasmin activates collecting duct ENaC current in preeclampsia

    DEFF Research Database (Denmark)

    Buhl, KB; Friis, Ulla Glenert; Svenningsen, Per

    2012-01-01

    In nephrotic syndrome, plasminogen is aberrantly filtered from plasma to the urinary space and activated along the tubular system. In vitro, plasmin increases ENaC current by proteolytic cleavage of the γ-subunit. It was hypothesized that preeclampsia is associated with plasmin-dependent ability...

  8. Where have all the Na+ channels gone? In search of functional ENaC in exocrine pancreas

    DEFF Research Database (Denmark)

    Novak, Ivana; Hansen, Mette R

    2002-01-01

    was to investigate if pancreatic ducts express functional ENaC. Membrane voltages (V) of ducts isolated from rat pancreas were measured with microelectrodes or whole-cell patch-clamp technique. Amiloride and benzamil given from bath or luminal sides did not hyperpolarize V. Lowering of extracellular Na...... with glucocorticoids had no effect on pancreatic fluid secretion evoked from ducts, or from acini. Hence, our study shows that pancreas especially pancreatic ducts do not express functional ENaC....

  9. Co-operation with Eastern Europe countries taking ENAC as an example

    International Nuclear Information System (INIS)

    Taylor, D.

    1994-01-01

    In the aftermath of the Chernobyl accident, the European Community launched an ambitious programme of nuclear safety assistance. The purpose of this programme is to improve the safety of the Nuclear Power stations in Eastern Europe and the former Soviet Union plants. It was felt in the Western European nuclear industry that the emphasis should be on finding practical solutions to improve the most urgent problems. To achieve this objective, the nuclear industry in Western Europe founded a consortium called ENAC (European Nuclear Assistance Consortium) comprising companies form seven European countries ( Great Britain, France, Germany, Spain, Belgium, Italy, Netherlands). The co-operation between theses companies and the Russian designers would ensure that the solutions developed meet the approval of all interested parties. This presentation outlines the overall objectives of ENAC. 2 tabs., 1 fig

  10. Modulation of epithelial sodium channel (ENaC expression in mouse lung infected with Pseudomonas aeruginosa

    Directory of Open Access Journals (Sweden)

    Radzioch Danuta

    2005-01-01

    Full Text Available Abstract Background The intratracheal instillation of Pseudomonas aeruginosa entrapped in agar beads in the mouse lung leads to chronic lung infection in susceptible mouse strains. As the infection generates a strong inflammatory response with some lung edema, we tested if it could modulate the expression of genes involved in lung liquid clearance, such as the α, β and γ subunits of the epithelial sodium channel (ENaC and the catalytic subunit of Na+-K+-ATPase. Methods Pseudomonas aeruginosa entrapped in agar beads were instilled in the lung of resistant (BalB/c and susceptible (DBA/2, C57BL/6 and A/J mouse strains. The mRNA expression of ENaC and Na+-K+-ATPase subunits was tested in the lung by Northern blot following a 3 hours to 14 days infection. Results The infection of the different mouse strains evoked regulation of α and β ENaC mRNA. Following Pseudomonas instillation, the expression of αENaC mRNA decreased to a median of 43% on days 3 and 7 after infection and was still decreased to a median of 45% 14 days after infection (p 1Na+-K+-ATPase mRNA, the catalytic subunit of the sodium pump, was recorded. The distinctive expression profiles of the three subunits were not different, between the susceptible and resistant mouse strains. Conclusions These results show that Pseudomonas infection, by modulating ENaC subunit expression, could influence edema formation and clearance in infected lungs.

  11. Regulación por proteasas del canal de sodio sensible al amiloride (ENaC

    Directory of Open Access Journals (Sweden)

    Luciano Galizia

    2011-04-01

    Full Text Available El ENaC es un canal que permite el movimiento de Na+ desde el líquido luminal hacia las células en numerosos epitelios reabsortivos y también en otros tejidos como la placenta. ENaC juega un papel crucial en la homeostasis de los electrolitos y volumen de líquido extracelular. Es regulado por numerosas hormonas, incluyendo la aldosterona y bloqueado por el diurético amiloride. El ENaC está formado por tres subunidades homólogas α, β y γ que forman el poro por el cual se mueven los iones Na+. Dos factores regulan la actividad del ENaC. 1 el número de canales insertos en la membrana celular y 2 la probabilidad de apertura o tiempo en que se encuentra abierto el canal. El número de canales es el resultado de un balance entre su síntesis y degradación. La probabilidad de apertura depende de la proteólisis de zonas específicas de las subunidades α y γ por múltiples proteasas dentro de la célula y en el espacio extracelular. Entre las proteasas más estudiadas se encuentran la furina, prostasina, elastasa, plasmina y tripsina. Existen sustancias endógenas que bloquean la actividad de estas proteasas como la aprotinina, la bikunina y la nexina-1 y la expresión de las proteasas y sus inhibidores es regulada a su vez por la aldosterona, la tasa de movimiento de Na y el TFGβ. En este trabajo presentamos algunos ejemplos de esta regulación y su potencial papel en condiciones normales y en ciertas enfermedades como la fibrosis quística, renales e hipertensión.

  12. Elastase-induced pulmonary emphysema: insights from experimental models

    Directory of Open Access Journals (Sweden)

    Mariana A. Antunes

    2011-12-01

    Full Text Available Several distinct stimuli can be used to reproduce histological and functional features of human emphysema, a leading cause of disability and death. Since cigarette smoke is the main cause of emphysema in humans, experimental researches have attempted to reproduce this situation. However, this is an expensive and cumbersome method of emphysema induction, and simpler, more efficacious alternatives have been sought. Among these approaches, elastolytic enzymes have been widely used to reproduce some characteristics of human cigarette smoke-induced disease, such as: augmentation of airspaces, inflammatory cell influx into the lungs, and systemic inflammation. Nevertheless, the use of elastase-induced emphysema models is still controversial, since the disease pathways involved in elastase induction may differ from those occurring in smoke-induced emphysema. This indicates that the choice of an emphysema model may impact the results of new therapies or drugs being tested. The aim of this review is to compare the mechanisms of disease induction in smoke and elastase emphysema models, to describe the differences among various elastase models, and to establish the advantages and disadvantages of elastase-induced emphysema models. More studies are required to shed light on the mechanisms of elastase-induced emphysema.Diversos estímulos podem ser utilizados para reproduzir características histológicas e funcionais do enfisema humano, uma das principais causas de incapacidade e morte. Uma vez que a fumaça de cigarro é a principal causa de enfisema em humanos, estudos experimentais têm tentado reproduzir esta situação. No entanto, esse é um método dispendioso e complicado para a indução do enfisema e, alternativas mais simples e eficazes, têm sido pesquisadas. Entre essas abordagens, enzimas elastolíticas vêm sendo amplamente utilizadas para reproduzir algumas das características do enfisema humano, tais como: aumento dos espaços a

  13. Increased systemic elastase and C-reactive protein in aggressive periodontitis (CLOI-D-00160R2).

    Science.gov (United States)

    Wohlfeil, Martin; Scharf, Susanne; Siegelin, Yasemin; Schacher, Beate; Oremek, Gerhard M; Sauer-Eppel, Hildegund; Schubert, Ralf; Eickholz, Peter

    2012-08-01

    The inflammatory mediators, serum elastase and C-reactive protein (CRP), are associated with an increased risk for coronary heart disease. Thus, the aim of this study is to compare systemic inflammatory mediators in periodontally healthy controls (C), patients with untreated aggressive (AgP) and chronic (ChP) periodontitis. C [periodontal pocket probing depth (PPD)  30% of sites; age >35 years), and AgP (clinically healthy; PDD ≥ 3.6 mm at >30% of sites, bone loss ≥50% at ≥2 teeth; age ≤35 years) were examined clinically, and the body mass index was assessed. Blood was sampled for assessment of serum levels of elastase, CRP, lipopolysaccharide binding protein (LBP), interleukin (IL) 6, 8, and leukocyte counts. Thirty C, 31 ChP, and 29 AgP were analyzed. Elastase, CRP, LBP, and IL-6 levels were elevated in AgP compared to C (p C. AgP patients exhibit a stronger systemic inflammatory burden than C patients.

  14. Cytochalasin E alters the cytoskeleton and decreases ENaC activity in Xenopus 2F3 cells.

    Science.gov (United States)

    Reifenberger, Matthew S; Yu, Ling; Bao, Hui-Fang; Duke, Billie Jeanne; Liu, Bing-Chen; Ma, He-Ping; Alli, Ahmed A; Eaton, Douglas C; Alli, Abdel A

    2014-07-01

    Numerous reports have linked cytoskeleton-associated proteins with the regulation of epithelial Na(+) channel (ENaC) activity. The purpose of the present study was to determine the effect of actin cytoskeleton disruption by cytochalasin E on ENaC activity in Xenopus 2F3 cells. Here, we show that cytochalasin E treatment for 60 min can disrupt the integrity of the actin cytoskeleton in cultured Xenopus 2F3 cells. We show using single channel patch-clamp experiments and measurements of short-circuit current that ENaC activity, but not its density, is altered by cytochalasin E-induced disruption of the cytoskeleton. In nontreated cells, 8 of 33 patches (24%) had no measurable ENaC activity, whereas in cytochalasin E-treated cells, 17 of 32 patches (53%) had no activity. Analysis of those patches that did contain ENaC activity showed channel open probability significantly decreased from 0.081 ± 0.01 in nontreated cells to 0.043 ± 0.01 in cells treated with cytochalasin E. Transepithelial current from mpkCCD cells treated with cytochalasin E, cytochalasin D, or latrunculin B for 60 min was decreased compared with vehicle-treated cells. The subcellular expression of fodrin changed significantly, and several protein elements of the cytoskeleton decreased at least twofold after 60 min of cytochalasin E treatment. Cytochalasin E treatment disrupted the association between ENaC and myristoylated alanine-rich C-kinase substrate. The results presented here suggest disruption of the actin cytoskeleton by different compounds can attenuate ENaC activity through a mechanism involving changes in the subcellular expression of fodrin, several elements of the cytoskeleton, and destabilization of the ENaC-myristoylated alanine-rich C-kinase substrate complex. Copyright © 2014 the American Physiological Society.

  15. Calmodulin and CaMKII modulate ENaC activity by regulating the association of MARCKS and the cytoskeleton with the apical membrane.

    Science.gov (United States)

    Alli, Abdel A; Bao, Hui-Fang; Liu, Bing-Chen; Yu, Ling; Aldrugh, Summer; Montgomery, Darrice S; Ma, He-Ping; Eaton, Douglas C

    2015-09-01

    Phosphatidylinositol bisphosphate (PIP2) regulates epithelial sodium channel (ENaC) open probability. In turn, myristoylated alanine-rich C kinase substrate (MARCKS) protein or MARCKS-like protein 1 (MLP-1) at the plasma membrane regulates the delivery of PIP2 to ENaC. MARCKS and MLP-1 are regulated by changes in cytosolic calcium; increasing calcium promotes dissociation of MARCKS from the membrane, but the calcium-regulatory mechanisms are unclear. However, it is known that increased intracellular calcium can activate calmodulin and we show that inhibition of calmodulin with calmidazolium increases ENaC activity presumably by regulating MARCKS and MLP-1. Activated calmodulin can regulate MARCKS and MLP-1 in two ways. Calmodulin can bind to the effector domain of MARCKS or MLP-1, inactivating both proteins by causing their dissociation from the membrane. Mutations in MARCKS that prevent calmodulin association prevent dissociation of MARCKS from the membrane. Calmodulin also activates CaM kinase II (CaMKII). An inhibitor of CaMKII (KN93) increases ENaC activity, MARCKS association with ENaC, and promotes MARCKS movement to a membrane fraction. CaMKII phosphorylates filamin. Filamin is an essential component of the cytoskeleton and promotes association of ENaC, MARCKS, and MLP-1. Disruption of the cytoskeleton with cytochalasin E reduces ENaC activity. CaMKII phosphorylation of filamin disrupts the cytoskeleton and the association of MARCKS, MLP-1, and ENaC, thereby reducing ENaC open probability. Taken together, these findings suggest calmodulin and CaMKII modulate ENaC activity by destabilizing the association between the actin cytoskeleton, ENaC, and MARCKS, or MLP-1 at the apical membrane. Copyright © 2015 the American Physiological Society.

  16. Activity of neutrophil elastase reflects the progression of acute pancreatitis

    DEFF Research Database (Denmark)

    Novovic, Srdan; Andersen, Anders M; Nord, Magnus

    2013-01-01

    Abstract Objective. Neutrophil elastase (NE) concentration is associated with progression of acute pancreatitis (AP), but measuring total NE concentration includes biologically inactive NE. This study aims to investigate the relationship between NE activity and the aetiology and severity of AP...... was associated with predicted severity of AP and AP-associated respiratory failure. Specific NE inhibitors may have therapeutic potential in acute pancreatitis....

  17. Physicochemical properties of elastase isolated from clinical Pseudomonas Aeruginosa

    International Nuclear Information System (INIS)

    Elbazza, Z.E.; Moroz, A.F.

    1989-01-01

    Purified elastase was obtained from clinical Pseudomonas Aeruginosa (P.A.-283). The enzyme showed not only elasto lytic activity, but also a broad proteolytic activity against various proteins. The activity of the enzyme on collagen and gelatin was also observed. The optimum pH for elastase was 7.8 to 8.0 for both the proteolytic and elasto lytic activities. The elastase was stable in a pH range from 6.6 to 9.0. Optimum temperature for proteolytic and elasto lytic activities was 40 and inhibition of elastase occurs at 80 . The D 1 0 value of the P.A-283 was found to be 0.11 kGy. Increasing the dose level value of gamma-irradiation decrease the proteolytic activity in the culture filtrate reaching only 16% at the dose level 0.5 kGy. Chelating agents and some metal ions inhibited both proteolytic and elasto lytic activities. Selective inhibition of elasto lytic activity was observed in high concentrations of sodium and ammonium salts without concurrent decrease in the proteolytic activity of the enzyme.4 fig., 3 tab

  18. Salt-Induced Hypertension in a Mouse Model of Liddle's Syndrome is Mediated by Epithelial Sodium Channels in the Brain

    Science.gov (United States)

    Van Huysse, James W.; Amin, Md. Shahrier; Yang, Baoli; Leenen, Frans H. H.

    2012-01-01

    Neural precursor cell expressed and developmentally downregulated 4-2 protein (Nedd4-2) facilitates the endocytosis of epithelial Na channels (ENaC). Both mice and humans with a loss of regulation of ENaC by Nedd4-2 have salt-induced hypertension. ENaC is also expressed in the brain, where it is critical for hypertension on high salt diet in salt-sensitive rats. In the present studies we assessed whether Nedd4-2 knockout (−/−) mice have: 1) increased brain ENaC; 2) elevated CSF sodium on high salt diet; and 3) enhanced pressor responses to CSF sodium and hypertension on high salt diet, both mediated by brain ENaC. Prominent choroid plexus and neuronal ENaC staining was present in −/− but not in wild-type (W/T) mice. In chronically instrumented mice, intracerebroventricular (icv) infusion of Na-rich aCSF increased MAP 3-fold higher in −/− than W/T. Icv infusion of the ENaC blocker benzamil abolished this enhancement. In telemetered −/− mice on high salt diet (8% NaCl), CSF [Na+], MAP and HR increased significantly, MAP by 30-35 mmHg. These MAP and HR responses were largely prevented by icv benzamil, but only to a minor extent by sc benzamil at the icv rate. We conclude that increased ENaC expression in the brain of Nedd 4-2 −/− mice mediates their hypertensive response to high salt diet, by causing increased sodium levels in the CSF as well as hyper-responsiveness to CSF sodium. These findings highlight the possible causative contribution of CNS ENaC in the etiology of salt-induced hypertension. PMID:22802227

  19. IL-23 Is Essential for the Development of Elastase-Induced Pulmonary Inflammation and Emphysema.

    Science.gov (United States)

    Fujii, Utako; Miyahara, Nobuaki; Taniguchi, Akihiko; Waseda, Koichi; Morichika, Daisuke; Kurimoto, Etsuko; Koga, Hikari; Kataoka, Mikio; Gelfand, Erwin W; Cua, Daniel J; Yoshimura, Akihiko; Tanimoto, Mitsune; Kanehiro, Arihiko

    2016-11-01

    We recently reported that IL-17A plays a critical role in the development of porcine pancreatic elastase (PPE)-induced emphysema. The proliferation of T-helper type 17 (Th17) cells was induced by IL-23. To determine the contribution of IL-23 to the development of pulmonary emphysema, a mouse model of PPE-induced emphysema was used in which responses of IL-23p19-deficient (IL-23 -/- ) and wild-type (WT) mice were compared. Intratracheal instillation of PPE induced emphysematous changes in the lungs and was associated with increased levels of IL-23 in lung homogenates. Compared with WT mice, IL-23 -/- mice developed significantly lower static compliance values and markedly reduced emphysematous changes on histological analyses after PPE instillation. These changes were associated with lower levels of IL-17A and fewer Th17 cells in the lung. The neutrophilia seen in bronchoalveolar lavage fluid of WT mice was attenuated in IL-23 -/- mice, and the reduction was associated with decreased levels of keratinocyte-derived cytokine and macrophage inflammatory protein-2 in bronchoalveolar lavage fluid. Treatment with anti-IL-23p40 monoclonal antibody significantly attenuated PPE-induced emphysematous changes in the lungs of WT mice. These data identify the important contributions of IL-23 to the development of elastase-induced pulmonary inflammation and emphysema, mediated through an IL-23/IL-17 pathway. Targeting IL-23 in emphysema is a potential therapeutic strategy for delaying disease progression.

  20. Plasmin in urine from patients with type 2 diabetes and treatment-resistant hypertension activates ENaC in vitro

    DEFF Research Database (Denmark)

    Buhl, Kristian B; Stolzenburg Oxlund, Christina; Friis, Ulla G

    2014-01-01

    diabetes mellitus (T2DM) and treatment-resistant hypertension excrete plasmin(ogen) in urine in proportion to albumin and that plasmin confers to urine the ability to activate ENaC. METHOD:: Patients (n = 113) with T2DM and resistant hypertension, defined as systolic blood pressure (SBP) more than 130 mm...... of plasmin in preurine may inappropriately activate ENaC in patients with type 2 diabetes and microalbuminuria. This may contribute to treatment-resistant hypertension.......BACKGROUND:: Aberrant filtration of plasminogen from plasma and subsequent activation to plasmin in the urinary space may activate proteolytically the epithelial sodium channel, ENaC. In conditions with chronic albuminuria, this may cause hypertension. It was hypothesized that patients with type 2...

  1. The role of secretory leukocyte proteinase inhibitor and elafin (elastase-specific inhibitor/skin-derived antileukoprotease as alarm antiproteinases in inflammatory lung disease

    Directory of Open Access Journals (Sweden)

    Sallenave Jean-Michel

    2000-08-01

    Full Text Available Abstract Secretory leukocyte proteinase inhibitor and elafin are two low-molecular-mass elastase inhibitors that are mainly synthesized locally at mucosal sites. It is thought that their physicochemical properties allow them to efficiently inhibit target enzymes, such as neutrophil elastase, released into the interstitium. Historically, in the lung, these inhibitors were first purified from secretions of patients with chronic obstructive pulmonary disease and cystic fibrosis. This suggested that they might be important in controlling excessive neutrophil elastase release in these pathologies. They are upregulated by 'alarm signals' such as bacterial lipopolysaccharides, and cytokines such as interleukin-1 and tumor necrosis factor and have been shown to be active against Gram-positive and Gram-negative bacteria, so that they have joined the growing list of antimicrobial 'defensin-like' peptides produced by the lung. Their site of synthesis and presumed functions make them very attractive candidates as potential therapeutic agents under conditions in which the excessive release of elastase by neutrophils might be detrimental. Because of its natural tropism for the lung, the use of adenovirus-mediated gene transfer is extremely promising in such applications.

  2. Serum elastase activity, serum elastase inhibitors, and occurrence of carotid atherosclerotic plaques: the Etude sur le Vieillissement Artériel (EVA) study.

    Science.gov (United States)

    Zureik, Mahmoud; Robert, Ladislas; Courbon, Dominique; Touboul, Pierre-Jean; Bizbiz, Latifa; Ducimetière, Pierre

    2002-06-04

    In the last decades, interest has increased in the potential deleterious atherogenic effects of some cellular elastase activities. The results of experimental and clinical investigations were inconsistent. In this report, we assessed the associations of serum elastase activity and serum elastase inhibitors with carotid plaque occurrence during the 4-year follow-up in a population of 859 subjects free of coronary heart disease and stroke (age, 59 to 71 years). Serum elastase activity and serum elastase inhibitors were measured at baseline examination. Carotid B-mode ultrasound examination was performed at baseline and 2 years and 4 years later. The occurrence of carotid plaques in subjects with the lowest serum elastase activity values (quartile 1), in those with the intermediate values (quartiles 2 to 3), and in those with the highest values (quartile 4) was, respectively, 24.6%, 18.9%, and 12.2% (P<0.001 for trend). The multivariate odds ratios of carotid plaque occurrence associated with the three groups (adjusted for major known cardiovascular risk factors) were, respectively, 1.00, 0.67 (CI, 0.44 to 1.02; P<0.06), and 0.40 (CI, 0.23 to 0.70, P<0.001). For serum elastase inhibitors, the occurrence of carotid plaques in quartile 1 (lowest values), quartiles 2 to 3, and quartile 4 (highest values) was, respectively, 11.7%, 18.8%, and 25.2% (P for trend<0.001). The corresponding multivariate adjusted odds ratios were 1.00, 1.98 (CI, 1.19 to 3.31, P<0.01), and 3.18 (CI, 1.80 to 5.60, P<0.001). Low values of serum elastase activity and high values of serum elastase inhibitors were strongly and independently associated with increased 4-year carotid plaque occurrence. Further studies are necessary to elucidate the nature of the associations between elastase parameters and atherosclerosis.

  3. Elastase-induced emphysema: retention of instilled proteinase in the rat

    International Nuclear Information System (INIS)

    Sandhaus, R.A.; Janoff, A.

    1982-01-01

    Airway instillation of proteinases with the ability to degrade elastin has been used to produce disease in the rat analogous to human pulmonary emphysema. This study examined the retention, localization, and fate of endotracheally instilled elastase using 125 I labeled enzyme and immunoperoxidase histochemistry. Porcine pancreatic elastase labeled with 125 I was detected in rat lungs through 96 h after instillation; over half of the label was still present after 7 h. Similar results were obtained when elastase was reacted with a specific, catalytic site inactivator prior to instillation. Trypsin and denatured elastase, however, were cleared much more rapidly from the lung (less than half of the label present after 30 min). When lungs were homogenized after instillation of active elastase, the soluble fraction contained elastase bound to rat alpha1-antitrypsin. In addition, a small amount of label (less than 10%) appeared bound to insoluble components for extended periods of time. Using immunoperoxidase histochemistry, it was found that exogenous elastase was rapidly contained with pulmonary alveolar macrophages, as well as associated with alveolar septums and other parenchymal structures. Similar results were obtained with elastase from both porcine pancreas and human neutrophils. These results suggest that exogenous elastase in the rat, and perhaps endogenous elastolytic enzymes in humans, may have several fates in the lungs: complex formation with endogenous inhibitors, containment within the macrophage, and/or association with connective tissue targets

  4. Neutrophil elastase and elastin-derived peptides in BAL fluid and emphysematous changes on CT scans

    International Nuclear Information System (INIS)

    Betsuyaku, Tomoko; Nishimura, Masaharu; Yoshioka, Aya; Takeyabu, Kimihiro; Miyamoto, Kenji; Kawakami, Yoshikazu

    1996-01-01

    We examined the relationship between neutrophil elastase, elastin-derived peptides in bronchoalveolar lavage (BAL) fluid, and the development of pulmonary emphysema. The level of neutrophil elastase was higher in asymptomatic current smokers with emphysematous changes on computed tomographic scans than in current smokers without emphysematous changes, and was found to be correlated with the level of elastin-derived peptides in BAL fluid. Subjects with high levels of neutrophil elastase in BAL fluid had faster annual declines in FEV 1 . We conclude that the level of neutrophil elastase in BAL fluid can be used to differentiate asymptomatic cigarette smokers who are at risk for pulmonary emphysema from those who are not. (author)

  5. ASIC and ENaC type sodium channels: conformational states and the structures of the ion selectivity filters.

    Science.gov (United States)

    Hanukoglu, Israel

    2017-02-01

    The acid-sensing ion channels (ASICs) and epithelial sodium channels (ENaC) are members of a superfamily of channels that play critical roles in mechanosensation, chemosensation, nociception, and regulation of blood volume and pressure. These channels look and function like a tripartite funnel that directs the flow of Na + ions into the cytoplasm via the channel pore in the membrane. The subunits that form these channels share a common structure with two transmembrane segments (TM1 and TM2) and a large extracellular part. In most vertebrates, there are five paralogous genes that code for ASICs (ASIC1-ASIC5), and four for ENaC subunits alpha, beta, gamma, and delta (α, β, γ, and δ). While ASICs can form functional channels as a homo- or heterotrimer, ENaC functions as an obligate heterotrimer composed of α-β-γ or β-γ-δ subunits. The structure of ASIC has been determined in several conformations, including desensitized and open states. This review presents a comparison of the structures of these states using easy-to-understand molecular models of the full complex, the central tunnel that includes an outer vestibule, the channel pore, and ion selectivity filter. The differences in the secondary, tertiary, and quaternary structures of the states are summarized to pinpoint the conformational changes responsible for channel opening. Results of site-directed mutagenesis studies of ENaC subunits are examined in light of ASIC1 models. Based on these comparisons, a molecular model for the selectivity filter of ENaC is built by in silico mutagenesis of an ASIC1 structure. These models suggest that Na + ions pass through the filter in a hydrated state. © 2016 Federation of European Biochemical Societies.

  6. Proteolytic activation of the epithelial sodium channel ENaC in preeclampsia examined with urinary exosomes

    DEFF Research Database (Denmark)

    Nielsen, Maria Ravn; Rytz, Mie; Frederiksen-Møller, Britta

    2015-01-01

    OBJECTIVES: Increased activity of the epithelial sodium channel (ENaC) in the kidneys may explain the coupling between proteinuria, edema, suppressed aldosterone and hypertension in preeclampsia. Preeclamptic women excrete plasminogen-plasmin in urine. In vitro, plasmin increases the activity...... as a positive control for the presence of collecting duct membrane. RESULTS: Urine plasmin-plasminogen/creatinine ratio was increased in the preeclampsia group (p... pregnancy and preeclampsia CONCLUSIONS: It is possible to examine collecting duct transport proteins in urine exosome from pregnant women including γ-ENaC, 2) Urine exosome fraction displays a variable pattern of γ-ENaC signal with a predominance of cleaved forms in both normal and preeclamptic women...

  7. An evaluation on elastase enzyme activity in gingival crevicular fluid in periodontitis

    Directory of Open Access Journals (Sweden)

    Qujeq D

    2003-08-01

    Full Text Available Statement of Problem: Changes in protein levels, host calls enzymes and inflammatory mediators in gingival"ncrevicular Fluid (GCF are considered as diagnostic indicators of Periodontitis."nPurpose: he aim of the present study was to measure the elastase enzyme activity in gingival crevicular Fluid"namong patients with periodontitis."nMaterial and Methods: In this study, 52 periodontitis patients (experimental group and 51 healthy subjects"nwithout any gingival inflammatio (control group were participated. Subjects of the periodontitis group"nshowed pockets of 4-5 mm depth without gingival enlargement and recession or pockets of 1-2 mm depth"nwith gingival recession. For enzyme activity measurement, lOOu,! of gingival fluid of each sample was mixed"nwith lOOu! of enzyme substrate on the tube. The mixture was incubated at 34°c for lh with a buffer solution"nof 1ml volume and absorbance was read at 410nm with spectrophotometer. The enzyme activity differences"nbetween two groups were analyzed by student t test."nResults: The elastase enzyme activity in gingival crevicular fluid in subjects with periodontium destruction"nand control subjects was 153±11.3 and 52.7±10.4 enzyme unit in ml per minute, respectively. The difference"nbetween groups was statistically significant (PO.05."nConclusion: Based on the findings of this study, the measurement of elastae enzyme activity could be a useful"nindication of tissue changes that may ultimately manifest clinically as periodontitis.

  8. Inhibitory effect of burdock leaves on elastase and tyrosinase activity

    Science.gov (United States)

    Horng, Chi-Ting; Wu, Hsing-Chen; Chiang, Ni-Na; Lee, Chiu-Fang; Huang, Yu-Syuan; Wang, Hui-Yun; Yang, Jai-Sing; Chen, Fu-An

    2017-01-01

    Burdock (Arctium lappa L.) leaves generate a considerable amount of waste following burdock root harvest in Taiwan. To increase the use of burdock leaves, the present study investigated the optimal methods for producing burdock leaf extract (BLE) with high antioxidant polyphenolic content, including drying methods and solvent extraction concentration. In addition, the elastase and tyrosinase inhibitory activity of BLE was examined. Burdock leaves were dried by four methods: Shadow drying, oven drying, sun drying and freeze-drying. The extract solution was then subjected to total polyphenol content analysis and the method that produced BLE with the highest amount of total antioxidant components was taken forward for further analysis. The 1,1-diphenyl-2-pycrylhydrazyl scavenging, antielastase and antityrosinase activity of the BLE were measured to enable the evaluation of the antioxidant and skin aging-associated enzyme inhibitory activities of BLE. The results indicated that the total polyphenolic content following extraction with ethanol (EtOH) was highest using the freeze-drying method, followed by the oven drying, shadow drying and sun drying methods. BLE yielded a higher polyphenol content and stronger antioxidant activity as the ratio of the aqueous content of the extraction solvent used increased. BLE possesses marked tyrosinase and elastase inhibitory activities, with its antielastase activity notably stronger compared with its antityrosinase activity. These results indicate that the concentration of the extraction solvent was associated with the antioxidant and skin aging-associated enzyme inhibitory activity of BLE. The reactive oxygen species scavenging theory of skin aging may explain the tyrosinase and elastase inhibitory activity of BLE. In conclusion, the optimal method for obtaining BLE with a high antioxidant polyphenolic content was freeze-drying followed by 30–50% EtOH extraction. In addition, the antielastase and antityrosinase activities of the

  9. Elastase production by B16-F10 melanoma cells

    International Nuclear Information System (INIS)

    Shrager, J.B.; Yusa, T.; Netland, P.A.; Zetter, B.R.

    1986-01-01

    Elastolytic activity was found in sonicates of mouse B16-F10 melanoma cells and in medium conditioned by these cells. Degradation of elastin was determined by measuring the release of soluble 3 H-peptides from labelled insoluble elastin. The activity secreted from B16-F10 cells was soluble and was not associated with membrane vesicles. The secreted activity was partially inhibited by incubation with phenymethylsulfonylfluoride (PMSF) and was abolished by incubation with the alpha-1-protease inhibitor, with pepstatin A or with L-1-tosylamide-2-phenylethyl chloromethyl ketone (TPCK). In contrast, the activity was unaffected by incubation with elastatinal, with the plasmin inhibitor Σ-aminocaproic acid (EACA), the metalloproteinase inhibitor ethylenediamine-tetra-acetic acid (EDTA), the soybean trypsin inhibitor or the trypsin inhibitor N proportional to-p-tosyl-L-lysine chloromethyl ketone (TLCK). These results suggest that the majority of the tumor cell-derived elastolytic activity is attributable to a serine protease that differs in specificity from the well characterized elastases previously isolated from neutrophils, macrophages or from mammalian pancreas. The authors postulate that the release of elastase from lung-colonizing B16-F10 cells may facilitate their invasion of elastin-rich lung tissue

  10. Application of chemical arrays in screening elastase inhibitors.

    Science.gov (United States)

    Gao, Feng; Du, Guan-Hua

    2006-06-01

    Protein chip technology provides a new and useful tool for high-throughput screening of drugs because of its high performance and low sample consumption. In order to screen elastase inhibitors on a large scale, we designed a composite microarray integrating enzyme chip containing chemical arrays on glass slides to screen for enzymatic inhibitors. The composite microarray includes an active proteinase film, screened chemical arrays distributed on the film, and substrate microarrays to demonstrate change of color. The detection principle is that elastase hydrolyzes synthetic colorless substrates and turns them into yellow products. Because yellow is difficult to detect, bromochlorophenol blue (BPB) was added into substrate solutions to facilitate the detection process. After the enzyme had catalyzed reactions for 2 h, effects of samples on enzymatic activity could be determined by detecting color change of the spots. When chemical samples inhibited enzymatic activity, substrates were blue instead of yellow products. If the enzyme retained its activity, the yellow color of the products combined with blue of BPB to make the spots green. Chromogenic differences demonstrated whether chemicals inhibited enzymatic activity or not. In this assay, 11,680 compounds were screened, and two valuable chemical hits were identified, which demonstrates that this assay is effective, sensitive and applicable for high-throughput screening (HTS).

  11. Role of LTB4 in the pathogenesis of elastase-induced murine pulmonary emphysema

    Science.gov (United States)

    Paige, Mikell; Hanna, Halim; Kim, Su H.; Burdick, Marie D.; Strieter, Robert M.

    2010-01-01

    Exaggerated levels of the leukotriene B4 (LTB4) frequently coexist at sites of inflammation and tissue remodeling. Therefore, we hypothesize that the LTB4 pathway plays an important role in the pathogenesis of neutrophilic inflammation that contributes to pulmonary emphysema. In this study, significant levels of LTB4 were detected in human lung tissues with emphysema compared with lungs without emphysema (9,497 ± 2,839 vs. 4,142 ± 1,173 pg/ml, n = 9 vs. 10, P = 0.04). To further determine the biological role of LTB4 in the pathogenesis of emphysema, we compared the lungs of wild-type (WT) and LTA4 hydrolase−/− mice (LTB4 deficient, LTA4H−/−) exposed to intranasal elastase or vehicle control. We found that intranasal elastase induced accumulation of LTB4 in the lungs and caused progressively worsening emphysema between 14 and 28 days after elastase exposure in WT mice but not in LTA4H−/− mice. Premortem physiology documented increased lung compliance in elastase-exposed WT mice compared with elastase-exposed LTA4H−/− mice as measured by Flexivent (0.058 ± 0.005 vs. 0.041 ± 0.002 ml/cmH2O pressure). Postmortem morphometry documented increased total lung volume and alveolar sizes in elastase-exposed WT mice compared with elastase-exposed LTA4H−/− mice as measured by volume displacement and alveolar chord length assessment. Furthermore, elastase-exposed LTA4H−/− mice were found to have significantly delayed influx of the CD45highCD11bhighLy6Ghigh leukocytes compatible with neutrophils compared with elastase-exposed WT mice. Mechanistic insights to these phenotypes were provided by demonstrating protection from elastase-induced murine emphysema with neutrophil depletion in the elastase-exposed WT mice and by demonstrating time-dependent modulation of cysteinyl leukotriene biosynthesis in the elastase-exposed LTA4H−/− mice compared with elastase-exposed WT mice. Together, these findings demonstrated that LTB4 played an important role in

  12. Identification and Characterization of Roseltide, a Knottin-type Neutrophil Elastase Inhibitor Derived from Hibiscus sabdariffa

    Science.gov (United States)

    Loo, Shining; Kam, Antony; Xiao, Tianshu; Nguyen, Giang K. T.; Liu, Chuan Fa; Tam, James P.

    2016-01-01

    Plant knottins are of therapeutic interest due to their high metabolic stability and inhibitory activity against proteinases involved in human diseases. The only knottin-type proteinase inhibitor against porcine pancreatic elastase was first identified from the squash family in 1989. Here, we report the identification and characterization of a knottin-type human neutrophil elastase inhibitor from Hibiscus sabdariffa of the Malvaceae family. Combining proteomic and transcriptomic methods, we identified a panel of novel cysteine-rich peptides, roseltides (rT1-rT8), which range from 27 to 39 residues with six conserved cysteine residues. The 27-residue roseltide rT1 contains a cysteine spacing and amino acid sequence that is different from the squash knottin-type elastase inhibitor. NMR analysis demonstrated that roseltide rT1 adopts a cystine-knot fold. Transcriptome analyses suggested that roseltides are bioprocessed by asparagine endopeptidases from a three-domain precursor. The cystine-knot structure of roseltide rT1 confers its high resistance against degradation by endopeptidases, 0.2 N HCl, and human serum. Roseltide rT1 was shown to inhibit human neutrophil elastase using enzymatic and pull-down assays. Additionally, roseltide rT1 ameliorates neutrophil elastase-stimulated cAMP accumulation in vitro. Taken together, our findings demonstrate that roseltide rT1 is a novel knottin-type neutrophil elastase inhibitor with therapeutic potential for neutrophil elastase associated diseases. PMID:27991569

  13. Purification and characterization of elastase from the pyloric caeca of rainbow trout (Oncorhynchus mykiss)

    DEFF Research Database (Denmark)

    Bassompierre, Marc; Nielsen, Henrik Hauch; Børresen, Torger

    1993-01-01

    1. An elastase-like enzyme was purified from the pyloric caeca of rainbow trout by hydrophobic interaction, cation exchange and gel-filtration chromatography. 2. The approximate molecular weight of the elastase was 27 kDa and the isoelectric point was remarkably basic. 3. The pH optimum of this e......1. An elastase-like enzyme was purified from the pyloric caeca of rainbow trout by hydrophobic interaction, cation exchange and gel-filtration chromatography. 2. The approximate molecular weight of the elastase was 27 kDa and the isoelectric point was remarkably basic. 3. The pH optimum...... of this enzyme was 8.0, when assayed with Succinyl-Ala-Ala-Ala-p-Nitroanilide. 4. When assayed with Succinyl-Ala-Ala-Ala-p-Nitroanilide, the enzyme activity had a temperature optimum of 45 degree C, and the enzyme was stable up to this temperature. 5. The trout elastase exhibited a higher specific activity than...... porcine elastase against Succinyl-Ala-Ala-Ala-p-Nitroanilide and elastin-orcein. 6. The trout elastase was inhibited by elastatinal, PMSF, TPCK, SBTI and Bowman-Birk inhibitor....

  14. Alendronate inhalation ameliorates elastase-induced pulmonary emphysema in mice by induction of apoptosis of alveolar macrophages.

    Science.gov (United States)

    Ueno, Manabu; Maeno, Toshitaka; Nishimura, Satoshi; Ogata, Fusa; Masubuchi, Hiroaki; Hara, Kenichiro; Yamaguchi, Kouichi; Aoki, Fumiaki; Suga, Tatsuo; Nagai, Ryozo; Kurabayashi, Masahiko

    2015-03-10

    Alveolar macrophages play a crucial role in the pathogenesis of emphysema, for which there is currently no effective treatment. Bisphosphonates are widely used to treat osteoclast-mediated bone diseases. Here we show that delivery of the nitrogen-containing bisphosphonate alendronate via aerosol inhalation ameliorates elastase-induced emphysema in mice. Inhaled, but not orally ingested, alendronate inhibits airspace enlargement after elastase instillation, and induces apoptosis of macrophages in bronchoalveolar fluid via caspase-3- and mevalonate-dependent pathways. Cytometric analysis indicates that the F4/80(+)CD11b(high)CD11c(mild) population characterizing inflammatory macrophages, and the F4/80(+)CD11b(mild)CD11c(high) population defining resident alveolar macrophages take up substantial amounts of the bisphosphonate imaging agent OsteoSense680 after aerosol inhalation. We further show that alendronate inhibits macrophage migratory and phagocytotic activities and blunts the inflammatory response of alveolar macrophages by inhibiting nuclear factor-κB signalling. Given that the alendronate inhalation effectively induces apoptosis in both recruited and resident alveolar macrophages, we suggest this strategy may have therapeutic potential for the treatment of emphysema.

  15. Does human leukocyte elastase degrade intact skin elastin?

    DEFF Research Database (Denmark)

    Schmelzer, Christian E H; Jung, Michael C; Wohlrab, Johannes

    2012-01-01

    This study aimed to investigate the susceptibility of intact fibrillar human elastin to human leukocyte elastase and cathepsin G. Elastin is a vital protein of the extracellular matrix of vertebrates, and provides exceptional properties including elasticity and tensile strength to many tissues...... and organs, including the aorta, lung, cartilage, elastic ligaments and skin, and is thus critical for their long-term function. Mature elastin is an insoluble and extremely durable protein that undergoes very little turnover, but sustained exposure to proteases may lead to irreversible and severe damage......, and thus to functional loss of the elastic fiber network. Hence, it is a key issue to understand which enzymes actually initiate elastolysis under certain pathological conditions or during intrinsic aging. In this paper, we provide a complete workflow for isolation of pure and intact elastin from very...

  16. Protective effects of an aptamer inhibitor of neutrophil elastase in lung inflammatory injury

    DEFF Research Database (Denmark)

    Bless, N M; Smith, D; Charlton, J

    1997-01-01

    Neutrophils play an important part in the development of acute inflammatory injury. Human neutrophils contain high levels of the serine protease elastase, which is stored in azurophilic granules and is secreted in response to inflammatory stimuli. Elastase is capable of degrading many components...... of extracellular matrix [1-4] and has cytotoxic effects on endothelial cells [5-7] and airway epithelial cells. Three types of endogenous protease inhibitors control the activity of neutrophil elastase, including alpha-1 protease inhibitor (alpha-1PI), alpha-2 macroglobulin and secreted leukoproteinase inhibitor...... (SLPI) [8-10]. A disturbed balance between neutrophil elastase and these inhibitors has been found in various acute clinical conditions (such as adult respiratory syndrome and ischemia-reperfusion injury) and in chronic diseases. We investigated the effect of NX21909, a selected oligonucleotide (aptamer...

  17. Angiogenic activity of bFGF and VEGF suppressed by proteolytic cleavage by neutrophil elastase

    International Nuclear Information System (INIS)

    Ai, Shingo; Cheng Xianwu; Inoue, Aiko; Nakamura, Kae; Okumura, Kenji; Iguchi, Akihisa; Murohara, Toyoaki; Kuzuya, Masafumi

    2007-01-01

    Neutrophil elastase (NE), a serine protease released from the azurophil granules of activated neutrophil, proteolytically cleaves multiple cytokines, and cell surface proteins. In the present study, we examined whether NE affects the biological abilities of angiogenic growth factors such as basic-fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF). NE degraded bFGF and VEGF in a time- and concentration-dependent manner, and these degradations were suppressed by sivelestat, a synthetic inhibitor of NE. The bFGF- or VEGF-mediated proliferative activity of human umbilical vein endothelial cells was inhibited by NE, and the activity was recovered by sivelestat. Furthermore, NE reduced the bFGF- or VEGF-induced tubulogenic response of the mice aortas, ex vivo angiogenesis assay, and these effects were also recovered by sivelestat. Neutrophil-derived NE degraded potent angiogenic factors, resulting in loss of their angiogenic activity. These findings provide additional insight into the role played by neutrophils in the angiogenesis process at sites of inflammation

  18. Inhibition of Pseudomonas aeruginosa elastase and Pseudomonas keratitis using a thiol-based peptide.

    OpenAIRE

    Burns, F R; Paterson, C A; Gray, R D; Wells, J T

    1990-01-01

    Pseudomonas aeruginosa elastase is a zinc metalloproteinase which is released during P. aeruginosa infections. Pseudomonas keratitis, which occurs following contact lens-induced corneal trauma, can lead to rapid, liquefactive necrosis of the cornea. This destruction has been attributed to the release of both host-derived enzymes and the bacterial products P. aeruginosa elastase, alkaline protease, exotoxin A, and lipopolysaccharide endotoxin. A synthetic metalloproteinase inhibitor, HSCH2 (DL...

  19. Thrombin Production and Human Neutrophil Elastase Sequestration by Modified Cellulosic Dressings and Their Electrokinetic Analysis

    Directory of Open Access Journals (Sweden)

    Nicolette Prevost

    2011-12-01

    Full Text Available Wound healing is a complex series of biochemical and cellular events. Optimally, functional material design addresses the overlapping acute and inflammatory stages of wound healing based on molecular, cellular, and bio-compatibility issues. In this paper the issues addressed are uncontrolled hemostasis and inflammation which can interfere with the orderly flow of wound healing. In this regard, we review the serine proteases thrombin and elastase relative to dressing functionality that improves wound healing and examine the effects of charge in cotton/cellulosic dressing design on thrombin production and elastase sequestration (uptake by the wound dressing. Thrombin is central to the initiation and propagation of coagulation, and elastase is released from neutrophils that can function detrimentally in a stalled inflammatory phase characteristic of chronic wounds. Electrokinetic fiber surface properties of the biomaterials of this study were determined to correlate material charge and polarity with function relative to thrombin production and elastase sequestration. Human neutrophil elastase sequestration was assessed with an assay representative of chronic wound concentration with cotton gauze cross-linked with three types of polycarboxylic acids and one phosphorylation finish; thrombin production, which was assessed in a plasma-based assay via a fluorogenic peptide substrate, was determined for cotton, cotton-grafted chitosan, chitosan, rayon/polyester, and two kaolin-treated materials including a commercial hemorrhage control dressing (QuickClot Combat Gauze. A correlation in thrombin production to zeta potential was found. Two polycarboxylic acid cross linked and a phosphorylated cotton dressing gave high elastase sequestration.

  20. Elastase effect on the extracellular matrix of rat aortic smooth muscle cells in culture

    International Nuclear Information System (INIS)

    Kispert, J.; Mogayzel, P.J. Jr.; Pratt, C.A.; Toselli, P.; Wolfe, B.L.; Faris, B.; Franzblau, C.

    1986-01-01

    The effect of porcine pancreatic elastase on the extracellular matrix (ECM) of neonatal rat aortic smooth muscle cell cultures was monitored both chemically and ultrastructurally. Initially, the elastin appeared as non-coalesced material closely associated with filaments, presumably microfibrils. The insoluble elastin accumulated in the ECM of cells in culture for 6 weeks accounted for 40-45% of the total protein. After exposure to elastase for 30-60 minutes, the elastin content was reduced to 14-20%. The reduction in the total protein content of the cultures after elastase treatment was due primarily to the loss of elastin. Although the amino acid compositions of the elastin isolated from cultures both before and after elastase treatment were similar, there were striking ultrastructural differences in the amorphous elastin. The elastin assumed a mottled appearance after elastase exposure, similar to that seen in in vivo emphysema models. Pulse experiments with 3 H-valine demonstrated an increase in protein synthesis by the cells 20 hours after elastase exposure, suggesting the potential for elastin repair. The use of this culture system will aid in clarifying the role of elastolysis in pulmonary and vascular injuries

  1. Lipopolysaccharide increases Na(+),K(+)-pump, but not ENaC, expression in guinea-pig airway epithelium.

    Science.gov (United States)

    Dodrill, Michael W; Beezhold, Donald H; Meighan, Terence; Kashon, Michael L; Fedan, Jeffrey S

    2011-01-25

    Earlier, we found in functional experiments that lipopolysaccharide (LPS; 4mg/kg; i.p.) hyperpolarized the epithelium by stimulating the transepithelial transport of Na(+) in guinea-pig tracheal epithelium. Epithelial sodium channel (ENaC) activity and Na(+),K(+)-pump activity were increased. In this study, we hypothesized that LPS increases the expression of ENaC and the Na(+),K(+)-pump in the epithelium and investigated the levels of transcription and protein abundance. Using qPCR, the effects of LPS on the transcription of αENaC, α(1) Na(+),K(+)-pump, COX-2, eNOS, iNOS, IL-1β, and TNF-α were measured at 3 and 18h. In the epithelium, LPS increased the transcription of COX-2, IL-1β, and, to a nonsignificant extent, TNF-α at 3h, but not at 18h. In alveolar macrophages, TNF-α, and, to a nonsignificant extent, COX-2 and IL-1β were up-regulated at 3h, but not at 18h. Even though LPS stimulated the transcription of some genes, αENaC and α(1) Na(+),K(+)-ATPase transcription were not affected. The expressions of α-, β-, and γ-ENaC and α(1) Na(+),K(+)-pump from the tracheal epithelium and kidney cortex/medulla were investigated by western blotting. All three ENaC subunits were detected as cleavage fragments, yet LPS had no effect on their expression. LPS increased the expression of the α(1) subunit and the α(1), α(2), and α(3) subunits, collectively, of the Na(+),K(+)-pump. Taken together, these data indicate that LPS increases Na(+) transport downstream of the genetic level, in part, by stimulating the expression of the Na(+),K(+)-pump. Published by Elsevier B.V.

  2. Effects of dietary Na+ deprivation on epithelial Na+ channel (ENaC, BDNF, and TrkB mRNA expression in the rat tongue

    Directory of Open Access Journals (Sweden)

    Stähler Frauke

    2009-03-01

    Full Text Available Abstract Background In rodents, dietary Na+ deprivation reduces gustatory responses of primary taste fibers and central taste neurons to lingual Na+ stimulation. However, in the rat taste bud cells Na+ deprivation increases the number of amiloride sensitive epithelial Na+ channels (ENaC, which are considered as the "receptor" of the Na+ component of salt taste. To explore the mechanisms, the expression of the three ENaC subunits (α, β and γ in taste buds were observed from rats fed with diets containing either 0.03% (Na+ deprivation or 1% (control NaCl for 15 days, by using in situ hybridization and real-time quantitative RT-PCR (qRT-PCR. Since BDNF/TrkB signaling is involved in the neural innervation of taste buds, the effects of Na+ deprivation on BDNF and its receptor TrkB expression in the rat taste buds were also examined. Results In situ hybridization analysis showed that all three ENaC subunit mRNAs were found in the rat fungiform taste buds and lingual epithelia, but in the vallate and foliate taste buds, only α ENaC mRNA was easily detected, while β and γ ENaC mRNAs were much less than those in the fungiform taste buds. Between control and low Na+ fed animals, the numbers of taste bud cells expressing α, β and γ ENaC subunits were not significantly different in the fungiform, vallate and foliate taste buds, respectively. Similarly, qRT-PCR also indicated that Na+ deprivation had no effect on any ENaC subunit expression in the three types of taste buds. However, Na+ deprivation reduced BDNF mRNA expression by 50% in the fungiform taste buds, but not in the vallate and foliate taste buds. The expression of TrkB was not different between control and Na+ deprived rats, irrespective of the taste papillae type. Conclusion The findings demonstrate that dietary Na+ deprivation does not change ENaC mRNA expression in rat taste buds, but reduces BDNF mRNA expression in the fungiform taste buds. Given the roles of BDNF in survival of

  3. Primary structure of human pancreatic elastase 2 determined by sequence analysis of the cloned mRNA

    International Nuclear Information System (INIS)

    Fletcher, T.S.; Shen, W.F.; Largman, C.

    1987-01-01

    A cDNA encoding elastase 2 has been cloned from a human pancreatic cDNA library. The cDNA contains a translation initiation site and a poly(A) recognition site and encodes a protein of 269 amino acids, including a proposed 16-residue signal peptide. The amino acid sequence of the deduced mature protein contains a 12-residue activation peptide containing a cysteine at residue 1 similar to that of chymotryspin. The proposed active enzyme contains all of the characteristic active-site amino acids, including His-57, Asp-102, and Ser-195. The S1 binding pocket is bounded by Gly-216 and Ser-226, making this pocket intermediate in size between chymotrypsins and elastase 1 or protease E, consistent with the substrate specificity of elastase 2 for long-chain aliphatic or aromatic amino acids. Computer modeling studies using the amino acid sequence of elastase 2 superimposed on the X-ray structure of porcine elastase 1 suggest that a change of Gln-192 in elastase 1 to Asn-192 in elastase 2 may account for the lower catalytic efficiency of the latter enzyme. Several basic residues appear to be near the ends of the extended binding pocket of elastases which might serve to anchor the enzyme to the elastin substrate. These studies indicate that elastases 2 and elastase 1 both contain an Arg-65A as well as a basic dipeptide at 223/224 which is not present in chymotrypsins. In addition, Arg-217A is present in humaan elastase 2 but absent in rat pancreatic protein which has been proposed to be an elastase 2 on the basis of sequence homology, but which was not isolated during screening of rat pancreatic tissue extracts for elastolytic activity

  4. Elastase-coupled beads as a tool for characterizing localized alveolar tissue destruction associated with the onset of emphysema

    Science.gov (United States)

    Craig, J. M.; Scott, A. L.

    2013-01-01

    Intratracheal elastase challenge of laboratory animals has long been established as a model for observing the physiological and morphological changes that result from alveolar destruction, the hallmark of emphysema. However, instillation of elastase suspended in buffer results in widespread inflammation and variable emphysematous lesions, which has made the identification of specific cellular and molecular events associated with the onset of emphysema difficult to define. Here we establish a bead-based elastase delivery system that induces localized tissue destruction, a key event in the initiation of emphysema. Elastase was coupled to bisacrylamide beads, which were shown to retain enzymatic activity prior to intratracheal administration in mice. C57BL/6 mice were given a single dose of 40,000 beads, which became distributed throughout the small airways and parenchyma of the lung. Elastase-coupled beads resulted in a quantifiable loss of alveolar tissue immediately surrounding the beads, an effect that was not observed with beads that lacked protein altogether or with beads containing elastase inactivated by an irreversible inhibitor. Furthermore, beads bound with active elastase elicited local recruitment of mononuclear cells, including macrophages, and polymorphonuclear neutrophils to the site of bead deposition, a feature consistent with the cellular infiltration observed following conventional solubilized elastase challenges. This work identifies a novel bead-based enzyme delivery system that also extends the elastase model of emphysema to permit the characterization of mechanisms that drive alveolar surface area loss following elastin degradation in focal emphysematous lesions. PMID:23558388

  5. Protein kinase D1 modulates aldosterone-induced ENaC activity in a renal cortical collecting duct cell line.

    LENUS (Irish Health Repository)

    McEneaney, Victoria

    2010-08-30

    Aldosterone treatment of M1-CCD cells stimulated an increase in epithelial Na(+) channel (ENaC) alpha-subunit expression that was mainly localized to the apical membrane. PKD1-suppressed cells constitutively expressed ENaCalpha at low abundance, with no increase after aldosterone treatment. In the PKD1-suppressed cells, ENaCalpha was mainly localized proximal to the basolateral surface of the epithelium both before and after aldosterone treatment. Apical membrane insertion of ENaCbeta in response to aldosterone treatment was also sensitive to PKD1 suppression as was the aldosterone-induced rise in the amiloride-sensitive, trans-epithelial current (I(TE)). The interaction of the mineralocorticoid receptor (MR) with specific elements in the promoters of aldosterone responsive genes is stabilized by ligand interaction and phosphorylation. PKD1 suppression inhibited aldosterone-induced SGK-1 expression. The nuclear localization of MR was also blocked by PKD1 suppression and MEK antagonism implicating both these kinases in MR nuclear stabilization. PKD1 thus modulates aldosterone-induced ENaC activity through the modulation of sub-cellular trafficking and the stabilization of MR nuclear localization.

  6. Solar ultraviolet irradiation induces decorin degradation in human skin likely via neutrophil elastase.

    Science.gov (United States)

    Li, Yong; Xia, Wei; Liu, Ying; Remmer, Henriette A; Voorhees, John; Fisher, Gary J

    2013-01-01

    Exposure of human skin to solar ultraviolet (UV) irradiation induces matrix metalloproteinase-1 (MMP-1) activity, which degrades type I collagen fibrils. Type I collagen is the most abundant protein in skin and constitutes the majority of skin connective tissue (dermis). Degradation of collagen fibrils impairs the structure and function of skin that characterize skin aging. Decorin is the predominant proteoglycan in human dermis. In model systems, decorin binds to and protects type I collagen fibrils from proteolytic degradation by enzymes such as MMP-1. Little is known regarding alterations of decorin in response to UV irradiation. We found that solar-simulated UV irradiation of human skin in vivo stimulated substantial decorin degradation, with kinetics similar to infiltration of polymorphonuclear (PMN) cells. Proteases that were released from isolated PMN cells degraded decorin in vitro. A highly selective inhibitor of neutrophil elastase blocked decorin breakdown by proteases released from PMN cells. Furthermore, purified neutrophil elastase cleaved decorin in vitro and generated fragments with similar molecular weights as those resulting from protease activity released from PMN cells, and as observed in UV-irradiated human skin. Cleavage of decorin by neutrophil elastase significantly augmented fragmentation of type I collagen fibrils by MMP-1. Taken together, these data indicate that PMN cell proteases, especially neutrophil elastase, degrade decorin, and this degradation renders collagen fibrils more susceptible to MMP-1 cleavage. These data identify decorin degradation and neutrophil elastase as potential therapeutic targets for mitigating sun exposure-induced collagen fibril degradation in human skin.

  7. Elastolytic activity of human blood monocytes characterized by a new monoclonal antibody against human leucocyte elastase. Relationship to rheumatoid arthritis

    DEFF Research Database (Denmark)

    Jensen, H S; Christensen, L D

    1990-01-01

    The leucocyte elastase of human blood monocytes was investigated by applying a new monoclonal antibody which did not block the enzyme activity against elastin. In a fixed population of mononuclear cells (MNC) and using fluorescence activated cell sorting (FACS), the human leucocyte elastase (HLE...

  8. The third serine proteinase with chymotrypsin specificity isolated from Atlantic cod (Gadus morhua) is a type-II elastase

    DEFF Research Database (Denmark)

    Asgeirsson, B; Leth-Larsen, Rikke; Thórólfsson, M

    1998-01-01

    -Ala-Ala-Pro-Phe-p-nitroanilide, but inactive against the typical elastase substrates succinyl-Ala-Ala-Ala-p-nitroanilide and orcein-elastin. Comparison of the kinetic properties of the cod elastase C with bovine chymotrypsin and cod chymotrypsin variants A and B, using succinyl-Ala-Ala-Pro-Phe-p-nitroanilide, showed a lower catalytic...

  9. Funciones de los canales iónicos CFTR y ENAC en la fibrosis quística

    Directory of Open Access Journals (Sweden)

    Alejandra G. Palma

    2014-04-01

    Full Text Available La fibrosis quística se debe a la ausencia o defecto del canal transmembrana regulador de la fibrosis quística (CFTR, un canal de cloruro codificado en el gen cftr que juega un papel clave en la homeostasis del agua e iones. El CFTR es activado por el AMPc y se localiza en las membranas apicales y basolaterales de las vías aéreas, intestino y glándulas exocrinas. Una de sus funciones primarias en los pulmones es mantener la capa de líquido superficial a través de su función de canal y regular el canal epitelial de sodio sensible al amiloride (ENaC. Se han identificado más de 1900 mutaciones en el gen cftr. La enfermedad se caracteriza por secreciones viscosas en las glándulas exocrinas y por niveles elevados de cloruro de sodio en el sudor. En la fibrosis quística el CFTR no funciona y el ENaC está desregulado; el resultado es un aumento en la reabsorción de sodio y agua con la formación de un líquido viscoso. En las glándulas sudoríparas tanto el Na+ como el Cl- se retienen en el lumen causando una pérdida de electrolitos durante la sudoración y el NaCl se elimina al sudor. Así, los niveles elevados de NaCl son la base del test del sudor inducido por pilocarpina, un método de diagnóstico para la enfermedad. En esta revisión se discuten los movimientos de Cl- y Na+ en las glándulas sudoríparas y pulmón así como el papel del ENaC en la patogénesis de la enfermedad.

  10. Non-surgical periodontal therapy decreases serum elastase levels in aggressive but not in chronic periodontitis.

    Science.gov (United States)

    Eickholz, Peter; Siegelin, Yasemin; Scharf, Susanne; Schacher, Beate; Oremek, Gerhard M; Sauer-Eppel, Hildegund; Schubert, Ralf; Wohlfeil, Martin

    2013-04-01

    Assessment of the effect of non-surgical periodontal therapy (SRP) on serum inflammatory parameters in patients with untreated aggressive (AgP) and chronic (ChP) periodontitis. Overall, 31 ChP and 29 AgP were examined clinically prior to and 12 weeks after SRP (subgingival scaling of all pockets within 2 days) with systemic antibiotics for patients positive for Aggregatibacter actinomycetemcomitans (14 AgP, 9 ChP). Blood was sampled prior to, one day, 6, and 12 weeks after the first SRP visit. Serum elastase, C-reactive protein (CRP), lipopolysaccharide-binding protein (LBP), interleukin (IL) 6, 8, and leukocyte counts were assessed. At baseline, serum elastase, CRP, and LBP were significantly (p < 0.01) higher in AgP than ChP. Serum elastase, CRP, LBP, and IL-6 were significantly (p < 0.001) elevated one day after scaling in both groups. Both groups showed significant clinical improvement (p < 0.001). A significant difference was observed regarding change of serum elastase 12 weeks after SRP between AgP and ChP (p = 0.015). Multiple regression analysis revealed AgP, African origin, and bleeding on probing to be associated with more pronounced elastase reduction. CRP reduction was associated with African origin, systemic antibiotics, and baseline probing pocket depth. SRP results in serum elastase reduction in AgP but not in ChP. © 2013 John Wiley & Sons A/S.

  11. Cell therapy with bone marrow mononuclear cells in elastase-induced pulmonary emphysema.

    Science.gov (United States)

    Longhini-Dos-Santos, Nathalia; Barbosa-de-Oliveira, Valter Abraão; Kozma, Rodrigo Heras; Faria, Carolina Arruda de; Stessuk, Talita; Frei, Fernando; Ribeiro-Paes, João Tadeu

    2013-04-01

    Emphysema is characterized by destruction of alveolar walls with loss of gas exchange surface and consequent progressive dyspnea. This study aimed to evaluate the efficiency of cell therapy with bone marrow mononuclear cells (BMMC) in an animal model of elastase-induced pulmonary emphysema. Emphysema was induced in C57Bl/J6 female mice by intranasal instillation of elastase. After 21 days, the mice received bone marrow mononuclear cells from EGFP male mice with C57Bl/J6 background. The groups were assessed by comparison and statistically significant differences (p pulmonary emphysema.

  12. High-yields heterologous production of the novel Aspergillus fumigatus elastase inhibitor AFUEI in Aspergillus oryzae.

    Science.gov (United States)

    Yamashita, Nobuo; Komori, Yumiko; Okumura, Yoshiyuki; Uchiya, Kei-Ichi; Matsui, Takeshi; Nishimura, Akira; Ogawa, Kenji; Nikai, Toshiaki

    2011-08-01

    AFUEI, an elastase inhibitor produced by Aspergillus fumigatus strongly inhibits the elastolytic activity of A. fumigatus etc. To purify AFUEI, we constructed a strain that overproduces AFUEI by introducing the gene encoding AFUEI (Genbank accession no. AB546725) under control of the amyB promoter into the heterologous host Aspergillus oryzae. A. oryzae TF-4 displayed strong elastase inhibitory activity and produced considerably more AFUEI than that of A. fumigatus. Furthermore, AFUEI could be purified using culture broth and single ultrafiltration (UF) treatment, allowing for the effective production of AFUEI for use in clinical trials. Copyright © 2011 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  13. Epithelial-to-Mesenchymal Transition in Pancreatic Ductal Adenocarcinoma and Pancreatic Tumor Cell Lines: The Role of Neutrophils and Neutrophil-Derived Elastase

    Directory of Open Access Journals (Sweden)

    Thomas Große-Steffen

    2012-01-01

    Full Text Available Pancreatic ductal adenocarcinoma (PDAC is frequently associated with fibrosis and a prominent inflammatory infiltrate in the desmoplastic stroma. Moreover, in PDAC, an epithelial-to-mesenchymal transition (EMT is observed. To explore a possible connection between the infiltrating cells, particularly the polymorphonuclear neutrophils (PMN and the tumor cell transition, biopsies of patients with PDAC (n=115 were analysed with regard to PMN infiltration and nuclear expression of β-catenin and of ZEB1, well-established indicators of EMT. In biopsies with a dense PMN infiltrate, a nuclear accumulation of β-catenin and of ZEB1 was observed. To address the question whether PMN could induce EMT, they were isolated from healthy donors and were cocultivated with pancreatic tumor cells grown as monolayers. Rapid dyshesion of the tumor cells was seen, most likely due to an elastase-mediated degradation of E-cadherin. In parallel, the transcription factor TWIST was upregulated, β-catenin translocated into the nucleus, ZEB1 appeared in the nucleus, and keratins were downregulated. EMT was also induced when the tumor cells were grown under conditions preventing attachment to the culture plates. Here, also in the absence of elastase, E-cadherin was downmodulated. PMN as well as prevention of adhesion induced EMT also in liver cancer cell line. In conclusion, PMN via elastase induce EMT in vitro, most likely due to the loss of cell-to-cell contact. Because in pancreatic cancers the transition to a mesenchymal phenotype coincides with the PMN infiltrate, a contribution of the inflammatory response to the induction of EMT and—by implication—to tumor progression is possible.

  14. The effect of NO-donors on chloride efflux, intracellular Ca(2+) concentration and mRNA expression of CFTR and ENaC in cystic fibrosis airway epithelial cells.

    Science.gov (United States)

    Oliynyk, Igor; Hussain, Rashida; Amin, Ahmad; Johannesson, Marie; Roomans, Godfried M

    2013-06-01

    Since previous studies showed that the endogenous bronchodilator, S-nitrosglutathione (GSNO), caused a marked increase in CFTR-mediated chloride (Cl(-)) efflux and improved the trafficking of CFTR to the plasma membrane, and that also the nitric oxide (NO)-donor GEA3162 had a similar, but smaller, effect on Cl(-) efflux, it was investigated whether the NO-donor properties of GSNO were relevant for its effect on Cl(-) efflux from airway epithelial cells. Hence, the effect of a number of other NO-donors, sodium nitroprusside (SNP), S-nitroso-N-acetyl-DL-penicillamine (SNAP), diethylenetriamine/nitric oxide adduct (DETA-NO), and diethylenetriamine/nitric oxide adduct (DEA-NONOate) on Cl(-) efflux from CFBE (∆F508/∆F508-CFTR) airway epithelial cells was tested. Cl(-) efflux was determined using the fluorescent N-(ethoxycarbonylmethyl)-6-methoxyquinoliniu bromide (MQAE)-technique. Possible changes in the intracellular Ca(2+) concentration were tested by the fluorescent fluo-4 method in a confocal microscope system. Like previously with GSNO, after 4 h incubation with the NO-donor, an increased Cl(-) efflux was found (in the order SNAP>DETA-NO>SNP). The effect of DEA-NONOate on Cl(-) efflux was not significant, and the compound may have (unspecific) deleterious effects on the cells. Again, as with GSNO, after a short (5 min) incubation, SNP had no significant effect on Cl(-) efflux. None of the NO-donors that had a significant effect on Cl(-) efflux caused significant changes in the intracellular Ca(2+) concentration. After 4 h preincubation, SNP caused a significant increase in the mRNA expression of CFTR. SNAP and DEA-NONOate decreased the mRNA expression of all ENaC subunits significantly. DETA-NO caused a significant decrease only in α-ENaC expression. After a short preincubation, none of the NO-donors had a significant effect, neither on the expression of CFTR, nor on that of the ENaC subunits in the presence and absence of L-cysteine. It can be concluded that

  15. In Vitro Activities against Cystic Fibrosis Pathogens of Synthetic Host Defence Propeptides Processed by Neutrophil Elastase.

    LENUS (Irish Health Repository)

    Desgranges, Stephane

    2011-02-22

    The antimicrobial and haemolytic activities of a host defence peptide can be controlled by modification as a propeptide of reduced net charge which can be processed by neutrophil elastase, a serine protease involved in chronic airway inflammation and infections associated with cystic fibrosis.

  16. Pharmacokinetics and whole body distribution of elastase derived angiostatin (k1-3) in rats

    NARCIS (Netherlands)

    Molema, Grietje; van Veen-Hof, Ingrid; van Loenen - Weemaes, Anne-miek; Proost, Johannes; de Leij, Lou F.M.H.; Meijer, Dirk K.F.

    2001-01-01

    In the current study, we determined short-term pharmacokinetics and whole body distribution of elastase derived angiostatin [angiostatin((k1-3))] in rats after i.v. injection of radiolabelled protein. Since In gamma-camera studies, no tumor specific angiostatin((k1-3)) accumulation was observed,

  17. Establishment of a new murine elastase-induced aneurysm model combined with transplantation.

    Directory of Open Access Journals (Sweden)

    Zuzanna Rowinska

    Full Text Available The aim of our study was to develop a reproducible murine model of elastase-induced aneurysm formation combined with aortic transplantation.Adult male mice (n = 6-9 per group underwent infrarenal, orthotopic transplantation of the aorta treated with elastase or left untreated. Subsequently, both groups of mice were monitored by ultrasound until 7 weeks after grafting.Mice receiving an elastase-pretreated aorta developed aneurysms and exhibited a significantly increased diastolic vessel diameter compared to control grafted mice at 7 week after surgery (1.11 ± 0.10 mm vs. 0.75 ± 0.03 mm; p ≤ 0,001. Histopathological examination revealed disruption of medial elastin, an increase in collagen content and smooth muscle cells, and neointima formation in aneurysm grafts.We developed a reproducible murine model of elastase-induced aneurysm combined with aortic transplantation. This model may be suitable to investigate aneurysm-specific inflammatory processes and for use in gene-targeted animals.

  18. Crystallization of porcine pancreatic elastase and a preliminary neutron diffraction experiment

    Energy Technology Data Exchange (ETDEWEB)

    Kinoshita, Takayoshi [Department of Biological Science, Graduate School of Science, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531 (Japan); Tamada, Taro [Molecular Structural Biology Group, Quantum Beam Science Directorate, Japan Atomic Energy Agency, 2-4 Shirakata-Shirane, Tokai, Ibaraki 319-1195 (Japan); Imai, Keisuke [Lead Discovery Research Laboratories, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba-shi, Ibaraki 305-8585 (Japan); Kurihara, Kazuo; Ohhara, Takashi [Molecular Structural Biology Group, Quantum Beam Science Directorate, Japan Atomic Energy Agency, 2-4 Shirakata-Shirane, Tokai, Ibaraki 319-1195 (Japan); Tada, Toshiji [Department of Biological Science, Graduate School of Science, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531 (Japan); Kuroki, Ryota, E-mail: kuroki.ryota@jaea.go.jp [Molecular Structural Biology Group, Quantum Beam Science Directorate, Japan Atomic Energy Agency, 2-4 Shirakata-Shirane, Tokai, Ibaraki 319-1195 (Japan); Department of Biological Science, Graduate School of Science, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531 (Japan)

    2007-04-01

    To investigate the structural characteristics of a covalent inhibitor bound to porcine pancreatic elastase (PPE), including H atoms and hydration by water, a crystal of porcine pancreatic elastase with its inhibitor was grown to a size of 1.6 mm{sup 3} for neutron diffraction study. The crystal diffracted to 2.3 Å resolution with sufficient quality for further structure determination owing to the similar atomic scattering properties of deuterium and carbon. Porcine pancreatic elastase (PPE) resembles the attractive drug target leukocyte elastase, which has been implicated in a number of inflammatory disorders. In order to investigate the structural characteristics of a covalent inhibitor bound to PPE, including H atoms and the hydration by water, a single crystal of PPE for neutron diffraction study was grown in D{sub 2}O containing 0.2 M sodium sulfate (pD 5.0) using the sitting-drop vapour-diffusion method. The crystal was grown to a size of 1.6 mm{sup 3} by repeated macroseeding. Neutron diffraction data were collected at room temperature using a BIX-3 diffractometer at the JRR-3 research reactor of the Japan Atomic Energy Agency (JAEA). The data set was integrated and scaled to 2.3 Å resolution in space group P2{sub 1}2{sub 1}2{sub 1}, with unit-cell parameters a = 51.2, b = 57.8, c = 75.6 Å.

  19. Serological assessment of neutrophil elastase activity on elastin during lung ECM remodeling

    DEFF Research Database (Denmark)

    Kristensen, Jacob Hull; Karsdal, Morten A.; Sand, Jannie M. B.

    2015-01-01

    Background: During the pathological destruction of lung tissue, neutrophil elastase (NE) degrades elastin, one of the major constituents of lung parenchyma. However there are no non-invasive methods to quantify NE degradation of elastin. We selected specific elastin fragments generated by NE for ...

  20. Gadolinium released by the linear gadolinium-based contrast-agent Gd-DTPA decreases the activity of human epithelial Na+ channels (ENaCs).

    Science.gov (United States)

    Knoepp, Fenja; Bettmer, Joerg; Fronius, Martin

    2017-05-01

    Gadolinium-based-contrast-agents (GBCAs) are used for magnetic-resonance-imaging and associated with renal and cardiovascular adverse reactions caused by released Gd 3+ ions. Gd 3+ is also a modulator of mechano-gated ion channels, including the epithelial Na + channel (ENaC) that is expressed in kidney epithelium and the vasculature. ENaC is important for salt-/water homeostasis and blood pressure regulation and a likely target of released Gd 3+ from GBCAs causing the above-mentioned adverse reactions. Therefore this study examined the effect of Gd 3+ and GBCAs on ENaC's activity. Human αβγENaC was expressed in Xenopus laevis oocytes and exposed to Gd 3+ , linear (Gd-DTPA, Magnevist) or cyclic (Dotarem) GBCAs. Transmembrane ion-currents (I M ) were recorded by the two-electrode-voltage-clamp technique and Gd 3+ -release by Gd-DTPA was confirmed by inductively coupled plasma-mass spectrometry. Gd 3+ exerts biphasic effects on ENaC's activity: ≤0.3mmol/l decreased I M which was preventable by DEPC (modifies histidines). Strikingly Gd 3+ ≥0.4mmol/l increased I M and this effect was prevented by cysteine-modifying MTSEA. Linear Gd-DTPA and Magnevist mimicked the effect of ≤0.3mmol/l Gd 3+ , whereas the chelator DTPA showed no effect. Gd 3+ and Gd-DTPA increased the IC 50 for amiloride, but did not affect ENaC's self-inhibition. Interestingly, cyclic Gd-DOTA (Dotarem) increased I M to a similar extent as its chelator DOTA, suggesting that the chelator rather than released Gd 3+ is responsible for this effect. These results confirm Gd 3+ -release from linear Gd-DTPA and indicate that the released Gd 3+ amount is sufficient to interfere with ENaC's activity to provide putative explanations for GBCA-related adverse effects. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Analyses of pancreas development by generation of gfp transgenic zebrafish using an exocrine pancreas-specific elastaseA gene promoter

    International Nuclear Information System (INIS)

    Wan Haiyan; Korzh, Svitlana; Li Zhen; Mudumana, Sudha Puttur; Korzh, Vladimir; Jiang Yunjin; Lin Shuo; Gong Zhiyuan

    2006-01-01

    In contrast to what we know on development of endocrine pancreas, the formation of exocrine pancreas remains poorly understood. To create an animal model that allows observation of exocrine cell differentiation, proliferation, and morphogenesis in living animals, we used the zebrafish elastaseA (elaA) regulatory sequence to develop transgenic zebrafish that display highly specific exocrine pancreas expression of GFP in both larvae and adult. By following GFP expression, we found that the pancreas in early development was a relatively compact organ and later extended posterior along the intestine. By transferring the elaA:gfp transgene into slow muscle omitted mutant that is deficient in receiving Hedgehog signals, we further showed that Hedgehog signaling is required for exocrine morphogenesis but not for cell differentiation. We also applied the morpholino knockdown and toxin-mediated cell ablation approaches to this transgenic line. We showed that the development of exocrine pancreas is Islet-1 dependent. Injection of the diphtheria toxin A (DTA) construct under the elastaseA promoter resulted in selective ablation of exocrine cells while the endocrine cells and other endodermal derivatives (liver and intestine) were not affected. Thus, our works demonstrated the new transgenic line provided a useful experimental tool in analyzing exocrine pancreas development

  2. Fecal pancreatic elastase-1 levels in older individuals without known gastrointestinal diseases or diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Idziak Joanna

    2011-01-01

    Full Text Available Abstract Background Structural changes occur in the pancreas as a part of the natural aging process. With aging, also the incidence of maldigestive symptoms and malnutrition increases, raising the possibility that these might be caused at least in part by inadequate pancreatic enzyme secretion due to degenerative processes and damage of the gland. Fecal elastase-1 is a good marker of pancreatic exocrine secretion. The aim of this study was to investigate the fecal elastase-1 levels among over 60 years old Finnish and Polish healthy individuals without any special diet, known gastrointestinal disease, surgery or diabetes mellitus. Methods A total of 159 patients participated in this cross-sectional study. 106 older individuals (aged 60-92 years were recruited from outpatient clinics and elderly homes. They were divided to three age groups: 60-69 years old (n = 31; 70-79 years old (n = 38 and over 80 years old (n = 37. 53 young subjects (20-28 years old were investigated as controls. Inclusion criteria were age over 60 years, normal status and competence. Exclusion criteria were any special diet, diabetes mellitus, any known gastrointestinal disease or prior gastrointestinal surgery. Fecal elastase-1 concentration was measured from stool samples with an ELISA that uses two monoclonal antibodies against different epitopes of human elastase-1. Results Fecal elastase-1 concentrations correlated negatively with age (Pearson r = -0,3531, P P Conclusion In our study one fifth of healthy older individuals without any gastrointestinal disorder, surgery or diabetes mellitus suffer from pancreatic exocrine insufficiency and might benefit from enzyme supplementation therapy.

  3. Plant Proteinase Inhibitor BbCI Modulates Lung Inflammatory Responses and Mechanic and Remodeling Alterations Induced by Elastase in Mice

    OpenAIRE

    Almeida-Reis, Rafael; Theodoro-Junior, Osmar A.; Oliveira, Bruno T. M.; Oliva, Leandro V.; Toledo-Arruda, Alessandra C.; Bonturi, Camila R.; Brito, Marlon V.; Lopes, Fernanda D. T. Q. S.; Prado, Carla M.; Florencio, Ariana C.; Martins, Mílton A.; Owen, Caroline A.; Leick, Edna A.; Oliva, Maria L. V.; Tibério, Iolanda F. L. C.

    2017-01-01

    Background. Proteinases play a key role in emphysema. Bauhinia bauhinioides cruzipain inhibitor (BbCI) is a serine-cysteine proteinase inhibitor. We evaluated BbCI treatment in elastase-induced pulmonary alterations. Methods.??C57BL/6 mice received intratracheal elastase (ELA group) or saline (SAL group). One group of mice was treated with BbCI (days 1, 15, and 21 after elastase instillation, ELABC group). Controls received saline and BbCI (SALBC group). After 28 days, we evaluated respirator...

  4. Mediatization

    DEFF Research Database (Denmark)

    Hjarvard, Stig

    2017-01-01

    Mediatization research shares media effects studies' ambition of answering the difficult questions with regard to whether and how media matter and influence contemporary culture and society. The two approaches nevertheless differ fundamentally in that mediatization research seeks answers...... to these general questions by distinguishing between two concepts: mediation and mediatization. The media effects tradition generally considers the effects of the media to be a result of individuals being exposed to media content, i.e. effects are seen as an outcome of mediated communication. Mediatization...... research is concerned with long-term structural changes involving media, culture, and society, i.e. the influences of the media are understood in relation to how media are implicated in social and cultural changes and how these processes come to create new conditions for human communication and interaction...

  5. Cotton Study: Albumin Binding and its Effect on Elastase Activity in the Chronic Non-Healing Wound

    Energy Technology Data Exchange (ETDEWEB)

    Castro, N.; Goheen, S.

    2005-01-01

    Cotton, as it is used in wound dressings is composed of nearly pure cellulose. During the wound-healing process, cotton is exposed to various blood components including water, salts, cells, and blood proteins. Albumin is the most prominent protein in blood. Elastase is an enzyme secreted by white blood cells and takes an active role in tissue reconstruction. In the chronic non-healing wound, elastase is often over-expressed such that this enzyme digests tissue and growth factors, and interferes with the normal healing process. Our goal is to design a cotton wound dressing that will sequester elastase or assist in reducing elastase activity in the presence of other blood proteins such as albumin. The ability of cotton and various cotton derivatives to sequester elastase and albumin has been studied by examining the adsorption of these two proteins separately. We undertook the present work to confirm the binding of albumin to cotton and to quantify the activity of elastase in the presence of various derivatives of cotton. We previously observed a slight increase in elastase activity when exposed to cotton. We also observed a continuous accumulation of albumin on cotton using high-performance liquid chromatography methods. In the present study, we used an open-column-absorption technique coupled with a colorimetric protein assay to confirm losses of albumin to cotton. We have also confirmed increased elastase activity after exposure to cotton. The results are discussed in relation to the porosity of cotton and the use of cotton for treating chronic non-healing wounds.

  6. Human leukocyte and porcine pancreatic elastase: X-ray crystal structures, mechanism, substrate specificity, and mechanism-based inhibitors

    International Nuclear Information System (INIS)

    Bode, W.; Meyer, E. Jr.; Powers, J.C.

    1989-01-01

    The serine protease family of enzymes is one of the most widely studied group of enzymes, as evidenced by the fact that more crystal structures are available for individuals of this superfamily than for any other homologous group of enzymes. These enzymes contain a conserved triad of catalytic residues including Ser-195, His-57, and Asp-102. The active-site serine is very nucleophilic, and serine proteases are inhibited by specific serine protease reagents such as diisopropyl phosphorofluoridate (DFP), phenylmethanesulfonyl fluoride, and 3,4-dichloroisocoumarin. Elastases are a group of proteases that possess the ability to cleave the important connective tissue protein elastin. Elastin has the unique property of elastic recoil, is widely distributed in vertebrate tissue, and is particularly abundant in the lungs, arteries, skin, and ligaments. Human neutrophil elastase and pancreatic elastase are two major serine proteases that cleave elastin. Neutrophil elastase is found in the dense granules of polymorphonuclear leukycytes and is essential for phagocytosis and defense against infection by invading microorganisms. Pancreatic elastase is stored as an inactive zymogen in the pancreas and is secreted into the intestines where it becomes activated by trypsin and then participates in digestion. Both elastases cleave substrates at peptide bonds where the P 1 residue is an amino acid residue with a small alkyl side chain

  7. High-density lipoproteins potentiate α1-antitrypsin therapy in elastase-induced pulmonary emphysema.

    Science.gov (United States)

    Moreno, Juan-Antonio; Ortega-Gomez, Almudena; Rubio-Navarro, Alfonso; Louedec, Liliane; Ho-Tin-Noé, Benoit; Caligiuri, Giuseppina; Nicoletti, Antonino; Levoye, Angelique; Plantier, Laurent; Meilhac, Olivier

    2014-10-01

    Several studies report that high-density lipoproteins (HDLs) can carry α1-antitrypsin (AAT; an elastase inhibitor). We aimed to determine whether injection of exogenous HDL, enriched or not in AAT, may have protective effects against pulmonary emphysema. After tracheal instillation of saline or elastase, mice were randomly treated intravenously with saline, human plasma HDL (75 mg apolipoprotein A1/kg), HDL-AAT (75 mg apolipoprotein A1-3.75 mg AAT/kg), or AAT alone (3.75 mg/kg) at 2, 24, 48, and 72 hours. We have shown that HDL-AAT reached the lung and prevented the development of pulmonary emphysema by 59.3% at 3 weeks (alveoli mean chord length, 22.9 ± 2.8 μm versus 30.7 ± 4.5 μm; P pulmonary emphysema than AAT alone, and may represent a significant development for the management of emphysema associated with AAT deficiency.

  8. Inhibitory effects of constituents of Morinda citrifolia seeds on elastase and tyrosinase.

    Science.gov (United States)

    Masuda, Megumi; Murata, Kazuya; Fukuhama, Akiko; Naruto, Shunsuke; Fujita, Tadashi; Uwaya, Akemi; Isami, Fumiyuki; Matsuda, Hideaki

    2009-07-01

    A 50% ethanolic extract (MCS-ext) from seeds of Morinda citrifolia ("noni" seeds) showed more potent in vitro inhibition of elastase and tyrosinase, and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity than extracts of M. citrifolia leaves or flesh. Activity-guided fractionation of MCS-ext using in vitro assays led to the isolation of ursolic acid as an active constituent of elastase inhibitory activity. 3,3'-Bisdemethylpinoresinol, americanin A, and quercetin were isolated as active constituents having both tyrosinase inhibitory and radical scavenging activities. Americanin A and quercetin also showed superoxide dismutase (SOD)-like activity. These active compounds were isolated from noni seeds for the first time.

  9. The Effect of Laser Surface Treatment on Structure and Mechanical Properties Aluminium Alloy ENAC-AlMg9

    Directory of Open Access Journals (Sweden)

    Pakieła W.

    2016-09-01

    Full Text Available In this work, the influence of a high power diode laser surface treatment on the structure and properties of aluminium alloy has been determined. The aim of this study was to improve the mechanical and tribological properties of the surface layer of the aluminium alloy by simultaneously melting and feeding tungsten carbide particles into the molten pool. During the process was used high-power diode laser HPDL. In order to remelt the aluminium alloy surface the HPDL laser of 1.8, 2.0 and 2.2 kW laser beam power has been used. The linear laser scan rate of the beam was set 0.5 cm/s. In order to protect the liquid metal during laser treatment was used argon. As a base material was used aluminium alloy ENAC-AlMg9. To improve the surface mechanical and wear properties of the applied aluminium alloy was used biphasic tungsten carbide WC/W2C. The size of alloying powder was in the range 110-210 µm. The ceramic powder was introduced in the remelting zone by a gravity feeder at a constant rate of 8 g/m.

  10. Localization and stretch-dependence of lung elastase activity in development and compensatory growth.

    Science.gov (United States)

    Young, Sarah Marie; Liu, Sheng; Joshi, Rashika; Batie, Matthew R; Kofron, Matthew; Guo, Jinbang; Woods, Jason C; Varisco, Brian Michael

    2015-04-01

    Synthesis and remodeling of the lung matrix is necessary for primary and compensatory lung growth. Because cyclic negative force is applied to developing lung tissue during the respiratory cycle, we hypothesized that stretch is a critical regulator of lung matrix remodeling. By using quantitative image analysis of whole-lung and whole-lobe elastin in situ zymography images, we demonstrated that elastase activity increased twofold during the alveolar stage of postnatal lung morphogenesis in the mouse. Remodeling was restricted to alveolar walls and ducts and was nearly absent in dense elastin band structures. In the mouse pneumonectomy model of compensatory lung growth, elastase activity increased threefold, peaking at 14 days postpneumonectomy and was higher in the accessory lobe compared with other lobes. Remodeling during normal development and during compensatory lung growth was different with increased major airway and pulmonary arterial remodeling during development but not regeneration, and with homogenous remodeling throughout the parenchyma during development, but increased remodeling only in subpleural regions during compensatory lung growth. Left lung wax plombage prevented increased lung elastin during compensatory lung growth. To test whether the adult lung retains an innate capacity to remodel elastin, we developed a confocal microscope-compatible stretching device. In ex vivo adult mouse lung sections, lung elastase activity increased exponentially with strain and in peripheral regions of lung more than in central regions. Our study demonstrates that lung elastase activity is stretch-dependent and supports a model in which externally applied forces influence the composition, structure, and function of the matrix during periods of alveolar septation. Copyright © 2015 the American Physiological Society.

  11. Neutrophil elastase inhibitor, ONO-5046, modulates acid-induced lung and systemic injury in rabbits.

    Science.gov (United States)

    Kaneko, K; Kudoh, I; Hattori, S; Yamada, H; Ohara, M; Wiener-Kronish, J; Okumura, F

    1997-09-01

    Acid instillation leads to direct lung and to secondary systemic organ injury, probably via activated macrophages and neutrophils. This study investigated the effects of neutrophil elastase on organ injury after unilateral lung acid instillation by administrating a specific neutrophil elastase inhibitor, ONO-5046, before acid instillation. Three groups of anesthetized rabbits (n = 12 in each group) underwent tracheostomies, and instillations were made into their right lower lobe airspaces with either phosphate buffered saline (pH, 7.4; volume, 1.2 ml/kg; n = 12) or HCl (pH, 1.25; volume, 1.2 ml/kg; n = 24). In half of the acid-instilled rabbits, ONO-5046, 10 mg/kg, was given intravenously 15 min before the HCl instillation, and then 10 mg x kg(-1) x h(-1) of the drug was continuously infused throughout the experiment. The other groups of animals received the vehicle intravenously. Anesthesia and mechanical ventilation was continued for 8 h, whereas arterial blood gases were sampled intermittently. Eight hours after saline or acid instillation, the animals were killed, and their lungs, heart, kidneys, liver, and small intestines were harvested. Wet-to-dry weight ratios (W/ D) and myeloperoxidase (MPO) assays of these organs were done, and elastase assays on the bronchoalveolar lavage fluids (BALF) obtained from each lung also were performed. Pretreatment with ONO-5046 attenuated the physiologic changes seen in the vehicle-treated animals. Significant decreases in W/D of the noninstilled lungs and of the small intestine and normalization of the oxygenation of the experimental animals occurred. The ONO-5046 pretreatment did not affect the neutrophil sequestration in the lungs or in the other organs as determined by neutrophil counts in BALF and by the MPO assays. A neutrophil elastase inhibitor, ONO-5046, administered immediately before acid instillation attenuated the physiologic changes seen in the vehicle-treated animals. The drug blocked neutrophil elastase but

  12. CNS sites activated by renal pelvic epithelial sodium channels (ENaCs) in response to hypertonic saline in awake rats.

    Science.gov (United States)

    Goodwill, Vanessa S; Terrill, Christopher; Hopewood, Ian; Loewy, Arthur D; Knuepfer, Mark M

    2017-05-01

    In some patients, renal nerve denervation has been reported to be an effective treatment for essential hypertension. Considerable evidence suggests that afferent renal nerves (ARN) and sodium balance play important roles in the development and maintenance of high blood pressure. ARN are sensitive to sodium concentrations in the renal pelvis. To better understand the role of ARN, we infused isotonic or hypertonic NaCl (308 or 500mOsm) into the left renal pelvis of conscious rats for two 2hours while recording arterial pressure and heart rate. Subsequently, brain tissue was analyzed for immunohistochemical detection of the protein Fos, a marker for neuronal activation. Fos-immunoreactive neurons were identified in numerous sites in the forebrain and brainstem. These areas included the nucleus tractus solitarius (NTS), the lateral parabrachial nucleus, the paraventricular nucleus of the hypothalamus (PVH) and the supraoptic nucleus (SON). The most effective stimulus was 500mOsm NaCl. Activation of these sites was attenuated or prevented by administration of benzamil (1μM) or amiloride (10μM) into the renal pelvis concomitantly with hypertonic saline. In anesthetized rats, infusion of hypertonic saline but not isotonic saline into the renal pelvis elevated ARN activity and this increase was attenuated by simultaneous infusion of benzamil or amiloride. We propose that renal pelvic epithelial sodium channels (ENaCs) play a role in activation of ARN and, via central visceral afferent circuits, this system modulates fluid volume and peripheral blood pressure. These pathways may contribute to the development of hypertension. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Characterization of cucurbita maxima phloem serpin-1 (CmPS-1). A developmentally regulated elastase inhibitor.

    Science.gov (United States)

    Yoo, B C; Aoki, K; Xiang, Y; Campbell, L R; Hull, R J; Xoconostle-Cázares, B; Monzer, J; Lee, J Y; Ullman, D E; Lucas, W J

    2000-11-10

    We report on the molecular, biochemical, and functional characterization of Cucurbita maxima phloem serpin-1 (CmPS-1), a novel 42-kDa serine proteinase inhibitor that is developmentally regulated and has anti-elastase properties. CmPS-1 was purified to near homogeneity from C. maxima (pumpkin) phloem exudate and, based on microsequence analysis, the cDNA encoding CmPS-1 was cloned. The association rate constant (k(a)) of phloem-purified and recombinant His(6)-tagged CmPS-1 for elastase was 3.5 +/- 1.6 x 10(5) and 2.7 +/- 0.4 x 10(5) m(-)(1) s(-)(1), respectively. The fraction of complex-forming CmPS-1, X(inh), was estimated at 79%. CmPS-1 displayed no detectable inhibitory properties against chymotrypsin, trypsin, or thrombin. The elastase cleavage sites within the reactive center loop of CmPS-1 were determined to be Val(347)-Gly(348) and Val(350)-Ser(351) with a 3:2 molar ratio. In vivo feeding assays conducted with the piercing-sucking aphid, Myzus persicae, established a close correlation between the developmentally regulated increase in CmPS-1 within the phloem sap and the reduced ability of these insects to survive and reproduce on C. maxima. However, in vitro feeding experiments, using purified phloem CmPS-1, failed to demonstrate a direct effect on aphid survival. Likely roles of this novel phloem serpin in defense against insects/pathogens are discussed.

  14. The preparation of aneurysm model in rabbits by vessel ligation and elastase-induced technique

    International Nuclear Information System (INIS)

    Lu Chuan; Xie Qianyu; Liu Linxiang

    2010-01-01

    Objective: To establish an aneurysm model, which is quite similar to the human intracranial aneurysm in morphology, in rabbits by means of vessel ligation together with elastase-induced technique. Methods: Sixteen New Zealand white rabbits were used in this study. Distal carotid ligation and intraluminal elastase incubation was employed in ten rabbits (study group) to create aneurysm on the right common carotid artery. And surgical suture of a segment of the left carotid common artery was carried out in six rabbits (used as control group) to establish the aneurysm model. DSA exam of the created aneurysms by using catheterization via femoral artery was performed at one week and at one month after surgery. The patency, morphology and pathology of the aneurysms were observed. The results were statistically analyzed. Results: The aneurysms in both groups remained patent after they were created. Angiography one week after the surgery showed that all the aneurysms in study group were patent, while in control group only two aneurysms showed opacification with contrast medium and the remaining four aneurysms were all occluded. DSA at one month after the procedure demonstrated that all the aneurysms in study group remained patent, and the previous two patent aneurysms in control group became occluded. The mean width and length of the aneurysmal cavity in study group immediately after the procedure were (3.70 ± 0.16) mm and (6.53 ± 0.65) mm respectively, which enlarged to (5.06 ± 0.31) mm and (9.0 ± 0.52) mm respectively one month after the surgery. The difference in size changes was statistically significant (P < 0.05). Pathologically, almost complete absence of the internal elastic lamina and medial wall elastin of the aneurysms was observed. Conclusion: The aneurysm model prepared with vessel ligation together with elastase-induced technique carries high patent rate and possesses the feature of spontaneous growing, moreover, its morphology is quite similar to the

  15. Association of Low Fecal Elastase-1 and Non-Ulcer Dyspepsia

    Directory of Open Access Journals (Sweden)

    Mustafa Tahtaci

    2018-06-01

    Full Text Available Non-ulcer dyspepsia (NUD is a term used to define a set of symptoms that are believed to originate from the gastroduodenal region, and no underlying organic, systemic, or metabolic reason can be found. The majority of patients suffer from chronic symptoms although half of the patients report improvement in symptoms with time. The potential role exocrine pancreatic insufficiency in NUD patients has not been clarified yet. We aimed to identify exocrine pancreas function with pancreatic fecal elastase-1 in patients diagnosed with non-ulcer dyspepsia and no typical exocrine pancreatic insufficiency (EPI symptoms. Thirty-five patients referred to gastroenterology clinics with NUD and 35 people with no dyspeptic symptoms as a control group were included in this prospective study. Non-ulcer dyspepsia patients were classified as group 1 and control subjects classified as group 2. Upper gastrointestinal endoscopies were performed in both groups. Assessment of exocrine pancreatic function was performed by measuring fecal elastase-1 concentration with a commercial ELISA kit using polyclonal antibodies (BioServ Diagnostics in NUD patients compared to control subjects. Mean fecal elastase-1 levels were significantly lower in group 1 patients compared with group 2 (367.47 ± 43.27; 502.48 ± 50.94 respectively; p = 0.04. The percentage of the patients with EPI was significantly higher in group 1 (p = 0.02. Patients with NUD should be re-evaluated if they do not show satisfactory improvement with treatment. Exocrine pancreatic insufficiency was significantly higher in patients with NUD in our study. Evaluation for the presence of EPI can be a cost effective approach in management of refractory patients during the process of ruling out organic reasons.

  16. Effect of Elastase-induced Emphysema on the Force-generating Ability of the Diaphragm

    Science.gov (United States)

    Supinski, Gerald S.; Kelsen, Steven G.

    1982-01-01

    The effect of emphysema on the ability of the diaphragm to generate force was examined in costal diaphragm muscle strips from 10 Golden hamsters killed 18 mo after intratracheal injection of pancreatic elastase in a dose producing hyperinflation (mean total lung capacity [TLC] = 163% of control) and generalized panacinar emphysema. 13 saline-injected normal animals served as controls. The time course of isometric tension and the effect of alterations in muscle fiber and sarcomere length on the isometric tension (T) generated in response to tetanizing electrical stimuli (length-tension [L-T] relationship) were examined. Elastase administration caused an increase in diaphragm muscle thickness and reduction in the length of costal diaphragm muscle fibers measured in situ. Emphysema significantly increased the maximum tetanic tension as a result of hypertrophy. Maximal tension corrected for increases in muscle cross-sectional area (T/cm2), however, was the same in emphysematous (E) and control (C) animals. Emphysema also shifted the muscle fiber L-T curve of the diaphragm but not of a control muscle, the soleus, toward shorter lengths. In contrast to the effects of E on the diaphragm muscle fiber L-T curve, the sarcomere L-T curve was the same in E and C. Since the length at which tension was maximal correlated closely with sarcomere number (r = 0.94; P < 0.001) reduction in the number of sarcomeres in series in muscles from emphysematous animals appeared to explain the shift in the muscle fiber L-T curve. We conclude that in elastase-induced emphysema adaptive changes both in diaphragm cross-sectional area and sarcomere number augment the force-generating ability of the diaphragm. We speculate that changes in sarcomere number compensate for alterations in muscle fiber length resulting from chronic hyperinflation of the thorax, while diaphragmatic muscle hypertrophy represents a response to changes in respiratory load and/or diaphragm configuration (La

  17. INACTIVITY OF RECOMBINANT ELA2B PROVIDES A NEW EXAMPLE OF EVOLUTIONARY ELASTASE SILENCING IN HUMANS

    OpenAIRE

    Szepessy, Edit; Sahin-Tóth, Miklós

    2005-01-01

    BACKGROUND. The archetypal mammalian elastase (ELA1) is not expressed in the human pancreas, because evolutionary mutations suppressed transcription of the ELA1 gene. AIMS. In this study we tested the theory that the unique duplication of the ELA2 gene in humans might compensate for the loss of ELA1. METHODS. Recombinant ELA2A and ELA2B were expressed in Escherichia coli, and their activity was tested on Glt-Ala-Ala-Pro-Leu-p-nitroanilide, DQ elastin and bovine milk protein. RESULTS. Surprisi...

  18. Plant Proteinase Inhibitor BbCI Modulates Lung Inflammatory Responses and Mechanic and Remodeling Alterations Induced by Elastase in Mice

    Directory of Open Access Journals (Sweden)

    Rafael Almeida-Reis

    2017-01-01

    Full Text Available Background. Proteinases play a key role in emphysema. Bauhinia bauhinioides cruzipain inhibitor (BbCI is a serine-cysteine proteinase inhibitor. We evaluated BbCI treatment in elastase-induced pulmonary alterations. Methods.  C57BL/6 mice received intratracheal elastase (ELA group or saline (SAL group. One group of mice was treated with BbCI (days 1, 15, and 21 after elastase instillation, ELABC group. Controls received saline and BbCI (SALBC group. After 28 days, we evaluated respiratory mechanics, exhaled nitric oxide, and bronchoalveolar lavage fluid. In lung tissue we measured airspace enlargement, quantified neutrophils, TNFα-, MMP-9-, MMP-12-, TIMP-1-, iNOS-, and eNOS-positive cells, 8-iso-PGF2α, collagen, and elastic fibers in alveolar septa and airways. MUC-5-positive cells were quantified only in airways. Results. BbCI reduced elastase-induced changes in pulmonary mechanics, airspace enlargement and elastase-induced increases in total cells, and neutrophils in BALF. BbCI reduced macrophages and neutrophils positive cells in alveolar septa and neutrophils and TNFα-positive cells in airways. BbCI attenuated elastic and collagen fibers, MMP-9- and MMP-12-positive cells, and isoprostane and iNOS-positive cells in alveolar septa and airways. BbCI reduced MUC5ac-positive cells in airways. Conclusions. BbCI improved lung mechanics and reduced lung inflammation and airspace enlargement and increased oxidative stress levels induced by elastase. BbCI may have therapeutic potential in chronic obstructive pulmonary disease.

  19. TGF-β1 and granulocyte elastase in the evaluation of activity of inflammatory bowel disease. A pilot study

    Directory of Open Access Journals (Sweden)

    Irena Ciećko-Michalska

    2014-01-01

    Full Text Available Introduction: The aim was to assess the usefulness of TGF-β1 and elastase in the evaluation of activity of ulcerative colitis (UC and Crohn’s disease (CD.Material and Methods: 32 patients diagnosed with UC, 31 with CD and 30 healthy volunteers were enrolled in this study. Diagnosis of the disease was confirmed by videocolonoscopy and histopathological evaluation of intestinal biopsies. Disease activity was assessed by use of the Mayo Scoring System for Assessment of Ulcerative Colitis Activity in UC patients and by CDAI in CD patients. hsCRP was determined by the immunonephelometric method, TGF-β1 and elastase plasma concentration by ELISA. The results of the study were analyzed using Statistica and R statistical language.Results: In UC a positive correlation between disease activity and platelet level, hsCRP and TGF-β1 concentration was noted. Elastase concentration in UC patients was significantly higher than in CD, but there was no correlation with the activity of the disease. In CD patients we observed a positive correlation between disease activity and leukocytes, platelet levels and elastase concentration, and a very low correlation with hsCRP and TGF-β1.Discussion: Determination of TGF-β1 can be used for evaluation of inflammatory activity in UC and it is connected with elevated concentrations of CRP and platelets. To a lower extent TGF-β1 can also be used for evaluation of inflammatory activity in CD. Examination of elastase concentration may be useful in the assessment of CD activity. Plasma elastase concentration may be helpful in UC and CD differentiation. The preliminary results of this investigation seem promising; nevertheless, more studies are necessary.

  20. The fibrinogen cleavage product Aα-Val360, a specific marker of neutrophil elastase activity in vivo

    DEFF Research Database (Denmark)

    Carter, Richard I; Mumford, Richard A; Treonze, Kelly M

    2011-01-01

    Alpha-1-antitrypsin (A1AT) deficiency is the only recognised genetic risk factor for chronic obstructive pulmonary disease (COPD), a leading cause of morbidity and mortality worldwide. Since A1AT is the major inhibitor of neutrophil elastase (NE), this enzyme has become widely implicated in the p......Alpha-1-antitrypsin (A1AT) deficiency is the only recognised genetic risk factor for chronic obstructive pulmonary disease (COPD), a leading cause of morbidity and mortality worldwide. Since A1AT is the major inhibitor of neutrophil elastase (NE), this enzyme has become widely implicated...

  1. El litio y su relación con la acuaporina-2 y el canal de sodio ENaC

    Directory of Open Access Journals (Sweden)

    Luciano Galizia

    2012-04-01

    Full Text Available Desde hace más de cuarenta años que el litio es usado para el tratamiento de la enfermedad bipolar; recientes estudios sugieren también su utilidad en el trastorno cognitivo mínimo tipo amnésico. El litio es filtrado en el glomérulo y un 65-75% del mismo es reabsorbido en el túbulo contorneado proximal y en el asa ascendente de Henle por el transportador Na+, K+, 2Cl- y vía paracelular. Una pequeña fracción del litio entra en las células principales del túbulo colector por medio del canal epitelial de sodio sensible al amiloride (ENaC localizado en la membrana apical de la célula. Luego de 10- 20 años de tratamiento con litio los enfermos pueden desarrollar poliuria, acidosis tubular e insuficiencia renal crónica que puede terminar en una forma de diabetes que no responde a la arginina vasopresina llamada diabetes insípida nefrogénica. Se cree que estas fallas renales son consecuencias de una reducción en el número de moléculas de acuaporina 2 en la membrana apical. Las causas para esto son complejas. El litio es un poderoso inhibidor de la isoforma beta de la enzima glicógeno sintetasa quinasa y esto está asociado a una menor actividad de la adenilato ciclasa que lleva a una disminución en la concentración intracelular de cAMP. Esto finalmente interferiría con la síntesis de nuevas moléculas de acuaporina 2 y con el tráfico de ellas desde la zona subapical de la célula hacia la membrana celular, causando la disminución en la reabsorción de agua en la parte distal del nefrón.

  2. Inhibition of elastase-pulmonary emphysema in dominant-negative MafB transgenic mice.

    Science.gov (United States)

    Aida, Yasuko; Shibata, Yoko; Abe, Shuichi; Inoue, Sumito; Kimura, Tomomi; Igarashi, Akira; Yamauchi, Keiko; Nunomiya, Keiko; Kishi, Hiroyuki; Nemoto, Takako; Sato, Masamichi; Sato-Nishiwaki, Michiko; Nakano, Hiroshi; Sato, Kento; Kubota, Isao

    2014-01-01

    Alveolar macrophages (AMs) play important roles in the pathogenesis of chronic obstructive pulmonary disease (COPD). We previously demonstrated upregulation of the transcription factor MafB in AMs of mice exposed to cigarette smoke. The aim of this study was to elucidate the roles of MafB in the development of pulmonary emphysema. Porcine pancreatic elastase was administered to wild-type (WT) and dominant-negative (DN)-MafB transgenic (Tg) mice in which MafB activity was suppressed only in macrophages. We measured the mean linear intercept and conducted cell differential analysis of bronchoalveolar lavage (BAL) cells, surface marker analysis using flow cytometry, and immunohistochemical staining using antibodies to matrix metalloproteinase (MMP)-9 and MMP-12. Airspace enlargement of the lungs was suppressed significantly in elastase-treated DN-MafB Tg mice compared with treated WT mice. AMs with projected pseudopods were decreased in DN-MafB Tg mice. The number of cells intermediately positive for F4/80 and weakly or intermediately positive for CD11b, which are considered cell subsets of matured AMs, decreased in the BAL of DN-MafB Tg mice. Furthermore, MMP-9 and -12 were significantly downregulated in BAL cells of DN-MafB Tg mice. Because MMPs exacerbate emphysema, MafB may be involved in pulmonary emphysema development through altered maturation of macrophages and MMP expression.

  3. Emphysema induced by elastase enhances acute inflammatory pulmonary response to intraperitoneal LPS in rats.

    Science.gov (United States)

    da Fonseca, Lídia Maria Carneiro; Reboredo, Maycon Moura; Lucinda, Leda Marília Fonseca; Fazza, Thaís Fernanda; Rabelo, Maria Aparecida Esteves; Fonseca, Adenilson Souza; de Paoli, Flavia; Pinheiro, Bruno Valle

    2016-12-01

    Abnormalities in lungs caused by emphysema might alter their response to sepsis and the occurrence of acute lung injury (ALI). This study compared the extension of ALI in response to intraperitoneal lipopolysaccharide (LPS) injection in Wistar rats with and without emphysema induced by elastase. Adult male Wistar rats were randomized into four groups: control, emphysema without sepsis, normal lung with sepsis and emphysema with sepsis. Sepsis was induced, and 24 h later the rats were euthanised. The following analysis was performed: blood gas measurements, bronchoalveolar lavage (BAL), lung permeability and histology. Animals that received LPS showed significant increase in a lung injury scoring system, inflammatory cells in bronchoalveolar lavage (BAL) and IL-6, TNF-α and CXCL2 mRNA expression in lung tissue. Animals with emphysema and sepsis showed increased alveolocapillary membrane permeability, demonstrated by higher BAL/serum albumin ratio. In conclusion, the presence of emphysema induced by elastase increases the inflammatory response in the lungs to a systemic stimulus, represented in this model by the intraperitoneal injection of LPS. © 2016 The Authors. International Journal of Experimental Pathology © 2016 International Journal of Experimental Pathology.

  4. Role of α-Helical Structure in Organic Solvent-Activated Homodimer of Elastase Strain K

    Directory of Open Access Journals (Sweden)

    Chee Fah Wong

    2011-09-01

    Full Text Available Recombinant elastase strain K overexpressed from E. coli KRX/pCon2(3 was purified to homogeneity by a combination of hydrophobic interaction chromatography and ion exchange chromatography, with a final yield of 48% and a 25-fold increase in specific activity. The purified protein had exhibited a first ever reported homodimer size of 65 kDa by SDS-PAGE and MALDI-TOF, a size which is totally distinct from that of typically reported 33 kDa monomer from P. aeruginosa. The organic solvent stability experiment had demonstrated a stability pattern which completely opposed the rules laid out in previous reports in which activity stability and enhancement were observed in hydrophilic organic solvents such as DMSO, methanol, ethanol and 1-propanol. The high stability and enhancement of the enzyme in hydrophilic solvents were explained from the view of alteration in secondary structures. Elastinolytic activation and stability were observed in 25 and 50% of methanol, respectively, despite slight reduction in α-helical structure caused upon the addition of the solvent. Further characterization experiments had postulated great stability and enhancement of elastase strain K in broad range of temperatures, pHs, metal ions, surfactants, denaturing agents and substrate specificity, indicating its potential application in detergent formulation.

  5. Overhauser-enhanced MRI of elastase activity from in vitro human neutrophil degranulation.

    Directory of Open Access Journals (Sweden)

    Elodie Parzy

    Full Text Available Magnetic resonance imaging can reveal exquisite anatomical details. However several diseases would benefit from an imaging technique able to specifically detect biochemical alterations. In this context protease activity imaging is one of the most promising areas of research.We designed an elastase substrate by grafting stable nitroxide free radicals on soluble elastin. This substrate generates a high Overhauser magnetic resonance imaging (OMRI contrast upon digestion by the target proteases through the modulation of its rotational correlation time. The sensitivity is sufficient to generate contrasted images of the degranulation of neutrophils induced by a calcium ionophore from 2×10(4 cells per milliliter, well under the physiological neutrophils concentrations.These ex-vivo experiments give evidence that OMRI is suitable for imaging elastase activity from neutrophil degranulation. Provided that a fast protease-substrate is used these results open the door to better diagnoses of a number of important pathologies (cystic fibrosis, inflammation, pancreatitis by OMRI or Electron Paramagnetic Resonance Imaging in vivo. It also provides a long-expected method to monitor anti-protease treatments efficiency and help pharmaceutical research.

  6. Pseudomonas aeruginosa elastase cleaves a C-terminal peptide from human thrombin that inhibits host inflammatory responses

    DEFF Research Database (Denmark)

    van der Plas, Mariena J A; Bhongir, Ravi K V; Kjellström, Sven

    2016-01-01

    Pseudomonas aeruginosa is an opportunistic pathogen known for its immune evasive abilities amongst others by degradation of a large variety of host proteins. Here we show that digestion of thrombin by P. aeruginosa elastase leads to the release of the C-terminal thrombin-derived peptide FYT21...

  7. Activation of Pseudomonas aeruginosa elastase in Pseudomonas putida by triggering dissociation of the propeptide-enzyme complex

    NARCIS (Netherlands)

    Braun, P; Bitter, W; Tommassen, J

    2000-01-01

    The propeptide of Pseudomonas aeruginosa elastase functions both as an intramolecular chaperone required for the folding of the enzyme and as an inhibitor that prevents activity of the enzyme before its secretion into the extracellular medium. Since expression of the lasB gene, which encodes

  8. Lysophosphatidic acid inhibition of the accumulation of Pseudomonas aeruginosa PAO1 alginate, pyoverdin, elastase and LasA

    DEFF Research Database (Denmark)

    Laux, D.C.; Corson, J.M.; Givskov, Michael Christian

    2002-01-01

    . In the present study, a lysophospholipid, 1-paimitoyl-2-hydroxy-sn-glycero-3-phosphate [also called monopalmitoylphosphatidic acid (MPPA)], which accumulates in inflammatory exudates, was shown to inhibit the extracellular accumulation of P. aeruginosa PAO1 alginate, elastase, LasA protease and the siderophore...

  9. Comparison of fecal elastase-1 and pancreatic function testing in children.

    Science.gov (United States)

    Wali, Prateek D; Loveridge-Lenza, Beth; He, Zhaoping; Horvath, Karoly

    2012-02-01

    The fecal pancreatic elastase-1 (FE-1) test is considered a simple, noninvasive, indirect measure of pancreatic function. We aimed to evaluate the performance of the FE-1 test compared with the direct pancreatic function test (PFT) with secretin stimulation in children. Data of 70 children (6 months-17 years of age) who had both FE-1 test and PFT were analyzed. The average FE-1 concentration was 403 ± 142 μg/g. Eleven children had concentrations below 200  μg/g, 23 between 201 to 500 μg/g, and 36 were above 500 μg/g. The average pancreatic elastase activity measured on direct stimulation was 49.1 ± 38.6  μmol · min (-1)· ml(-1) and 11 children had activity below the established cutoff (10.5 μmol · min(-1) · ml(-1)). Among the 11 children with pathologic PFT, 7 had normal FE-1, 4 were in the intermediate range (201-500 μg/g), and none were in the low range (g). Among the 59 children with normal direct PFT 11 (19%) had pathologic (g) and 19 (32%) had intermediate FE-1 tests. Twenty-nine children had both normal FE-1 concentration and normal PFT, giving a negative predictive value of 80%. The correlation between pancreatic elastase activity and FE-1 concentration was poor (r = 0.190). The sensitivity of the FE-1 test was found to be 41.7%, whereas the specificity was 49.2%. The positive predictive value of the FE-1 test was only 14%. The FE-1 test is a simple, noninvasive, indirect method; however, ordering physicians should be aware of its limitations. It can give false-positive results and has low sensitivity in children with mild pancreatic insufficiency without cystic fibrosis and in those with isolated pancreatic enzyme deficiencies.

  10. Analogues of Cucurbita maxima trypsin inhibitor III (CMTI-III) with elastase inhibitory activity.

    Science.gov (United States)

    Rózycki, J; Kupryszewski, G; Rolka, K; Ragnarsson, U; Zbyryt, T; Krokoszyńska, I; Wilusz, T

    1994-04-01

    Three new CMTI-III analogues containing the Val residue in the reactive site (position 5) were synthesized by the solid-phase method. The analogues displayed an elastase inhibitory activity. It is shown that the removal of the N-terminal Arg residue and the introduction of the Gly-Pro-Gln tripeptide in the region 23-25 decreases the antielastase activity by two orders of magnitude. The removal of the disulfide bridge in positions 16-28 and the substitution of Ala for Cys16 and Gly for Cys28 decreases the activity (measured as Ka with HLE) by five orders of magnitude as compared with [Val5]CMTI-III.

  11. Characterization of a Mouse Model of Emphysema Induced by Multiple Instillations of Low-Dose Elastase

    Directory of Open Access Journals (Sweden)

    Milena V. Oliveira

    2016-10-01

    Full Text Available Many experimental models have been proposed to study the pathophysiological features of emphysema, as well as to search for new therapeutic approaches for acute or chronically injured lung parenchyma. We aimed to characterize an emphysema model induced by multiple instillations of elastase by tracking the changes in inflammation, remodeling, and cardiac function after each instillation. Forty-eight C57BL/6 mice were randomly assigned across 2 groups. Emphysema (ELA animals received 1, 2, 3, or 4 intratracheal instillations of pancreatic porcine elastase (PPE, 0.2 IU with a 1-week interval between them. Controls (C received saline following the same protocol. Before and after implementation of the protocol, animals underwent echocardiographic analysis. After the first instillation of PPE, the percentage of mononuclear cells in the lung parenchyma was increased compared to C (p = 0.0001. The second instillation resulted in hyperinflated alveoli, increased mean linear intercept, and reduced elastic fiber content in lung parenchyma compared to C (p=0.0197. Following the third instillation, neutrophils and collagen fiber content in alveolar septa and airways were increased, whereas static lung elastance was reduced compared to C (p=0.0094. After the fourth instillation, the percentage of M1 macrophages in lungs; levels of interleukin-1beta, keratinocyte-derived chemokine, hepatocyte growth factor, and vascular endothelial growth factor; and collagen fiber content in the pulmonary vessel wall were increased compared to C (p=0.0096. At this time point, pulmonary arterial hypertension was apparent, with increased diastolic right ventricular wall thickness. In conclusion, the initial phase of emphysema was characterized by lung inflammation with predominance of mononuclear cells, whereas at the late stage, impairment of pulmonary and cardiovascular functions was observed. This model enables analysis of therapies at different time points during controlled

  12. Constitutive and inducible expression of SKALP/elafin provides anti-elastase defense in human epithelia.

    Science.gov (United States)

    Pfundt, R; van Ruissen, F; van Vlijmen-Willems, I M; Alkemade, H A; Zeeuwen, P L; Jap, P H; Dijkman, H; Fransen, J; Croes, H; van Erp, P E; Schalkwijk, J

    1996-01-01

    Skin-derived antileukoproteinase (SKALP), also known as elafin, is a serine proteinase inhibitor first discovered in keratinocytes from hyperproliferative human epidermis. In addition to the proteinase inhibiting domain which is directed against polymorphonuclear leukocyte (PMN) derived enzymes such as elastase and proteinase 3, SKALP contains multiple transglutaminase (TGase) substrate domains which enable crosslinking to extracellular and cell envelope proteins. Here we show that SKALP is constitutively expressed in several epithelia that are continuously subjected to inflammatory stimuli, such as the oral cavity and the vagina where it co-localizes with type 1 TGase. All epithelia from sterile body cavities are negative for SKALP. In general, stratified squamous epithelia are positive, whereas pseudostratified epithelia, simple/glandular epithelia and normal epidermis are negative. SKALP was found in fetal tissues of the oral cavity from 17 wk gestation onwards where it continued to be expressed up to adult life. Remarkably, in fetal epidermis SKALP was found from week 28 onwards, but was downregulated to undetectable levels in neonatal skin within three months, suggesting a role during pregnancy in feto-maternal interactions or in the early maturation phase of the epidermis. Immunoelectron microscopy revealed the presence of SKALP in secretory vesicles including the lamellar granules. In culture models for epidermal keratinocytes we found that expression of the endogenous SKALP gene provided protection against cell detachment caused by purified elastase or activated PMNs. Addition of exogenous recombinant SKALP fully protected the keratinocytes against PMN-dependent detachment whereas superoxide dismutase and catalase were only marginally effective. These findings strongly suggest that the constitutive expression of SKALP in squamous epithelia, and the inducible expression in epidermis participate in the control of epithelial integrity, by inhibiting PMN

  13. Elafin, an elastase-specific inhibitor, is cleaved by its cognate enzyme neutrophil elastase in sputum from individuals with cystic fibrosis.

    LENUS (Irish Health Repository)

    Guyot, Nicolas

    2008-11-21

    Elafin is a neutrophil serine protease inhibitor expressed in lung and displaying anti-inflammatory and anti-bacterial properties. Previous studies demonstrated that some innate host defense molecules of the cystic fibrosis (CF) and chronic obstructive pulmonary disease airways are impaired due to increased proteolytic degradation observed during lung inflammation. In light of these findings, we thus focused on the status of elafin in CF lung. We showed in the present study that elafin is cleaved in sputum from individuals with CF. Pseudomonas aeruginosa-positive CF sputum, which was found to contain lower elafin levels and higher neutrophil elastase (NE) activity compared with P. aeruginosa-negative samples, was particularly effective in cleaving recombinant elafin. NE plays a pivotal role in the process as only NE inhibitors are able to inhibit elafin degradation. Further in vitro studies demonstrated that incubation of recombinant elafin with excess of NE leads to the rapid cleavage of the inhibitor. Two cleavage sites were identified at the N-terminal extremity of elafin (Val-5-Lys-6 and Val-9-Ser-10). Interestingly, purified fragments of the inhibitor (Lys-6-Gln-57 and Ser-10-Gln-57) were shown to still be active for inhibiting NE. However, NE in excess was shown to strongly diminish the ability of elafin to bind lipopolysaccharide (LPS) and its capacity to be immobilized by transglutamination. In conclusion, this study provides evidence that elafin is cleaved by its cognate enzyme NE present at excessive concentration in CF sputum and that P. aeruginosa infection promotes this effect. Such cleavage may have repercussions on the innate immune function of elafin.

  14. Anti–elastase, anti–tyrosinase and matrix metalloproteinase–1 inhibitory activity of earthworm extracts as potential new anti–aging agent

    Directory of Open Access Journals (Sweden)

    Nurhazirah Azmi

    2014-05-01

    Conclusions: Earthworms extract showed effective inhibition of tyrosinase, elastase and MMP-1 activities. Therefore, this experiment further rationalizes the traditional use of this worm extracts which may be useful as an anti-wrinkle agent.

  15. Adenovirus vector expressing keratinocyte growth factor using CAG promoter impairs pulmonary function of mice with elastase-induced emphysema.

    Science.gov (United States)

    Oki, Hiroshi; Yazawa, Takuya; Baba, Yasuko; Kanegae, Yumi; Sato, Hanako; Sakamoto, Seiko; Goto, Takahisa; Saito, Izumu; Kurahashi, Kiyoyasu

    2017-07-01

    Pulmonary emphysema impairs quality of life and increases mortality. It has previously been shown that administration of adenovirus vector expressing murine keratinocyte growth factor (KGF) before elastase instillation prevents pulmonary emphysema in mice. We therefore hypothesized that therapeutic administration of KGF would restore damage to lungs caused by elastase instillation and thus improve pulmonary function in an animal model. KGF expressing adenovirus vector, which prevented bleomycin-induced pulmonary fibrosis in a previous study, was constructed. Adenovirus vector (1.0 × 10 9 plaque-forming units) was administered intratracheally one week after administration of elastase into mouse lungs. One week after administration of KGF-vector, exercise tolerance testing and blood gas analysis were performed, after which the lungs were removed under deep anesthesia. KGF-positive pneumocytes were more numerous, surfactant protein secretion in the airspace greater and mean linear intercept of lungs shorter in animals that had received KGF than in control animals. Unexpectedly, however, arterial blood oxygenation was worse in the KGF group and maximum running speed, an indicator of exercise capacity, had not improved after KGF in mice with elastase-induced emphysema, indicating that KGF-expressing adenovirus vector impaired pulmonary function in these mice. Notably, vector lacking KGF-expression unit did not induce such impairment, implying that the KGF expression unit itself may cause the damage to alveolar cells. Possible involvement of the CAG promoter used for KGF expression in impairing pulmonary function is discussed. © 2017 The Societies and John Wiley & Sons Australia, Ltd.

  16. The effect of garlic extract on the expression of genes elastase and exotoxin A in Pseudomonas aeruginosa

    Directory of Open Access Journals (Sweden)

    Batoul Kavyani

    2016-11-01

    Full Text Available Background: Multidrug-resistant bacteria make many problems in clinical therapy, design and manufacture of synthetic drugs. Pseudomonas aeruginosa is one of the most important multidrug-resistance bacteria leads to variety infections in human especially in immunocompromised, patients with severe burns, and nosocomial infections. It Recent years, this organism makes a big challenge in clinical treatment of infections using a wide range of antibiotics. Medicinal herbs for thousands of years to prevent or treat infectious diseases were considered. Today, pharmacists have high interest of using medicinal herbs to prepare a new antimicrobial compounds. The goal of this study was to investigation the effect of aqueous and alcoholic extract of fresh garlic on the expression of genes encoding elastase and exotoxin A virulence factors, in P. aeruginosa PAO1 strain. Methods: Present study was an experimental study and performed from 2015 to 2016 in Hamadan University of Medical Science, Iran. The minimal inhibitory concentration (MIC and minimal bactericidal concentration (MBC of aqueous and alcoholic extract of garlic was determined. Then in order to investigation the gene expression of elastase and exotoxin A genes, quantitative real-time polymerase chain reaction (qPCR method was performed at sub-MBC concentrations. Results: According to the results aqueous extracts of garlic had better impact in comparison with alcoholic alone. At concentration of 64 and 8 mg/ml of aqueous extract the expression of both elastase and exotoxin A genes were decreased. Although, the expression of elastase gene was most affected by garlic at different concentrations than exotoxin A. Conclusion: The results suggested that the compositions of garlic extracts can inhibit the production of virulence factors in P. aeruginosa. So in order to treat infectious diseases in the near future, medicinal plants known as new antimicrobial drugs can be used alone or with antibiotic drugs

  17. Alterations in pulmonary structure by elastase administration in a model of emphysema in mice is associated with functional disturbances

    Directory of Open Access Journals (Sweden)

    D. Vidal

    2012-05-01

    Full Text Available Several experimental studies of pulmonary emphysema using animal models have been described in the literature. However, only a few of these studies have focused on the assessment of ergometric function as a non-invasive technique to validate the methodology used for induction of experimental emphysema. Additionally, functional assessments of emphysema are rarely correlated with morphological pulmonary abnormalities caused by induced emphysema. The present study aimed to evaluate the effects of elastase administered by tracheal puncture on pulmonary parenchyma and their corresponding functional impairment. This was evaluated by measuring exercise capacity in C57Bl/6 mice in order to establish a reproducible and safe methodology of inducing experimental emphysema. Thirty six mice underwent ergometric tests before and 28 days after elastase administration. Pancreatic porcine elastase solution was administered by tracheal puncture, which resulted in a significantly decreased exercise capacity, shown by a shorter distance run (−30.5% and a lower mean velocity (−15%, as well as in failure to increase the elimination of carbon dioxide. The mean linear intercept increased significantly by 50% in tracheal elastase administration. In conclusion, application of elastase by tracheal function in C57Bl/6 induces emphysema, as validated by morphometric analyses, and resulted in a significantly lower exercise capacity, while resulting in a low mortality rate. Resumo: Vários estudos experimentais de enfisema pulmonar em modelos animais têm sido descritos na literatura científica. No entanto, apenas alguns destes estudos têm sido concentrados na avaliação da função ergométrica como técnica não-invasiva para validar a metodologia utilizada para a indução do enfisema experimental. Além disso, as avaliações funcionais de enfisema raramente se encontram correlacionadas com anomalias morfológicas pulmonares

  18. Inhibition of neutrophil elastase and metalloprotease-9 of human adenocarcinoma gastric cells by chamomile (Matricaria recutita L.) infusion.

    Science.gov (United States)

    Bulgari, Michela; Sangiovanni, Enrico; Colombo, Elisa; Maschi, Omar; Caruso, Donatella; Bosisio, Enrica; Dell'Agli, Mario

    2012-12-01

    This study investigated whether the antiinflammatory effect of chamomile infusion at gastric level could be ascribed to the inhibition of metalloproteinase-9 and elastase. The infusions from capitula and sifted flowers (250-1500 µg/mL) and individual flavonoids (10 µM) were tested on phorbol 12-myristate 13-acetate-stimulated AGS cells and human neutrophil elastase. The results indicate that the antiinflammatory activity associated with chamomile infusions from both the capitula and sifted flowers is most likely due to the inhibition of neutrophil elastase and gastric metalloproteinase-9 activity and secretion; the inhibition occurring in a concentration dependent manner. The promoter activity was inhibited as well and the decrease of metalloproteinase-9 expression was found to be associated with the inhibition of NF-kB driven transcription. The results further indicate that the flavonoid-7-glycosides, major constituents of chamomile flowers, may be responsible for the antiinflammatory action of the chamomile infusion observed here. Copyright © 2012 John Wiley & Sons, Ltd.

  19. Comparison of monoclonal and polyclonal ELISAs for fecal elastase in patients with cystic fibrosis and pancreatic insufficiency.

    Science.gov (United States)

    Borowitz, Drucy; Lin, Rong; Baker, Susan S

    2007-02-01

    Two enzyme-linked immunosorbent assay methodologies are used to detect pancreatic insufficiency: monoclonal and polyclonal. We sought to compare these assays in patients with cystic fibrosis and to correlate these with the coefficient of fat absorption (CFA). As part of a larger study, subjects had stool elastase measured by both methods while taking exogenous enzymes. Subjects subsequently stopped enzymes and had a fecal fat balance study performed; the CFA was then calculated. One hundred twenty-four subjects participated in this substudy. The median values for the monoclonal and polyclonal assays were 0.3 and 22.75 microg/g, respectively. The correlation coefficient between the 2 tests was 0.86 (P definition of pancreatic insufficiency was set at a CFA definition of pancreatic insufficiency was set at <100 microg/g, then the monoclonal and polyclonal assay positive predictive values were 97.6% (120 of 123) and 97.4% (111 of 114), respectively. The positive predictive value of both monoclonal and polyclonal fecal elastase in patients with cystic fibrosis is extremely good; however, correlation of either test with CFA was poor. The median value for the polyclonal elastase assay is higher than for the monoclonal assay, which could potentially lead to lower sensitivity of the polyclonal assay at lower cutpoints for the monoclonal assay is used.

  20. Establishment of qualities mammography according to the standard IEC-61267 in the laboratory of metrology of ionizing radiation of the National Center of Dosimetry and enlargement of the accreditation by ENAC

    International Nuclear Information System (INIS)

    Roig Petit, F.; Mestre de Juan, V.; Alabau Albors, J.; Palma Copete, J.; Ruiz Rodriguez, J. C.; Pons Mocholi, S.

    2013-01-01

    The extension of the accreditation of the laboratory of the National Center Dosimetry (No. 58/LC10.036) by the national accreditation entity (ENAC), according to the ISO 17025 standard [2], for the standard qualities of mammography by the IEC 61267 comes to meet part of the needs that demand our health care environment in terms of radiation measuring instruments calibration. This work intends to publicize this enlargement commenting on the different phases of the process to get the accreditation. (Author)

  1. Multimodal imaging in the elastase-induced aneurysm model in rabbits: a comparative study using serial DSA, MRA and CTA

    International Nuclear Information System (INIS)

    Doerfler, A.; Becker, W.; Wanke, I.; Goericke, S.; Oezkan, N.; Forsting, M.

    2004-01-01

    Background and Purpose: The elastase-induced aneurysm model in rabbits has proved to be suitable for testing new endovascular occlusion devices. The purpose of this study was to evaluate different imaging modalities for the depiction of anatomy and size of elastase-induced aneurysms and for serial follow-up imaging. Materials and Methods: Elastase-induced aneurysms were created in eight Chinchilla bastard rabbits by endoluminal incubation of porcine elastase. Serial imaging was performed using intravenous DSA (IVDSA), contrast-enhanced MRA (CEMRA), and time-of-flight MRA (TOF) 14 days, 4 weeks and 3 months after aneurysm creation. Intraarterial DSA (IADSA) and CT angiography (CTA) were performed after 3 months. Aneurysm size and geometry (height H, width W, neck width N) were compared. Results: On IVDSA after two weeks mean aneurysm height was 6.2 mm (range 2.8-11.0 mm), mean aneurysm neck width was 2.7 mm (range 2.0-4.2 mm) and mean aneurysm neck width was 2.7 mm (range 2.0-4.2 mm). We did not observed any statistically significant change in aneurysm dimensions during follow-up at 4 weeks (CEMRA: H: 5.4, W: 2.4, N: 2.4; TOF: H: 5.7, W: 2.4, N: 2.7) and 3 months (CEMRA: H: 5.8, W: 2.6, N: 2.6; TOF: H: 6.9, W: 2.8, N: 3.0). Aneurysm dimensions could be best seen on IADSA (H: 6.2, W: 3.0, N: 2.7) with good correlation to CTA (r=0.94; H: 6.1, W: 2.8, N: 2.6), CE-MRA (r=0.92), and TOF (r=0.97). TOF was superior to CEMRA in delineating the aneurysm wall. Conclusions: Serial imaging using MRA, CTA or intravenous and intraarterial angiography is feasible in the elastase-induced aneurysm model. Contrast-enhanced MRA, TOF-MRA and CTA showed good correlation to IADSA and are all suitable for non-invasive pretherapeutic measurement of aneurysm size. (orig.) [de

  2. Establishment of qualities mammography according to the standard IEC-61267 in the laboratory of metrology of ionizing radiation of the National Center of Dosimetry and enlargement of the accreditation by ENAC; Establecimiento de las calidades de mamografia segun la norma IEC-61267 en el laboratorio de metrologia de radiaciones ionizantes del centro nacional de dosimetria (CND) y proceso de ampliacion de su acreditacion por ENAC

    Energy Technology Data Exchange (ETDEWEB)

    Roig Petit, F.; Mestre de Juan, V.; Alabau Albors, J.; Palma Copete, J.; Ruiz Rodriguez, J. C.; Pons Mocholi, S.

    2013-07-01

    The extension of the accreditation of the laboratory of the National Center Dosimetry (No. 58/LC10.036) by the national accreditation entity (ENAC), according to the ISO 17025 standard [2], for the standard qualities of mammography by the IEC 61267 comes to meet part of the needs that demand our health care environment in terms of radiation measuring instruments calibration. This work intends to publicize this enlargement commenting on the different phases of the process to get the accreditation. (Author)

  3. Leukotriene B4-Neutrophil Elastase Axis Drives Neutrophil Reverse Transendothelial Cell Migration In Vivo

    Science.gov (United States)

    Colom, Bartomeu; Bodkin, Jennifer V.; Beyrau, Martina; Woodfin, Abigail; Ody, Christiane; Rourke, Claire; Chavakis, Triantafyllos; Brohi, Karim; Imhof, Beat A.; Nourshargh, Sussan

    2015-01-01

    Summary Breaching endothelial cells (ECs) is a decisive step in the migration of leukocytes from the vascular lumen to the extravascular tissue, but fundamental aspects of this response remain largely unknown. We have previously shown that neutrophils can exhibit abluminal-to-luminal migration through EC junctions within mouse cremasteric venules and that this response is elicited following reduced expression and/or functionality of the EC junctional adhesion molecule-C (JAM-C). Here we demonstrate that the lipid chemoattractant leukotriene B4 (LTB4) was efficacious at causing loss of venular JAM-C and promoting neutrophil reverse transendothelial cell migration (rTEM) in vivo. Local proteolytic cleavage of EC JAM-C by neutrophil elastase (NE) drove this cascade of events as supported by presentation of NE to JAM-C via the neutrophil adhesion molecule Mac-1. The results identify local LTB4-NE axis as a promoter of neutrophil rTEM and provide evidence that this pathway can propagate a local sterile inflammatory response to become systemic. PMID:26047922

  4. Leukotriene B4-Neutrophil Elastase Axis Drives Neutrophil Reverse Transendothelial Cell Migration In Vivo.

    Science.gov (United States)

    Colom, Bartomeu; Bodkin, Jennifer V; Beyrau, Martina; Woodfin, Abigail; Ody, Christiane; Rourke, Claire; Chavakis, Triantafyllos; Brohi, Karim; Imhof, Beat A; Nourshargh, Sussan

    2015-06-16

    Breaching endothelial cells (ECs) is a decisive step in the migration of leukocytes from the vascular lumen to the extravascular tissue, but fundamental aspects of this response remain largely unknown. We have previously shown that neutrophils can exhibit abluminal-to-luminal migration through EC junctions within mouse cremasteric venules and that this response is elicited following reduced expression and/or functionality of the EC junctional adhesion molecule-C (JAM-C). Here we demonstrate that the lipid chemoattractant leukotriene B4 (LTB4) was efficacious at causing loss of venular JAM-C and promoting neutrophil reverse transendothelial cell migration (rTEM) in vivo. Local proteolytic cleavage of EC JAM-C by neutrophil elastase (NE) drove this cascade of events as supported by presentation of NE to JAM-C via the neutrophil adhesion molecule Mac-1. The results identify local LTB4-NE axis as a promoter of neutrophil rTEM and provide evidence that this pathway can propagate a local sterile inflammatory response to become systemic. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Association of faecal elastase 1 with non-fasting triglycerides in type 2 diabetes.

    Science.gov (United States)

    Rathmann, Wolfgang; Haastert, Burkhard; Oscarsson, Jan; Berglind, Niklas; Lindkvist, Björn; Wareham, Nicholas J

    2016-01-01

    Intestinal absorption of esterified fatty acids depends on exocrine pancreatic function and influences plasma triglycerides levels. The aim was to investigate the association of reduced exocrine pancreatic function (low fecal elastase-1; FE1) with plasma triglycerides in type 2 diabetes and controls without diabetes. FE1 (μg/g stool) and non-fasting plasma triglyceride measurements were undertaken in 544 type 2 diabetes patients (age: 63 ± 8 years) randomly selected from diabetes registers in Cambridgeshire (UK), and 544 matched controls (age, sex, practice) without diabetes. Linear regression models were fitted using FE1 as dependent and log-triglycerides as independent variable adjusting for sex, age, body mass index, alcohol consumption, serum lipase, HbA1c, and smoking. FE1 concentrations were lower (mean ± SD: 337 ± 204 vs. 437 ± 216 μg/g, p triglycerides were higher (geometric mean */: standard deviation factor: 2.2*/:1.9 vs. 1.6*/:1.8 mmol/l, p triglycerides was associated with 4.5 μg/g higher FE1 concentrations (p triglycerides (significant only in controls). Non-fasting triglycerides were positively related to FE1 in both type 2 diabetes and controls suggesting that impairment of exocrine pancreas function is influencing plasma triglycerides. Marked loss of exocrine pancreatic function had the opposite effect, resulting in higher levels of plasma triglycerides. Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  6. A murine model of elastase- and cigarette smoke-induced emphysema

    Directory of Open Access Journals (Sweden)

    Rubia Rodrigues

    Full Text Available ABSTRACT Objective: To describe a murine model of emphysema induced by a combination of exposure to cigarette smoke (CS and instillation of porcine pancreatic elastase (PPE. Methods: A total of 38 C57BL/6 mice were randomly divided into four groups: control (one intranasal instillation of 0.9% saline solution; PPE (two intranasal instillations of PPE; CS (CS exposure for 60 days; and CS + PPE (two intranasal instillations of PPE + CS exposure for 60 days. At the end of the experimental protocol, all animals were anesthetized and tracheostomized for calculation of respiratory mechanics parameters. Subsequently, all animals were euthanized and their lungs were removed for measurement of the mean linear intercept (Lm and determination of the numbers of cells that were immunoreactive to macrophage (MAC-2 antigen, matrix metalloproteinase (MMP-12, and glycosylated 91-kDa glycoprotein (gp91phox in the distal lung parenchyma and peribronchial region. Results: Although there were no differences among the four groups regarding the respiratory mechanics parameters assessed, there was an increase in the Lm in the CS + PPE group. The numbers of MAC-2-positive cells in the peribronchial region and distal lung parenchyma were higher in the CS + PPE group than in the other groups, as were the numbers of cells that were positive for MMP-12 and gp91phox, although only in the distal lung parenchyma. Conclusions: Our model of emphysema induced by a combination of PPE instillation and CS exposure results in a significant degree of parenchymal destruction in a shorter time frame than that employed in other models of CS-induced emphysema, reinforcing the importance of protease-antiprotease imbalance and oxidant-antioxidant imbalance in the pathogenesis of emphysema.

  7. Serological assessment of neutrophil elastase activity on elastin during lung ECM remodeling.

    Science.gov (United States)

    Kristensen, Jacob H; Karsdal, Morten A; Sand, Jannie Mb; Willumsen, Nicholas; Diefenbach, Claudia; Svensson, Birte; Hägglund, Per; Oersnes-Leeming, Diana J

    2015-05-03

    During the pathological destruction of lung tissue, neutrophil elastase (NE) degrades elastin, one of the major constituents of lung parenchyma. However there are no non-invasive methods to quantify NE degradation of elastin. We selected specific elastin fragments generated by NE for antibody generation and developed an ELISA assay (EL-NE) for the quantification of NE-degraded elastin. Monoclonal antibodies were developed against 10 NE-specific cleavage sites on elastin. One EL-NE assay was tested for analyte stability, linearity and intra- and inter-assay variation. The NE specificity was demonstrated using elastin cleaved in vitro with matrix metalloproteinases (MMPs), cathepsin G (CatG), NE and intact elastin. Clinical relevance was assessed by measuring levels of NE-generated elastin fragments in serum of patients diagnosed with idiopathic pulmonary fibrosis (IPF, n = 10) or lung cancer (n = 40). Analyte recovery of EL-NE for human serum was between 85% and 104%, the analyte was stable for four freeze/thaw cycles and after 24 h storage at 4°C. EL-NE was specific for NE-degraded elastin. Levels of NE-generated elastin fragments for elastin incubated in the presence of NE were 900% to 4700% higher than those seen with CatG or MMP incubation or in intact elastin. Serum levels of NE-generated elastin fragments were significantly increased in patients with IPF (137%, p = 0.002) and in patients with lung cancer (510%, p elastin. The EL-NE assay was able to specifically quantify NE-degraded elastin in serum. Serum levels of NE-degraded elastin might be used to detect excessive lung tissue degradation in lung cancer and IPF.

  8. Characterisation of Neutropenia-Associated Neutrophil Elastase Mutations in a Murine Differentiation Model In Vitro and In Vivo.

    Directory of Open Access Journals (Sweden)

    Michael Wiesmeier

    Full Text Available Severe congenital neutropenia (SCN is characterised by a differentiation block in the bone marrow and low neutrophil numbers in the peripheral blood, which correlates with increased risk of bacterial infections. Several underlying gene defects have been identified in SCN patients. Mutations in the neutrophil elastase (ELANE gene are frequently found in SCN and cyclic neutropenia. Both mislocalization and misfolding of mutant neutrophil elastase protein resulting in ER stress and subsequent induction of the unfolded protein response (UPR have been proposed to be responsible for neutrophil survival and maturation defects. However, the detailed molecular mechanisms still remain unclear, in part due to the lack of appropriate in vitro and in vivo models. Here we used a system of neutrophil differentiation from immortalised progenitor lines by conditional expression of Hoxb8, permitting the generation of mature near-primary neutrophils in vitro and in vivo. NE-deficient Hoxb8 progenitors were reconstituted with murine and human forms of typical NE mutants representative of SCN and cyclic neutropenia, and differentiation of the cells was analysed in vitro and in vivo. ER stress induction by NE mutations could be recapitulated during neutrophil differentiation in all NE mutant-reconstituted Hoxb8 cells. Despite ER stress induction, no change in survival, maturation or function of differentiating cells expressing either murine or human NE mutants was observed. Further analysis of in vivo differentiation of Hoxb8 cells in a murine model of adoptive transfer did not reveal any defects in survival or differentiation in the mouse. Although the Hoxb8 system has been found to be useful for dissection of defects in neutrophil development, our findings indicate that the use of murine systems for analysis of NE-mutation-associated pathogenesis is complicated by differences between humans and mice in the physiology of granulopoiesis, which may go beyond possible

  9. The influence of hemodynamic forces on biomarkers in the walls of elastase-induced aneurysms in rabbits

    Energy Technology Data Exchange (ETDEWEB)

    Kadirvel, Ramanathan; Ding, Yong-Hong; Dai, Daying; Danielson, Mark A.; Lewis, Debra A.; Cloft, Harry J.; Kallmes, David F. [Mayo Clinic College of Medicine, Department of Radiology, Rochester, MN (United States); Zakaria, Hasballah; Robertson, Anne M. [University of Pittsburgh, Department of Mechanical Engineering, Pittsburgh, PA (United States)

    2007-12-15

    Biological and biophysical factors have been shown to play an important role in the initiation, progression, and rupture of intracranial aneurysms. The purpose of this study was to evaluate the association between hemodynamic forces and markers of vascular remodeling in elastase-induced saccular aneurysms in rabbits. Elastase-induced aneurysms were created at the origin of the right common carotid artery in rabbits. Hemodynamic parameters were estimated using computational fluid dynamic simulations based on 3-D-reconstructed models of the vasculature. Expression of matrix metalloproteinases (MMPs), their inhibitors (TIMPs) and markers of vascular remodeling were measured in different spatial regions within the aneurysms. Altered expression of biological markers relative to controls was correlated with the locations of subnormal time-averaged wall shear stress (WSS) but not with the magnitude of pressure. In the aneurysms, WSS was low and expression of biological markers was significantly altered in a time-dependent fashion. At 2 weeks, an upregulation of active-MMP-2, downregulation of TIMP-1 and TIMP-2, and intact endothelium were found in aneurysm cavities. However, by 12 weeks, endothelial cells were absent or scattered, and levels of pro- and active-MMP-2 were not different from those in control arteries, but pro-MMP-9 and both TIMPs were upregulated. These results reveal a strong, spatially localized correlation between diminished WSS and differential expression of biological markers of vascular remodeling in elastase-induced saccular aneurysms. The ability of the wall to function and maintain a healthy endothelium in a low shear environment appears to be significantly impaired by chronic exposure to low WSS. (orig.)

  10. Selective modulation of the CD4 molecular complex by Pseudomonas aeruginosa alkaline protease and elastase

    DEFF Research Database (Denmark)

    Pedersen, B K; Kharazmi, A; Theander, T G

    1987-01-01

    The binding of monoclonal antibodies against CD4 was specifically inhibited by treatment of human CD4+ cells with either alkaline protease (AP) or elastase (Ela), purified from Pseudomonas aeruginosa. Binding of antibodies against CD3 (pan T), CD5 (pan T), CD8 (T suppressor/cytotoxic), HLA-ABC, HLA......-DR, HLA-DQ, HLA-DP/DR, and beta 2 microglobulin was not inhibited by AP or Ela. Heat-inactivation of the proteases at 65 degrees C for 20 min or treatment with the metal chelator EDTA abolished the inhibitory activity of both proteases. These findings may serve to develop novel immunological methods...

  11. Measurement of fecal elastase improves performance of newborn screening for cystic fibrosis.

    Science.gov (United States)

    Barben, Juerg; Rueegg, Corina S; Jurca, Maja; Spalinger, Johannes; Kuehni, Claudia E

    2016-05-01

    The aim of newborn screening (NBS) for CF is to detect children with 'classic' CF where early treatment is possible and improves prognosis. Children with inconclusive CF diagnosis (CFSPID) should not be detected, as there is no evidence for improvement through early treatment. No algorithm in current NBS guidelines explains what to do when sweat test (ST) fails. This study compares the performance of three different algorithms for further diagnostic evaluations when first ST is unsuccessful, regarding the numbers of children detected with CF and CFSPID, and the time until a definite diagnosis. In Switzerland, CF-NBS was introduced in January 2011 using an IRT-DNA-IRT algorithm followed by a ST. In children, in whom ST was not possible (no or insufficient sweat), 3 different protocols were applied between 2011 and 2014: in 2011, ST was repeated until it was successful (protocol A), in 2012 we proceeded directly to diagnostic DNA testing (protocol B), and 2013-2014, fecal elastase (FE) was measured in the stool, in order to determine a pancreas insufficiency needing immediate treatment (protocol C). The ratio CF:CFSPID was 7:1 (27/4) with protocol A, 2:1 (22/10) with protocol B, and 14:1 (54/4) with protocol C. The mean time to definite diagnosis was significantly shorter with protocol C (33days) compared to protocol A or B (42 and 40days; p=0.014 compared to A, and p=0.036 compared to B). The algorithm for the diagnostic part of the newborn screening used in the CF centers is important and affects the performance of a CF-NBS program with regard to the ratio CF:CFSPID and the time until definite diagnosis. Our results suggest to include FE after initial sweat test failure in the CF-NBS guidelines to keep the proportion of CFSPID low and the time until definite diagnosis short. Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  12. A murine model of elastase- and cigarette smoke-induced emphysema.

    Science.gov (United States)

    Rodrigues, Rubia; Olivo, Clarice Rosa; Lourenço, Juliana Dias; Riane, Alyne; Cervilha, Daniela Aparecida de Brito; Ito, Juliana Tiyaki; Martins, Milton de Arruda; Lopes, Fernanda Degobbi Tenório Quirino Dos Santos

    2017-01-01

    To describe a murine model of emphysema induced by a combination of exposure to cigarette smoke (CS) and instillation of porcine pancreatic elastase (PPE). A total of 38 C57BL/6 mice were randomly divided into four groups: control (one intranasal instillation of 0.9% saline solution); PPE (two intranasal instillations of PPE); CS (CS exposure for 60 days); and CS + PPE (two intranasal instillations of PPE + CS exposure for 60 days). At the end of the experimental protocol, all animals were anesthetized and tracheostomized for calculation of respiratory mechanics parameters. Subsequently, all animals were euthanized and their lungs were removed for measurement of the mean linear intercept (Lm) and determination of the numbers of cells that were immunoreactive to macrophage (MAC)-2 antigen, matrix metalloproteinase (MMP)-12, and glycosylated 91-kDa glycoprotein (gp91phox) in the distal lung parenchyma and peribronchial region. Although there were no differences among the four groups regarding the respiratory mechanics parameters assessed, there was an increase in the Lm in the CS + PPE group. The numbers of MAC-2-positive cells in the peribronchial region and distal lung parenchyma were higher in the CS + PPE group than in the other groups, as were the numbers of cells that were positive for MMP-12 and gp91phox, although only in the distal lung parenchyma. Our model of emphysema induced by a combination of PPE instillation and CS exposure results in a significant degree of parenchymal destruction in a shorter time frame than that employed in other models of CS-induced emphysema, reinforcing the importance of protease-antiprotease imbalance and oxidant-antioxidant imbalance in the pathogenesis of emphysema. Descrever um modelo murino de enfisema induzido por exposição a fumaça de cigarro (FC) e instilação de elastase pancreática porcina (EPP). Trinta e oito camundongos C57BL/6 foram aleatoriamente divididos em quatro grupos: controle (uma instilação intranasal

  13. Influence of elastase-induced emphysema and the inhalation of an irritant aerosol on deposition and retention of an inhaled insoluble aerosol in Fischer-344 rats

    International Nuclear Information System (INIS)

    Damon, E.G.; Mokler, B.V.; Jones, R.K.

    1983-01-01

    The purpose of this study was to assess the effects of elastase-induced pulmonary emphysema and the inhalation of an irritant aerosol (Triton X-100, a nonionic surfactant similar to those used in a number of pressurized consumer products) on pulmonary deposition and retention of an insoluble test aerosol, 59 FE-labeled Fe 2 O 3 . Untreated rats or rats pretreated by intratracheal in stillation with elastase were exposed to an aerosol of 59 Fe-labeled Fe 2 O 3 either 18 hr or 7 days after exposure to aerosslized Triton X-100 which was administered in doses of 20, 100, or 200 μg/g of lung. Rats pretreated with elastase had significantly lower pulmonary deposition of 59 Fe than the untreated controls (p 2 O 3 was unaffected by pretreatment with Triton X-100. Elastase treatment alone had no effect on retention of Fe 2 O 3 . Triton X-100 administered 18 hr prior to exposure of rats to Fe 2 O 3 aerosol resulted in dose-related increases in whole-body retention of 59 Fe. When rats were exposed to Triton X-100 7 days before exposure to Fe 2 O 3 , increased retention of 59 Fe was noted only in those treated at the highest Triton X-100 dose level (200 μg/g). 20 references, 5 tables

  14. Elastase-2, a Tissue Alternative Pathway for Angiotensin II Generation, Plays a Role in Circulatory Sympathovagal Balance in Mice.

    Science.gov (United States)

    Becari, Christiane; Durand, Marina T; Guimaraes, Alessander O; Lataro, Renata M; Prado, Cibele M; de Oliveira, Mauro; Candido, Sarai C O; Pais, Paloma; Ribeiro, Mauricio S; Bader, Michael; Pesquero, Joao B; Salgado, Maria C O; Salgado, Helio C

    2017-01-01

    In vitro and ex vivo experiments indicate that elastase-2 (ELA-2), a chymotrypsin-serine protease elastase family member 2A, is an alternative pathway for angiotensin II (Ang II) generation. However, the role played by ELA-2 in vivo is unclear. We examined ELA-2 knockout (ELA-2KO) mice compared to wild-type (WT) mice and determined whether ELA-2 played a role in hemodynamics [arterial pressure (AP) and heart rate (HR)], cardiocirculatory sympathovagal balance and baroreflex sensitivity. The variability of systolic arterial pressure (SAP) and pulse interval (PI) for evaluating autonomic modulation was examined for time and frequency domains (spectral analysis), whereas a symbolic analysis was also used to evaluate PI variability. In addition, baroreflex sensitivity was examined using the sequence method. Cardiac function was evaluated echocardiographically under anesthesia. The AP was normal whereas the HR was reduced in ELA-2KO mice (425 ± 17 vs. 512 ± 13 bpm from WT). SAP variability and baroreflex sensitivity were similar in both strains. The LF power from the PI spectrum (33.6 ± 5 vs. 51.8 ± 4.8 nu from WT) and the LF/HF ratio (0.60 ± 0.1 vs. 1.45 ± 0.3 from WT) were reduced, whereas the HF power was increased (66.4 ± 5 vs. 48.2 ± 4.8 nu from WT) in ELA-2KO mice, indicating a shift toward parasympathetic modulation of HR. Echocardiographic examination showed normal fractional shortening and an ejection fraction in ELA-2KO mice; however, the cardiac output, stroke volume, and ventricular size were reduced. These findings provide the first evidence that ELA-2 acts on the sympathovagal balance of the heart, as expressed by the reduced sympathetic modulation of HR in ELA-2KO mice.

  15. A new flow-diverter(the FloWise): In vivo evaluation in an elastase-induced rabbit aneurysm model

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Byung Moon; Kim, Dong Joon; Kim, Dong Ik [Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2016-02-15

    We aimed to evaluate the efficacy and safety of a newly developed, partially retrievable flow-diverter (the FloWise) in an elastase-induced rabbit aneurysm model. We developed a partially retrievable flow diverter composed of 48 strands of Nitinol and platinum wire. The FloWise is compatible with any microcatheter of 0.027-inch inner diameter, and is retrievable up to 70% deployment. The efficacy and safety of the FloWise were evaluated in the elastase-induced rabbit aneurysm model. The rate of technical success (full coverage of aneurysm neck) and assessment of aneurysm occlusion and stent patency was conducted by angiograms and histologic examinations at the 1-month, 3-month, and 6-month follow-up. The patency of small arterial branches (intercostal or lumbar arteries) covered by the FloWise were also assessed in the 5 subjects. We attempted FloWise insertion in a total of 32 aneurysm models. FloWise placement was successful in 31 subjects (96.9%). Two stents (6.2%) were occluded at the 3-month follow-up, but there was no evidence of in-stent stenosis in other subjects. All stented aneurysms showed progressive occlusion: grade I (complete aneurysm occlusion) in 44.4% and grade II (aneurysm occlusion > 90%) in 55.6% at 1 month; grade I in 90% and II in 10% at 3 months; and grade I in 90% and II in 10% at 6 months. All small arterial branches covered by the FloWise remained patent. A newly developed, partially retrievable flow-diverter seems to be a safe and effective tool of aneurysm occlusion, as evaluated in the rabbit aneurysm model.

  16. Poly herbal formulation with anti-elastase and anti-oxidant properties for skin anti-aging.

    Science.gov (United States)

    Kalyana Sundaram, Induja; Sarangi, Deepika Deeptirekha; Sundararajan, Vignesh; George, Shinomol; Sheik Mohideen, Sahabudeen

    2018-01-29

    Skin forms an important part of human innate immune system. Wrinkles, thinning and roughening of skin are some of the symptoms that affect the skin as it ages. Reactive oxygen species induced oxidative stress plays a major role in skin aging by modulating the elastase enzyme level in the skin. Extrinsic factors that affect skin aging such as UV radiation can also cause malignant melanoma. Here we selected four medicinal plant materials, namely, leaves of Nyctanthes arbor-tristis, unripe and ripe Aegle marmelos fruit pulp and the terminal meristem of Musa paradisiaca flower and investigated their anti-aging properties and cytotoxicity in vitro individually as well as in a poly herbal formulation containing the four plant extracts in different ratios. The phytochemical contents of the plant extracts were investigated for radical scavenging activity and total reducing power. Based upon its anti-oxidant properties, a poly herbal formulation containing leaves of Nyctanthes arbor-tristis, unripe and ripe fruit pulp of Aegle marmelos, and the terminal meristem of Musa paradisiaca flower in the ratio 6:2:1:1 (Poly Herbal Formulation 1) and 1:1:1:1 (Poly Herbal Formulation 2), respectively were formulated. It has been observed that the Poly Herbal Formulation 1 was more potent than Poly Herbal Formulation 2 due to better anti-oxidant and anti-elastase activities in NIH3T3 fibroblast cells. In addition Poly Herbal formulation 1 also had better anti-cancer activity in human malignant melanoma cells. Based on these results these beneficial plant extracts were identified for its potential application as an anti-aging agent in skin creams as well as an anti-proliferation compound against cancer cells.

  17. Cutaneous expressions of interleukin-6 and neutrophil elastase as well as levels of serum IgA antibodies to gliadin nonapeptides, tissue transglutaminase and epidermal transglutaminase: implications for both autoimmunity and autoinflammation involvement in dermatitis herpetiformis.

    Science.gov (United States)

    Gornowicz-Porowska, Justyna; Bowszyc-Dmochowska, Monika; Seraszek-Jaros, Agnieszka; Kaczmarek, Elżbieta; Pietkiewicz, Paweł; Dmochowski, Marian

    2014-01-01

    Dermatitis herpetiformis (DH) seems to be a chronic immune-mediated inflammatory disease of partially known origin. In light of its known biological functions and its involvement in tissue pathology in other disease states, particularly in nickel-induced allergic contact dermatitis coexisting with DH, it would appear that the central and peripheral response by neutrophils and their mediators (e.g. neutrophil elastase - NE) in DH may be partially mediated by interleukin-6 (IL-6). The aim of the study was to assess the role of IL -6 in DH lesions by examining the relationships between IL -6/NE cutaneous expression and levels of serum anti-nonapeptides of gliadin (npG) IgA, anti-tissue transglutaminase (tTG) immunoglobulin A (IgA), anti-epidermal transglutaminase (eTG) IgA in DH. In total, 24 DH patients having IgA cutaneous deposition were studied. Immunohistochemistry on paraffin-embedded sections with quantitative digital morphometry was used to measure the intensity of IL -6 and NE cutaneous expressions. Levels of serum anti-npG IgA, anti-tTG IgA and anti-eTG IgA were evaluated with ELISA. We found no statistically significant correlation between the NE and IL -6 expression intensities. Our results revealed also a lack of correlations between NE/IL -6 expressions and levels of anti-npG IgA, anti-tTG IgA, anti-eTG IgA in DH. However, the IL -6 expression level was significantly lower than that of NE. The lack of correlations suggested no substantial interactions between IL -6, NE, IgA/npG, IgA/tTG or IgA/eTG in DH. Presented results might indicate the heterogenetic nature of DH pathogenesis suggesting further that both autoimmune and autoinflammatory phenomena may be involved in DH cutaneous pathology.

  18. Increased galectin-3 levels are associated with abdominal aortic aneurysm progression and inhibition of galectin-3 decrease elastase-induced AAA development

    DEFF Research Database (Denmark)

    Fernandez-García, Carlos-Ernesto; Tarin, Carlos; Roldan-Montero, Raquel

    2017-01-01

    Abdominal aortic aneurysm (AAA) evolution is unpredictable. Moreover, no specific treatment exists for AAA, except surgery to prevent aortic rupture. Galectin-3 has been previously associated with CVD, but its potential role in AAA have not been addressed. Galectin-3 levels were increased in plasma...... of AAA patients (n=225) compared to controls (n=100). Moreover, galectin-3 concentrations were associated with need for surgical repair, independently of potential confounding factors. Galectin-3 mRNA and protein expression were increased in human AAA samples compared to healthy aortas. Experimental AAA...... in mice was induced by aortic elastase perfusion. Mice were treated i.v. with the galectin-3 inhibitor modified citrus pectin (MCP, 10mg/kg, every other day) or saline. Similar to humans, galectin-3 serum and aortic mRNA levels were also increased in elastase-induced AAA mice compared to control mice...

  19. Immunohistochemical study of tumor markers (CEA, TPA, CA19-9, POA and Ferritin) and pancreatic exocrine enzymes(Amylase and Elastase 1) in pancreatic tumors

    OpenAIRE

    脇谷, 勇夫

    1987-01-01

    The distribution of carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA), carbohydrate antigen 19-9 (CA19-9), pancreatic oncofetal antigen (POA), Ferritin, Amylase and Elastase 1 was studied immunohistochemically using an immunoperoxidase method in 26 conventional histopathologic sections of pancreatic tumor. CEA and CA19-9 were regarded as markers secreted into the glandular lumina from cancer cells, but TPA and POA were not. The expression of these markers was different from one...

  20. Structurally Related Monoterpenes p-Cymene, Carvacrol and Thymol Isolated from Essential Oil from Leaves of Lippia sidoides Cham. (Verbenaceae) Protect Mice against Elastase-Induced Emphysema.

    Science.gov (United States)

    Games, Ellen; Guerreiro, Marina; Santana, Fernanda R; Pinheiro, Nathalia M; de Oliveira, Emerson A; Lopes, Fernanda D T Q S; Olivo, Clarice R; Tibério, Iolanda F L C; Martins, Mílton A; Lago, João Henrique G; Prado, Carla M

    2016-10-20

    Chronic obstructive pulmonary disease (COPD) is characterized by irreversible airflow obstruction and inflammation. Natural products, such as monoterpenes, displayed anti-inflammatory and anti-oxidant activities and can be used as a source of new compounds to COPD treatment. Our aim was to evaluate, in an elastase-induced pulmonary emphysema in mice, the effects of and underlying mechanisms of three related natural monoterpenes ( p -cymene, carvacrol and thymol) isolated from essential oil from leaves Lippia sidoides Cham. (Verbenaceae). Mices received porcine pancreatic elastase (PPE) and were treated with p -cymene, carvacrol, thymol or vehicle 30 min later and again on 7th, 14th and 28th days. Lung inflammatory profile and histological sections were evaluated. In the elastase-instilled animals, the tested monoterpenes reduced alveolar enlargement, macrophages and the levels of IL-1β, IL-6, IL-8 and IL-17 in bronchoalveolar lavage fluid (BALF), and collagen fibers, MMP-9 and p-65-NF-κB-positive cells in lung parenchyma ( p < 0.05). All treatments attenuated levels of 8-iso-PGF2α but only thymol was able to reduced exhaled nitric oxide ( p < 0.05). Monoterpenes p -cymene, carvacrol and thymol reduced lung emphysema and inflammation in mice. No significant differences among the three monoterpenes treatments were found, suggesting that the presence of hydroxyl group in the molecular structure of thymol and carvacrol do not play a central role in the anti-inflammatory effects.

  1. Direct interaction between caffeic acid phenethyl ester and human neutrophil elastase inhibits the growth and migration of PANC-1 cells.

    Science.gov (United States)

    Duan, Jianhui; Xiaokaiti, Yilixiati; Fan, Shengjun; Pan, Yan; Li, Xin; Li, Xuejun

    2017-05-01

    Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignant tumors of the digestive system, but the mechanisms of its development and progression are unclear. Inflammation is thought to be fundamental to pancreatic cancer development and caffeic acid phenethyl ester (CAPE) is an active component of honey bee resin or propolis with anti-inflammatory and anticancer activities. We investigated the inhibitory effects of CAPE on cell growth and migration induced by human neutrophil elastase (HNE) and report that HNE induced cancer cell migration at low doses and growth at higher doses. In contrast, lower CAPE doses inhibited migration and higher doses of CAPE inhibited the growth induced by HNE. HNE activity was significantly inhibited by CAPE (7.5-120 µM). Using quantitative real-time PCR and western blotting, we observed that CAPE (18-60 µM) did not affect transcription and translation of α1-antitrypsin (α1-AT), an endogenous HNE inhibitor. However, in an in silico drug target docking model, we found that CAPE directly bound to the binding pocket of HNE (25.66 kcal/mol) according to CDOCKER, and the residue of the catalytic site stabilized the interaction between CAPE and HNE as evidenced by molecular dynamic simulation. Response unit (RU) values of surface plasmon resonance (SPR) significantly increased with incremental CAPE doses (7.5-120 µM), indicating that CAPE could directly bind to HNE in a concentration-dependent manner. Thus, CAPE is an effective inhibitor of HNE via direct interaction whereby it inhibits the migration and growth of PANC-1 cells in a dose-dependent manner.

  2. Mechanism of inactivation of human leukocyte elastase by a chloromethyl ketone: kinetic and solvent isotope effect studies

    International Nuclear Information System (INIS)

    Stein, R.L.; Trainor, D.A.

    1986-01-01

    The mechanism of inactivation of human leukocyte elastase (HLE) by the chloromethyl ketone MeOSuc-Ala-Ala-Pro-Val-CH 2 Cl was investigated. The dependence of the first-order rate constant for inactivation on concentration of chloromethyl ketone is hyperbolic and suggests formation of a reversible Michaelis complex prior to covalent interaction between the enzyme and inhibitor. However, the observed Ki value is 10 microM, at least 10-fold lower than dissociation constants for complexes formed from interaction of HLE with structurally related substrates or reversible inhibitors, and suggests that Ki is a complex kinetic constant, reflecting the formation and accumulation of both the Michaelis complex and a second complex. It is proposed that this second complex is a hemiketal formed from attack of the active site serine on the carbonyl carbon of the inhibitor. The accumulation of this intermediate may be a general feature of reactions of serine proteases and chloromethyl ketones derived from specific peptides and accounts for the very low Ki values observed for these reactions. The solvent deuterium isotope effect (SIE) on the inactivation step (ki) is 1.58 +/- 0.07 and is consistent with rate-limiting, general-catalyzed attack of the active site His on the methylene carbon of the inhibitor with displacement of chloride anion. The general catalyst is thought to be the active site Asp. In contrast, the SIE on the second-order rate constant for HLE inactivation, ki/Ki, is inverse and equals 0.64 +/- 0.05

  3. Pulmonary Administration of GW0742, a High-Affinity Peroxisome Proliferator-Activated Receptor Agonist, Repairs Collapsed Alveoli in an Elastase-Induced Mouse Model of Emphysema.

    Science.gov (United States)

    Ozawa, Chihiro; Horiguchi, Michiko; Akita, Tomomi; Oiso, Yuki; Abe, Kaori; Motomura, Tomoki; Yamashita, Chikamasa

    2016-01-01

    Pulmonary emphysema is a disease in which lung alveoli are irreversibly damaged, thus compromising lung function. Our previous study revealed that all-trans-retinoic acid (ATRA) induces the differentiation of human lung alveolar epithelial type 2 progenitor cells and repairs the alveoli of emphysema model mice. ATRA also reportedly has the ability to activate peroxisome proliferator-activated receptor (PPAR) β/δ. A selective PPARβ/δ ligand has been reported to induce the differentiation of human keratinocytes during wound repair. Here, we demonstrate that treatment using a high-affinity PPARβ/δ agonist, GW0742, reverses the lung tissue damage induced by elastase in emphysema-model mice and improves respiratory function. Mice treated with elastase, which collapsed their alveoli, were then treated with either 10% dimethyl sulfoxide (DMSO) in saline (control group) or GW0742 (1.0 mg/kg twice a week) by pulmonary administration. Treatment with GW0742 for 2 weeks increased the in vivo expression of surfactant proteins A and D, which are known alveolar type II epithelial cell markers. GW0742 treatment also shortened the average distance between alveolar walls in the lungs of emphysema model mice, compared with a control group treated with 10% DMSO in saline. Treatment with GW0742 for 3 weeks also improved tissue elastance (cm H2O/mL), as well as the ratio of the forced expiratory volume in the first 0.05 s to the forced vital capacity (FEV 0.05/FVC). In each of these experiments, GW0742 treatment reversed the damage caused by elastase. In conclusion, PPARβ/δ agonists are potential therapeutic agents for pulmonary emphysema.

  4. Oxidative and proteolysis-related parameters of skeletal muscle from hamsters with experimental pulmonary emphysema: a comparison between papain and elastase induction.

    Science.gov (United States)

    Brunnquell, Cláudia R; Vieira, Nichelle A; Sábio, Laís R; Sczepanski, Felipe; Cecchini, Alessandra L; Cecchini, Rubens; Guarnier, Flávia A

    2015-06-01

    The objective of this study was to investigate whether emphysema induced by elastase or papain triggers the same effects on skeletal muscle, related to oxidative stress and proteolysis, in hamsters. For this purpose, we evaluated pulmonary lesions, body weight, muscle loss, oxidative stress (thiobarbituric acid-reactive substances, total and oxidized glutathiones, chemiluminescence stimulated by tert-butyl hydroperoxide and carbonyl proteins), chymotrypsin-like and calpain-like proteolytic activities and muscle fibre cross-sectional area in the gastrocnemius muscles of emphysemic hamsters. Two groups of animals received different intratracheal inductions of experimental emphysema: by 40 mg/ml papain (EP) or 5.2 IU/100 g animal (EE) elastase (n = 10 animals/group). The control group received intratracheal instillation of 300 μl sterile NaCl 0.9%. Compared with the control group, the EP group had reduced muscle weight (18.34%) and the EE group had increased muscle weight (8.37%). Additionally, tert-butyl hydroperoxide-initiated chemiluminescence, carbonylated proteins and chymotrypsin-like proteolytic activity were all elevated in the EP group compared to the CS group, while total glutathione was decreased compared to the EE group. The EE group showed more fibres with increased cross-sectional areas and increased calpain-like activity. Together, these data show that elastase and papain, when used to induce experimental models of emphysema, lead to different speeds and types of adaptation. These findings provide more information on choosing a suitable experimental model for studying skeletal muscle adaptations in emphysema. © 2015 The Authors. International Journal of Experimental Pathology © 2015 International Journal of Experimental Pathology.

  5. Increased galectin-3 levels are associated with abdominal aortic aneurysm progression and inhibition of galectin-3 decreases elastase-induced AAA development.

    Science.gov (United States)

    Fernandez-García, Carlos-Ernesto; Tarin, Carlos; Roldan-Montero, Raquel; Martinez-Lopez, Diego; Torres-Fonseca, Monica; Lindhot, Jes S; Vega de Ceniga, Melina; Egido, Jesus; Lopez-Andres, Natalia; Blanco-Colio, Luis-Miguel; Martín-Ventura, Jose-Luis

    2017-11-15

    Abdominal aortic aneurysm (AAA) evolution is unpredictable and no specific treatment exists for AAA, except surgery to prevent aortic rupture. Galectin-3 has been previously associated with CVD, but its potential role in AAA has not been addressed. Galectin-3 levels were increased in the plasma of AAA patients ( n =225) compared with the control group ( n =100). In addition, galectin-3 concentrations were associated with the need for surgical repair, independently of potential confounding factors. Galectin-3 mRNA and protein expression were increased in human AAA samples compared with healthy aortas. Experimental AAA in mice was induced via aortic elastase perfusion. Mice were treated intravenously with the galectin-3 inhibitor modified citrus pectin (MCP, 10 mg/kg, every other day) or saline. Similar to humans, galectin-3 serum and aortic mRNA levels were also increased in elastase-induced AAA mice compared with control mice. Mice treated with MCP showed decreased aortic dilation, as well as elastin degradation, vascular smooth muscle cell (VSMC) loss, and macrophage content at day 14 postelastase perfusion compared with control mice. The underlying mechanism(s) of the protective effect of MCP was associated with a decrease in galectin-3 and cytokine (mainly CCL5) mRNA and protein expression. Interestingly, galectin-3 induced CCL5 expression by a mechanism involving STAT3 activation in VSMC. Accordingly, MCP treatment decreased STAT3 phosphorylation in elastase-induced AAA. In conclusion, increased galectin-3 levels are associated with AAA progression, while galectin-3 inhibition decreased experimental AAA development. Our data suggest the potential role of galectin-3 as a therapeutic target in AAA. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  6. SU-E-QI-14: Quantitative Variogram Detection of Mild, Unilateral Disease in Elastase-Treated Rats

    Energy Technology Data Exchange (ETDEWEB)

    Jacob, R [Pacific Northwest National Laboraory, Richland, WA (United States); Carson, J [Texas Advanced Computing Center, Austin, TX (United States)

    2014-06-15

    Purpose: Determining the presence of mild or early disease in the lungs can be challenging and subjective. We present a rapid and objective method for evaluating lung damage in a rat model of unilateral mild emphysema based on a new approach to heterogeneity assessment. We combined octree decomposition (used in three-dimensional (3D) computer graphics) with variograms (used in geostatistics to assess spatial relationships) to evaluate 3D computed tomography (CT) lung images for disease. Methods: Male, Sprague-Dawley rats (232 ± 7 g) were intratracheally dosed with 50 U/kg of elastase dissolved in 200 μL of saline to a single lobe (n=6) or with saline only (n=5). After four weeks, 3D micro-CT images were acquired at end expiration on mechanically ventilated rats using prospective gating. Images were masked, and lungs were decomposed to homogeneous blocks of 2×2×2, 4×4×4, and 8×8×8 voxels using octree decomposition. The spatial variance – the square of the difference of signal intensity – between all pairs of the 8×8×8 blocks was calculated. Variograms – graphs of distance vs. variance - were made, and data were fit to a power law and the exponent determined. The mean HU values, coefficient of variation (CoV), and the emphysema index (EI) were calculated and compared to the variograms. Results: The variogram analysis showed that significant differences between groups existed (p<0.01), whereas the mean HU (p=0.07), CoV (p=0.24), and EI (p=0.08) did not. Calculation time for the variogram for a typical 1000 block decomposition was ∼6 seconds, and octree decomposition took ∼2 minutes. Decomposing the images prior to variogram calculation resulted in a ∼700x decrease in time as compared to other published approaches. Conclusions: Our results suggest that the approach combining octree decomposition and variogram analysis may be a rapid, non-subjective, and sensitive imaging-based biomarker for quantitative characterization of lung disease.

  7. Low molecular weight heparin may benefit nephrotic remission in steroid‑sensitive nephrotic syndrome via inhibiting elastase.

    Science.gov (United States)

    Zhai, Songhui; Hu, Lijuan; Zhong, Lin; Tao, Yuhong; Wang, Zheng

    2017-12-01

    Low molecular weight heparin (LMWH) has a structure similar to heparan sulfate, which exerts anti‑inflammatory effects via inhibiting elastase (Ela) activity. Release of Ela along the glomerular capillary wall may induce glomerular injury and proteinuria. The present study aimed to investigate the influence of LMWH on steroid‑sensitive nephrotic syndrome (SSNS) and the potential underlying mechanism. A total of 40 SSNS patients and 20 healthy controls were recruited. SSNS patients were treated with LMWH and prednisone simultaneously (LMWH+pred group) or with prednisone alone (pred group). Proteinuria, urinary glycosaminoglycans (GAGs), serum Ela and urinary creatinine levels were measured. The nephrotic period of SSNS was 15.93±5.78 days. The nephrotic period of SSNS in LMWH+pred group was significantly reduced compared with the pred group (14.13±4.56 vs. 18.63±6.49 days; PEla levels (77.64±10.99 ng/l) were significantly greater in the nephrotic period of SSNS compared with the remission period (0.107±0.026 g/24 h, 1.53±0.27 mg/mmol Cr and 41.92±7.81 ng/l, respectively) and the healthy control group (0.098±0.027 g/24 h, 1.40±0.26 mg/mmol creatinine and 38.43±9.83 ng/l, respectively; PEla levels in the LMWH+pred group were significantly reduced compared with the pred group (P0.05). Positive correlations were revealed between urinary GAG excretion and proteinuria (r=0.877; PEla levels (r=0.844; PEla levels and urinary GAG excretion (r=0.881; PEla levels may induce proteinuria by degrading GAGs in the glomerular basement membrane in children with SSNS. LMWH may benefit nephrotic remission of SSNS via inhibiting Ela.

  8. Morphological and Biomechanical Differences in the Elastase and AngII apoE−/− Rodent Models of Abdominal Aortic Aneurysms

    Directory of Open Access Journals (Sweden)

    Evan H. Phillips

    2015-01-01

    Full Text Available An abdominal aortic aneurysm (AAA is a potentially fatal cardiovascular disease with multifactorial development and progression. Two preclinical models of the disease (elastase perfusion and angiotensin II infusion in apolipoprotein-E-deficient animals have been developed to study the disease during its initiation and progression. To date, most studies have used ex vivo methods to examine disease characteristics such as expanded aortic diameter or analytic methods to look at circulating biomarkers. Herein, we provide evidence from in vivo ultrasound studies of the temporal changes occurring in biomechanical parameters and macromolecules of the aortic wall in each model. We present findings from 28-day studies in elastase-perfused rats and AngII apoE−/− mice. While each model develops AAAs specific to their induction method, they both share characteristics with human aneurysms, such as marked changes in vessel strain and blood flow velocity. Histology and nonlinear microscopy confirmed that both elastin and collagen, both important extracellular matrix molecules, are similarly affected in their levels and spatial distribution. Future studies could make use of the differences between these models in order to investigate mechanisms of disease progression or evaluate potential AAA treatments.

  9. Aggressive re-warming at 38.5 degrees C following deep hypothermia at 21 degrees C increases neutrophil membrane bound elastase activity and pro-inflammatory factor release

    NARCIS (Netherlands)

    Tang, Min; Zhao, Xiao-gang; He, Yi; Gu, Yan; Mei, Ju

    2016-01-01

    Background: Cardiopulmonary bypass (CPB) is often performed under hypothermic condition. The effects of hypothermia and re-warming on neutrophil activity are unclear. This study aimed to compare the effects of different hypothermia and re-warming regimens on neutrophil membrane bound elastase (MBE)

  10. A dietary supplement improves facial photoaging and skin sebum, hydration and tonicity modulating serum fibronectin, neutrophil elastase 2, hyaluronic acid and carbonylated proteins.

    Science.gov (United States)

    Di Cerbo, Alessandro; Laurino, Carmen; Palmieri, Beniamino; Iannitti, Tommaso

    2015-03-01

    Excessive exposure to the sun can cause severe photoaging as early as the second decade of life resulting in a loss of physiological elastic fiber functions. We designed a first study to assess differences in facial skin pH, sebum, elasticity, hydration and tonicity and serum levels of fibronectin, elastin, neutrophil elastase 2, hyaluronic acid and carbonylated proteins between patients affected by facial photoaging and healthy controls. In a second study we tested the hypothesis that a dietary supplement would improve facial photoaging, also promoting changes in the above mentioned skin and serum parameters. In the first study we enrolled 30 women [age: 47.5 ± 1.6 years (mean ± standard error of the mean)] affected by moderate facial photoaging (4 cm ≤ Visual Analogue Scale (VAS)Skin Tester was used to analyze differences in facial skin parameters between patients affected by facial photoaging and healthy controls. Skin Tester was also used to assess the effect of VISCODERM Pearls on facial skin parameters and compared with placebo 2 weeks after the end of treatment. Serum levels of fibronectin, elastin, neutrophil elastase 2, hyaluronic acid and carbonylated proteins were measured by enzyme-linked immunosorbent assay in the first cohort of patients affected by facial photoaging and healthy controls and, at baseline and 2 weeks after the end of treatment, in the second cohort of patients who underwent treatment with VISCODERM Pearls and placebo. VAS photoaging score was higher in patients affected by photoaging, if compared with healthy controls (p hydration and tonicity were decreased in patients affected by photoaging, if compared with healthy controls (all p hydration and tonicity were increased in the active treatment group vs. placebo (p skin hydration, tonicity and elasticity and increased skin pH and sebum. Treatment with the dietary supplement VISCODERM Pearls significantly improved VAS photoaging score and skin hydration, sebum and tonicity 2 weeks

  11. El litio y su relación con la acuaporina-2 y el canal de sodio ENaC Lithium and its relation with the epithelial sodium channel and aquaporin-2

    Directory of Open Access Journals (Sweden)

    Luciano Galizia

    2012-04-01

    Full Text Available Desde hace más de cuarenta años que el litio es usado para el tratamiento de la enfermedad bipolar; recientes estudios sugieren también su utilidad en el trastorno cognitivo mínimo tipo amnésico. El litio es filtrado en el glomérulo y un 65-75% del mismo es reabsorbido en el túbulo contorneado proximal y en el asa ascendente de Henle por el transportador Na+, K+, 2Cl- y vía paracelular. Una pequeña fracción del litio entra en las células principales del túbulo colector por medio del canal epitelial de sodio sensible al amiloride (ENaC localizado en la membrana apical de la célula. Luego de 10- 20 años de tratamiento con litio los enfermos pueden desarrollar poliuria, acidosis tubular e insuficiencia renal crónica que puede terminar en una forma de diabetes que no responde a la arginina vasopresina llamada diabetes insípida nefrogénica. Se cree que estas fallas renales son consecuencias de una reducción en el número de moléculas de acuaporina 2 en la membrana apical. Las causas para esto son complejas. El litio es un poderoso inhibidor de la isoforma beta de la enzima glicógeno sintetasa quinasa y esto está asociado a una menor actividad de la adenilato ciclasa que lleva a una disminución en la concentración intracelular de cAMP. Esto finalmente interferiría con la síntesis de nuevas moléculas de acuaporina 2 y con el tráfico de ellas desde la zona subapical de la célula hacia la membrana celular, causando la disminución en la reabsorción de agua en la parte distal del nefrón.For more than 40 years lithium has been used to treat bipolar disorder and recent trials suggest a potential efficacy also in the treatment of the amnestic mild cognitive impairment. Lithium is filtered by the glomerulus and 65% - 75% of the filtered amount is reabsorbed along the proximal tubule and in the thick ascending limb of Henle's loop by the Na+, K+, 2Cl- transporter and via paracellular. A small fraction of lithium is reabsorbed in

  12. Characterization of Total Phenolic Constituents from the Stems of Spatholobus suberectus Using LC-DAD-MSn and Their Inhibitory Effect on Human Neutrophil Elastase Activity

    Directory of Open Access Journals (Sweden)

    Yiming Li

    2013-06-01

    Full Text Available Spatholobus suberectus Dunn, belonging to the legume family (Fabaceae, has been used as a Traditional Chinese Medicine for the treatment of anemia, menoxenia and rheumatism. A limited number of studies report that various types of flavonoids are the main characteristic constituents of this herb. We have now found that S. suberectus contains about 2% phenolic components and characterized the major phenolic components as homogeneous B-type procyanidin conjugates using a liquid chromatography with diode-array detection-ESI mass spectrometry (LC-DAD/ESI-MS method. This is the first report on occurrence of most B-type procyanidins in this herb. Moreover, the total phenolics extract was assayed for inhibitory activity on human neutrophil elastase and its IC50 was found to be 1.33 μg/mL.

  13. Eunicellin-based diterpenoids from the Formosan soft coral Klyxum molle with inhibitory activity on superoxide generation and elastase release by neutrophils.

    Science.gov (United States)

    Lin, Ming-Chang; Chen, Bo-Wei; Huang, Chiung-Yao; Dai, Chang-Feng; Hwang, Tsong-Long; Sheu, Jyh-Horng

    2013-09-27

    Eleven new eunicellin-based diterpenoids possessing a cladiellane skeleton with a C-2, C-9 ether bridge, klymollins I-S (1-11), have been isolated from the EtOAc extract of the soft coral Klyxum molle from Taiwan waters. The structures of compounds 1-11 were elucidated by extensive spectroscopic analysis, including 2D NMR spectroscopy (COSY, HSQC, HMBC, and NOESY). Compound 5 exhibited cytotoxicity toward several cancer cell lines. Compound 5 is the first eunicellin-based metabolite bearing a phenyl group and displays significant inhibition of both superoxide anion generation and elastase release in N-formyl-methionyl-leucyl-phenylalanine/cytochalasin B (fMLP/CB)-induced human neutrophils.

  14. Potential role of recombinant secretory leucoprotease inhibitor in the prevention of neutrophil mediated matrix degradation.

    Science.gov (United States)

    Llewellyn-Jones, C G; Lomas, D A; Stockley, R A

    1994-06-01

    Neutrophil elastase is able to degrade connective tissue matrices and is thought to be involved in the pathogenesis of destructive lung diseases. The ability of recombinant secretory leucoprotease inhibitor (rSLPI) to inhibit neutrophil mediated degradation of fibronectin in vitro is demonstrated and its efficacy compared with native alpha-1-proteinase inhibitor (n alpha 1-PI), recombinant alpha-1-proteinase inhibitor (r alpha 1-PI), and the chemical elastase inhibitor ICI 200,355. When preincubated with neutrophils both rSLPI and r alpha 1-PI were effective inhibitors of fibronectin degradation although n alpha 1-PI and ICI 200,355 were less effective. Recombinant SLPI was the most effective inhibitor when the cells were allowed to adhere to fibronectin before the addition of the inhibitors. Preincubation of rSLPI (0.1 mumol/l) with the fibronectin plate resulted in almost total inhibition of fibronectin degradation (reduced to 3.3 (SE 0.9)% of control). Pretreating the fibronectin plate with 1 mumol/l rSLPI, r alpha 1-PI and ICI 200,355 followed by thorough washing before the addition of cells resulted in no inhibition of fibronectin degradation with r alpha 1-PI and the ICI inhibitor, but rSLPI retained its inhibitory effect. This effect could be reduced by adding rSLPI in high pH buffer or 2 mol/1 NaCl. It is postulated that rSLPI binds to fibronectin to form a protective layer which prevents its degradation by neutrophil elastase. It may prove to be the most useful therapeutic agent in the prevention of neutrophil mediated lung damage.

  15. Roles of oxygen radicals and elastase in citric acid-induced airway constriction of guinea-pigs

    OpenAIRE

    Lai, Y -L; Chiou, W -Y; Lu, F J; Chiang, L Y

    1999-01-01

    Antioxidants attenuate noncholinergic airway constriction. To further investigate the relationship between tachykinin-mediated airway constriction and oxygen radicals, we explored citric acid-induced bronchial constriction in 48 young Hartley strain guinea-pigs, divided into six groups: control; citric acid; hexa(sulphobutyl)fullerenes+citric acid; hexa(sulphobutyl)fullerenes+phosphoramidon+citric acid; dimethylthiourea (DMTU)+citric acid; and DMTU+phosphoramidon+citric acid. Hexa(sulphobutyl...

  16. Inefficient cationic lipid-mediated siRNA and antisense oligonucleotide transfer to airway epithelial cells in vivo

    Directory of Open Access Journals (Sweden)

    Hu Jim

    2006-02-01

    Full Text Available Abstract Background The cationic lipid Genzyme lipid (GL 67 is the current "gold-standard" for in vivo lung gene transfer. Here, we assessed, if GL67 mediated uptake of siRNAs and asODNs into airway epithelium in vivo. Methods Anti-lacZ and ENaC (epithelial sodium channel siRNA and asODN were complexed to GL67 and administered to the mouse airway epithelium in vivo Transfection efficiency and efficacy were assessed using real-time RT-PCR as well as through protein expression and functional studies. In parallel in vitro experiments were carried out to select the most efficient oligonucleotides. Results In vitro, GL67 efficiently complexed asODNs and siRNAs, and both were stable in exhaled breath condensate. Importantly, during in vitro selection of functional siRNA and asODN we noted that asODNs accumulated rapidly in the nuclei of transfected cells, whereas siRNAs remained in the cytoplasm, a pattern consistent with their presumed site of action. Following in vivo lung transfection siRNAs were only visible in alveolar macrophages, whereas asODN also transfected alveolar epithelial cells, but no significant uptake into conducting airway epithelial cells was seen. SiRNAs and asODNs targeted to β-galactosidase reduced βgal mRNA levels in the airway epithelium of K18-lacZ mice by 30% and 60%, respectively. However, this was insufficient to reduce protein expression. In an attempt to increase transfection efficiency of the airway epithelium, we increased contact time of siRNA and asODN using the in vivo mouse nose model. Although highly variable and inefficient, transfection of airway epithelium with asODN, but not siRNA, was now seen. As asODNs more effectively transfected nasal airway epithelial cells, we assessed the effect of asODN against ENaC, a potential therapeutic target in cystic fibrosis; no decrease in ENaC mRNA levels or function was detected. Conclusion This study suggests that although siRNAs and asODNs can be developed to inhibit

  17. Sulfated caffeic acid dehydropolymer attenuates elastase and cigarette smoke extract-induced emphysema in rats: sustained activity and a need of pulmonary delivery.

    Science.gov (United States)

    Saluja, Bhawana; Li, Hua; Desai, Umesh R; Voelkel, Norbert F; Sakagami, Masahiro

    2014-08-01

    Although emphysema destroys alveolar structures progressively and causes death eventually, no drug has been discovered to prevent, intervene, and/or resolve this life-threatening disease. We recently reported that sulfated caffeic acid dehydropolymer CDSO3 is a novel potent triple-action inhibitor of elastolysis, oxidation, and inflammation in vitro, and therefore, a potential anti-emphysema agent. However, the in vivo therapeutic potency, duration and mode of actions, and effective route remain to be demonstrated. Emphysema was induced in rats with human sputum elastase (HSE) combined with cigarette smoke extract (CSE). CDSO3 at 5, 30, or 100 μg/kg was dosed to the lung or injected subcutaneously at 2, 6, or 24 h before or 1 or 24 h or 1 week after the HSE/CSE instillation. At 1 h or 48 h or on day 21-22 or day 28, lungs were examined for airway-to-blood injurious barrier damage; their elastolytic, oxidative, and inflammatory activities; lung luminal leukocytes infiltration; functional treadmill exercise endurance; and/or morphological airspace enlargement. CDSO3, when dosed to the lung at 30 or 100 μg/kg, but not via systemic subcutaneous injection, significantly (43-93 %) attenuated HSE/CSE-induced (1) barrier damage measured by luminal hemorrhage and protein leak; (2) elastolytic, oxidative, and inflammatory activities measured with elastase, reduced glutathione, and TNFα levels, respectively; (3) luminal neutrophil infiltration and tissue myeloperoxidase activity; (4) functional impairment of exercise endurance; and (5) airspace enlargement, in both preventive and interventional dosing protocols. Notably, the effects were shown to last for 24 h at the greater 100-μg/kg dose, and the 1-week-delayed administration was also capable of attenuating the development of emphysema. CDSO3 is a novel, potent, long-acting, nonpeptidic macromolecule that inhibits HSE/CSE-induced elastolysis, oxidation, and inflammation in the lung and thereby attenuates the development

  18. Synthesized zinc peroxide nanoparticles (ZnO2-NPs): a novel antimicrobial, anti-elastase, anti-keratinase, and anti-inflammatory approach toward polymicrobial burn wounds.

    Science.gov (United States)

    Ali, Sameh Samir; Morsy, Reda; El-Zawawy, Nessma Ahmed; Fareed, Mervat F; Bedaiwy, Mohamed Yaser

    2017-01-01

    Increasing of multidrug resistance (MDR) remains an intractable challenge for burn patients. Innovative nanomaterials are also in high demand for the development of new antimicrobial biomaterials that inevitably have opened new therapeutic horizons in medical approaches and lead to many efforts for synthesizing new metal oxide nanoparticles (NPs) for better control of the MDR associated with the polymicrobial burn wounds. Recently, it seems that metal oxides can truly be considered as highly efficient inorganic agents with antimicrobial properties. In this study, zinc peroxide NPs (ZnO 2 -NPs) were synthesized using the co-precipitation method. Synthesized ZnO 2 -NPs were characterized by X-ray diffraction, Fourier transformed infrared, transmission electron microscopy, thermogravimetric analysis, differential scanning calorimetry, and ultraviolet-visible spectroscopy. The characterization techniques revealed synthesis of the pure phase of non-agglomerated ZnO 2 -NPs having sizes in the range of 15-25 nm with a transition temperature of 211°C. Antimicrobial activity of ZnO 2 -NPs was determined against MDR Pseudomonas aeruginosa (PA) and Aspergillus niger (AN) strains isolated from burn wound infections. Both strains, PA6 and AN4, were found to be more susceptible strains to ZnO 2 -NPs. In addition, a significant decrease in elastase and keratinase activities was recorded with increased concentrations of ZnO 2 -NPs until 200 µg/mL. ZnO 2 -NPs revealed a significant anti-inflammatory activity against PA6 and AN4 strains as demonstrated by membrane stabilization, albumin denaturation, and proteinase inhibition. Moreover, the results of in vivo histopathology assessment confirmed the potential role of ZnO 2 -NPs in the improvement of skin wound healing in the experimental animal models. Clearly, the synthesized ZnO 2 -NPs have demonstrated a competitive capability as antimicrobial, anti-elastase, anti-keratinase, and anti-inflammatory candidates, suggesting that the

  19. Intercultural Mediation

    OpenAIRE

    Dragos Marian Radulescu; Denisa Mitrut

    2012-01-01

    The Intercultural Mediator facilitates exchanges between people of different socio-cultural backgrounds and acts as a bridge between immigrants and national and local associations, health organizations, services and offices in order to foster integration of every single individual. As the use mediation increases, mediators are more likely to be involved in cross-cultural mediation, but only the best mediators have the opportunity to mediate cross border business disputes or international poli...

  20. Biological Mechanisms Underlying the Ultraviolet Radiation-Induced Formation of Skin Wrinkling and Sagging I: Reduced Skin Elasticity, Highly Associated with Enhanced Dermal Elastase Activity, Triggers Wrinkling and Sagging

    Science.gov (United States)

    Imokawa, Genji; Ishida, Koichi

    2015-01-01

    The repetitive exposure of skin to ultraviolet B (UVB) preferentially elicits wrinkling while ultraviolet A (UVA) predominantly elicits sagging. In chronically UVB or UVA-exposed rat skin there is a similar tortuous deformation of elastic fibers together with decreased skin elasticity, whose magnitudes are greater in UVB-exposed skin than in UVA-exposed skin. Comparison of skin elasticity with the activity of matrix metalloproteinases (MMPs) in the dermis of ovariectomized rats after UVB or UVA irradiation demonstrates that skin elasticity is more significantly decreased in ovariectomized rats than in sham-operated rats, which is accompanied by a reciprocal increase in elastase activity but not in the activities of collagenases I or IV. Clinical studies using animal skin and human facial skin demonstrated that topical treatment with a specific inhibitor or an inhibitory extract of skin fibroblast-derived elastase distinctly attenuates UVB and sunlight-induced formation of wrinkling. Our results strongly indicated that the upregulated activity of skin fibroblast-derived elastase plays a pivotal role in wrinkling and/or sagging of the skin via the impairment of elastic fiber configuration and the subsequent loss of skin elasticity. PMID:25856675

  1. Keratinocyte Growth Factor Gene Electroporation into Skeletal Muscle as a Novel Gene Therapeutic Approach for Elastase-Induced Pulmonary Emphysema in Mice

    International Nuclear Information System (INIS)

    Tobinaga, Shuichi; Matsumoto, Keitaro; Nagayasu, Takeshi; Furukawa, Katsuro; Abo, Takafumi; Yamasaki, Naoya; Tsuchiya, Tomoshi; Miyazaki, Takuro; Koji, Takehiko

    2015-01-01

    Pulmonary emphysema is a progressive disease with airspace destruction and an effective therapy is needed. Keratinocyte growth factor (KGF) promotes pulmonary epithelial proliferation and has the potential to induce lung regeneration. The aim of this study was to determine the possibility of using KGF gene therapy for treatment of a mouse emphysema model induced by porcine pancreatic elastase (PPE). Eight-week-old BALB/c male mice treated with intra-tracheal PPE administration were transfected with 80 μg of a recombinant human KGF (rhKGF)-expressing FLAG-CMV14 plasmid (pKGF-FLAG gene), or with the pFLAG gene expressing plasmid as a control, into the quadriceps muscle by electroporation. In the lung, the expression of proliferating cell nuclear antigen (PCNA) was augmented, and surfactant protein A (SP-A) and KGF receptor (KGFR) were co-expressed in PCNA-positive cells. Moreover, endogenous KGF and KGFR gene expression increased significantly by pKGF-FLAG gene transfection. Arterial blood gas analysis revealed that the PaO 2 level was not significantly reduced on day 14 after PPE instillation with pKGF-FLAG gene transfection compared to that of normal mice. These results indicated that KGF gene therapy with electroporation stimulated lung epithelial proliferation and protected depression of pulmonary function in a mouse emphysema model, suggesting a possible method of treating pulmonary emphysema

  2. Mediation Analysis with Multiple Mediators.

    Science.gov (United States)

    VanderWeele, T J; Vansteelandt, S

    2014-01-01

    Recent advances in the causal inference literature on mediation have extended traditional approaches to direct and indirect effects to settings that allow for interactions and non-linearities. In this paper, these approaches from causal inference are further extended to settings in which multiple mediators may be of interest. Two analytic approaches, one based on regression and one based on weighting are proposed to estimate the effect mediated through multiple mediators and the effects through other pathways. The approaches proposed here accommodate exposure-mediator interactions and, to a certain extent, mediator-mediator interactions as well. The methods handle binary or continuous mediators and binary, continuous or count outcomes. When the mediators affect one another, the strategy of trying to assess direct and indirect effects one mediator at a time will in general fail; the approach given in this paper can still be used. A characterization is moreover given as to when the sum of the mediated effects for multiple mediators considered separately will be equal to the mediated effect of all of the mediators considered jointly. The approach proposed in this paper is robust to unmeasured common causes of two or more mediators.

  3. Evaluation of occurring complications after flow diverter treatment of elastase-induced aneurysm in rabbits using micro-CT and MRI at 9.4 T

    Energy Technology Data Exchange (ETDEWEB)

    Simgen, Andreas; Ley, Desiree; Muehl-Benninghaus, Ruben; Koerner, Heiko; Reith, Wolfgang; Yilmaz, Umut [Saarland University Hospital, Department of Neuroradiology, Homburg, Saar (Germany); Roth, Christian [Clinic Bremen-Mitte, Department of Neuroradiology, Bremen (Germany); Cattaneo, Giorgio Franco Maria [Acandis GmbH, Pforzheim (Germany); Mueller, Andreas [Saarland University Hospital, Department of Experimental Surgery, Homburg, Saar (Germany); Kim, Yoo-Jin [Saarland University Hospital, Department of Pathology, Homburg, Saar (Germany); Scheller, Bruno [Saarland University Hospital, Department of Cardiology, Homburg, Saar (Germany)

    2016-10-15

    Flow diverters are increasingly being used to treat intracranial aneurysms. This study evaluates occurring complications of flow-diverting devices in the treatment of experimental aneurysms, involving the use of micro-CT and small animal MRI at 9.4 T, in correlation to angiographic and histological findings. We previously published two preclinical studies, in which we assessed two different flow diverters in the treatment of elastase-induced aneurysms. Devices have been implanted across the aneurysm neck as well as in the abdominal aorta. From these studies, a total of 65 devices (prototype FD (n = 30) and Derivo embolization device (n = 35)) additionally underwent micro-CT and MRI after angiographic follow-up and before being histologically examined. The different architectures of both devices were precisely comparable due to high-resolution micro-CT imaging. Micro-CT revealed wire fractures in nine cases (30 %) only with the prototype FD. In three cases (10 %), severe wire fractures correlated with an in-stent stenosis due to intimal hyperplasia. Other complications, like distal stent occlusions and post-stent stenosis, were seen in both groups and verified with both imaging techniques. Osseous metaplasia were correlated to calcifications seen with micro-CT. MRI enabled visualization of the position of the implanted devices relative to the aneurysm and revealed incomplete aneurysm neck coverage with the prototype FD in two cases (6.7 %). Micro-CT and 9.4-T MRI are valid to discover and understand occurring complications of flow diverters in the preclinical phase and can serve as evaluation tools to minimize complication rates of endovascular devices in the future. (orig.)

  4. Concomitant elevations of MMP-9, NGAL, proMMP-9/NGAL and neutrophil elastase in serum of smokers with chronic obstructive pulmonary disease.

    Science.gov (United States)

    Bchir, Sarra; Nasr, Hela Ben; Bouchet, Sandrine; Benzarti, Mohamed; Garrouch, Abdelhamid; Tabka, Zouhair; Susin, Santos; Chahed, Karim; Bauvois, Brigitte

    2017-07-01

    A growing body of evidence points towards smoking-related phenotypic differences in chronic obstructive pulmonary disease (COPD). As COPD is associated with systemic inflammation, we determined whether smoking status is related to serum levels of matrix metalloproteinase-9 (pro- and active MMP-9), neutrophil gelatinase-associated lipocalin (NGAL) and the proMMP-9/NGAL complex in patients with COPD. Serum samples were collected in 100 stable-phase COPD patients (82 smokers, 18 never-smokers) and 28 healthy adults (21 smokers, 7 never-smokers). Serum levels of studied factors were measured in ELISA. Our data provide the first evidence of simultaneously elevated serum levels of MMP-9, NGAL and proMMP-9/NGAL in COPD smokers. While the triad discriminated between smokers and non-smokers in the COPD group, MMP-9 and proMMP-9/NGAL (but not NGAL) discriminated between smokers with and without COPD. Adjustment for age and smoking pack-years did not alter the findings. Serum MMP-9, NGAL and proMMP-9/NGAL levels were not correlated with the GOLD stage or FEV1 decline. Furthermore, serum levels of neutrophil elastase (NE) and MMP-3 (but not of IL-6 and MMP-12) were also higher in COPD smokers than in healthy smokers before and after adjustment for age and pack-years. Among COPD smokers, levels of MMP-9, NGAL and proMMP-9/NGAL were positively correlated with NE (P < 0.0001) but not with the remaining factors. Gelatin zymography detected proMMP-9 in serum samples of healthy and COPD smoking groups. Our results suggest that associated serum levels of proMMP-9, NGAL, proMMP-9/NGAL and NE may reflect the state of systemic inflammation in COPD related to cigarette smoking. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  5. Polar Desolvation and Position 226 of Pancreatic and Neutrophil Elastases Are Crucial to their Affinity for the Kunitz-Type Inhibitors ShPI-1 and ShPI-1/K13L.

    Science.gov (United States)

    Hernández González, Jorge Enrique; García-Fernández, Rossana; Valiente, Pedro Alberto

    2015-01-01

    The Kunitz-type protease inhibitor ShPI-1 inhibits human neutrophil elastase (HNE, Ki = 2.35·10-8 M) but does not interact with the porcine pancreatic elastase (PPE); whereas its P1 site variant, ShPI-1/K13L, inhibits both HNE and PPE (Ki = 1.3·10-9 M, and Ki = 1.2·10-8 M, respectively). By employing a combination of molecular modeling tools, e.g., structural alignment, molecular dynamics simulations and Molecular Mechanics Generalized-Born/Poisson-Boltzmann Surface Area free energy calculations, we showed that D226 of HNE plays a critical role in the interaction of this enzyme with ShPI-1 through the formation of a strong salt bridge and hydrogen bonds with K13 at the inhibitor's P1 site, which compensate the unfavorable polar-desolvation penalty of the latter residue. Conversely, T226 of PPE is unable to establish strong interactions with K13, thereby precluding the insertion of K13 side-chain into the S1 subsite of this enzyme. An alternative conformation of K13 site-chain placed at the entrance of the S1 subsite of PPE, similar to that observed in the crystal structure of ShPI-1 in complex with chymotrypsin (PDB: 3T62), is also unfavorable due to the lack of stabilizing pair-wise interactions. In addition, our results suggest that the higher affinity of ShPI-1/K13L for both elastases mainly arises from the lower polar-desolvation penalty of L13 compared to that of K13, and not from stronger pair-wise interactions of the former residue with those of each enzyme. These results provide insights into the PPE and HNE inhibition and may contribute to the design of more potent and/or specific inhibitors toward one of these proteases.

  6. Mediation Analysis with Multiple Mediators

    OpenAIRE

    VanderWeele, T.J.; Vansteelandt, S.

    2014-01-01

    Recent advances in the causal inference literature on mediation have extended traditional approaches to direct and indirect effects to settings that allow for interactions and non-linearities. In this paper, these approaches from causal inference are further extended to settings in which multiple mediators may be of interest. Two analytic approaches, one based on regression and one based on weighting are proposed to estimate the effect mediated through multiple mediators and the effects throu...

  7. Endothelin‐1 mediates natriuresis but not polyuria during vitamin D‐induced acute hypercalcaemia

    Science.gov (United States)

    Tokonami, Natsuko; Cheval, Lydie; Monnay, Isabelle; Meurice, Guillaume; Loffing, Johannes; Feraille, Eric

    2017-01-01

    Key points Hypercalcaemia can occur under various pathological conditions, such as primary hyperparathyroidism, malignancy or granulomatosis, and it induces natriuresis and polyuria in various species via an unknown mechanism.A previous study demonstrated that hypercalcaemia induced by vitamin D in rats increased endothelin (ET)‐1 expression in the distal nephron, which suggests the involvement of the ET system in hypercalcaemia‐induced effects.In the present study, we demonstrate that, during vitamin D‐induced hypercalcaemia, the activation of ET system by increased ET‐1 is responsible for natriuresis but not for polyuria.Vitamin D‐treated hypercalcaemic mice showed a blunted response to amiloride, suggesting that epithelial sodium channel function is inhibited.We have identified an original pathway that specifically mediates the effects of vitamin D‐induced hypercalcaemia on sodium handling in the distal nephron without affecting water handling. Abstract Acute hypercalcaemia increases urinary sodium and water excretion; however, the underlying molecular mechanism remains unclear. Because vitamin D‐induced hypercalcaemia increases the renal expression of endothelin (ET)‐1, we hypothesized that ET‐1 mediates the effects of hypercalcaemia on renal sodium and water handling. Hypercalcaemia was induced in 8‐week‐old, parathyroid hormone‐supplemented, male mice by oral administration of dihydrotachysterol (DHT) for 3 days. DHT‐treated mice became hypercalcaemic and displayed increased urinary water and sodium excretion compared to controls. mRNA levels of ET‐1 and the transcription factors CCAAT‐enhancer binding protein β and δ were specifically increased in the distal convoluted tubule and downstream segments in DHT‐treated mice. To examine the role of the ET system in hypercalcaemia‐induced natriuresis and polyuria, mice were treated with the ET‐1 receptor antagonist macitentan, with or without DHT. Mice treated with both

  8. Endothelin-1 mediates natriuresis but not polyuria during vitamin D-induced acute hypercalcaemia.

    Science.gov (United States)

    Tokonami, Natsuko; Cheval, Lydie; Monnay, Isabelle; Meurice, Guillaume; Loffing, Johannes; Feraille, Eric; Houillier, Pascal

    2017-04-15

    Hypercalcaemia can occur under various pathological conditions, such as primary hyperparathyroidism, malignancy or granulomatosis, and it induces natriuresis and polyuria in various species via an unknown mechanism. A previous study demonstrated that hypercalcaemia induced by vitamin D in rats increased endothelin (ET)-1 expression in the distal nephron, which suggests the involvement of the ET system in hypercalcaemia-induced effects. In the present study, we demonstrate that, during vitamin D-induced hypercalcaemia, the activation of ET system by increased ET-1 is responsible for natriuresis but not for polyuria. Vitamin D-treated hypercalcaemic mice showed a blunted response to amiloride, suggesting that epithelial sodium channel function is inhibited. We have identified an original pathway that specifically mediates the effects of vitamin D-induced hypercalcaemia on sodium handling in the distal nephron without affecting water handling. Acute hypercalcaemia increases urinary sodium and water excretion; however, the underlying molecular mechanism remains unclear. Because vitamin D-induced hypercalcaemia increases the renal expression of endothelin (ET)-1, we hypothesized that ET-1 mediates the effects of hypercalcaemia on renal sodium and water handling. Hypercalcaemia was induced in 8-week-old, parathyroid hormone-supplemented, male mice by oral administration of dihydrotachysterol (DHT) for 3 days. DHT-treated mice became hypercalcaemic and displayed increased urinary water and sodium excretion compared to controls. mRNA levels of ET-1 and the transcription factors CCAAT-enhancer binding protein β and δ were specifically increased in the distal convoluted tubule and downstream segments in DHT-treated mice. To examine the role of the ET system in hypercalcaemia-induced natriuresis and polyuria, mice were treated with the ET-1 receptor antagonist macitentan, with or without DHT. Mice treated with both macitentan and DHT displayed hypercalcaemia and polyuria

  9. Isolation of Microsporum gypseum in soil samples from different geographical regions of Brazil, evaluation of the extracellular proteolytic enzymes activities (keratinase and elastase and molecular sequencing of selected strains

    Directory of Open Access Journals (Sweden)

    Mauro Cintra Giudice

    2012-09-01

    Full Text Available A survey of Microsporum gypseum was conducted in soil samples in different geographical regions of Brazil. The isolation of dermatophyte from soil samples was performed by hair baiting technique and the species were identified by morphology studies. We analyzed 692 soil samples and the recuperating rate was 19.2%. The activities of keratinase and elastase were quantitatively performed in 138 samples. The sequencing of the ITS region of rDNA was performed in representatives samples. M. gypseum isolates showed significant quantitative differences in the expression of both keratinase and elastase, but no significant correlation was observed between these enzymes. The sequencing of the representative samples revealed the presence of two teleomorphic species of M. gypseum (Arthroderma gypseum and A. incurvatum. The enzymatic activities may play an important role in the pathogenicity and a probable adaptation of this fungus to the animal parasitism. Using the phenotypical and molecular analysis, the Microsporum identification and their teleomorphic states will provide a useful and reliable identification system.

  10. Complex Mediation

    DEFF Research Database (Denmark)

    Bødker, Susanne; Andersen, Peter Bøgh

    2005-01-01

    This article has its starting point in a large number of empirical findings regarding computer-mediated work. These empirical findings have challenged our understanding of the role of mediation in such work; on the one hand as an aspect of communication and cooperation at work and on the other hand...... as an aspect of human engagement with instruments of work. On the basis of previous work in activity-theoretical and semiotic human—computer interaction, we propose a model to encompass both of these aspects. In a dialogue with our empirical findings we move on to propose a number of types of mediation...... that have helped to enrich our understanding of mediated work and the design of computer mediation for such work....

  11. Oenothera paradoxa defatted seeds extract and its bioactive component penta-O-galloyl-β-D-glucose decreased production of reactive oxygen species and inhibited release of leukotriene B4, interleukin-8, elastase, and myeloperoxidase in human neutrophils.

    Science.gov (United States)

    Kiss, Anna K; Filipek, Agnieszka; Czerwińska, Monika; Naruszewicz, Marek

    2010-09-22

    In this study, we analyzed ex vivo the effect of an aqueous extract of Oenothera paradoxa defatted seeds on the formation of neutrophil-derived oxidants. For defining active compounds, we also tested lypophilic extract constituents such as gallic acid, (+)-catechin, ellagic acid, and penta-O-galloyl-β-D-glucose and a hydrophilic fraction containing polymeric procyanidins. The anti-inflammatory potential of the extract and compounds was tested by determining the release from activated neutrophils of elastase, myeloperoxidase, interleukin-8 (IL-8), and leukotriene B4 (LTB4), which are considered relevant for the pathogenesis of cardiovascular diseases. The extract of O. paradoxa defatted seeds displays potent antioxidant effects against both 4β-phorbol-12β-myristate-α13-acetate- and formyl-met-leu-phenylalanine-induced reactive oxygen species production in neutrophils with IC50 values around 0.2 μg/mL. All types of polyphenolics present in the extract contributed to the extract antioxidant activity. According to their IC50 values, penta-O-galloyl-β-D-glucose was the more potent constituent of the extract. In cell-free assays, we demonstrated that this effect is partially due to the scavenging of O2- and H2O2 oxygen species. The extract and especially penta-O-galloyl-β-D-glucose significantly inhibit elastase, myeloperoxidase IL-8, and LTB4 release with an IC50 for penta-O-galloyl-β-D-glucose of 17±1, 15±1, 6.5±2.5, and around 20 μM, respectively. The inhibition of penta-O-galloyl-β-D-glucose on reactive oxygen species and especially on O2- production, myeloperoxidase, and chemoattractant release may reduce the interaction of polymorphonuclear leukocyte with the vascular endothelium and by that potentially diminish the risk of progression of atherosclerosis development.

  12. Mediatized play

    DEFF Research Database (Denmark)

    Johansen, Stine Liv

    Children’s play must nowadays be understood as a mediatized field in society and culture. Media – understood in a very broad sense - holds severe explanatory power in describing and understanding the practice of play, since play happens both with, through and inspired by media of different sorts........ In this presentation the case of ‘playing soccer’ will be outlined through its different mediated manifestations, including soccer games and programs on TV, computer games, magazines, books, YouTube videos and soccer trading cards....

  13. Mediating Business

    DEFF Research Database (Denmark)

    "Mediating Business" is a study of the expansion of business journalism. Building on evidence from Denmark, Finland, Norway and Sweden, "Mediating Business" is a comparative and multidisciplinary study of one of the major transformations of the mass media and the realm of business - nationally...... and globally. The book explores the history of key innovations and innovators in the business press. It analyzes changes in the discourse of business journalism associated with the growth in business news and the development of new ways of framing business issues and events. Finally, it examines...... the organizational implications of the increased media visibility of business and, in particular, the development of corporate governance and media relations....

  14. Estrogen, progesterone, and genistein differentially regulate levels of expression of α-, β-, and γ-epithelial sodium channel (ENaC) and α-sodium potassium pump (Na⁺/K⁺-ATPase) in the uteri of sex steroid-deficient rats.

    Science.gov (United States)

    Chinigarzadeh, Asma; Muniandy, Sekaran; Salleh, Naguib

    2015-10-01

    Estrogen, progesterone, and genistein could induce changes in uterine fluid volume and Na(+) concentration. Progesterone upregulates expression of epithelial sodium channel (ENaC) and Na(+)/K(+)-ATPase which contributed toward these changes. However, effects of estrogen and genistein were unknown. This study therefore investigated changes in expression of these proteins in the uterus under estrogen, progesterone, and genistein influences to further understand mechanisms underlying sex steroids and phytoestrogen effects on uterine fluid Na(+) regulation. In this study, uteri of ovariectomized female rats receiving 7-day treatment with genistein (25, 50, and 100 mg/kg/day), estrogen (0.8 × 10(-4) mg/kg/day), or progesterone (4 mg/kg/day) were harvested, and expression levels of α-, β-, and γ-ENaC proteins and messenger RNAs (mRNAs) and α-Na(+)/K(+)-ATPase protein were determined by Western blotting (proteins) and real-time polymerase chain reaction (mRNA). Meanwhile, distribution of α-, β-, and γ-ENaC and α-Na(+)/K(+)-ATPase proteins in the uterus was identified by immunohistochemistry. Our findings indicated that expression of α-, β-, and γ-ENaC proteins and mRNAs and α-Na(+)/K(+)-ATPase protein were enhanced under progesterone influence. Lower expressions were noted under estrogen and genistein influences compared to progesterone. Under estrogen, progesterone, and genistein influences, α- and β-ENaC were distributed at apical membrane and γ-ENaC was distributed at apical and basolateral membranes of uterine luminal epithelia. Under progesterone influence, α-Na(+)/K(+)-ATPase was highly expressed at basolateral membrane. In conclusion, high expression of α-, β-, and γ-ENaC and α-Na(+)/K(+)-ATPase under progesterone influence would contribute toward increased uterine fluid Na(+) reabsorption, whereas lesser expression of these proteins under estrogen and genistein influences would contribute toward lower reabsorption of uterine fluid Na

  15. mediation: R package for causal mediation analysis

    OpenAIRE

    Tingley, Dustin; Yamamoto, Teppei; Hirose, Kentaro; Keele, Luke; Imai, Kosuke

    2012-01-01

    In this paper, we describe the R package mediation for conducting causal mediation analysis in applied empirical research. In many scientific disciplines, the goal of researchers is not only estimating causal effects of a treatment but also understanding the process in which the treatment causally affects the outcome. Causal mediation analysis is frequently used to assess potential causal mechanisms. The mediation package implements a comprehensive suite of statistical tools for conducting su...

  16. The endothelial αENaC contributes to vascular endothelial function in vivo

    DEFF Research Database (Denmark)

    Tarjus, Antoine; Maase, Martina; Jeggle, Pia

    2017-01-01

    The Epithelial Sodium Channel (ENaC) is a key player in renal sodium homeostasis. The expression of α β γ ENaC subunits has also been described in the endothelium and vascular smooth muscle, suggesting a role in vascular function. We recently demonstrated that endothelial ENaC is involved in aldo......-mediated dilation. Our data suggest that endothelial αENaC contributes to vascular endothelial function in vivo....

  17. Micro dynamics in mediation

    OpenAIRE

    Boserup, Hans

    2014-01-01

    The author has identified a number of styles in mediation, which lead to different processes and different outcomes. Through discourse and conversation analysis he examines the micro dynamics in three of these, the postmodern styles: systemic, transformative and narrative mediation. The differences between the three mediation ideologies and practice is illustrated through role play scripts enacted in each style. Mediator and providers of mediation and trainers in mediation are encouraged to a...

  18. Mutations in the ELA2 gene encoding neutrophil elastase are present in most patients with sporadic severe congenital neutropenia but only in some patients with the familial form of the disease.

    Science.gov (United States)

    Ancliff, P J; Gale, R E; Liesner, R; Hann, I M; Linch, D C

    2001-11-01

    Severe congenital neutropenia (SCN) was originally described as an autosomal recessive disorder. Subsequently, autosomal dominant and sporadic forms of the disease have been recognized. All forms are manifest by persistent severe neutropenia and recurrent bacterial infection. In contrast, cyclical hematopoiesis is characterized by periodic neutropenia inter-spaced with (near) normal neutrophil counts. Recently, linkage analysis on 13 affected pedigrees identified chromosome 19p13.3 as the likely position for mutations in cyclical hematopoiesis. Heterozygous mutations in the ELA2 gene encoding neutrophil elastase were detected in all families studied. Further work also demonstrated mutations in ELA2 in sporadic and autosomal dominant SCN. However, all mutations described to date are heterozygous and thus appear to act in a dominant fashion, which is inconsistent with an autosomal recessive disease. Therefore, the current study investigated whether mutations in ELA2 could account for the disease phenotype in classical autosomal recessive SCN and in the sporadic and autosomal dominant types. All 5 exons of ELA2 and their flanking introns were studied in 18 patients (3 autosomal recessive, 5 autosomal dominant [from 3 kindreds], and 10 sporadic) using direct automated sequencing. No mutations were found in the autosomal recessive families. A point mutation was identified in 1 of 3 autosomal dominant families, and a base substitution was identified in 8 of 10 patients with the sporadic form, though 1 was subsequently shown to be a low-frequency polymorphism. These results suggest that mutations in ELA2 are not responsible for classical autosomal recessive Kostmann syndrome but provide further evidence for the role of ELA2 in SCN.

  19. Regulation of Epithelial Sodium Transport via Epithelial Na+ Channel

    Science.gov (United States)

    Marunaka, Yoshinori; Niisato, Naomi; Taruno, Akiyuki; Ohta, Mariko; Miyazaki, Hiroaki; Hosogi, Shigekuni; Nakajima, Ken-ichi; Kusuzaki, Katsuyuki; Ashihara, Eishi; Nishio, Kyosuke; Iwasaki, Yoshinobu; Nakahari, Takashi; Kubota, Takahiro

    2011-01-01

    Renal epithelial Na+ transport plays an important role in homeostasis of our body fluid content and blood pressure. Further, the Na+ transport in alveolar epithelial cells essentially controls the amount of alveolar fluid that should be kept at an appropriate level for normal gas exchange. The epithelial Na+ transport is generally mediated through two steps: (1) the entry step of Na+ via epithelial Na+ channel (ENaC) at the apical membrane and (2) the extrusion step of Na+ via the Na+, K+-ATPase at the basolateral membrane. In general, the Na+ entry via ENaC is the rate-limiting step. Therefore, the regulation of ENaC plays an essential role in control of blood pressure and normal gas exchange. In this paper, we discuss two major factors in ENaC regulation: (1) activity of individual ENaC and (2) number of ENaC located at the apical membrane. PMID:22028593

  20. alphaENaC-mediated lithium absorption promotes nephrogenic diabetes insipidus

    NARCIS (Netherlands)

    Christensen, B.M.; Zuber, A.M.; Loffing, J.; Stehle, J.C.; Deen, P.M.T.; Rossier, B.C.; Hummler, E.

    2011-01-01

    Lithium-induced nephrogenic diabetes insipidus (NDI) is accompanied by polyuria, downregulation of aquaporin 2 (AQP2), and cellular remodeling of the collecting duct (CD). The amiloride-sensitive epithelial sodium channel (ENaC) is a likely candidate for lithium entry. Here, we subjected transgenic

  1. Autophagy Mediates Interleukin-1β Secretion in Human Neutrophils

    Directory of Open Access Journals (Sweden)

    Leonardo Iula

    2018-02-01

    AEBSF reduced IL-1β secretion. Moreover, IL-1β could be also found colocalizing with elastase, suggesting both some vesicles containing IL-1β intersect azurophil granules content and that serine proteases also regulate IL-1β secretion. Altogether, our findings indicate that an unconventional autophagy-mediated secretory pathway mediates IL-1β secretion in human neutrophils.

  2. Nordic Mediation Reseach

    DEFF Research Database (Denmark)

    A presentation of 12 studies on mediation from researchers from Denmark, Finland, Norway and Sweden.......A presentation of 12 studies on mediation from researchers from Denmark, Finland, Norway and Sweden....

  3. Bayesian Mediation Analysis

    OpenAIRE

    Yuan, Ying; MacKinnon, David P.

    2009-01-01

    This article proposes Bayesian analysis of mediation effects. Compared to conventional frequentist mediation analysis, the Bayesian approach has several advantages. First, it allows researchers to incorporate prior information into the mediation analysis, thus potentially improving the efficiency of estimates. Second, under the Bayesian mediation analysis, inference is straightforward and exact, which makes it appealing for studies with small samples. Third, the Bayesian approach is conceptua...

  4. mediation: R Package for Causal Mediation Analysis

    Directory of Open Access Journals (Sweden)

    Dustin Tingley

    2014-09-01

    Full Text Available In this paper, we describe the R package mediation for conducting causal mediation analysis in applied empirical research. In many scientific disciplines, the goal of researchers is not only estimating causal effects of a treatment but also understanding the process in which the treatment causally affects the outcome. Causal mediation analysis is frequently used to assess potential causal mechanisms. The mediation package implements a comprehensive suite of statistical tools for conducting such an analysis. The package is organized into two distinct approaches. Using the model-based approach, researchers can estimate causal mediation effects and conduct sensitivity analysis under the standard research design. Furthermore, the design-based approach provides several analysis tools that are applicable under different experimental designs. This approach requires weaker assumptions than the model-based approach. We also implement a statistical method for dealing with multiple (causally dependent mediators, which are often encountered in practice. Finally, the package also offers a methodology for assessing causal mediation in the presence of treatment noncompliance, a common problem in randomized trials.

  5. Bayesian Mediation Analysis

    Science.gov (United States)

    Yuan, Ying; MacKinnon, David P.

    2009-01-01

    In this article, we propose Bayesian analysis of mediation effects. Compared with conventional frequentist mediation analysis, the Bayesian approach has several advantages. First, it allows researchers to incorporate prior information into the mediation analysis, thus potentially improving the efficiency of estimates. Second, under the Bayesian…

  6. Esophageal desalination is mediated by Na⁺, H⁺ exchanger-2 in the gulf toadfish (Opsanus beta).

    Science.gov (United States)

    Esbaugh, Andrew J; Grosell, Martin

    2014-05-01

    Esophageal desalination is a crucial step in the gastrointestinal water absorption pathway, as this pre-intestinal processing establishes the osmotic conditions necessary for water absorption. Previous work has shown that esophageal Na(+) absorption is amiloride sensitive; however, it is as yet unclear if Na(+), H(+) exchangers (NHE) or Na(+) channels (ENaC) are responsible. The purpose of the current study was therefore to investigate the roles that NHE isoforms may play in this process in a marine teleost, the gulf toadfish (Opsanus beta), as well as what role NHE isoforms may play in the downstream intestinal Na(+) transport. A combination of symmetrical current clamp and asymmetrical voltage clamp experiments showed the esophagus to contain both an ion absorptive current (I(sc)=0.83±0.68) and serosal side negative transepithelial potential (TEP=-4.9±0.6). (22)Na uptake (J(Na)(m→s)) was inhibited by 0.5 mM EIPA, with no effect of 0.1 mM amiloride, 1 mM furosemide or 1 mM thiazide. A Cl(-) free saline reduced J(Na)(m→s) by 40% while also reducing conductance and reversing TEP. These results suggest that both transcellular and paracellular components contribute to esophageal Na(+) transport, with transcellular transport mediated by NHE. The NHE1, NHE2 and NHE3 genes were amplified and tissue distribution analysis by real-time PCR showed high NHE2 expression levels in the esophagus and stomach. Little NHE3 expression was observed throughout the gastrointestinal tract, and NHE2 expression was absent from the intestine. Hypersalinity (60 ppt) had no effect on the expression profile of NHE2, slc4a2, scl26a6, CAc or V-type ATPase (β-subunit), suggesting that esophageal desalination is less flexible in response to osmotic stress than the intestine. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. General gauge mediation

    International Nuclear Information System (INIS)

    Meade, Patrick; Seiberg, Nathan; Shih, David

    2009-01-01

    We give a general definition of gauge mediated supersymmetry breaking which encompasses all the known gauge mediation models. In particular, it includes both models with messengers as well as direct mediation models. A formalism for computing the soft terms in the generic model is presented. Such a formalism is necessary in strongly-coupled direct mediation models where perturbation theory cannot be used. It allows us to identify features of the entire class of gauge mediation models and to distinguish them from specific signatures of various subclasses. (author)

  8. Bayesian dynamic mediation analysis.

    Science.gov (United States)

    Huang, Jing; Yuan, Ying

    2017-12-01

    Most existing methods for mediation analysis assume that mediation is a stationary, time-invariant process, which overlooks the inherently dynamic nature of many human psychological processes and behavioral activities. In this article, we consider mediation as a dynamic process that continuously changes over time. We propose Bayesian multilevel time-varying coefficient models to describe and estimate such dynamic mediation effects. By taking the nonparametric penalized spline approach, the proposed method is flexible and able to accommodate any shape of the relationship between time and mediation effects. Simulation studies show that the proposed method works well and faithfully reflects the true nature of the mediation process. By modeling mediation effect nonparametrically as a continuous function of time, our method provides a valuable tool to help researchers obtain a more complete understanding of the dynamic nature of the mediation process underlying psychological and behavioral phenomena. We also briefly discuss an alternative approach of using dynamic autoregressive mediation model to estimate the dynamic mediation effect. The computer code is provided to implement the proposed Bayesian dynamic mediation analysis. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  9. Causal mediation analysis with multiple mediators.

    Science.gov (United States)

    Daniel, R M; De Stavola, B L; Cousens, S N; Vansteelandt, S

    2015-03-01

    In diverse fields of empirical research-including many in the biological sciences-attempts are made to decompose the effect of an exposure on an outcome into its effects via a number of different pathways. For example, we may wish to separate the effect of heavy alcohol consumption on systolic blood pressure (SBP) into effects via body mass index (BMI), via gamma-glutamyl transpeptidase (GGT), and via other pathways. Much progress has been made, mainly due to contributions from the field of causal inference, in understanding the precise nature of statistical estimands that capture such intuitive effects, the assumptions under which they can be identified, and statistical methods for doing so. These contributions have focused almost entirely on settings with a single mediator, or a set of mediators considered en bloc; in many applications, however, researchers attempt a much more ambitious decomposition into numerous path-specific effects through many mediators. In this article, we give counterfactual definitions of such path-specific estimands in settings with multiple mediators, when earlier mediators may affect later ones, showing that there are many ways in which decomposition can be done. We discuss the strong assumptions under which the effects are identified, suggesting a sensitivity analysis approach when a particular subset of the assumptions cannot be justified. These ideas are illustrated using data on alcohol consumption, SBP, BMI, and GGT from the Izhevsk Family Study. We aim to bridge the gap from "single mediator theory" to "multiple mediator practice," highlighting the ambitious nature of this endeavor and giving practical suggestions on how to proceed. © 2014 The Authors Biometrics published by Wiley Periodicals, Inc. on behalf of International Biometric Society.

  10. Flexible Mediation Analysis With Multiple Mediators.

    Science.gov (United States)

    Steen, Johan; Loeys, Tom; Moerkerke, Beatrijs; Vansteelandt, Stijn

    2017-07-15

    The advent of counterfactual-based mediation analysis has triggered enormous progress on how, and under what assumptions, one may disentangle path-specific effects upon combining arbitrary (possibly nonlinear) models for mediator and outcome. However, current developments have largely focused on single mediators because required identification assumptions prohibit simple extensions to settings with multiple mediators that may depend on one another. In this article, we propose a procedure for obtaining fine-grained decompositions that may still be recovered from observed data in such complex settings. We first show that existing analytical approaches target specific instances of a more general set of decompositions and may therefore fail to provide a comprehensive assessment of the processes that underpin cause-effect relationships between exposure and outcome. We then outline conditions for obtaining the remaining set of decompositions. Because the number of targeted decompositions increases rapidly with the number of mediators, we introduce natural effects models along with estimation methods that allow for flexible and parsimonious modeling. Our procedure can easily be implemented using off-the-shelf software and is illustrated using a reanalysis of the World Health Organization's Large Analysis and Review of European Housing and Health Status (WHO-LARES) study on the effect of mold exposure on mental health (2002-2003). © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  11. Technology-Use Mediation

    DEFF Research Database (Denmark)

    Bansler, Jørgen P.; Havn, Erling C.

    2003-01-01

    This study analyzes how a group of ‘mediators’ in a large, multinational company adapted a computer-mediated communication technology (a ‘virtual workspace’) to the organizational context (and vice versa) by modifying features of the technology, providing ongoing support for users, and promoting...... appropriate conventions of use. Our findings corroborate earlier research on technology-use mediation, which suggests that such mediators can exert considerable influence on how a particular technology will be established and used in an organization. However, this study also indicates that the process...... of technology-use mediation is more complex and indeterminate than earlier literature suggests. In particular, we want to draw attention to the fact that advanced computer-mediated communication technologies are equivocal and that technology-use mediation consequently requires ongoing sensemaking (Weick 1995)....

  12. The Schizosaccharomyces pombe Mediator

    DEFF Research Database (Denmark)

    Venturi, Michela

    , Schizosaccharomyces pombe and mammalian Mediator. In our study, we have taken the S. pombe Mediator into consideration and characterized genetically and biochemically two subunits already know in S. cerevisiae, Med9 and Med11, but still not identified in the S. pombe Mediator. Genetic analysis has shown that med9......In the past several years great attention has been dedicated to the characterization of the Mediator complex in a different range of model organisms. Mediator is a conserved co-activator complex involved in transcriptional regulation and it conveys signals from regulatory transcription factors...... to the basal transcription machinery. Mediator was initially isolated from Saccharomyces cerevisiae based on its ability to render a RNA polymerase II in vitro transcription system responsive to activators. Additionally, structural studies have revealed striking structural similarities between S. cerevisiae...

  13. Applied mediation analyses

    DEFF Research Database (Denmark)

    Lange, Theis; Hansen, Kim Wadt; Sørensen, Rikke

    2017-01-01

    In recent years, mediation analysis has emerged as a powerful tool to disentangle causal pathways from an exposure/treatment to clinically relevant outcomes. Mediation analysis has been applied in scientific fields as diverse as labour market relations and randomized clinical trials of heart...... disease treatments. In parallel to these applications, the underlying mathematical theory and computer tools have been refined. This combined review and tutorial will introduce the reader to modern mediation analysis including: the mathematical framework; required assumptions; and software implementation...

  14. Immunologically mediated oral diseases

    OpenAIRE

    Jimson, Sudha; Balachader, N.; Anita, N.; Babu, R.

    2015-01-01

    Immune mediated diseases of oral cavity are uncommon. The lesions may be self-limiting and undergo remission spontaneously. Among the immune mediated oral lesions the most important are lichen planus, pemphigus, erythema multiformi, epidermolysis bullosa, systemic lupus erythematosis. Cellular and humoral mediated immunity play a major role directed against epithelial and connective tissue in chronic and recurrent patterns. Confirmatory diagnosis can be made by biopsy, direct and indirect imm...

  15. Implementing general gauge mediation

    International Nuclear Information System (INIS)

    Carpenter, Linda M.; Dine, Michael; Festuccia, Guido; Mason, John D.

    2009-01-01

    Recently there has been much progress in building models of gauge mediation, often with predictions different than those of minimal gauge mediation. Meade, Seiberg, and Shih have characterized the most general spectrum which can arise in gauge-mediated models. We discuss some of the challenges of building models of general gauge mediation, especially the problem of messenger parity and issues connected with R symmetry breaking and CP violation. We build a variety of viable, weakly coupled models which exhibit some or all of the possible low energy parameters.

  16. Teaching Mediated Public Relations.

    Science.gov (United States)

    Kent, Michael L.

    2001-01-01

    Discusses approaches to teaching a mediated public relations course, emphasizing the World Wide Web. Outlines five course objectives, assignments and activities, evaluation, texts, and lecture topics. Argues that students mastering these course objectives will understand ethical issues relating to media use, using mediated technology in public…

  17. Fashion, Mediations & Method Assemblages

    DEFF Research Database (Denmark)

    Sommerlund, Julie; Jespersen, Astrid Pernille

    of handling multiple, fluid realities with multiple, fluid methods. Empirically, the paper works with mediation in fashion - that is efforts the active shaping of relations between producer and consumer through communication, marketing and PR. Fashion mediation is by no means simple, but organise complex...

  18. The Mediated Transparent Society

    DEFF Research Database (Denmark)

    Backer, Lise

    2001-01-01

    in the mediated transparent society. The paper concludes that, based on these analyses, the mediated panopticism working on the business segment is not an effective disciplinary apparatus, which can guarantee that business corporations are carrying out important ecological or ethical improvements....

  19. Laccase/Mediator Systems

    NARCIS (Netherlands)

    Hilgers, Roelant; Vincken, Jean Paul; Gruppen, Harry; Kabel, Mirjam A.

    2018-01-01

    Laccase-mediator systems (LMS) have been widely studied for their capacity to oxidize the nonphenolic subunits of lignin (70-90% of the polymer). The phenolic subunits (10-30% of the polymer), which can also be oxidized without mediators, have received considerably less attention. Consequently, it

  20. The multitalented Mediator complex.

    Science.gov (United States)

    Carlsten, Jonas O P; Zhu, Xuefeng; Gustafsson, Claes M

    2013-11-01

    The Mediator complex is needed for regulated transcription of RNA polymerase II (Pol II)-dependent genes. Initially, Mediator was only seen as a protein bridge that conveyed regulatory information from enhancers to the promoter. Later studies have added many other functions to the Mediator repertoire. Indeed, recent findings show that Mediator influences nearly all stages of transcription and coordinates these events with concomitant changes in chromatin organization. We review the multitude of activities associated with Mediator and discuss how this complex coordinates transcription with other cellular events. We also discuss the inherent difficulties associated with in vivo characterization of a coactivator complex that can indirectly affect diverse cellular processes via changes in gene transcription. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Music, radio and mediatization

    DEFF Research Database (Denmark)

    Michelsen, Morten; Krogh, Mads

    2016-01-01

    of mediatization where media as such seem to be ascribed agency. Instead, we consider historical accounts of music–radio in order to address the complex nonlinearity of concrete processes of mediatization as they take place in the multiple meetings between a decentred notion of radio and musical life.......Mediatization has become a key concept for understanding the relations between media and other cultural and social fields. Contributing to the discussions related to the concept of mediatization, this article discusses how practices of radio and music(al life) influence each other. We follow Deacon......’s and Stanyer’s advice to supplement the concept of mediatization with ‘a series of additional concepts at lower levels of abstraction’ and suggest, in this respect, the notion of heterogeneous milieus of music–radio. Hereby, we turn away from the all-encompassing perspectives related to the concept...

  2. General resonance mediation

    International Nuclear Information System (INIS)

    McGarrie, Moritz

    2012-07-01

    We extend the framework of general gauge mediation to cases where the mediating fields have a nontrivial spectral function, as might arise from strong dynamics. We demonstrate through examples that this setup describes a broad class of possible models of gauge mediated supersymmetry breaking. A main emphasis is to give general formulas for cross sections for σ(visible → hidden) in these resonance models. We will also give formulas for soft masses, A-terms and demonstrate the framework with a holographic setup.

  3. General resonance mediation

    Energy Technology Data Exchange (ETDEWEB)

    McGarrie, Moritz

    2012-07-15

    We extend the framework of general gauge mediation to cases where the mediating fields have a nontrivial spectral function, as might arise from strong dynamics. We demonstrate through examples that this setup describes a broad class of possible models of gauge mediated supersymmetry breaking. A main emphasis is to give general formulas for cross sections for {sigma}(visible {yields} hidden) in these resonance models. We will also give formulas for soft masses, A-terms and demonstrate the framework with a holographic setup.

  4. Positively deflected anomaly mediation

    International Nuclear Information System (INIS)

    Okada, Nobuchika

    2002-01-01

    We generalize the so-called 'deflected anomaly mediation' scenario to the case where threshold corrections of heavy messengers to the sparticle squared masses are positive. A concrete model realizing this scenario is also presented. The tachyonic slepton problem can be fixed with only a pair of messengers. The resultant sparticle mass spectrum is quite different from that in the conventional deflected anomaly mediation scenario, but is similar to the one in the gauge mediation scenario. The lightest sparticle is mostly B-ino

  5. Polyarene mediators for mediated redox flow battery

    Science.gov (United States)

    Delnick, Frank M.; Ingersoll, David; Liang, Chengdu

    2018-01-02

    The fundamental charge storage mechanisms in a number of currently studied high energy redox couples are based on intercalation, conversion, or displacement reactions. With exception to certain metal-air chemistries, most often the active redox materials are stored physically in the electrochemical cell stack thereby lowering the practical gravimetric and volumetric energy density as a tradeoff to achieve reasonable power density. In a general embodiment, a mediated redox flow battery includes a series of secondary organic molecules that form highly reduced anionic radicals as reaction mediator pairs for the reduction and oxidation of primary high capacity redox species ex situ from the electrochemical cell stack. Arenes are reduced to stable anionic radicals that in turn reduce a primary anode to the charged state. The primary anode is then discharged using a second lower potential (more positive) arene. Compatible separators and solvents are also disclosed herein.

  6. Making mediation work.

    Science.gov (United States)

    Arif, Zeba

    2016-10-26

    Mediation can be an effective way of solving conflict between staff members. It signifies a willingness for people to work together to discuss their differences in a constructive way, before going down the official grievance route.

  7. Technology-Use Mediation

    DEFF Research Database (Denmark)

    Bansler, Jørgen P.; Havn, Erling C.

    2004-01-01

    Implementation of new computer-mediated communication (CMC) systems in organizations is a complex socio-technical endeavour, involving the mutual adaptation of technology and organization over time. Drawing on the analytic concept of sensemaking, this paper provides a theoretical perspective...... that deepens our understanding of how organizations appropriate new electronic communication media. The paper analyzes how a group of mediators in a large, multinational company adapted a new web-based CMC technology (a virtual workspace) to the local organizational context (and vice versa) by modifying...... features of the technology, providing ongoing support for users, and promoting appropriate conventions of use. We found that these mediators exerted considerable influence on how the technology was established and used in the organization. The mediators were not neutral facilitators of a well...

  8. Understanding Mediation Support

    OpenAIRE

    Lanz, David; Pring, Jamie; von Burg, Corinne; Zeller, Mathias

    2017-01-01

    Recent decades have witnessed increasing institutionalization of mediation support through the establishment of mediation support structures (MSS) within foreign ministries and secretariats of multilateral organizations. This study sheds light on this trend and aims to better understand the emergence, design and development of different MSS. This study analyzes six MSS, namely those established in the United Nations (UN), the Organization for Security and Co-operation in Europe (OSCE), the Eu...

  9. ENVIRONMENTAL CONFLICT MEDIATION

    Directory of Open Access Journals (Sweden)

    GABRIELA G. MIHUT

    2011-04-01

    Full Text Available At a time of global economic crisis followed by resource crisis, a period in which the world seeks alternative resources through eco-investment, environmental conflicts are inevitable. Romania is among the few countries that do not pay enough attention to environmental conflicts and to the advantages to of solving them through mediation procedure. The present paper deals with areas in which conflicts can be applied in environmental mediation and its benefits.

  10. mma: An R Package for Mediation Analysis with Multiple Mediators

    OpenAIRE

    Qingzhao Yu; Bin Li

    2017-01-01

    Mediation refers to the effect transmitted by mediators that intervene in the relationship between an exposure and a response variable. Mediation analysis has been broadly studied in many fields. However, it remains a challenge for researchers to consider complicated associations among variables and to differentiate individual effects from multiple mediators. [1] proposed general definitions of mediation effects that were adaptable to all different types of response (categorical or continuous...

  11. Analysis of multiparty mediation processes

    NARCIS (Netherlands)

    Vuković, Siniša

    2013-01-01

    Crucial challenges for multiparty mediation processes include the achievement of adequate cooperation among the mediators and consequent coordination of their activities in the mediation process. Existing literature goes only as far as to make it clear that successful mediation requires necessary

  12. Mediation: The Wise Advocacy

    Directory of Open Access Journals (Sweden)

    Towseef Ahmad

    2016-01-01

    Full Text Available AbstractAdversarial litigation is not the only means of resolving disputes and settling of claims. There are various options. Alternative means of dispute resolution can save money and time, and can help to anchor and resolve the dispute while exploring valuable good offices, amicable approaches and facilitation. Mediation, as used in law, is a process of managing negotiation by a neutral third party in the form of Alternative Dispute Resolution (ADR, as a convenient way of resolving disputes between two or more parties with speediation processes. On the sidelines typically, a neutral third party, the mediator assists the parties to negotiate a settlement. The term “mediation” broadly refers to any instance in which a neutral third party helps others to reach an amicable and mutually acceptable agreement. More specifically, mediation has a structure, timetable and dynamic approaches that “ordinary” negotiations usually lack. The process helps the parties to flourish the healthy ideas which are different and distinct from the legal rights in a Court of law. It is well known in International Law also and disputants can submit their disputes to mediation in a variety of matters such as commercial, legal, diplomatic, workplace, community and family matters, which assumes a great significance and it is bricolaged within the framework of this article.Keywords: Adversarial, Litigation, Mediation, Negotiation and Amicable.

  13. Immunologically mediated oral diseases.

    Science.gov (United States)

    Jimson, Sudha; Balachader, N; Anita, N; Babu, R

    2015-04-01

    Immune mediated diseases of oral cavity are uncommon. The lesions may be self-limiting and undergo remission spontaneously. Among the immune mediated oral lesions the most important are lichen planus, pemphigus, erythema multiformi, epidermolysis bullosa, systemic lupus erythematosis. Cellular and humoral mediated immunity play a major role directed against epithelial and connective tissue in chronic and recurrent patterns. Confirmatory diagnosis can be made by biopsy, direct and indirect immunoflouresence, immune precipitation and immunoblotting. Therapeutic agents should be selected after thorough evaluation of immune status through a variety of tests and after determining any aggravating or provoking factors. Early and appropriate diagnosis is important for proper treatment planning contributing to better prognosis and better quality of life of patient.

  14. Immunologically mediated oral diseases

    Directory of Open Access Journals (Sweden)

    Sudha Jimson

    2015-01-01

    Full Text Available Immune mediated diseases of oral cavity are uncommon. The lesions may be self-limiting and undergo remission spontaneously. Among the immune mediated oral lesions the most important are lichen planus, pemphigus, erythema multiformi, epidermolysis bullosa, systemic lupus erythematosis. Cellular and humoral mediated immunity play a major role directed against epithelial and connective tissue in chronic and recurrent patterns. Confirmatory diagnosis can be made by biopsy, direct and indirect immunoflouresence, immune precipitation and immunoblotting. Therapeutic agents should be selected after thorough evaluation of immune status through a variety of tests and after determining any aggravating or provoking factors. Early and appropriate diagnosis is important for proper treatment planning contributing to better prognosis and better quality of life of patient.

  15. Causal mediation analysis with multiple causally non-ordered mediators.

    Science.gov (United States)

    Taguri, Masataka; Featherstone, John; Cheng, Jing

    2018-01-01

    In many health studies, researchers are interested in estimating the treatment effects on the outcome around and through an intermediate variable. Such causal mediation analyses aim to understand the mechanisms that explain the treatment effect. Although multiple mediators are often involved in real studies, most of the literature considered mediation analyses with one mediator at a time. In this article, we consider mediation analyses when there are causally non-ordered multiple mediators. Even if the mediators do not affect each other, the sum of two indirect effects through the two mediators considered separately may diverge from the joint natural indirect effect when there are additive interactions between the effects of the two mediators on the outcome. Therefore, we derive an equation for the joint natural indirect effect based on the individual mediation effects and their interactive effect, which helps us understand how the mediation effect works through the two mediators and relative contributions of the mediators and their interaction. We also discuss an extension for three mediators. The proposed method is illustrated using data from a randomized trial on the prevention of dental caries.

  16. Regulation of ENaC-mediated alveolar fluid clearance by insulin via PI3K/Akt pathway in LPS-induced acute lung injury.

    Science.gov (United States)

    Deng, Wang; Li, Chang-Yi; Tong, Jin; Zhang, Wei; Wang, Dao-Xin

    2012-03-30

    Stimulation of epithelial sodium channel (ENaC) increases Na(+) transport, a driving force of alveolar fluid clearance (AFC) to keep alveolar spaces free of edema fluid that is beneficial for acute lung injury (ALI). It is well recognized that regulation of ENaC by insulin via PI3K pathway, but the mechanism of this signaling pathway to regulate AFC and ENaC in ALI remains unclear. The aim of this study was to investigate the effect of insulin on AFC in ALI and clarify the pathway in which insulin regulates the expression of ENaC in vitro and in vivo. A model of ALI (LPS at a dose of 5.0 mg/kg) with non-hyperglycemia was established in Sprague-Dawley rats receiving continuous exogenous insulin by micro-osmotic pumps and wortmannin. The lungs were isolated for measurement of bronchoalveolar lavage fluid(BALF), total lung water content(TLW), and AFC after ALI for 8 hours. Alveolar epithelial type II cells were pre-incubated with LY294002, Akt inhibitor and SGK1 inhibitor 30 minutes before insulin treatment for 2 hours. The expressions of α-,β-, and γ-ENaC were detected by immunocytochemistry, reverse transcriptase polymerase chain reaction (RT-PCR) and western blotting. In vivo, insulin decreased TLW, enchanced AFC, increased the expressions of α-,β-, and γ-ENaC and the level of phosphorylated Akt, attenuated lung injury and improved the survival rate in LPS-induced ALI, the effects of which were blocked by wortmannin. Amiloride, a sodium channel inhibitor, significantly reduced insulin-induced increase in AFC. In vitro, insulin increased the expressions of α-,β-, and γ-ENaC as well as the level of phosphorylated Akt but LY294002 and Akt inhibitor significantly prevented insulin-induced increase in the expression of ENaC and the level of phosphorylated Akt respectively. Immunoprecipitation studies showed that levels of Nedd4-2 binding to ENaC were decreased by insulin via PI3K/Akt pathway. Our study demonstrated that insulin alleviated pulmonary edema and

  17. Regulation of ENaC-mediated alveolar fluid clearance by insulin via PI3K/Akt pathway in LPS-induced acute lung injury

    Directory of Open Access Journals (Sweden)

    Deng Wang

    2012-03-01

    Full Text Available Abstract Background Stimulation of epithelial sodium channel (ENaC increases Na+ transport, a driving force of alveolar fluid clearance (AFC to keep alveolar spaces free of edema fluid that is beneficial for acute lung injury (ALI. It is well recognized that regulation of ENaC by insulin via PI3K pathway, but the mechanism of this signaling pathway to regulate AFC and ENaC in ALI remains unclear. The aim of this study was to investigate the effect of insulin on AFC in ALI and clarify the pathway in which insulin regulates the expression of ENaC in vitro and in vivo. Methods A model of ALI (LPS at a dose of 5.0 mg/kg with non-hyperglycemia was established in Sprague-Dawley rats receiving continuous exogenous insulin by micro-osmotic pumps and wortmannin. The lungs were isolated for measurement of bronchoalveolar lavage fluid(BALF, total lung water content(TLW, and AFC after ALI for 8 hours. Alveolar epithelial type II cells were pre-incubated with LY294002, Akt inhibitor and SGK1 inhibitor 30 minutes before insulin treatment for 2 hours. The expressions of α-,β-, and γ-ENaC were detected by immunocytochemistry, reverse transcriptase polymerase chain reaction (RT-PCR and western blotting. Results In vivo, insulin decreased TLW, enchanced AFC, increased the expressions of α-,β-, and γ-ENaC and the level of phosphorylated Akt, attenuated lung injury and improved the survival rate in LPS-induced ALI, the effects of which were blocked by wortmannin. Amiloride, a sodium channel inhibitor, significantly reduced insulin-induced increase in AFC. In vitro, insulin increased the expressions of α-,β-, and γ-ENaC as well as the level of phosphorylated Akt but LY294002 and Akt inhibitor significantly prevented insulin-induced increase in the expression of ENaC and the level of phosphorylated Akt respectively. Immunoprecipitation studies showed that levels of Nedd4-2 binding to ENaC were decreased by insulin via PI3K/Akt pathway. Conclusions Our study

  18. Mediation analysis with time varying exposures and mediators.

    Science.gov (United States)

    VanderWeele, Tyler J; Tchetgen Tchetgen, Eric J

    2017-06-01

    In this paper we consider causal mediation analysis when exposures and mediators vary over time. We give non-parametric identification results, discuss parametric implementation, and also provide a weighting approach to direct and indirect effects based on combining the results of two marginal structural models. We also discuss how our results give rise to a causal interpretation of the effect estimates produced from longitudinal structural equation models. When there are time-varying confounders affected by prior exposure and mediator, natural direct and indirect effects are not identified. However, we define a randomized interventional analogue of natural direct and indirect effects that are identified in this setting. The formula that identifies these effects we refer to as the "mediational g-formula." When there is no mediation, the mediational g-formula reduces to Robins' regular g-formula for longitudinal data. When there are no time-varying confounders affected by prior exposure and mediator values, then the mediational g-formula reduces to a longitudinal version of Pearl's mediation formula. However, the mediational g-formula itself can accommodate both mediation and time-varying confounders and constitutes a general approach to mediation analysis with time-varying exposures and mediators.

  19. When Memories are Mediated

    DEFF Research Database (Denmark)

    Frølunde, Lisbeth; Bjerregaard, Mette

    2013-01-01

    that are mediated through stories: told and retold as oral stories through generations, as myths or sagas, or remediated as contemporary documentary film accounts or more fictional film accounts. In these processes of retelling acts of violence, transformations of meanings across time, cultural, social...

  20. Mediated Cultural Memories

    DEFF Research Database (Denmark)

    Frølunde, Lisbeth; Bjerregaard, Mette

    2013-01-01

    generations. Acts of mass violence also construct a sort of looking glass of culturally dominant memories that are mediated through stories: retold as oral stories through generations, as myths or sagas, or remediated in contemporary documentary or fiction films. In these processes of retelling acts...

  1. Cultural mediation in museums

    Directory of Open Access Journals (Sweden)

    Gherghina Boda

    2017-12-01

    Full Text Available If we perceive the museum not only as a place of storing and conserving the patrimony, but also of transmitting it, then we can also see it as a mediator through which cultures can become collective patrimony. Tightly connected to patrimonial appropriation, mediation appears from this perspective as a process and not an end, as it manifests itself in animation, communication and making knowledge popular in relation to a precise patrimony. That is why we can see cultural mediation as a transmission, as a transformation, as an action or social project which aims at creating social bonds, the museum thus being not only a place of meeting for the public with the objects exposed, but also as a place of meeting between different cultures. Thus, cultural mediation presents itself as the most efficient means for access to culture of all categories of the public, situated as the crossroads of culture, continuous education and entertainment and is inscribed in the field of informal education.

  2. The Bensberg Mediation Model

    Directory of Open Access Journals (Sweden)

    Raluca - Marilena Mihalcioiu

    2011-05-01

    Full Text Available The basis of the conflict through the mediation represents the objectives and procedures ofmediation, mediation of a conflict. The conflict will not be disclosed to others, but the parties will be creditedthe authority to resolve the conflict, the conflict among themselves with the help of a mediator. The disputeshould be resolved by the parties with help of a third party. The parties in conflict (it may be several personsare jointly responsible for the solution. They seek together a way that leads to long-term settlement of theconflict. The assumption of responsibility in this process strengthens the confidence and the importance oftheir decision. Important is that losers usually have no peace, because they are out for revenge. Winners don’tneed peace. If both parties lose, remains disappointing, with the understanding of which the conflict isresolved, will understand each other better developed. Reconciliation is therefore a longer-term goal.Conflicts also help to clarify roles. The paper presents Bensberg Model of Mediation, because this isdeveloped as a win win solution and his possible implementation in Romanian schools.

  3. Axionic mirage mediation

    International Nuclear Information System (INIS)

    Nakamura, Shuntaro; Okumura, Ken-ichi; Yamaguchi, Masahiro

    2008-01-01

    Although mirage mediation is one of the most plausible mediation mechanisms of supersymmetry breaking, it suffers from two crucial problems. One is the μ/Bμ problem, and the second is the cosmological one. The former stems from the fact that the B parameter tends to be comparable with the gravitino mass, which is 2 orders of magnitude larger than the other soft masses. The latter problem is caused by the decay of the modulus whose branching ratio into the gravitino pair is sizable. In this paper, we propose a model of mirage mediation, in which Peccei-Quinn symmetry is incorporated. In this axionic mirage mediation, it is shown that the Peccei-Quinn symmetry breaking scale is dynamically determined around 10 10 GeV to 10 12 GeV due to the supersymmetry breaking effects, and the μ problem can be solved naturally. Furthermore, in our model, the lightest supersymmetric particle (LSP) is the axino, that is, the superpartner of the axion. The overabundance of the LSPs due to decays of the modulus/gravitino, which is the most serious cosmological difficulty in the mirage mediation, can be avoided if the axino is sufficiently light. The next-LSPs (NLSPs) produced by the gravitino decay eventually decay into the axino LSPs, yielding the dominant component of the axinos remaining today. It is shown that the axino with a mass of O(100) MeV is naturally realized, which can constitute the dark matter of the Universe, with a free-streaming length of the order of 0.1 Mpc. The saxion, the real scalar component of the axion supermultiplet, can also be cosmologically harmless due to the dilution of the modulus decay. The lifetime of the NLSP is relatively long, but much shorter than 1 sec, when the big-bang nucleosynthesis commences. The decay of the NLSP would provide intriguing collider signatures

  4. Interventional Effects for Mediation Analysis with Multiple Mediators.

    Science.gov (United States)

    Vansteelandt, Stijn; Daniel, Rhian M

    2017-03-01

    The mediation formula for the identification of natural (in)direct effects has facilitated mediation analyses that better respect the nature of the data, with greater consideration of the need for confounding control. The default assumptions on which it relies are strong, however. In particular, they are known to be violated when confounders of the mediator-outcome association are affected by the exposure. This complicates extensions of counterfactual-based mediation analysis to settings that involve repeatedly measured mediators, or multiple correlated mediators. VanderWeele, Vansteelandt, and Robins introduced so-called interventional (in)direct effects. These can be identified under much weaker conditions than natural (in)direct effects, but have the drawback of not adding up to the total effect. In this article, we adapt their proposal to achieve an exact decomposition of the total effect, and extend it to the multiple mediator setting. Interestingly, the proposed effects capture the path-specific effects of an exposure on an outcome that are mediated by distinct mediators, even when-as often-the structural dependence between the multiple mediators is unknown, for instance, when the direction of the causal effects between the mediators is unknown, or there may be unmeasured common causes of the mediators.

  5. Mediation analysis with multiple versions of the mediator.

    Science.gov (United States)

    Vanderweele, Tyler J

    2012-05-01

    The causal inference literature has provided definitions of direct and indirect effects based on counterfactuals that generalize the approach found in the social science literature. However, these definitions presuppose well-defined hypothetical interventions on the mediator. In many settings, there may be multiple ways to fix the mediator to a particular value, and these various hypothetical interventions may have very different implications for the outcome of interest. In this paper, we consider mediation analysis when multiple versions of the mediator are present. Specifically, we consider the problem of attempting to decompose a total effect of an exposure on an outcome into the portion through the intermediate and the portion through other pathways. We consider the setting in which there are multiple versions of the mediator but the investigator has access only to data on the particular measurement, not information on which version of the mediator may have brought that value about. We show that the quantity that is estimated as a natural indirect effect using only the available data does indeed have an interpretation as a particular type of mediated effect; however, the quantity estimated as a natural direct effect, in fact, captures both a true direct effect and an effect of the exposure on the outcome mediated through the effect of the version of the mediator that is not captured by the mediator measurement. The results are illustrated using 2 examples from the literature, one in which the versions of the mediator are unknown and another in which the mediator itself has been dichotomized.

  6. Current Directions in Mediation Analysis

    Science.gov (United States)

    MacKinnon, David P.; Fairchild, Amanda J.

    2010-01-01

    Mediating variables continue to play an important role in psychological theory and research. A mediating variable transmits the effect of an antecedent variable on to a dependent variable, thereby providing more detailed understanding of relations among variables. Methods to assess mediation have been an active area of research for the last two decades. This paper describes the current state of methods to investigate mediating variables. PMID:20157637

  7. Current Directions in Mediation Analysis

    OpenAIRE

    MacKinnon, David P.; Fairchild, Amanda J.

    2009-01-01

    Mediating variables continue to play an important role in psychological theory and research. A mediating variable transmits the effect of an antecedent variable on to a dependent variable, thereby providing more detailed understanding of relations among variables. Methods to assess mediation have been an active area of research for the last two decades. This paper describes the current state of methods to investigate mediating variables.

  8. Dissociation in mediation

    Directory of Open Access Journals (Sweden)

    Daniela Muraru

    2008-01-01

    Full Text Available This paper approaches several texts that are part of the so-called discourse of mediation, adopting a pragma-dialectical perspective of the theory of dissociation. It is an attempt to identify the uses of dissociative patterns, with special emphasis on the indicators of dissociation. The paper investigates the various uses of the concept of dissociation as a discursive technique in the argumentation on the different aspects that are involved in international conflict, such as the discussion of the notion of peace. The purpose is to identify the role of dissociation, as a device strategically used by the mediator to help the parties minimize the disagreement space, and come to a conflict resolution.

  9. [Mediation in schools].

    Science.gov (United States)

    Mickley, Angela

    2006-01-01

    In this article the guiding questions concern the objectives and effectiveness of introducing mediation into an existing school culture of dominance, competition and selection. In addition the necessity will be shown of combining conflict resolution with organisational development and the introduction of a consensual ethics and behaviour code to attain sustainable results in creating a constructive and healthy school environment. Given scarce resources and little time the decisive role of artistic methods will be looked at in providing young people with flexible methods of expressing and negotiating their interests in a changing environment of values and power structures. Some aspects of the development of nonviolent communication, conflict resolution and mediation methods in schools in Germany will be focused on with special emphasis on the type of intervention used and its long term sustainable effects.

  10. Church mediation - een vak apart

    NARCIS (Netherlands)

    Annelies Klinefelter; dr Hans A.J. Jonker

    2009-01-01

    Welke rol kan mediation in de kerk spelen in de diverse geledingen en specifieke activiteiten? In dit artikel wordt ingegaan op kerkelijke conflicten, gelaagdheid in church mediation, en specifieke dilemma's van church mediation. Daarnaast komen enkele benaderingen aan bod zoals: helende

  11. The Mediatization of Philanthropy

    OpenAIRE

    Mitchell, Matthew

    2014-01-01

    This study seeks to better understand the motivations and mechanics of individuals contributing to nonprofits organizations today.  Through the prism of our highly mediatized (Hjarvard, 2008) social environment, this study examines the individual motivations and actions of cause-champions running in the 2013 NYC marathon and fundraising through social media and offline on behalf of the Michael J Fox Foundation (MJFF).  To gain the necessary detail and understanding of these micro-actions of a...

  12. Teachers as mediators

    DEFF Research Database (Denmark)

    Dorf, Hans; Kelly, Peter; Hohmann, Ulrike

    2012-01-01

    Within the context of lower secondary English teaching in South West England, this study identifies in broad terms the competing goals between which English teachers mediate and the explicit and hidden tensions that result. To understand the interactions of competing goals, teachers’ goal...... and cultural influences on practice. Yet the teachers observed moved smoothly between goal-oriented behaviours in a continuous and comfortable style, easily and without reflecting any tensions between them. Thus, this article elaborates an account of situated English teaching....

  13. mma: An R Package for Mediation Analysis with Multiple Mediators

    Directory of Open Access Journals (Sweden)

    Qingzhao Yu

    2017-04-01

    Full Text Available Mediation refers to the effect transmitted by mediators that intervene in the relationship between an exposure and a response variable. Mediation analysis has been broadly studied in many fields. However, it remains a challenge for researchers to consider complicated associations among variables and to differentiate individual effects from multiple mediators. [1] proposed general definitions of mediation effects that were adaptable to all different types of response (categorical or continuous, exposure, or mediation variables. With these definitions, multiple mediators of different types can be considered simultaneously, and the indirect effects carried by individual mediators can be separated from the total effect. Moreover, the derived mediation analysis can be performed with general predictive models. That is, the relationships among variables can be modeled using not only generalized linear models but also nonparametric models such as the Multiple Additive Regression Trees. Therefore, more complicated variable transformations and interactions can be considered in analyzing the mediation effects. The proposed method is realized by the R package 'mma'. We illustrate in this paper the proposed method and how to use 'mma' to estimate mediation effects and make inferences.

  14. Causal Mediation Analysis of Survival Outcome with Multiple Mediators.

    Science.gov (United States)

    Huang, Yen-Tsung; Yang, Hwai-I

    2017-05-01

    Mediation analyses have been a popular approach to investigate the effect of an exposure on an outcome through a mediator. Mediation models with multiple mediators have been proposed for continuous and dichotomous outcomes. However, development of multimediator models for survival outcomes is still limited. We present methods for multimediator analyses using three survival models: Aalen additive hazard models, Cox proportional hazard models, and semiparametric probit models. Effects through mediators can be characterized by path-specific effects, for which definitions and identifiability assumptions are provided. We derive closed-form expressions for path-specific effects for the three models, which are intuitively interpreted using a causal diagram. Mediation analyses using Cox models under the rare-outcome assumption and Aalen additive hazard models consider effects on log hazard ratio and hazard difference, respectively; analyses using semiparametric probit models consider effects on difference in transformed survival time and survival probability. The three models were applied to a hepatitis study where we investigated effects of hepatitis C on liver cancer incidence mediated through baseline and/or follow-up hepatitis B viral load. The three methods show consistent results on respective effect scales, which suggest an adverse estimated effect of hepatitis C on liver cancer not mediated through hepatitis B, and a protective estimated effect mediated through the baseline (and possibly follow-up) of hepatitis B viral load. Causal mediation analyses of survival outcome with multiple mediators are developed for additive hazard and proportional hazard and probit models with utility demonstrated in a hepatitis study.

  15. Immune mediated liver failure.

    Science.gov (United States)

    Wang, Xiaojing; Ning, Qin

    2014-01-01

    Liver failure is a clinical syndrome of various etiologies, manifesting as jaundice, encephalopathy, coagulopathy and circulatory dysfunction, which result in subsequent multiorgan failure. Clinically, liver failure is classified into four categories: acute, subacute, acute-on-chronic and chronic liver failure. Massive hepatocyte death is considered to be the core event in the development of liver failure, which occurs when the extent of hepatocyte death is beyond the liver regenerative capacity. Direct damage and immune-mediated liver injury are two major factors involved in this process. Increasing evidence has suggested the essential role of immune-mediated liver injury in the pathogenesis of liver failure. Here, we review the evolved concepts concerning the mechanisms of immune-mediated liver injury in liver failure from human and animal studies. Both innate and adaptive immunity, especially the interaction of various immune cells and molecules as well as death receptor signaling system are discussed. In addition, we highlight the concept of "immune coagulation", which has been shown to be related to the disease progression and liver injury exacerbation in HBV related acute-on-chronic liver failure.

  16. Lopsided Gauge Mediation

    CERN Document Server

    De Simone, Andrea; Giudice, Gian Francesco; Pappadopulo, Duccio; Rattazzi, Riccardo

    2011-01-01

    It has been recently pointed out that the unavoidable tuning among supersymmetric parameters required to raise the Higgs boson mass beyond its experimental limit opens up new avenues for dealing with the so called $\\mu$-$B_\\mu$ problem of gauge mediation. In fact, it allows for accommodating, with no further parameter tuning, large values of $B_\\mu$ and of the other Higgs-sector soft masses, as predicted in models where both $\\mu$ and $B_\\mu$ are generated at one-loop order. This class of models, called Lopsided Gauge Mediation, offers an interesting alternative to conventional gauge mediation and is characterized by a strikingly different phenomenology, with light higgsinos, very large Higgs pseudoscalar mass, and moderately light sleptons. We discuss general parametric relations involving the fine-tuning of the model and various observables such as the chargino mass and the value of $\\tan\\beta$. We build an explicit model and we study the constraints coming from LEP and Tevatron. We show that in spite of ne...

  17. What carries a mediation process? Configural analysis of mediation.

    Science.gov (United States)

    von Eye, Alexander; Mun, Eun Young; Mair, Patrick

    2009-09-01

    Mediation is a process that links a predictor and a criterion via a mediator variable. Mediation can be full or partial. This well-established definition operates at the level of variables even if they are categorical. In this article, two new approaches to the analysis of mediation are proposed. Both of these approaches focus on the analysis of categorical variables. The first involves mediation analysis at the level of configurations instead of variables. Thus, mediation can be incorporated into the arsenal of methods of analysis for person-oriented research. Second, it is proposed that Configural Frequency Analysis (CFA) can be used for both exploration and confirmation of mediation relationships among categorical variables. The implications of using CFA are first that mediation hypotheses can be tested at the level of individual configurations instead of variables. Second, this approach leaves the door open for different types of mediation processes to exist within the same set. Using a data example, it is illustrated that aggregate-level analysis can overlook mediation processes that operate at the level of individual configurations.

  18. Urban Songlines as Mediator

    DEFF Research Database (Denmark)

    Corlin, Anne

    2016-01-01

    The aim of this paper is to present an investigation of the method The Urban Songlines Book and how it works as a mediator for mapping the experienced space. The method contains a combination of aerial maps, photographs, and interviews as a way to understand the respondent´s use, relations...... and experiences of their neighborhood and the city. Through a presentation of the origin of the method, a description of the conducted study, and an analysis of the process in relation to theories about participatory design, social design, ANT and architectural sociology, the paper reveals how this method...

  19. Sociocultural mediators of remembering

    DEFF Research Database (Denmark)

    Wagoner, Brady; Gillespie, Alex

    2014-01-01

    , questioning and deferring contribute to the transformation and conventionalization of the material. These diverse sociocultural mediators are integrated into a partially coherent recollection by participants self-reflecting, or as Bartlett termed it, turning around upon their schemas. We demonstrate...... that this self-reflection is both a social and a psychological process, occurring because participants are responding to their own utterances in the same way that they respond to the utterances of other people. These empirical findings are used to make a case for using discursive data to look not only...

  20. DNA-Mediated Electrochemistry

    Science.gov (United States)

    Gorodetsky, Alon A.; Buzzeo, Marisa C.

    2009-01-01

    The base pair stack of DNA has been demonstrated as a medium for long range charge transport chemistry both in solution and at DNA-modified surfaces. This chemistry is exquisitely sensitive to structural perturbations in the base pair stack as occur with lesions, single base mismatches, and protein binding. We have exploited this sensitivity for the development of reliable electrochemical assays based on DNA charge transport at self-assembled DNA monolayers. Here we discuss the characteristic features, applications, and advantages of DNA-mediated electrochemistry. PMID:18980370

  1. Holographic Gauge Mediation

    Energy Technology Data Exchange (ETDEWEB)

    Benini, Francesco; /Princeton U.; Dymarsky, Anatoly; /Stanford U., ITP; Franco, Sebastian; /Santa Barbara, KITP; Kachru, Shamit; Simic, Dusan; /Stanford U., ITP /SLAC; Verlinde, Herman; /Princeton, Inst. Advanced Study

    2009-06-19

    We discuss gravitational backgrounds where supersymmetry is broken at the end of a warped throat, and the SUSY-breaking is transmitted to the Standard Model via gauginos which live in (part of) the bulk of the throat geometry. We find that the leading effect arises from splittings of certain 'messenger mesons,' which are adjoint KK-modes of the D-branes supporting the Standard Model gauge group. This picture is a gravity dual of a strongly coupled field theory where SUSY is broken in a hidden sector and transmitted to the Standard Model via a relative of semi-direct gauge mediation.

  2. 45 CFR 16.18 - Mediation.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Mediation. 16.18 Section 16.18 Public Welfare... BOARD § 16.18 Mediation. (a) In cases pending before the Board. If the Board decides that mediation... mediation techniques and will provide or assist in selecting a mediator. The mediator may take any steps...

  3. Interventional effects for mediation analysis with multiple mediators

    OpenAIRE

    Vansteelandt, Stijn; Daniel, Rhian M.

    2017-01-01

    The mediation formula for the identification of natural (in)direct effects has facilitated mediation analyses that better respect the nature of the data, with greater consideration of the need for confounding control. The default assumptions on which it relies are strong, however. In particular, they are known to be violated when confounders of the mediator–outcome association are affected by the exposure. This complicates extensions of counterfactual-based mediation analysis to settings that...

  4. Interpreter-mediated dentistry.

    Science.gov (United States)

    Bridges, Susan; Drew, Paul; Zayts, Olga; McGrath, Colman; Yiu, Cynthia K Y; Wong, H M; Au, T K F

    2015-05-01

    The global movements of healthcare professionals and patient populations have increased the complexities of medical interactions at the point of service. This study examines interpreter mediated talk in cross-cultural general dentistry in Hong Kong where assisting para-professionals, in this case bilingual or multilingual Dental Surgery Assistants (DSAs), perform the dual capabilities of clinical assistant and interpreter. An initial language use survey was conducted with Polyclinic DSAs (n = 41) using a logbook approach to provide self-report data on language use in clinics. Frequencies of mean scores using a 10-point visual analogue scale (VAS) indicated that the majority of DSAs spoke mainly Cantonese in clinics and interpreted for postgraduates and professors. Conversation Analysis (CA) examined recipient design across a corpus (n = 23) of video-recorded review consultations between non-Cantonese speaking expatriate dentists and their Cantonese L1 patients. Three patterns of mediated interpreting indicated were: dentist designated expansions; dentist initiated interpretations; and assistant initiated interpretations to both the dentist and patient. The third, rather than being perceived as negative, was found to be framed either in response to patient difficulties or within the specific task routines of general dentistry. The findings illustrate trends in dentistry towards personalized care and patient empowerment as a reaction to product delivery approaches to patient management. Implications are indicated for both treatment adherence and the education of dental professionals. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Mediation Analysis: A Practitioner's Guide.

    Science.gov (United States)

    VanderWeele, Tyler J

    2016-01-01

    This article provides an overview of recent developments in mediation analysis, that is, analyses used to assess the relative magnitude of different pathways and mechanisms by which an exposure may affect an outcome. Traditional approaches to mediation in the biomedical and social sciences are described. Attention is given to the confounding assumptions required for a causal interpretation of direct and indirect effect estimates. Methods from the causal inference literature to conduct mediation in the presence of exposure-mediator interactions, binary outcomes, binary mediators, and case-control study designs are presented. Sensitivity analysis techniques for unmeasured confounding and measurement error are introduced. Discussion is given to extensions to time-to-event outcomes and multiple mediators. Further flexible modeling strategies arising from the precise counterfactual definitions of direct and indirect effects are also described. The focus throughout is on methodology that is easily implementable in practice across a broad range of potential applications.

  6. A higher form (of) mediation

    International Nuclear Information System (INIS)

    Verlinde, Herman; Wang, L-T; Yavin, Itay; Wijnholt, Martijn

    2008-01-01

    We exhibit a simple and robust mechanism for bulk mediation of supersymmetry breaking between hidden and visible sectors localized on geometrically separated D-branes in type II string theory. The mediation proceeds via RR p-forms that couple via linear Chern-Simons terms to the abelian vector bosons on the branes. From a 4-d low energy perspective, the mechanism reduces to U(1) mediation

  7. Mediating Trust in Terrorism Coverage

    DEFF Research Database (Denmark)

    Mogensen, Kirsten

    crisis. While the framework is presented in the context of television coverage of a terror-related crisis situation, it can equally be used in connection with all other forms of mediated trust. Key words: National crisis, risk communication, crisis management, television coverage, mediated trust.......Mass mediated risk communication can contribute to perceptions of threats and fear of “others” and/or to perceptions of trust in fellow citizens and society to overcome problems. This paper outlines a cross-disciplinary holistic framework for research in mediated trust building during an acute...

  8. Substrate mediated enzyme prodrug therapy

    DEFF Research Database (Denmark)

    Fejerskov, Betina; Jarlstad Olesen, Morten T; Zelikin, Alexander N

    2017-01-01

    Substrate mediated enzyme prodrug therapy (SMEPT) is a biomedical platform developed to perform a localized synthesis of drugs mediated by implantable biomaterials. This approach combines the benefits and at the same time offers to overcome the drawbacks for traditional pill-based drug administra......Substrate mediated enzyme prodrug therapy (SMEPT) is a biomedical platform developed to perform a localized synthesis of drugs mediated by implantable biomaterials. This approach combines the benefits and at the same time offers to overcome the drawbacks for traditional pill-based drug...

  9. The Strategic Mediator

    DEFF Research Database (Denmark)

    Rossignoli, Cecilia; Carugati, Andrea; Mola, Lapo

    2009-01-01

    process. Through the study of services evolving over time we show that, as marketplaces support increasingly complex business processes, the market participants begin to privilege the well connected small number to the convenience of the openness to the entire market. The participants see the marketplace......The last 10 years have witnessed the emergence of electronic marketplaces as players that leverage new technologies to facilitate B2B internet-mediated collaborative business. Nowadays these players are augmenting their services from simple intermediation to include new inter......-organizational relationships. The interest of this paper is to investigate the shift in the role and evolution of services proposed by e-marketplaces in response to the demands of the market participants. We carried out a longitudinal qualitative field study of an e-marketplace providing the outsourcing of the procurement...

  10. Mediating Potency and Fear

    DEFF Research Database (Denmark)

    Christiansen, Steen Ledet

    2018-01-01

    Action movies participate in the administration of fear [Virilio, P., 2012. The administration of fear. Translated by Ames Hodges. Los Angeles, CA: Semiotext(e)], and the networked affects of contemporary warfare [Anderson, B., 2013. Targeting affective life from above: morale and airpower. In: P......’ [Shaviro, S., 2010. Post-cinematic affect. Winchester: Zero Books]. These intensity effects mediate between the age of terror's ecology of fear [Massumi, Brian, 2002. Parables for the virtual: movement, affect, sensation. Durham: Duke University Press] and our bodies. Rather than producing fear, action...... movies work to dispel fear by producing potency and bolstering resolve. We can thus understand action movies as participating in the biopolitical effects of contemporary warfare. Affect is globalized and intensified through action movies’ aesthetics, with the aim of producing a kind of drone subject...

  11. Den sundhedsfremmende mediator

    DEFF Research Database (Denmark)

    Læssøe, Jeppe

    2009-01-01

      Mediatorer er en relativ ny aktør-type og job-funktion, som passer godt ind i det dynamiske videns- og netværkssamfund. I sundhedsfremmende arbejde med vægt på borgernes deltagelse kan mediatorer spille en nøglerolle. Det er derfor vigtigt begrebsmæssigt at kunne skelne mellem forskellige typer...... mediering samt mellem forskellige mediator-roller og tilhørsforhold. Det er også vigtigt at være bevidst om de centrale kvaliteter, risici og dilemmaer, som mediering indebærer i forhold til involvering af borgerne. Denne artikel rummer et bud på en sådan nuanceret begrebsliggørelse og refleksion, relateret...

  12. Soluble lymphocytic mediators

    Science.gov (United States)

    Pick, E.

    1974-01-01

    The effect of a number of drugs on the production of macrophage migration inhibitory factor (MIF) by antigen-stimulated sensitized guinea-pig lymph node cells was studied. The drugs were present during the entire culture period and eliminated from supernatants by dialysis. It was found that MIF secretion is inhibited by exogenous dibutyryl cyclic AMP and by theophylline and chlorphenesin, two agents raising the endogenous level of cyclic AMP. On the other hand, isoproterenol, which stimulates cyclic AMP generation in several tissues, did not block MIF production. The formation of the mediator was also suppressed by the microfilament-affecting drug, cytochalasin B. The microtubular disruptive agents, colchicine and vinblastine sulphate, did not influence MIF production. It is concluded that: (a) endogenous cyclic AMP may act as a regulator of MIF production; (b) the activity of contractile microfilaments is probably required for MIF formation; and (c) microtubules are not involved in the secretory process. PMID:4369184

  13. Protein- mediated enamel mineralization

    Science.gov (United States)

    Moradian-Oldak, Janet

    2012-01-01

    Enamel is a hard nanocomposite bioceramic with significant resilience that protects the mammalian tooth from external physical and chemical damages. The remarkable mechanical properties of enamel are associated with its hierarchical structural organization and its thorough connection with underlying dentin. This dynamic mineralizing system offers scientists a wealth of information that allows the study of basic principals of organic matrix-mediated biomineralization and can potentially be utilized in the fields of material science and engineering for development and design of biomimetic materials. This chapter will provide a brief overview of enamel hierarchical structure and properties as well as the process and stages of amelogenesis. Particular emphasis is given to current knowledge of extracellular matrix protein and proteinases, and the structural chemistry of the matrix components and their putative functions. The chapter will conclude by discussing the potential of enamel for regrowth. PMID:22652761

  14. Mediating environmental disputes

    Energy Technology Data Exchange (ETDEWEB)

    Lake, L.M.

    1977-09-01

    Environmental disputes and lawsuits are examined. Site-specific disputes focus on visible physical phenomena, such as a power plant or local river, and have an immediacy and intensity about them that make it politically hazardous for public officials to assume responsibility for resolving them. As new precedents in environmental case law become less frequent and the number of disputes increases, alternative processes for environmental conflict resolution, such as third-party intervention, become appropriate. Third-party intervention techniques of fact finding, conflict avoidance, conciliation and mediation have been applied to international, labor, prison, school, racial, and hospital disputes. Underlying concepts are described. Two case studies, the Snoqualmie Dam dispute in Washington and the West Side Highway dispute in New York City, illustrate the basic elements associated with third-party intervention. 1 map, 17 references.

  15. Mediatization and Government Communication

    DEFF Research Database (Denmark)

    Laursen, Bo; Valentini, Chiara

    2015-01-01

    do not tend to get a media coverage that matches the EU’s considerable influence on European citizens’ daily lives. This study, which is based on in-depth interviews with European Parliament press officers, concludes that these professionals are indeed attuned to a “media logic......Social actors see exposure in the news media as attractive for publicity purposes and are under pressure to adapt their press work to a “media logic” to be attractive sources for journalists and editors. This article investigates the European Parliament’s press officers’ professional practices...... in the light of mediatization and government communication theories. Without one pan-European public sphere, the European Parliament, like the other European Union (EU) institutions, competes with national actors for the news media’s attention in the EU’s twenty-eight national public spheres, where EU affairs...

  16. The mediation procedure in Romania

    Directory of Open Access Journals (Sweden)

    Alexandrina Zaharia

    2009-06-01

    Full Text Available The mediation activity as an alternative way of solving conflicts occupies an important place in modernsociety. Currently, the mediation reached its maturity worldwide being adopted without reservations.The future of solving conflicts is undoubtedly closely related to mediation. XXth century is the century of solvingconflicts amiably outside the court room. In Romania and the mediation profession were regulated by the Law no.192/2006, on the basis of the idea that mediation is one of the major themes of the reform strategy of the judicialsystem 2005-2007. By adopting the mentioned law it was followed the idea of reducing the volume of activitycourts, and therefore, relieve them of as many cases, with the direct effect on the quality of justice. Mediation is avoluntary process in which the parties with a neutral and impartial third party, without power of decision - themediator - who is qualified to assist the parties to negotiate, facilitating the communication between them andhelping them to reach a unanimous effective and sustainable agreement. The parties may resort to mediation beforeor after triggering a trial. Mediation can be applied, in principle, on any type of conflict. However, theRomanian legislator has established special stipulations on conflict mediation in criminal, civil and familylaw. Although not expressly provided, the stipulations regarding the civil conflicts and also apply to commercialconflicts. Therefore, the mediation is applicable to most types of lawsuits, except those relating to personalrights. As a "win- win" principle, the mediation does not convert any of the parties defeated or victorious; allthose involved have gained by applying this procedure.

  17. Anomaly mediation deformed by axion

    Energy Technology Data Exchange (ETDEWEB)

    Nakayama, Kazunori, E-mail: kazunori@hep-th.phys.s.u-tokyo.ac.jp [Department of Physics, University of Tokyo, Bunkyo-ku, Tokyo 113-0033 (Japan); Kavli Institute for the Physics and Mathematics of the Universe, University of Tokyo, Kashiwa 277-8583 (Japan); Yanagida, Tsutomu T. [Kavli Institute for the Physics and Mathematics of the Universe, University of Tokyo, Kashiwa 277-8583 (Japan)

    2013-05-13

    We show that in supersymmetric axion models the axion supermultiplet obtains a sizable F-term due to a non-supersymmetric dynamics and it generally gives the gaugino masses comparable to the anomaly mediation contribution. Thus the gaugino mass relation predicted by the anomaly mediation effect can be significantly modified in the presence of axion to solve the strong CP problem.

  18. Theorizing with/out "Mediators".

    Science.gov (United States)

    Roth, Wolff-Michael; Jornet, Alfredo

    2017-01-05

    Mediation is one of the most often cited concepts in current cultural-historical theory literature, in which cultural actions and artifacts are often characterized as mediators standing between situational stimuli and behavioral responses. Most often presented as a means to overcome Cartesian dualism between subject and object, and between individual and society, some scholars have nonetheless raised criticism suggesting that such mediators are problematic for a dialectical psychology that takes a unit analysis (monist) approach. In fact, Spinoza develops a monist theory of mind and body that goes without and even excludes every form of mediation. In this study, we follow up on the latter criticisms and explore what we consider to be problematic uses of the notion of mediation as an analytical construct in the literature. We elaborate an empirically grounded discussion on the ways the concept of mediation may lead to dualistic readings; and we offer an alternative account where the notion of mediator is not needed. We conclude discussing prospects for and implications of a cultural-historical theory where the notion of mediation no longer is invoked to account for human action and development.

  19. Comments on general gauge mediation

    International Nuclear Information System (INIS)

    Intriligator, Kenneth; Sudano, Matthew

    2008-01-01

    There has been interest in generalizing models of gauge mediation of supersymmetry breaking. As shown by Meade, Seiberg, and Shih (MSS), the soft masses of general gauge mediation can be expressed in terms of the current two-point functions of the susy-breaking sector. We here give a simple extension of their result which provides, for general gauge mediation, the full effective potential for squark pseudo-D-flat directions. The effective potential reduces to the sfermion soft masses near the origin, and the full potential, away from the origin, can be useful for cosmological applications. We also generalize the soft masses and effective potential to allow for general gauge mediation by Higgsed gauge groups. Finally, we discuss general gauge mediation in the limit of small F-terms, and how the results of MSS connect with the analytic continuation in superspace results, based on a spurion analysis.

  20. Practical Guide to Civil Mediation

    CERN Document Server

    2006-01-01

    The Permanent Mission of Switzerland has informed CERN that the Département des Institutions of the Republic and Canton of Geneva and the Groupement suisse des Magistrats pour la médiation (GEMME) - Swiss Association of Magistrates for Mediation have published a multilingual Practical Guide to Civil Mediation (including English). In this context, the Swiss Mission has underlined the benefits of resorting to mediation, especially for the personnel of international organizations, and which the Secretary-General of the GEMME has summarised as follows: it is a private process not requiring the waiver of the parties' immunities; the confidentiality of the mediation process is guaranteed both by the mediator and the parties to it; the search for an amicable settlement does not need to be determined by reference to law (provided that public order is respected); the process is faster (2 to 3 sessions), less costly and more flexible than civil or arbitration procedures; in order to reinforce the agreeme...

  1. Practical Guide to Civil Mediation

    CERN Multimedia

    2006-01-01

    The Permanent Mission of Switzerland has informed CERN that the Département des Institutions of the Republic and Canton of Geneva and the Groupement suisse des Magistrats pour la médiation (GEMME) - Swiss Association of Magistrates for Mediation have published a multilingual Practical Guide to Civil Mediation (including English). In this context, the Swiss Mission has underlined the benefits of resorting to mediation, especially for the personnel of International Organizations, and which the Secretary-General of the GEMME has summarised as follows: it is a private process not requiring the waiver of the parties' immunities; the confidentiality of the mediation process is guaranteed both by the mediator and the parties to it; the search for an amicable settlement does not need to be determined by reference to law (provided that public order is respected); the process is faster (2 to 3 sessions), less costly and more flexible than civil or arbitration procedures; in order to reinforce the agreem...

  2. 29 CFR 35.32 - Mediation.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 1 2010-07-01 2010-07-01 true Mediation. 35.32 Section 35.32 Labor Office of the Secretary... Mediation. (a) Referral to mediation. CRC will promptly refer to the Federal Mediation and Conciliation Service or the mediation agency designated by the Secretary of Health and Human Services under 45 CFR part...

  3. 22 CFR 143.33 - Mediation.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Mediation. 143.33 Section 143.33 Foreign... Mediation. (a) Referral of complaints for mediation. The agency will refer to the Federal Mediation and... participate in the mediation process to the extent necessary to reach an agreement or make an informed...

  4. 29 CFR 1203.1 - Mediation services.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 4 2010-07-01 2010-07-01 false Mediation services. 1203.1 Section 1203.1 Labor Regulations Relating to Labor (Continued) NATIONAL MEDIATION BOARD APPLICATIONS FOR SERVICE § 1203.1 Mediation services. Applications for the mediation services of the National Mediation Board under section 5, First, of the Railway...

  5. 34 CFR 81.13 - Mediation.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Mediation. 81.13 Section 81.13 Education Office of the... Mediation. (a) Voluntary mediation is available for proceedings that are pending before the OALJ. (b) A... mediation by filing a motion with the ALJ assigned to the case. The OALJ arranges for a mediator if the...

  6. 24 CFR 3288.35 - Mediation.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 5 2010-04-01 2010-04-01 false Mediation. 3288.35 Section 3288.35...-Administered States § 3288.35 Mediation. (a) Mediator. The dispute resolution provider will provide for the... identifies any other party that should be included in the mediation, the mediator will contact the other...

  7. 44 CFR 7.942 - Mediation.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Mediation. 7.942 Section 7..., Conciliation, and Enforcement Procedures § 7.942 Mediation. (a) FEMA will promptly refer to a mediation agency... participate in the mediation process to the extent necessary to reach an agreement or for the mediator to make...

  8. 32 CFR 776.38 - Mediation.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 5 2010-07-01 2010-07-01 false Mediation. 776.38 Section 776.38 National... Professional Conduct § 776.38 Mediation. (a) Mediation: (1) A covered attorney may act as a mediator between... mediation, including the advantages and risks involved, and the effect on the attorney-client...

  9. 29 CFR 1202.1 - Mediation.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 4 2010-07-01 2010-07-01 false Mediation. 1202.1 Section 1202.1 Labor Regulations Relating to Labor (Continued) NATIONAL MEDIATION BOARD RULES OF PROCEDURE § 1202.1 Mediation. The mediation..., or where conferences are refused. The National Mediation Board may proffer its services in case any...

  10. Microbially mediated mineral carbonation

    Science.gov (United States)

    Power, I. M.; Wilson, S. A.; Dipple, G. M.; Southam, G.

    2010-12-01

    Mineral carbonation involves silicate dissolution and carbonate precipitation, which are both natural processes that microorganisms are able to mediate in near surface environments (Ferris et al., 1994; Eq. 1). (Ca,Mg)SiO3 + 2H2CO3 + H2O → (Ca,Mg)CO3 + H2O + H4SiO4 + O2 (1) Cyanobacteria are photoautotrophs with cell surface characteristics and metabolic processes involving inorganic carbon that can induce carbonate precipitation. This occurs partly by concentrating cations within their net-negative cell envelope and through the alkalinization of their microenvironment (Thompson & Ferris, 1990). Regions with mafic and ultramafic bedrock, such as near Atlin, British Columbia, Canada, represent the best potential sources of feedstocks for mineral carbonation. The hydromagnesite playas near Atlin are a natural biogeochemical model for the carbonation of magnesium silicate minerals (Power et al., 2009). Field-based studies at Atlin and corroborating laboratory experiments demonstrate the ability of a microbial consortium dominated by filamentous cyanobacteria to induce the precipitation of carbonate minerals. Phototrophic microbes, such as cyanobacteria, have been proposed as a means for producing biodiesel and other value added products because of their efficiency as solar collectors and low requirement for valuable, cultivable land in comparison to crops (Dismukes et al., 2008). Carbonate precipitation and biomass production could be facilitated using specifically designed ponds to collect waters rich in dissolved cations (e.g., Mg2+ and Ca2+), which would allow for evapoconcentration and provide an appropriate environment for growth of cyanobacteria. Microbially mediated carbonate precipitation does not require large quantities of energy or chemicals needed for industrial systems that have been proposed for rapid carbon capture and storage via mineral carbonation (e.g., Lackner et al., 1995). Therefore, this biogeochemical approach may represent a readily

  11. Nanoparticle mediated micromotor motion

    Science.gov (United States)

    Liu, Mei; Liu, Limei; Gao, Wenlong; Su, Miaoda; Ge, Ya; Shi, Lili; Zhang, Hui; Dong, Bin; Li, Christopher Y.

    2015-03-01

    In this paper, we report the utilization of nanoparticles to mediate the motion of a polymer single crystal catalytic micromotor. Micromotors have been fabricated by directly self-assembling functional nanoparticles (platinum and iron oxide nanoparticles) onto one or both sides of two-dimensional polymer single crystals. We show that the moving velocity of these micromotors in fluids can be readily tuned by controlling the nanoparticles' surface wettability and catalytic activity. A 3 times velocity increase has been achieved for a hydrophobic micromotor as opposed to the hydrophilic ones. Furthermore, we demonstrate that the catalytic activity of platinum nanoparticles inside the micromotor can be enhanced by their synergetic interactions with iron oxide nanoparticles and an electric field. Both strategies lead to dramatically increased moving velocities, with the highest value reaching ~200 μm s-1. By decreasing the nanoparticles' surface wettability and increasing their catalytic activity, a maximum of a ~10-fold increase in the moving speed of the nanoparticle based micromotor can be achieved. Our results demonstrate the advantages of using nanoparticles in micromotor systems.In this paper, we report the utilization of nanoparticles to mediate the motion of a polymer single crystal catalytic micromotor. Micromotors have been fabricated by directly self-assembling functional nanoparticles (platinum and iron oxide nanoparticles) onto one or both sides of two-dimensional polymer single crystals. We show that the moving velocity of these micromotors in fluids can be readily tuned by controlling the nanoparticles' surface wettability and catalytic activity. A 3 times velocity increase has been achieved for a hydrophobic micromotor as opposed to the hydrophilic ones. Furthermore, we demonstrate that the catalytic activity of platinum nanoparticles inside the micromotor can be enhanced by their synergetic interactions with iron oxide nanoparticles and an electric

  12. Estimation of Causal Mediation Effects for a Dichotomous Outcome in Multiple-Mediator Models using the Mediation Formula

    OpenAIRE

    Wang, Wei; Nelson, Suchitra; Albert, Jeffrey M.

    2013-01-01

    Mediators are intermediate variables in the causal pathway between an exposure and an outcome. Mediation analysis investigates the extent to which exposure effects occur through these variables, thus revealing causal mechanisms. In this paper, we consider the estimation of the mediation effect when the outcome is binary and multiple mediators of different types exist. We give a precise definition of the total mediation effect as well as decomposed mediation effects through individual or sets ...

  13. Mediation of information and educational mediation: conceptual discussions

    Directory of Open Access Journals (Sweden)

    Helena Célia de Souza Sacerdote

    2016-04-01

    Full Text Available Introduction: This is systematization of theoretical and methodological contributions related to the concepts of mediation information and pedagogical mediation in the literature. Objective: To understand possible intersection of information science and Online Education with regard to these concepts to check that both can be considered as analogous in its essence and practice. Methodology: Literature review based on literature by consulting the scientific productions selected in search of SciELO.ORG databases and EBSCO Host, the portal of CAPES / MEC and Google Scholar. Results: The most cited concepts in information science and education were de Almeida Junior (2009 and Masetto (2013, respectively. Conclusion: It is observed that the concept of mediation can move interchangeably between both areas. This is because the evidence found in the productions of the last five years indicate that the concept of information of mediation seems to have found its bases in education (educational psychology.

  14. The mediatization of ethical consumption

    DEFF Research Database (Denmark)

    Eskjær, Mikkel Fugl

    2013-01-01

    Over the years, mediatization studies have investigated the influence of media in numerous sections of contemporary society. One area that has received limited attention is the mediatization of consumption, particularly issues concerning ethical consumption. This article presents a study of how...... mediatization is transforming modern consumption and contributing to the mainstreaming of ethical consumption. Based on a study of a Danish online eco-store, the article argues that modern ethical consumption increasingly depends on new media practices to present sustainable consumption as practical...

  15. Assay of mast cell mediators

    DEFF Research Database (Denmark)

    Rådinger, Madeleine; Jensen, Bettina M; Swindle, Emily

    2015-01-01

    Mediator release from activated mast cells is a major initiator of the symptomology associated with allergic disorders such as anaphylaxis and asthma. Thus, methods to monitor the generation and release of such mediators have widespread applicability in studies designed to understand the processes...... regulating mast cell activation and for the identification of therapeutic approaches to block mast cell-driven disease. In this chapter, we discuss approaches used for the determination of mast cell degranulation, lipid-derived inflammatory mediator production, and cytokine/chemokine gene expression as well...

  16. Doing statistical mediation and moderation

    CERN Document Server

    Jose, Paul E

    2013-01-01

    Written in a friendly, conversational style, this book offers a hands-on approach to statistical mediation and moderation for both beginning researchers and those familiar with modeling. Starting with a gentle review of regression-based analysis, Paul Jose covers basic mediation and moderation techniques before moving on to advanced topics in multilevel modeling, structural equation modeling, and hybrid combinations, such as moderated mediation. User-friendly features include numerous graphs and carefully worked-through examples; ""Helpful Suggestions"" about procedures and pitfalls; ""Knowled

  17. Estimation of causal mediation effects for a dichotomous outcome in multiple-mediator models using the mediation formula.

    Science.gov (United States)

    Wang, Wei; Nelson, Suchitra; Albert, Jeffrey M

    2013-10-30

    Mediators are intermediate variables in the causal pathway between an exposure and an outcome. Mediation analysis investigates the extent to which exposure effects occur through these variables, thus revealing causal mechanisms. In this paper, we consider the estimation of the mediation effect when the outcome is binary and multiple mediators of different types exist. We give a precise definition of the total mediation effect as well as decomposed mediation effects through individual or sets of mediators using the potential outcomes framework. We formulate a model of joint distribution (probit-normal) using continuous latent variables for any binary mediators to account for correlations among multiple mediators. A mediation formula approach is proposed to estimate the total mediation effect and decomposed mediation effects based on this parametric model. Estimation of mediation effects through individual or subsets of mediators requires an assumption involving the joint distribution of multiple counterfactuals. We conduct a simulation study that demonstrates low bias of mediation effect estimators for two-mediator models with various combinations of mediator types. The results also show that the power to detect a nonzero total mediation effect increases as the correlation coefficient between two mediators increases, whereas power for individual mediation effects reaches a maximum when the mediators are uncorrelated. We illustrate our approach by applying it to a retrospective cohort study of dental caries in adolescents with low and high socioeconomic status. Sensitivity analysis is performed to assess the robustness of conclusions regarding mediation effects when the assumption of no unmeasured mediator-outcome confounders is violated. Copyright © 2013 John Wiley & Sons, Ltd.

  18. Estimation of Causal Mediation Effects for a Dichotomous Outcome in Multiple-Mediator Models using the Mediation Formula

    Science.gov (United States)

    Nelson, Suchitra; Albert, Jeffrey M.

    2013-01-01

    Mediators are intermediate variables in the causal pathway between an exposure and an outcome. Mediation analysis investigates the extent to which exposure effects occur through these variables, thus revealing causal mechanisms. In this paper, we consider the estimation of the mediation effect when the outcome is binary and multiple mediators of different types exist. We give a precise definition of the total mediation effect as well as decomposed mediation effects through individual or sets of mediators using the potential outcomes framework. We formulate a model of joint distribution (probit-normal) using continuous latent variables for any binary mediators to account for correlations among multiple mediators. A mediation formula approach is proposed to estimate the total mediation effect and decomposed mediation effects based on this parametric model. Estimation of mediation effects through individual or subsets of mediators requires an assumption involving the joint distribution of multiple counterfactuals. We conduct a simulation study that demonstrates low bias of mediation effect estimators for two-mediator models with various combinations of mediator types. The results also show that the power to detect a non-zero total mediation effect increases as the correlation coefficient between two mediators increases, while power for individual mediation effects reaches a maximum when the mediators are uncorrelated. We illustrate our approach by applying it to a retrospective cohort study of dental caries in adolescents with low and high socioeconomic status. Sensitivity analysis is performed to assess the robustness of conclusions regarding mediation effects when the assumption of no unmeasured mediator-outcome confounders is violated. PMID:23650048

  19. Mediation analysis with multiple versions of the mediator

    OpenAIRE

    VanderWeele, Tyler J.

    2012-01-01

    The causal inference literature has provided definitions of direct and indirect effects based on counterfactuals that generalize the approach found in the social science literature. However, these definitions presuppose well defined hypothetical interventions on the mediator. In many settings there may be multiple ways to fix the mediator to a particular value and these different hypothetical interventions may have very different implications for the outcome of interest. In this paper we cons...

  20. Dimensional reduction in anomaly mediation

    International Nuclear Information System (INIS)

    Boyda, Ed; Murayama, Hitoshi; Pierce, Aaron

    2002-01-01

    We offer a guide to dimensional reduction in theories with anomaly-mediated supersymmetry breaking. Evanescent operators proportional to ε arise in the bare Lagrangian when it is reduced from d=4 to d=4-2ε dimensions. In the course of a detailed diagrammatic calculation, we show that inclusion of these operators is crucial. The evanescent operators conspire to drive the supersymmetry-breaking parameters along anomaly-mediation trajectories across heavy particle thresholds, guaranteeing the ultraviolet insensitivity

  1. 22 CFR 218.33 - Mediation.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Mediation. 218.33 Section 218.33 Foreign... § 218.33 Mediation. (a) Referral of complaints for mediation. The agency will refer to the Federal Mediation and Conciliation Service all complaints that: (1) fall within the jurisdiction of these...

  2. 15 CFR 923.54 - Mediation.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Mediation. 923.54 Section 923.54... Mediation. (a) Section 307(h) of the Act provides for mediation of serious disagreement between any Federal... cases, mediation by the Secretary, with the assistance of the Executive Office of the President, may be...

  3. 10 CFR 4.333 - Mediation.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Mediation. 4.333 Section 4.333 Energy NUCLEAR REGULATORY... Investigation, Conciliation, and Enforcement Procedures § 4.333 Mediation. (a) Referral of complaints for mediation. NRC will refer to a mediation agency designated by the Secretary of the Department of Health and...

  4. 45 CFR 1156.16 - Mediation.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Mediation. 1156.16 Section 1156.16 Public Welfare... Procedures § 1156.16 Mediation. (a) Referral of complaints for mediation. The Endowment will promptly refer all complaints to the agency designated by the Secretary of HHS to manage the mediation process that...

  5. 15 CFR 930.111 - OCRM mediation.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false OCRM mediation. 930.111 Section 930... FEDERAL CONSISTENCY WITH APPROVED COASTAL MANAGEMENT PROGRAMS Secretarial Mediation § 930.111 OCRM mediation. The availability of mediation does not preclude use by the parties of alternative means for...

  6. 14 CFR 1252.402 - Mediation.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Mediation. 1252.402 Section 1252.402... Procedures § 1252.402 Mediation. (a) Referral of complaints for mediation. NASA will refer to the Federal Mediation and Conciliation Service all complaints that: (1) Fall within the jurisdiction of the Act and...

  7. 10 CFR 1040.89-6 - Mediation.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Mediation. 1040.89-6 Section 1040.89-6 Energy DEPARTMENT... Enforcement Procedures § 1040.89-6 Mediation. (a) Referral of complaints for mediation. DOE will refer to the Federal Mediation and Conciliation Service, in accordance with 45 CFR 90.43(c)(3), all complaints that: (1...

  8. 34 CFR 110.32 - Mediation.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Mediation. 110.32 Section 110.32 Education Regulations..., Conciliation, and Enforcement Procedures § 110.32 Mediation. (a) ED promptly refers to the Federal Mediation and Conciliation Service or to the mediation agency designated by the Secretary of Health and Human...

  9. 7 CFR 780.9 - Mediation.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 7 2010-01-01 2010-01-01 false Mediation. 780.9 Section 780.9 Agriculture Regulations... PROGRAMS APPEAL REGULATIONS § 780.9 Mediation. (a) Any request for mediation must be submitted after... once: (1) If resolution of an adverse decision is not achieved in mediation, a participant may exercise...

  10. 24 CFR 146.35 - Mediation.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Mediation. 146.35 Section 146.35... ASSISTANCE Investigation, Settlement, and Enforcement Procedures § 146.35 Mediation. (a) HUD shall refer to the Federal Mediation and Conciliation Service, a mediation agency designated by the Secretary of...

  11. 7 CFR 614.11 - Mediation.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 6 2010-01-01 2010-01-01 false Mediation. 614.11 Section 614.11 Agriculture... AGRICULTURE CONSERVATION OPERATIONS NRCS APPEAL PROCEDURES § 614.11 Mediation. (a) A participant who wishes to pursue mediation must file request for mediation under this part with the NRCS official designated in the...

  12. 15 CFR 20.12 - Mediation.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Mediation. 20.12 Section 20.12... Procedures § 20.12 Mediation. (a) DOC will refer to a mediation service designated by the Secretary all... further processing. (b) Both the complainant and the recipient shall participate in the mediation process...

  13. 38 CFR 18.543 - Mediation.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Mediation. 18.543 Section... Enforcement Procedures § 18.543 Mediation. (a) Referral of complaints for mediation. VA will refer to the Federal Mediation and Conciliation Service all complaints that: (1) Fall within the jurisdiction of the...

  14. Mediation in Schools: Tapping the Potential

    Science.gov (United States)

    Hendry, Richard

    2010-01-01

    This article explores the developing role of mediation as a conflict resolution process in schools. It gives an accepted definition and clarifies the purposes of mediation, outlining the range of contexts in and beyond schools in which mediation is already offered as a formal intervention. The typical process of mediation itself is described. The…

  15. Mediation and Counseling Services: A Viable Partnership

    Science.gov (United States)

    Hodges, Shannon

    2009-01-01

    Mediation has become common in many areas of society, including marital dissolution, community disputes, governmental agencies, and business and industry. Though higher education has been slower than society to adopt mediation services, campus mediation is becoming increasingly more common. This article explains why mediation is a viable…

  16. 45 CFR 91.43 - Mediation.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Mediation. 91.43 Section 91.43 Public Welfare... Enforcement Procedures § 91.43 Mediation. (a) HHS will promptly refer to a mediation agency designated by the... mediation process to the extent necessary to reach an agreement or make an informed judgment that an...

  17. 43 CFR 17.332 - Mediation.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Mediation. 17.332 Section 17.332 Public..., and Enforcement Procedures § 17.332 Mediation. (a) Referral of complaints for mediation. DOI will... participate in the mediation process to the extent necessary to reach an agreement or make an informed...

  18. Neutrality in mediation: an ambiguous ethical value

    OpenAIRE

    Bailey, Paul

    2014-01-01

    Mediator neutrality would appear, by definition, to be a necessary and required ethical principle for all mediators to practice. But what is meant by neutrality in mediation? Is it practically possible to be completely neutral between parties in mediation while at the same time being fair to both of them? This paper attempts to answer these two questions.

  19. 7 CFR 900.108 - Mediator's report.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Mediator's report. 900.108 Section 900.108 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Mediator's report. The mediator, upon the completion of mediation proceedings, shall submit to the...

  20. Strongly coupled semidirect mediation of supersymmetry breaking

    International Nuclear Information System (INIS)

    Ibe, M.; Izawa, K.-I.; Nakai, Y.

    2009-01-01

    Strongly coupled semidirect gauge mediation models of supersymmetry breaking through massive mediators with standard-model charges are investigated by means of composite degrees of freedom. Sizable mediation is realized to generate the standard-model gaugino masses for a small mediator mass without breaking the standard-model symmetries.

  1. Gaugino-assisted anomaly mediation

    International Nuclear Information System (INIS)

    Kribs, Graham D.

    2001-01-01

    I present a model of supersymmetry breaking mediated through a small extra dimension. Standard model matter multiplets and a supersymmetry-breaking (or 'hidden') sector are confined to opposite four-dimensional boundaries while gauge multiplets live in the bulk. The hidden sector does not contain a singlet and the dominant contribution to gaugino masses is via anomaly-mediated supersymmetry breaking. Scalar masses get contributions from both anomaly mediation and a tiny hard breaking of supersymmetry by operators on the hidden-sector boundary. These operators contribute to scalar masses at one loop and in most of parameter space, their contribution dominates. Thus it is easy to make all squared scalar masses positive. As no additional fields or symmetries are required below the Planck scale, this is among the simplest working models of anomaly mediation. The gaugino spectrum is left untouched and the phenomenology of the model is roughly similar to anomaly mediated supersymmetry breaking with a universal scalar mass added. Finally, the main differences in the spectrum between this model and other approaches are identified. This talk is based on work [1] done in collaboration with David E. Kaplan

  2. Gaugino-Assisted Anomaly Mediation

    International Nuclear Information System (INIS)

    Kaplan, David Elazzar; Kribs, Graham D.

    2000-01-01

    We present a model of supersymmetry breaking mediated through a small extra dimension. Standard model matter multiplets and a supersymmetry-breaking (or ''hidden'') sector are confined to opposite four-dimensional boundaries while gauge multiplets live in the bulk. The hidden sector does not contain a singlet and the dominant contribution to gaugino masses is via anomaly-mediated supersymmetry breaking. Scalar masses get contributions from both anomaly mediation and a tiny hard breaking of supersymmetry by operators on the hidden-sector boundary. These operators contribute to scalar masses at one loop and in most of parameter space, their contribution dominates. Thus it is easy to make all squared scalar masses positive. As no additional fields or symmetries are required below the Planck scale, we consider this the simplest working model of anomaly mediation. The gaugino spectrum is left untouched and the phenomenology of the model is roughly similar to anomaly mediated supersymmetry breaking with a universal scalar mass added. We identify the main differences in the spectrum between this model and other approaches. We also discuss mechanisms for generating the μ term and constraints on additional bulk fields. (author)

  3. Three tasks for mediatization research

    DEFF Research Database (Denmark)

    Ekstrøm, Mats; Fornäs, Johan; Jansson, André

    2016-01-01

    Based on the interdisciplinary experience of a Swedish research committee, this article discusses critical conceptual issues raised by the current debate on mediatization – a concept that holds great potential to constitute a space for synthesized understandings of media-related social transforma......Based on the interdisciplinary experience of a Swedish research committee, this article discusses critical conceptual issues raised by the current debate on mediatization – a concept that holds great potential to constitute a space for synthesized understandings of media-related social...... that mediatization researchers have sometimes formulated too grand claims as to mediatization’s status as a unitary approach, a meta-theory or a paradigm. Such claims have led to problematic confusions around the concept and should be abandoned in favour of a more open agenda. In line with such a call for openness...

  4. Gauge mediated mini-split

    Energy Technology Data Exchange (ETDEWEB)

    Cohen, Timothy [Institute of Theoretical Science, University of Oregon,Eugene, OR 97403 (United States); Craig, Nathaniel [Department of Physics, University of California,Santa Barbara, CA 93106 (United States); Knapen, Simon [Berkeley Center for Theoretical Physics,University of California, Berkeley, CA 94720 (United States); Theoretical Physics Group,Lawrence Berkeley National Laboratory, Berkeley, CA 94720 (United States)

    2016-03-15

    We propose a simple model of split supersymmetry from gauge mediation. This model features gauginos that are parametrically a loop factor lighter than scalars, accommodates a Higgs boson mass of 125 GeV, and incorporates a simple solution to the μ−b{sub μ} problem. The gaugino mass suppression can be understood as resulting from collective symmetry breaking. Imposing collider bounds on μ and requiring viable electroweak symmetry breaking implies small a-terms and small tan β — the stop mass ranges from 10{sup 5} to 10{sup 8} GeV. In contrast with models with anomaly + gravity mediation (which also predict a one-loop loop suppression for gaugino masses), our gauge mediated scenario predicts aligned squark masses and a gravitino LSP. Gluinos, electroweakinos and Higgsinos can be accessible at the LHC and/or future colliders for a wide region of the allowed parameter space.

  5. Mediation in Legal English Teaching

    Directory of Open Access Journals (Sweden)

    Chovancová Barbora

    2016-06-01

    Full Text Available Mediation is a language activity that has been unjustly neglected when preparing law students for their future professional careers. When trained in a professional context, students need to develop and improve complex communicative skills. These include not only the traditional language skills such as reading, writing, listening and speaking, but also more advanced skills such as summarizing, providing definitions, changing registers etc. All these are involved in the students’ acquisition of ‘soft skills’ that are particularly important for students of law since much of their future work involves interpersonal lawyer-client interaction. This article argues that mediation is a crucial (though previously underestimated skill and that law-oriented ESP instruction should provide training aimed at developing this skill. Showing a practical application of this approach, the paper demonstrates that mediation can be successfully integrated in the legal English syllabus and make the learning of legal English more effective.

  6. Radical-Mediated Enzymatic Polymerizations

    Science.gov (United States)

    Zavada, Scott R.; Battsengel, Tsatsral; Scott, Timothy F.

    2016-01-01

    Polymerization reactions are commonly effected by exposing monomer formulations to some initiation stimulus such as elevated temperature, light, or a chemical reactant. Increasingly, these polymerization reactions are mediated by enzymes―catalytic proteins―owing to their reaction efficiency under mild conditions as well as their environmental friendliness. The utilization of enzymes, particularly oxidases and peroxidases, for generating radicals via reduction-oxidation mechanisms is especially common for initiating radical-mediated polymerization reactions, including vinyl chain-growth polymerization, atom transfer radical polymerization, thiol–ene step-growth polymerization, and polymerization via oxidative coupling. While enzyme-mediated polymerization is useful for the production of materials intended for subsequent use, it is especially well-suited for in situ polymerizations, where the polymer is formed in the place where it will be utilized. Such polymerizations are especially useful for biomedical adhesives and for sensing applications. PMID:26848652

  7. Mediatization Theory and Digital Media

    DEFF Research Database (Denmark)

    Finnemann, Niels Ole

    2011-01-01

    In the 20th century, the term "media logic" was introduced to denote the influence of independent mass media on political systems and other institutions. In recent years the idea has been reworked and labelled "mediatization" to widen the framework by including new media and new areas of applicat......In the 20th century, the term "media logic" was introduced to denote the influence of independent mass media on political systems and other institutions. In recent years the idea has been reworked and labelled "mediatization" to widen the framework by including new media and new areas...

  8. Surfactant-Mediated Growth Revisited

    International Nuclear Information System (INIS)

    Meyerheim, H. L.; Sander, D.; Popescu, R.; Pan, W.; Kirschner, J.; Popa, I.

    2007-01-01

    The x-ray structure analysis of the oxygen-surfactant-mediated growth of Ni on Cu(001) identifies up to 0.15 monolayers of oxygen in subsurface octahedral sites. This questions the validity of the general view that surfactant oxygen floats on top of the growing Ni film. Rather, the surfactant action is ascribed to an oxygen-enriched zone extending over the two topmost layers. Surface stress measurements support this finding. Our results have important implications for the microscopic understanding of surfactant-mediated growth and the change of the magnetic anisotropy of the Ni films

  9. Playful mediation and virtual sociality

    Directory of Open Access Journals (Sweden)

    Sihem NAJJAR

    2010-01-01

    Full Text Available As a space of sociability, virtual games, especially online role playing games, allow us to capture the interest of the playfulness in social life, but they are means by which users are able to experiment their relationship to others. The virtual games as a mediation device, constitute a "pretext" to forge friendships, develop love relationships, improve language skills, discover other cultures, etc. Based on a sociological survey of Tunisian Internet users (both sexes fans of virtual games we try to show how playful mediation is producing a multifaceted virtual sociality inherent in our contemporary societies.

  10. Family education and television mediation

    Directory of Open Access Journals (Sweden)

    Paz CÁNOVAS LEONHARDT

    2010-07-01

    Full Text Available This article try to deal with the complex influence of television viewing in the process of socialization of children and adolescents, focusing our attention on the importance of the family as the mediator-educator agency of particular relevance. Once analyzed the basic theoretical assumptions, we deepened in reality under study by providing data about how the studied population lives television and what extent parental mediation influences and affects the process. The article concludes with some reflections and pedagogical suggestions which trying to help to the optimization of the educational reality.

  11. Dynamical Messengers for Gauge Mediation

    Energy Technology Data Exchange (ETDEWEB)

    Hook, Anson; Torroba, Gonzalo; /SLAC /Stanford U., Phys. Dept.

    2011-08-17

    We construct models of indirect gauge mediation where the dynamics responsible for breaking supersymmetry simultaneously generates a weakly coupled subsector of messengers. This provides a microscopic realization of messenger gauge mediation where the messenger and hidden sector fields are unified into a single sector. The UV theory is SQCD with massless and massive quarks plus singlets, and at low energies it flows to a weakly coupled quiver gauge theory. One node provides the primary source of supersymmetry breaking, which is then transmitted to the node giving rise to the messenger fields. These models break R-symmetry spontaneously, produce realistic gaugino and sfermion masses, and give a heavy gravitino.

  12. Instrumentation and control engineering at ENACE (Argentine Nuclear Enterprise of Electric Power Plants S.A.)

    International Nuclear Information System (INIS)

    Roca, J.L.; Garzon, D.

    1987-01-01

    This paper describes the techniques used in the project of instrumentation and control for the Atucha II nuclear power plant, from the original flow diagram of the system whose instrumentation and control is requested to the functional binary diagrams and control loops, through measurement sheets and other documentation. An account of the organization and handling of this mass of information is given, using an electronic processing system of data file for the project. A brief description of the task implied in the completing and updating of these files defines the scheme in which all the documentation development associated with a given process is included. (Author)

  13. Mediating Multilingual Children's Language Resources

    Science.gov (United States)

    Potts, D.; Moran, M. J.

    2013-01-01

    The everyday reality of children's multilingualism is a significant resource for expanding students' perspectives on the world, but many questions remain regarding the negotiation of these resources in mainstream classrooms. Drawing on research from a long-term Canadian study of multiliterate pedagogies, this paper explores mediation of home…

  14. Trilinear-augmented gaugino mediation

    DEFF Research Database (Denmark)

    Heisig, Jan; Kersten, Jörn; Murphy, Nick

    2017-01-01

    We consider a gaugino-mediated supersymmetry breaking scenario where in addition to the gauginos the Higgs fields couple directly to the field that breaks supersymmetry. This yields non-vanishing trilinear scalar couplings in general, which can lead to large mixing in the stop sector providing...

  15. Anomaly mediation in superstring theory

    Energy Technology Data Exchange (ETDEWEB)

    Conlon, Joseph P. [Rudolf Peierls Center for Theoretical Physics, Oxford (United Kingdom); Balliol College, Oxford (United Kingdom); Goodsell, Mark [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Palti, Eran [Centre de Physique Theoretique, Ecole Polytechnique, CNRS, Palaiseau (France)

    2010-08-15

    We study anomaly mediated supersymmetry breaking in type IIB string theory and use our results to test the supergravity formula for anomaly mediated gaugino masses. We compute 1-loop gaugino masses for models of D3-branes on orbifold singularities with 3-form fluxes by calculating the annulus correlator of 3-form flux and two gauginos in the zero momentum limit. Consistent with supergravity expectations we find both anomalous and running contributions to 1-loop gaugino masses. For background Neveu-Schwarz H-flux we find an exact match with the supergravity formula. For Ramond-Ramond flux there is an off-shell ambiguity that precludes a full matching. The anomaly mediated gaugino masses, while determined by the infrared spectrum, arise from an explicit sum over UV open string winding modes. We also calculate brane-to-brane tree-level gravity mediated gaugino masses and show that there are two contributions coming from the dilaton and from the twisted modes, which are suppressed by the full T{sup 6} volume and the untwisted T{sup 2} volume respectively. (orig.)

  16. Sonic mediations: body, sound, technology

    NARCIS (Netherlands)

    Birdsall, C.; Enns, A.

    2008-01-01

    Sonic Mediations: Body, Sound, Technology is a collection of original essays that represents an invaluable contribution to the burgeoning field of sound studies. While sound is often posited as having a bridging function, as a passive in-between, this volume invites readers to rethink the concept of

  17. Diselenolane-mediated cellular uptake.

    Science.gov (United States)

    Chuard, Nicolas; Poblador-Bahamonde, Amalia I; Zong, Lili; Bartolami, Eline; Hildebrandt, Jana; Weigand, Wolfgang; Sakai, Naomi; Matile, Stefan

    2018-02-21

    The emerging power of thiol-mediated uptake with strained disulfides called for a move from sulfur to selenium. We report that according to results with fluorescent model substrates, cellular uptake with 1,2-diselenolanes exceeds uptake with 1,2-dithiolanes and epidithiodiketopiperazines with regard to efficiency as well as intracellular localization. The diselenide analog of lipoic acid performs best. This 1,2-diselenolane delivers fluorophores efficiently to the cytosol of HeLa Kyoto cells, without detectable endosomal capture as with 1,2-dithiolanes or dominant escape into the nucleus as with epidithiodiketopiperazines. Diselenolane-mediated cytosolic delivery is non-toxic (MTT assay), sensitive to temperature but insensitive to inhibitors of endocytosis (chlorpromazine, methyl-β-cyclodextrin, wortmannin, cytochalasin B) and conventional thiol-mediated uptake (Ellman's reagent), and to serum. Selenophilicity, the extreme CSeSeC dihedral angle of 0° and the high but different acidity of primary and secondary selenols might all contribute to uptake. Thiol-exchange affinity chromatography is introduced as operational mimic of thiol-mediated uptake that provides, in combination with rate enhancement of DTT oxidation, direct experimental evidence for existence and nature of the involved selenosulfides.

  18. Mediated Encryption: Analysis and Design

    Directory of Open Access Journals (Sweden)

    I. Elashry1

    2015-01-01

    Full Text Available Boneh, Ding and Tsudik presented identity-based mediated RSA encryption and signature systems in which the users are not allowed to decrypt/sign messages without the authorisation of a security mediator.We show that ID-MRSA is not secure and we present a secure modified version of it which is as efficient as the original system. We also propose a generic mediated encryption that translates any identity based encryption to a mediated version of this IBE. It envelops an IBE encrypted message using a user’s identity into an IBE envelope using the identity of the SEM. We present two security models based on the role of the adversary whether it is a revoked user or a hacked SEM. We prove that GME is as secure as the SEM’s IBE against a revoked user and as secure as the user’s IBE against a hacked SEM. We also present two implementations of GME based on Boneh-Franklin FullIBE system which is a pairing-based system and Boneh, Gentry and Hamburg (BGH system which is pairing-free system.

  19. Crime fiction and mediatized religion

    DEFF Research Database (Denmark)

    Hansen, Kim Toft

    Scandinavian media where religion has become mediatized. Consumers of popular culture no longer endorse confidence in institutionalized religion, but that does not mean that people are losing faith: Faith only seems to adjust itself and tiptoe into popular media and popular fiction. Hence, this paper seeks...

  20. Mediation –Voluntary or Mandatory Procedure

    Directory of Open Access Journals (Sweden)

    Angelica ROSU

    2010-03-01

    Full Text Available Part of modifications brought through 370/2009 Act to the 192/2006 Law concerning mediation and structure of mediator profession have been interpreted as establishing a preliminary mediation procedure before intimating the courts of law, in civil and commercial matters. This interpretation is in excess of operative legal provisions. Although the law in modified form stipulates the compulsoriness of judicial authorities and other jurisdictional bodies to inform the parties about the possibility and the dvantages of using mediation procedure and the obligation to guide the parties to resort at mediation, this circumstances does not affect the mediation particular voluntary nature.

  1. Profession of mediator as the professional provider of the mediation process

    Directory of Open Access Journals (Sweden)

    Jernej Šoštar

    2017-03-01

    Full Text Available The civil mediation programme, which is a court-connected programme, established as a form of alternative dispute resolution, is increasingly gaining ground as a field with its own theoretical and practical knowledge, principles and basic rules. Mediation has already set up its own body of knowledge, based on studies, classification of cases and the analyses of the results. In this article, we examine whether in the context of the development of mediation in Slovenia we might already talk about the profession of the mediator, defined as a provider of the mediation process. We examine the court-connected civil mediation and mediators who mediate at the court-connected civil mediation, and define them theoretically. By interviewing the mediation experts and mediators we examine their opinions about mediators and the court mediation. We examine the legal basis for the court-connected mediation programmes in Slovenia as well as in the European Union. Proceeding from our findings we conclude that the legal regulation of the court mediation in Slovenia is well established, and that the mediators of the court-connected civil mediation programmes can be accepted as the professional providers of the mediation process.

  2. Ratio-of-Mediator-Probability Weighting for Causal Mediation Analysis in the Presence of Treatment-by-Mediator Interaction

    Science.gov (United States)

    Hong, Guanglei; Deutsch, Jonah; Hill, Heather D.

    2015-01-01

    Conventional methods for mediation analysis generate biased results when the mediator--outcome relationship depends on the treatment condition. This article shows how the ratio-of-mediator-probability weighting (RMPW) method can be used to decompose total effects into natural direct and indirect effects in the presence of treatment-by-mediator…

  3. Mediation Works: An Action Research Study Evaluating the Peer Mediation Program from the Eyes of Mediators and Faculty

    Science.gov (United States)

    Cook, Jacqueline Yvonne; Boes, Susan R.

    2013-01-01

    A literature review was conducted to understand how mediators and faculty view a Peer Mediation Program (PMP). The review identified four subgroups: mediators, teachers, administrators, and school counselors as well as their views on the success or lack of success of PMPs. The research also reflects how to best engage stakeholders in the mediation…

  4. The effect of the Z mutation on the ability of alpha 1-antitrypsin to prevent neutrophil mediated tissue damage.

    Science.gov (United States)

    Llewellyn-Jones, C G; Lomas, D A; Carrell, R W; Stockley, R A

    1994-11-29

    Recent studies have shown that alpha 1-antitrypsin (alpha 1-AT) from Z antitrypsin deficiency subjects has a slightly lower association rate constant with neutrophil elastase (NE) than alpha 1-AT from normal subjects, although it is unknown whether this is of clinical importance. We have purified alpha 1-AT from a normal (M alpha 1-AT) and from a deficient (Z alpha 1-AT) subject and have confirmed that the association rate constants for NE are different (5.28; S.E. 0.06.10(7) M-1 s-1 and 1.2; S.E. 0.2.10(7) M-1 s-1, respectively). We have assessed the ability of both of these proteins to inhibit neutrophil mediated fibronectin (FN) degradation in vitro. Both proteins inhibited FN degradation in a dose dependant manner although Z alpha 1-AT was less effective than M alpha 1-AT at equivalent concentrations of active inhibitor (P < 0.05). Inhibition by M alpha 1-AT was 28.5% S.E. 3.9 at 0.01 microM; 35.5% S.E. 7.3 at 0.1 microM and 37% S.E. 8.4 at 0.5 microM, whereas inhibition by Z alpha 1-AT was 9.25% S.E. 3.9; 19.25% S.E. 7.7 and 21.2% S.E. 9.7, respectively. When the time course of inhibition of FN degradation was studied the difference (although less at 1.0 microM) became greater over the 3 h period of the assay. These results suggest that Z alpha 1-AT is less able than the M phenotype to inhibit connective tissue degradation by neutrophils at equivalent concentrations. This is probably due to the lower association rate constant although the reduced stability of the Z molecule may play a role. The differences, together with the reduced plasma concentration, may accentuate the susceptibility of deficient subjects to the development of emphysema.

  5. Parameter space of general gauge mediation

    International Nuclear Information System (INIS)

    Rajaraman, Arvind; Shirman, Yuri; Smidt, Joseph; Yu, Felix

    2009-01-01

    We study a subspace of General Gauge Mediation (GGM) models which generalize models of gauge mediation. We find superpartner spectra that are markedly different from those of typical gauge and gaugino mediation scenarios. While typical gauge mediation predictions of either a neutralino or stau next-to-lightest supersymmetric particle (NLSP) are easily reproducible with the GGM parameters, chargino and sneutrino NLSPs are generic for many reasonable choices of GGM parameters.

  6. Mediation Analysis in Psychosomatic Medicine Research

    OpenAIRE

    Lockhart, Ginger; MacKinnon, David P.; Ohlrich, Vanessa

    2010-01-01

    This article presents an overview of statistical mediation analysis and its application to psychosomatic medicine research. The article begins with a description of the major approaches to mediation analysis and an evaluation of the strengths and limits of each. Emphasis is placed on longitudinal mediation models, and an application using latent growth modeling is presented. The article concludes with a description of recent developments in mediation analysis and suggestions for the use of me...

  7. Mediator oxidation systems in organic electrosynthesis

    International Nuclear Information System (INIS)

    Ogibin, Yurii N; Elinson, Michail N; Nikishin, Gennady I

    2009-01-01

    The data on the use of mediator oxidation systems activated by electric current (anodic or parallel anodic and cathodic) in organic electrosynthesis are considered and generalised. Electrochemical activation of these systems permits successful application of catalytic versions and easy scaling of mediator-promoted processes. Chemical and environmental advantages of electrochemical processes catalysed by mediator oxidation systems are demonstrated. Examples of the application of organic and inorganic mediators for the oxidation of various classes of organic compounds under conditions of electrolysis are given.

  8. LEGAL CULTURES AND MEDIATION. INTERACTIONS AND EVOLUTIONS

    Directory of Open Access Journals (Sweden)

    Claudiu Ramon D. BUTCULESCU

    2014-05-01

    Full Text Available Mediation, as an alternative dispute resolution method, is closely connected with the system of legal cultures. Mediation is an important link between legal culture and the judicial system. Mediation also acts as an interface between internal legal culture and external legal culture. This paper addresses the issues regarding the links and interactions between mediation and legal cultures, as well as the effects that arise from these interactions.

  9. Agrobacterium tumefaciens-Mediated Transformation

    DEFF Research Database (Denmark)

    Frandsen, Rasmus John Normand

    2015-01-01

    The use of Agrobacterium tumefaciens-mediated transformation for achieving genetic transformation of fungi has steadily increased over the last decade, and has proven to be almost universally applicable technique once suitable selection markers have been developed. In recent years the major...... technical advances has been made within the initial steps of the process, more specifically the efficient construction of plasmids for performing targeted genome modifications. This chapter provides a generic protocol for performing genetic transformation of ascomycetes via A. tumefaciens......-mediated transformation (AMT) and guidelines for optimizing the AMT process with new fungal species. The chapter also includes a highly efficient vector construction system based on Uracil Specific Excisions Reagent (USER) cloning and specific PCR generated building blocks, which can be combined ad hoc to create complex...

  10. Introduction: Mediating and Remediating Death

    DEFF Research Database (Denmark)

    Christensen, Dorthe Refslund; Sandvik, Kjetil

    2014-01-01

    In this second volume we explore how people, groups and institutions deal with death through processes of mediation (the presentation of something through media), remediation (the representation of one medium in another, see below) and mediatization (the process through which core elements...... of a social or cultural activity assume media form, see below). The volume presents a wide variety of ethnographies of death from Norway, Finland, Sweden, the US, Papua New Guinea, Bosnia and Hercegovina, Libya, Tibet, Uganda and Denmark as well as a number of online sites and social media material....... These are analyzed through a vast number of theoretical and analytical perspectives in order to investigate how very diverse practices surrounding death and dying - mourning and commemoration, ritualization, politicization, re-enactment, traditionalization, activism or documentarism: private or public, offline...

  11. Mediatization: a concept, multiple voices

    Directory of Open Access Journals (Sweden)

    Pedro Gilberto GOMES

    2016-12-01

    Full Text Available Mediatization has become increasingly a key concept, fundamental, essential to describe the present and the history of media and communicative change taking place. Thus, it became part of a whole, one can not see them as a separate sphere. In this perspective, the media coverage is used as a concept to describe the process of expansion of the different technical means and consider the interrelationships between the communicative change, means and sociocultural change. However, although many researchers use the concept of mediatization, each gives you the meaning that best suits your needs. Thus, the concept of media coverage is treated with multiple voices. This paper discusses this problem and present a preliminary pre-position on the matter.

  12. 41 CFR 101-8.717 - Mediation.

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 2 2010-07-01 2010-07-01 true Mediation. 101-8.717... FINANCIAL ASSISTANCE 8.7-Discrimination Prohibited on the Basis of Age § 101-8.717 Mediation. (a) GSA promptly refers to the mediation agency designated by the Secretary, HHS, all sufficient complaints that...

  13. 34 CFR 303.419 - Mediation.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 2 2010-07-01 2010-07-01 false Mediation. 303.419 Section 303.419 Education... DISABILITIES Procedural Safeguards Mediation and Due Process Procedures for Parents and Children § 303.419 Mediation. (a) General. Each State shall ensure that procedures are established and implemented to allow...

  14. 45 CFR 617.10 - Mediation.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Mediation. 617.10 Section 617.10 Public Welfare... OF AGE IN PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE FROM NSF § 617.10 Mediation. (a) NSF will refer to the Federal Mediation and Conciliation Service all complaints that fall within...

  15. 34 CFR 300.506 - Mediation.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 2 2010-07-01 2010-07-01 false Mediation. 300.506 Section 300.506 Education... DISABILITIES Procedural Safeguards Due Process Procedures for Parents and Children § 300.506 Mediation. (a... due process complaint, to resolve disputes through a mediation process. (b) Requirements. The...

  16. Single-Level and Multilevel Mediation Analysis

    Science.gov (United States)

    Tofighi, Davood; Thoemmes, Felix

    2014-01-01

    Mediation analysis is a statistical approach used to examine how the effect of an independent variable on an outcome is transmitted through an intervening variable (mediator). In this article, we provide a gentle introduction to single-level and multilevel mediation analyses. Using single-level data, we demonstrate an application of structural…

  17. 7 CFR 900.109 - Mediation agreement.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Mediation agreement. 900.109 Section 900.109 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing... Mediation agreement. An agreement arrived at by mediation shall not become effective until approved by the...

  18. The Merits of Using Longitudinal Mediation

    Science.gov (United States)

    Jose, Paul E.

    2016-01-01

    Many of the mediation analyses reported in the literature are based on concurrent or single-occasion data sets. The 2 overarching themes of the present article are: Results of concurrent mediations are inherently ambiguous, and researchers would be wise to conduct mediations on longitudinal data sets instead. An example included here demonstrates…

  19. 13 CFR 117.12 - Mediation.

    Science.gov (United States)

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Mediation. 117.12 Section 117.12... Mediation. (a) SBA shall, after ensuring that the complaint falls within the coverage of this Act and all... clearly within an exception, promptly refer the complaint to the Federal Mediation and Conciliation...

  20. 7 CFR 400.94 - Mediation.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 6 2010-01-01 2010-01-01 false Mediation. 400.94 Section 400.94 Agriculture... AGRICULTURE GENERAL ADMINISTRATIVE REGULATIONS Appeal Procedure § 400.94 Mediation. For adverse decisions only: (a) Appellants have the right to seek mediation or other forms of alternative dispute resolution in...

  1. Causal Mediation Analysis: Warning! Assumptions Ahead

    Science.gov (United States)

    Keele, Luke

    2015-01-01

    In policy evaluations, interest may focus on why a particular treatment works. One tool for understanding why treatments work is causal mediation analysis. In this essay, I focus on the assumptions needed to estimate mediation effects. I show that there is no "gold standard" method for the identification of causal mediation effects. In…

  2. Methods for Mediation Analysis with Missing Data

    Science.gov (United States)

    Zhang, Zhiyong; Wang, Lijuan

    2013-01-01

    Despite wide applications of both mediation models and missing data techniques, formal discussion of mediation analysis with missing data is still rare. We introduce and compare four approaches to dealing with missing data in mediation analysis including list wise deletion, pairwise deletion, multiple imputation (MI), and a two-stage maximum…

  3. Axino dark matter in mirage mediation

    International Nuclear Information System (INIS)

    Nakamura, Shuntaro; Okumura, Ken-ichi; Yamaguchi, Masahiro

    2009-01-01

    The mirage mediation of supersymmetry breaking is a phenomenologically quite interesting possibility, however, it suffers from two major problems: the moduli-induced gravitino problem and the μ-Bμ problem. In this paper, we propose that the axionic extension of mirage mediation, axionic mirage mediation can solve both problems simultaneously. We address the cosmological consequences of the scenario extensively.

  4. Mediation in complex multi-party disputes

    NARCIS (Netherlands)

    Kamminga, Y.P.; Blohorn-Brenneur, B.

    2013-01-01

    Mediation is on the rise but it is lagging behind in certain fields such as in the resolution of complex disputes. This article addresses how biases in the decision-making process for selecting either mediation or litigation surrounding dispute resolution works in the disadvantage of mediation. It

  5. Direct mediation, duality and unification

    International Nuclear Information System (INIS)

    Abel, Steven; Khoze, Valentin V.

    2008-01-01

    It is well-known that in scenarios with direct gauge mediation of supersymmetry breaking the messenger fields significantly affect the running of Standard Model couplings and introduce Landau poles which are difficult to avoid. Among other things, this appears to remove any possibility of a meaningful unification prediction and is often viewed as a strong argument against direct mediation. We propose two ways that Seiberg duality can circumvent this problem. In the first, which we call 'deflected-unification', the SUSY-breaking hidden sector is a magnetic theory which undergoes a Seiberg duality to an electric phase. Importantly, the electric version has fewer fundamental degrees of freedom coupled to the MSSM compared to the magnetic formulation. This changes the β-functions of the MSSM gauge couplings so as to push their Landau poles above the unification scale. We show that this scenario is realised for recently suggested models of gauge mediation based on a metastable SCQD-type hidden sector directly coupled to MSSM. The second possibility for avoiding Landau poles, which we call 'dual-unification', begins with the observation that, if the mediating fields fall into complete SU(5) multiplets, then the MSSM+messengers exhibits a fake unification at unphysical values of the gauge couplings. We show that, in known examples of electric/magnetic duals, such a fake unification in the magnetic theory reflects a real unification in the electric theory. We therefore propose that the Standard Model could itself be a magnetic dual of some unknown electric theory in which the true unification takes place. This scenario maintains the unification prediction (and unification scale) even in the presence of Landau poles in the magnetic theory below the GUT scale. We further note that this dual realization of grand unification can explain why Nature appears to unify, but the proton does not decay.

  6. Minimal ancilla mediated quantum computation

    International Nuclear Information System (INIS)

    Proctor, Timothy J.; Kendon, Viv

    2014-01-01

    Schemes of universal quantum computation in which the interactions between the computational elements, in a computational register, are mediated by some ancillary system are of interest due to their relevance to the physical implementation of a quantum computer. Furthermore, reducing the level of control required over both the ancillary and register systems has the potential to simplify any experimental implementation. In this paper we consider how to minimise the control needed to implement universal quantum computation in an ancilla-mediated fashion. Considering computational schemes which require no measurements and hence evolve by unitary dynamics for the global system, we show that when employing an ancilla qubit there are certain fixed-time ancilla-register interactions which, along with ancilla initialisation in the computational basis, are universal for quantum computation with no additional control of either the ancilla or the register. We develop two distinct models based on locally inequivalent interactions and we then discuss the relationship between these unitary models and the measurement-based ancilla-mediated models known as ancilla-driven quantum computation. (orig.)

  7. Male-mediated developmental toxicity

    Directory of Open Access Journals (Sweden)

    Diana Anderson

    2014-02-01

    Full Text Available Male-mediated developmental toxicity has been of concern for many years. The public became aware of male-mediated developmental toxicity in the early 1990s when it was reported that men working at Sellafield might be causing leukemia in their children. Human and animal studies have contributed to our current understanding of male-mediated effects. Animal studies in the 1980s and 1990s suggested that genetic damage after radiation and chemical exposure might be transmitted to offspring. With the increasing understanding that there is histone retention and modification, protamine incorporation into the chromatin and DNA methylation in mature sperm and that spermatozoal RNA transcripts can play important roles in the epigenetic state of sperm, heritable studies began to be viewed differently. Recent reports using molecular approaches have demonstrated that DNA damage can be transmitted to babies from smoking fathers, and expanded simple tandem repeats minisatellite mutations were found in the germline of fathers who were exposed to radiation from the Chernobyl nuclear power plant disaster. In epidemiological studies, it is possible to clarify whether damage is transmitted to the sons after exposure of the fathers. Paternally transmitted damage to the offspring is now recognized as a complex issue with genetic as well as epigenetic components.

  8. Substrate mediated enzyme prodrug therapy.

    Directory of Open Access Journals (Sweden)

    Betina Fejerskov

    Full Text Available In this report, we detail Substrate Mediated Enzyme Prodrug Therapy (SMEPT as a novel approach in drug delivery which relies on enzyme-functionalized cell culture substrates to achieve a localized conversion of benign prodrug(s into active therapeutics with subsequent delivery to adhering cells or adjacent tissues. For proof-of-concept SMEPT, we use surface adhered micro-structured physical hydrogels based on poly(vinyl alcohol, β-glucuronidase enzyme and glucuronide prodrugs. We demonstrate enzymatic activity mediated by the assembled hydrogel samples and illustrate arms of control over rate of release of model fluorescent cargo. SMEPT was not impaired by adhering cells and afforded facile time - and dose - dependent uptake of the in situ generated fluorescent cargo by hepatic cells, HepG2. With the use of a glucuronide derivative of an anticancer drug, SN-38, SMEPT afforded a decrease in cell viability to a level similar to that achieved using parent drug. Finally, dose response was achieved using SMEPT and administration of judiciously chosen concentration of SN-38 glucuronide prodrug thus revealing external control over drug delivery using drug eluting surface. We believe that this highly adaptable concept will find use in diverse biomedical applications, specifically surface mediated drug delivery and tissue engineering.

  9. Mediators and Metaphorical Analysis: A Phenomenological Study of Florida Family Court Mediators

    Science.gov (United States)

    Storrow, Rebecca A.

    2012-01-01

    Florida family court mediation programs have typically been assessed with quantitative analysis. To understand the complexity of the experience of being a family mediator, it was necessary to explore how mediators practiced through qualitative research. Metaphors have been considered to be representations of mediators' mental models regarding…

  10. Mediation – Mandatory Information and Facultative Applicability

    Directory of Open Access Journals (Sweden)

    Monica Pocora

    2015-12-01

    Full Text Available Considering that mediation is a facilitating way to access the alternative solving of litigations in conciliatory terms, the study is encouraging using the mediation and providing a balanced relationship between mediation and judiciary procedures. As an aftermath of summary definition, we can say that role of mediation is to overcome the communicative barriers in order to solve the conflict and save the fact situation on both parts. The study aims at analyzing objectively all consequences of both solving ways of litigations: traditional one, through the law court and mediation, with the advantages derived from them (celerity vs. time consuming, expensive judiciary proceedings vs. low costs, etc.

  11. Preeclampsia, migración celular y canales iónicos Preeclampsia, cellular migration and ion channels

    Directory of Open Access Journals (Sweden)

    Silvana M. del Mónaco

    2008-10-01

    Full Text Available En la placenta humana, el sinciciotrofoblasto es la barrera que regula el transporte de nutrientes, solutos y agua entre la sangre materna y fetal. Dentro de este movimiento transepitelial se encuentra el del Na+, su contribución a la presión osmótica es fundamental en la regulación del volumen de líquido extracelular. El canal epitelial de sodio sensible al amiloride (ENaC media el transporte de Na+ desde el lumen hacia el interior celular en numerosos epitelios absortivos. Está regulado por la aldosterona, vasopresina, catecolaminas, estrógenos y progesterona. Es bloqueado por el amiloride y sus análogos. Para su activación, diversas proteasas lo escinden en la membrana plasmática y esto a su vez es regulado por la aldosterona. El ENaC está expresado también en la placenta humana y aunque su función no es conocida, podría participar en la homeostasis de agua y electrolitos. El ENaC también es influenciado por el estado de las proteínas del citoesqueleto y los cambios en el volumen celular alteran a su vez a éste. De esta manera existe una relación entre el ENaC y el citoesqueleto. Además, las corrientes de Na+ por el ENaC y otros canales de sodio participan en la migración celular en células normales y cancerosas. Aquí presentamos evidencias que avalan la hipótesis que el ENaC es necesario para la migración celular en células BeWo, derivadas del trofoblasto humano, que sintetizan hormonas y expresan el ENaC. Las células BeWO han sido utilizadas como modelo experimental para estudiar el transporte en células de placenta.The syncytiotrophoblast acts in human placenta as a transporting barrier regulating the transference of nutrients, solutes and water between maternal and fetal blood. This transepithelial transport involves movement of Na+ and its contribution to the osmotic pressure is an important determinant of the extracellular fluid volume. ENaC is a channel that mediates entry of Na+ from the luminal fluid into

  12. Immunoglobulin E-Mediated Autoimmunity

    Directory of Open Access Journals (Sweden)

    Marcus Maurer

    2018-04-01

    Full Text Available The study of autoimmunity mediated by immunoglobulin E (IgE autoantibodies, which may be termed autoallergy, is in its infancy. It is now recognized that systemic lupus erythematosus, bullous pemphigoid (BP, and chronic urticaria, both spontaneous and inducible, are most likely to be mediated, at least in part, by IgE autoantibodies. The situation in other conditions, such as autoimmune uveitis, rheumatoid arthritis, hyperthyroid Graves’ disease, autoimmune pancreatitis, and even asthma, is far less clear but evidence for autoallergy is accumulating. To be certain of an autoallergic mechanism, it is necessary to identify both IgE autoantibodies and their targets as has been done with the transmembrane protein BP180 and the intracellular protein BP230 in BP and IL-24 in chronic spontaneous urticaria. Also, IgE-targeted therapies, such as anti-IgE, must have been shown to be of benefit to patients as has been done with both of these conditions. This comprehensive review of the literature on IgE-mediated autoallergy focuses on three related questions. What do we know about the prevalence of IgE autoantibodies and their targets in different diseases? What do we know about the relevance of IgE autoantibodies in different diseases? What do we know about the cellular and molecular effects of IgE autoantibodies? In addition to providing answers to these questions, based on a broad review of the literature, we outline the current gaps of knowledge in our understanding of IgE autoantibodies and describe approaches to address them.

  13. Hydrological models are mediating models

    Science.gov (United States)

    Babel, L. V.; Karssenberg, D.

    2013-08-01

    Despite the increasing role of models in hydrological research and decision-making processes, only few accounts of the nature and function of models exist in hydrology. Earlier considerations have traditionally been conducted while making a clear distinction between physically-based and conceptual models. A new philosophical account, primarily based on the fields of physics and economics, transcends classes of models and scientific disciplines by considering models as "mediators" between theory and observations. The core of this approach lies in identifying models as (1) being only partially dependent on theory and observations, (2) integrating non-deductive elements in their construction, and (3) carrying the role of instruments of scientific enquiry about both theory and the world. The applicability of this approach to hydrology is evaluated in the present article. Three widely used hydrological models, each showing a different degree of apparent physicality, are confronted to the main characteristics of the "mediating models" concept. We argue that irrespective of their kind, hydrological models depend on both theory and observations, rather than merely on one of these two domains. Their construction is additionally involving a large number of miscellaneous, external ingredients, such as past experiences, model objectives, knowledge and preferences of the modeller, as well as hardware and software resources. We show that hydrological models convey the role of instruments in scientific practice by mediating between theory and the world. It results from these considerations that the traditional distinction between physically-based and conceptual models is necessarily too simplistic and refers at best to the stage at which theory and observations are steering model construction. The large variety of ingredients involved in model construction would deserve closer attention, for being rarely explicitly presented in peer-reviewed literature. We believe that devoting

  14. Mediated electrochemical hazardous waste destruction

    International Nuclear Information System (INIS)

    Hickman, R.G.; Farmer, J.C.; Wang, F.T.

    1992-03-01

    There are few permitted processes for mixed waste (radioactive plus chemically hazardous) treatment. We are developing an electrochemical process, based upon mediated electrochemical oxidation (MEO), that converts toxic organic components of mixed waste to water, carbon dioxide, and chloride or chloride precipitates. Aggressive oxidizer ions such as Ag 2+ , Co 3+ , or Fe 3+ are produced at an anode. These can attack organic molecules directly, and may also produce hydroxyl free radicals that promote destruction. Solid and liquid radioactive waste streams containing only inorganic radionuclide forms may be treated with existing technology and prepared for final disposal. The coulombic efficiency of the process has been determined, as well as the destruction efficiency for ethylene glycol, a surrogate waste. In addition, hazardous organic materials are becoming very expensive to dispose of and when they are combined with transuranic radioactive elements no processes are presently permitted. Mediated electrochemical oxidation is an ambient- temperature aqueous-phase process that can be used to oxidize organic components of mixed wastes. Problems associated with incineration, such as high-temperature volatilization of radionuclides, are avoided. Historically, Ag(II) has been used as a mediator in this process. Fe(III) and Co(III) are attractive alternatives to Ag(II) since they form soluble chlorides during the destruction of chlorinated solvents. Furthermore, silver itself is toxic heavy metal. Quantitative data have been obtained for the complete oxidation of ethylene glycol by Fe(III) and Co(III). Though ethylene glycol is a nonhalogenated organic, these data have enabled us to make direct comparisons of activities of Fe(III) and Co(III) with Ag(II). Very good quantitative data for the oxidation of ethylene glycol by Ag(II) had already been collected

  15. Mediation for resolving family disputes

    Directory of Open Access Journals (Sweden)

    Kamenecka-Usova M.

    2016-01-01

    Full Text Available Nowadays the understanding of the institute of marriage and its importance in the society has changed. Marriage is no longer assumed to be a commitment for a lifetime. As the principle of equality has replaced hierarchy as the guiding principle of family law it gave more grounds for family disputes and it became socially acceptable to leave marriages that are intolerable or merely unfulfilling. The aim of this article is to suggest an alternative dispute resolution method-mediation as a worthy option for resolving family conflicts.

  16. Trilinear-augmented gaugino mediation

    Energy Technology Data Exchange (ETDEWEB)

    Heisig, Jan [Institute for Theoretical Particle Physics and Cosmology, RWTH Aachen University,52056 Aachen (Germany); Kersten, Jörn [Department of Physics and Technology, University of Bergen,5020 Bergen (Norway); Murphy, Nick [CP-Origins, University of Southern Denmark,5230 Odense M (Denmark); Strümke, Inga [Department of Physics and Technology, University of Bergen,5020 Bergen (Norway)

    2017-05-02

    We consider a gaugino-mediated supersymmetry breaking scenario where in addition to the gauginos the Higgs fields couple directly to the field that breaks supersymmetry. This yields non-vanishing trilinear scalar couplings in general, which can lead to large mixing in the stop sector providing a sufficiently large Higgs mass. Using the most recent release of FeynHiggs, we show the implications on the parameter space. Assuming a gravitino LSP, we find allowed points with a neutralino, sneutrino or stau NLSP. We test these points against the results of Run 1 of the LHC, considering in particular searches for heavy stable charged particles.

  17. Trilinear-augmented gaugino mediation

    International Nuclear Information System (INIS)

    Heisig, Jan; Kersten, Jörn; Murphy, Nick; Strümke, Inga

    2017-01-01

    We consider a gaugino-mediated supersymmetry breaking scenario where in addition to the gauginos the Higgs fields couple directly to the field that breaks supersymmetry. This yields non-vanishing trilinear scalar couplings in general, which can lead to large mixing in the stop sector providing a sufficiently large Higgs mass. Using the most recent release of FeynHiggs, we show the implications on the parameter space. Assuming a gravitino LSP, we find allowed points with a neutralino, sneutrino or stau NLSP. We test these points against the results of Run 1 of the LHC, considering in particular searches for heavy stable charged particles.

  18. Mediation designs for tobacco prevention research

    Science.gov (United States)

    MacKinnon, David P.; Taborga, Marcia P.; Morgan-Lopez, Antonio A.

    2010-01-01

    This paper describes research designs and statistical analyses to investigate how tobacco prevention programs achieve their effects on tobacco use. A theoretical approach to program development and evaluation useful for any prevention program guides the analysis. The theoretical approach focuses on action theory for how the program affects mediating variables and on conceptual theory for how mediating variables are related to tobacco use. Information on the mediating mechanisms by which tobacco prevention programs achieve effects is useful for the development of efficient programs and provides a test of the theoretical basis of prevention efforts. Examples of these potential mediating mechanisms are described including mediated effects through attitudes, social norms, beliefs about positive consequences, and accessibility to tobacco. Prior research provides evidence that changes in social norms are a critical mediating mechanism for successful tobacco prevention. Analysis of mediating variables in single group designs with multiple mediators are described as well as multiple group randomized designs which are the most likely to accurately uncover important mediating mechanisms. More complicated dismantling and constructive designs are described and illustrated based on current findings from tobacco research. Mediation analysis for categorical outcomes and more complicated statistical methods are outlined. PMID:12324176

  19. The Mediator complex and transcription regulation

    Science.gov (United States)

    Poss, Zachary C.; Ebmeier, Christopher C.

    2013-01-01

    The Mediator complex is a multi-subunit assembly that appears to be required for regulating expression of most RNA polymerase II (pol II) transcripts, which include protein-coding and most non-coding RNA genes. Mediator and pol II function within the pre-initiation complex (PIC), which consists of Mediator, pol II, TFIIA, TFIIB, TFIID, TFIIE, TFIIF and TFIIH and is approximately 4.0 MDa in size. Mediator serves as a central scaffold within the PIC and helps regulate pol II activity in ways that remain poorly understood. Mediator is also generally targeted by sequence-specific, DNA-binding transcription factors (TFs) that work to control gene expression programs in response to developmental or environmental cues. At a basic level, Mediator functions by relaying signals from TFs directly to the pol II enzyme, thereby facilitating TF-dependent regulation of gene expression. Thus, Mediator is essential for converting biological inputs (communicated by TFs) to physiological responses (via changes in gene expression). In this review, we summarize an expansive body of research on the Mediator complex, with an emphasis on yeast and mammalian complexes. We focus on the basics that underlie Mediator function, such as its structure and subunit composition, and describe its broad regulatory influence on gene expression, ranging from chromatin architecture to transcription initiation and elongation, to mRNA processing. We also describe factors that influence Mediator structure and activity, including TFs, non-coding RNAs and the CDK8 module. PMID:24088064

  20. Transporter-mediated biofuel secretion.

    Science.gov (United States)

    Doshi, Rupak; Nguyen, Tuan; Chang, Geoffrey

    2013-05-07

    Engineering microorganisms to produce biofuels is currently among the most promising strategies in renewable energy. However, harvesting these organisms for extracting biofuels is energy- and cost-intensive, limiting the commercial feasibility of large-scale production. Here, we demonstrate the use of a class of transport proteins of pharmacological interest to circumvent the need to harvest biomass during biofuel production. We show that membrane-embedded transporters, better known to efflux lipids and drugs, can be used to mediate the secretion of intracellularly synthesized model isoprenoid biofuel compounds to the extracellular milieu. Transporter-mediated biofuel secretion sustainably maintained an approximate three- to fivefold boost in biofuel production in our Escherichia coli test system. Because the transporters used in this study belong to the ubiquitous ATP-binding cassette protein family, we propose their use as "plug-and-play" biofuel-secreting systems in a variety of bacteria, cyanobacteria, diatoms, yeast, and algae used for biofuel production. This investigation showcases the potential of expressing desired membrane transport proteins in cell factories to achieve the export or import of substances of economic, environmental, or therapeutic importance.

  1. Multifunctional Curcumin Mediate Multitherapeutic Effects.

    Science.gov (United States)

    Shehzad, Adeeb; Qureshi, Munibah; Anwar, Muhammad Nabeel; Lee, Young Sup

    2017-09-01

    Inflammation can promote the development of arthritis, obesity, cardiovascular, type II diabetes, pancreatitis, metabolic and neurodegenerative diseases, and certain types of cancer. Compounds isolated from plants have been practiced since ancient times for curing various ailments including inflammatory disorders and to support normal physiological functions. Curcumin (diferuloylmethane) is a yellow coloring agent, extracted from turmeric that has been used for the prevention and treatment of various inflammatory diseases. Numerous studies have shown that curcumin modulate multiple molecular targets and can be translated to the clinics for multiple therapeutic processes. There is compelling evidence that curcumin can block cell proliferation, invasion, and angiogenesis as well as reduced the prolonged survival of cancer cells. Curcumin mediates anti-inflammatory effect through downregulation of inflammatory cytokines, transcription factors, protein kinases, and enzymes that promote inflammation and development of chronic diseases. In addition, curcumin induces apoptosis through mitochondrial and receptor-mediated pathways by activating caspase cascades. Curcumin is a safe and nontoxic drug that has been reported to be well tolerated. Available clinical trials support the potential role of curcumin for treatment of various inflammatory disorders. However, curcumin's efficacy is hindered by poor absorption and low bioavailability, which limit its translation into clinics. This review outlines the potential pharmacological and clinical role of curcumin, which provide a gateway for the beneficial role of plant isolated compounds in treatment of various inflammatory diseases and cancer. © 2017 Institute of Food Technologists®.

  2. Desperately Trying to Mediate Immediacy

    Directory of Open Access Journals (Sweden)

    Andreas Oliver Schellewald

    2018-01-01

    Full Text Available Evermore aspects of contemporary cultures, societies and human life appear to be changed through processes of digitization and mediatization. A great body of work is touching on these processes of change. However, not many discuss aspects of leisure and aesthetics. And if they do so, seldom regarding bodily and worldly aspects. This paper thus seeks to discuss such changes alongside the phenomenon of esports. More precisely, the paper situates the aesthetic dimension and practices of watching and doing esports in contemporary cultures and societies, focusing on lived experiences (ästhetisches Erleben in digital and mediated contexts. The failing attempt to understand, the attempt to re-present and Gelassenheit (composure or serenity are introduced as modes of coping with immediate aesthetic experiences. Here, especially the constitutive transition from a physical to a meta-physical dimension of reality will be grasped on. By that, ongoing philosophical debates about the constitution of reality and being can be supported in their progress.

  3. Direct detection with dark mediators

    Energy Technology Data Exchange (ETDEWEB)

    Curtin, David; Surujon, Ze' ev [C. N. Yang Institute for Theoretical Physics, Stony Brook University, Stony Brook, NY 11794 (United States); Tsai, Yuhsin [Physics Department, University of California Davis, Davis, CA 95616 (United States)

    2014-11-10

    We introduce dark mediator Dark Matter (dmDM) where the dark and visible sectors are connected by at least one light mediator ϕ carrying the same dark charge that stabilizes DM. ϕ is coupled to the Standard Model via an operator q{sup ¯}qϕϕ{sup ⁎}/Λ, and to dark matter via a Yukawa coupling y{sub χ}χ{sup c¯}χϕ. Direct detection is realized as the 2→3 process χN→χ{sup ¯}Nϕ at tree-level for m{sub ϕ}≲10 keV and small Yukawa coupling, or alternatively as a loop-induced 2→2 process χN→χN. We explore the direct-detection consequences of this scenario and find that a heavy O(100 GeV) dmDM candidate fakes different O(10 GeV) standard WIMPs in different experiments. Large portions of the dmDM parameter space are detectable above the irreducible neutrino background and not yet excluded by any bounds. Interestingly, for the m{sub ϕ} range leading to novel direct detection phenomenology, dmDM is also a form of Self-Interacting Dark Matter (SIDM), which resolves inconsistencies between dwarf galaxy observations and numerical simulations.

  4. Robust Mediation Analysis Based on Median Regression

    Science.gov (United States)

    Yuan, Ying; MacKinnon, David P.

    2014-01-01

    Mediation analysis has many applications in psychology and the social sciences. The most prevalent methods typically assume that the error distribution is normal and homoscedastic. However, this assumption may rarely be met in practice, which can affect the validity of the mediation analysis. To address this problem, we propose robust mediation analysis based on median regression. Our approach is robust to various departures from the assumption of homoscedasticity and normality, including heavy-tailed, skewed, contaminated, and heteroscedastic distributions. Simulation studies show that under these circumstances, the proposed method is more efficient and powerful than standard mediation analysis. We further extend the proposed robust method to multilevel mediation analysis, and demonstrate through simulation studies that the new approach outperforms the standard multilevel mediation analysis. We illustrate the proposed method using data from a program designed to increase reemployment and enhance mental health of job seekers. PMID:24079925

  5. Legal and Psychological Aspects of Mediation

    Directory of Open Access Journals (Sweden)

    Dobrokhotova E. N.

    2016-01-01

    Full Text Available The article focuses on gradual innovation of mediation into the practice of social conflict resolution in the light of legal and psychological means of mediation. While mediation is perceived as a conflictological concept and is more widely used in dispute settlement and resolution, a new interdisciplinary field of theoretical knowledge with its own conceptual framework as well as a new professional and practical field are beginning to form both in Russia and in other countries. As theoretical and practical aspects of innovation in mediation require consolidation not only for its national development but also for the guaranteed international cooperation, the article touches upon some of the particular theoretical issues of the topic in question: terminological consistency, consolidation of the system of mediation principles, the phenomenon of juridisation of mediation and its limits.

  6. Regulation of metabolism by the Mediator complex.

    Science.gov (United States)

    Youn, Dou Yeon; Xiaoli, Alus M; Pessin, Jeffrey E; Yang, Fajun

    2016-01-01

    The Mediator complex was originally discovered in yeast, but it is conserved in all eukaryotes. Its best-known function is to regulate RNA polymerase II-dependent gene transcription. Although the mechanisms by which the Mediator complex regulates transcription are often complicated by the context-dependent regulation, this transcription cofactor complex plays a pivotal role in numerous biological pathways. Biochemical, molecular, and physiological studies using cancer cell lines or model organisms have established the current paradigm of the Mediator functions. However, the physiological roles of the mammalian Mediator complex remain poorly defined, but have attracted a great interest in recent years. In this short review, we will summarize some of the reported functions of selective Mediator subunits in the regulation of metabolism. These intriguing findings suggest that the Mediator complex may be an important player in nutrient sensing and energy balance in mammals.

  7. DISTANCE LEARNERSÕ PERCEPTIONS OF COMPUTER MEDIATED COMMUNICATION

    OpenAIRE

    Mujgan Bozkaya; Irem Erdem Aydin

    2011-01-01

    In this study, perspectives of the first year students in the completely online Information Management Associate Degree Program at Anadolu University regarding computer as a communication medium were investigated. StudentsÕ perspectives on computer-mediated communications were analyzed in the light of three different views in the area of computer-mediated communications: The first view suggests that face-to-face settings are better communication environments compared to computer-mediated envi...

  8. Community Mediation. A Model for Romania

    Directory of Open Access Journals (Sweden)

    Christian Radu CHEREJI

    2014-02-01

    Full Text Available Community mediation takes all forms and shapes all over the world. In order to better understand its limitations in adapting to different contexts, we have compared the evolution of community mediation services in two totally different systems, USA and Sri Lanka. Based on this analysis and the results of a research conducted in Cluj-Napoca in the fall of 2013, we have recommended a community mediation model suitable for the current Romanian social, economic and cultural framework.

  9. Parental mediation and cyberbullying - a longitudinal study.

    Science.gov (United States)

    Chng, Grace S; Liau, Albert; Khoo, Angeline; Li, Dongdong

    2014-01-01

    Parents use active and restrictive mediation strategies to guide and regulate children's online participation and the online risks they encounter. However, changes in parental mediation do occur over time and the effectiveness of these strategies on cyberbullying demands for further empirical investigation. The current study addresses these issues with a sample of 1084 students (49% girls) in a longitudinal, three-wave design. Gender differences were tested via multi-group analyses. Longitudinal growth models showed that parental use of both active and restrictive mediation decreased over time. For both types of mediation, the mean rate of change had a significant effect on boys' engagement in cyberbullying, but not for girls. Initial levels of restrictive mediation, but not active mediation, were found to be significantly predictive of cyberbullying in both genders. Girls had higher initial levels of both parental mediation types in comparison to boys. The results reveal that the effectiveness of active and restrictive mediation in relation to students' cyberbullying differs and informs us on gender differences. The implications of these results for parental education in online mediation are discussed.

  10. Digital methods for mediated discourse analysis

    DEFF Research Database (Denmark)

    Kjær, Malene; Larsen, Malene Charlotte

    2015-01-01

    , restrictions or privately mediated settings. Having used mediated discourse analysis (Scollon 2002, Scollon & Scollon, 2004) as a framework in two different research projects, we show how the framework, in correlation with digital resources for data gathering, provides new understandings of 1) the daily......In this paper we discuss methodological strategies for collecting multimodal data using digital resources. The aim is to show how digital resources can provide ethnographic insights into mediated actions (Scollon, 2002) that can otherwise be difficult to observe or engage in, due to, for instance......) and online questionnaire data in order to capture mediated actions and discourses in practice....

  11. Transcription regulation by the Mediator complex.

    Science.gov (United States)

    Soutourina, Julie

    2018-04-01

    Alterations in the regulation of gene expression are frequently associated with developmental diseases or cancer. Transcription activation is a key phenomenon in the regulation of gene expression. In all eukaryotes, mediator of RNA polymerase II transcription (Mediator), a large complex with modular organization, is generally required for transcription by RNA polymerase II, and it regulates various steps of this process. The main function of Mediator is to transduce signals from the transcription activators bound to enhancer regions to the transcription machinery, which is assembled at promoters as the preinitiation complex (PIC) to control transcription initiation. Recent functional studies of Mediator with the use of structural biology approaches and functional genomics have revealed new insights into Mediator activity and its regulation during transcription initiation, including how Mediator is recruited to transcription regulatory regions and how it interacts and cooperates with PIC components to assist in PIC assembly. Novel roles of Mediator in the control of gene expression have also been revealed by showing its connection to the nuclear pore and linking Mediator to the regulation of gene positioning in the nuclear space. Clear links between Mediator subunits and disease have also encouraged studies to explore targeting of this complex as a potential therapeutic approach in cancer and fungal infections.

  12. Computer-Mediated Communication Systems

    Directory of Open Access Journals (Sweden)

    Bin Yu

    2011-10-01

    Full Text Available The essence of communication is to exchange and share information. Computers provide a new medium to human communication. CMC system, composed of human and computers, absorbs and then extends the advantages of all former formats of communication, embracing the instant interaction of oral communication, the abstract logics of printing dissemination, and the vivid images of movie and television. It also creates a series of new communication formats, such as Hyper Text, Multimedia etc. which are the information organizing methods, and cross-space message delivering patterns. Benefiting from the continuous development of technique and mechanism, the computer-mediated communication makes the dream of transmitting information cross space and time become true, which will definitely have a great impact on our social lives.

  13. Lepton-flavor violating mediators

    Energy Technology Data Exchange (ETDEWEB)

    Galon, Iftah; Kwa, Anna [Department of Physics & Astronomy, University of California,Irvine, CA 92697 (United States); Tanedo, Philip [Department of Physics & Astronomy, University of California,Riverside, CA 92521 (United States)

    2017-03-13

    We present a framework where dark matter interacts with the Standard Model through a light, spin-0 mediator that couples chirally to pairs of different-flavor leptons. This flavor violating final state weakens bounds on new physics coupled to leptons from terrestrial experiments and cosmic-ray measurements. As an example, we apply this framework to construct a model for the Fermi-LAT excess of GeV γ-rays from the galactic center. We comment on the viability of this portal for self-interacting dark matter explanations of small scale structure anomalies and embeddings in flavor models. Models of this type are shown to be compatible with the muon anomalous magnetic moment anomaly. We review current experimental constraints and identify possible future theoretical and experimental directions.

  14. Phenomenological aspects of mirage mediation

    Energy Technology Data Exchange (ETDEWEB)

    Loewen, Valeri

    2009-07-15

    We consider the possibility that string theory vacua with spontaneously broken supersymmetry and a small positive cosmological constant arise due to hidden sector matter interactions, known as F-uplifting/F-downlifting. We analyze this procedure in a model-independent way in the context of type IIB and heterotic string theory. Our investigation shows that the uplifting/downlifting sector has very important consequences for the resulting phenomenology. Not only does it adjust the vacuum energy, but it can also participate in the process of moduli stabilization. In addition, we find that this sector is the dominant source of supersymmetry breaking. It leads to a hybrid mediation scheme and its signature is a relaxed mirage pattern of the soft supersymmetry breaking terms. The low energy spectra exhibit distinct phenomenological properties and di er from conventional schemes considered so far. (orig.)

  15. Phenomenological aspects of mirage mediation

    International Nuclear Information System (INIS)

    Loewen, Valeri

    2009-07-01

    We consider the possibility that string theory vacua with spontaneously broken supersymmetry and a small positive cosmological constant arise due to hidden sector matter interactions, known as F-uplifting/F-downlifting. We analyze this procedure in a model-independent way in the context of type IIB and heterotic string theory. Our investigation shows that the uplifting/downlifting sector has very important consequences for the resulting phenomenology. Not only does it adjust the vacuum energy, but it can also participate in the process of moduli stabilization. In addition, we find that this sector is the dominant source of supersymmetry breaking. It leads to a hybrid mediation scheme and its signature is a relaxed mirage pattern of the soft supersymmetry breaking terms. The low energy spectra exhibit distinct phenomenological properties and di er from conventional schemes considered so far. (orig.)

  16. Lepton-mediated electroweak baryogenesis

    International Nuclear Information System (INIS)

    Chung, Daniel J. H.; Garbrecht, Bjorn; Ramsey-Musolf, Michael J.; Tulin, Sean

    2010-01-01

    We investigate the impact of the tau and bottom Yukawa couplings on the transport dynamics for electroweak baryogenesis in supersymmetric extensions of the standard model. Although it has generally been assumed in the literature that all Yukawa interactions except those involving the top quark are negligible, we find that the tau and bottom Yukawa interaction rates are too fast to be neglected. We identify an illustrative 'lepton-mediated electroweak baryogenesis' scenario in which the baryon asymmetry is induced mainly through the presence of a left-handed leptonic charge. We derive analytic formulas for the computation of the baryon asymmetry that, in light of these effects, are qualitatively different from those in the established literature. In this scenario, for fixed CP-violating phases, the baryon asymmetry has opposite sign compared to that calculated using established formulas.

  17. Vasoactive mediators and splanchnic perfusion.

    Science.gov (United States)

    Reilly, P M; Bulkley, G B

    1993-02-01

    To provide an overview of the splanchnic hemodynamic response to circulatory shock. Previous studies performed in our own laboratory, as well as a computer-assisted search of the English language literature (MEDLINE, 1966 to 1991), followed by a selective review of pertinent articles. Studies were selected that demonstrated relevance to the splanchnic hemodynamic response to circulatory shock, either by investigating the pathophysiology or documenting the sequelae. Article selection included clinical studies as well as studies in appropriate animal models. Pertinent data were abstracted from the cited articles. The splanchnic hemodynamic response to circulatory shock is characterized by a selective vasoconstriction of the mesenteric vasculature mediated largely by the renin-angiotensin axis. This vasospasm, while providing a natural selective advantage to the organism in mild-to-moderate shock (preserving relative perfusion of the heart, kidneys, and brain), may, in more severe shock, cause consequent loss of the gut epithelial barrier, or even hemorrhagic gastritis, ischemic colitis, or ischemic hepatitis. From a physiologic standpoint, nonpulsatile cardiopulmonary bypass, a controlled form of circulatory shock, has been found experimentally to significantly increase circulating levels of angiotensin II, the hormone responsible for this selective splanchnic vasoconstriction. While angiotensin II has been viewed primarily as the mediator responsible for the increased total vascular resistance seen during (and after) cardiopulmonary bypass, it may also cause the disproportionate decrease in mesenteric perfusion, as measured in human subjects by intraluminal gastric tonometry and galactose clearance by the liver, as well as the consequent development of the multiple organ failure syndrome seen in 1% to 5% of patients after cardiac surgery.

  18. Mediated electrochemical hazardous waste destruction

    International Nuclear Information System (INIS)

    Hickman, R.G.; Farmer, J.C.; Wang, F.T.

    1991-08-01

    There are few permitted processes for mixed waste (radioactive plus chemically hazardous) treatment. We are developing electrochemical processes that convert the toxic organic components of mixed waste to water, carbon dioxide, an innocuous anions such as chloride. Aggressive oxidizer ions such as Ag 2+ or Ce +4 are produced at an anode. These can attack the organic molecules directly. They can also attack water which yields hydroxyl free radicals that in turn attack the organic molecules. The condensed (i.e., solid and/or liquid) effluent streams contain the inorganic radionuclide forms. These may be treated with existing technology and prepared for final disposal. Kinetics and the extent of destruction of some toxic organics have been measured. Depending on how the process is operated, coulombic efficiency can be nearly 100%. In addition, hazardous organic materials are becoming very expensive to dispose of and when they are combined with transuranic radioactive elements no processes are presently permitted. Mediated electrochemical oxidation is an ambient-temperature aqueous-phase process that can be used to oxidize organic components of mixed wastes. Problems associated with incineration, such as high-temperature volatilization of radionuclides, are avoided. Historically, Ag (2) has been used as a mediator in this process. Fe(6) and Co(3) are attractive alternatives to Ag(2) since they form soluble chlorides during the destruction of chlorinated solvents. Furthermore, silver itself is a toxic heavy metal. Quantitative data has been obtained for the complete oxidation of ethylene glycol by Fe(6) and Co(3). Though ethylene glycol is a nonhalogenated organic, this data has enabled us to make direct comparisons of activities of Fe(6) and Co(3) with Ag(2). Very good quantitative data for the oxidation of ethylene glycol by Ag(2) had already been collected. 4 refs., 6 figs

  19. Designing business rules for mediation : a process towards agent-mediated business coordination

    OpenAIRE

    Zhao, Z.; Dignum, M.V.; Dignum, F.P.M.

    2008-01-01

    Business process integration is a very active research area, in which mediation is one of the fundamental architectural choices. Mediators have difficulties to design mediation services that meet the requirements of the different stakeholders. Business rules play an important role in the decision process of mediation. In this paper, we analyze the role of business rules in the decision process, and use some examples to illustrate how business rules should be designed in order to help the deci...

  20. MEDIATOR18 and MEDIATOR20 confer susceptibility to Fusarium oxysporum in Arabidopsis thaliana

    OpenAIRE

    Fallath, Thorya; Kidd, Brendan N.; Stiller, Jiri; Davoine, Celine; Bj?rklund, Stefan; Manners, John M.; Kazan, Kemal; Schenk, Peer M.

    2017-01-01

    The conserved protein complex known as Mediator conveys transcriptional signals by acting as an intermediary between transcription factors and RNA polymerase II. As a result, Mediator subunits play multiple roles in regulating developmental as well as abiotic and biotic stress pathways. In this report we identify the head domain subunits MEDIATOR18 and MEDIATOR20 as important susceptibility factors for Fusarium oxysporum infection in Arabidopsis thaliana. Mutants of MED18 and MED20 display do...

  1. Forms of Mediation: The Case of Interpreter-Mediated Interactions in Medical Systems

    Science.gov (United States)

    Baraldi, Claudio

    2009-01-01

    This paper analyses the forms of mediation in interlinguistic interactions performed in Italian healthcare services and in contexts of migration. The literature encourages dialogic transformative mediation, empowering participants' voices and changing cultural presuppositions in social systems. It may be doubtful, however, whether mediation can…

  2. Designing business rules for mediation : a process towards agent-mediated business coordination

    NARCIS (Netherlands)

    Zhao, Z.; Dignum, M.V.; Dignum, F.P.M.

    2008-01-01

    Business process integration is a very active research area, in which mediation is one of the fundamental architectural choices. Mediators have difficulties to design mediation services that meet the requirements of the different stakeholders. Business rules play an important role in the

  3. Factor affecting Agrobacterium -mediated transformation of rice ...

    African Journals Online (AJOL)

    Potato is a very important food crop and is adversely affected by fungus. Agrobacterium-mediated transformation can play an important role in the improvement of potato. The present study was conducted to optimize the different factors affecting Agrobacterium-mediated transformation of chitinase gene. Nodes were used as ...

  4. Regional Organisations and International Mediation: The ...

    African Journals Online (AJOL)

    Regional Organisations and International Mediation: The Effectiveness of Insider Mediators. ... During the last two decades of the twentieth century, the world witnessed an increasing number of regional conflict management efforts undertaken by regional inter-governmental organisations. There are therefore strong reasons ...

  5. Parent Mediation Empowers Sibling Conflict Resolution

    Science.gov (United States)

    Ross, Hildy S.; Lazinski, Marysia J.

    2014-01-01

    Research Findings: For the current study, formal mediation procedures were adapted for families and parents were trained and asked to mediate their children's disputes; control group parents intervened as they normally would. Conflict negotiations with parents and their children (ages 3½-11 years) occurring 3 and 7 weeks following training, and…

  6. Semiotic Mediation within an AT Frame

    Science.gov (United States)

    Maracci, Mirko; Mariotti, Maria Alessandra

    2013-01-01

    This article is meant to present a specific elaboration of the notion of mediation in relation to the use of artefacts to enhance mathematics teaching and learning: the elaboration offered by the Theory of Semiotic Mediation. In particular, it provides an explicit model--consistent with the activity-actions-operations framework--of the actions…

  7. A General Approach to Causal Mediation Analysis

    Science.gov (United States)

    Imai, Kosuke; Keele, Luke; Tingley, Dustin

    2010-01-01

    Traditionally in the social sciences, causal mediation analysis has been formulated, understood, and implemented within the framework of linear structural equation models. We argue and demonstrate that this is problematic for 3 reasons: the lack of a general definition of causal mediation effects independent of a particular statistical model, the…

  8. Integrating Mediators and Moderators in Research Design

    Science.gov (United States)

    MacKinnon, David P.

    2011-01-01

    The purpose of this article is to describe mediating variables and moderating variables and provide reasons for integrating them in outcome studies. Separate sections describe examples of moderating and mediating variables and the simplest statistical model for investigating each variable. The strengths and limitations of incorporating mediating…

  9. Elaborative Retrieval: Do Semantic Mediators Improve Memory?

    Science.gov (United States)

    Lehman, Melissa; Karpicke, Jeffrey D.

    2016-01-01

    The elaborative retrieval account of retrieval-based learning proposes that retrieval enhances retention because the retrieval process produces the generation of semantic mediators that link cues to target information. We tested 2 assumptions that form the basis of this account: that semantic mediators are more likely to be generated during…

  10. Histone modifications influence mediator interactions with chromatin

    Science.gov (United States)

    Zhu, Xuefeng; Zhang, Yongqiang; Bjornsdottir, Gudrun; Liu, Zhongle; Quan, Amy; Costanzo, Michael; Dávila López, Marcela; Westholm, Jakub Orzechowski; Ronne, Hans; Boone, Charles; Gustafsson, Claes M.; Myers, Lawrence C.

    2011-01-01

    The Mediator complex transmits activation signals from DNA bound transcription factors to the core transcription machinery. Genome wide localization studies have demonstrated that Mediator occupancy not only correlates with high levels of transcription, but that the complex also is present at transcriptionally silenced locations. We provide evidence that Mediator localization is guided by an interaction with histone tails, and that this interaction is regulated by their post-translational modifications. A quantitative, high-density genetic interaction map revealed links between Mediator components and factors affecting chromatin structure, especially histone deacetylases. Peptide binding assays demonstrated that pure wild-type Mediator forms stable complexes with the tails of Histone H3 and H4. These binding assays also showed Mediator—histone H4 peptide interactions are specifically inhibited by acetylation of the histone H4 lysine 16, a residue critical in transcriptional silencing. Finally, these findings were validated by tiling array analysis that revealed a broad correlation between Mediator and nucleosome occupancy in vivo, but a negative correlation between Mediator and nucleosomes acetylated at histone H4 lysine 16. Our studies show that chromatin structure and the acetylation state of histones are intimately connected to Mediator localization. PMID:21742760

  11. Mediator: A key regulator of plant development.

    Science.gov (United States)

    Buendía-Monreal, Manuel; Gillmor, C Stewart

    2016-11-01

    Mediator is a multiprotein complex that regulates transcription at the level of RNA pol II assembly, as well as through regulation of chromatin architecture, RNA processing and recruitment of epigenetic marks. Though its modular structure is conserved in eukaryotes, its subunit composition has diverged during evolution and varies in response to environmental and tissue-specific inputs, suggesting different functions for each subunit and/or Mediator conformation. In animals, Mediator has been implicated in the control of differentiation and morphogenesis through modulation of numerous signaling pathways. In plants, studies have revealed roles for Mediator in regulation of cell division, cell fate and organogenesis, as well as developmental timing and hormone responses. We begin this review with an overview of biochemical mechanisms of yeast and animal Mediator that are likely to be conserved in all eukaryotes, as well as a brief discussion of the role of Mediator in animal development. We then present a comprehensive review of studies of the role of Mediator in plant development. Finally, we point to important questions for future research on the role of Mediator as a master coordinator of development. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Understanding and Using Mediators and Moderators

    Science.gov (United States)

    Wu, Amery D.; Zumbo, Bruno D.

    2008-01-01

    Mediation and moderation are two theories for refining and understanding a causal relationship. Empirical investigation of mediators and moderators requires an integrated research design rather than the data analyses driven approach often seen in the literature. This paper described the conceptual foundation, research design, data analysis, as…

  13. A default Bayesian hypothesis test for mediation

    NARCIS (Netherlands)

    Nuijten, M.B.; Wetzels, R.; Matzke, D.; Dolan, C.V.; Wagenmakers, E.J.

    2015-01-01

    In order to quantify the relationship between multiple variables, researchers often carry out a mediation analysis. In such an analysis, a mediator (e.g., knowledge of a healthy diet) transmits the effect from an independent variable (e.g., classroom instruction on a healthy diet) to a dependent

  14. Que Es la Mediacion? (What Is Mediation?).

    Science.gov (United States)

    Consortium for Appropriate Dispute Resolution in Special Education (CADRE), Eugene, OR.

    This brief paper, in Spanish, discusses the use of mediation as a method for resolving disagreements between schools or early intervention programs and parents of children with disabilities. It identifies benefits of mediation such as maintenance of an ongoing and positive relationship between the school and family, simple resolution of conflicts…

  15. Mediator-dependent Nuclear Receptor Functions

    Science.gov (United States)

    Chen, Wei; Roeder, Robert

    2011-01-01

    As gene-specific transcription factors, nuclear hormone receptors are broadly involved in many important biological processes. Their function on target genes requires the stepwise assembly of different coactivator complexes that facilitate chromatin remodeling and subsequent preinitiation complex (PIC) formation and function. Mediator has proved to be a crucial, and general, nuclear receptor-interacting coactivator, with demonstrated functions in transcription steps ranging from chromatin remodeling to subsequent PIC formation and function. Here we discuss (i) our current understanding of pathways that nuclear receptors and other interacting cofactors employ to recruit Mediator to target gene enhancers and promoters, including conditional requirements for the strong NR-Mediator interactions mediated by the NR AF2 domain and the MED1 LXXLLL motifs and (ii) mechanisms by which Mediator acts to transmit signals from enhancer-bound nuclear receptors to the general transcription machinery at core promoters to effect PIC formation and function. PMID:21854863

  16. A computational description of simple mediation analysis

    Directory of Open Access Journals (Sweden)

    Caron, Pier-Olivier

    2018-04-01

    Full Text Available Simple mediation analysis is an increasingly popular statistical analysis in psychology and in other social sciences. However, there is very few detailed account of the computations within the model. Articles are more often focusing on explaining mediation analysis conceptually rather than mathematically. Thus, the purpose of the current paper is to introduce the computational modelling within simple mediation analysis accompanied with examples with R. Firstly, mediation analysis will be described. Then, the method to simulate data in R (with standardized coefficients will be presented. Finally, the bootstrap method, the Sobel test and the Baron and Kenny test all used to evaluate mediation (i.e., indirect effect will be developed. The R code to implement the computation presented is offered as well as a script to carry a power analysis and a complete example.

  17. Elder mediation in theory and practice: study results from a national caregiver mediation demonstration project.

    Science.gov (United States)

    Crampton, Alexandra

    2013-01-01

    Mediation is a process through which a third party facilitates discussion among disputing parties to help them identify interests and ideally reach an amicable solution. Elder mediation is a growing subspecialty to address conflicts involving older adults, primarily involving caregiving or finances. Mediation is theorized to empower participants but critics argue that it can exacerbate power imbalances among parties and coerce consensus. These contested claims are examined through study of a national caregiver mediation demonstration project. Study implications underscore the importance of gerontological social work expertise to ensure the empowerment of vulnerable older adults in mediation sessions.

  18. 7 CFR 785.5 - Fees for mediation services.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 7 2010-01-01 2010-01-01 false Fees for mediation services. 785.5 Section 785.5... AGRICULTURE SPECIAL PROGRAMS CERTIFIED STATE MEDIATION PROGRAM § 785.5 Fees for mediation services. A requirement that non-USDA parties who elect to participate in mediation pay a fee for mediation services will...

  19. Atomic Force Microscope Mediated Chromatography

    Science.gov (United States)

    Anderson, Mark S.

    2013-01-01

    The atomic force microscope (AFM) is used to inject a sample, provide shear-driven liquid flow over a functionalized substrate, and detect separated components. This is demonstrated using lipophilic dyes and normal phase chromatography. A significant reduction in both size and separation time scales is achieved with a 25-micron-length column scale, and one-second separation times. The approach has general applications to trace chemical and microfluidic analysis. The AFM is now a common tool for ultra-microscopy and nanotechnology. It has also been demonstrated to provide a number of microfluidic functions necessary for miniaturized chromatography. These include injection of sub-femtoliter samples, fluidic switching, and sheardriven pumping. The AFM probe tip can be used to selectively remove surface layers for subsequent microchemical analysis using infrared and tip-enhanced Raman spectroscopy. With its ability to image individual atoms, the AFM is a remarkably sensitive detector that can be used to detect separated components. These diverse functional components of microfluidic manipulation have been combined in this work to demonstrate AFM mediated chromatography. AFM mediated chromatography uses channel-less, shear-driven pumping. This is demonstrated with a thin, aluminum oxide substrate and a non-polar solvent system to separate a mixture of lipophilic dyes. In conventional chromatographic terms, this is analogous to thin-layer chromatography using normal phase alumina substrate with sheardriven pumping provided by the AFM tip-cantilever mechanism. The AFM detection of separated components is accomplished by exploiting the variation in the localized friction of the separated components. The AFM tip-cantilever provides the mechanism for producing shear-induced flows and rapid pumping. Shear-driven chromatography (SDC) is a relatively new concept that overcomes the speed and miniaturization limitations of conventional liquid chromatography. SDC is based on a

  20. Immunomodulatory Effects Mediated by Dopamine

    Science.gov (United States)

    Alvarez-Herrera, Samantha; Pérez-Sánchez, Gilberto; Becerril-Villanueva, Enrique; Cruz-Fuentes, Carlos; Flores-Gutierrez, Enrique Octavio; Quintero-Fabián, Saray

    2016-01-01

    Dopamine (DA), a neurotransmitter in the central nervous system (CNS), has modulatory functions at the systemic level. The peripheral and central nervous systems have independent dopaminergic system (DAS) that share mechanisms and molecular machinery. In the past century, experimental evidence has accumulated on the proteins knowledge that is involved in the synthesis, reuptake, and transportation of DA in leukocytes and the differential expression of the D1-like (D1R and D5R) and D2-like receptors (D2R, D3R, and D4R). The expression of these components depends on the state of cellular activation and the concentration and time of exposure to DA. Receptors that are expressed in leukocytes are linked to signaling pathways that are mediated by changes in cAMP concentration, which in turn triggers changes in phenotype and cellular function. According to the leukocyte lineage, the effects of DA are associated with such processes as respiratory burst, cytokine and antibody secretion, chemotaxis, apoptosis, and cytotoxicity. In clinical conditions such as schizophrenia, Parkinson disease, Tourette syndrome, and multiple sclerosis (MS), there are evident alterations during immune responses in leukocytes, in which changes in DA receptor density have been observed. Several groups have proposed that these findings are useful in establishing clinical status and clinical markers. PMID:27795960

  1. Immunomodulatory Effects Mediated by Dopamine

    Directory of Open Access Journals (Sweden)

    Rodrigo Arreola

    2016-01-01

    Full Text Available Dopamine (DA, a neurotransmitter in the central nervous system (CNS, has modulatory functions at the systemic level. The peripheral and central nervous systems have independent dopaminergic system (DAS that share mechanisms and molecular machinery. In the past century, experimental evidence has accumulated on the proteins knowledge that is involved in the synthesis, reuptake, and transportation of DA in leukocytes and the differential expression of the D1-like (D1R and D5R and D2-like receptors (D2R, D3R, and D4R. The expression of these components depends on the state of cellular activation and the concentration and time of exposure to DA. Receptors that are expressed in leukocytes are linked to signaling pathways that are mediated by changes in cAMP concentration, which in turn triggers changes in phenotype and cellular function. According to the leukocyte lineage, the effects of DA are associated with such processes as respiratory burst, cytokine and antibody secretion, chemotaxis, apoptosis, and cytotoxicity. In clinical conditions such as schizophrenia, Parkinson disease, Tourette syndrome, and multiple sclerosis (MS, there are evident alterations during immune responses in leukocytes, in which changes in DA receptor density have been observed. Several groups have proposed that these findings are useful in establishing clinical status and clinical markers.

  2. Thigmotaxis Mediates Trail Odour Disruption.

    Science.gov (United States)

    Stringer, Lloyd D; Corn, Joshua E; Sik Roh, Hyun; Jiménez-Pérez, Alfredo; Manning, Lee-Anne M; Harper, Aimee R; Suckling, David M

    2017-05-10

    Disruption of foraging using oversupply of ant trail pheromones is a novel pest management application under investigation. It presents an opportunity to investigate the interaction of sensory modalities by removal of one of the modes. Superficially similar to sex pheromone-based mating disruption in moths, ant trail pheromone disruption lacks an equivalent mechanistic understanding of how the ants respond to an oversupply of their trail pheromone. Since significant compromise of one sensory modality essential for trail following (chemotaxis) has been demonstrated, we hypothesised that other sensory modalities such as thigmotaxis could act to reduce the impact on olfactory disruption of foraging behaviour. To test this, we provided a physical stimulus of thread to aid trailing by Argentine ants otherwise under disruptive pheromone concentrations. Trail following success was higher using a physical cue. While trail integrity reduced under continuous over-supply of trail pheromone delivered directly on the thread, provision of a physical cue in the form of thread slightly improved trail following and mediated trail disruption from high concentrations upwind. Our results indicate that ants are able to use physical structures to reduce but not eliminate the effects of trail pheromone disruption.

  3. Mediators and moderators in early intervention research.

    Science.gov (United States)

    Breitborde, Nicholas J K; Srihari, Vinod H; Pollard, Jessica M; Addington, Donald N; Woods, Scott W

    2010-05-01

    The goal of this paper is to provide clarification with regard to the nature of mediator and moderator variables and the statistical methods used to test for the existence of these variables. Particular attention will be devoted to discussing the ways in which the identification of mediator and moderator variables may help to advance the field of early intervention in psychiatry. We completed a literature review of the methodological strategies used to test for mediator and moderator variables. Although several tests for mediator variables are currently available, recent evaluations suggest that tests which directly evaluate the indirect effect are superior. With regard to moderator variables, two approaches ('pick-a-point' and regions of significance) are available, and we provide guidelines with regard to how researchers can determine which approach may be most appropriate to use for their specific study. Finally, we discuss how to evaluate the clinical importance of mediator and moderator relationships as well as the methodology to calculate statistical power for tests of mediation and moderation. Further exploration of mediator and moderator variables may provide valuable information with regard to interventions provided early in the course of a psychiatric illness.

  4. Function and regulation of the Mediator complex.

    Science.gov (United States)

    Conaway, Ronald C; Conaway, Joan Weliky

    2011-04-01

    Over the past few years, advances in biochemical and genetic studies of the structure and function of the Mediator complex have shed new light on its subunit architecture and its mechanism of action in transcription by RNA polymerase II (pol II). The development of improved methods for reconstitution of recombinant Mediator subassemblies is enabling more in-depth analyses of basic features of the mechanisms by which Mediator interacts with and controls the activity of pol II and the general initiation factors. The discovery and characterization of multiple, functionally distinct forms of Mediator characterized by the presence or absence of the Cdk8 kinase module have led to new insights into how Mediator functions in both Pol II transcription activation and repression. Finally, progress in studies of the mechanisms by which the transcriptional activation domains (ADs) of DNA binding transcription factors target Mediator have brought to light unexpected complexities in the way Mediator participates in signal transduction. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. Are mediation clauses binding and mandatory?

    Directory of Open Access Journals (Sweden)

    Constantinescu Miruna

    2017-06-01

    Full Text Available This study analyses the legal force of mediation clauses in the common law systems and civil law systems with a main focus on the Romanian approach. First, the introductory section illustrates the paradox between the concept of binding and mandatory effect and the mediation mechanism, a voluntary manner to settle disputes. Notwithstanding, the possibility to coerce the parties to engage into a mediation, the voluntary character of the process is illustrated by the parties’ freedom to decide whether they settle or not. Second, the role of mediation clause is analysed and its advantages are briefly described. Third, the non-compliance of the prior mediation mechanism is presented, the starting point of the discussion being represented by the manner in which the parties drafted the mediation clause. A carefully drafted mediation clause, reflecting the parties’ consent, can determine a court or an arbitral tribunal to enforce such clause. Fourth, the study ends by mentioning the approach adopted by different national courts, emphasizing the Romanian legal perspective.

  6. Mediators as the Walrasian Auctioneers of Exchange Theory

    OpenAIRE

    Dickenson, David

    2003-01-01

    This article opens up mediation to systematic economic analysis by considering mediators as analogous to the Walrasian auctioneers of exchange theory. By altering trade-off rates among bargaining issues, mediators facilitate a process leading towards Pareto efficient voluntary settlements.

  7. Potential Roles of Amiloride-Sensitive Sodium Channels in Cancer Development

    Directory of Open Access Journals (Sweden)

    Siguang Xu

    2016-01-01

    Full Text Available The ENaC/degenerin ion channel superfamily includes the amiloride-sensitive epithelial sodium channel (ENaC and acid sensitive ionic channel (ASIC. ENaC is a multimeric ion channel formed by heteromultimeric membrane glycoproteins, which participate in a multitude of biological processes by mediating the transport of sodium (Na+ across epithelial tissues such as the kidney, lungs, bladder, and gut. Aberrant ENaC functions contribute to several human disease states including pseudohypoaldosteronism, Liddle syndrome, cystic fibrosis, and salt-sensitive hypertension. Increasing evidence suggests that ion channels not only regulate ion homeostasis and electric signaling in excitable cells but also play important roles in cancer cell behaviors such as proliferation, apoptosis, invasion, and migration. Indeed, ENaCs/ASICs had been reported to be associated with cancer characteristics. Given their cell surface localization and pharmacology, pharmacological strategies to target ENaC/ASIC family members may be promising cancer therapeutics.

  8. Energy National Mediator activity report 2009

    International Nuclear Information System (INIS)

    2009-01-01

    After some data illustrating the activity of the Energy National Mediator in 2009, and an interview of a representative of this institution who comments its practice, this report proposes the opinions of the different involved actors (communities, consumer associations, providers, and so on) about the mediator. It puts the adopted strategy in perspective from the past year to the coming one. It describes the missions: information, advice, protection. It reports actions, recommendations and facts for 2009 in terms of consumer information, group mediation, poverty management, samples of analysed disputes. It presents the social organisation and gives a financial assessment of the institution

  9. Current rectification by mediating electroactive polymers

    Energy Technology Data Exchange (ETDEWEB)

    Ybarra, Gabriel; Moina, Carlos [Centro de Investigacion sobre Electrodeposicion y Procesos Superficiales, Instituto Nacional de Tecnologia Industrial, CC 157, (1650) San Martin (Argentina); Florit, M. Ines [INIFTA, Facultad de Ciencias Exactas, UNLP, Suc. 4, CC 16, (1900) La Plata (Argentina); Posadas, Dionisio [INIFTA, Facultad de Ciencias Exactas, UNLP, Suc. 4, CC 16, (1900) La Plata (Argentina)], E-mail: dposadas@inifta.unlp.edu.ar

    2008-04-20

    In this work we briefly review the theoretical basis for the electrochemical rectification in mediated redox reactions at redox polymer modified electrodes. Electrochemical rectification may have two distinct origins. It is either caused by a slow kinetics of the reaction between the external redox couple and the mediator or it is originated by a slow electronic transport within the film under an unfavorable thermodynamic condition. We show experimental results for the redox mediation reaction of poly(o-aminophenol) (POAP) on the Fe{sup 2+/3+} and on the Fe(CN){sub 6}{sup 3-/4-} redox couples in solution that prove the proposed mechanisms of electrochemical rectification.

  10. Singlet deflected anomaly/gauge mediation

    International Nuclear Information System (INIS)

    Blas, J. de; Delgado, A.

    2012-01-01

    We study an extension of the standard anomaly/gauge mediation scenario where the messenger fields have direct interactions with an extra gauge singlet. This realizes a phenomenologically viable NMSSM-like scenario free of the μ-b μ problem. Current cosmological constraints imply a small size for the anomaly-mediation contributions, unless some source of R-parity violation is permitted. In the latter case the allowed regions in the parameter space can be substantially larger than in the corresponding gauge-mediation scenario.

  11. Current rectification by mediating electroactive polymers

    International Nuclear Information System (INIS)

    Ybarra, Gabriel; Moina, Carlos; Florit, M. Ines; Posadas, Dionisio

    2008-01-01

    In this work we briefly review the theoretical basis for the electrochemical rectification in mediated redox reactions at redox polymer modified electrodes. Electrochemical rectification may have two distinct origins. It is either caused by a slow kinetics of the reaction between the external redox couple and the mediator or it is originated by a slow electronic transport within the film under an unfavorable thermodynamic condition. We show experimental results for the redox mediation reaction of poly(o-aminophenol) (POAP) on the Fe 2+/3+ and on the Fe(CN) 6 3-/4- redox couples in solution that prove the proposed mechanisms of electrochemical rectification

  12. CELLULAR INTERACTIONS MEDIATED BY GLYCONECTIDS

    Directory of Open Access Journals (Sweden)

    O.Popescu

    1999-01-01

    Full Text Available Cellular interactions involve many types of cell surface molecules and operate via homophilic and/or heterophilic protein-protein and protein-carbohydrate binding. Our investigations in different model-systems (marine invertebrates and mammals have provided direct evidence that a novel class of primordial proteoglycans, named by us gliconectins, can mediate cell adhesion via a new alternative molecular mechanism of polyvalent carbohydrate-carbohydrate binding. Biochemical characterization of isolated and purified glyconectins revealed the presence of specific carbohydrate structures, acidic glycans, different from classical glycosaminoglycans. Such acidic glycans of high molecular weight containing fucose, glucuronic or galacturonic acids, and sulfate groups, originally found in sponges and sea urchin embryos, may represent a new class of carbohydrate carcino-embryonal antigens in mice and humans. Such interactions between biological macromolecules are usually investigated by kinetic binding studies, calorimetric methods, X-ray diffraction, nuclear magnetic resonance, and other spectroscopic analyses. However, these methods do not supply a direct estimation of the intermolecular binding forces that are fundamental for the function of the ligand-receptor association. Recently, we have introduced atomic force microscopy to quantify the binding strength between cell adhesion proteoglycans. Measurement of binding forces intrinsic to cell adhesion proteoglycans is necessary to assess their contribution to the maintenance of the anatomical integrity of multicellular organisms. As a model, we selected the glyconectin 1, a cell adhesion proteoglycan isolated from the marine sponge Microciona prolifera. This glyconectin mediates in vivo cell recognition and aggregation via homophilic, species-specific, polyvalent, and calcium ion-dependent carbohydrate-carbohydrate interactions. Under physiological conditions, an adhesive force of up to 400 piconewtons

  13. Towards the natural gauge mediation

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Ran [Center for High-Energy Physics, Peking University,Beijing, 100871 (China); Li, Tianjun [State Key Laboratory of Theoretical Physics andKavli Institute for Theoretical Physics, China (KITPC), Institute of Theoretical Physics,Chinese Academy of Sciences, Beijing 100190 (China); School of Physical Electronics, University of Electronic Science and Technology of China,Chengdu 610054 (China); Wang, Liucheng [Bartol Research Institute, Department of Physics and Astronomy,University of Delaware, Newark, DE 19716 (United States); Zhu, Bin [State Key Laboratory of Theoretical Physics andKavli Institute for Theoretical Physics, China (KITPC), Institute of Theoretical Physics,Chinese Academy of Sciences, Beijing 100190 (China); Institute of Physics Chinese Academy of sciences,Beijing 100190 (China)

    2015-10-23

    The sweet spot supersymmetry (SUSY) solves the μ/B{sub μ} problem in the Minimal Supersymmetric Standard Model (MSSM) with gauge mediated SUSY breaking (GMSB) via the generalized Giudice-Masiero (GM) mechanism where only the μ-term and soft Higgs masses are generated at the unification scale of the Grand Unified Theory (GUT) due to the approximate PQ symmetry. Because all the other SUSY breaking soft terms are generated via the GMSB below the GUT scale, there exists SUSY electroweak (EW) fine-tuning problem to explain the 125 GeV Higgs boson mass due to small trilinear soft term. Thus, to explain the Higgs boson mass, we propose the GMSB with both the generalized GM mechanism and Higgs-messenger interactions. The renormalization group equations are runnings from the GUT scale down to EW scale. So the EW symmetry breaking can be realized easier. We can keep the gauge coupling unification and solution to the flavor problem in the GMSB, as well as solve the μ/B{sub μ}-problem. Moreover, there are only five free parameters in our model. So we can determine the characteristic low energy spectra and explore its distinct phenomenology. The fine-tuning measure can be as low as 100. For some benchmark points, the stop mass can be as low as 1.7 TeV while the glunio mass is around 2.5 TeV. The gravitino dark matter can come from a thermal production with the correct relic density and be consistent with the thermal leptogenesis. Because gluino and stop can be relatively light in our model, how to search for such GMSB at the upcoming run II of the LHC experiment could be very interesting.

  14. Causal mediation analysis with multiple mediators in the presence of treatment noncompliance.

    Science.gov (United States)

    Park, Soojin; Kürüm, Esra

    2018-05-20

    Randomized experiments are often complicated because of treatment noncompliance. This challenge prevents researchers from identifying the mediated portion of the intention-to-treated (ITT) effect, which is the effect of the assigned treatment that is attributed to a mediator. One solution suggests identifying the mediated ITT effect on the basis of the average causal mediation effect among compliers when there is a single mediator. However, considering the complex nature of the mediating mechanisms, it is natural to assume that there are multiple variables that mediate through the causal path. Motivated by an empirical analysis of a data set collected in a randomized interventional study, we develop a method to estimate the mediated portion of the ITT effect when both multiple dependent mediators and treatment noncompliance exist. This enables researchers to make an informed decision on how to strengthen the intervention effect by identifying relevant mediators despite treatment noncompliance. We propose a nonparametric estimation procedure and provide a sensitivity analysis for key assumptions. We conduct a Monte Carlo simulation study to assess the finite sample performance of the proposed approach. The proposed method is illustrated by an empirical analysis of JOBS II data, in which a job training intervention was used to prevent mental health deterioration among unemployed individuals. Copyright © 2018 John Wiley & Sons, Ltd.

  15. Gene Therapy Mediated Breast Cancer Immunity

    National Research Council Canada - National Science Library

    Nesbit, Heike

    1999-01-01

    .... POE2 is produced by the cyclooxygenase (COX) mediated oxidation of arachidonic acid. The inhibition of COX activity in B7-1 expressing MDA-MB 231 cells restored the proliferative response of T cells...

  16. Dark matter prospects in deflected mirage mediation

    International Nuclear Information System (INIS)

    Holmes, Michael; Nelson, Brent D.

    2009-01-01

    The recently introduced deflected mirage mediation (DMM) model is a string-motivated paradigm in which all three of the major supersymmetry-breaking transmission mechanisms are operative. We begin a systematic exploration of the parameter space of this rich model context, paying special attention to the pattern of gaugino masses which arise. In this work we focus on the dark matter phenomenology of the DMM model as such signals are the least influenced by the model-dependent scalar masses. We find that a large portion of the parameter space in which the three mediation mechanisms have a similar effective mass scale of 1 TeV or less will be probed by future direct and indirect detection experiments. Distinguishing deflected mirage mediation from the mirage model without gauge mediation will prove difficult without collider input, though we indicate how gamma ray signals may provide an opportunity for distinguishing between the two paradigms

  17. Selecting a model of supersymmetry breaking mediation

    International Nuclear Information System (INIS)

    AbdusSalam, S. S.; Allanach, B. C.; Dolan, M. J.; Feroz, F.; Hobson, M. P.

    2009-01-01

    We study the problem of selecting between different mechanisms of supersymmetry breaking in the minimal supersymmetric standard model using current data. We evaluate the Bayesian evidence of four supersymmetry breaking scenarios: mSUGRA, mGMSB, mAMSB, and moduli mediation. The results show a strong dependence on the dark matter assumption. Using the inferred cosmological relic density as an upper bound, minimal anomaly mediation is at least moderately favored over the CMSSM. Our fits also indicate that evidence for a positive sign of the μ parameter is moderate at best. We present constraints on the anomaly and gauge mediated parameter spaces and some previously unexplored aspects of the dark matter phenomenology of the moduli mediation scenario. We use sparticle searches, indirect observables and dark matter observables in the global fit and quantify robustness with respect to prior choice. We quantify how much information is contained within each constraint.

  18. Unwrapping Court-Connected Mediation Agreements

    DEFF Research Database (Denmark)

    Adrian, Lin; Mykland, Solfrid

    2018-01-01

    Court-connected mediated agreements seem to both fulfil and fail the ideal of self-determination in mediation theory. In a study of 134 agreements from court-connected mediation, we found that the majority of agreements contain creative elements and display great variation in the provisions...... and understand them. The judicial language is well known for the drafters of the agreement but not the parties. Thus, court-connected mediation seems to fail aspects of self-determination when it comes to drafting agreements. We draw on new-institutional theory when we explore and explain this apparent...... they contain. These results indicate that the parties play an important role in crafting the substance of their agreements. However, we also found that the wording of the agreements is characterised by legal and bureaucratic language to the extent that people without legal training find it difficult to read...

  19. BRIEF CONSIDERATIONS REGARDING MEDIATION IN CRIMINAL MATTERS

    Directory of Open Access Journals (Sweden)

    LUMINITA DRAGNE

    2012-05-01

    Full Text Available Mediation is an alternative means of conflict resolution, is designed as a flexible procedure whose utility was observed in contrast to the deficiencies of the judiciary system. In the field of criminal law, mediation is part of the larger concept of the restorative justice whose aim is restoring the main victim in its rights. From this perspective, to the criminal process is intended, in principal, repairing of the victim's prejudice and, subsequently, to encourage the delinquent in taking responsibility and to acknowledge his guilt, and also to determine him to actively participate in repairing the damage caused. The ultimate goal of the process is giving back the delinquent to society and consequently, reducing the relapse. Romanian legislator has not taken this concept, and how it is regulated mediation in criminal matters is hesitant, cautious and ultimately ineffective. Specifically, in situations that will actually occur, victim-delinquent mediation will only take the form of "assisted reconciliation."

  20. Mediatized Extreme Right Activism and Discourse

    DEFF Research Database (Denmark)

    Peters, Rikke Alberg

    2015-01-01

    This paper presents a case study of the German neo-fascist network The Immortals (Die Unsterblichen) who in 2011 performed a flash-mob disseminated on YouTube for the so- called ‘Become Immortal’ campaign. The street protest was designed for and adapted to the specific characteristics of online...... activism. It is a good example of how new contentious action repertoires in which online and street activism intertwine have also spread to extreme right groups. Despite its neo-fascist and extreme right content the ‘Become Immortal’ campaign serves as an illustrative case for the study of mediated...... and mediatized activism. In order to analyse of the protest form, the visual aesthetics and the discourse of ‘The Immortals’, the paper mobilises two concepts from media and communication studies: mediation and mediatization. It will be argued that that the current transformation of the extreme right: that is...

  1. BOOKTUBERS MOVEMENT: EMERGING PRACTICES OF READING MEDIATION

    Directory of Open Access Journals (Sweden)

    Claudia Souza Teixeira

    2016-12-01

    Full Text Available This paper intents to investigate reading mediation practices develop by the booktubers, young people that use the YouTube in order to share information about books and to interact with other readers. We begin presenting some concepts related to reading and mediation activities, and then, talk about some aspects of cyberspace, the formation of virtual communities and the Booktubers phenomena. At last, as a result of a documental analysis of 100 videos posted by booktubers, we show the characteristics of these emerging mediation reading practices and the types of books that are more commented by them. We conclude that the conventional practices of reading mediation are the bases for the booktubers’ actuation, but they are adapted to the new kinds of elaboration, creation and organization enabled by the Internet.

  2. Mediated moderation or moderated mediation: relationship between length of unemployment, resilience, coping and health.

    Science.gov (United States)

    Sojo, Víctor; Guarino, Leticia

    2011-05-01

    The aim of the present research was to evaluate a model of mediated moderation vs. moderated mediation that could explain the relationship between length of unemployment, dispositional resilience, coping styles and depression and social functioning of Venezuelan unemployed individuals. Self-report measures were administered to a sample of 328 unemployed residents in Caracas, Venezuela. Results indicated that emotional coping acted as a mediator in the relationship between resilience and depression. Individuals with greater resilience used more detachment coping when unemployment was longer, while individuals with poorer resilience in the same situation used less avoidance coping. Resilience acted as a protective moderating factor between longer periods of unemployment and social functioning, a process mediated by detachment coping. Overall, results supported a mediated moderation model, with resilience as the moderating factor and coping as the mediator in the relation between stress due to the length of unemployment and well-being.

  3. From Mediatized Emotion to Digital Affect Cultures

    OpenAIRE

    Döveling, Katrin; Harju, Anu Annika; Sommer, Denise

    2018-01-01

    Research on the processes of mediatization aims to explore the mutual shaping of media and social life and how new media technologies influence and infiltrate social practices and cultural life. We extend this discussion of media’s role in transforming the everyday by including in the discussion the mediatization of emotion and discuss what we conceptualize as digital affect culture(s). We understand these as relational, contextual, globally emergent spaces in the digital environment where af...

  4. Nordic Mediation - Comparing Denmark and Finland

    DEFF Research Database (Denmark)

    Lappi-Seppälä, Tapio; Storgaard, Anette

    2015-01-01

    The Nordic Countries have a long common history in criminal policy but a closer look also indicates individual Development. the introduction of Victim Offender Mediation is one example of Nordic diversity in details.......The Nordic Countries have a long common history in criminal policy but a closer look also indicates individual Development. the introduction of Victim Offender Mediation is one example of Nordic diversity in details....

  5. Developing the conversation about workplace mediation

    OpenAIRE

    Kenny, Treasa

    2014-01-01

    This article examines some of the latest writing and research in relation to conflict in work and workplace mediation. It considers three specific issues of size and sector of organisations, the attitude of organisations to conflict and the employee relations environment in organisations. It reviews the various views in relation to fundamental aspects of mediation such as the neutral third party, voluntarism, informality and confidentiality to inform thinking as well as practitioner and acade...

  6. CONFLICT MANAGEMENT VIA SYSTEMICALLY PLANNED PEER MEDIATION

    OpenAIRE

    Evangelos C. Papakitsos; Konstantinos Karakiozis

    2016-01-01

    Conflicts and confrontations between students are a key-feature of school life. Especially in recent years, both the scientific and the educational community are particularly sensitive to bullying issues in the school context. Peer mediation (or school mediation) is an alternative way to manage conflicts at school. A critical evaluation of this practice is attempted, as well as its contribution to the formation of a positive attitude in school and to the decreasing of school-bullying incident...

  7. Efficient nonparametric estimation of causal mediation effects

    OpenAIRE

    Chan, K. C. G.; Imai, K.; Yam, S. C. P.; Zhang, Z.

    2016-01-01

    An essential goal of program evaluation and scientific research is the investigation of causal mechanisms. Over the past several decades, causal mediation analysis has been used in medical and social sciences to decompose the treatment effect into the natural direct and indirect effects. However, all of the existing mediation analysis methods rely on parametric modeling assumptions in one way or another, typically requiring researchers to specify multiple regression models involving the treat...

  8. Frequency and timing of leaders' mediation attempts

    OpenAIRE

    Demirağ, Elif Gizem; Demirag, Elif Gizem

    2015-01-01

    How do a state's political regime type and power status influence leader's mediation attempts? This study develops an explanation as a response to this question derived from the democratic peace theory which underlines the role of democratic norms in motivating state leaders to play a third party role in peace processes. Based on this approach, the expectation is that democratic country representatives are more likely to mediate especially in the early stage of their careers. In addition, I a...

  9. Gazetteer Brokering through Semantic Mediation

    Science.gov (United States)

    Hobona, G.; Bermudez, L. E.; Brackin, R.

    2013-12-01

    web technologies, including ontologies and a semantic mediator. The semantically-enhanced SPEGG allowed a client to submit a single query (e.g. ';hills') and to retrieve data from two separate gazetteers with different vocabularies (e.g. where one refers to ';summits' another refers to ';hills'). Supporting the SPEGG was a SPARQL server that held the ontologies and processed queries on them. Earth Science surveys and forecast always have a place on Earth. Being able to share the information about a place and solve inconsistencies about that place from different sources will enable geoscientists to better do their research. In the advent of mobile geo computing and location based services (LBS), brokering gazetteers will provide geoscientists with access to gazetteer services rich with information and functionality beyond that offered by current generic gazetteers.

  10. Ombuds’ corner: Consider mediation - some rules

    CERN Multimedia

    Vincent Vuillemin

    2013-01-01

    Mediation is a structured process in which an external party, called a mediator, helps participants generate and evaluate options that would allow them to reach a mutual agreement. It is an informal and confidential process.   The mediator does not have the power to impose an agreement on the parties, who should find it by themselves. However, the mediator controls the process. He arranges the meetings in agreement with the parties, and coordinates the details (concerning the speaking times, for example) and ensures that the parties respect of the rules which have been agreed on. He also favours advancing of the process towards a solution. The mediation process is centred on the search for a solution and a mutual agreement. In such a process, the mediator takes a neutral and impartial position, and does not advocate for a single party. He favours good communication between the parties, and will ensure that mutual respect is maintained and that the correct language is used during the discussi...

  11. Flavorful hybrid anomaly-gravity mediation

    International Nuclear Information System (INIS)

    Gross, Christian; Hiller, Gudrun

    2011-01-01

    We consider supersymmetric models where anomaly and gravity mediation give comparable contributions to the soft terms and discuss how this can be realized in a five-dimensional brane world. The gaugino mass pattern of anomaly mediation is preserved in such a hybrid setup. The flavorful gravity-mediated contribution cures the tachyonic slepton problem of anomaly mediation. The supersymmetric flavor puzzle is solved by alignment. We explicitly show how a working flavor-tachyon link can be realized with Abelian flavor symmetries and give the characteristic signatures of the framework, including O(1) slepton mass splittings between different generations and between doublets and singlets. This provides opportunities for same flavor dilepton edge measurements with missing energy at the Large Hadron Collider (LHC). Rare lepton decay rates could be close to their current experimental limit. Compared to pure gravity mediation, the hybrid model is advantageous because it features a heavy gravitino which can avoid the cosmological gravitino problem of gravity-mediated models combined with leptogenesis.

  12. Inside the mediation room - efficiency, voice and equity in workplace mediation

    OpenAIRE

    Saundry, R; Bennett, T; Wibberley, G

    2016-01-01

    Existing research into workplace mediation in the UK has tended to focus on managerial perceptions. Consequently, there has been a unitarist emphasis on the business case for mediation, revolving around its alleged superior efficiency properties compared to conventional rights-based procedures. This paper develops the research agenda in two respects: first, it foregrounds the experiences of participants in mediation through 25 interviews with individuals drawn from a variety of contexts. Seco...

  13. Mediating social media use : connecting parents mediation strategies and social media literacy

    OpenAIRE

    Daneels, Rowan; Vanwynsberghe, Hadewijch

    2017-01-01

    Abstract: Increasingly complex and multipurpose social media platforms require digital competences from parents and adolescents alike. While adolescents grow up with social media, parents have more difficulties with them, leading to uncertainties regarding their adolescents social media mediation. This study contributes to parental mediation research by (1) investigating whether mediation strategies defined by previous research are also relevant for social media use, and (2) exploring whether...

  14. Assessing moderated mediation in linear models requires fewer confounding assumptions than assessing mediation.

    Science.gov (United States)

    Loeys, Tom; Talloen, Wouter; Goubert, Liesbet; Moerkerke, Beatrijs; Vansteelandt, Stijn

    2016-11-01

    It is well known from the mediation analysis literature that the identification of direct and indirect effects relies on strong no unmeasured confounding assumptions of no unmeasured confounding. Even in randomized studies the mediator may still be correlated with unobserved prognostic variables that affect the outcome, in which case the mediator's role in the causal process may not be inferred without bias. In the behavioural and social science literature very little attention has been given so far to the causal assumptions required for moderated mediation analysis. In this paper we focus on the index for moderated mediation, which measures by how much the mediated effect is larger or smaller for varying levels of the moderator. We show that in linear models this index can be estimated without bias in the presence of unmeasured common causes of the moderator, mediator and outcome under certain conditions. Importantly, one can thus use the test for moderated mediation to support evidence for mediation under less stringent confounding conditions. We illustrate our findings with data from a randomized experiment assessing the impact of being primed with social deception upon observer responses to others' pain, and from an observational study of individuals who ended a romantic relationship assessing the effect of attachment anxiety during the relationship on mental distress 2 years after the break-up. © 2016 The British Psychological Society.

  15. Combined gauge-mediated and anomaly-mediated supersymmetry breaking and conformal sequestering

    International Nuclear Information System (INIS)

    Sundrum, Raman

    2005-01-01

    Anomaly-mediated supersymmetry breaking in the context of 4D conformally sequestered models is combined with Poppitz-Trivedi D-type gauge-mediation. The implementation of the two mediation mechanisms naturally leads to visible soft masses at the same scale so that they can cooperatively solve the μ and flavor problems of weak scale supersymmetry, as well as the tachyonic-slepton problem of pure anomaly-mediation. The tools are developed in a modular fashion for more readily fitting into the general program of optimizing supersymmetric dynamics in hunting for the most attractive weak scale phenomenologies combined with Planck-scale plausibility

  16. A State Space Modeling Approach to Mediation Analysis

    Science.gov (United States)

    Gu, Fei; Preacher, Kristopher J.; Ferrer, Emilio

    2014-01-01

    Mediation is a causal process that evolves over time. Thus, a study of mediation requires data collected throughout the process. However, most applications of mediation analysis use cross-sectional rather than longitudinal data. Another implicit assumption commonly made in longitudinal designs for mediation analysis is that the same mediation…

  17. 29 CFR 1207.2 - Requests for Mediation Board action.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 4 2010-07-01 2010-07-01 false Requests for Mediation Board action. 1207.2 Section 1207.2 Labor Regulations Relating to Labor (Continued) NATIONAL MEDIATION BOARD ESTABLISHMENT OF SPECIAL ADJUSTMENT BOARDS § 1207.2 Requests for Mediation Board action. (a) Requests for the National Mediation Board...

  18. 15 CFR 923.83 - Mediation of amendments.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Mediation of amendments. 923.83... Programs § 923.83 Mediation of amendments. (a) Section 307(h)(2) of the Act provides for mediation of... management program. Accordingly mediation is available to states or federal agencies when a serious...

  19. 15 CFR 930.115 - Termination of mediation.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Termination of mediation. 930.115... MANAGEMENT FEDERAL CONSISTENCY WITH APPROVED COASTAL MANAGEMENT PROGRAMS Secretarial Mediation § 930.115 Termination of mediation. Mediation shall terminate: (a) At any time the Federal and State agencies agree to a...

  20. Estimating and Testing Mediation Effects with Censored Data

    Science.gov (United States)

    Wang, Lijuan; Zhang, Zhiyong

    2011-01-01

    This study investigated influences of censored data on mediation analysis. Mediation effect estimates can be biased and inefficient with censoring on any one of the input, mediation, and output variables. A Bayesian Tobit approach was introduced to estimate and test mediation effects with censored data. Simulation results showed that the Bayesian…

  1. Surveying Parental Mediation: Connections, Challenges and Questions for Media Literacy

    Science.gov (United States)

    Mendoza, Kelly

    2009-01-01

    This paper examines three strategies of parental mediation--coviewing, restrictive mediation, and active mediation--in order to make connections, challenge, and raise questions for media literacy. Coviewing, whether it is intentional practice, or whether it functions to promote media literacy, is explored. Restrictive mediation, how it connects to…

  2. Integrating mediation and moderation to advance theory development and testing.

    Science.gov (United States)

    Karazsia, Bryan T; Berlin, Kristoffer S; Armstrong, Bridget; Janicke, David M; Darling, Katherine E

    2014-03-01

    The concepts and associated analyses of mediation and moderation are important to the field of psychology. Although pediatric psychologists frequently incorporate mediation and moderation in their theories and empirical research, on few occasions have we integrated mediation and moderation. In this article, conceptual reasons for integrating mediation and moderation are offered. We illustrate a model that integrates mediation and moderation. In our illustration, the strength of an indirect or a mediating effect varied as a function of a moderating variable. Clinical implications of the integration of mediation and moderation are discussed, as is the potential of integrated models to advance research programs in pediatric psychology.

  3. Guidelines for the Investigation of Mediating Variables in Business Research.

    Science.gov (United States)

    MacKinnon, David P; Coxe, Stefany; Baraldi, Amanda N

    2012-03-01

    Business theories often specify the mediating mechanisms by which a predictor variable affects an outcome variable. In the last 30 years, investigations of mediating processes have become more widespread with corresponding developments in statistical methods to conduct these tests. The purpose of this article is to provide guidelines for mediation studies by focusing on decisions made prior to the research study that affect the clarity of conclusions from a mediation study, the statistical models for mediation analysis, and methods to improve interpretation of mediation results after the research study. Throughout this article, the importance of a program of experimental and observational research for investigating mediating mechanisms is emphasized.

  4. In the Name of Mediation: An empirical inquiry into the Chinese court mediation practices

    NARCIS (Netherlands)

    Li, Yedan

    2015-01-01

    The statistics on the numbers of cases handled through mediation in Chinese courts show remarkable ups and downs. A strong downturn before 2004 was followed by a sharp upturn in the years 2004-2011. The return of mediation has drawn the attention of various scholars who provide different readings of

  5. Search for SUSY in gauge mediated and anomaly mediated supersymmetry breaking models

    International Nuclear Information System (INIS)

    Nunnnemann, Thomas

    2004-01-01

    In this note, recent results on the search for Gauge Mediated Supersymmetry Breaking (GMSB) and Anomaly Mediated Supersymmetry Breaking (AMSB) at the LEP and Tevatron colliders are summarized. We report on DOe's search for GMSB in di-photon events with large missing transverse energy and discuss the sensitivity of similar searches based on future Tevatron integrated luminosities. (orig.)

  6. An exponential decay model for mediation.

    Science.gov (United States)

    Fritz, Matthew S

    2014-10-01

    Mediation analysis is often used to investigate mechanisms of change in prevention research. Results finding mediation are strengthened when longitudinal data are used because of the need for temporal precedence. Current longitudinal mediation models have focused mainly on linear change, but many variables in prevention change nonlinearly across time. The most common solution to nonlinearity is to add a quadratic term to the linear model, but this can lead to the use of the quadratic function to explain all nonlinearity, regardless of theory and the characteristics of the variables in the model. The current study describes the problems that arise when quadratic functions are used to describe all nonlinearity and how the use of nonlinear functions, such as exponential decay, address many of these problems. In addition, nonlinear models provide several advantages over polynomial models including usefulness of parameters, parsimony, and generalizability. The effects of using nonlinear functions for mediation analysis are then discussed and a nonlinear growth curve model for mediation is presented. An empirical example using data from a randomized intervention study is then provided to illustrate the estimation and interpretation of the model. Implications, limitations, and future directions are also discussed.

  7. Light mediators in dark matter direct detections

    International Nuclear Information System (INIS)

    Li, Tai; Miao, Sen; Zhou, Yu-Feng

    2015-01-01

    In an extended effective operator framework, we investigate in detail the effects of light mediators on the event spectra of dark matter (DM)-nucleus scatterings. The presence of light mediators changes the interpretation of the current experimental data, especially the determination of DM particle mass. We show by analytic and numerical illustrations that in general for all the operators relevant to spin-independent scatterings, the DM particle mass allowed by a given set of experimental data increases significantly when the mediator particle becomes lighter. For instance, in the case of CDMS-II-Si experiment, the allowed DM particle mass can reach ∼50 (100) GeV at 68% (90%) confidence level, which is much larger than ∼10 GeV in the case with contact interactions. The increase of DM particle mass saturates when the mediator mass is below O(10) MeV. The upper limits from other experiments such as SuperCDMS, CDMSlite, CDEX, XENON10/100, LUX, PandaX etc. all tend to be weaker toward high DM mass regions. In a combined analysis, we show that the presence of light mediators can partially relax the tension in the current results of CDMS-II-Si, SuperCDMS and LUX

  8. A default Bayesian hypothesis test for mediation.

    Science.gov (United States)

    Nuijten, Michèle B; Wetzels, Ruud; Matzke, Dora; Dolan, Conor V; Wagenmakers, Eric-Jan

    2015-03-01

    In order to quantify the relationship between multiple variables, researchers often carry out a mediation analysis. In such an analysis, a mediator (e.g., knowledge of a healthy diet) transmits the effect from an independent variable (e.g., classroom instruction on a healthy diet) to a dependent variable (e.g., consumption of fruits and vegetables). Almost all mediation analyses in psychology use frequentist estimation and hypothesis-testing techniques. A recent exception is Yuan and MacKinnon (Psychological Methods, 14, 301-322, 2009), who outlined a Bayesian parameter estimation procedure for mediation analysis. Here we complete the Bayesian alternative to frequentist mediation analysis by specifying a default Bayesian hypothesis test based on the Jeffreys-Zellner-Siow approach. We further extend this default Bayesian test by allowing a comparison to directional or one-sided alternatives, using Markov chain Monte Carlo techniques implemented in JAGS. All Bayesian tests are implemented in the R package BayesMed (Nuijten, Wetzels, Matzke, Dolan, & Wagenmakers, 2014).

  9. The Mediator Complex and Lipid Metabolism.

    Science.gov (United States)

    Zhang, Yi; Xiaoli; Zhao, Xiaoping; Yang, Fajun

    2013-03-01

    The precise control of gene expression is essential for all biological processes. In addition to DNA-binding transcription factors, numerous transcription cofactors contribute another layer of regulation of gene transcription in eukaryotic cells. One of such transcription cofactors is the highly conserved Mediator complex, which has multiple subunits and is involved in various biological processes through directly interacting with relevant transcription factors. Although the current understanding on the biological functions of Mediator remains incomplete, research in the past decade has revealed an important role of Mediator in regulating lipid metabolism. Such function of Mediator is dependent on specific transcription factors, including peroxisome proliferator-activated receptor-gamma (PPARγ) and sterol regulatory element-binding proteins (SREBPs), which represent the master regulators of lipid metabolism. The medical significance of these findings is apparent, as aberrant lipid metabolism is intimately linked to major human diseases, such as type 2 diabetes and cardiovascular disease. Here, we briefly review the functions and molecular mechanisms of Mediator in regulation of lipid metabolism.

  10. DISPUTE RESOLUTION AND MEDIATION ON CAPITAL MARKET

    Directory of Open Access Journals (Sweden)

    CRISTIAN GHEORGHE

    2011-04-01

    Full Text Available Capital Market is usually depicted as a place for experts, for people with high trading skills. This is a half truth. There are entities established and functioning under strict scrutiny of Romanian National Securities Commission (RNSC, in compliance with Capital Market Law and regulations. There are also the investors, in many cases individuals involved in shares/financial instruments trade. In both cases disputes can rise. Disputes are inevitable a part of human interaction, hence the need for dispute resolution. First option is the judicial court system. Alternative dispute resolution comprises arbitration and mediation. Arbitration is an alternative choice to provide simpler, speedier and more accessible justice than ordinary courts as well as expertise in matters that are technical in nature and require special knowledge to adjudicate upon. Capital Market environment provides an institutional arbitration court for all participants, including investors. In many cases the agreement executed between participants under RNSC scrutiny The other option for settling disputes outside the court is mediation. Mediation can provide a much cheaper and quick extrajudicial resolution of disputes in commercial matters without time consuming procedures and rigid rules. Agreements resulting from mediation are more likely to be complied with voluntarily and are more likely to foster the commercial relationship between the parties. The interaction between investors and brokerage houses is based on investment services agreement concluded by parties. This is the usual framework for disputes between parties and the usual “landscape” for mediation on capital market.

  11. MEDIATOR18 and MEDIATOR20 confer susceptibility to Fusarium oxysporum in Arabidopsis thaliana

    Science.gov (United States)

    Stiller, Jiri; Davoine, Celine; Björklund, Stefan; Manners, John M.; Kazan, Kemal; Schenk, Peer M.

    2017-01-01

    The conserved protein complex known as Mediator conveys transcriptional signals by acting as an intermediary between transcription factors and RNA polymerase II. As a result, Mediator subunits play multiple roles in regulating developmental as well as abiotic and biotic stress pathways. In this report we identify the head domain subunits MEDIATOR18 and MEDIATOR20 as important susceptibility factors for Fusarium oxysporum infection in Arabidopsis thaliana. Mutants of MED18 and MED20 display down-regulation of genes associated with jasmonate signaling and biosynthesis while up-regulation of salicylic acid associated pathogenesis related genes and reactive oxygen producing and scavenging genes. We propose that MED18 and MED20 form a sub-domain within Mediator that controls the balance of salicylic acid and jasmonate associated defense pathways. PMID:28441405

  12. Surmounting elusive barriers: the case for bioethics mediation.

    Science.gov (United States)

    Bergman, Edward J

    2013-01-01

    This article describes, analyzes, and advocates for management of clinical healthcare conflict by a process commonly referred to as bioethics mediation. Section I provides a brief introduction to classical mediation outside the realm of clinical healthcare. Section II highlights certain distinguishing characteristics of bioethics mediation. Section III chronicles the history of bioethics mediation and references a number of seminal writings on the subject. Finally, Section IV analyzes barriers that have, thus far, limited the widespread implementation of bioethics mediation.

  13. Protease signaling through protease activated receptor 1 mediate nerve activation by mucosal supernatants from irritable bowel syndrome but not from ulcerative colitis patients.

    Science.gov (United States)

    Buhner, Sabine; Hahne, Hannes; Hartwig, Kerstin; Li, Qin; Vignali, Sheila; Ostertag, Daniela; Meng, Chen; Hörmannsperger, Gabriele; Braak, Breg; Pehl, Christian; Frieling, Thomas; Barbara, Giovanni; De Giorgio, Roberto; Demir, Ihsan Ekin; Ceyhan, Güralp Onur; Zeller, Florian; Boeckxstaens, Guy; Haller, Dirk; Kuster, Bernhard; Schemann, Michael

    2018-01-01

    The causes of gastrointestinal complaints in irritable bowel syndrome (IBS) remain poorly understood. Altered nerve function has emerged as an important pathogenic factor as IBS mucosal biopsy supernatants consistently activate enteric and sensory neurons. We investigated the neurally active molecular components of such supernatants from patients with IBS and quiescent ulcerative colitis (UC). Effects of supernatants from 7 healthy controls (HC), 20 IBS and 12 UC patients on human and guinea pig submucous neurons were studied with neuroimaging techniques. We identify differentially expressed proteins with proteome analysis. Nerve activation by IBS supernatants was prevented by the protease activated receptor 1 (PAR1) antagonist SCHE79797. UC supernatants also activated enteric neurons through protease dependent mechanisms but without PAR1 involvement. Proteome analysis of the supernatants identified 204 proteins, among them 17 proteases as differentially expressed between IBS, UC and HC. Of those the four proteases elastase 3a, chymotrypsin C, proteasome subunit type beta-2 and an unspecified isoform of complement C3 were significantly more abundant in IBS compared to HC and UC supernatants. Of eight proteases, which were upregulated in IBS, the combination of elastase 3a, cathepsin L and proteasome alpha subunit-4 showed the highest prediction accuracy of 98% to discriminate between IBS and HC groups. Elastase synergistically potentiated the effects of histamine and serotonin-the two other main neuroactive substances in the IBS supernatants. A serine protease inhibitor isolated from the probiotic Bifidobacterium longum NCC2705 (SERPINBL), known to inhibit elastase-like proteases, prevented nerve activation by IBS supernatants. Proteases in IBS and UC supernatants were responsible for nerve activation. Our data demonstrate that proteases, particularly those signalling through neuronal PAR1, are biomarker candidates for IBS, and protease profiling may be used to

  14. Practical guidance for conducting mediation analysis with multiple mediators using inverse odds ratio weighting.

    Science.gov (United States)

    Nguyen, Quynh C; Osypuk, Theresa L; Schmidt, Nicole M; Glymour, M Maria; Tchetgen Tchetgen, Eric J

    2015-03-01

    Despite the recent flourishing of mediation analysis techniques, many modern approaches are difficult to implement or applicable to only a restricted range of regression models. This report provides practical guidance for implementing a new technique utilizing inverse odds ratio weighting (IORW) to estimate natural direct and indirect effects for mediation analyses. IORW takes advantage of the odds ratio's invariance property and condenses information on the odds ratio for the relationship between the exposure (treatment) and multiple mediators, conditional on covariates, by regressing exposure on mediators and covariates. The inverse of the covariate-adjusted exposure-mediator odds ratio association is used to weight the primary analytical regression of the outcome on treatment. The treatment coefficient in such a weighted regression estimates the natural direct effect of treatment on the outcome, and indirect effects are identified by subtracting direct effects from total effects. Weighting renders treatment and mediators independent, thereby deactivating indirect pathways of the mediators. This new mediation technique accommodates multiple discrete or continuous mediators. IORW is easily implemented and is appropriate for any standard regression model, including quantile regression and survival analysis. An empirical example is given using data from the Moving to Opportunity (1994-2002) experiment, testing whether neighborhood context mediated the effects of a housing voucher program on obesity. Relevant Stata code (StataCorp LP, College Station, Texas) is provided. © The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  15. Accreditation of the Personal Dosimetry internal Service Tecnatom by the National Entity (ENAC); Acreditacion del Servicio de Dosimetria Personal Interna de Tecnatom por la Entidad Nacional de Acreditacion (ENAC)

    Energy Technology Data Exchange (ETDEWEB)

    Bravo, B.; Marchena, P.

    2014-07-01

    The service of personal Dosimetry internal Tecnatom has made the process of adapting its methodology and quality assurance, requirements technical and management will be required to obtain accreditation from the National Accreditation Entity according to ISO / IEC 170251 standard {sup G}eneral Requirements competence of testing and calibration laboratories. To carry out this process, the laboratory has defined quality criteria set out in their test procedures, based on ISO Standards 27048: 2011; ISO 20553: 2005 and ISO 28218: 2010. This paper describes what has been the methodology used to implement the requirements of different ISO test methods of SDPI Tecnatom. (Author)

  16. LEGAL AND INSTITUTIONAL FRAMEWORK OF MEDIATION IN REPUBLIC OF MACEDONIA

    Directory of Open Access Journals (Sweden)

    Andon Majhoshev

    2014-10-01

    Full Text Available Mediation as an alternative dispute resolution enables faster, more efficient and less costly resolution of disputes in relation to the proceedings. Its operation is based on the following principles: voluntary, equality of the parties, neutrality of the mediator, exclusion of the public, efficiency of the procedure, confidentiality of information, fairness. In Macedonia the mediation as an alternative dispute resolution was introduced by the Law on Mediation in 2006. However, besides this law, the resolution of disputes by mediation is regulated by other special laws such as the Family Law Act, Consumer Law, the Juvenile Justice, Law for the peaceful resolution of labor disputes, etc.. For effective functioning of the mediation, except legal regulation of mediation, and established appropriate institutional framework is an important link for a successful mediation. The institutional framework of mediation includes: Ministry of Justice - Sector for Mediation, Board for Mediation, the Mediators Chamber of Macedonia and mediator. All the above institutions have proper function in the system of mediation and their jurisdiction is governed normative-legal. The legal and institutional framework actually consists of mediation system in the country and represent a whole.

  17. Considerations about mediative in initial petition

    Directory of Open Access Journals (Sweden)

    Maria das Vitórias Nunes Silva Lourenço

    2013-12-01

    Full Text Available This paper presents considerations about Initial Petition, textual/discursive genre, which is a genre circumscribed in the judicial domain with relation to the Commitment. For this purpose, this article exposes the text plan of the Initial Petition from the postulations of Adam (2011. In the same way, it studies the mediative frameworks based on Guentchéva (1994, 1996, which develop the notion of mediative grammatical categories, that permits the linguistic marking of distance and engagement of the enunciator with regard to the information expressed. It evidences the relevance of the use of mediated constructions in the judicial text, as they function as attenuated strategies to the responsibility of the producer of the text with what is said, and at the same time points to a discourse of authority through the entrance of the sources of law.

  18. U(1) mediation of flux supersymmetry breaking

    Science.gov (United States)

    Grimm, Thomas W.; Klemm, Albrecht

    2008-10-01

    We study the mediation of supersymmetry breaking triggered by background fluxes in Type II string compactifications with Script N = 1 supersymmetry. The mediation arises due to an U(1) vector multiplet coupling to both a hidden supersymmetry breaking flux sector and a visible D-brane sector. The required internal manifolds can be constructed by non-Kähler resolutions of singular Calabi-Yau manifolds. The effective action encoding the U(1) coupling is then determined in terms of the global topological properties of the internal space. We investigate suitable local geometries for the hidden and visible sector in detail. This includes a systematic study of orientifold symmetries of del Pezzo surfaces realized in compact geometries after geometric transition. We construct compact examples admitting the key properties to realize flux supersymmetry breaking and U(1) mediation. Their toric realization allows us to analyze the geometry of curve classes and confirm the topological connection between the hidden and visible sector.

  19. Revisiting R-invariant direct gauge mediation

    Energy Technology Data Exchange (ETDEWEB)

    Chiang, Cheng-Wei [Center for Mathematics and Theoretical Physics andDepartment of Physics, National Central University,Taoyuan, Taiwan 32001, R.O.C. (China); Institute of Physics, Academia Sinica,Taipei, Taiwan 11529, R.O.C. (China); Physics Division, National Center for Theoretical Sciences,Hsinchu, Taiwan 30013, R.O.C. (China); Kavli IPMU (WPI), UTIAS, University of Tokyo,Kashiwa, Chiba 277-8583 (Japan); Harigaya, Keisuke [Department of Physics, University of California,Berkeley, California 94720 (United States); Theoretical Physics Group, Lawrence Berkeley National Laboratory,Berkeley, California 94720 (United States); ICRR, University of Tokyo,Kashiwa, Chiba 277-8582 (Japan); Ibe, Masahiro [Kavli IPMU (WPI), UTIAS, University of Tokyo,Kashiwa, Chiba 277-8583 (Japan); ICRR, University of Tokyo,Kashiwa, Chiba 277-8582 (Japan); Yanagida, Tsutomu T. [Kavli IPMU (WPI), UTIAS, University of Tokyo,Kashiwa, Chiba 277-8583 (Japan)

    2016-03-21

    We revisit a special model of gauge mediated supersymmetry breaking, the “R-invariant direct gauge mediation.” We pay particular attention to whether the model is consistent with the minimal model of the μ-term, i.e., a simple mass term of the Higgs doublets in the superpotential. Although the incompatibility is highlighted in view of the current experimental constraints on the superparticle masses and the observed Higgs boson mass, the minimal μ-term can be consistent with the R-invariant gauge mediation model via a careful choice of model parameters. We derive an upper limit on the gluino mass from the observed Higgs boson mass. We also discuss whether the model can explain the 3σ excess of the Z+jets+E{sub T}{sup miss} events reported by the ATLAS collaboration.

  20. Sensemaking in Technology-Use Mediation

    DEFF Research Database (Denmark)

    Bansler, Jørgen P.; Havn, Erling C.

    2006-01-01

    of advanced CSCW technologies is basically a problem of sensemaking. We analyze how a group of “technology-use mediators” (Orlikowski et al. Org. Sci. (1995) 6(4), 423) in a large, multinational company adapted a groupware technology (a “virtual workspace”) to the local organizational context (and vice versa......) by modifying features of the technology, providing ongoing support for users, and promoting appropriate conventions of use. Our findings corroborate earlier research on technology-use mediation, which suggests that such mediators can exert considerable influence on how a particular technology...... will be established and used in an organization. However, we also find that the process of technology-use mediation is much more complex and indeterminate than prior research suggests. The reason being, we argue, that new, advanced CSCW technologies, such as “virtual workspaces” and other groupware applications...

  1. U(1) mediation of flux supersymmetry breaking

    International Nuclear Information System (INIS)

    Grimm, Thomas W.; Klemm, Albrecht

    2008-01-01

    We study the mediation of supersymmetry breaking triggered by background fluxes in Type II string compactifications with N = 1 supersymmetry. The mediation arises due to an U(1) vector multiplet coupling to both a hidden supersymmetry breaking flux sector and a visible D-brane sector. The required internal manifolds can be constructed by non-Kaehler resolutions of singular Calabi-Yau manifolds. The effective action encoding the U(1) coupling is then determined in terms of the global topological properties of the internal space. We investigate suitable local geometries for the hidden and visible sector in detail. This includes a systematic study of orientifold symmetries of del Pezzo surfaces realized in compact geometries after geometric transition. We construct compact examples admitting the key properties to realize flux supersymmetry breaking and U(1) mediation. Their toric realization allows us to analyze the geometry of curve classes and confirm the topological connection between the hidden and visible sector.

  2. Gravity mediated supersymmetry breaking in six dimensions

    International Nuclear Information System (INIS)

    Falkowski, A.; Lee, H.M.; Luedeling, C.

    2005-04-01

    We study gravity mediated supersymmetry breaking in four-dimensional effective theories derived from six-dimensional brane-world supergravities. Using the Noether method we construct a locally supersymmetric action for a bulk-brane system consisting of the minimal six-dimensional supergravity coupled to vector and chiral multiplets located at four-dimensional branes. We compactify this system on T 2 /Z 2 and derive the four-dimensional effective supergravity. Most interestingly, sequestering of the matter living on different branes is not explicit in the tree-level Kaehler potential (but of course the action obtained from this Kaehler potential is consistent with higher dimensional locality). As a consequence, the features of gravity mediation are different than in five-dimensional models. We identify one scenario of moduli stabilization that yields positive gravity mediated soft scalar masses squared. (orig.)

  3. Mediator kinase module and human tumorigenesis.

    Science.gov (United States)

    Clark, Alison D; Oldenbroek, Marieke; Boyer, Thomas G

    2015-01-01

    Mediator is a conserved multi-subunit signal processor through which regulatory informatiosn conveyed by gene-specific transcription factors is transduced to RNA Polymerase II (Pol II). In humans, MED13, MED12, CDK8 and Cyclin C (CycC) comprise a four-subunit "kinase" module that exists in variable association with a 26-subunit Mediator core. Genetic and biochemical studies have established the Mediator kinase module as a major ingress of developmental and oncogenic signaling through Mediator, and much of its function in signal-dependent gene regulation derives from its resident CDK8 kinase activity. For example, CDK8-targeted substrate phosphorylation impacts transcription factor half-life, Pol II activity and chromatin chemistry and functional status. Recent structural and biochemical studies have revealed a precise network of physical and functional subunit interactions required for proper kinase module activity. Accordingly, pathologic change in this activity through altered expression or mutation of constituent kinase module subunits can have profound consequences for altered signaling and tumor formation. Herein, we review the structural organization, biological function and oncogenic potential of the Mediator kinase module. We focus principally on tumor-associated alterations in kinase module subunits for which mechanistic relationships as opposed to strictly correlative associations are established. These considerations point to an emerging picture of the Mediator kinase module as an oncogenic unit, one in which pathogenic activation/deactivation through component change drives tumor formation through perturbation of signal-dependent gene regulation. It follows that therapeutic strategies to combat CDK8-driven tumors will involve targeted modulation of CDK8 activity or pharmacologic manipulation of dysregulated CDK8-dependent signaling pathways.

  4. Extended tree-level gauge mediation

    DEFF Research Database (Denmark)

    Monaco, M.; Nardecchia, M.; Romanino, A.

    2011-01-01

    Tree-level gauge mediation (TGM) is a scenario of SUSY breaking in which the tree-level exchange of heavy (possibly GUT) vector fields generates flavor-universal sfermion masses. In this work we extend this framework to the case of E(6) that is the natural extension of the minimal case studied so...... if the gauge group does not contain SU(5). If SUSY breaking is mediated purely by the U(1) generator that commutes with SO(10) we obtain universal sfermion masses and thus can derive the CMSSM boundary conditions in a novel scenario....

  5. Barley Transformation Using Agrobacterium-Mediated Techniques

    Science.gov (United States)

    Harwood, Wendy A.; Bartlett, Joanne G.; Alves, Silvia C.; Perry, Matthew; Smedley, Mark A.; Leyland, Nicola; Snape, John W.

    Methods for the transformation of barley using Agrobacterium-mediated techniques have been available for the past 10 years. Agrobacterium offers a number of advantages over biolistic-mediated techniques in terms of efficiency and the quality of the transformed plants produced. This chapter describes a simple system for the transformation of barley based on the infection of immature embryos with Agrobacterium tumefaciens followed by the selection of transgenic tissue on media containing the antibiotic hygromycin. The method can lead to the production of large numbers of fertile, independent transgenic lines. It is therefore ideal for studies of gene function in a cereal crop system.

  6. Auxin-dependent compositional change in Mediator in ARF7- and ARF19-mediated transcription.

    Science.gov (United States)

    Ito, Jun; Fukaki, Hidehiro; Onoda, Makoto; Li, Lin; Li, Chuanyou; Tasaka, Masao; Furutani, Masahiko

    2016-06-07

    Mediator is a multiprotein complex that integrates the signals from transcription factors binding to the promoter and transmits them to achieve gene transcription. The subunits of Mediator complex reside in four modules: the head, middle, tail, and dissociable CDK8 kinase module (CKM). The head, middle, and tail modules form the core Mediator complex, and the association of CKM can modify the function of Mediator in transcription. Here, we show genetic and biochemical evidence that CKM-associated Mediator transmits auxin-dependent transcriptional repression in lateral root (LR) formation. The AUXIN/INDOLE 3-ACETIC ACID 14 (Aux/IAA14) transcriptional repressor inhibits the transcriptional activity of its binding partners AUXIN RESPONSE FACTOR 7 (ARF7) and ARF19 by making a complex with the CKM-associated Mediator. In addition, TOPLESS (TPL), a transcriptional corepressor, forms a bridge between IAA14 and the CKM component MED13 through the physical interaction. ChIP assays show that auxin induces the dissociation of MED13 but not the tail module component MED25 from the ARF7 binding region upstream of its target gene. These findings indicate that auxin-induced degradation of IAA14 changes the module composition of Mediator interacting with ARF7 and ARF19 in the upstream region of their target genes involved in LR formation. We suggest that this regulation leads to a quick switch of signal transmission from ARFs to target gene expression in response to auxin.

  7. A classical regression framework for mediation analysis: fitting one model to estimate mediation effects.

    Science.gov (United States)

    Saunders, Christina T; Blume, Jeffrey D

    2017-10-26

    Mediation analysis explores the degree to which an exposure's effect on an outcome is diverted through a mediating variable. We describe a classical regression framework for conducting mediation analyses in which estimates of causal mediation effects and their variance are obtained from the fit of a single regression model. The vector of changes in exposure pathway coefficients, which we named the essential mediation components (EMCs), is used to estimate standard causal mediation effects. Because these effects are often simple functions of the EMCs, an analytical expression for their model-based variance follows directly. Given this formula, it is instructive to revisit the performance of routinely used variance approximations (e.g., delta method and resampling methods). Requiring the fit of only one model reduces the computation time required for complex mediation analyses and permits the use of a rich suite of regression tools that are not easily implemented on a system of three equations, as would be required in the Baron-Kenny framework. Using data from the BRAIN-ICU study, we provide examples to illustrate the advantages of this framework and compare it with the existing approaches. © The Author 2017. Published by Oxford University Press.

  8. El litio y su relación con la acuaporina-2 y el canal de sodio ENaC

    OpenAIRE

    Luciano Galizia; Gabriela I. Marino; Basilio A. Kotsias

    2012-01-01

    Desde hace más de cuarenta años que el litio es usado para el tratamiento de la enfermedad bipolar; recientes estudios sugieren también su utilidad en el trastorno cognitivo mínimo tipo amnésico. El litio es filtrado en el glomérulo y un 65-75% del mismo es reabsorbido en el túbulo contorneado proximal y en el asa ascendente de Henle por el transportador Na+, K+, 2Cl- y vía paracelular. Una pequeña fracción del litio entra en las células principales del túbulo colector por medio del canal epi...

  9. Canales iónicos TRP y DEG/ENAC en órganos sensitivos del pez cebra

    OpenAIRE

    Viña Fernández, Eliseo

    2016-01-01

    En los vertebrados la capacidad para detectar y discriminar entre estímulos del entorno, y del medio interno, se consigue gracias a órganos sensoriales y receptores sensitivos dispersos por todo el cuerpo que dependen de la activación de canales iónicos para transducir los estímulos específicos en señales eléctricas. El presente trabajo de tesis se inscribe en una línea de investigación desarrollada en el Grupo SINPOS del Departamento de Morfología y Biología Celular de la Universidad d...

  10. Establishment of an efficient Agrobacterium tumefaciens -mediated ...

    African Journals Online (AJOL)

    Spine gourd (Momordica dioica Roxb. ex Willd) is a medicinally and economically important plant and also used as vegetable. In this study, we established an Agrobacterium tumefaciens-mediated transformation procedure for M. dioica. Leaf explants were incubated with A. tumefaciens strain LBA4404 containing a binary ...

  11. Mediators of mucosal inflammation : Implications for therapy

    NARCIS (Netherlands)

    VanDullemen, H; Meenan, J; Stronkhorst, A; Tytgat, GNJ; VanDenenter, SJH

    1997-01-01

    Treatment of inflammatory bowel disease remains a challenge. The major shortcoming in the development of new therapeutic approaches is the fact that the cause of inflammatory bowel disease is still unknown. Recognition of the importance of the arachidonic acid cascade of inflammatory mediators

  12. Eicosanoid-mediated immunity in insects

    Science.gov (United States)

    Eicosanoid is a collective term for oxygenated metabolites of C20 polyunsaturated fatty acids. As seen in mammals, eicosanoids play crucial roles in mediating various physiological processes, including immune responses, in insects. Upon microbial pathogen infection, non-self recognition signals are ...

  13. Regional Organisations and International Mediation: The ...

    African Journals Online (AJOL)

    Angela

    increasing number of regional conflict management efforts undertaken by ... to study the advantages and disadvantages of mediation efforts by regional ... Elgström is Professor at the Department of Political Science, Lund University,. Sweden. .... partial or full settlement) in 42.1 per cent of cases; the UN achieved success.

  14. Mediating Artifact in Teacher Professional Development

    Science.gov (United States)

    Svendsen, Bodil

    2015-01-01

    This article focuses on teacher professional development (TPD) in natural science through the 5E model as mediating artifact. The study was conducted in an upper secondary school, grounded in a school-based intervention research project. My contribution to the field of research on TPD is founded on the hypothesis that teachers would be best…

  15. Nutritionally Mediated Oxidative Stress and Inflammation

    Directory of Open Access Journals (Sweden)

    Alexandra Muñoz

    2013-01-01

    Full Text Available There are many sources of nutritionally mediated oxidative stress that trigger inflammatory cascades along short and long time frames. These events are primarily mediated via NFκB. On the short-term scale postprandial inflammation is characterized by an increase in circulating levels of IL-6 and TNF-α and is mirrored on the long-term by proinflammatory gene expression changes in the adipocytes and peripheral blood mononuclear cells (PBMCs of obese individuals. Specifically the upregulation of CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1β, CXCL2/MIP-2α, and CXCL3/MIP-2β is noted because these changes have been observed in both adipocytes and PBMC of obese humans. In comparing numerous human intervention studies it is clear that pro-inflammatory and anti-inflammatory consumption choices mediate gene expression in humans adipocytes and peripheral blood mononuclear cells. Arachidonic acid and saturated fatty acids (SFAs both demonstrate an ability to increase pro-inflammatory IL-8 along with numerous other inflammatory factors including IL-6, TNFα, IL-1β, and CXCL1 for arachidonic acid and IGB2 and CTSS for SFA. Antioxidant rich foods including olive oil, fruits, and vegetables all demonstrate an ability to lower levels of IL-6 in PBMCs. Thus, dietary choices play a complex role in the mediation of unavoidable oxidative stress and can serve to exacerbate or dampen the level of inflammation.

  16. Comments: Causal Interpretations of Mediation Effects

    Science.gov (United States)

    Jo, Booil; Stuart, Elizabeth A.

    2012-01-01

    The authors thank Dr. Lindsay Page for providing a nice illustration of the use of the principal stratification framework to define causal effects, and a Bayesian model for effect estimation. They hope that her well-written article will help expose education researchers to these concepts and methods, and move the field of mediation analysis in…

  17. Microbial ecology of bacterially mediated PCB biodegradation

    International Nuclear Information System (INIS)

    Pettigrew, C.A. Jr.

    1989-01-01

    The roles of plasmid mediated and consortia mediated polychlorinated biphenyl (PCB) biodegradation by bacterial populations isolated from PCB contaminated freshwater sediments were investigated. PCB degrading bacteria were isolated by DNA:DNA colony hybridization, batch enrichments, and chemostat enrichment. Analysis of substrate removal and metabolite production were done using chlorinated biphenyl spray plates, reverse phase high pressure liquid chromatography, Cl - detection, and 14 C-labeled substrate mineralization methods. A bacterial consortium, designated LPS10, involved in a concerted metabolic attack on chlorinated biphenyls, was shown to mineralize 4-chlorobiphenyl (4CB) and 4,4'-dichlorobiphenyl (4,4' CB). The LPS10 consortium was isolated by both batch and chemostat enrichment using 4CB and biphenyl (BP) as sole carbon source and was found to have tree bacterial isolates that predominated; these included: Pseudomonas, testosteroni LPS10A which mediated the breakdown of 4CB and 4,4' CB to the putative meta-cleavage product and subsequently to 4-chlorobenzoic acid (4CBA), an isolate tentatively identified as an Arthrobacter sp. LPS10B which mediated 4CBA degradation, and Pseudomonas putida by A LPS10C whose role in the consortium has not been determined

  18. Design research into mobile museum mediation

    DEFF Research Database (Denmark)

    Baggesen, Rikke Haller

    2013-01-01

    community. 
The PhD research project “Mobile Mediation of Fashion by Museums” explores how aesthetic and ethnographic design methods can be used to develop mobile experiences and articulate museological matters of concern. Building on user perspectives, expressed in response to cultural probes, the project...

  19. Teaching Task Sequencing via Verbal Mediation.

    Science.gov (United States)

    Rusch, Frank R.; And Others

    1987-01-01

    Verbal sequence training was used to teach a moderately mentally retarded woman to sequence job-related tasks. Learning to say the tasks in the proper sequence resulted in the employee performing her tasks in that sequence, and the employee was capable of mediating her own work behavior when scheduled changes occurred. (Author/JDD)

  20. Genetic transformation of Physcomitrella patens mediated by ...

    African Journals Online (AJOL)

    USER

    2010-06-21

    Jun 21, 2010 ... plants could be obtained after 4 generations of selective culture. PCR analysis showed that gene ... 5'-triphosphate; SDS, sodium dodecyl sulfate; YFP, your favorite protein. ..... affected the transformation rate mediated by Agro- bacterium, this was confirmed and the result showed only the gametophores ...

  1. Analyzing the mediated voice - a datasession

    DEFF Research Database (Denmark)

    Lawaetz, Anna

    Broadcasted voices are technologically manipulated. In order to achieve a certain autencity or sound of “reality” paradoxically the voices are filtered and trained in order to reach the listeners. This “mis-en-scene” is important knowledge when it comes to the development of a consistent method o...... of analysis of the mediated voice...

  2. RETHINKING RESEARCH ETHICS FOR MEDIATED SETTINGS

    NARCIS (Netherlands)

    Beaulieu, Anne; Estalella, Adolfo

    2012-01-01

    An important feature of e-research is the increased mediation of research practices, which changes not only the objects and tools of research, but also the relation between researcher and object, between researchers, and between researchers and their constituencies and stakeholders. This article

  3. Optimization of Agrobacterium -mediated transformation parameters ...

    African Journals Online (AJOL)

    Agrobacterium-mediated transformation factors for sweet potato embryogenic calli were optimized using -glucuronidase (GUS) as a reporter. The binary vector pTCK303 harboring the modified GUS gene driven by the CaMV 35S promoter was used. Transformation parameters were optimized including bacterial ...

  4. Improving Undergraduates' Critique via Computer Mediated Communication

    Science.gov (United States)

    Mohamad, Maslawati; Musa, Faridah; Amin, Maryam Mohamed; Mufti, Norlaila; Latiff, Rozmel Abdul; Sallihuddin, Nani Rahayu

    2014-01-01

    Our current university students, labeled as "Generation Y" or Millennials, are different from previous generations due to wide exposure to media. Being technologically savvy, they are accustomed to Internet for information and social media for socializing. In line with this current trend, teaching through computer mediated communication…

  5. Detergent-Mediated Reconstitution of Membrane Proteins

    NARCIS (Netherlands)

    Knol, J; Sjollema, K.A; Poolman, B.

    1998-01-01

    The efficiency of reconstitution of the lactose transport protein (LacS) of Streptococcus thermophilus is markedly higher with Triton X-100 than with other detergents commonly employed to mediate the membrane insertion. To rationalize these differences, the lipid/detergent structures that are formed

  6. The Role of Artefacts in Presence Mediation

    NARCIS (Netherlands)

    Vyas, Dhaval; Tzovaras, D

    2007-01-01

    Approaches to support computer mediated communication (CMC) have predominantly relied on the face-to-face communication paradigm. However, interaction and coordination can also be supported by different technological artefacts. In fact, most researches [1, 2, 3] related to ethnomethodology have

  7. Proteinaceous molecules mediating Bifidobacterium-host interactions

    Directory of Open Access Journals (Sweden)

    Lorena Ruiz

    2016-08-01

    Full Text Available Bifidobacteria are commensal microoganisms found in the gastrointestinal tract.Several strains have been attributed beneficial traits at local and systemic levels, through pathogen exclusion or immune modulation, among other benefits. This has promoted a growing industrial and scientific interest in bifidobacteria as probiotic supplements. However, the molecular mechanisms mediating this cross-talk with the human host remain unknown. High-throughput technologies, from functional genomics to transcriptomics, proteomics and interactomics coupled to the development of both in vitro and in vivo models to study the dynamics of the intestinal microbiota and their effects on host cells, have eased the identification of key molecules in these interactions. Numerous secreted or surface-associated proteins or peptides have been identified as potential mediators of bifidobacteria-host interactions and molecular cross-talk, directly participating in sensing environmental factors, promoting intestinal colonization or mediating a dialogue with mucosa-associated immune cells. On the other hand, bifidobacteria induce the production of proteins in the intestine, by epithelial or immune cells, and other gut bacteria, which are key elements in orchestrating interactions among bifidobacteria, gut microbiota and host cells. This review aims to give a comprehensive overview on proteinaceous molecules described and characterized to date, as mediators of the dynamic interplay between bifidobacteria and the human host, providing a framework to identify knowledge gaps and future research needs.

  8. Mediation Analyses in the Real World

    DEFF Research Database (Denmark)

    Lange, Theis; Starkopf, Liis

    2016-01-01

    The paper by Nguyen et al.1 published in this issue of Epidemiology presents a comparison of the recently suggested inverse odds ratio approach for addressing mediation and a more conventional Baron and Kenny-inspired method. Interestingly, the comparison is not done through a discussion of restr......The paper by Nguyen et al.1 published in this issue of Epidemiology presents a comparison of the recently suggested inverse odds ratio approach for addressing mediation and a more conventional Baron and Kenny-inspired method. Interestingly, the comparison is not done through a discussion...... it simultaneously ensures that the comparison is based on properties, which matter in actual applications, and makes the comparison accessible for a broader audience. In a wider context, the choice to stay close to real-life problems mirrors a general trend within the literature on mediation analysis namely to put...... applications using the inverse odds ration approach, as it simply has not had enough time to move from theoretical concept to published applied paper, we do expect to be able to judge the willingness of authors and journals to employ the causal inference-based approach to mediation analyses. Our hope...

  9. Sonication assisted Agrobacterium -mediated transformation of ...

    African Journals Online (AJOL)

    In this study, a protocol was developed to obtain stable lines of the Spring Dendrobium cultivar 'Sanya' via sonication assisted Agrobacterium-mediated transformation (SAAT) of protocorm-like bodies (PLBs). Agrobacterium tumefaciens strain LBA4404 was used with the binary vector AG205 containing the chalcone ...

  10.  Fashion Mediators and Distributed Agency

    DEFF Research Database (Denmark)

    Sommerlund, Julie

    intermediaries" (Bourdieu, 1984) which designates a certain class of people. Empirically, the paper works with the cultural and aesthetic economies - and with fashion in particular. Using the mediator as central concept, the paper presents empirical stories from the field of fashion, and fashion marketing...

  11. Plasmid mediated quinolone resistance in Enterobacteriaceae

    NARCIS (Netherlands)

    Veldman, K.T.; LS Klinisch Onderzoek Wagenaar

    2014-01-01

    This thesis describes the occurrence of Plasmid Mediated Quinolone Resistance (PMQR) in Salmonella and E. coli from The Netherlands and other European countries. Furthermore, the genetic background of these genes was characterized. Fluoroquinolones are widely used antibiotics in both human and

  12. Identification as a Mediator of Celebrity Effects.

    Science.gov (United States)

    Basil, Michael D.

    1996-01-01

    This study examined personal concern, perceived risk, and sexual behavior of 147 college students a year after Magic Johnson announced he tested positive for HIV (Human Immunodeficiency Virus). It found that identification mediates message effects, suggesting that a spokesperson with whom an audience can identify insures the greatest likelihood of…

  13. Characterization of BASP1-mediated neurite outgrowth

    DEFF Research Database (Denmark)

    Korshunova, Irina; Caroni, Pico; Kolkova, Kateryna

    2008-01-01

    The brain acid-soluble protein BASP1 (CAP-23, NAP-22) belongs to the family of growth-associated proteins, which also includes GAP-43, a protein recently shown to regulate neural cell adhesion molecule (NCAM)-mediated neurite outgrowth. Here, the effects of BASP1 overexpression were investigated...

  14. Volatile-mediated interactions in the rhizosphere

    NARCIS (Netherlands)

    Cordovez da Cunha, Viviane

    2016-01-01

    Plants and microorganisms are constantly engaged in highly dynamic interactions both above- and belowground. Several of these interactions are mediated by volatile organic compounds (VOCs), small carbon-based compounds with high vapor pressure at ambient temperature. In the rhizosphere, VOCs have

  15. A Comparison of Three Tests of Mediation

    Science.gov (United States)

    Warbasse, Rosalia E.

    2009-01-01

    A simulation study was conducted to evaluate the performance of three tests of mediation: the bias-corrected and accelerated bootstrap (Efron & Tibshirani, 1993), the asymmetric confidence limits test (MacKinnon, 2008), and a multiple regression approach described by Kenny, Kashy, and Bolger (1998). The evolution of these methods is reviewed and…

  16. Structure of Energetic Particle Mediated Shocks Revisited

    International Nuclear Information System (INIS)

    Mostafavi, P.; Zank, G. P.; Webb, G. M.

    2017-01-01

    The structure of collisionless shock waves is often modified by the presence of energetic particles that are not equilibrated with the thermal plasma (such as pickup ions [PUIs] and solar energetic particles [SEPs]). This is relevant to the inner and outer heliosphere and the Very Local Interstellar Medium (VLISM), where observations of shock waves (e.g., in the inner heliosphere) show that both the magnetic field and thermal gas pressure are less than the energetic particle component pressures. Voyager 2 observations revealed that the heliospheric termination shock (HTS) is very broad and mediated by energetic particles. PUIs and SEPs contribute both a collisionless heat flux and a higher-order viscosity. We show that the incorporation of both effects can completely determine the structure of collisionless shocks mediated by energetic ions. Since the reduced form of the PUI-mediated plasma model is structurally identical to the classical cosmic ray two-fluid model, we note that the presence of viscosity, at least formally, eliminates the need for a gas sub-shock in the classical two-fluid model, including in that regime where three are possible. By considering parameters upstream of the HTS, we show that the thermal gas remains relatively cold and the shock is mediated by PUIs. We determine the structure of the weak interstellar shock observed by Voyager 1 . We consider the inclusion of the thermal heat flux and viscosity to address the most general form of an energetic particle-thermal plasma two-fluid model.

  17. Cultural Mediators Seduced by Mad Men:

    DEFF Research Database (Denmark)

    Kristensen, Nete Nørgaard; Hellman, Heikki; Riegert, Kristina

    2017-01-01

    Based on theories about the role of cultural mediators in cultural production and using the TV series Mad Men as a case, this article investigates how cultural journalists in the Nordic countries have contributed to legitimizing “quality TV series” as a worthy field of aesthetic consumption. Key...

  18. Holographic gauge mediation via strongly coupled messengers

    International Nuclear Information System (INIS)

    McGuirk, Paul; Shiu, Gary; Sumitomo, Yoske

    2010-01-01

    We consider a relative of semidirect gauge mediation where the hidden sector exists at large 't Hooft coupling. Such scenarios can be difficult to describe using perturbative field theory methods but may fall into the class of holographic gauge mediation scenarios, meaning that they are amenable to the techniques of gauge/gravity duality. We use a recently found gravity solution to examine one such case, where the hidden sector is a cascading gauge theory resulting in a confinement scale not much smaller than the messenger mass. In the original construction of holographic gauge mediation, as in other examples of semidirect gauge mediation at strong coupling, the primary contributions to visible sector soft terms come from weakly coupled messenger mesons. In contrast to these examples, we describe the dual of a gauge theory where there are significant contributions from scales in which the strongly coupled messenger quarks are the effective degrees of freedom. In this regime, the visible sector gaugino mass can be calculated entirely from holography.

  19. [Children in family mediation: A practice model].

    Science.gov (United States)

    Mayer, Stefan; Normann, Katrin

    2006-01-01

    The authors briefly describe the history of family mediation under the perspective of the role of the children in the process of mediation. They state that originally children were not directly included. But through empirical studies and different higher escalated families asking for help by mediation, the inclusion of children got an important issue in theory and practice. The discussion began with the question in which phases of the mediation process the children should be included - it went to the issue of the age of the children - and the authors propose to take the amount of escalation in the family as the most important point of reference to decide if and how the children should be included. They suggest to diagnose the loss of responsibility and autonomy of the parents on a nine level scale (from F. Glasl) with the parents and to decide and negotiate with them how the children will be included. They describe five different settings of inclusion of the children.

  20. Mitogen-activated protein kinases mediate Mycobacterium ...

    Indian Academy of Sciences (India)

    2012-01-19

    Jan 19, 2012 ... CD44, an adhesion molecule, has been reported to be a binding site for ... receptors in mediating mitogen-activated protein kinase activation. ... surface expression and tumour necrosis factor-alpha levels, ... Abbreviations used: Abs, antibodies; ANOVA, analysis of variance; AP-1, activator protein -1; BCG, ...