Colorectal cancer: can nutrients modulate NF-kappaB and apoptosis?

Science.gov (United States)

Ravasco, Paula; Aranha, Márcia M; Borralho, Pedro M; Moreira da Silva, Isabel B; Correia, Luís; Fernandes, Afonso; Rodrigues, Cecília M P; Camilo, Maria

2010-02-01

NF-kappaB may promote carcinogenesis by altering cell cycle, inflammatory responses and apoptosis-related gene expression, though cell mechanisms relating diet and colorectal cancer (CRC) remain unveiled in humans. This study in patients with CRC aimed to explore potential interactions between the dietary pattern, nutrient intake, expression of NF-kappaB, apoptosis and tumour histological aggressiveness. Usual diet was assessed by diet history; nutrient composition was determined by DIETPLAN software. Histologically classified patient tissue samples (adenoma, adenocarcinoma and normal surrounding mucosa) were obtained via biopsies during colonoscopy (n=16) or surgery (n=8). NF-kappaB expression was determined by immunohistochemistry and apoptosis by TUNEL assay. NF-kappaB expression and apoptosis were higher in tumours (p<0.01), greater along with histological aggressiveness (p<0.01). Highest intake terciles of animal protein, refined carbohydrates, saturated fat, n-6 fatty acids and alcohol were associated with higher NF-kappaB, apoptosis and histological aggressiveness (p<0.01); the opposite tissue characteristics were associated with highest intake terciles of n-3 fatty acids, fibre, vitamin E, flavonoids, isoflavones, beta-carotene and selenium (p<0.002). Additionally, higher n-6:n-3 fatty acids ratio (median 26:1) was associated with higher NF-kappaB (p<0.006) and apoptosis (p<0.01), and more aggressive histology (p<0.01). Conversely, lower n-6:n-3 fatty acids ratio (median 6:1) was associated with lower NF-kappaB (p<0.002) and apoptosis (p<0.002), and less aggressive histology (p<0.002). NF-kappaB expression and apoptosis increased from adenoma to poorly differentiated adenocarcinoma. This degenerative transition, recognized as key in carcinogenesis, appear to have been influenced by a diet promoting a pro-inflammatory milieu that can trigger NF-kappaB. Copyright 2009 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Mechanism by which nuclear factor-kappa beta (NF-kB regulates ovine fetal pulmonary vascular smooth muscle cell proliferation

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Uchenna D. Ogbozor

2015-09-01

Full Text Available Platelet activating factor (PAF modulates ovine fetal pulmonary hemodynamic. PAF acts through its receptors (PAFR in pulmonary vascular smooth muscle cells (PVSMC to phosphorylate and induce nuclear translocation of NF-kB p65 leading to PVSMC proliferation. However, the interaction of NF-kB p65 and PAF in the nuclear domain to effect PVSMC cell growth is not clearly defined. We used siRNA-dependent translation initiation arrest to study a mechanism by which NF-kB p65 regulates PAF stimulation of PVSMC proliferation. Our hypotheses are: (a PAF induces NF-kB p65 DNA binding and (b NF-kB p65 siRNA attenuates PAF stimulation of PVSMC proliferation. For DNA binding, cells were fed 10 nM PAF with and without PAFR antagonists WEB 2170, CV 3988 or BN 52021 and incubated for 12 h. DNA binding was measured by specific ELISA. For NF-kB p65 siRNA effect, starved cells transfected with the siRNA were incubated for 24 h with and without 10 nM PAF. Cell proliferation was measured by DNA synthesis while expression of NF-kB p65 and PAFR protein was measured by Western blotting. In both studies, the effect of 10% FBS alone was used as the positive control. In general, PAF stimulated DNA binding which was inhibited by PAFR antagonists. siRNAs to NF-kB p65 and PAFR significantly attenuated cell proliferation compared to 10% FBS and PAF effect. Inclusion of PAF in siRNA-treated cells did not reverse inhibitory effect of NF-kB p65 siRNA on DNA synthesis. PAFR expression was inhibited in siRNA-treated cells. These data show that PAF-stimulation of PVSMC proliferation occurs via a PAFR-NF-kB p65 linked pathway.

Mechanism by which nuclear factor-kappa beta (NF-kB) regulates ovine fetal pulmonary vascular smooth muscle cell proliferation.

Science.gov (United States)

Ogbozor, Uchenna D; Opene, Michael; Renteria, Lissette S; McBride, Shaemion; Ibe, Basil O

2015-09-01

Platelet activating factor (PAF) modulates ovine fetal pulmonary hemodynamic. PAF acts through its receptors (PAFR) in pulmonary vascular smooth muscle cells (PVSMC) to phosphorylate and induce nuclear translocation of NF-kB p65 leading to PVSMC proliferation. However, the interaction of NF-kB p65 and PAF in the nuclear domain to effect PVSMC cell growth is not clearly defined. We used siRNA-dependent translation initiation arrest to study a mechanism by which NF-kB p65 regulates PAF stimulation of PVSMC proliferation. Our hypotheses are: (a) PAF induces NF-kB p65 DNA binding and (b) NF-kB p65 siRNA attenuates PAF stimulation of PVSMC proliferation. For DNA binding, cells were fed 10 nM PAF with and without PAFR antagonists WEB 2170, CV 3988 or BN 52021 and incubated for 12 h. DNA binding was measured by specific ELISA. For NF-kB p65 siRNA effect, starved cells transfected with the siRNA were incubated for 24 h with and without 10 nM PAF. Cell proliferation was measured by DNA synthesis while expression of NF-kB p65 and PAFR protein was measured by Western blotting. In both studies, the effect of 10% FBS alone was used as the positive control. In general, PAF stimulated DNA binding which was inhibited by PAFR antagonists. siRNAs to NF-kB p65 and PAFR significantly attenuated cell proliferation compared to 10% FBS and PAF effect. Inclusion of PAF in siRNA-treated cells did not reverse inhibitory effect of NF-kB p65 siRNA on DNA synthesis. PAFR expression was inhibited in siRNA-treated cells. These data show that PAF-stimulation of PVSMC proliferation occurs via a PAFR-NF-kB p65 linked pathway.

Dissociation of NF3 in shock waves

International Nuclear Information System (INIS)

Breshears, W.D.; Bird, P.F.

1978-01-01

The thermal dissociation rate of NF 3 in mixtures of 5% and 10%NF 3 in Ar has been measured behind incident shock waves over the temperature range 1330-2000 K. Dissociation rates were determined from postshock density gradients measured by laser beam deflection. The second order rate coefficient determined for NF 3 -Ar collisions is k/sub d/=2.31 x 10 15 exp(-20500/T) cm 3 mole sec

Applicability of Sol-Gel Derived Adsorbent for the Production of (n,f) 99Mo Generator

International Nuclear Information System (INIS)

Lee, Jun-Sig; Lee, Jong-Sup; Park, Ul-Jae; Son, Kwang-Jae; Han, Hyon-Soo; Kim, Myung Sic; Koo, Sung Chan; Chung, Young-Ju

2007-01-01

High performance adsorbents as the column material for (n,γ) 99 Mo/ 99 mTc and 188 W/ 188 Re generators have been developed at KAERI. These adsorbents should have enough loading capacities to produce such generators with high activities as the loading isotopes are not carrier-free. In this regard, the adsorbents are synthesized by sol-gel processing in which the ligand density can easily be adjusted and maximized. The marginal capacity of such adsorbents should be higher than 200 mg/g for molybdenum. From the previous works, the sol-gel processing techniques are adequately applied to meet the criteria. Further studies are being undertaken to employ the adsorbents for the production of high capacity (n,f) 99 Mo/ 99 mTc. Domestically, a private company has lined up the production facility of the molybdenum generator in the activity range of 300 ∼ 1,000 mCi/ea. The column elements are composed of manganese oxide doped on silica and alumina at the backup layer. In this column, the manganese oxide is the main reactive layer to retain (n,f) 99 Mo. The sol-gel derived adsorbent, in this study, is employed as the replacement of the manganese oxide doped silica in the column and tested for the loading efficiency of (n,f) 99 Mo, elution of 99 mTc, labeling property of the eluted 99 mTc. The same loading and elution procedures as the commercial production are applied for the tests and quality controls

Regulation of NF-κB activity in astrocytes: effects of flavonoids at dietary-relevant concentrations

International Nuclear Information System (INIS)

Spilsbury, Alison; Vauzour, David; Spencer, Jeremy P.E.; Rattray, Marcus

2012-01-01

Highlights: ► We tested the hypothesis that low concentrations of flavonoids inhibit NF-κB in astrocytes. ► Primary cultured astrocytes possess a functional κB-system, measured using luciferase assays. ► Seven flavonoids (100 nM–1 μM) failed to reduce NF-κB activity in astrocytes. ► Four flavonoids (100 nM–1 μM) failed to reduce TNFa-stimulated NF-κB activity in astrocytes. ► (−)-Epicatechin did not regulate nuclear translocation of the NF-κB subunit, p65. -- Abstract: Neuroinflammation plays an important role in the progression of neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease. Sustained activation of nuclear transcription factor κB (NF-κB) is thought to play an important role in the pathogenesis of neurodegenerative disorders. Flavonoids have been shown to possess antioxidant and anti-inflammatory properties and we investigated whether flavonoids, at submicromolar concentrations relevant to their bioavailability from the diet, were able to modulate NF-κB signalling in astrocytes. Using luciferase reporter assays, we found that tumour necrosis factor (TNFα, 150 ng/ml) increased NF-κB-mediated transcription in primary cultures of mouse cortical astrocytes, which was abolished on co-transfection of a dominant-negative IκBα construct. In addition, TNFα increased nuclear localisation of p65 as shown by immunocytochemistry. To investigate potential flavonoid modulation of NF-κB activity, astrocytes were treated with flavonoids from different classes; flavan-3-ols ((−)-epicatechin and (+)-catechin), flavones (luteolin and chrysin), a flavonol (kaempferol) or the flavanones (naringenin and hesperetin) at dietary-relevant concentrations (0.1–1 μM) for 18 h. None of the flavonoids modulated constitutive or TNFα-induced NF-κB activity. Therefore, we conclude that NF-κB signalling in astrocytes is not a major target for flavonoids.

Temperature-dependent interaction potential between NF3 molecules and thermophysical properties of gaseous NF3

International Nuclear Information System (INIS)

Damyanova, M; Balabanova, E; Hohm, U

2014-01-01

A temperature-dependent effective intermolecular interaction potential is applied to describe the interaction between two nitrogen fluoride (NF 3 ) molecules in gas phase. To this end, a spherically-symmetric (n-6) Lennard-Jones temperature-dependent potential (LJTDP) is used. The (n-6) LJTDP takes into account the influence of vibrational excitation of the molecules on the potential parameters, namely, the equilibrium distance r m and the potential well depth ε. The potential parameters at T = 0 K were obtained from the very small amount of existing thermophysical equilibrium and transport properties of low-density NF 3 gas. Fitting formulae are tabulated for a fast and reliable prediction of the thermophysical properties and potential parameters in the temperature range between 200 K and 1200 K. A comparison is also presented between our estimates for some thermophysical properties of the NF 3 gas with the available experimental and calculated data.

Collagen-derived N-acetylated proline-glycine-proline upregulates the expression of pro-inflammatory cytokines and extracellular matrix proteases in nucleus pulposus cells via the NF-κB and MAPK signaling pathways.

Science.gov (United States)

Feng, Chencheng; He, Jinyue; Zhang, Yang; Lan, Minghong; Yang, Minghui; Liu, Huan; Huang, Bo; Pan, Yong; Zhou, Yue

2017-07-01

N-acetylated proline-glycine-proline (N-Ac-PGP) is a chemokine involved in inflammatory diseases and is found to accumulate in degenerative discs. N-Ac-PGP has been demonstrated to have a pro-inflammatory effect on human cartilage endplate stem cells. However, the effect of N-Ac-PGP on human intervertebral disc cells, especially nucleus pulposus (NP) cells, remains unknown. The purpose of this study was to investigate the effect of N-Ac-PGP on the expression of pro-inflammatory factors and extracellular matrix (ECM) proteases in NP cells and the molecular mechanism underlying this effect. Therefore, Milliplex assays were used to detect the levels of various inflammatory cytokines in conditioned culture medium of NP cells treated with N-Ac-PGP, including interleukin-1β (IL-1β), IL-6, IL-17, tumor necrosis factor-α (TNF-α) and C-C motif ligand 2 (CCL2). RT-qPCR was also used to determine the expression of pro-inflammatory cytokines and ECM proteases in the NP cells treated with N-Ac-PGP. Moreover, the role of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways in mediating the effect of N-Ac-PGP on the phenotype of NP cells was investigated using specific signaling inhibitors. Milliplex assays showed that NP cells treated with N-Ac-PGP (10 and 100 µg/ml) secreted higher levels of IL-1β, IL-6, IL-17, TNF-α and CCL2 compared with the control. RT-qPCR assays showed that NP cells treated with N-Ac-PGP (100 µg/ml) had markedly upregulated expression of matrix metalloproteinase 3 (MMP3), MMP13, a disintegrin and metalloproteinase with thrombospondin motif 4 (ADAMTS4), ADAMTS5, IL-6, CCL-2, CCL-5 and C-X-C motif chemokine ligand 10 (CXCL10). Moreover, N-Ac-PGP was shown to activate the MAPK and NF-κB signaling pathways in NP cells. MAPK and NF-κB signaling inhibitors suppressed the upregulation of proteases and pro-inflammatory cytokines in NP cells treated with N-Ac-PGP. In conclusion, N-Ac-PGP induces the

Regulation of NF-{kappa}B activity in astrocytes: effects of flavonoids at dietary-relevant concentrations

Energy Technology Data Exchange (ETDEWEB)

Spilsbury, Alison [Reading School of Pharmacy, University of Reading, Reading RG6 6UB (United Kingdom); Vauzour, David; Spencer, Jeremy P.E. [Molecular Nutrition Group, Centre for Integrative Neuroscience and Neurodynamics, School of Chemistry, Food and Pharmacy, University of Reading, Reading RG6 6AP (United Kingdom); Rattray, Marcus, E-mail: m.a.n.rattray@reading.ac.uk [Reading School of Pharmacy, University of Reading, Reading RG6 6UB (United Kingdom)

2012-02-17

Highlights: Black-Right-Pointing-Pointer We tested the hypothesis that low concentrations of flavonoids inhibit NF-{kappa}B in astrocytes. Black-Right-Pointing-Pointer Primary cultured astrocytes possess a functional {kappa}B-system, measured using luciferase assays. Black-Right-Pointing-Pointer Seven flavonoids (100 nM-1 {mu}M) failed to reduce NF-{kappa}B activity in astrocytes. Black-Right-Pointing-Pointer Four flavonoids (100 nM-1 {mu}M) failed to reduce TNFa-stimulated NF-{kappa}B activity in astrocytes. Black-Right-Pointing-Pointer (-)-Epicatechin did not regulate nuclear translocation of the NF-{kappa}B subunit, p65. -- Abstract: Neuroinflammation plays an important role in the progression of neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. Sustained activation of nuclear transcription factor {kappa}B (NF-{kappa}B) is thought to play an important role in the pathogenesis of neurodegenerative disorders. Flavonoids have been shown to possess antioxidant and anti-inflammatory properties and we investigated whether flavonoids, at submicromolar concentrations relevant to their bioavailability from the diet, were able to modulate NF-{kappa}B signalling in astrocytes. Using luciferase reporter assays, we found that tumour necrosis factor (TNF{alpha}, 150 ng/ml) increased NF-{kappa}B-mediated transcription in primary cultures of mouse cortical astrocytes, which was abolished on co-transfection of a dominant-negative I{kappa}B{alpha} construct. In addition, TNF{alpha} increased nuclear localisation of p65 as shown by immunocytochemistry. To investigate potential flavonoid modulation of NF-{kappa}B activity, astrocytes were treated with flavonoids from different classes; flavan-3-ols ((-)-epicatechin and (+)-catechin), flavones (luteolin and chrysin), a flavonol (kaempferol) or the flavanones (naringenin and hesperetin) at dietary-relevant concentrations (0.1-1 {mu}M) for 18 h. None of the flavonoids modulated constitutive or

Role of S100A1 in hypoxia-induced inflammatory response in cardiomyocytes via TLR4/ROS/NF-κB pathway.

Science.gov (United States)

Yu, Jiangkun; Lu, Yanyu; Li, Yapeng; Xiao, Lili; Xing, Yu; Li, Yanshen; Wu, Leiming

2015-09-01

S100A1 plays a crucial role in hypoxia-induced inflammatory response in cardiomyocytes. However, the role of S100A1 in hypoxia-induced inflammatory response in cardiomyocytes is still unknown. enzyme-linked immunosorbent assay (ELISA) was performed for the determination of inflammatory cytokines. Immunocytochemistry and immunofluorescence, Western blot analysis and Real-time polymerase chain reaction (RT-PCR) were conducted to assess protein or mRNA expressions. Fluorogenic probe dihydroethidium (DHE) was used to evaluate the generation of reactive oxygen species (ROS) while Hoechst 33342 staining for apoptosis. Small interfering RNA (siRNA) for S100A1 was used to evaluate the role of S100A1. The levels of ROS and inflammatory cytokine including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and IL-8 in H9c2 cells were increased remarkably by hypoxia. However, IL-37 protein or mRNA levels were decreased significantly. Both Toll-like receptor 4 (TLR4) inhibitor Ethyl (6R)-6-[N-(2-Chloro-4fluorophenyl)sulfamoyl]cyclohex-1-ene-1-carboxylate (TAK-242) treatment or siRNA S100A1 downregulated TLR4 expression and inflammatory cytokine level and mRNA in H9c2 cells, as well as weakening ROS and phospho-p65 Nuclear factor (NF)-κB levels. Further, S100A1 treatment significantly reduced TNF-α protein or mRNA level whereas enhanced IL-37 protein or mRNA level, and could attenuate ROS and phospho-p65 NF-κB levels. Our results demonstrate that S100A1 can regulate the inflammatory response and oxidative stress in H9C2 cells via TLR4/ROS/NF-κB pathway. These findings provide an interesting strategy for protecting cardiomyocytes from hypoxia-induced inflammatory response. © 2015 Royal Pharmaceutical Society.

Effects of Cordyceps sinensis on the Expressions of NF-κB and TGF-β1 in Myocardium of Diabetic Rats

Directory of Open Access Journals (Sweden)

You-you Gu

2015-01-01

Full Text Available Objective. To investigate the effect of Cordyceps sinensis (CS on the expressions of NF-κB and TGF-β1 in myocardium of streptozotocin-induced diabetic rats. Methods. A total of 53 healthy male SD rats, mice age of 8 weeks and weight of 220 ± 20 g, were randomly divided into five groups by randomized block design: normal control group (n=10, diabetic group (n=10, low dose of CS group (n=12; CS 0.6 g·kg−1·d−1, middle dose of CS group (n=11; CS 2.5 g·kg−1·d−1, and high dose of CS group (n=10; CS 5 g·kg−1·d−1. The diabetic models with tail intravenous injection by streptozotocin (45 mg·kg−1. Diabetic rats were sacrificed after 8 weeks; the expressions of NF-κB and TGF-β1 proteins and mRNA in the cardiac muscle were determined by using immunohistochemistry staining and reverse transcription polymerase chain reaction (RT-PCR method. The data were analyzed using one factor analysis of variance. Result. The expressions of NF-κB and TGF-β1 proteins and mRNA in the cardiac muscle of diabetic rats were significantly raised (P<0.05, which could be decreased by CS (P<0.05. Conclusions. The changes on the expressions of NF-κB and TGF-β1 in myocardium may be involved in the occurrence of diabetic cardiomyopathy (DC. CS may play its role on myocardial protection by regulating the expressions of NF-κB and TGF-β1 in myocardium.

Increased expression of NF-AT3 and NF-AT4 in the atria correlates with procollagen I carboxyl terminal peptide and TGF-β1 levels in serum of patients with atrial fibrillation.

Science.gov (United States)

Zhao, Fei; Zhang, ShiJiang; Chen, YiJiang; Gu, WeiDong; Ni, BuQing; Shao, YongFeng; Wu, YanHu; Qin, JianWei

2014-11-25

Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice. Unfortunately, the precise mechanisms and sensitive serum biomarkers of atrial remodeling in AF remain unclear. The aim of this study was to determine whether the expression of the transcription factors NF-AT3 and NF-AT4 correlate with atrial structural remodeling of atrial fibrillation and serum markers for collagen I and III synthesis. Right and left atrial specimens were obtained from 90 patients undergoing valve replacement surgery. The patients were divided into sinus rhythm (n = 30), paroxysmal atrial fibrillation (n = 30), and persistent atrial fibrillation (n = 30) groups. NF-AT3, NF-AT4, and collagen I and III mRNA and protein expression in atria were measured. We also tested the levels of the carboxyl-terminal peptide from pro-collagen I, the N-terminal type I procollagen propeptides, the N-terminal type III procollagen propeptides, and TGF-β1 in serum using an enzyme immunosorbent assay. NF-AT3 and NF-AT4 mRNA and protein expression were increased in the AF groups, especially in the left atrium. NF-AT3 and NF-AT4 expression in the right atrium was increased in the persistent atrial fibrillation group compared the sinus rhythm group with similar valvular disease. In patients with AF, the expression levels of nuclear NF-AT3 and NF-AT4 correlated with those of collagens I and III in the atria and with PICP and TGF-β1 in blood. These data support the hypothesis that nuclear NF-AT3 and NF-AT4 participates in atrial structural remodeling, and that PICP and TGF-β1 levels may be sensitive serum biomarkers to estimate atrial structural remodeling with atrial fibrillation.

A direct hybrid S{sub N} method for slab-geometry lattice calculations

Energy Technology Data Exchange (ETDEWEB)

Silva, Davi J.M.; Barros, Ricardo C., E-mail: rcbarros@pq.cnpq.b [Universidade do Estado do Rio de Janeiro (IPRJ/UERJ), Nova Friburgo, RJ (Brazil). Programa de Pos-graduacao em Modelagem Computacional; Zani, Jose H. [Fundacao Educacional Serra dos Orgaos, Teresopolis, RJ (Brazil). Ciencia da Computacao

2011-07-01

In this work we describe a hybrid direct method for calculating the thermal disadvantage factor and the neutron flux distribution in fuel-moderator lattices. For the mathematical model, we use the one-speed slab-geometry discrete ordinates (S{sub N}) transport equation with linearly anisotropic scattering. The basic idea is to use higher order angular quadrature set in the highly absorbing fuel region (S{sub NF}) and lower order angular quadrature set in the diffusive moderator region (S{sub NM}) , i.e., N{sub F} > N{sub M}. We apply special continuity conditions based on the equivalence of the S{sub N} and P{sub N-1} equations, which characterize the hybrid model. Numerical results to a typical model problem are given to illustrate the accuracy and the efficiency of the offered hybrid method. (author)

NF-κB Protects NKT Cells from Tumor Necrosis Factor Receptor 1-induced Death.

Science.gov (United States)

Kumar, Amrendra; Gordy, Laura E; Bezbradica, Jelena S; Stanic, Aleksandar K; Hill, Timothy M; Boothby, Mark R; Van Kaer, Luc; Joyce, Sebastian

2017-11-15

Semi-invariant natural killer T (NKT) cells are innate-like lymphocytes with immunoregulatory properties. NKT cell survival during development requires signal processing by activated RelA/NF-κB. Nonetheless, the upstream signal(s) integrated by NF-κB in developing NKT cells remains incompletely defined. We show that the introgression of Bcl-x L -coding Bcl2l1 transgene into NF-κB signalling-deficient IκBΔN transgenic mouse rescues NKT cell development and differentiation in this mouse model. We reasoned that NF-κB activation was protecting developing NKT cells from death signals emanating either from high affinity agonist recognition by the T cell receptor (TCR) or from a death receptor, such as tumor necrosis factor receptor 1 (TNFR1) or Fas. Surprisingly, the single and combined deficiency in PKC-θ or CARMA-1-the two signal transducers at the NKT TCR proximal signalling node-only partially recapitulated the NKT cell deficiency observed in IκBΔN tg mouse. Accordingly, introgression of the Bcl2l1 transgene into PKC-θ null mouse failed to rescue NKT cell development. Instead, TNFR1-deficiency, but not the Fas-deficiency, rescued NKT cell development in IκBΔN tg mice. Consistent with this finding, treatment of thymocytes with an antagonist of the inhibitor of κB kinase -which blocks downstream NF-κB activation- sensitized NKT cells to TNF-α-induced cell death in vitro. Hence, we conclude that signal integration by NF-κB protects developing NKT cells from death signals emanating from TNFR1, but not from the NKT TCR or Fas.

Computing K and D meson masses with N-f=2+1+1 twisted mass lattice QCD

NARCIS (Netherlands)

Baron, Remi; Boucaud, Philippe; Carbonell, Jaume; Drach, Vincent; Farchioni, Federico; Herdoiza, Gregorio; Jansen, Karl; Michael, Chris; Montvay, Istvan; Pallante, Elisabetta; Pene, Olivier; Reker, Siebren; Urbach, Carsten; Wagner, Marc; Wenger, Urs

We discuss the computation of the mass of the K and D mesons within the framework of N-f = 2 + 1 + 1 twisted mass lattice QCD from a technical point of view. These quantities are essential, already at the level of generating gauge configurations, being obvious candidates to tune the strange and

Bcl10 links saturated fat overnutrition with hepatocellular NF-kB activation and insulin resistance

NARCIS (Netherlands)

Beek, M.H. van; Oravecz-Wilson, K.I.; Delekta, P.C.; Gu, S.; Li, X.; Jin, X.; Apel, I.J.; Konkle, K.S.; Feng, Y.; Teitelbaum, D.H.; Ruland, J.; McAllister-Lucas, L.M.; Lucas, P.C.

2012-01-01

Excess serum free fatty acids (FFAs) are fundamental to the pathogenesis of insulin resistance. With high-fat feeding, FFAs activate NF-kB in target tissues, initiating negative crosstalk with insulin signaling. However, the mechanisms underlying FFA-dependent NF-kB activation remain unclear. Here,

Inhibidores del NF-kB en la dieta y su papel en las enfermedades alérgicas

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Eloina Zárate Peñata

2017-01-01

Full Text Available El NF - κ B tiene un papel central como regulador de las respuestas inflamatoria e inmune. Se encuentra en forma inactiva en el citoplasma de las células. Después de la activación de estas, el NF - κ B se disocia de su proteína inhibidora y se transloca al núcleo, donde participa en la transcripción de genes como los de las citoquinas inflamatorias, moléculas de adhesión, inmu - noglobulinas y diversos receptores presentes en células de la respuesta inmune, entre otros. Este factor de transcripción posee un grupo de inhibidores fisiológicos y no fisiológicos. Dentro de los no fisiológicos se destacan algunos presentes en la dieta, como los carotenoides y los polifenoles, que reducen su actividad como inductor transcripcional. Diversos estudios epidemiológicos muestran que el consumo de frutas y verduras protege del desarrollo de alergias. Se ha postulado que este efecto protector se debe al contenido de polife - noles y carotenoides presentes en estos alimentos. Estos compuestos actúan en diversos niveles de la respuesta inmune de tipo alérgico. Inhibiendo las citoquinas T h2, el infiltrado de células inflamatorias en los tejidos, la síntesis de I g E y la liberación de mediadores farmacológicos, entre otras. Esto debido al efecto de estos compuestos sobre la fosforilación, ubiquitinación y degradación de diversas proteínas que participan en los procesos de inhibición y/o activación del NF - κ B . En esta revisión analizamos aspectos moleculares del NF - κ B y describimos inhibidores presentes en la dieta, como polifenoles y carotenoides, su papel en los procesos inflamatorios de tipo alérgico y en el desarrollo de enfermedades alérgicas.

Compact modelling of InAlN/GaN HEMT for low noise applications

International Nuclear Information System (INIS)

Sakalas, P; Šimukovič, A; Matulionis, A; Piotrowicz, S; Jardel, O; Delage, S L; Mukherjee, A

2014-01-01

This paper presents results of high-frequency noise modelling of InAlN/GaN high electron mobility transistors (HEMTs) with different formulations of the minimum noise figure NF min . Current–voltage characteristics and s-parameters of 0.15 μm gate length and 2 × 75 μm gate width InAlN/GaN HEMTs were measured at room temperature in a wide frequency range (300 MHz to 50 GHz) and bias range (V GS from −4.8 to 1 V and V DS from 0 to 21 V). Both the EEHEMT1 and Angelov GaN compact models yielded excellent agreement for transfer and output characteristics, transconductance g m , and f T , f max. High-frequency noise parameters NF min , R n , Γ OPT of InAlN/GaN HEMT were measured in 8–50 GHz frequency band. Noise formulation within the EEHEMT1 model underestimates the measured NF min and R n . The well known three-parameter PRC noise model is in a better agreement with the measured data but neglects the shot noise resulting from the gate leakage. The inductive degenerated source matching method and EEHEMT1 were used to design a single stage LNA operated at 8 GHz frequency. A 10 dB gain with an input reflection of −12 dB with a 2.5 dB of noise factor were obtained at 8 GHz. (paper)

Direct non transcriptional role of NF-Y in DNA replication.

Science.gov (United States)

Benatti, Paolo; Belluti, Silvia; Miotto, Benoit; Neusiedler, Julia; Dolfini, Diletta; Drac, Marjorie; Basile, Valentina; Schwob, Etienne; Mantovani, Roberto; Blow, J Julian; Imbriano, Carol

2016-04-01

NF-Y is a heterotrimeric transcription factor, which plays a pioneer role in the transcriptional control of promoters containing the CCAAT-box, among which genes involved in cell cycle regulation, apoptosis and DNA damage response. The knock-down of the sequence-specific subunit NF-YA triggers defects in S-phase progression, which lead to apoptotic cell death. Here, we report that NF-Y has a critical function in DNA replication progression, independent from its transcriptional activity. NF-YA colocalizes with early DNA replication factories, its depletion affects the loading of replisome proteins to DNA, among which Cdc45, and delays the passage from early to middle-late S phase. Molecular combing experiments are consistent with a role for NF-Y in the control of fork progression. Finally, we unambiguously demonstrate a direct non-transcriptional role of NF-Y in the overall efficiency of DNA replication, specifically in the DNA elongation process, using a Xenopus cell-free system. Our findings broaden the activity of NF-Y on a DNA metabolism other than transcription, supporting the existence of specific TFs required for proper and efficient DNA replication. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Hydrogen bonded networks in formamide [HCONH2]n (n = 1 – 10 ...

Indian Academy of Sciences (India)

gns

Table S1: Comparison of interaction energy (I.E) in kcal/mol in four arrangements of formamide n=1-10 at B3LYP/D95** level of theory. n = #monomers. Table S2: O---H bond length (in Å) for formamide clusters n = (2-10). Table S3: N-H bond stretching frequency (in cm-1) for four arrangements of formamide clusters n.

Regulation of Fn14 Receptor and NF-κB Underlies Inflammation in Meniere’s Disease

Directory of Open Access Journals (Sweden)

Lidia Frejo

2017-12-01

Full Text Available Meniere’s disease (MD is a rare disorder characterized by episodic vertigo, sensorineural hearing loss, tinnitus, and aural fullness. It is associated with a fluid imbalance between the secretion of endolymph in the cochlear duct and its reabsorption into the subarachnoid space, leading to an accumulation of endolymph in the inner ear. Epidemiological evidence, including familial aggregation, indicates a genetic contribution and a consistent association with autoimmune diseases (AD. We conducted a case–control study in two phases using an immune genotyping array in a total of 420 patients with bilateral MD and 1,630 controls. We have identified the first locus, at 6p21.33, suggesting an association with bilateral MD [meta-analysis leading signal rs4947296, OR = 2.089 (1.661–2.627; p = 1.39 × 10−09]. Gene expression profiles of homozygous genotype-selected peripheral blood mononuclear cells (PBMCs demonstrated that this region is a trans-expression quantitative trait locus (eQTL in PBMCs. Signaling analysis predicted several tumor necrosis factor-related pathways, the TWEAK/Fn14 pathway being the top candidate (p = 2.42 × 10−11. This pathway is involved in the modulation of inflammation in several human AD, including multiple sclerosis, systemic lupus erythematosus, or rheumatoid arthritis. In vitro studies with genotype-selected lymphoblastoid cells from patients with MD suggest that this trans-eQTL may regulate cellular proliferation in lymphoid cells through the TWEAK/Fn14 pathway by increasing the translation of NF-κB. Taken together; these findings suggest that the carriers of the risk genotype may develop an NF-κB-mediated inflammatory response in MD.

Synergistic activation of NF-κB by nontypeable H. influenzae and S. pneumoniae is mediated by CK2, IKKβ-IκBα, and p38 MAPK

International Nuclear Information System (INIS)

Kweon, Soo-Mi; Wang, Beinan; Rixter, Davida; Lim, Jae Hyang; Koga, Tomoaki; Ishinaga, Hajime; Chen, L.-F.; Jono, Hirofumi; Xu Haidong; Li, J.-D.

2006-01-01

In review of the past studies on NF-κB regulation, most of them have focused on investigating how NF-κB is activated by a single inducer at a time. Given the fact that, in mixed bacterial infections in vivo, multiple inflammation inducers, including both nontypeable Haemophilus influenzae (NTHi) and Streptococcus pneumoniae, are present simultaneously, a key issue that has yet to be addressed is whether NTHi and S. pneumoniae simultaneously activate NF-κB and the subsequent inflammatory response in a synergistic manner. Here, we show that NTHi and S. pneumoniae synergistically induce NF-κB-dependent inflammatory response via activation of multiple signaling pathways in vitro and in vivo. The classical IKKβ-IκBα and p38 MAPK pathways are involved in synergistic activation of NF-κB via two distinct mechanisms, p65 nuclear translocation-dependent and -independent mechanisms. Moreover, casein kinase 2 (CK2) is involved in synergistic induction of NF-κB via a mechanism dependent on phosphorylation of p65 at both Ser536 and Ser276 sites. These studies bring new insights into the molecular mechanisms underlying the NF-κB-dependent inflammatory response in polymicrobial infections and may lead to development of novel therapeutic strategies for modulating inflammation in mixed infections for patients with otitis media and chronic obstructive pulmonary diseases

Binimetinib inhibits MEK and is effective against neuroblastoma tumor cells with low NF1 expression

International Nuclear Information System (INIS)

Woodfield, Sarah E.; Zhang, Linna; Scorsone, Kathleen A.; Liu, Yin; Zage, Peter E.

2016-01-01

Novel therapies are needed for children with high-risk and relapsed neuroblastoma. We hypothesized that MAPK/ERK kinase (MEK) inhibition with the novel MEK1/2 inhibitor binimetinib would be effective in neuroblastoma preclinical models. Levels of total and phosphorylated MEK and extracellular signal-regulated kinase (ERK) were examined in primary neuroblastoma tumor samples and in neuroblastoma cell lines by Western blot. A panel of established neuroblastoma tumor cell lines was treated with increasing concentrations of binimetinib, and their viability was determined using MTT assays. Western blot analyses were performed to examine changes in total and phosphorylated MEK and ERK and to measure apoptosis in neuroblastoma tumor cells after binimetinib treatment. NF1 protein levels in neuroblastoma cell lines were determined using Western blot assays. Gene expression of NF1 and MEK1 was examined in relationship to neuroblastoma patient outcomes. Both primary neuroblastoma tumor samples and cell lines showed detectable levels of total and phosphorylated MEK and ERK. IC 50 values for cells sensitive to binimetinib ranged from 8 nM to 1.16 μM, while resistant cells did not demonstrate any significant reduction in cell viability with doses exceeding 15 μM. Sensitive cells showed higher endogenous expression of phosphorylated MEK and ERK. Gene expression of NF1, but not MEK1, correlated with patient outcomes in neuroblastoma, and NF1 protein expression also correlated with responses to binimetinib. Neuroblastoma tumor cells show a range of sensitivities to the novel MEK inhibitor binimetinib. In response to binimetinib, sensitive cells demonstrated complete loss of phosphorylated ERK, while resistant cells demonstrated either incomplete loss of ERK phosphorylation or minimal effects on MEK phosphorylation, suggesting alternative mechanisms of resistance. NF1 protein expression correlated with responses to binimetinib, supporting the use of NF1 as a biomarker to identify

Styrene process condensate treatment with a combination process of UF and NF for reuse.

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Wang, Aijun; Liu, Guangmin; Huang, Jin; Wang, Lijuan; Li, Guangbin; Su, Xudong; Qi, Hong

2013-01-15

Aiming at reusing the SPC to save water resource and heat energy, a combination treatment process of UF/NF was applied to remove inorganic irons, suspended particles and little amount of organic contaminants in this article. To achieve the indexes of CODM≤5.00 mg L(-1), oil≤2.00 mg L(-1), conductivity≤10.00 μs cm(-1), pH of 6.0-8.0, the NF membrane process was adopted. It was necessary to employ a pretreatment process to reduce NF membrane fouling. Hence UF membrane as an efficient pretreatment unit was proposed to remove the inorganic particles, such as iron oxide catalyst, to meet the influent demands of NF. The effluent of UF, which was less than 0.02 mg L(-1) of total iron, went into a security filter and then was pumped into the NF process unit. High removal efficiencies of CODM, oil and conductivity were achieved by using NF process. The ABS grafting copolymerization experiment showed that the effluent of the combination process met the criteria of ABS production process, meanwhile the process could alleviate the environment pollution. It was shown that this combination process concept was feasible and successful in treating the SPC. Copyright © 2012 Elsevier B.V. All rights reserved.

Epigenetic down-regulated DDX10 promotes cell proliferation through Akt/NF-κB pathway in ovarian cancer

International Nuclear Information System (INIS)

Gai, Muhuizi; Bo, Qifang; Qi, Lixia

2016-01-01

Ovarian cancer contributes to the majority of ovarian cancer, while the molecular mechanisms remain elusive. Recently, some DEAD box protein 1 has been reported play a tumor suppressor role in ovarian cancer progression. However, the functions of DEAD box protein (DDX) members in ovarian cancer development remain largely unknown. In current study, we retrieved GEO databases and surprisingly found that DDX10 is significantly down-regulated in ovarian cancer tissues compared with normal ovary. These findings suggest that DDX10 might also play a suppressive role in ovarian cancer. We then validated the down-regulated expression pattern of DDX10 in fresh ovarian cancer tissues. Furthermore, both loss- and gain-functions assays reveal that the down-regulated DDX10 could promote ovarian cancer proliferation in vitro and the xenograft subcutaneous tumor formation assays confirmed these findings in vivo. In addition, we found that DDX10 is epigenetic silenced by miR-155-5p in ovarian cancer. Moreover, we further preliminary illustrated that down-regulated DDX10 promotes ovarian cancer cell proliferation through Akt/NF-κB pathway. Taken together, in current study, we found a novel tumor suppressor, DDX10, is epigenetic silenced by miR-155-5p in ovarian cancer, and the down-regulated expression pattern of DDX10 promotes ovarian cancer proliferation through Akt/NF-κB pathway. Our findings shed the light that DDX families might be a novel for ovarian cancer treatment. - Highlights: • A novel DEAD box protein, DDX10 is significantly down-regulated in ovarian cancer tissues. • Down-regulated DDX10 promotes ovarian cancer cell proliferation and growth both in vitro and in vivo. • miR-155-5p is highly expressed in ovarian cancer tissues and epigenetically targets DDX10. • DDX10 and miR-155-5p regulates Akt/p65 axis in ovarian cancer cells.

Epigenetic down-regulated DDX10 promotes cell proliferation through Akt/NF-κB pathway in ovarian cancer

Energy Technology Data Exchange (ETDEWEB)

Gai, Muhuizi; Bo, Qifang; Qi, Lixia, E-mail: lixiaqi_dph@sina.com

2016-01-22

Ovarian cancer contributes to the majority of ovarian cancer, while the molecular mechanisms remain elusive. Recently, some DEAD box protein 1 has been reported play a tumor suppressor role in ovarian cancer progression. However, the functions of DEAD box protein (DDX) members in ovarian cancer development remain largely unknown. In current study, we retrieved GEO databases and surprisingly found that DDX10 is significantly down-regulated in ovarian cancer tissues compared with normal ovary. These findings suggest that DDX10 might also play a suppressive role in ovarian cancer. We then validated the down-regulated expression pattern of DDX10 in fresh ovarian cancer tissues. Furthermore, both loss- and gain-functions assays reveal that the down-regulated DDX10 could promote ovarian cancer proliferation in vitro and the xenograft subcutaneous tumor formation assays confirmed these findings in vivo. In addition, we found that DDX10 is epigenetic silenced by miR-155-5p in ovarian cancer. Moreover, we further preliminary illustrated that down-regulated DDX10 promotes ovarian cancer cell proliferation through Akt/NF-κB pathway. Taken together, in current study, we found a novel tumor suppressor, DDX10, is epigenetic silenced by miR-155-5p in ovarian cancer, and the down-regulated expression pattern of DDX10 promotes ovarian cancer proliferation through Akt/NF-κB pathway. Our findings shed the light that DDX families might be a novel for ovarian cancer treatment. - Highlights: • A novel DEAD box protein, DDX10 is significantly down-regulated in ovarian cancer tissues. • Down-regulated DDX10 promotes ovarian cancer cell proliferation and growth both in vitro and in vivo. • miR-155-5p is highly expressed in ovarian cancer tissues and epigenetically targets DDX10. • DDX10 and miR-155-5p regulates Akt/p65 axis in ovarian cancer cells.

Curcumin improves prostanoid ratio in diabetic mesenteric arteries associated with cyclooxygenase-2 and NF-κB suppression

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Patumraj S

2010-12-01

Full Text Available Sirada Rungseesantivanon1, Naris Thengchaisri4, Preecha Ruangvejvorachai2, Suthiluk Patumraj31Interdepartment of Physiology, Graduate School, 2Department of Pathology, 3Department of Physiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; 4Department of Companion Animal Clinical Sciences, Faculty of Veterinary Medicine, Kasetsart University, Bangkok, ThailandBackground: Curcumin, the active ingredient from turmeric rhizomes, has been shown to have a wide range of pharmacological properties including antioxidant and anti-inflammatory effects. Curcumin has been reviewed for its multiple molecular action on inhibiting tumor angiogenesis via its mechanisms of cyclooxygenase (COX-2, and vascular endothelial growth factor (VEGF inhibition. In this present study, we aimed to assess the effects of curcumin on preventing diabetes-induced vascular dysfunction in association with COX-2, nuclear factor-κB (NF-κB expression, and prostanoid production.Methods: Twelve-week-old male Wistar rats were separated into five groups: 1 diabetes with 0.9% normal saline (DM-NSS; n = 10, 2 diabetes treated with curcumin 30 mg/kg (n = 10, 3 diabetes treated with curcumin 300 mg/kg (n = 10, 4 the control with 0.9% normal saline (n = 10, and 5 the control treated with 300 mg/kg (n = 10. Daily oral feeding of curcumin was started at 6 weeks after the streptozotocin injection. Levels of 6-keto prostaglandin (PG F1α and thromboxane (TX B2 were determined from mesenteric perfusates using enzyme immunoassay kits. Protein kinase C (PKC-ßII and COX-2 with NF-κB levels were analyzed in the mesenteric arteries by immunofluorescent staining and immunohistochemistry, respectively.Results: The ratio of 6-keto-PGF1α and TXB2 was significantly decreased in DM-NSS compared with the control (P < 0.05. Double-immunofluorescent staining with specific antibodies for PKC-βII and a-smooth muscle actins showed that the diabetic mesenteric arteries contained increased

Local and Systemic IKKε and NF-κB Signaling Associated with Sjögren’s Syndrome Immunopathogenesis

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Weiqian Chen

2015-01-01

Full Text Available The activated NF-κB signaling pathway plays an important role in pathogenesis of primary Sjögren’s syndrome (pSS. The inhibitor of κB (IκB kinase (IKK family such as IKKα, IKKβ, IKKγ, and IKKε, is required for this signaling. Our aim was to investigate the role of IKKα/β/γ/ε in patients with untreated pSS. In minor salivary glands from pSS patients, phosphorylated IKKε (pIKKε, pIκBα, and pNF-κB p65 (p-p65 were highly expressed in ductal epithelium and infiltrating mononuclear cells by immunohistochemistry, compared to healthy individuals. pIKKα/β and pIKKγ were both negative. And pIKKε positively related to expression of p-p65. Furthermore, pIKKε and p-p65 expression significantly correlated with biopsy focus score and overall disease activity. Meanwhile, in peripheral blood mononuclear cells from pSS patients, pIKKε, total IKKε, pIKKα/β, and p-p65 were significantly increased by western blot, compared to healthy controls. However, there was no difference in IKKγ and IκBα between pSS patients and healthy individuals. These results demonstrated an abnormality of IKKε, IκBα, and NF-κB in pSS, suggesting a potential target of treatment for pSS based on the downregulation of IKKε expression and deregulation of NF-κB pathway.

Influence of 17β-estradiol treatment on the expression of NF-κB in complete hydatidiform mole culture

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Tatit Nurseta

2013-12-01

Full Text Available Background:  Genetic evidence has established a role of nuclear factor kappa B (NF-κB signaling in oncogenesis. However, activity of NF-κB in complete hydatidiform mole (CHM cell culture under 17β-estradiol (E2 treatment is not yet known. Recently, a positive cross-talk between estrogen receptor (ER and NF-κB to promote survival and progress of cancer cells to a more aggressive phenotype was established. In the present study, we examined the influence of E2 treatment on the NF-κB expression in CHM’s culture.Methods:  This experimental study measured the expression of NF-κB in CHM culture treated with E2: 10, 100, 300, 600, and 1000 pg/mL and without E2. Imunohistochemistry staining was used to assess the expression of NF-κB. Microphotographs were taken using 400x magnification. Adobe photoshop CS2 was used to assess the NF-κB expression in cell nucleus. The lower the color intensity of cell RGBbv, is the higher the expression of NF-κB in cells. ANOVA test was performed to compare the expression of NF-κB.Results: NF-κB expression as indicated by color intensity in control group was 114.84 ± 9.02. NF-κB expression in E2 treatment groups were respectively: E2 10 pg/mL: 106.30 ± 13.95; E2 100 pg/mL: 82.47 ± 4.72; E2 300 pg/mL: 82.24 ± 2.67; E2 600 pg/mL: 69.05 ± 6.47; E2 1000 pg/mL: 68.49 ± 2.37. There was progressive decline in color intensity of cells with E2 treatment indicating the increase expression of NF-κB. Significant differences with the control group occurred in doses of E2 100, 300, 600, dan 1000 pg/mL.Conclusion: Treatment of CHM trophoblast culture with escalating doses of E2 was associated with the increase of NF-κB expression in a dose dependent manner. (Med J Indones. 2013;22:197-201. doi: 10.13181/mji.v22i4.599Keywords: 17-β Estradiol, Hydatidiform mole, NF-κB

27 CFR 21.65 - Formula No. 38-B.

Science.gov (United States)

2010-04-01

.... Cinnamic aldehyde, N.F. IX. Cinnamon oil, N.F. Citronella oil, natural. Clove oil, N.F. Coal tar, U.S.P....P. Methyl salicylate, N.F. Mustard oil, volatile (allyl isothiocyanate), U.S.P. XII. Peppermint oil... pounds of any one, or a total of 10 pounds of two or more, of the oils and substances listed below: Alpha...

C26 cancer-induced muscle wasting is IKKβ-dependent and NF-kappaB-independent.

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Evangeline W Cornwell

Full Text Available Existing data suggest that NF-kappaB signaling is a key regulator of cancer-induced skeletal muscle wasting. However, identification of the components of this signaling pathway and of the NF-κB transcription factors that regulate wasting is far from complete. In muscles of C26 tumor bearing mice, overexpression of dominant negative (d.n. IKKβ blocked muscle wasting by 69% and the IκBα-super repressor blocked wasting by 41%. In contrast, overexpression of d.n. IKKα or d.n. NIK did not block C26-induced wasting. Surprisingly, overexpression of d.n. p65 or d.n. c-Rel did not significantly affect muscle wasting. Genome-wide mRNA expression arrays showed upregulation of many genes previously implicated in muscle atrophy. To test if these upregulated genes were direct targets of NF-κB transcription factors, we compared genome-wide p65 binding to DNA in control and cachectic muscle using ChIP-sequencing. Bioinformatic analysis of ChIP-sequencing data from control and C26 muscles showed very little p65 binding to genes in cachexia and little to suggest that upregulated p65 binding influences the gene expression associated with muscle based cachexia. The p65 ChIP-seq data are consistent with our finding of no significant change in protein binding to an NF-κB oligonucleotide in a gel shift assay, no activation of a NF-κB-dependent reporter, and no effect of d.n.p65 overexpression in muscles of tumor bearing mice. Taken together, these data support the idea that although inhibition of IκBα, and particularly IKKβ, blocks cancer-induced wasting, the alternative NF-κB signaling pathway is not required. In addition, the downstream NF-κB transcription factors, p65 and c-Rel do not appear to regulate the transcriptional changes induced by the C26 tumor. These data are consistent with the growing body of literature showing that there are NF-κB-independent substrates of IKKβ and IκBα that regulate physiological processes.

Circuló la edición número 10.000. EL PAÍS de Madrid y su liderazgo

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Juan Varela

2015-01-01

Full Text Available El País (1978 renovador del periodismo, diario identificado como conservador en economía, de centro izquierda en lo político y más radical en los temas sociales, en el 2004 acaba de publicar la edición 10.000 luego de 28 años como líder de la prensa española.

Identification and characterization of NF-YB family genes in tung tree.

Science.gov (United States)

Yang, Susu; Wang, Yangdong; Yin, Hengfu; Guo, Haobo; Gao, Ming; Zhu, Huiping; Chen, Yicun

2015-12-01

The NF-YB transcription factor gene family encodes a subunit of the CCAAT box-binding factor (CBF), a highly conserved trimeric activator that strongly binds to the CCAAT box promoter element. Studies on model plants have shown that NF-YB proteins participate in important developmental and physiological processes, but little is known about NF-YB proteins in trees. Here, we identified seven NF-YB transcription factor-encoding genes in Vernicia fordii, an important oilseed tree in China. A phylogenetic analysis separated the genes into two groups; non-LEC1 type (VfNF-YB1, 5, 7, 9, 11, 13) and LEC1-type (VfNF-YB 14). A gene structure analysis showed that VfNF-YB 5 has three introns and the other genes have no introns. The seven VfNF-YB sequences contain highly conserved domains, a disordered region at the N terminus, and two long helix structures at the C terminus. Phylogenetic analyses showed that VfNF-YB family genes are highly homologous to GmNF-YB genes, and many of them are closely related to functionally characterized NF-YBs. In expression analyses of various tissues (root, stem, leaf, and kernel) and the root during pathogen infection, VfNF-YB1, 5, and 11 were dominantly expressed in kernels, and VfNF-YB7 and 9 were expressed only in the root. Different VfNF-YB family genes showed different responses to pathogen infection, suggesting that they play different roles in the pathogen response. Together, these findings represent the first extensive evaluation of the NF-YB family in tung tree and provide a foundation for dissecting the functions of VfNF-YB genes in seed development, stress adaption, fatty acid synthesis, and pathogen response.

N S Saxena

Indian Academy of Sciences (India)

Home; Journals; Bulletin of Materials Science. N S Saxena. Articles written in Bulletin of Materials Science. Volume 23 Issue 5 October 2000 pp 369-375 Glasses. Differential scanning calorimetry studies of Se85Te15–Pb ( = 4, 6, 8 and 10) glasses · N B Maharajan N S Saxena Deepika Bhandari Mousa M Imran D D ...

Masses and decay constants of D(s) * and B(s) * mesons with Nf=2 +1 +1 twisted mass fermions

Science.gov (United States)

Lubicz, V.; Melis, A.; Simula, S.; ETM Collaboration

2017-08-01

We present a lattice calculation of the masses and decay constants of D(s) * and B(s) * mesons using the gauge configurations produced by the European Twisted Mass Collaboration (ETMC) with Nf=2 +1 +1 dynamical quarks at three values of the lattice spacing a ˜(0.06 -0.09 ) fm . Pion masses are simulated in the range Mπ≃(210 - 450 ) MeV , while the strange and charm sea-quark masses are close to their physical values. We compute the ratios of vector to pseudoscalar masses and decay constants for various values of the heavy-quark mass mh in the range 0.7 mcphys≲mh≲3 mcphys . In order to reach the physical b -quark mass, we exploit the heavy quark effective theory prediction that, in the static limit of infinite heavy-quark mass, the considered ratios are equal to one. At the physical point our results are MD*/MD=1.0769 (79 ) , MDs*/MDs=1.0751(56 ), fD*/fD=1.078 (36 ), fDs*/fD s=1.087 (20 ), MB*/MB=1.0078 (15 ), MBs*/MBs=1.0083(10 ), fB*/fB=0.958 (22 ) and fBs*/fB s=0.974 (10 ). Combining them with the experimental values of the pseudoscalar meson masses (used as input to fix the quark masses) and the values of the pseudoscalar decay constants calculated by ETMC, we get MD*=2013 (14 ), MDs*=2116 (11 ), fD*=223.5 (8.4 ), fDs*=268.8 (6.6 ), MB*=5320.5 (7.6 ), MBs*=5411.36 (5.3 ), fB*=185.9 (7.2 ) and fBs*=223.1 (5.4 ) MeV .

Pathogenesis of Germline and Somatic NF1 Rearrangements

Science.gov (United States)

1998-10-01

tilt of the occlusal plane upwards to the left and severe malocclusion class II with left cross-bite. Eye examination documented visual acuities of 6...9 on the right and 6/12 on the left, mild hypermetropia, mild amblyopia , divergent strabismus and Lisch nodules. He had minor webbing of the neck... therapy -related myeloid leukemias in Nf +1- mice show both LOH and disomy at the NF1 locus (N. Mahgoub et al, submitted). How do the LOH regions

In silico CrNF, a half-metallic ferromagnetic nitride–fluoride mimicking CrO2

International Nuclear Information System (INIS)

Matar, Samir F.

2014-01-01

Isoelectronic with CrO 2 , CrNF is proposed in silico based on rutile derived structures with DFT computations. The ground state structure defined from cohesive energies is of MgUO 4 -type, characterized by short covalent Cr–N and long ionic Cr–F distances. Like CrO 2 it is a half-metallic ferromagnet with M=2 μ B /FU integer magnetization with reduced band gap at minority spins. Major difference of magnetic response to pressure characterizes CrNF as a soft ferromagnet versus hard magnetic CrO 2 . The chemical bonding properties point to prevailing covalent Cr–N versus ionic Cr–F bonding. Different synthesis routes are examined. - Highlights: • DFT identification of CrNF is based on isoelectronicity and rutile derivatives. • Similarly to CrO 2 , CrNF is a half-metallic ferromagnet with reduced band gap. • Strong pressure dependence of magnetization of CrNF oppositely to CrO 2 . • Covalent Cr–N bonding prevails in spite of the presence of ionic Cr–F. • Cohesive energies favor the synthesis for which protocols are proposed

Generation and quenching of NF(a) and NF(b) molecules

International Nuclear Information System (INIS)

Setser, D.W.; Cha, H.; Quinones, E.; Du, K.

1987-01-01

The Ar( 3 Po,2) + NF 2 and 2F + HN 3 reactions have been developed as sources of NF(b 1 Σ + ) and NF(a 1 Δ) molecules, respectively, in a flow reactor. The decay kinetics for these molecules in the presence of added reagent can be studied using standard flow reactor techniques. Room temperature quenching rate constants for both molecules are reported for several reagents and compared to results for the isoelectronic O 2 (a) and O 2 (b) molecules

Prevalence of bortezomib-resistant constitutive NF-kappaB activity in mantle cell lymphoma

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Kahl Brad S

2008-05-01

Full Text Available Abstract Background The proteasome inhibitor bortezomib can inhibit activation of the transcription factor NF-κB, a mechanism implicated in its anti-neoplastic effects observed in mantle cell lymphoma (MCL. However, NF-κB can be activated through many distinct mechanisms, including proteasome independent pathways. While MCL cells have been shown to harbor constitutive NF-κB activity, what fraction of this activity in primary MCL samples is sensitive or resistant to inhibition by bortezomib remains unclear. Results Proteasome activity in the EBV-negative MCL cell lines Jeko-1 and Rec-1 is inhibited by greater than 80% after exposure to 20 nM bortezomib for 4 hours. This treatment decreased NF-κB activity in Jeko-1 cells, but failed to do so in Rec-1 cells when assessed by electrophoretic mobility shift assay (EMSA. Concurrently, Rec-1 cells were more resistant to the cytotoxic effects of bortezomib than Jeko-1 cells. Consistent with a proteasome inhibitor resistant pathway of activation described in mouse B-lymphoma cells (WEHI231 and a breast carcinoma cell line (MDA-MB-468, the bortezomib-resistant NF-κB activity in Rec-1 cells is inhibited by calcium chelators, calmodulin inhibitors, and perillyl alcohol, a monoterpene capable of blocking L-type calcium channels. Importantly, the combination of perillyl alcohol and bortezomib is synergistic in eliciting Rec-1 cell cytotoxicity. The relevance of these results is illuminated by the additional finding that a considerable fraction of primary MCL samples (8 out of 10 displayed bortezomib-resistant constitutive NF-κB activity. Conclusion Our findings show that bortezomib-resistant NF-κB activity is frequently observed in MCL samples and suggest that this activity may be relevant to MCL biology as well as serve as a potential therapeutic target.

The chiral critical line of $N_{f}=2+1$ QCD at ero and non-zero baryon density

CERN Document Server

De Forcrand, Philippe; Forcrand, Philippe de; Philipsen, Owe

2007-01-01

We present numerical results for the location of the chiral critical line at finite temperature and zero and non-zero baryon density for QCD with N_f=2+1 flavours of staggered fermions on lattices with temporal extent N_t=4. For degenerate quark masses, we compare our results obtained with the exact RHMC algorithm with earlier, inexact R-algorithm results and find a reduction of 25% in the critical quark mass, for which the first order phase transition changes to a smooth crossover. Extending our analysis to non-degenerate quark masses, we map out the chiral critical line up to the neighbourhood of the physical point, which we confirm to be in the crossover region. Our data are consistent with a tricritical point at a strange quark mass of ~500 MeV. Finally, we investigate the shift of the critical line with finite baryon density, by simulating with an imaginary chemical potential for which there is no sign problem. We observe this shift to be very small or, conversely, the critical endpoint \\mu^c(m_{u,d},m_s...

10−7 m 17β-oestradiol enhances odonto/osteogenic potency of human dental pulp stem cells by activation of the NF-κB pathway

Science.gov (United States)

Wang, Y; Zheng, Y; Wang, Z; Li, J; Wang, Z; Zhang, G; Yu, J

2013-01-01

Objectives Oestrogen has been proven to significantly enhance osteogenic potency, while oestrogen deficiency usually leads to impaired osteogenic differentiation of mesenchymal stem cells. However, little is known concerning direct effects of oestrogen on differentiation of human dental pulp stem cells (DPSCs). Materials and methods In this study, human DPSCs were isolated and treated with 10−7 m 17β-oestradiol (E2). Alkaline phosphatase (ALP) assay and alizarin red staining were performed. Results Alkaline phosphatase and alizarin red showed that E2 treatment significantly enhanced ALP activity and mineralization ability of DPSCs, but had no effect on cell proliferation. Real-time RT-PCR and western blot assay demonstrated that odonto/osteogenic markers (ALP, RUNX2/RUNX2, OSX/OSX, OCN/OCN and DSPP/DSP) were significantly upregulated in the cells after E2 treatment. Moreover, phosphorylation of cytoplasmic IκBα/P65 and expression of nuclear P65 were enhanced in a time-dependent manner following E2 treatment, suggesting activation of NF-κB signaling. Conversely, inhibition of the NF-κB pathway suppressed E2-mediated upregulation of odonto/osteogenic markers, indicating that the NF-κB pathway was pivotal for E2-mediated differentiation. Conclusion These findings provide evidence that 10−7 m 17β-oestradiol promoted odonto/osteogenic differentiation of human DPSCs via activation of the NF-κB signaling pathway. PMID:24152244

Large-nf contributions to the four-loop splitting functions in QCD

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J. Davies

2017-02-01

Full Text Available We have computed the fourth-order nf2 contributions to all three non-singlet quark–quark splitting functions and their four nf3 flavour-singlet counterparts for the evolution of the parton distributions of hadrons in perturbative QCD with nf effectively massless quark flavours. The analytic form of these functions is presented in both Mellin N-space and momentum-fraction x-space; the large-x and small-x limits are discussed. Our results agree with all available predictions derived from lower-order information. The large-x limit of the quark–quark cases provides the complete nf2 part of the four-loop cusp anomalous dimension which agrees with two recent partial computations.

Expresión vascular de factores de transcripción proinflamatorios en un modelo de síndrome metabólico

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Nicolás Renna

2007-01-01

Full Text Available Con el objetivo de estudiar la expresión de factores de transcripción sensibles a redox en las arterias en un modelo experimental de hipertensión arterial asociada con síndromemetabólico (FFHR, ratas Wistar Kyoto (WKY y espontáneamente hipertensas (SHR macho de 30 días fueron distribuidas en forma aleatoria en cuatro grupos (n = 8 c/u: 1 WKY (control, 2 FFR: administración de fructosa 10% P/V en el agua de bebida durante unperíodo de 10 semanas, 3 SHR y 4 FFHR: ídem 3 + 2. Los grupos FFR y FFHR presentaron valores de HOMA y área bajo la curva en la prueba de tolerancia característicos de resistencia a la insulina. También mostraron diferencias significativas en los niveles de triglicéridos y colesterol HDL respecto de sus controles y aumentaron su presión arterial sistólica. El estado de estrés oxidativo, demostrado por la actividad de NAD(PH oxidasa y TBARS fue significativamente mayor en FFR y FFHR, en tanto que en estos mismos grupos disminuyó significativamente la actividad de eNOS. El peso cardíacorelativo aumentó en FFR y FFHR, con mayor área de los miocitos de la pared libre ventricular. Los cortes de arteria carótida izquierda mostraron crecimiento de su capa media de tipo eutrófico en FFHR. La densidad óptica media para los anticuerpos anti-c-fos, anti-NF-κB y anti-VCAM-1 fue mayor en las arterias renales de resistencia y en la carótida de los grupos FFHR y FFR. Los datos confirman el desarrollo del modelo experimental patológico y sugieren que el estrés oxidativo y la consecuente activación de genes que participan en el proceso inflamatorio intervienen activamente en el desarrollo de remodelación vascular.

Ability to Gain Control Over One’s Own Brain Activity and its Relation to Spiritual Practice: A Multimodal Imaging Study

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Silvia E. Kober

2017-05-01

Full Text Available Spiritual practice, such as prayer or meditation, is associated with focusing attention on internal states and self-awareness processes. As these cognitive control mechanisms presumably are also important for neurofeedback (NF, we investigated whether people who pray frequently (N = 20 show a higher ability of self-control over their own brain activity compared to a control group of individuals who rarely pray (N = 20. All participants underwent structural magnetic resonance imaging (MRI and one session of sensorimotor rhythm (SMR, 12–15 Hz based NF training. Individuals who reported a high frequency of prayer showed improved NF performance compared to individuals who reported a low frequency of prayer. The individual ability to control one’s own brain activity was related to volumetric aspects of the brain. In the low frequency of prayer group, gray matter volumes in the right insula and inferior frontal gyrus were positively associated with NF performance, supporting prior findings that more general self-control networks are involved in successful NF learning. In contrast, participants who prayed regularly showed a negative association between gray matter volume in the left medial orbitofrontal cortex (Brodmann’s area (BA 10 and NF performance. Due to their regular spiritual practice, they might have been more skillful in gating incoming information provided by the NF system and avoiding task-irrelevant thoughts.

NF45/ILF2 tissue expression, promoter analysis, and interleukin-2 transactivating function

International Nuclear Information System (INIS)

Zhao Guohua; Shi Lingfang; Qiu Daoming; Hu Hong; Kao, Peter N.

2005-01-01

NF45/ILF2 associates with NF90/ILF3 in the nucleus and regulates IL-2 gene transcription at the antigen receptor response element (ARRE)/NF-AT DNA target sequence (P.N. Kao, L. Chen, G. Brock, J. Ng, A.J. Smith, B. Corthesy, J. Biol. Chem. 269 (1994) 20691-20699). NF45 is widely expressed in normal tissues, especially testis, brain, and kidney, with a predominantly nuclear distribution. NF45 mRNA expression is increased in lymphoma and leukemia cell lines. The human and murine NF45 proteins differ only by substitution of valine by isoleucine at amino acid 142. Fluorescence in situ hybridization localized the human NF45 gene to chromosome 1q21.3, and mouse NF45 gene to chromosome 3F1. Promoter analysis of 2.5 kB of the murine NF45 gene reveals that significant activation is conferred by factors, possible including NF-Y, that bind to the CCAAT-box sequence. The function of human NF45 in regulating IL-2 gene expression was characterized in Jurkat T-cells stably transfected with plasmids directing expression of NF45 cDNA in sense or antisense orientations. NF45 sense expression increased IL-2 luciferase reporter gene activity 120-fold, and IL-2 protein expression 2-fold compared to control cells. NF45 is a highly conserved, regulated transcriptional activator, and one target gene is IL-2

The Arabidopsis NF-YA3 and NF-YA8 genes are functionally redundant and are required in early embryogenesis.

Directory of Open Access Journals (Sweden)

Monica Fornari

Full Text Available Nuclear factor Y (NF-Y is a trimeric transcription factor composed of three distinct subunits called NF-YA, NF-YB and NF-YC. In Arabidopsis thaliana, NF-Y subunits are known to play roles in many processes, such as gametogenesis, embryogenesis, seed development, drought resistance, ABA signaling, flowering time, primary root elongation, Endoplasmic Reticulum (ER stress response and blue light responses. Here, we report that the closely related NF-YA3 and NF-YA8 genes control early embryogenesis. Detailed GUS and in situ analyses showed that NF-YA3 and NF-YA8 are expressed in vegetative and reproductive tissues with the highest expression being during embryo development from the globular to the torpedo embryo stage. Plants from the nf-ya3 and nf-ya8 single mutants do not display any obvious phenotypic alteration, whereas nf-ya3 nf-ya8 double mutants are embryo lethal. Morphological analyses showed that the nf-ya3 nf-ya8 embryos fail to undergo to the heart stage and develop into abnormal globular embryos with both proembryo and suspensor characterized by a disordered cell cluster with an irregular shape, suggesting defects in embryo development. The suppression of both NF-YA3 and NF-YA8 gene expression by RNAi experiments resulted in defective embryos that phenocopied the nf-ya3 nf-ya8 double mutants, whereas complementation experiments partially rescued the abnormal globular nf-ya3 nf-ya8 embryos, confirming that NF-YA3 and NF-YA8 are required in early embryogenesis. Finally, the lack of GFP expression of the auxin responsive DR5rev::GFP marker line in double mutant embryos suggested that mutations in both NF-YA3 and NF-YA8 affect auxin response in early developing embryos. Our findings indicate that NF-YA3 and NF-YA8 are functionally redundant genes required in early embryogenesis of Arabidopsis thaliana.

The b-quark mass from non-perturbative $N_f=2$ Heavy Quark Effective Theory at $O(1/m_h)$

DEFF Research Database (Denmark)

Bernardoni, F.; Blossier, B.; Bulava, J.

2014-01-01

We report our final estimate of the b-quark mass from $N_f=2$ lattice QCD simulations using Heavy Quark Effective Theory non-perturbatively matched to QCD at $O(1/m_h)$. Treating systematic and statistical errors in a conservative manner, we obtain $\\overline{m}_{\\rm b}^{\\overline{\\rm MS}}(2 {\\rm...

Kaempferol ameliorates H9N2 swine influenza virus-induced acute lung injury by inactivation of TLR4/MyD88-mediated NF-κB and MAPK signaling pathways.

Science.gov (United States)

Zhang, Ruihua; Ai, Xia; Duan, Yongjie; Xue, Man; He, Wenxiao; Wang, Cunlian; Xu, Tong; Xu, Mingju; Liu, Baojian; Li, Chunhong; Wang, Zhijun; Zhang, Ruihong; Wang, Guohua; Tian, Shufei; Liu, Huifeng

2017-05-01

Kaempferol, a very common type of dietary flavonoids, has been found to exert antioxidative and anti-inflammatory properties. The purpose of our investigation was designed to reveal the effect of kaempferol on H9N2 influenza virus-induced inflammation in vivo and in vitro. In vivo, BALB/C mice were infected intranasally with H9N2 influenza virus with or without kaempferol treatment to induce acute lung injury (ALI) model. In vitro, MH-S cells were infected with H9N2 influenza virus with or without kaempferol treatment. In vivo, kaempferol treatment attenuated pulmonary edema, the W/D mass ratio, pulmonary capillary permeability, myeloperoxidase (MPO) activity, and the numbers of inflammatory cells. Kaempferol reduced ROS and Malondialdehyde (MDA) production, and increased the superoxide dismutase (SOD) activity. Kaempferol also reduced overproduction of TNF-α, IL-1β and IL-6. In addition, kaempferol decreased the H9N2 viral titre. In vitro, ROS, MDA, TNF-α, IL-1β and IL-6 was also reduced by kaempferol. Moreover, our data showed that kaempferol significantly inhibited the upregulation of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), phosphorylation level of IκBα and nuclear factor-κB (NF-κB) p65, NF-κB p65 DNA binding activity, and phosphorylation level of MAPKs, both in vivo and in vitro. These results suggest that kaempferol exhibits a protective effect on H9N2 virus-induced inflammation via suppression of TLR4/MyD88-mediated NF-κB and MAPKs pathways, and kaempferol may be considered as an effective drug for the potential treatment of influenza virus-induced ALI. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Reconstitution of the NF1 GAP-related domain in NF1-deficient human Schwann cells

International Nuclear Information System (INIS)

Thomas, Stacey L.; Deadwyler, Gail D.; Tang, Jun; Stubbs, Evan B.; Muir, David; Hiatt, Kelly K.; Clapp, D. Wade; De Vries, George H.

2006-01-01

Schwann cells derived from peripheral nerve sheath tumors from individuals with Neurofibromatosis Type 1 (NF1) are deficient for the protein neurofibromin, which contains a GAP-related domain (NF1-GRD). Neurofibromin-deficient Schwann cells have increased Ras activation, increased proliferation in response to certain growth stimuli, increased angiogenic potential, and altered cell morphology. This study examined whether expression of functional NF1-GRD can reverse the transformed phenotype of neurofibromin-deficient Schwann cells from both benign and malignant peripheral nerve sheath tumors. We reconstituted the NF1-GRD using retroviral transduction and examined the effects on cell morphology, growth potential, and angiogenic potential. NF1-GRD reconstitution resulted in morphologic changes, a 16-33% reduction in Ras activation, and a 53% decrease in proliferation in neurofibromin-deficient Schwann cells. However, NF1-GRD reconstitution was not sufficient to decrease the in vitro angiogenic potential of the cells. This study demonstrates that reconstitution of the NF1-GRD can at least partially reverse the transformation of human NF1 tumor-derived Schwann cells

10(-7)  m 17β-oestradiol enhances odonto/osteogenic potency of human dental pulp stem cells by activation of the NF-κB pathway.

Science.gov (United States)

Wang, Y; Zheng, Y; Wang, Z; Li, J; Wang, Z; Zhang, G; Yu, J

2013-12-01

Oestrogen has been proven to significantly enhance osteogenic potency, while oestrogen deficiency usually leads to impaired osteogenic differentiation of mesenchymal stem cells. However, little is known concerning direct effects of oestrogen on differentiation of human dental pulp stem cells (DPSCs). In this study, human DPSCs were isolated and treated with 10(-7)  m 17β-oestradiol (E2). Alkaline phosphatase (ALP) assay and alizarin red staining were performed. Alkaline phosphatase and alizarin red showed that E2 treatment significantly enhanced ALP activity and mineralization ability of DPSCs, but had no effect on cell proliferation. Real-time RT-PCR and western blot assay demonstrated that odonto/osteogenic markers (ALP, RUNX2/RUNX2, OSX/OSX, OCN/OCN and DSPP/DSP) were significantly upregulated in the cells after E2 treatment. Moreover, phosphorylation of cytoplasmic IκBα/P65 and expression of nuclear P65 were enhanced in a time-dependent manner following E2 treatment, suggesting activation of NF-κB signaling. Conversely, inhibition of the NF-κB pathway suppressed E2-mediated upregulation of odonto/osteogenic markers, indicating that the NF-κB pathway was pivotal for E2-mediated differentiation. These findings provide evidence that 10(-7)  m 17β-oestradiol promoted odonto/osteogenic differentiation of human DPSCs via activation of the NF-κB signaling pathway. © 2013 The Authors. Cell Proliferation published by John Wiley & Sons Ltd.

Effects of Different Ratio of n-6/n-3 Polyunsaturated Fatty Acids on the PI3K/Akt Pathway in Rats with Reflux Esophagitis.

Science.gov (United States)

Zhuang, Jia-Yuan; Chen, Zhi-Yao; Zhang, Tao; Tang, Du-Peng; Jiang, Xiao-Yin; Zhuang, Ze-Hao

2017-01-30

BACKGROUND We designed this study to investigate the influence of different ratios of n-6/n-3 polyunsaturated fatty acid in the diet of reflux esophagitis (RE) rats' and the effect on the PI3K/Akt pathway. MATERIAL AND METHODS RE rats were randomly divided into a sham group and modeling groups of different concentrations of n-6/n-3 polyunsaturated fatty acid (PUFA): 12:1 group, 10:1 group, 5:1 group, and 1:1 group. RT-PCR and Western-blot were used to detect the expression of PI3K, Akt, p-Akt, NF-κBp50, and NF-κBp65 proteins in esophageal tissue. RESULTS In the n-6/n-3 PUFAs groups the expression of PI3K, Akt, p-Akt, nf-κbp50, and NF-κBp65 mRNA decreased with the decrease in n-6/n-3 ratios in the diet. The lowest expression of each indicator occurred in the 1:1 n-6/n-3 group compared with other n-6/n-3 groups, the difference was statistically significant (p<0.05). CONCLUSIONS The inhibition of n-3 PUFAs in the development of esophageal inflammation in rats with RE was attributed to the function of PI3K/Akt-NF-κB signaling pathway.

Ambient temperature regulates the expression of a small set of sRNAs influencing plant development through NF-YA2 and YUC2.

Science.gov (United States)

Gyula, Péter; Baksa, Ivett; Tóth, Tamás; Mohorianu, Irina; Dalmay, Tamás; Szittya, György

2018-06-01

Plants substantially alter their developmental program upon changes in the ambient temperature. The 21-24 nt small RNAs (sRNAs) are important gene expression regulators, which play a major role in development and adaptation. However, little is known about how the different sRNA classes respond to changes in the ambient temperature. We profiled the sRNA populations in four different tissues of Arabidopsis thaliana plants grown at 15, 21 and 27 °C. We found that only a small fraction (0.6%) of the sRNA loci are ambient temperature-controlled. We identified thermoresponsive miRNAs and identified their target genes using degradome libraries. We verified that the target of the thermoregulated miR169, NF-YA2, is also ambient temperature-regulated. NF-YA2, as the component of the conserved transcriptional regulator NF-Y complex, binds the promoter of the flowering time regulator FT and the auxin biosynthesis gene YUC2. Other differentially expressed loci include thermoresponsive phased siRNA loci that target various auxin pathway genes and tRNA fragments. Furthermore, a temperature dependent 24-nt heterochromatic siRNA locus in the promoter of YUC2 may contribute to the epigenetic regulation of auxin homeostasis. This holistic approach facilitated a better understanding of the role of different sRNA classes in ambient temperature adaptation of plants. This article is protected by copyright. All rights reserved.

B-physics from Nf=2 tmQCD: the Standard Model and beyond

CERN Document Server

Carrasco, N; Dimopoulos, P; Frezzotti, R; Giménez, V; Herdoiza, G; Lubicz, V; Michael, C; Picca, E; Rossi, G C; Sanfilippo, F; Shindler, A; Silvestrini, L; Simula, S; Tarantino, C

2014-01-01

We present a lattice QCD computation of the b-quark mass, the B and B_s decay constants, the B-mixing bag parameters for the full four-fermion operator basis as well as determinations for \\xi and f_{Bq}\\sqrt{B_i^{(q)}} extrapolated to the continuum limit and to the physical pion mass. We used N_f = 2 twisted mass Wilson fermions at four values of the lattice spacing with pion masses ranging from 280 to 500 MeV. Extrapolation in the heavy quark mass from the charm to the bottom quark region has been carried out on ratios of physical quantities computed at nearby quark masses, exploiting the fact that they have an exactly known infinite mass limit. Our results are m_b(m_b, \\overline{\\rm{MS}})=4.29(12) GeV, f_{Bs}=228(8) MeV, f_{B}=189(8) MeV and f_{Bs}/f_B=1.206(24). Moreover with our results for the bag-parameters we find \\xi=1.225(31), B_1^{(s)}/B_1^{(d)}=1.01(2), f_{Bd}\\sqrt{\\hat{B}_{1}^{(d)}} = 216(10) MeV and f_{Bs}\\sqrt{\\hat{B}_{1}^{(s)}} = 262(10) MeV. We also computed the bag parameters for the complete...

Downregulation of NF-ΚB1 enhances the radiosensitivity of renal cell carcinoma

International Nuclear Information System (INIS)

Ikegami, Amanda; Silva, Luiz Felipe Teixeira da; Bellini, Maria Helena

2017-01-01

Full text: Introduction: Clear cell renal cell carcinoma (ccRCC) accounts for ∼80% of all renal cell carcinomas (RCC) and has the Von Hippel-Lindau (VHL) tumor suppressor gene mutated. The lack of VHL protein leads to a constitutionally active Hypoxia Inducible Factor (HIF) pathway that confers both chemoresistance and radioresistance for renal tumor. HIF pathway is known to interact with the transcription factor nuclear factor kappa B (NF-kB). Increased NF-κB activity is associated with the development and progression of RCC (IKEGAMI A, TEIXEIRA LF. BRAGA MS et al. The American Society for Cell Biology 2016; 26: 3948-3955). Objective: Evaluate the synergistic effect of NF-kB1 knockdown and ionizing radiation in murine renal adenocarcinoma cell line. Methods: The murine renal adenocarcinoma cell line (Renca cells) (ATCC, USA) was cultured in RPMI 1640 supplemented with 10% FBS and penicillin/streptomycin. Lentiviral shRNA vector was used to knockdown of NF-KB1 gene in Renca cells, as described previously (1). In the clonogenic cell survival assay, the cells were irradiated by 60 Co source in the range from 0 to 10 Gy, using the GammaCell 220 – Irradiation Unit of Canadian-Atomic Energy Commision Ltd. (CTR-IPEN). After 10-14 days of culture, cell colonies were fixed and stained with formaldehyde 4% and rhodamine B 2% and counted. To assess cell viability, tetrazolium [3-(4,5-dimethylthiazol-2-yl)-5- (3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-MTS] was performed within 24 hours after irradiation at a dose of 10Gy. The survival variables α e β were fitted according to the linear quadratic equation (SF=exp[-αD-βD2]); SF=survival fraction, D=dose of irradiation and P value was determined by F test. Multiple comparisons were assessed by One-way ANOVA followed by Bonferroni´s tests with GraphPad Prism version 6.0 software. P< 0.05 was considered statistically significant. Data are shown as the mean ± SD. Results: The Renca-shRNA-NF-kB1 cells were found to be

Downregulation of NF-ΚB1 enhances the radiosensitivity of renal cell carcinoma

Energy Technology Data Exchange (ETDEWEB)

Ikegami, Amanda; Silva, Luiz Felipe Teixeira da; Bellini, Maria Helena [Instituto De Pesquisas Energéticas e Nucleares (IPEN/CNEN-SP), São Paulo, SP (Brazil)

2017-07-01

Full text: Introduction: Clear cell renal cell carcinoma (ccRCC) accounts for ∼80% of all renal cell carcinomas (RCC) and has the Von Hippel-Lindau (VHL) tumor suppressor gene mutated. The lack of VHL protein leads to a constitutionally active Hypoxia Inducible Factor (HIF) pathway that confers both chemoresistance and radioresistance for renal tumor. HIF pathway is known to interact with the transcription factor nuclear factor kappa B (NF-kB). Increased NF-κB activity is associated with the development and progression of RCC (IKEGAMI A, TEIXEIRA LF. BRAGA MS et al. The American Society for Cell Biology 2016; 26: 3948-3955). Objective: Evaluate the synergistic effect of NF-kB1 knockdown and ionizing radiation in murine renal adenocarcinoma cell line. Methods: The murine renal adenocarcinoma cell line (Renca cells) (ATCC, USA) was cultured in RPMI 1640 supplemented with 10% FBS and penicillin/streptomycin. Lentiviral shRNA vector was used to knockdown of NF-KB1 gene in Renca cells, as described previously (1). In the clonogenic cell survival assay, the cells were irradiated by {sup 60}Co source in the range from 0 to 10 Gy, using the GammaCell 220 – Irradiation Unit of Canadian-Atomic Energy Commision Ltd. (CTR-IPEN). After 10-14 days of culture, cell colonies were fixed and stained with formaldehyde 4% and rhodamine B 2% and counted. To assess cell viability, tetrazolium [3-(4,5-dimethylthiazol-2-yl)-5- (3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-MTS] was performed within 24 hours after irradiation at a dose of 10Gy. The survival variables α e β were fitted according to the linear quadratic equation (SF=exp[-αD-βD2]); SF=survival fraction, D=dose of irradiation and P value was determined by F test. Multiple comparisons were assessed by One-way ANOVA followed by Bonferroni´s tests with GraphPad Prism version 6.0 software. P< 0.05 was considered statistically significant. Data are shown as the mean ± SD. Results: The Renca-shRNA-NF-kB1 cells were found

Kaon semileptonic decays with $N_f=2+1+1$ HISQ fermions and physical light-quark masses

Energy Technology Data Exchange (ETDEWEB)

Gámiz, E. [Granada U., Theor. Phys. Astrophys.; Bazavov, A. [Brookhaven; Bernard, C. [Washington U., St. Louis; DeTar, C. [Utah U.; Du, D. [Syracuse U.; El-Khadra, A. X. [Illinois U., Urbana; Freeland, E. D. [Art Inst. of Chicago; Gottlieb, Steven [Indiana U.; Heller, U. M. [APS, New York; Komijani, J. [TUM-IAS, Munich; Kronfeld, A. S. [Fermilab; Laiho, J. [Syracuse U.; Mackenzie, P. B. [Fermilab; Neil, E. T. [Colorado U.; Primer, T. [Arizona U.; Simone, J. N. [Fermilab; Sugar, R. [UC, Santa Barbara; Toussaint, D. [Arizona U.; Van de Water, R. S. [Fermilab; Zhou, Ran [Fermilab

2016-11-13

We discuss the reduction of errors in the calculation of the form factor $f_+^{K \\pi}(0)$ with HISQ fermions on the $N_f=2+1+1$ MILC configurations from increased statistics on some key ensembles, new data on ensembles with lattice spacings down to 0.042 fm and the study of finite-volume effects within staggered ChPT. We also study the implications for the unitarity of the CKM matrix in the first row and for current tensions with leptonic determinations of $\\vert V_{us}\\vert$.

Endothelial glutathione-S-transferase A4-4 protects against oxidative stress and modulates iNOS expression through NF-κB translocation

International Nuclear Information System (INIS)

Yang Yongzhen; Yang Yusong; Xu Ya; Lick, Scott D.; Awasthi, Yogesh C.; Boor, Paul J.

2008-01-01

Our recent work in endothelial cells and human atherosclerotic plaque showed that overexpression of glutathione-S-tranferases (GSTs) in endothelium protects against oxidative damage from aldehydes such as 4-HNE. Nuclear factor (NF)-κB plays a crucial role during inflammation and immune responses by regulating the expression of inducible genes such as inducible nitric oxide synthase (iNOS). 4-HNE induces apoptosis and affects NF-κB mediated gene expression, but conflicting results on 4-HNE's effect on NF-κB have been reported. We compared the effect of 4-HNE on iNOS and the NF-κB pathway in control mouse pancreatic islet endothelial (MS1) cells and those transfected with mGSTA4, a α-class GST with highest activity toward 4-HNE. When treated with 4-HNE, mGSTA4-transfected cells showed significant upregulation of iNOS and nitric oxide (NO) through (NF)-κB (p65) translocation in comparison with wild-type or vector-transfected cells. Immunohistochemical studies of early human plaques showed lower 4-HNE content and upregulation of iNOS, which we take to indicate that GSTA4-4 induction acts as an enzymatic defense against high levels of 4-HNE, since 4-HNE accumulated in more advanced plaques, when detoxification and exocytotic mechanisms are likely to be overwhelmed. These studies suggest that GSTA4-4 may play an important defensive role against atherogenesis through detoxification of 4-HNE and upregulation of iNOS

NF-kappa B genes have a major role in Inflammatory Breast Cancer

International Nuclear Information System (INIS)

Lerebours, Florence; Vacher, Sophie; Andrieu, Catherine; Espie, Marc; Marty, Michel; Lidereau, Rosette; Bieche, Ivan

2008-01-01

IBC (Inflammatory Breast cancer) is a rare form of breast cancer with a particular phenotype. New molecular targets are needed to improve the treatment of this rapidly fatal disease. Given the role of NF-κB-related genes in cell proliferation, invasiveness, angiogenesis and inflammation, we postulated that they might be deregulated in IBC. We measured the mRNA expression levels of 60 NF-κB-related genes by using real-time quantitative RT-PCR in a well-defined series of 35 IBCs, by comparison with 22 stage IIB and III non inflammatory breast cancers. Twenty-four distant metastases of breast cancer served as 'poor prognosis' breast tumor controls. Thirty-five (58%) of the 60 NF-κB-related genes were significantly upregulated in IBC compared with non IBC. The upregulated genes were NF-κB genes (NFKB1, RELA, IKBKG, NFKBIB, NFKB2, REL, CHUK), apoptosis genes (MCL1L, TNFAIP3/A20, GADD45B, FASLG, MCL1S, IER3L, TNFRSF10B/TRAILR2), immune response genes (CD40, CD48, TNFSF11/RANKL, TNFRSF11A/RANK, CCL2/MCP-1, CD40LG, IL15, GBP1), proliferation genes (CCND2, CCND3, CSF1R, CSF1, SOD2), tumor-promoting genes (CXCL12, SELE, TNC, VCAM1, ICAM1, PLAU/UPA) or angiogenesis genes (PTGS2/COX2, CXCL1/GRO1). Only two of these 35 genes (PTGS2/COX2 and CXCL1/GRO1)were also upregulated in breast cancer metastases. We identified a five-gene molecular signature that matched patient outcomes, consisting of IL8 and VEGF plus three NF-κB-unrelated genes that we had previously identified as prognostic markers in the same series of IBC. The NF-κB pathway appears to play a major role in IBC, possibly contributing to the unusual phenotype and aggressiveness of this form of breast cancer. Some upregulated NF-κB-related genes might serve as novel therapeutic targets in IBC

Fouling characteristics and cleaning strategies of NF membranes for the advanced treatment of antibiotic production wastewater.

Science.gov (United States)

Wang, Jianxing; Li, Kun; Yu, Dawei; Zhang, Junya; Wei, Yuansong

2017-04-01

The nanofiltration (NF) membrane fouling characteristics and cleaning strategies were investigated through a laboratory-scale NF fouling test treating membrane bioreactor (MBR) effluent and MBR-granular activated carbon (GAC) effluent of an antibiotic production wastewater by DK and NF90 membranes, respectively. Results showed that organic fouling is the main NF membrane fouling for treating both the MBR effluent and MBR-GAC effluent. Soluble microbial by-product (SMP)-like and aromatic protein-like substances were the dominant components in the foulants, whereas humic-like substances had little contribution to the NF fouling. The fouling of DK was more severe than that of NF90. However, foulants respond by UV 254 were more easily to foul NF90 membrane. It could get satisfactory effect using combined cleaning of acid (HCl, pH 2.0∼2.5) and alkali (NaOH + 0.3 wt% NaDS, pH 10.0∼10.5). The favorable cleaning strategy is "acid + alkali" for treating MBR-GAC effluent, while it is "alkali + acid" for treating MBR effluent.

N-anti N oscillation in SO(10) and SU(6) supersymmetric grand unified models

International Nuclear Information System (INIS)

Fujimoto, Y.; Zhiyong, Z.

1982-06-01

N-anti N oscillation in SO(10) and SU(6) S.G.U.M. is considered. We find a new type of diagram leading to a faster oscillation rate than in non-supersymmetric case. It is also noted that in SO(10) S.G.U.M. with intermediate SU(4)sub(C)xSU(2)sub(L)xSU(2)sub(R) symmetry N-anti N oscillation would be highly suppressed, which may not necessarily be the case for SU(6) S.G.U.M. (author)

Foxtail millet NF-Y families: genome-wide survey and evolution analyses identified two functional genes important in abiotic stresses

Directory of Open Access Journals (Sweden)

Zhi-Juan eFeng

2015-12-01

Full Text Available It was reported that Nuclear Factor Y (NF-Y genes were involved in abiotic stress in plants. Foxtail millet (Setaria italica, an elite stress tolerant crop, provided an impetus for the investigation of the NF-Y families in abiotic responses. In the present study, a total of 39 NF-Y genes were identified in foxtail millet. Synteny analyses suggested that foxtail millet NF-Y genes had experienced rapid expansion and strong purifying selection during the process of plant evolution. De novo transcriptome assembly of foxtail millet revealed 11 drought up-regulated NF-Y genes. SiNF-YA1 and SiNF-YB8 were highly activated in leaves and/or roots by drought and salt stresses. Abscisic acid (ABA and H2O2 played positive roles in the induction of SiNF-YA1 and SiNF-YB8 under stress treatments. Transient luciferase (LUC expression assays revealed that SiNF-YA1 and SiNF-YB8 could activate the LUC gene driven by the tobacco (Nicotiana tobacam NtERD10, NtLEA5, NtCAT, NtSOD or NtPOD promoter under normal or stress conditions. Overexpression of SiNF-YA1 enhanced drought and salt tolerance by activating stress-related genes NtERD10 and NtCAT1 and by maintaining relatively stable relative water content (RWC and contents of chlorophyll, superoxide dismutase (SOD, peroxidase (POD, catalase (CAT and malondialdehyde (MDA in transgenic lines under stresses. SiNF-YB8 regulated expression of NtSOD, NtPOD, NtLEA5 and NtERD10 and conferred relatively high RWC and chlorophyll contents and low MDA content, resulting in drought and osmotic tolerance in transgenic lines under stresses. Therefore, SiNF-YA1 and SiNF-YB8 could activate stress-related genes and improve physiological traits, resulting in tolerance to abiotic stresses in plants. All these results will facilitate functional characterization of foxtail millet NF-Ys in future studies.

NF-κB RelA renders tumor-associated macrophages resistant to and capable of directly suppressing CD8+ T cells for tumor promotion.

Science.gov (United States)

Li, Liwen; Han, Lei; Sun, Fan; Zhou, Jingjiao; Ohaegbulam, Kim C; Tang, Xudong; Zang, Xingxing; Steinbrecher, Kris A; Qu, Zhaoxia; Xiao, Gutian

2018-01-01

Activation of the inflammatory transcription factor NF-κB in tumor-associated macrophages (TAMs) is assumed to contribute to tumor promotion. However, whether and how NF-κB drives the antitumor macrophages to become pro-tumorigenic have not been determined in any cancer type yet. Similarly, how TAMs repress CD8 + cytotoxic T lymphocytes (CTLs) remains largely unknown, although their importance in regulatory T (Treg) cell regulation and tumor promotion has been well appreciated. Here, using an endogenous lung cancer model we uncover a direct crosstalk between TAMs and CTLs. TAMs suppress CTLs through the T-cell inhibitory molecule B7x (B7-H4/B7S1) in a cell-cell contact manner, whereas CTLs kill TAMs in a tumor antigen-specific manner. Remarkably, TAMs secrete the known T-cell suppressive cytokine interleukin-10 (IL-10) to activate, but not to repress, CTLs. Notably, one major role of cell-intrinsic NF-κB RelA is to drive TAMs to suppress CTLs for tumor promotion. It induces B7x expression in TAMs directly, and restricts IL-10 expression indirectly by repressing expression of the NF-κB cofactor Bcl3 and subsequent Bcl3/NF-κB1-mediated transcription of IL-10. It also renders TAMs resistant to CTLs by up-regulating anti-apoptotic genes. These studies help understand how immunity is shaped in lung tumorigenesis, and suggest a RelA-targeted immunotherapy for this deadliest cancer.

Shigella dysenteriae infection activates proinflammatory response through β-catenin/NF-κB signaling pathway.

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Ashidha Gopal

Full Text Available Shigella dysenteriae (S.dysenteriae the causative agent of bacillary dysentery invades the human colonic epithelium resulting in severe intestinal inflammatory response and epithelial destruction. However, the mechanism by which S.dysenteriae infection regulates proinflammatory cytokines during intestinal inflammation is still obscure. In this study, we evaluated whether the interaction of β-catenin and NF-κB regulates proinflammatory cytokines TNF-α and IL-8 by modulating GSK-3β activity during S.dysenteriae infection in rat ileal loop model. Here we demonstrated that S.dysenteriae infection stimulate β-catenin degradation which in turn decreased the association between NF-κB and β-catenin. Also, we showed that S.dysenteriae infection increased GSK-3β kinase activity which in turn phosphorylates β-catenin for its degradation by ubiquitination and upregulates IL-8 through NF-κB activation thereby leading to inflammation. Thus these findings revealed the role of β-catenin/ NF-κB and GSK-3β in modulating the inflammatory response during bacterial infection and also showed that β-catenin acts as a critical regulator of inflammation.

[NF-κB signaling pathways and the future perspectives of bone disease therapy using selective inhibitors of NF-κB].

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Jimi, Eijiro; Fukushima, Hidefumi

2016-02-01

The transcriptional factor nuclear factor κB(NF-κB)regulates the expression of a wide variety of genes that are involved in immune and inflammatory responses, proliferation, and tumorigenesis. NF-κB consists of five members, such as p65(RelA), RelB, c-Rel, p50/p105(NF-κB1), and p52/p100(NF-κB2). There are two distinct NF-κB activation pathways, termed the classical and alternative NF-κB signaling pathways. Since mice lacking both p50 and p52 subunits developed typical osteopetrosis, due to total lack of osteoclasts, NF-κB is also important osteoclast differentiation. A selective NF-κB inhibitor blocked receptor activator of NF-κB ligand(RANKL)-induced osteoclastogenesis both in vitro and in vivo. Recent findings have shown that inactivation of NF-κB enhances osteoblast differentiation in vitro and bone formation in vivo. NF-κB is constitutively activated in many cancers including oral squamous cell carcinoma(OSCC), and is involved in the invasive characteristics of OSCC. A selective NF-κB inhibitor also prevented jaw bone destruction by OSCC by reduced osteoclast numbers in animal model. Thus the inhibition of NF-κB might useful for the treatment of bone diseases, such as arthritis, osteoporosis, periodontitis, and bone invasion by OSCC by inhibiting bone resorption and by stimulating bone formation.

Inspection, maintenance and voyage repair experiene during 10 years operation of the N.S. Savannah

International Nuclear Information System (INIS)

Jackson, E.L. Jr.

1978-01-01

This paper covers the development and performance of annual inspections on the N.S. Savannah over a 10 year period. Modifications and revisions to the inspection criteria were made during this period without sacrificing the safe performance of the reactor plant. The inspection experience gained during this period provides a information for future safe nuclear ship operations

NF-κB regulation of endothelial cell function during LPS-induced toxemia and cancer

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Kisseleva, Tatiana; Song, Li; Vorontchikhina, Marina; Feirt, Nikki; Kitajewski, Jan; Schindler, Christian

2006-01-01

The transcription factor NF-κB is an important regulator of homeostatic growth and inflammation. Although gene-targeting studies have revealed important roles for NF-κB, they have been complicated by component redundancy and lethal phenotypes. To examine the role of NF-κB in endothelial tissues, Tie2 promoter/enhancer–IκBαS32A/S36A transgenic mice were generated. These mice grew normally but exhibited enhanced sensitivity to LPS-induced toxemia, notable for an increase in vascular permeability and apoptosis. Moreover, B16-BL6 tumors grew significantly more aggressively in transgenic mice, underscoring a new role for NF-κB in the homeostatic response to cancer. Tumor vasculature in transgenic mice was extensive and disorganized. This correlated with a marked loss in tight junction formation and suggests that NF-κB plays an important role in the maintenance of vascular integrity and response to stress. PMID:17053836

Inhibition of NF-κB by a cell permeable form of IκBα induces apoptosis in eosinophils

International Nuclear Information System (INIS)

Fujihara, Satoko; Jaffray, Ellis; Farrow, Stuart N.; Rossi, Adriano G.; Haslett, Christopher; Hay, Ronald T.

2005-01-01

An 11 amino acid HIV-TAT peptide can deliver target proteins into a variety of cells in a receptor-independent manner. To generate a highly specific inhibitor of the transcription factor NF-κB, we have fused the TAT-peptide to a version of IκBα that is resistant to signal-induced degradation. TAT-IκBα(S32A, S36A) inhibited NF-κB-dependent transcription in HeLa and A549 cells by retaining NF-κB p65 in the cytoplasm. Introduction of TAT-IκBα(S32A, S36A) into human eosinophils inhibited the nuclear translocation of NF-κB and induced apoptosis. Thus, continuous NF-κB-dependent transcription is important for eosinophil survival. While eosinophils are normally refractive to standard methods of gene delivery, the ability of TAT fusion proteins to be taken up by these cells should enable a detailed molecular analysis of survival pathways in these cells

A facile one-step route to RGO/Ni3S2 for high-performance supercapacitors

International Nuclear Information System (INIS)

Zhang, Zhuomin; Zhao, Chongjun; Min, Shudi; Qian, Xiuzhen

2014-01-01

Graphical abstract: - Highlights: • A uniform 3D nest-like nanostructure of RGO/Ni 3 S 2 nanocomposite on Ni foam, in-situ synthesized using a simple, green one-pot hydrothermal approach, exhibits superior capacitive performance (7440 mF cm −2 at 10 mA cm −2 , i.e., 2188.8 F g −1 at 2.9 A g −1 and 1016 F g −1 at 29.0 A g −1 ).Highlights. • RGO/Ni 3 S 2 /NF composite was in-situ synthesized through a one-step hydrothermal process. • No other reagent except Ni foam, GO and S powder was added. • RGO/Ni 3 S 2 , RGO/Ni(OH) 2 , and RGO/Ni 3 S 2 /Ni(OH) 2 can be controllably synthesized. • As-prepared RGO/Ni 3 S 2 /NF nanocomposite exhibits high capability and cyclability. - Abstract: A facile one-step solution-phase route to RGO/Ni 3 S 2 on nickel foam (RGO/Ni 3 S 2 /NF) was presented. The RGO/Ni 3 S 2 /NF (RNS) nanocomposites were hydrothermal-assisted synthesized, in which nickel foam acted as an auxiliary reductant of GO and S, a Ni source of Ni 3 S 2 , and a substrate for composite film. RGO/Ni 3 S 2 /NF composites were characterized by X-ray diffraction (XRD), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), field-emission scanning electron microscope (FESEM), and transmission electron microscopy (TEM). The electrochemical performances of the supercapacitor with as-synthesized RGO/Ni 3 S 2 /NF (RNS) electrodes are evaluated using cyclic voltammetry (CV), galvanostatic charge-discharge (GCD), and electrochemical impedance spectrometry (EIS) in 2 M KOH aqueous solution. It is found that the RGO/Ni 3 S 2 /NF electrode exhibits superior supercapacitor performance (7440 mF cm −2 at 10 mA cm −2 , i.e., 2188.8 F g −1 at 2.9 A g −1 ), compared with the Ni 3 S 2 /NF electrode (4360 mF cm −2 at 10 mA cm −2 ) and the RGO/Ni(OH) 2 /NF electrode (3400 mF cm −2 at 10 mA cm −2 ) prepared under identical conditions. Both the temperature and sulfur content play important roles in the controlled synthesis of RNS and its

GeNF - experimental report 2003

International Nuclear Information System (INIS)

Schreyer, A.; Vollbrandt, J.; Willumeit, R.

2004-01-01

At the Geesthacht Neutron Facility GeNF about 210 experiments were performed in 2003 by GKSS and by or for external users, partners or contractors. In most cases the measurements were performed and analysed in cooperation by the guest and by the GKSS staff or by the permanent external user group staff. The activities, which are based on a proposal procedure and on the in house R and D program, are reported in 76 contributions in the present annual experimental report for the year 2003. The contributions may contain one or also several combined experiments. During 2003 the GKSS research reactor FRG-1 achieved an operation time of 252 days at the full 5 MW reactor power providing a neutron flux of ca. 1,4 x 10 14 thermal neutrons / cm 2 s. The cold neutron source was available during the complete operation time. The focus of the in house R and D work at GeNF instruments was the characterisation of metal alloys, the analysis of stresses in welds and technical structures at ARES, FSS, DCD and SANS-2, the structural investigation of hydrogen containing substances such as polymers, colloids and biological macromolecules at SANS-1 as well as the characterisation of magnetic thin films at PNR and ROeDI. The reflectomer TOREMA was thoroughly upgraded to the instrument NeRo and now offers new measurement possibilities. In the appendices the progress of the project REFSANS at FRM-II is reported as well as the experimental activities of the newly installed GKSS outstation HARWI-II at DESY. (orig.)

GeNF - experimental report 2003

Energy Technology Data Exchange (ETDEWEB)

Schreyer, A; Vollbrandt, J; Willumeit, R [GKSS-Forschungszentrum Geesthacht GmbH (Germany). Inst. for Materials Research

2004-07-01

At the Geesthacht Neutron Facility GeNF about 210 experiments were performed in 2003 by GKSS and by or for external users, partners or contractors. In most cases the measurements were performed and analysed in cooperation by the guest and by the GKSS staff or by the permanent external user group staff. The activities, which are based on a proposal procedure and on the in house R and D program, are reported in 76 contributions in the present annual experimental report for the year 2003. The contributions may contain one or also several combined experiments. During 2003 the GKSS research reactor FRG-1 achieved an operation time of 252 days at the full 5 MW reactor power providing a neutron flux of ca. 1,4 x 10{sup 14} thermal neutrons / cm{sup 2} s. The cold neutron source was available during the complete operation time. The focus of the in house R and D work at GeNF instruments was the characterisation of metal alloys, the analysis of stresses in welds and technical structures at ARES, FSS, DCD and SANS-2, the structural investigation of hydrogen containing substances such as polymers, colloids and biological macromolecules at SANS-1 as well as the characterisation of magnetic thin films at PNR and ROeDI. The reflectomer TOREMA was thoroughly upgraded to the instrument NeRo and now offers new measurement possibilities. In the appendices the progress of the project REFSANS at FRM-II is reported as well as the experimental activities of the newly installed GKSS outstation HARWI-II at DESY. (orig.)

Viral Restriction Activity of Feline BST2 Is Independent of Its N-Glycosylation and Induction of NF-κB Activation.

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Weiran Wang

Full Text Available BST2 (CD317, tetherin, HM1.24 is an interferon-inducible transmembrane protein which can directly inhibit the release of enveloped virus particles from infected cells, and its anti-viral activity is reported to be related to the specific topological arrangement of its four structural domains. The N-terminal cytoplasmic tail of feline BST2 (fBST2 is characterized by a shorter N-terminal region compared to those of other known homologs. In this study, we investigated the functional impact of modifying the cytoplasmic tail region of fBST2 and its molecular mechanism. The fBST2 protein with the addition of a peptide at the N-terminus retained anti-release activity against human immunodeficiency virus type-1 and pseudovirus based on feline immunodeficiency virus at a weaker level compared with the wild-type fBST2. However, the fBST2 protein with addition of a peptide internally in the ectodomain proximal to the GPI anchor still retained its anti-viral activity well. Notably, the N-glycosylation state and the cell surface level of the N-terminally modified variants were unlike those of the wild-type protein, while no difference was observed in their intracellular localizations. However, in contrast to human BST2, the wild-type fBST2 did not show the ability to activate NF-κB. Consistent with previous reports, our findings showed that adding a peptide in the cytoplasmic tail region of fBST2 may influence its anti-viral activity. The shorter N-terminal cytoplasmic region of fBST2 compared with human BST2 did not apparently affect its anti-viral activity, which is independent of its N-glycosylation and ability to activate NF-κB.

The C-terminal domains of NF-H and NF-M subunits maintain axonal neurofilament content by blocking turnover of the stationary neurofilament network.

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Mala V Rao

Full Text Available Newly synthesized neurofilaments or protofilaments are incorporated into a highly stable stationary cytoskeleton network as they are transported along axons. Although the heavily phosphorylated carboxyl-terminal tail domains of the heavy and medium neurofilament (NF subunits have been proposed to contribute to this process and particularly to stability of this structure, their function is still obscure. Here we show in NF-H/M tail deletion [NF-(H/M(tailΔ] mice that the deletion of both of these domains selectively lowers NF levels 3-6 fold along optic axons without altering either rates of subunit synthesis or the rate of slow axonal transport of NF. Pulse labeling studies carried out over 90 days revealed a significantly faster rate of disappearance of NF from the stationary NF network of optic axons in NF-(H/M(tailΔ mice. Faster NF disappearance was accompanied by elevated levels of NF-L proteolytic fragments in NF-(H/M(tailΔ axons. We conclude that NF-H and NF-M C-terminal domains do not normally regulate NF transport rates as previously proposed, but instead increase the proteolytic resistance of NF, thereby stabilizing the stationary neurofilament cytoskeleton along axons.

Simulation of QCD with N_f=2+1 flavors of non-perturbatively improved Wilson fermions

International Nuclear Information System (INIS)

Bruno, Mattia; Djukanovic, Dalibor; Engel, Georg P.; Francis, Anthony; Herdoiza, Gregorio; Horch, Hanno; Korcyl, Piotr; Korzec, Tomasz; Papinutto, Mauro; Schaefer, Stefan; Scholz, Enno E.; Simeth, Jakob; Simma, Hubert; Söldner, Wolfgang

2015-01-01

We describe a new set of gauge configurations generated within the CLS effort. These ensembles have N_f=2+1 flavors of non-perturbatively improved Wilson fermions in the sea with the Lüscher-Weisz action used for the gluons. Open boundary conditions in time are used to address the problem of topological freezing at small lattice spacings and twisted-mass reweighting for improved stability of the simulations. We give the bare parameters at which the ensembles have been generated and how these parameters have been chosen. Details of the algorithmic setup and its performance are presented as well as measurements of the pion and kaon masses alongside the scale parameter t_0.

Regorafenib induces extrinsic and intrinsic apoptosis through inhibition of ERK/NF-κB activation in hepatocellular carcinoma cells.

Science.gov (United States)

Tsai, Jai-Jen; Pan, Po-Jung; Hsu, Fei-Ting

2017-02-01

The aim of the present study was to investigate the role of NF-κB inactivation in regorafenib-induced apoptosis in human hepatocellular carcinoma SK-HEP-1 cells. SK-HEP-1 cells were treated with different concentrations of the NF-κB inhibitor 4-N-[2-(4-phenoxyphenyl)ethyl]quinazoline-4,6-diamine (QNZ) or regorafenib for different periods. The effects of QNZ and regorafenib on cell viability, expression of NF-κB-modulated anti-apoptotic proteins and apoptotic pathways were analyzed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, western blotting, DNA gel electrophoresis, flow cytometry and NF-κB reporter gene assay. Inhibitors of various kinases including AKT, c-Jun N-terminal kinase (JNK), P38 and extracellular signal-regulated kinase (ERK) were used to evaluate the mechanism of regorafenib-induced NF-κB inactivation. The results demonstrated that both QNZ and regorafenib significantly inhibited the expression of anti-apoptotic proteins and triggered extrinsic and intrinsic apoptosis. We also demonstrated that regorafenib inhibited NF-κB activation through ERK dephosphorylation. Taken all together, our findings indicate that regorafenib triggers extrinsic and intrinsic apoptosis through suppression of ERK/NF-κB activation in SK-HEP-1 cells.

κ-Carrageenan Enhances Lipopolysaccharide-Induced Interleukin-8 Secretion by Stimulating the Bcl10-NF-κB Pathway in HT-29 Cells and Aggravates C. freundii-Induced Inflammation in Mice

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Wei Wu

2017-01-01

Full Text Available Background. The dietary usage of carrageenan as common food additive has increased observably over the last 50 years. But there is substantial controversy about its safety. Methods. We investigated whether the κ-carrageenan could enhance lipopolysaccharide-induced IL-8 expression by studying its actions on the TLR4-NF-κB pathway. The aggravating effect of κ-carrageenan on Citrobacter freundii DBS100-induced intestinal inflammation was also investigated in a mouse model. Results. Our data show that κ-carrageenan pretreatment promoted LPS-induced IL-8 expression in HT-29 cells. Although CD14, MD-2, and TLR4 were upregulated, the binding of LPS was not enhanced. However, the pathway of Bcl10-NF-κB was triggered. Interestingly, κ-carrageenan competitively blocked the binding of FITC-LPS. Furthermore, pretreatment with κ-carrageenan for one week previous to gavage with C. freundii DBS100 markedly aggravated weight loss, mortality, and colonic damage. The secretion of cytokines was unbalanced and the ratio of Tregs was decreased significantly. In addition, κ-carrageenan, together with C. freundii DBS100, enhanced the transcription and secretion of TLR4 and NF-κB. Conclusions. κ-Carrageenan can synergistically activate LPS-induced inflammatory through the Bcl10-NF-κB pathway, as indicated by its aggravation of C. freundii DBS100-induced colitis in mice. General Significance. Our results suggest that κ-carrageenan serves as a potential inflammatory agent that magnifies existing intestinal inflammation.

Airway epithelial NF-κB activation promotes Mycoplasma pneumoniae clearance in mice.

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Di Jiang

Full Text Available Respiratory infections including atypical bacteria Mycoplasma pneumoniae (Mp contribute to the pathobiology of asthma and chronic obstructive pulmonary disease (COPD. Mp infection mainly targets airway epithelium and activates various signaling pathways such as nuclear factor κB (NF-κB. We have shown that short palate, lung, and nasal epithelium clone 1 (SPLUNC1 serves as a novel host defense protein and is up-regulated upon Mp infection through NF-κB activation in cultured human and mouse primary airway epithelial cells. However, the in vivo role of airway epithelial NF-κB activation in host defense against Mp infection has not been investigated. In the current study, we investigated the effects of in vivo airway epithelial NF-κB activation on lung Mp clearance and its association with airway epithelial SPLUNC1 expression.Non-antimicrobial tetracycline analog 9-t-butyl doxycycline (9-TB was initially optimized in mouse primary tracheal epithelial cell culture, and then utilized to induce in vivo airway epithelial specific NF-κB activation in conditional NF-κB transgenic mice (CC10-(CAIKKβ with or without Mp infection. Lung Mp load and inflammation were evaluated, and airway epithelial SPLUNC1 protein was examined by immunohistochemistry. We found that 9-TB treatment in NF-κB transgene positive (Tg+, but not transgene negative (Tg- mice significantly reduced lung Mp load. Moreover, 9-TB increased airway epithelial SPLUNC1 protein expression in NF-κB Tg+ mice.By using the non-antimicrobial 9-TB, our study demonstrates that in vivo airway epithelial NF-κB activation promotes lung bacterial clearance, which is accompanied by increased epithelial SPLUNC1 expression.

The Regulation of NF-κB Subunits by Phosphorylation

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Frank Christian

2016-03-01

Full Text Available The NF-κB transcription factor is the master regulator of the inflammatory response and is essential for the homeostasis of the immune system. NF-κB regulates the transcription of genes that control inflammation, immune cell development, cell cycle, proliferation, and cell death. The fundamental role that NF-κB plays in key physiological processes makes it an important factor in determining health and disease. The importance of NF-κB in tissue homeostasis and immunity has frustrated therapeutic approaches aimed at inhibiting NF-κB activation. However, significant research efforts have revealed the crucial contribution of NF-κB phosphorylation to controlling NF-κB directed transactivation. Importantly, NF-κB phosphorylation controls transcription in a gene-specific manner, offering new opportunities to selectively target NF-κB for therapeutic benefit. This review will focus on the phosphorylation of the NF-κB subunits and the impact on NF-κB function.

Cobalt(II phthalocyanine bonded to 3-n-propylimidazole immobilized on silica gel surface: preparation and electrochemical properties

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Fujiwara Sergio T.

1999-01-01

Full Text Available Co-Phthalocyanine complex was immobilized on 3-n-propylimidazole groups grafted on a porous SiO2 surface (specific surface area S BET = 500 m² g-1 and efficiently electrocatalyzed the oxalic acid oxidation on a carbon paste electrode surface made of this material. Intermolecular interactions of the complex species which can normally interfere in the redox process practically are not observed in the present case because of a low average surface density, delta = 4.7 x 10-13 mol cm-2 (delta = Nf/S BET, where Nf is the amount of adsorbed Co-phtalocyanine per gram of modified silica gel of the complex species material prepared. The linear response of the electrode to oxalic acid concentration, between 6.5 x 10-4 and 3.2 x 10-3 mol L-1, associated with its high chemical stability makes the covalently immobilized Co-phtalocyanine complex material very attractive in preparing a new class of chemical sensors.

Identification of a novel TIF-IA-NF-κB nucleolar stress response pathway.

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Chen, Jingyu; Lobb, Ian T; Morin, Pierre; Novo, Sonia M; Simpson, James; Kennerknecht, Kathrin; von Kriegsheim, Alex; Batchelor, Emily E; Oakley, Fiona; Stark, Lesley A

2018-06-05

p53 as an effector of nucleolar stress is well defined, but p53 independent mechanisms are largely unknown. Like p53, the NF-κB transcription factor plays a critical role in maintaining cellular homeostasis under stress. Many stresses that stimulate NF-κB also disrupt nucleoli. However, the link between nucleolar function and activation of the NF-κB pathway is as yet unknown. Here we demonstrate that artificial disruption of the PolI complex stimulates NF-κB signalling. Unlike p53 nucleolar stress response, this effect does not appear to be linked to inhibition of rDNA transcription. We show that specific stress stimuli of NF-κB induce degradation of a critical component of the PolI complex, TIF-IA. This degradation precedes activation of NF-κB and is associated with increased nucleolar size. It is mimicked by CDK4 inhibition and is dependent upon a novel pathway involving UBF/p14ARF and S44 of the protein. We show that blocking TIF-IA degradation blocks stress effects on nucleolar size and NF-κB signalling. Finally, using ex vivo culture, we show a strong correlation between degradation of TIF-IA and activation of NF-κB in freshly resected, human colorectal tumours exposed to the chemopreventative agent, aspirin. Together, our study provides compelling evidence for a new, TIF-IA-NF-κB nucleolar stress response pathway that has in vivo relevance and therapeutic implications.

Casticin Inhibits A375.S2 Human Melanoma Cell Migration/Invasion through Downregulating NF-κB and Matrix Metalloproteinase-2 and -1

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Zih-Yun Wu

2016-03-01

Full Text Available Casticin is one of the main components from Fructus Viticis, which is widely used as an anti-inflammatory agent. The mechanism of how casticin affects melanoma cell migration and invasion is still not well known. Here we studied the anti-metastasis effects of casticin on A375.S2 melanoma cells by using a non-lethal concentration. First; we used an adhesion assay to test the A375.S2 cells’ adhesion ability after treatment with casticin. We next investigated the cell migration ability after casticin treatment by using a wound healing assay to prove that the migration of A375.S2 cells can be inhibited by casticin and double checked the results using the transwell-migration assay. The suppressive effects on matrix metalloproteinase-2; and -9 (MMP-2; and -9 activities were examined by gelatin zymography. Furthermore, western blotting was used to investigate the protein level changes in A375.S2 cells. We found that p-EGFR; Ras and p-ERK1/2 are decreased by casticin, indicating that casticin can down-regulate the migration and invasion ability of A375.S2 cells via the p-EGFR/Ras/p-ERK pathway. The NF-κB p65 and p-ERK levels in nuclear proteins are also decreased by treatment with casticin. An EMSA assay also discovered that the NF-κB p65 and DNA interaction is decreased. NF-κB p65 protein level was examined by immunofluorescence staining and also decreased. Our findings suggest that casticin has anti-metastatic potential by decreasing the invasiveness of A375.S2 cells. We also found that casticin suppressed A375.S2 cell proliferation and cell adhesion ability, but did not affect cell death, as examined using cytometry and a collagen adhesion assay. Based on these observations, casticin could be used as an inhibitor of migration and invasion of human melanoma cells in the future.

The garlic NF-YC gene, AsNF-YC8, positively regulates non-ionic hyperosmotic stress tolerance in tobacco.

Science.gov (United States)

Sun, Xiudong; Lian, Haifeng; Liu, Xingchen; Zhou, Shumei; Liu, Shiqi

2017-05-01

To investigate the relationship between nuclear factor Y (NF-Y) and stress tolerance in garlic, we cloned a NF-Y family gene AsNF-YC8 from garlic, which was largely upregulated at dehydrate stage. Expression pattern analyses in garlic revealed that AsNF-YC8 is induced through abscisic acid (ABA) and abiotic stresses, such as NaCl and PEG. Compared with wild-type plants, the overexpressing-AsNF-YC8 transgenic tobacco plants showed higher seed germination rates, longer root length and better plant growth under salt and drought stresses. Under drought stress, the transgenic plants maintained higher relative water content (RWC), net photosynthesis, lower levels of malondialdehyde (MDA), and less ion leakage (IL) than wild-type control plants. These results indicate the high tolerance of the transgenic plants to drought stress compared to the WT. The transgenic tobacco lines accumulated less reactive oxygen species (ROS) and exhibited higher antioxidative enzyme activities compared with wild-type (WT) plants under drought stress, which suggested that the overexpression of AsNF-YC8 improves the antioxidant defense system by regulating the activities of these antioxidant enzymes, which in turn protect transgenic lines against drought stress. These results suggest that AsNF-YC8 plays an important role in tolerance to drought and salt stresses.

Styrene induces an inflammatory response in human lung epithelial cells via oxidative stress and NF-κB activation

International Nuclear Information System (INIS)

Roeder-Stolinski, Carmen; Fischaeder, Gundula; Oostingh, Gertie Janneke; Feltens, Ralph; Kohse, Franziska; Bergen, Martin von; Moerbt, Nora; Eder, Klaus; Duschl, Albert; Lehmann, Irina

2008-01-01

Styrene is a volatile organic compound (VOC) that is widely used as a solvent in many industrial settings. Chronic exposure to styrene can result in irritation of the mucosa of the upper respiratory tract. Contact of styrene with epithelial cells stimulates the expression of a variety of inflammatory mediators, including the chemotactic cytokine monocyte chemoattractant protein-1 (MCP-1). To characterise the underlying mechanisms of the induction of inflammatory signals by styrene, we investigated the influence of this compound on the induction of oxidative stress and the activation of the nuclear factor-kappa B (NF-κB) signalling pathway in human lung epithelial cells (A549). The results demonstrate that styrene-induced MCP-1 expression, as well as the expression of the oxidative stress marker glutathione S-transferase (GST), is associated with a concentration dependent pattern of NF-κB activity. An inhibitor of NF-κB, IKK-NBD, and the anti-inflammatory antioxidant N-acetylcysteine (NAC) were both effective in suppressing styrene-induced MCP-1 secretion. In addition, NAC was capable of inhibiting the upregulation of GST expression. Our findings suggest that the activation of the NF-κB signalling pathway by styrene is mediated via a redox-sensitive mechanism

Targeting the ECM to Enhance Drug Delivery in Nf1-Associated Nerve Sheath Tumors

Science.gov (United States)

2016-10-01

development of the principal discipline(s) of the project? • We have learned that the drug PEGPH20, which degrades a component of connective tissue called...AWARD NUMBER: W81XWH-15-1-0114 TITLE: Targeting the ECM to Enhance Drug Delivery in Nf1-Associated Nerve Sheath Tumors PRINCIPAL INVESTIGATOR...14 Sep 2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER NF140089 Targeting the ECM to Enhance Drug Delivery in Nf1-Associated Nerve Sheath Tumors 5b

Supervisión pedagógica y estrés laboral de docentes en IEE, Red 10, UGEL 06, Ate, 2015

OpenAIRE

Aliaga Pongo, Yolanda

2015-01-01

El presente trabajo de investigación titulado Supervisión pedagógica y estrés laboral de docentes en IEE Red 10, UGEL 06, Ate, 2015, tuvo como objetivo determinar la relación que existe entre la supervisión pedagógica con el estrés laboral. La población de estudio estuvo constituída por 171 docentes y la muestra fue de 120 aplicando la fórmula de Arkin y Colton. Esta investigación se desarrolló bajo un diseño no experimental de nivel correlacional de corte transeccional, con...

NF1 Neuronal Genotype Phenotype Relationships

Science.gov (United States)

2017-06-01

interesting results from the Drosophila functional assays, at present we have decided to focus our attention on selected NF1 patient missense mutations...complexity of NF1 disease phenotypes in different tissues, age and sex dependency of symptoms, impact of environmental factors and genetic heterogeneity...suggesting the role of modifier genes [12]. This work aims to shed light on this issue by studying the functional consequences of selected NF1

Theoretical Stark widths and shifts of spectral lines of 2p5nf and 2p55g configurations of Mg III

International Nuclear Information System (INIS)

Moreno-Díaz, Cristina; Alonso-Medina, Aurelia; Colón, Cristóbal

2014-01-01

In this paper, we report theoretical Stark widths and shifts calculated using the Griem semi-empirical approach, which corresponds to 111 spectral lines of Mg III. The values of these Stark broadening parameters of spectral lines that arise from levels of 2p 5 nf and 2p 5 5g configurations of Mg III are presented in the literature for the first time. The aim of this work is to provide values to estimate the electron density of plasma Mg III in astrophysics and industrial applications. The data are presented for the temperatures T = 0.5–10.0 (10 4 K) and for an electron density of 10 17 cm −3 . The matrix of elements used in these calculations has been determined from 23 configurations of Mg III: 2s 2 2p 6 , 2s 2 2p 5 3p, 2s 2 2p 5 4p, 2s 2 2p 5 4f and 2s 2 2p 5 5f for the even parity and 2s 2 2p 5 ns (n = 3–6), 2s 2 2p 5 nd (n = 3–9), 2s 2 2p 5 5g and 2s2p 6 np (n = 3–8) for the odd parity. For the intermediate coupling calculations, we use the standard method of least square fitting from experimental energy levels by means of Cowan’s computer code. Lines with wavelengths of 134.6460, 135.2800, 189.0380, 190.0043, 192.8424, 408.2939 and 409.4375 nm have high probabilities and also have high values of broadening. Therefore, these lines can be used in some applications. A common regularity for the Stark width of the 189.038 nm spectral line of Mg III is discussed. (paper)

Blocking NF-κB: an inflammatory issue.

Science.gov (United States)

Rahman, Arshad; Fazal, Fabeha

2011-11-01

The nuclear factor (NF)-κB is considered the master regulator of inflammatory responses. Studies in mouse models have established this transcription factor as an important mediator of many inflammatory disease states, including pulmonary diseases such as acute lung injury and acute respiratory distress syndrome. Endothelial cells provide the first barrier for leukocytes migrating to the inflamed sites and hence offer an attractive cellular context for targeting NF-κB for treatment of these diseases. However, recent studies showing that NF-κB also plays an important role in resolution phase of inflammation and in tissue repair and homeostasis have challenged the view of therapeutic inhibition of NF-κB. This article reviews the regulation of NF-κB in the context of endothelial cell signaling and provides a perspective on why "dampening" rather than "abolishing" NF-κB activation may be a safe and effective treatment strategy for inflammation-associated pulmonary and other inflammatory diseases.

S100-A9 protein in exosomes from chronic lymphocytic leukemia cells promotes NF-κB activity during disease progression.

Science.gov (United States)

Prieto, Daniel; Sotelo, Natalia; Seija, Noé; Sernbo, Sandra; Abreu, Cecilia; Durán, Rosario; Gil, Magdalena; Sicco, Estefanía; Irigoin, Victoria; Oliver, Carolina; Landoni, Ana Inés; Gabus, Raúl; Dighiero, Guillermo; Oppezzo, Pablo

2017-08-10

Chronic lymphocytic leukemia (CLL) is an incurable disease characterized by accumulation of clonal B lymphocytes, resulting from a complex balance between cell proliferation and apoptotic death. Continuous crosstalk between cancer cells and local/distant host environment is required for effective tumor growth. Among the main actors of this dynamic interplay between tumoral cells and their microenvironment are the nano-sized vesicles called exosomes. Emerging evidence indicates that secretion, composition, and functional capacity of exosomes are altered as tumors progress to an aggressive phenotype. In CLL, no data exist exploring the specific changes in the proteomic profile of plasma-derived exosomes from patients during disease evolution. We hereby report for the first time different proteomic profiles of plasma exosomes, both between indolent and progressive CLLs as well as within the individual patients at the onset of disease and during its progression. Next, we focus on the changes of the exosome protein cargoes, which are found exclusively in patients with progressive CLL after disease progression. The alterations in the proteomic cargoes underline different networks specific for leukemia progression related to inflammation, oxidative stress, and NF-κB and phosphatidylinositol 3-kinase/AKT pathway activation. Finally, our results suggest a preponderant role for the protein S100-A9 as an activator of the NFκB pathway during CLL progression and suggest that the leukemic clone can generate an autoactivation loop through S100-A9 expression, NF-κB activation, and exosome secretion. Collectively, our data propose a new pathway for NF-κB activation in CLL and highlight the importance of exosomes as extracellular mediators promoting tumor progression in CLL. © 2017 by The American Society of Hematology.

Estudio del rechazo de especies iónicas en procesos de nanofiltración

OpenAIRE

Marín Daniel, Miguel

2013-01-01

En este proyecto se estudia la modelización del transporte de especies iónicas (concretamente fosfatos y carbonatos) a través de membranas planas de nanofiltración (NF), en procesos de potabilización de aguas salobres. El fin de la investigación es la aplicación y validación de un modelo matemático predictivo del comportamiento de iones en disolución cuando se trabaje con una membrana de NF. Las pruebas experimentales se realizan en una planta piloto, a escala de laboratorio, compuesta ...

Long-term performance and fouling analysis of full-scale direct nanofiltration (NF) installations treating anoxic groundwater

NARCIS (Netherlands)

Beyer, F.; Rietman, B.M.; Zwijnenburg, A.; Brink, van den P.; Vrouwenvelder, J.S.; Jarzembowska, M.; Laurinonyte, J.; Stams, A.J.M.; Plugge, C.M.

2014-01-01

Long-term performance and fouling behavior of four full-scale nanofiltration (NF) plants, treating anoxic groundwater at 80% recovery for drinking water production, were characterized and compared with oxic NF and reverse osmosis systems. Plant operating times varied between 6 and 10 years and

Eliminación de sal inorgánica residual producida en la fermentación farmacéutica por nanofiltración y ósmosis inversa: experimento y modelo matemático

Directory of Open Access Journals (Sweden)

Jesús Mora Molina

2007-05-01

Full Text Available El problema del agua residual con altos contenidos de sal es una importante preocupación de las autoridades medioambientalistas. Los metódos de tratamientos de aguas residuales existentes, tanto municipales como industriales, son incapaces de retener eficientemente los compuestos inorgánicos. En este trabajo se presentan nuevos resultados con membranas de ósmosis inversa (OI y nanofiltración (NF preparadas por las compañías Filmtec y Millipore. Los objetivos principales de esta investigación fueron estos: 1. Encontrar un sistema con alta eficiencia para separar la sal del agua residual generada en el proceso fermentativo farmacéutico y obtener una concentración según lo establecido por la legislación ambiental (concentración de sal: 2500 mg/l, y concentración de los sólidos totales: 1200 mgO2/l; además, que a la planta de tratamiento biológico o directamente al medio ambiente. 2.Determinar la retención de sal demanda química de oxígeno y el flujo del filtrado con sistemas de NF y OI. Asimismo, con base en los datos experimentales, poder describir soluciones similares a las basadas en el modelo de ósmosis a aguas residuales. La temperatura experimental, la presión y el flujo de recirculación fueron mantenidos constantes, en la NF 30°C, 30 bar y 200 l/h, en la OI 30-40°C, 40-50 bar y 300 l/h. En los experimentos de la NF y la OI el factor de concentración fue de Cff = Vaguaori(m3 /Vretenido (m3 = 2,67. Se midieron y se calcularon el flujo del filtrado, la conductividad eléctrica del filtrado, la demanda química de oxígeno y los sólidos totales. En el sistema de OI se obtuvieron los siguientes resultados: contenido de sólidos totales en el agua original 2,06%, en el filtrado, 0,048%; demanda química de oxígeno en el agua original 8750 mg O2/l, en el filtrado 289 mgO2/l. Los resultados demostraron claramente que las membranas de NF investigadas no fueron lo suficientemente eficientes en la retención de sal del agua

Chronic Dosing with Membrane Sealant Poloxamer 188 NF Improves Respiratory Dysfunction in Dystrophic Mdx and Mdx/Utrophin-/- Mice.

Directory of Open Access Journals (Sweden)

Bruce E Markham

Full Text Available Poloxamer 188 NF (national formulary (NF grade of P-188 improves cardiac muscle function in the mdx mouse and golden retriever muscular dystrophy models. However in vivo effects on skeletal muscle have not been reported. We postulated that P-188 NF might protect diaphragm muscle membranes from contraction-induced injury in mdx and mdx/utrophin-/- (dko muscular dystrophy models. In the first study 7-month old mdx mice were treated for 22 weeks with subcutaneous (s.c. injections of saline or P-188 NF at 3 mg/Kg. In the second, dkos were treated with saline or P-188 NF (1 mg/Kg for 8 weeks beginning at age 3 weeks. Prednisone was the positive control in both studies. Respiratory function was monitored using unrestrained whole body plethysmography. P-188 NF treatment affected several respiratory parameters including tidal volume/BW and minute volume/BW in mdx mice. In the more severe dko model, P-188 NF (1 mg/Kg significantly slowed the decline in multiple respiratory parameters compared with saline-treated dko mice. Prednisone's effects were similar to those seen with P-188 NF. Diaphragms from P-188 NF or prednisone treated mdx and dko mice showed signs of muscle fiber protection including less centralized nuclei, less variation in fiber size, greater fiber density, and exhibited a decreased amount of collagen deposition. P-188 NF at 3 mg/Kg s.c. also improved parameters of systolic and diastolic function in mdx mouse hearts. These results suggest that P-188 NF may be useful in treating respiratory and cardiac dysfunction, the leading causes of death in Duchenne muscular dystrophy patients.

Andrographolide derivative CX-10 ameliorates dextran sulphate sodium-induced ulcerative colitis in mice: Involvement of NF-κB and MAPK signalling pathways.

Science.gov (United States)

Gao, Zhenfang; Yu, Cuicui; Liang, Haiyue; Wang, Xuekai; Liu, Yue; Li, Xin; Ji, Kai; Xu, Hui; Yang, Mingyan; Liu, Ke; Qi, Dong; Fan, Huaying

2018-04-01

Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD), which is characterized by chronic intestinal inflammation and leads to an increased risk of colon cancer. There are many studies using phyto-ingredients as a novel approach for the treatment of UC. The plant Andrographis paniculata (Acanthaceae) is a safe and edible vegetable that has been extensively adopted in traditional Chinese medicine for conditions involving inflammation, and the most active phytochemical agent is andrographolide. The andrographolide derivative 3,14,19-triacetyl andrographolide, which is known as CX-10 (a hemi chemical synthesized from andrographolide), has been found to possess strong anti-inflammatory properties. In the present study, we investigated the therapeutic potential of CX-10 as a complementary and alternative medicine against dextran sulphate sodium (DSS)-induced ulcerative colitis in mice. Our results revealed that CX-10 treatment reduced body weight loss, reduced colon length shortening, decreased colon weight, decreased the spleen index, decreased the disease activity index (DAI), and alleviated histological damage in the colon. The expression of TNF-α and IL-6 and the activity of myeloperoxidase (MPO) in colonic tissues were significantly reduced in CX-10 supplemented mice. It is noteworthy that the efficacy of 200 mg/kg of CX-10 was equivalent to that of the mesalazine positive control (200 mg/kg). Furthermore, western blot analysis revealed that CX-10 treatment reduced the expression of nuclear factor-κB (NF-κB) p65 and p-IκBα, increased the expression of IκBα and down-regulated the phosphorylation of p38 mitogen-activated protein kinase (MAPK), ERK and JNK. In conclusion, CX-10 treatment attenuated DSS-induced UC in mice through inhibiting the activation of NF-κB and MAPK pathways and reducing TNF-α and IL-6 levels, suggesting that CX-10 is a potential therapeutic drug for UC. Copyright © 2018. Published by Elsevier B.V.

Modulation of the nuclear factor-kappa B (NF-κB) signalling pathway by glutamine in peritoneal macrophages of a murine model of protein malnutrition.

Science.gov (United States)

da Silva Lima, Fabiana; Rogero, Marcelo Macedo; Ramos, Mayara Caldas; Borelli, Primavera; Fock, Ricardo Ambrósio

2013-06-01

Protein malnutrition affects resistance to infection by impairing the inflammatory response, modifying the function of effector cells, such as macrophages. Recent studies have revealed that glutamine-a non-essential amino acid, which could become conditionally essential in some situations like trauma, infection, post-surgery and sepsis-is able to modulate the synthesis of cytokines. The aim of this study was to evaluate the effect of glutamine on the expression of proteins involved in the nuclear factor-kappa B (NF-κB) signalling pathway of peritoneal macrophages from malnourished mice. Two-month-old male Balb/c mice were submitted to protein-energy malnutrition (n = 10) with a low-protein diet containing 2 % protein, whereas control mice (n = 10) were fed a 12 % protein-containing diet. The haemogram and analysis of plasma glutamine and corticosterone were evaluated. Peritoneal macrophages were pre-treated in vitro with glutamine (0, 0.6, 2 and 10 mmol/L) for 24 h and then stimulated with 1.25 μg LPS for 30 min, and the synthesis of TNF-α and IL-1α and the expression of proteins related to the NF-κB pathway were evaluated. Malnourished animals had anaemia, leucopoenia, lower plasma glutamine and increased corticosterone levels. TNF-α production of macrophages stimulated with LPS was significantly lower in cells from malnourished animals when cultivated in supraphysiological (2 and 10 mmol/L) concentrations of glutamine. Further, glutamine has a dose-dependent effect on the activation of macrophages, in both groups, when stimulated with LPS, inducing a decrease in TNF-α and IL-1α production and negatively modulating the NF-κB signalling pathway. These data lead us to infer that the protein malnutrition state interferes with the activation of macrophages and that higher glutamine concentrations, in vitro, have the capacity to act negatively in the NF-κB signalling pathway.

Zb(10 610) and Zb(10 650) structures produced by the initial single pion emission in the Υ(5S) decays

International Nuclear Information System (INIS)

Chen Dianyong; Liu Xiang

2011-01-01

We propose a unique mechanism called initial single pion emission existing in the Υ(5S) decays, and further study the line shapes of dΓ(Υ(5S→Υ(nS)π + π - ))/dm Υ(nS)π + (n=1,2,3) and dΓ(Υ(5S→h b (mP)π + π - ))/dm h b (mP)π + (m=1,2). We find sharp structures around 10 610 MeV and 10 650 MeV in the obtained theoretical line shapes of dΓ(Υ(5S→Υ(nS)π + π - ))/dm Υ(nS)π + and dΓ(Υ(5S→h b (mP)π + π - ))/dm h b (mP)π + distributions, which could naturally correspond to the Z b (10 610) and Z b (10 650) structures newly observed by Belle.

Novel Mechanism of Attenuation of LPS-Induced NF-κB Activation by the Heat Shock Protein 90 Inhibitor, 17-N-allylamino-17-demethoxygeldanamycin, in Human Lung Microvascular Endothelial Cells

Science.gov (United States)

Thangjam, Gagan S.; Dimitropoulou, Chistiana; Joshi, Atul D.; Barabutis, Nektarios; Shaw, Mary C.; Kovalenkov, Yevgeniy; Wallace, Chistopher M.; Fulton, David J.; Patel, Vijay

2014-01-01

Heat shock protein (hsp) 90 inhibition attenuates NF-κB activation and blocks inflammation. However, the precise mechanism of NF-κB regulation by hsp90 in the endothelium is not clear. We investigated the mechanisms of hsp90 inhibition by 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) on NF-κB activation by LPS in primary human lung microvascular endothelial cells. Transcriptional activation of NF-κB was measured by luciferase reporter assay, gene expression by real-time RT-PCR, DNA binding of transcription factors by chromatin immunoprecipitation assay, protein–protein interaction by coimmunoprecipitation/immunoblotting, histone deacetylase (HDAC)/histone acetyltransferase enzyme activity by fluorometry, and nucleosome eviction by partial microccocal DNase digestion. In human lung microvascular endothelial cells, 17-AAG–induced degradation of IKBα was accomplished regardless of the phosphorylation/ubiquitination state of the protein. Hence, 17-AAG did not block LPS-induced NF-κB nuclear translocation and DNA binding activity. Instead, 17-AAG blocked the recruitment of the coactivator, cAMP response element binding protein binding protein, and prevented the assembly of a transcriptionally competent RNA polymerase II complex at the κB elements of the IKBα (an NF-κB–responsive gene) promoter. The effect of LPS on IKBα mRNA expression was associated with rapid deacetylation of histone-H3(Lys9) and a dramatic down-regulation of core histone H3 binding. Even though treatment with an HDAC inhibitor produced the same effect as hsp90 inhibition, the effect of 17-AAG was independent of HDAC. We conclude that hsp90 inhibition attenuates NF-κB transcriptional activation by preventing coactivator recruitment and nucleosome eviction from the target promoter in human lung endothelial cells. PMID:24303801

GeNF - Experimental report 2006

International Nuclear Information System (INIS)

Pranzas, P.K.; Schreyer, A.; Willumeit, R.

2007-01-01

At the Geesthacht Neutron Facility GeNF about 212 experiments were performed in 2006 by GKSS and by or for external users, partners or contractors. In most cases the measurements were performed and analysed in cooperation by the guests and by the GKSS staff or by the permanent external user group staff. The activities, which are based on a proposal procedure and on the in house R and D program, are reported in 71 contributions in the present annual experimental report for the year 2006. The contributions may contain one or also several combined experiments. During 2006 the GKSS research reactor FRG-1 achieved an operation time of 197 days at the full 5 MW reactor power providing a neutron flux of ca. 1.4 x 10 14 thermal neutrons/cm 2 s. The cold neutron source was available during the complete operation time. The focus of the in house R and D work at GeNF instruments was the characterisation of nanostructures in engineering materials, the analysis of stresses and textures in welds and technical structures at ARES-2, TEX-2, DCD and SANS-2, the structural investigation of hydrogen containing substances such as polymers, colloids and biological macromolecules at SANS-1 as well as the characterisation of magnetic thin films at PNR, NeRo, POLDI and ROeDI. The thoroughly upgraded residual stress diffractomer ARES-2 went in full operation in spring 2006 as well as the new neutron tomography device at GENRA-3. The installation of modern experiment control hardware and software based on LabView was completed on all designated instruments. In the appendices I and II the experimental reports of REFSANS at FRM II are attached as well as of the GKSS outstation HARWI-II at DESY. Both instruments started full operation in 2006. (orig.)

GeNF - Experimental report 2006

Energy Technology Data Exchange (ETDEWEB)

Pranzas, P K; Schreyer, A; Willumeit, R [GKSS-Forschungszentrum Geesthacht GmbH (Germany). Inst. of Materials Research

2007-07-01

At the Geesthacht Neutron Facility GeNF about 212 experiments were performed in 2006 by GKSS and by or for external users, partners or contractors. In most cases the measurements were performed and analysed in cooperation by the guests and by the GKSS staff or by the permanent external user group staff. The activities, which are based on a proposal procedure and on the in house R and D program, are reported in 71 contributions in the present annual experimental report for the year 2006. The contributions may contain one or also several combined experiments. During 2006 the GKSS research reactor FRG-1 achieved an operation time of 197 days at the full 5 MW reactor power providing a neutron flux of ca. 1.4 x 10{sup 14} thermal neutrons/cm{sup 2}s. The cold neutron source was available during the complete operation time. The focus of the in house R and D work at GeNF instruments was the characterisation of nanostructures in engineering materials, the analysis of stresses and textures in welds and technical structures at ARES-2, TEX-2, DCD and SANS-2, the structural investigation of hydrogen containing substances such as polymers, colloids and biological macromolecules at SANS-1 as well as the characterisation of magnetic thin films at PNR, NeRo, POLDI and ROeDI. The thoroughly upgraded residual stress diffractomer ARES-2 went in full operation in spring 2006 as well as the new neutron tomography device at GENRA-3. The installation of modern experiment control hardware and software based on LabView was completed on all designated instruments. In the appendices I and II the experimental reports of REFSANS at FRM II are attached as well as of the GKSS outstation HARWI-II at DESY. Both instruments started full operation in 2006. (orig.)

Extracts of Porphyra tenera (Nori Seaweed) Activate the Immune Response in Mouse RAW264.7 Macrophages via NF-κB Signaling.

Science.gov (United States)

Song, Ji-Hye; Kang, Hee-Bum; Park, Seung-Ho; Jeong, Ji-Hoon; Park, Jeongjin; You, Yanghee; Lee, Yoo-Hyun; Lee, Jeongmin; Kim, Eungpil; Choi, Kyung-Chul; Jun, Woojin

2017-12-01

Porphyra tenera, also known as nori, is a red algal species of seaweed. It is cultivated in Asia for culinary purposes. We report that P. tenera extract (PTE) enhances the immune response in mouse macrophages. We found that P. tenera extract regulates the NF-κB IκB kinase (IKK) signaling pathway, and we assessed the expression and translocation of p65, a subunit of NF-κB, in RAW264.7 mouse macrophage cells after treatment with PTE. We also investigated the effects of 10% ethanol PTE (PTE10) in RAW264.7 cells. The production of IL-10, IL-6, TNF-α, and IFN-γ was induced by PTE treatment of the macrophages, and PTE also enhanced p-IκB and p-AKT. PTE10 showed no cytotoxicity at 10-20 μg/mL in RAW264.7 cells. PTE10, in fact, increased cell viability at 24 h, stimulated macrophage cells, and induced the phosphorylation of Akt. Akt stimulates IKK activity through the phosphorylation of IKKα and enhances immune activity through the activation of NF-κB. In this study, NF-κB activation was induced by increasing p-NF-κB and p-IKK. A subunit of NF-κB, p65, was located in the nucleus and increased the expression of various cytokines. PTE thus enhanced the immune response through IκB-α immunostimulation signaling in RAW264.7 cells. PTE10 has potential therefore for development of future treatments requiring immune system stimulation.

Investigations on GSK-3β/NF-kB signaling in stress and stress adaptive behavior in electric foot shock subjected mice.

Science.gov (United States)

Bali, Anjana; Jaggi, Amteshwar Singh

2016-04-01

The present study was designed to explore the role of GSK-3β and NF-kB signaling in electric foot shock-induced stress and stress adaptation. Mice were subjected to foot shocks of 0.5mA intensity and 1s duration of 1h to produce acute stress. Animals were exposed to the same stressor for 5 days to induce stress adaptation. The behavioral alterations were assessed using the actophotometer, hole board, open field and social interaction tests. The serum corticosterone levels were assessed as a marker of the HPA axis. The levels of total GSK-3β, p-GSK-3β-S9 and p-NF-kB were determined in the hippocampus, frontal cortex and amygdala. Acute electric foot shock stress produced behavioral and biochemical changes; decreased the levels of p-GSK-3β-S9, produced no change in total GSK-3β levels and increased p-NF-kB levels in the brain. However, repeated exposure of foot shock stress restored the behavioral and biochemical changes along with normalization of p-GSK-3β-S9 and p-NF-kB levels. Administration of AR-A01, a selective GSK-3β inhibitor, or diethyldithiocarbamic acid (DDTC), a selective NF-kB inhibitor, diminished acute stress-induced behavioral and biochemical changes. Furthermore, AR-A014418 normalized acute stress-induced alterations in p-GSK-3β-S9 and p-NF-kB levels, however, DDTC selectively restored NF-kB levels without any change in p-GSK-3β-S9 levels. It probably suggests that NF-kB is a downstream mediator of the GSK-3 signaling cascade. It may conclude that acute stress associated decrease in p-GSK-3β-S9 and increase in p-NF-kB levels in the brain contribute in the development of behavioral and biochemical alterations and normalization of GSK-3β/NF-kB signaling may contribute in stress adaptive behavior in response to repeated electric foot shock-subjected mice. Copyright © 2016 Elsevier B.V. All rights reserved.

A mouse dry eye model induced by topical administration of the air pollutant particulate matter 10.

Science.gov (United States)

Li, Juan; Tan, Gang; Ding, Xiaoyan; Wang, Yahong; Wu, Anhua; Yang, Qichen; Ye, Lei; Shao, Yi

2017-12-01

To introduce a novel dry eye mouse model induced by topical administration of the air pollutant particulate matter 10 (PM 10 ). A total of 60 male BALB/c mice were used in this study and divided into two groups: group A (PBS eye drops, n=30) and group B (PM 10 eye drop group, n=30). Each treatment was dosed four times a day, every time 50ul with the concentration of 5mg/ml PM10, for 14 consecutive days in the right eye. The clinical manifestations of dry eye were measured before therapy and 4, 7 and 14days post-treatment respectively, which included the tear volume, tear break-up (BUT) time, corneal fluorescein staining, rose bengal staining, Lissamine Green staining and inflammatory index. Eye samples were collected on D14 and examined by histologic light microscopy, transmission electron microscopy (TEM) and scanning electron microscopy (SEM), corneal cytokeration 10 (K10) immunnostaining, and tumor necrosis factor-α (TNF-α), NF-κB-p65 and NF-κB Western Blot analysis. At 0d, 7d and 14d, there were no statistical changes in tear volume, BUT after treatment (P>0.05) with PBS in group A. In group B, all items showed statistical differences at each time point (Plevels of K10 and reduced number of goblet cells in the conjunctival fornix in group B. PM 10 significantly increased the levels of TNF-α, NF-κB-p65 and NF-κB in the cornea. PM 10 can damage the tear film function and cause the destruction of the structural organization of ocular surface in mice. Topical administration of PM 10 in mice induces ocular surface changes that are similar to those of dry eye in humans, representing a novel model of DES. Copyright © 2017. Published by Elsevier Masson SAS.

(-)-Epigallocatechin gallate inhibition of osteoclastic differentiation via NF-κB

International Nuclear Information System (INIS)

Lin, R.-W.; Chen, C.-H.; Wang, Y.-H.; Ho, M.-L.; Hung, S.-H.; Chen, I.-S.; Wang, G.-J.

2009-01-01

People who regularly drink tea have been found to have a higher bone mineral density (BMD) and to be at less risk of hip fractures than those who do not drink it. Green tea catechins such as (-)-epigallocatechin gallate (EGCG) have been reported to increase osteogenic functioning in mesenchymal stem cells. However, its effect on osteoclastogenesis remains unclear. In this study, we investigated the effect of EGCG on RANKL-activation osteoclastogenesis and NF-κB in RAW 264.7, a murine preosteoclast cell line. EGCG (10-100 μM) significantly suppressed the RANKL-induced differentiation of osteoclasts and the formation of pits in murine RAW 264.7 cells and bone marrow macrophages (BMMs). EGCG appeared to target osteoclastic differentiation at an early stage but had no cytotoxic effect on osteoclast precursors. In addition, it significantly inhibited RANKL-induced NF-κB transcriptional activity and nuclear translocation. We conclude that EGCG inhibits osteoclastogenesis through its activation of NF-κB.

Prolyl hydroxylase-1 regulates hepatocyte apoptosis in an NF-κB-dependent manner

Energy Technology Data Exchange (ETDEWEB)

Fitzpatrick, Susan F.; Fábián, Zsolt; Schaible, Bettina; Lenihan, Colin R.; Schwarzl, Thomas [School of Medicine and Medical Science, The Conway Institute, University College Dublin, Belfield, Dublin 4 Ireland (Ireland); Rodriguez, Javier [Systems Biology Ireland, University College Dublin, Dublin 4 (Ireland); Zheng, Xingnan; Li, Zongwei [Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC (United States); Tambuwala, Murtaza M. [School of Pharmacy and Pharmaceutical Sciences, Ulster University, Coleraine, BT52 1SA, Northern Ireland (United Kingdom); Higgins, Desmond G.; O' Meara, Yvonne [School of Medicine and Medical Science, The Conway Institute, University College Dublin, Belfield, Dublin 4 Ireland (Ireland); Slattery, Craig [School of Biomolecular and Biomedical Science, The Conway Institute, University College Dublin, Belfield, Dublin 4 Ireland (Ireland); Manresa, Mario C. [School of Medicine and Medical Science, The Conway Institute, University College Dublin, Belfield, Dublin 4 Ireland (Ireland); Fraisl, Peter; Bruning, Ulrike [Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, University of Leuven, Vesalius Research Center, VIB, B-3000 (Belgium); Baes, Myriam [Laboratory for Cell Metabolism, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven (Belgium); Carmeliet, Peter; Doherty, Glen [Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, University of Leuven, Vesalius Research Center, VIB, B-3000 (Belgium); Kriegsheim, Alex von [Systems Biology Ireland, University College Dublin, Dublin 4 (Ireland); Cummins, Eoin P. [School of Medicine and Medical Science, The Conway Institute, University College Dublin, Belfield, Dublin 4 Ireland (Ireland); and others

2016-06-03

Hepatocyte death is an important contributing factor in a number of diseases of the liver. PHD1 confers hypoxic sensitivity upon transcription factors including the hypoxia inducible factor (HIF) and nuclear factor-kappaB (NF-κB). Reduced PHD1 activity is linked to decreased apoptosis. Here, we investigated the underlying mechanism(s) in hepatocytes. Basal NF-κB activity was elevated in PHD1{sup −/−} hepatocytes compared to wild type controls. ChIP-seq analysis confirmed enhanced binding of NF-κB to chromatin in regions proximal to the promoters of genes involved in the regulation of apoptosis. Inhibition of NF-κB (but not knock-out of HIF-1 or HIF-2) reversed the anti-apoptotic effects of pharmacologic hydroxylase inhibition. We hypothesize that PHD1 inhibition leads to altered expression of NF-κB-dependent genes resulting in reduced apoptosis. This study provides new information relating to the possible mechanism of therapeutic action of hydroxylase inhibitors that has been reported in pre-clinical models of intestinal and hepatic disease. -- Highlights: •Genetic ablation of PHD1 upregulates NF-kappaB (NF-κB) in hepatocytes. •Activation of NF-κB leads to differential DNA-binding of p50/p65 and results in differential regulation of apoptotic genes. •We identified proline 191 in the beta subunit of the I-kappaB kinase as a target for PHD1-mediated hydroxylation. •Blockade of prolyl-4-hydroxylases has been found cytoprotective in liver cells.

Thiazolidinediones inhibit airway smooth muscle release of the chemokine CXCL10: in vitro comparison with current asthma therapies

Directory of Open Access Journals (Sweden)

Seidel Petra

2012-10-01

Full Text Available Abstract Background Activated mast cells are present within airway smooth muscle (ASM bundles in eosinophilic asthma. ASM production of the chemokine CXCL10 plays a role in their recruitment. Thus the effects of glucocorticoids (fluticasone, budesonide, long-acting β2-agonists (salmeterol, formoterol and thiazolidinediones (ciglitazone, rosiglitazone on CXCL10 production by ASM cells (ASMC from people with and without asthma were investigated in vitro. Methods Confluent serum-deprived cells were treated with the agents before and during cytokine stimulation for 0-24 h. CXCL10 protein/mRNA, IκB-α levels and p65 activity were measured using ELISA, RT PCR, immunoblotting and p65 activity assays respectively. Data were analysed using ANOVA followed by Fisher’s post-hoc test. Results Fluticasone and/or salmeterol at 1 and 100 nM inhibited CXCL10 release induced by IL-1β and TNF-α, but not IFNγ or all three cytokines (cytomix. The latter was also not affected by budesonide and formoterol. In asthmatic ASMC low salmeterol, but not formoterol, concentrations increased cytomix-induced CXCL10 release and at 0.01 nM enhanced NF-κB activity. Salmeterol 0.1nM together with fluticasone 0.1 and 10 nM still increased CXCL10 release. The thiazolidinediones ciglitazone and rosiglitazone (at 25 and 100 μM inhibited cytomix-induced CXCL10 release but these inhibitory effects were not prevented by the PPAR-g antagonist GW9662. Ciglitazone did not affect early NF-κB activity and CXCL10 mRNA production. Conclusions Thus the thiazolidinediones inhibited asthmatic ASMC CXCL10 release under conditions when common asthma therapies were ineffective or enhanced it. They may provide an alternative strategy to reduce mast cell-ASM interactions and restore normal airway physiology in asthma.

Transient degradation of NF-κB proteins in macrophages after interaction with mast cell granules

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Noriko Ito

1998-01-01

Full Text Available The exposure of the macrophage cell line, J774 to mast cell granules (MCG led to the form ation of altered nuclear transcription factor proteins (NFκBx, which had faster electrophoretic mobility than the p50 homodimer of NF-κB, but retained comparable DNA binding capacity. Antibodies to N-terminal peptides of p50, p52, p65 or c-Rel supershifted only a fraction of NF-κBx. Western blot analyses revealed that nuclear p65 and c-Rel were progressively degraded after exposure to MCG, whereas nuclear p50 appeared to be unaffected. In contrast, cytoplasmic p50, p65, c-Rel as well as IkBα remained intact after MCG treatment, although p52 was clearly degraded. In comparison to J774 cells, incubation of m ouse peritoneal macrophages with MCG resulted in more extensive alterations to NF-κB proteins. The alterations in NF-κB proteins did not affect the expression of inducible nitric oxide synthase (iNOS or TNF-α mRNA in J774 cells. These data indicate that exposure of J774 cells to MCG leads to generation of altered nuclear p52, p65 and c-Rel, which retain intact N-terminal peptides, specific oligonucleotide binding and transactivating activity. On the other hand, in peritoneal macrophages, MCG induce more extensive modifications to NF-κB proteins with associated inhibition of iNOS or TNF-α mRNA expression.

Measurement of fission yields for 232-Th (n,f) at 14,7 MeV by direct gamma spectrometric method

International Nuclear Information System (INIS)

Chouak, K.; Berrada, M.; Embarech, K.

1994-01-01

Fission yields for the reaction 232-Th (n,f) were measured at 14,7 MeV using the activation technique with direct gamma spectrometric method. Neutrons were produced via the T(d,n) sup 4 He reaction. The neutron fluences were determined relative to the well-known sup 2 sup 7 Al(n,p) sup 2 sup 7 Mg or sup 2 sup 7 Al(n,alpha) sup 2 sup 4 Na cross section, according to the irradiation time. Yields of fission products were determined by measuring the induced gamma ray activities of the irradiated Th foils, using a calibrated Ge(Li) detector. All necessary corrections were taken into account: self absorption, coincidence losses and natural gamma rays. Fifty six cumulative yields were measured and only twenty one corresponding results were found in the literature (Crouch,1977). A satisfactory agreement is observed between our results and the published data with the exception of the masses:A=134 and A=140. 1 tab., 2 refs. (author)

Eggshell membrane hydrolyzates activate NF-κB in vitro: possible implications for in vivo efficacy

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Ruff KJ

2015-02-01

Full Text Available Kevin J Ruff,1 Paul L Durham,2 Austin O’Reilly,2 F Daniel Long1 1ESM Technologies, LLC, Carthage, MO, USA; 2Center for Biomedical and Life Sciences, Missouri State University, Springfield, MO, USA Purpose: Eggshell membrane (ESM has been shown to contain naturally occurring bioactive components, and biological activities such as reducing proinflammatory cytokines, liver fibrosis, and joint pain in osteoarthritis sufferers have also been reported for ESM matrix as a whole. Nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB is a signaling protein found in the cytoplasm of nearly all human and animal cell types and is a primary regulator of immune function. The studies reported herein were designed to investigate the possible role that NF-κB activity might play in the reported biological activities of ESM. Methods: Three ESM hydrolyzates produced via fermentation, enzymatic, or chemical hydrolysis were evaluated in vitro in either human peripheral blood mononuclear cell or THP-1 (human leukemic monocyte cell cultures for NF-κB activity following 4-hour exposure. The hydrolyzates were compared with untreated control cells or cells incubated with lipopolysaccharide or ascorbic acid. The source of ESM activity was also evaluated. Results: NF-κB levels were increased above levels found in untreated cells at all three dilutions (1:100, 1:1,000, and 1:10,000 for the fermentation hydrolyzate of ESM (ESM-FH (P=0.021, P=0.020, P=0.009, respectively in peripheral blood mononuclear cells. The enzymatic hydrolyzate of ESM (ESM-EH also produced statistically significant levels of activated NF-κB at the 1:100 and 1:1,000 dilutions (P=0.004, P=0.006, respectively but fell just shy of significance at the 1:10,000 dilution (P=0.073. Similarly, ESM-FH (P=0.021, P=0.002 and ESM-EH (P=0.007, P=0.007 activated NF-κB in THP-1 cells at 1:1,000 and 1:10,000 dilutions, respectively. The chemical hydrolyzate of ESM (ESM-CH showed statistically

Type 2 diabetes is associated with altered NF-¿B DNA binding activity, JNK phosphorylation, and AMPK phosphorylation in skeletal muscle after LPS

DEFF Research Database (Denmark)

Andreasen, Anne Sofie; Kelly, Meghan; Berg, Ronan Martin Griffin

2011-01-01

Systemic inflammation is often associated with impaired glucose metabolism. We therefore studied the activation of inflammatory pathway intermediates that interfere with glucose uptake during systemic inflammation by applying a standardised inflammatory stimulus in vivo. After ethical approval......, informed consent and a thorough physical examination, 10 patients with type 2 diabetes and 10 participants with normal glucose tolerance (NGT) were given an intravenous bolus of E. coli lipopolysaccharide (LPS) of 0.3 ng/kg. Skeletal muscle biopsies and plasma were obtained at baseline and two, four...... and six hours after LPS. Nuclear factor (NF)-¿B p65 DNA binding activity measured by ELISA, tumor necrosis factor-a and interleukin-6 mRNA expression analysed by real time reverse transcription polymerase chain reaction, and abundance of inhibitor of NF-¿B (I¿B)a, phosphorylated c-Jun-N-terminal kinase...

Acrylamide-induced oxidative stress and inflammatory response are alleviated by N-acetylcysteine in PC12 cells: Involvement of the crosstalk between Nrf2 and NF-κB pathways regulated by MAPKs.

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Pan, Xiaoqi; Wu, Xu; Yan, Dandan; Peng, Cheng; Rao, Chaolong; Yan, Hong

2018-05-15

Acrylamide (ACR) is a classic neurotoxin in animals and humans. However, the mechanism underlying ACR neurotoxicity remains controversial, and effective prevention and treatment measures against this condition are scarce. This study focused on clarifying the crosstalk between the involved signaling pathways in ACR-induced oxidative stress and inflammatory response and investigating the protective effect of antioxidant N-acetylcysteine (NAC) against ACR in PC12 cells. Results revealed that ACR exposure led to oxidative stress characterized by significant increase in reactive oxygen species (ROS) and malondialdehyde (MDA) levels and glutathione (GSH) consumption. Inflammatory response was observed based on the dose-dependently increased levels of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6). NAC attenuated ACR-induced enhancement of MDA and ROS levels and TNF-α generation. In addition, ACR activated nuclear transcription factor E2-related factor 2 (Nrf2) and nuclear factor-κB (NF-κB) signaling pathways. Knockdown of Nrf2 by siRNA significantly blocked the increased NF-κB p65 protein expression in ACR-treated PC12 cells. Down-regulation of NF-κB by specific inhibitor BAY11-7082 similarly reduced ACR-induced increase in Nrf2 protein expression. NAC treatment increased Nrf2 expression and suppressed NF-κB p65 expression to ameliorate oxidative stress and inflammatory response caused by ACR. Further results showed that mitogen-activated protein kinases (MAPKs) pathway was activated prior to the activation of Nrf2 and NF-κB pathways. Inhibition of MAPKs blocked Nrf2 and NF-κB pathways. Collectively, ACR activated Nrf2 and NF-κB pathways which were regulated by MAPKs. A crosstalk between Nrf2 and NF-κB pathways existed in ACR-induced cell damage. NAC protected against oxidative damage and inflammatory response induced by ACR by activating Nrf2 and inhibiting NF-κB pathways in PC12 cells. Copyright © 2018 Elsevier B

Improved iris localization by using wide and narrow field of view cameras for iris recognition

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Kim, Yeong Gon; Shin, Kwang Yong; Park, Kang Ryoung

2013-10-01

Biometrics is a method of identifying individuals by their physiological or behavioral characteristics. Among other biometric identifiers, iris recognition has been widely used for various applications that require a high level of security. When a conventional iris recognition camera is used, the size and position of the iris region in a captured image vary according to the X, Y positions of a user's eye and the Z distance between a user and the camera. Therefore, the searching area of the iris detection algorithm is increased, which can inevitably decrease both the detection speed and accuracy. To solve these problems, we propose a new method of iris localization that uses wide field of view (WFOV) and narrow field of view (NFOV) cameras. Our study is new as compared to previous studies in the following four ways. First, the device used in our research acquires three images, one each of the face and both irises, using one WFOV and two NFOV cameras simultaneously. The relation between the WFOV and NFOV cameras is determined by simple geometric transformation without complex calibration. Second, the Z distance (between a user's eye and the iris camera) is estimated based on the iris size in the WFOV image and anthropometric data of the size of the human iris. Third, the accuracy of the geometric transformation between the WFOV and NFOV cameras is enhanced by using multiple matrices of the transformation according to the Z distance. Fourth, the searching region for iris localization in the NFOV image is significantly reduced based on the detected iris region in the WFOV image and the matrix of geometric transformation corresponding to the estimated Z distance. Experimental results showed that the performance of the proposed iris localization method is better than that of conventional methods in terms of accuracy and processing time.

6d N=(1,0) theories on S{sup 1}/T{sup 2} and class S theories: part II

Energy Technology Data Exchange (ETDEWEB)

Ohmori, Kantaro; Shimizu, Hiroyuki [Department of Physics, Faculty of Science, University of Tokyo,Bunkyo-ku, Tokyo 133-0022 (Japan); Tachikawa, Yuji [Department of Physics, Faculty of Science, University of Tokyo,Bunkyo-ku, Tokyo 133-0022 (Japan); Institute for the Physics and Mathematics of the Universe, University of Tokyo,Kashiwa, Chiba 277-8583 (Japan); Yonekura, Kazuya [Institute for the Physics and Mathematics of the Universe, University of Tokyo,Kashiwa, Chiba 277-8583 (Japan); School of Natural Sciences, Institute for Advanced Study,Princeton, NJ 08540 (United States)

2015-12-21

We study the T{sup 2} compactification of a class of 6d N=(1,0) theories that is Higgsable to N=(2,0) theories. We show that the resulting 4d N=2 theory at the origin of the Coulomb branch and the parameter space is generically given by two superconformal matter sectors coupled by an infrared-free gauge multiplet and another conformal gauge multiplet. Our analysis utilizes the 5d theories obtained by putting the same class of 6d theories on S{sup 1}. Our class includes, among others, the 6d theories describing multiple M5 branes on an ALE singularity, and we analyze them in detail. The resulting 4d theory has manifestly both the SL(2,ℤ) and the full flavor symmetry. We also discuss in detail the special cases of 6d theories where the infrared-free gauge multiplet is absent. In an appendix, we give a field-theoretical argument for an F-theoretic constraint that forbids a particular 6d anomaly-free matter content, as an application of our analysis.

Thromboxane synthase suppression induces lung cancer cell apoptosis via inhibiting NF-κB

International Nuclear Information System (INIS)

Leung, Kin Chung; Li, Ming-Yue; Leung, Billy C.S.; Hsin, Michael K.Y.; Mok, Tony S.K.; Underwood, Malcolm J.; Chen, George G.

2010-01-01

Accumulating evidence shows that the inhibition of thromboxane synthase (TXS) induced apoptosis in cancer cells. TXS inhibitor 1-Benzylimidzole (1-BI) can trigger apoptosis in lung cancer cells but the mechanism is not fully defined. In this study, lung cancer cells were treated with 1-BI. In this study, the level of reactive oxygen species (ROS) was measured and NF-κB activity was determined in human lung cancer cells. The roles of ROS and NF-κB in 1-BI-mediated cell death were analyzed. The results showed that 1-BI induced ROS generation but decreased the activity of NF-κB by reducing phosphorylated IκBα (p-IκBα) and inhibiting the translocation of p65 into the nucleus. In contrast to 1-BI, antioxidant N-acetyl cysteine (NAC) stimulated cell proliferation and significantly protected the cells from 1-BI-mediated cell death by neutralizing ROS. Collectively, apoptosis induced by 1-BI is associated with the over-production of ROS and the reduction of NF-κB. Antioxidants can significantly block the inhibitory effect of 1-BI.

Gastroesophageal reflux activates the NF-κB pathway and impairs esophageal barrier function in mice

Science.gov (United States)

Fang, Yu; Chen, Hao; Hu, Yuhui; Djukic, Zorka; Tevebaugh, Whitney; Shaheen, Nicholas J.; Orlando, Roy C.; Hu, Jianguo

2013-01-01

The barrier function of the esophageal epithelium is a major defense against gastroesophageal reflux disease. Previous studies have shown that reflux damage is reflected in a decrease in transepithelial electrical resistance associated with tight junction alterations in the esophageal epithelium. To develop novel therapies, it is critical to understand the molecular mechanisms whereby contact with a refluxate impairs esophageal barrier function. In this study, surgical models of duodenal and mixed reflux were developed in mice. Mouse esophageal epithelium was analyzed by gene microarray. Gene set enrichment analysis showed upregulation of inflammation-related gene sets and the NF-κB pathway due to reflux. Significance analysis of microarrays revealed upregulation of NF-κB target genes. Overexpression of NF-κB subunits (p50 and p65) and NF-κB target genes (matrix metalloproteinases-3 and -9, IL-1β, IL-6, and IL-8) confirmed activation of the NF-κB pathway in the esophageal epithelium. In addition, real-time PCR, Western blotting, and immunohistochemical staining also showed downregulation and mislocalization of claudins-1 and -4. In a second animal experiment, treatment with an NF-κB inhibitor, BAY 11-7085 (20 mg·kg−1·day−1 ip for 10 days), counteracted the effects of duodenal and mixed reflux on epithelial resistance and NF-κB-regulated cytokines. We conclude that gastroesophageal reflux activates the NF-κB pathway and impairs esophageal barrier function in mice and that targeting the NF-κB pathway may strengthen esophageal barrier function against reflux. PMID:23639809

Neuronal RING finger protein 11 (RNF11 regulates canonical NF-κB signaling

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Pranski Elaine L

2012-04-01

Full Text Available Abstract Background The RING domain-containing protein RING finger protein 11 (RNF11 is a member of the A20 ubiquitin-editing protein complex and modulates peripheral NF-κB signaling. RNF11 is robustly expressed in neurons and colocalizes with a population of α-synuclein-positive Lewy bodies and neurites in Parkinson disease patients. The NF-κB pathway has an important role in the vertebrate nervous system, where the absence of NF-κB activity during development can result in learning and memory deficits, whereas chronic NF-κB activation is associated with persistent neuroinflammation. We examined the functional role of RNF11 with respect to canonical NF-κB signaling in neurons to gain understanding of the tight association of inflammatory pathways, including NF-κB, with the pathogenesis of neurodegenerative diseases. Methods and results Luciferase assays were employed to assess NF-κB activity under targeted short hairpin RNA (shRNA knockdown of RNF11 in human neuroblastoma cells and murine primary neurons, which suggested that RNF11 acts as a negative regulator of canonical neuronal NF-κB signaling. These results were further supported by analyses of p65 translocation to the nucleus following depletion of RNF11. Coimmunoprecipitation experiments indicated that RNF11 associates with members of the A20 ubiquitin-editing protein complex in neurons. Site-directed mutagenesis of the myristoylation domain, which is necessary for endosomal targeting of RNF11, altered the impact of RNF11 on NF-κB signaling and abrogated RNF11’s association with the A20 ubiquitin-editing protein complex. A partial effect on canonical NF-κB signaling and an association with the A20 ubiquitin-editing protein complex was observed with mutagenesis of the PPxY motif, a proline-rich region involved in Nedd4-like protein interactions. Last, shRNA-mediated reduction of RNF11 in neurons and neuronal cell lines elevated levels of monocyte chemoattractant protein 1 and

Cloning, expression, purification, crystallization and preliminary X-ray analysis of NodS N-methyltransferase from Bradyrhizobium japonicum WM9

International Nuclear Information System (INIS)

Cakici, Ozgur; Sikorski, Michal; Stepkowski, Tomasz; Bujacz, Grzegorz; Jaskolski, Mariusz

2008-01-01

The NodS N-methyltransferase, an enzyme participating in the biosynthesis of the bacterial nodulation (Nod) factor necessary to establish symbiotic nitrogen fixation with a legume plant host, has been crystallized in the apo form as well as in complex with SAH. SAH is a byproduct of SAM degradation during the SAM-dependent methylation reaction. The Nod factor (NF) is a rhizobial signal molecule that is involved in recognition of a legume host and the formation of root and stem nodules. Some unique enzymes are involved in the biosynthesis of NF, which is a variously but specifically substituted lipochitooligosaccharide. One of these enzymes is NodS, an N-methyltransferase that methylates end-deacetylated chitooligosaccharide substrates. In the methylation reaction, NodS uses S-adenosyl-l-methionine (SAM) as a methyl donor. To date, no structural information is available about NodS from any rhizobium. X-ray crystallographic studies of the NodS protein from Bradyrhizobium japonicum WM9, which infects the legumes lupin and serradella, have been undertaken. The nodS gene was cloned and the recombinant protein was expressed in Escherichia coli cells using natural amino acids and as an SeMet derivative. NodS without ligands was crystallized in the presence of PEG 3350 and MgCl 2 . The protein was also crystallized in complex with S-adenosyl-l-homocysteine (SAH) in the presence of PEG 8000 and MgCl 2 . SAH is produced from SAM as a byproduct of the methylation reaction. The crystals of apo NodS are tetragonal and diffracted X-rays to 2.42 Å resolution. The NodS–SAH complex crystallizes in an orthorhombic space group and the crystals diffracted X-rays to 1.85 Å resolution

Glaucocalyxin B Alleviates Lipopolysaccharide-Induced Parkinson’s Disease by Inhibiting TLR/NF-κB and Activating Nrf2/HO-1 Pathway

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Wei Xu

2017-12-01

Full Text Available Background/Aims: Parkinson’s disease (PD is a common neurodegenerative disease in the old population, characterized by dopaminergic neuron loss, inflammation and oxidative stress injury in the substantia nigra. Glaucocalyxin B (GLB, an ent-kauranoid diterpenoid isolated from Rabdosia japonica, has anti-inflammation and anti-tumor effects. However, its effects on PD remain unclear. Methods: PD was introduced in rats via injection of lipopolysaccharide (LPS into cerebral corpus striatum, and GLB was given intracerebroventricularly to these rats. Their walking, climbing and sensory states were detected by Stepping, Whisker and Cylinder Tests. The expression of tyrosine hydroxylase (TH, glial fibrillary acidic protein (GFAP, CD11b and ionized calcium binding adaptor molecule (IBA-1 were detected by immunohischemical staining. The levels of a series of inflammatory factors, oxidative stress-related factors and apoptosis-related factors were measured by real-time PCR, immunoblotting and ELISA. In addition, Toll-like receptor (TLR/nuclear factor kappa B (NF-κB and nuclear factor erythroid 2-related factor 2 (Nrf2/heme oxygenase (HO-1 pathways were investigated to illustrate the underlying mechanism. In vitro, microglial cells exposed to LPS were treated with GLB. Results: The injection of LPS caused walking, climbing and sensory disturbances in rats, induced inflammation, oxidative stress response and apoptosis, and activated TLR/NF-κB and Nrf2/ HO-1 pathways in the cerebral tissue. GLB administration attenuated LPS-induced alterations. The TLR/NF-κB pathway was deactivated and Nrf2/HO-1 was activated after application of GLB. In vitro, cytotoxic effects induced by the conditioned medium derived from microglial cells exposed to LPS in PC12 cells were attenuated by GLB. Conclusion: GLB suppresses LPS-induced PD symptoms by modification of TLR/NF-κB and Nrf2/HO-1 pathways in vivo and in vitro.

Cocoa consumption reduces NF-κB activation in peripheral blood mononuclear cells in humans.

Science.gov (United States)

Vázquez-Agell, M; Urpi-Sarda, M; Sacanella, E; Camino-López, S; Chiva-Blanch, G; Llorente-Cortés, V; Tobias, E; Roura, E; Andres-Lacueva, C; Lamuela-Raventós, R M; Badimon, L; Estruch, R

2013-03-01

Epidemiological studies have demonstrated an association between high-polyphenol intake and reduced incidence of atherosclerosis. The healthy effects of cocoa-polyphenols may be due to their antioxidant and anti-inflammatory actions, although the exact mechanisms are unknown and depend on the matrix in which cocoa-polyphenols are delivered. Nuclear factor κB (NF-κB) is a key molecule in the pathophysiology of atherosclerosis involved in the regulation of adhesion molecules(AM) and cytokine expression and its activation is the first step in triggering the inflammatory process. The aim of this study was to evaluate the effect of acute cocoa consumption in different matrices related to the bioavailability of cocoa-polyphenols in NF-κB activation and the expression of AM. Eighteen healthy volunteers randomly received 3 interventions: 40g of cocoa powder with milk (CM), with water (CW), and only milk (M). NF-κB activation in leukocytes and AM (sICAM, sVCAM, E-selectin) were measured before and 6h after each intervention. Consumption of CW significantly decreased NF-κB activation compared to baseline and to CM (P cocoa intake may depend on the bioavailability of bioactive compounds and may be mediated at least in part by the modulation of NF-κB activation and downstream molecules reinforcing the link between cocoa intake and health. Copyright © 2011 Elsevier B.V. All rights reserved.

Histamine Induces Bovine Rumen Epithelial Cell Inflammatory Response via NF-κB Pathway.

Science.gov (United States)

Sun, Xudong; Yuan, Xue; Chen, Liang; Wang, Tingting; Wang, Zhe; Sun, Guoquan; Li, Xiaobing; Li, Xinwei; Liu, Guowen

2017-01-01

Subacute ruminal acidosis (SARA) is a common disease in high-producing lactating cows. Rumenitis is the initial insult of SARA and is associated with the high concentrations of histamine produced in the rumen of dairy cows during SARA. However, the exact mechanism remains unclear. The objective of the current study is to investigate whether histamine induces inflammation of rumen epithelial cells and the underlying mechanism of this process. Bovine rumen epithelial cells were cultured and treated with different concentrations of histamine and pyrrolidine dithiocarbamate (PDTC, an NF-κB inhibitor) cultured in different pH medium (pH 7.2 or 5.5). qRT-PCR, Western-blotting, ELISA and immunocytofluorescence were used to evaluate whether histamine activated the NF-κB pathway and inflammatory cytokines. The results showed that histamine significantly increased the activity of IKK β and the phosphorylation levels of IκB α, as well as upregulated the mRNA and protein expression levels of NF-κB p65 in the rumen epithelial cells cultured in neutral (pH=7.2) and acidic (pH=5.5) medium. Furthermore, histamine treatment also significantly increased the transcriptional activity of NF-κB p65. High expression and transcriptional activity of NF-κB p65 significantly increased the mRNA expressions and concentrations of inflammatory cytokines, tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6) and interleukin 1 beta (IL-1β), thereby inducing the inflammatory response in bovine rumen epithelial cells. However, inhibition of NF-κB p65 by PDTC significantly decreased the expressions and concentrations of the inflammatory cytokines induced by histamine in the rumen epithelial cells cultured in the neutral and acidic medium. The present data indicate that histamine induces the inflammatory response of bovine rumen epithelial cells through the NF-κB pathway. © 2017 The Author(s). Published by S. Karger AG, Basel.

Cocaine promotes both initiation and elongation phase of HIV-1 transcription by activating NF-κB and MSK1 and inducing selective epigenetic modifications at HIV-1 LTR

International Nuclear Information System (INIS)

Sahu, Geetaram; Farley, Kalamo; El-Hage, Nazira; Aiamkitsumrit, Benjamas; Fassnacht, Ryan; Kashanchi, Fatah; Ochem, Alex; Simon, Gary L.; Karn, Jonathan; Hauser, Kurt F.; Tyagi, Mudit

2015-01-01

Cocaine accelerates human immunodeficiency virus (HIV-1) replication by altering specific cell-signaling and epigenetic pathways. We have elucidated the underlying molecular mechanisms through which cocaine exerts its effect in myeloid cells, a major target of HIV-1 in central nervous system (CNS). We demonstrate that cocaine treatment promotes HIV-1 gene expression by activating both nuclear factor-kappa B (NF-ĸB) and mitogen- and stress-activated kinase 1 (MSK1). MSK1 subsequently catalyzes the phosphorylation of histone H3 at serine 10, and p65 subunit of NF-ĸB at 276th serine residue. These modifications enhance the interaction of NF-ĸB with P300 and promote the recruitment of the positive transcription elongation factor b (P-TEFb) to the HIV-1 LTR, supporting the development of an open/relaxed chromatin configuration, and facilitating the initiation and elongation phases of HIV-1 transcription. Results are also confirmed in primary monocyte derived macrophages (MDM). Overall, our study provides detailed insights into cocaine-driven HIV-1 transcription and replication. - Highlights: • Cocaine induces the initiation phase of HIV transcription by activating NF-ĸB. • Cocaine induced NF-ĸB phosphorylation promotes its interaction with P300. • Cocaine enhances the elongation phase of HIV transcription by stimulating MSK1. • Cocaine activated MSK1 catalyzes the phosphorylation of histone H3 at its Ser10. • Cocaine induced H3S10 phosphorylation facilitates the recruitment of P-TEFb at LTR

Cocaine promotes both initiation and elongation phase of HIV-1 transcription by activating NF-κB and MSK1 and inducing selective epigenetic modifications at HIV-1 LTR

Energy Technology Data Exchange (ETDEWEB)

Sahu, Geetaram; Farley, Kalamo [Division of Infectious Diseases, Department of Medicine, George Washington University, Washington, DC (United States); El-Hage, Nazira [Virginia Commonwealth University, Richmond, VA (United States); Aiamkitsumrit, Benjamas; Fassnacht, Ryan [Division of Infectious Diseases, Department of Medicine, George Washington University, Washington, DC (United States); Kashanchi, Fatah [George Mason University, Manassas, VA (United States); Ochem, Alex [ICGEB, Wernher and Beit Building, Anzio Road, Observatory, 7925 Cape Town (South Africa); Simon, Gary L. [Division of Infectious Diseases, Department of Medicine, George Washington University, Washington, DC (United States); Karn, Jonathan [Case Western Reserve University, Cleveland, OH (United States); Hauser, Kurt F. [Virginia Commonwealth University, Richmond, VA (United States); Tyagi, Mudit, E-mail: tmudit@email.gwu.edu [Division of Infectious Diseases, Department of Medicine, George Washington University, Washington, DC (United States); Department of Microbiology, Immunology and Tropical Medicine, George Washington University, Washington, DC 20037 (United States)

2015-09-15

Cocaine accelerates human immunodeficiency virus (HIV-1) replication by altering specific cell-signaling and epigenetic pathways. We have elucidated the underlying molecular mechanisms through which cocaine exerts its effect in myeloid cells, a major target of HIV-1 in central nervous system (CNS). We demonstrate that cocaine treatment promotes HIV-1 gene expression by activating both nuclear factor-kappa B (NF-ĸB) and mitogen- and stress-activated kinase 1 (MSK1). MSK1 subsequently catalyzes the phosphorylation of histone H3 at serine 10, and p65 subunit of NF-ĸB at 276th serine residue. These modifications enhance the interaction of NF-ĸB with P300 and promote the recruitment of the positive transcription elongation factor b (P-TEFb) to the HIV-1 LTR, supporting the development of an open/relaxed chromatin configuration, and facilitating the initiation and elongation phases of HIV-1 transcription. Results are also confirmed in primary monocyte derived macrophages (MDM). Overall, our study provides detailed insights into cocaine-driven HIV-1 transcription and replication. - Highlights: • Cocaine induces the initiation phase of HIV transcription by activating NF-ĸB. • Cocaine induced NF-ĸB phosphorylation promotes its interaction with P300. • Cocaine enhances the elongation phase of HIV transcription by stimulating MSK1. • Cocaine activated MSK1 catalyzes the phosphorylation of histone H3 at its Ser10. • Cocaine induced H3S10 phosphorylation facilitates the recruitment of P-TEFb at LTR.

Long-term performance and fouling analysis of full-scale direct nanofiltration (NF) installations treating anoxic groundwater

KAUST Repository

Beyer, Florian

2014-10-01

Long-term performance and fouling behavior of four full-scale nanofiltration (NF) plants, treating anoxic groundwater at 80% recovery for drinking water production, were characterized and compared with oxic NF and reverse osmosis systems. Plant operating times varied between 6 and 10 years and pretreatment was limited to 10μm pore size cartridge filtration and antiscalant dosage (2-2.5mgL-1) only. Membrane performance parameters normalized pressure drop (NPD), normalized specific water permeability (Kw) and salt retention generally were found stable over extended periods of operation (>6 months). Standard acid-base cleanings (once per year or less) were found to be sufficient to maintain satisfying operation during direct NF of the described iron rich (≤8.4mgL-1) anoxic groundwaters. Extensive autopsies of eight NF membrane elements, which had been in service since the plant startup (6-10 years), were performed to characterize and quantify the material accumulated in the membrane elements. Investigations using scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), total organic carbon (TOC) and adenosine triphosphate (ATP) measurements revealed a complex mixture of organic, biological and inorganic materials. The fouling layers that developed during half to one year of operation without chemical cleaning were very thin (<2. μm). Most bio(organic) accumulates were found in the lead elements of the installations while inorganic precipitates/deposits (aluminosilicates and iron(II)sulfides) were found in all autopsied membrane elements. The high solubility of reduced metal ions and the very slow biofilm development under anoxic conditions prevented rapid fouling during direct NF of the studied groundwaters. When compared to oxic NF and RO systems in general (e.g. aerated ground waters or surface waters), the operation and performance of the described anoxic installations (with minimal pretreatment) can be described as very stable. © 2014

Quantification of cellular NEMO content and its impact on NF-κB activation by genotoxic stress.

Directory of Open Access Journals (Sweden)

Byounghoon Hwang

Full Text Available NF-κB essential modulator, NEMO, plays a key role in canonical NF-κB signaling induced by a variety of stimuli, including cytokines and genotoxic agents. To dissect the different biochemical and functional roles of NEMO in NF-κB signaling, various mutant forms of NEMO have been previously analyzed. However, transient or stable overexpression of wild-type NEMO can significantly inhibit NF-κB activation, thereby confounding the analysis of NEMO mutant phenotypes. What levels of NEMO overexpression lead to such an artifact and what levels are tolerated with no significant impact on NEMO function in NF-κB activation are currently unknown. Here we purified full-length recombinant human NEMO protein and used it as a standard to quantify the average number of NEMO molecules per cell in a 1.3E2 NEMO-deficient murine pre-B cell clone stably reconstituted with full-length human NEMO (C5. We determined that the C5 cell clone has an average of 4 x 10(5 molecules of NEMO per cell. Stable reconstitution of 1.3E2 cells with different numbers of NEMO molecules per cell has demonstrated that a 10-fold range of NEMO expression (0.6-6x10(5 molecules per cell yields statistically equivalent NF-κB activation in response to the DNA damaging agent etoposide. Using the C5 cell line, we also quantified the number of NEMO molecules per cell in several commonly employed human cell lines. These results establish baseline numbers of endogenous NEMO per cell and highlight surprisingly normal functionality of NEMO in the DNA damage pathway over a wide range of expression levels that can provide a guideline for future NEMO reconstitution studies.

Bradykinin B2 receptor expression in the bronchial mucosa of allergic asthmatics: the role of NF-kB.

Science.gov (United States)

Ricciardolo, F L M; Petecchia, L; Sorbello, V; Di Stefano, A; Usai, C; Massaglia, G M; Gnemmi, I; Mognetti, B; Hiemstra, P S; Sterk, P J; Sabatini, F

2016-03-01

Bradykinin (BK) mediates acute allergic asthma and airway remodelling. Nuclear factor-kappa B (NF-kB) is potentially involved in BK B2 receptor (B2R) regulation. In this observational cross-sectional study, B2R and NF-kB expression was evaluated in bronchial biopsies from mild asthmatics (after diluent/allergen challenge) and healthy controls, examining the role of NF-kB in B2R expression in primary human fibroblasts from normal and asthmatic subjects (HNBFb and HABFb). B2R and NF-kB (total and nuclear) expression was analysed by immunohistochemistry in biopsies from 10 mild intermittent asthmatics (48 h after diluent/allergen challenge) and 10 controls undergoing bronchoscopy. B2R co-localization in 5B5(+) and αSMA(+) mesenchymal cells was studied by immunofluorescence/confocal microscopy, and B2R expression in HABFb/HNBFb incubated with interleukin (IL)-4/IL-13 with/without BK, and after NF-kB inhibitor, by Western blotting. Bronchial mucosa B2R and nuclear NF-kB expression was higher in asthmatics after diluent (B2R only) and allergen challenge than in controls (P kB (total and nuclear) increased after allergen compared with after diluent (P kB inhibitor (P kB expression. NF-kB inhibitor blocked IL-4/IL-13-induced increase in B2R expression in cultured fibroblasts, suggesting a role as potential anti-asthma drug. © 2015 John Wiley & Sons Ltd.

Prime Contract Awards Alphabetically by Contractor, by State or Country, and Place, Fiscal Year 1985. Part 11 (International Computer Corp - Kloze N S Inc).

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1985-01-01

N 0 mC. m.( m( m0 C) (0 (0 (0 0 Nf.0 r. cNNr4NO (0 en (0 MSP (0 *50 -W (0 -1 0 0 0 0 NC) 000 0 "-4 0 I(( (0 (1 1) P7 L) (0 in 4. -.4-4 m -& (D U (0... acCA -4N NN CcC4c xC4 NN N4 10L 0 ( Z-4 -I 4N . ".. (0 N 1-.U -4 .4 co -lOI m a) a) mne M 0. N r. I0 I0 I 0- 0. nc c n CI C% 004 0 00 0 04 " "N . .0

DMS triggers apoptosis associated with the inhibition of SPHK1/NF-κB activation and increase in intracellular Ca2+ concentration in human cancer cells.

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Chen, Kan; Pan, Qiuwei; Gao, Ying; Yang, Xinyan; Wang, Shibing; Peppelenbosch, Maikel P; Kong, Xiangdong

2014-01-01

N,N-Dimethyl-D-erythro-sphingosine (DMS) is known to induce cell apoptosis by specifically inhibiting sphingosine kinase 1 (SPHK1) and modulating the activity of cellular ceramide levels. The present study investigated the effects and the mechanism(s) of action of DMS in human lung cancer cells. We found that DMS dose-dependently suppressed cell proliferation and induced cell apoptosis in the human lung cancer cell line, A549. Mechanistically, treatment with DMS suppressed the activation of SPHK1 and nuclear factor-κB (NF-κB) p65, but increased intracellular [Ca2+]i in A549 cells. This study demonstrates that DMS triggers the apoptosis of human lung cancer cells through the modulation of SPHK1, NF-κB and calcium signaling. These molecules may represent targets for anticancer drug design.

Non-coding RNA ANRIL and the number of plexiform neurofibromas in patients with NF1 microdeletions

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Mußotter Tanja

2012-10-01

Full Text Available Abstract Background Neurofibromatosis type-1 (NF1 is caused by mutations of the NF1 gene at 17q11.2. In 95% of non-founder NF1 patients, NF1 mutations are identifiable by means of a comprehensive mutation analysis. 5-10% of these patients harbour microdeletions encompassing the NF1 gene and its flanking regions. NF1 is characterised by tumours of the peripheral nerve sheaths, the pathognomonic neurofibromas. Considerable inter- and intra-familial variation in expressivity of the disease has been observed which is influenced by genetic modifiers unrelated to the constitutional NF1 mutation. The number of plexiform neurofibromas (PNF in NF1 patients is a highly heritable genetic trait. Recently, SNP rs2151280 located within the non-coding RNA gene ANRIL at 9p21.3, was identified as being strongly associated with PNF number in a family-based association study. The T-allele of rs2151280, which correlates with reduced ANRIL expression, appears to be associated with higher PNF number. ANRIL directly binds to the SUZ12 protein, an essential component of polycomb repressive complex 2, and is required for SUZ12 occupancy of the CDKN2A/CDKN2B tumour suppressor genes as well as for their epigenetic silencing. Methods Here, we explored a potential association of PNF number and PNF volume with SNP rs2151280 in 29 patients with constitutional NF1 microdeletions using the exact Cochran-Armitage test for trends and the exact Mann–Whitney–Wilcoxon test. Both the PNF number and total tumour volume in these 29 NF1 patients were assessed by whole-body MRI. The NF1 microdeletions observed in these 29 patients encompassed the NF1 gene as well as its flanking regions, including the SUZ12 gene. Results In the 29 microdeletion patients investigated, neither the PNF number nor PNF volume was found to be associated with the T-allele of rs2151280. Conclusion Our findings imply that, at least in patients with NF1 microdeletions, PNF susceptibility is not associated with

Development of NF3 Deposit Removal Technology for the Portsmouth Gaseous Diffusion Plant

International Nuclear Information System (INIS)

Scheele, R.D.; McNamara, B.K.; Rapko, B.M.; Edwards, M.K.; Kozelisky, A.E.; Daniel, R.C.; McSweeney, T.I.; Maharas, S.J.; Weaver, P.J.; Iwamasa, K.J.; Kefgen, R.B.

2006-01-01

This paper summarizes the Battelle, Stoller, and WASTREN (BSW) team's efforts, to date, in support of the United States Department of Energy's plans to remove uranium and technetium deposits before decommissioning the Portsmouth Gaseous Diffusion Plant. The BSW team investigated nitrogen trifluoride (NF 3 ) as a safer yet effective alternative gaseous treatment to the chlorine trifluoride (ClF 3 )-elemental fluorine (F 2 ) treatment currently used to remove uranium and technetium deposits from the uranium enrichment cascade. Both ClF 3 and F 2 are highly reactive, toxic, and hazardous gases, while NF 3 , although toxic [1], is no more harmful than moth balls [2]. BSW's laboratory thermo-analytical and laboratory-scale prototype studies with NF 3 established that thermal NF 3 can effectively remove likely and potential uranium (UO 2 F 2 and UF 4 ) and technetium deposits (a surrogate deposit material, TcO 2 , and pertechnetates) by conversion to volatile compounds. Our engineering evaluations suggest that NF 3 's effectiveness could be enhanced by combining with a lesser concentration of ClF 3 . BSW's and other's studies indicate compatibility with Portsmouth materials of construction (aluminum, copper, and nickel). (authors)

(2S,7S-10-Ethyl-1,8,10,12-tetraazatetracyclo[8.3.1.18,12.02,7]pentadecan-10-ium iodide

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Augusto Rivera

2012-10-01

Full Text Available The title chiral quaternary ammonium salt, C13H25N4+·I−, was synthesized through the Menschutkin reaction between the cage aminal (2S,7S-1,8,10,12-tetraazatetracyclo[8.3.1.18,12.02,7]pentadecane and ethyl iodide. The quaternization occurred regioselectively on the nitrogen with major sp3 character. The crystal structure consists of anions and cations separated by normal distances. Ions are not linked through C—H...I hydrogen bonds.

The novel NF-κB inhibitor IMD-0354 induces apoptosis in chronic lymphocytic leukemia

International Nuclear Information System (INIS)

Kanduri, M; Tobin, G; Åleskog, A; Nilsson, K; Rosenquist, R

2011-01-01

Nuclear factor-κB (NF-κB) is an important regulator of cell survival and has been shown to be constitutively active in chronic lymphocytic leukemia (CLL) cells. Recently, a novel NF-κB inhibitor, IMD-0354 (N-(3, 5-bis-trifluoromethyl-phenyl)-5-chloro-2-hydroxy-benzamide), was shown to specifically inhibit the phosphorylation of IκBα by IkB kinases, thus preventing NF-κB release. In this study, we investigated if IMD-0354 can inhibit NF-κB activation and induce apoptosis in CLL cells in vitro. The rate of increase in apoptosis, drug sensitivity and DNA-binding activity of NF-κB were studied using Annexin V stainings, the fluorometric microculture cytotoxicity assay and electrophoretic mobility shift assay, respectively. Finally, the impact of IMD-0354 treatment on the expression of a set of apoptosis-related genes was investigated. The results clearly show that IMD-0354 induced apoptosis (mean 26%, range 8–48%) in CLL cells, independent of immunoglobulin heavy variable (IGHV) gene mutational status, and showed a dose-dependent cytotoxic effect. IMD-0354 treatment also significantly lowered the DNA-binding activity of NF-κB in CLL cells. In addition, we identified differences in expression levels of pro- and antiapoptotic genes following IMD-0354 treatment. In summary, our novel findings show that IMD-0354 can induce apoptosis in CLL cells, and thus merits further investigation as an anticancer agent in vivo

The novel NF-κB inhibitor IMD-0354 induces apoptosis in chronic lymphocytic leukemia

Science.gov (United States)

Kanduri, M; Tobin, G; Åleskog, A; Nilsson, K; Rosenquist, R

2011-01-01

Nuclear factor-κB (NF-κB) is an important regulator of cell survival and has been shown to be constitutively active in chronic lymphocytic leukemia (CLL) cells. Recently, a novel NF-κB inhibitor, IMD-0354 (N-(3, 5-bis-trifluoromethyl-phenyl)-5-chloro-2-hydroxy-benzamide), was shown to specifically inhibit the phosphorylation of IκBα by IkB kinases, thus preventing NF-κB release. In this study, we investigated if IMD-0354 can inhibit NF-κB activation and induce apoptosis in CLL cells in vitro. The rate of increase in apoptosis, drug sensitivity and DNA-binding activity of NF-κB were studied using Annexin V stainings, the fluorometric microculture cytotoxicity assay and electrophoretic mobility shift assay, respectively. Finally, the impact of IMD-0354 treatment on the expression of a set of apoptosis-related genes was investigated. The results clearly show that IMD-0354 induced apoptosis (mean 26%, range 8–48%) in CLL cells, independent of immunoglobulin heavy variable (IGHV) gene mutational status, and showed a dose-dependent cytotoxic effect. IMD-0354 treatment also significantly lowered the DNA-binding activity of NF-κB in CLL cells. In addition, we identified differences in expression levels of pro- and antiapoptotic genes following IMD-0354 treatment. In summary, our novel findings show that IMD-0354 can induce apoptosis in CLL cells, and thus merits further investigation as an anticancer agent in vivo. PMID:22829125

The novel NF-κB inhibitor IMD-0354 induces apoptosis in chronic lymphocytic leukemia

Energy Technology Data Exchange (ETDEWEB)

Kanduri, M; Tobin, G [Rudbeck Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala (Sweden); Åleskog, A [Department of Medical Sciences, Clinical Pharmacology, Uppsala University, Uppsala (Sweden); Nilsson, K; Rosenquist, R [Rudbeck Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala (Sweden)

2011-03-01

Nuclear factor-κB (NF-κB) is an important regulator of cell survival and has been shown to be constitutively active in chronic lymphocytic leukemia (CLL) cells. Recently, a novel NF-κB inhibitor, IMD-0354 (N-(3, 5-bis-trifluoromethyl-phenyl)-5-chloro-2-hydroxy-benzamide), was shown to specifically inhibit the phosphorylation of IκBα by IkB kinases, thus preventing NF-κB release. In this study, we investigated if IMD-0354 can inhibit NF-κB activation and induce apoptosis in CLL cells in vitro. The rate of increase in apoptosis, drug sensitivity and DNA-binding activity of NF-κB were studied using Annexin V stainings, the fluorometric microculture cytotoxicity assay and electrophoretic mobility shift assay, respectively. Finally, the impact of IMD-0354 treatment on the expression of a set of apoptosis-related genes was investigated. The results clearly show that IMD-0354 induced apoptosis (mean 26%, range 8–48%) in CLL cells, independent of immunoglobulin heavy variable (IGHV) gene mutational status, and showed a dose-dependent cytotoxic effect. IMD-0354 treatment also significantly lowered the DNA-binding activity of NF-κB in CLL cells. In addition, we identified differences in expression levels of pro- and antiapoptotic genes following IMD-0354 treatment. In summary, our novel findings show that IMD-0354 can induce apoptosis in CLL cells, and thus merits further investigation as an anticancer agent in vivo.

Recovery of iron after Fenton-like secondary treatment of olive mill wastewater by nano-filtration and low-pressure reverse osmosis membranes; Recuperación de hierro tras tratamiento secundario tipo Fenton de agua residual de la industria oleícola por membranas de nanofiltración y ósmosis inversa de baja presión

Energy Technology Data Exchange (ETDEWEB)

Ochando-Pulido, J.M.; Victor-Ortega, M.D.; Martinez-Ferez, A.

2016-07-01

, las corrientes de permeado podrían ser reutilizadas para riego. Por otro lado, la productividad asegurada por la membrana de NF seleccionada fue mayor, en horno a 47.4 L/hm2 a 9 bar, mientras que 30.9 L/hm2 pudieron ser producidos por la membrana de OI bajo una presión operativa de 8 bar. Además, un índice de fouling sensiblemente menor fue medido en la membrana de NF (0.0072 en contraste con 0.065), lo que asegura mayor rendimiento en estado estacionario para esta membrana, y mayor vida de servicio. Además, ello también resultó en una menor área de membrana y sobredimensionamiento de la planta requeridas (4 módulos en caso de OI mientras que sólo para NF).

Design Concept of a Seal-off Type 14 MeV Neutron Generator of 10''1''1n/s Range

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In, S. R.; Oh, B. H. [KAERI, Daejeon (Korea, Republic of)

2015-05-15

The total neutron fluence during the life time is expected to be around 10MW·yr/m''2 which may cause a damage of -100 dpa in materials. To estimate the adaptability of candidate materials in a few years, a 14MeV neutron source with a flux level of 3 - 5 x 10''1''8 n/s·m''2, which is the goal of the IFMIF facility costing more than ¤1000M, is necessitated. The problem in making an intense neutron generator of beam target type is really not on the neutron production rate, but on the huge heat generated in the target, because the fusion power is only one of thousands of beam power exerted on the target. We have a plan to develop neutron generators step by step from a 10''8 n/s level. The final goal is establishing a 14MeV neutron irradiation facility at 10''1''4 intensity level.. Up to the 10''1''0 n/s level, there occurs basically no critical thermal problem, because beam power density is in the range of tens W/cm''2. The neutron generator designed in a sealed-off type because of tritium safety is mainly composed of an ion source, target, reaction chamber, and getter pump.. The major design concepts for the neutron generator with the neutron production rate of 10''1''1 n/s range were presented. The specifications of the ion source, target and getter have been determined for attaining the goal of the neutron generation rate.

A novel Toxoplasma gondii nuclear factor TgNF3 is a dynamic chromatin-associated component, modulator of nucleolar architecture and parasite virulence.

Directory of Open Access Journals (Sweden)

Alejandro Olguin-Lamas

2011-03-01

Full Text Available In Toxoplasma gondii, cis-acting elements present in promoter sequences of genes that are stage-specifically regulated have been described. However, the nuclear factors that bind to these cis-acting elements and regulate promoter activities have not been identified. In the present study, we performed affinity purification, followed by proteomic analysis, to identify nuclear factors that bind to a stage-specific promoter in T. gondii. This led to the identification of several nuclear factors in T. gondii including a novel factor, designated herein as TgNF3. The N-terminal domain of TgNF3 shares similarities with the N-terminus of yeast nuclear FK506-binding protein (FKBP, known as a histone chaperone regulating gene silencing. Using anti-TgNF3 antibodies, HA-FLAG and YFP-tagged TgNF3, we show that TgNF3 is predominantly a parasite nucleolar, chromatin-associated protein that binds specifically to T. gondii gene promoters in vivo. Genome-wide analysis using chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq identified promoter occupancies by TgNF3. In addition, TgNF3 has a direct role in transcriptional control of genes involved in parasite metabolism, transcription and translation. The ectopic expression of TgNF3 in the tachyzoites revealed dynamic changes in the size of the nucleolus, leading to a severe attenuation of virulence in vivo. We demonstrate that TgNF3 physically interacts with H3, H4 and H2A/H2B assembled into bona fide core and nucleosome-associated histones. Furthermore, TgNF3 interacts specifically to histones in the context of stage-specific gene silencing of a promoter that lacks active epigenetic acetylated histone marks. In contrast to virulent tachyzoites, which express the majority of TgNF3 in the nucleolus, the protein is exclusively located in the cytoplasm of the avirulent bradyzoites. We propose a model where TgNF3 acts essentially to coordinate nucleolus and nuclear functions by modulating

NF-kappaB in Lung Tumorigenesis

International Nuclear Information System (INIS)

Cai, Zhenjian; Tchou-Wong, Kam-Meng; Rom, William N.

2011-01-01

The development of lung cancer in humans can be divided into three steps initiation, promotion and progression. This process is driven by alterations in related signal transduction pathways. These pathways signal the aberrant activation of NF-kappaB, a transcription factor that regulates the expression of genes important for lung tumorigenesis. Our current knowledge about the role of the NF-kappaB signaling pathway in the development of lung cancer has been bolstered by animal models demonstrating the connection between K-ras and tobacco induced lung transformation with NF-kappaB. Activation of downstream genes leads to cell proliferation, inhibition of apoptosis, angiogenesis, inflammation, invasion, and metastasis

NF-kappaB in Lung Tumorigenesis

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Cai, Zhenjian [Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, New York University School of Medicine, 462 First Avenue, NBV 7N24, New York, NY 10016 (United States); Tchou-Wong, Kam-Meng; Rom, William N., E-mail: william.rom@nyumc.org [Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, New York University School of Medicine, 462 First Avenue, NBV 7N24, New York, NY 10016 (United States); Department of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo, NY 10987 (United States)

2011-12-14

The development of lung cancer in humans can be divided into three steps initiation, promotion and progression. This process is driven by alterations in related signal transduction pathways. These pathways signal the aberrant activation of NF-kappaB, a transcription factor that regulates the expression of genes important for lung tumorigenesis. Our current knowledge about the role of the NF-kappaB signaling pathway in the development of lung cancer has been bolstered by animal models demonstrating the connection between K-ras and tobacco induced lung transformation with NF-kappaB. Activation of downstream genes leads to cell proliferation, inhibition of apoptosis, angiogenesis, inflammation, invasion, and metastasis.

NF-kappaB: Two Sides of the Same Coin.

Science.gov (United States)

Pires, Bruno R B; Silva, Rafael C M C; Ferreira, Gerson M; Abdelhay, Eliana

2018-01-09

Nuclear Factor-kappa B (NF-κB) is a transcription factor family that regulates a large number of genes that are involved in important physiological processes, including survival, inflammation, and immune responses. More recently, constitutive expression of NF-κB has been associated with several types of cancer. In addition, microorganisms, such as viruses and bacteria, cooperate in the activation of NF-κB in tumors, confirming the multifactorial role of this transcription factor as a cancer driver. Recent reports have shown that the NF-κB signaling pathway should receive attention for the development of therapies. In addition to the direct effects of NF-κB in cancer cells, it might also impact immune cells that can both promote or prevent tumor development. Currently, with the rise of cancer immunotherapy, the link among immune cells, inflammation, and cancer is a major focus, and NF-κB could be an important regulator for the success of these therapies. This review discusses the contrasting roles of NF-κB as a regulator of pro- and antitumor processes and its potential as a therapeutic target.

A new structural class of proteasome inhibitors that prevent NF-kappa B activation.

Science.gov (United States)

Lum, R T; Kerwar, S S; Meyer, S M; Nelson, M G; Schow, S R; Shiffman, D; Wick, M M; Joly, A

1998-05-01

The multicatalytic proteinase or proteasome is a highly conserved cellular structure that is responsible for the ATP-dependent proteolysis of many proteins involved in important regulatory cellular processes. We have identified a novel class of inhibitors of the chymotrypsin-like proteolytic activity of the 20S proteasome that exhibit IC50 values ranging from 0.1 to 0.5 microgram/mL (0.1 to 1 microM). In cell proliferation assays, these compounds inhibit growth with an IC50 ranging from 5 to 10 micrograms/mL (10-20 microM). A representative member of this class of inhibitors was tested in other biological assays. CVT-634 (5-methoxy-1-indanone-3-acetyl-leu-D-leu-1-indanylamide) prevented lipopolysaccharide (LPS), tumor necrosis factor (TNF)-, and phorbol ester-induced activation of nuclear factor kappa B (NF-kappa B) in vitro by preventing signal-induced degradation of I kappa B-alpha. In these studies, the I kappa B-alpha that accumulated was hyperphosphorylated, indicating that CVT-634 did not inhibit I kappa B-alpha kinase, the enzyme responsible for signal-induced phosphorylation of I kappa B-alpha. In vivo studies indicated that CVT-634 prevented LPS-induced TNF synthesis in a murine macrophage cell line. In addition, in mice pretreated with CVT-634 at 25 and 50 mg/kg and subsequently treated with LPS, serum TNF levels were significantly lower (225 +/- 59 and 83 +/- 41 pg/mL, respectively) than in those mice that were treated only with LPS (865 +/- 282 pg/mL). These studies suggest that specific inhibition of the chymotrypsin-like activity of the proteasome is sufficient to prevent signal-induced NF-kappa B activation and that the proteasome is a novel target for the identification of agents that may be useful in the treatment of diseases whose etiology is dependent upon the activation of NF-kappa B.

Phorbol-ester-induced activation of the NF-κB transcription factor involves dissociation of an apparently cytoplasmic NF-κB/inhibitor complex

International Nuclear Information System (INIS)

Baeuerle, P.A.; Lenardo, M.; Pierce, J.W.; Baltimore, D.

1988-01-01

There is increasing evidence that inducible transcription of genes is mediated through the induction of the activity of trans-acting protein factors. The NF-κB transcription factor provides a model system to study the posttranslational activation of a phorbol-ester-inducible transcription factor. The finding that NF-κB activity is undectable in subcellular fractions from unstimulated cells suggests that NF-κB exists as an inactive precursor. The authors showed that NF-κB is detectable in two different forms. After selective removal of endogenous NF-κB, they demonstrate the existence of a protein inhibitor in cytosolic fractions of unstimulated cells that is able in vitro to convert NF-κB into an inactive desoxycholate-dependent form. The data are consistent with a molecular mechanism of inducible gene expression by which an apparently cytoplasmic transcription factor-inhibitor complex is dissociated by the action of TPA-activated protein kinase C

Single Hind Limb Burn Injury to Mice Alters NF Kappa B (NF-κB) Expression and [18F] 2-Fluoro-2-Deoxy-d-Glucose (FDG) Uptake

Science.gov (United States)

Carter, Edward A.; Hamrahi, Victoria; Paul, Kasie; Bonab, Ali A.; Jung, Walter; Tompkins, Ronald G.; Fischman, Alan J.

2014-01-01

Burn trauma to the extremities can produce marked systemic effects in mice1, 6, 7. Burn injury to the dorsal surface of mice is also associated with changes in glucose metabolism (18FDG uptake) by brown adipose tissue (BAT) and NF-κB activity in a number of tissues including skeletal muscle. This study examined the effect of a single hindlimb burn in mice on 18FDG uptake by in vivo, NF-κB activity in vivo, and blood flow determined by laser Doppler techniques. Male mice NF-κB luciferase reporter mice (28 grams- 30 grams, male) were anesthetized, both legs were shaven, and the right leg was subjected to scald injury by immersion in 90°C water for 5 seconds. Sham treated animals were used as controls. Each burned and sham mouse was resuscitated with saline (2 ml, IP). The individual animals were placed in wire bottom cages with no food and free access to water. 24 hrs later, the animals were imaged with Laser Doppler for measurements of blood flow in the hind limb. The animals were then injected unanesthetized with 50 µCi of FDG or luciferin (1.0 mg), I.V. via tail vein. Five minutes after luciferin injection, NF-kB mice were studied by bioluminescence imaging with a CCD camera. One hour after 18FDG injection the animals were euthanized with carbon dioxide overdose and 18FDG biodistribution was measured. Tissues were also analyzed for NF-κB luciferase activity. The scalding procedure used here produced a full thickness burn injury to the leg with sharp margins. 18FDG uptake by the burned leg was lower than in the contralateral limb. Similarly luciferase activity and blood flow in the burned leg were lower than in the contralateral leg. 18FDG uptake by BAT and heart was increased, while brain was decreased. In conclusion, the present study suggests that burn injury to a single leg reduced 18FDG uptake by skeletal muscle but increased 18FDG uptake by BAT. The injury to the leg reduced NF-κB expression as compared to the contralateral leg and the uninjured

The epigenetic effect of glucosamine and a nuclear factor-kappa B (NF-kB) inhibitor on primary human chondrocytes - Implications for osteoarthritis

Energy Technology Data Exchange (ETDEWEB)

Imagawa, Kei, E-mail: k.Imagawa@soton.ac.uk [University of Southampton Medical School, Bone and Joint Research Group, Southampton (United Kingdom); Tohoku University School of Medicine, Sendai (Japan); Andres, MC de [University of Southampton Medical School, Bone and Joint Research Group, Southampton (United Kingdom); Hashimoto, Ko [Hospital for Special Surgery, NY (United States); Pitt, Dominic [University of Southampton Medical School, Bone and Joint Research Group, Southampton (United Kingdom); Itoi, Eiji [Tohoku University School of Medicine, Sendai (Japan); Goldring, Mary B. [Hospital for Special Surgery, NY (United States); Roach, Helmtrud I.; Oreffo, Richard O.C. [University of Southampton Medical School, Bone and Joint Research Group, Southampton (United Kingdom)

2011-02-18

-acetyl GlcN (Sigma-Aldrich), (iv) cultured with a mixture of 2.5 ng/ml IL-1{beta}, 2.5 ng/ml OSM and 2 mM GlcN, (v) cultured with 1.0 {mu}M BAY 11-7082 (BAY; NF-kB inhibitor: Calbiochem, Darmstadt, Germany) and, (vi) cultured with a mixture of 2.5 ng/ml IL-1{beta}, 2.5 ng/ml OSM and 1.0 {mu}M BAY. The levels of IL1B and MMP13 mRNA were examined using qRT-PCR. The percentage DNA methylation in the CpG sites of the IL1{beta} and MMP13 proximal promoter were quantified by pyrosequencing. Result:IL1{beta} expression was enhanced over 580-fold in articular chondrocytes treated with IL-1{beta} and OSM. GlcN dramatically ameliorated the cytokine-induced expression by 4-fold. BAY alone increased IL1{beta} expression by 3-fold. In the presence of BAY, IL-1{beta} induced IL1B mRNA levels were decreased by 6-fold. The observed average percentage methylation of the -256 CpG site in the IL1{beta} promoter was 65% in control cultures and decreased to 36% in the presence of IL-1{beta}/OSM. GlcN and BAY alone had a negligible effect on the methylation status of the IL1B promoter. The cytokine-induced loss of methylation status in the IL1B promoter was ameliorated by both GlcN and BAY to 44% and 53%, respectively. IL-1{beta}/OSM treatment increased MMP13 mRNA levels independently of either GlcN or BAY and no change in the methylation status of the MMP13 promoter was observed. Conclusion: We demonstrate for the first time that GlcN and BAY can prevent cytokine-induced demethylation of a specific CpG site in the IL1{beta} promoter and this was associated with decreased expression of IL1{beta}. These studies provide a potential mechanism of action for OA disease modifying agents via NF-kB and, critically, demonstrate the need for further studies to elucidate the role that NF-kB may play in DNA demethylation in human chondrocytes.

The epigenetic effect of glucosamine and a nuclear factor-kappa B (NF-kB) inhibitor on primary human chondrocytes - Implications for osteoarthritis

International Nuclear Information System (INIS)

Imagawa, Kei; Andres, MC de; Hashimoto, Ko; Pitt, Dominic; Itoi, Eiji; Goldring, Mary B.; Roach, Helmtrud I.; Oreffo, Richard O.C.

2011-01-01

-Aldrich), (iv) cultured with a mixture of 2.5 ng/ml IL-1β, 2.5 ng/ml OSM and 2 mM GlcN, (v) cultured with 1.0 μM BAY 11-7082 (BAY; NF-kB inhibitor: Calbiochem, Darmstadt, Germany) and, (vi) cultured with a mixture of 2.5 ng/ml IL-1β, 2.5 ng/ml OSM and 1.0 μM BAY. The levels of IL1B and MMP13 mRNA were examined using qRT-PCR. The percentage DNA methylation in the CpG sites of the IL1β and MMP13 proximal promoter were quantified by pyrosequencing. Result:IL1β expression was enhanced over 580-fold in articular chondrocytes treated with IL-1β and OSM. GlcN dramatically ameliorated the cytokine-induced expression by 4-fold. BAY alone increased IL1β expression by 3-fold. In the presence of BAY, IL-1β induced IL1B mRNA levels were decreased by 6-fold. The observed average percentage methylation of the -256 CpG site in the IL1β promoter was 65% in control cultures and decreased to 36% in the presence of IL-1β/OSM. GlcN and BAY alone had a negligible effect on the methylation status of the IL1B promoter. The cytokine-induced loss of methylation status in the IL1B promoter was ameliorated by both GlcN and BAY to 44% and 53%, respectively. IL-1β/OSM treatment increased MMP13 mRNA levels independently of either GlcN or BAY and no change in the methylation status of the MMP13 promoter was observed. Conclusion: We demonstrate for the first time that GlcN and BAY can prevent cytokine-induced demethylation of a specific CpG site in the IL1β promoter and this was associated with decreased expression of IL1β. These studies provide a potential mechanism of action for OA disease modifying agents via NF-kB and, critically, demonstrate the need for further studies to elucidate the role that NF-kB may play in DNA demethylation in human chondrocytes.

Cross sections and reaction rates for 23Na(p,n) 23Mg, 27Al(p,n) 27Si, 27Al(α,n) 30P, 29Si(α,n) 32S, and 30Si(α,n) 33S

International Nuclear Information System (INIS)

Flynn, D.S.; Sekharan, K.K.; Hiller, B.A.; Laumer, H.; Weil, J.L.; Gabbard, F.

1978-01-01

The total neutron production cross sections for the 23 Na(p,n) 23 Mg, 27 Al(p,n) 27 Si, 27 Al(α,n) 30 P, 29 Si(α,n) 32 S, and 30 Si(α,n) 33 S reactions have been measured for bombarding energies from threshold to 6.3 MeV. The neutron detector was a 60-cm diameter sphere of polyethylene with eight 10 BF 3 counters and was insensitive to the angle and energy of the emitted neutrons. Cross sections for inverse reactions have been obtained using the principle of detailed balance. The data have been used to determine parameters for statistical model calculations to facilitate extrapolation of cross sections to higher bombarding energies. These reactions are relevant to problems of nucleosynthesis and stellar evolution and to studies of radiation damage. Nucleosynthesis reaction rates, N/sub A/(sigmav), were determined for the reactions studied and are tabulated for temperatures ranging from 0.4 x 10 9 to 10.0 x 10 9 K

Piperlongumine selectively suppresses ABC-DLBCL through inhibition of NF-κB p65 subunit nuclear import

Energy Technology Data Exchange (ETDEWEB)

Niu, Mingshan [Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu (China); Jiangsu Key Laboratory of Bone Marrow Stem Cell, Xuzhou Medical College, Xuzhou, Jiangsu (China); Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu (China); Shen, Yangling; Xu, Xiaoyu [Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu (China); Jiangsu Key Laboratory of Bone Marrow Stem Cell, Xuzhou Medical College, Xuzhou, Jiangsu (China); Yao, Yao; Fu, Chunling [Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu (China); Jiangsu Key Laboratory of Bone Marrow Stem Cell, Xuzhou Medical College, Xuzhou, Jiangsu (China); Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu (China); Yan, Zhiling [Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu (China); Wu, Qingyun [Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu (China); Jiangsu Key Laboratory of Bone Marrow Stem Cell, Xuzhou Medical College, Xuzhou, Jiangsu (China); Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu (China); Cao, Jiang; Sang, Wei [Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu (China); Zeng, Lingyu [Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu (China); Jiangsu Key Laboratory of Bone Marrow Stem Cell, Xuzhou Medical College, Xuzhou, Jiangsu (China); Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu (China); Li, Zhenyu [Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu (China); Liu, Xuejiao, E-mail: liuxuejiao0923@126.com [Insititute of Nervous System Diseases, Xuzhou Medical College, Xuzhou, Jiangsu (China); and others

2015-07-10

Constitutive NF-κB activation is required for survival of activated B cell-like subtype of diffuse large B cell lymphoma (ABC-DLBCL). However, current NF-κB targeting strategies lack cancer cell specificity. Here, we identified a novel inhibitor, piperlongumine, features direct binding to NF-κB p65 subunit and suppression of p65 nuclear import. This was accompanied by NF-κB reporter activity suppression and NF-κB target gene downregulation. Moreover, mutation of Cys{sup 38} to Ser in p65 abolished this effect of piperlongumine on inhibition of p65 nuclear import. Furthermore, we show that piperlongumine selectively inhibited proliferation and induced apoptosis of ABC-DLBCL cells. Most notably, it has been reported that piperlongumine did not affect normal cells even at high doses and was nontoxic to animals. Hence, our current study provides new insight into piperlongumine's mechanism of action and novel approach to ABC-DLBCL target therapy. - Highlights: • Current NF-κB targeting strategies lack cancer cell specificity. • Piperlongumine inhibits NF-κB p65 subunit nuclear import via directly binding to p65. • Piperlongumine selectively inhibits proliferation of ABC-DLBCL cells. • This study provides a novel approach to ABC-DLBCL target therapy.

Piperlongumine selectively suppresses ABC-DLBCL through inhibition of NF-κB p65 subunit nuclear import

International Nuclear Information System (INIS)

Niu, Mingshan; Shen, Yangling; Xu, Xiaoyu; Yao, Yao; Fu, Chunling; Yan, Zhiling; Wu, Qingyun; Cao, Jiang; Sang, Wei; Zeng, Lingyu; Li, Zhenyu; Liu, Xuejiao

2015-01-01

Constitutive NF-κB activation is required for survival of activated B cell-like subtype of diffuse large B cell lymphoma (ABC-DLBCL). However, current NF-κB targeting strategies lack cancer cell specificity. Here, we identified a novel inhibitor, piperlongumine, features direct binding to NF-κB p65 subunit and suppression of p65 nuclear import. This was accompanied by NF-κB reporter activity suppression and NF-κB target gene downregulation. Moreover, mutation of Cys 38 to Ser in p65 abolished this effect of piperlongumine on inhibition of p65 nuclear import. Furthermore, we show that piperlongumine selectively inhibited proliferation and induced apoptosis of ABC-DLBCL cells. Most notably, it has been reported that piperlongumine did not affect normal cells even at high doses and was nontoxic to animals. Hence, our current study provides new insight into piperlongumine's mechanism of action and novel approach to ABC-DLBCL target therapy. - Highlights: • Current NF-κB targeting strategies lack cancer cell specificity. • Piperlongumine inhibits NF-κB p65 subunit nuclear import via directly binding to p65. • Piperlongumine selectively inhibits proliferation of ABC-DLBCL cells. • This study provides a novel approach to ABC-DLBCL target therapy

Inflammation and pancreatic cancer: molecular and functional interactions between S100A8, S100A9, NT-S100A8 and TGFβ1.

Science.gov (United States)

Basso, Daniela; Bozzato, Dania; Padoan, Andrea; Moz, Stefania; Zambon, Carlo-Federico; Fogar, Paola; Greco, Eliana; Scorzeto, Michele; Simonato, Francesca; Navaglia, Filippo; Fassan, Matteo; Pelloso, Michela; Dupont, Sirio; Pedrazzoli, Sergio; Fassina, Ambrogio; Plebani, Mario

2014-03-26

In order to gain further insight on the crosstalk between pancreatic cancer (PDAC) and stromal cells, we investigated interactions occurring between TGFβ1 and the inflammatory proteins S100A8, S100A9 and NT-S100A8, a PDAC-associated S100A8 derived peptide, in cell signaling, intracellular calcium (Cai2+) and epithelial to mesenchymal transition (EMT). NF-κB, Akt and mTOR pathways, Cai2+ and EMT were studied in well (Capan1 and BxPC3) and poorly differentiated (Panc1 and MiaPaCa2) cell lines. NT-S100A8, one of the low molecular weight N-terminal peptides from S100A8 to be released by PDAC-derived proteases, shared many effects on NF-κB, Akt and mTOR signaling with S100A8, but mainly with TGFβ1. The chief effects of S100A8, S100A9 and NT-S100A8 were to inhibit NF-κB and stimulate mTOR; the molecules inhibited Akt in Smad4-expressing, while stimulated Akt in Smad4 negative cells. By restoring Smad4 expression in BxPC3 and silencing it in MiaPaCa2, S100A8 and NT-S100A8 were shown to inhibit NF-κB and Akt in the presence of an intact TGFβ1 canonical signaling pathway. TGFβ1 counteracted S100A8, S100A9 and NT-S100A8 effects in Smad4 expressing, not in Smad4 negative cells, while it synergized with NT-S100A8 in altering Cai2+ and stimulating PDAC cell growth. The effects of TGFβ1 on both EMT (increased Twist and decreased N-Cadherin expression) and Cai2+ were antagonized by S100A9, which formed heterodimers with TGFβ1 (MALDI-TOF/MS and co-immuno-precipitation). The effects of S100A8 and S100A9 on PDAC cell signaling appear to be cell-type and context dependent. NT-S100A8 mimics the effects of TGFβ1 on cell signaling, and the formation of complexes between TGFβ1 with S100A9 appears to be the molecular mechanism underlying the reciprocal antagonism of these molecules on cell signaling, Cai2+ and EMT.

The bio-complex "reaction pattern in vertebrate cells" reduces cytokine-induced cellular adhesion molecule mRNA expression in human endothelial cells by attenuation of NF-kappaB translocation.

Science.gov (United States)

Rönnau, Cindy; Liebermann, Herbert E H; Helbig, Franz; Staudt, Alexander; Felix, Stephan B; Ewert, Ralf; Landsberger, Martin

2009-02-28

The bio-complex "reaction pattern in vertebrate cells" (RiV) is mainly represented by characteristic exosome-like particles--probably as reaction products of cells to specific stress. The transcription factor NF-kappaB plays a central role in inflammation. We tested the hypothesis that RiV particle preparations (RiV-PP) reduce cellular adhesion molecule (CAM) expression (ICAM-1, VCAM-1, E-selectin) by the attenuation of NF-kappaB translocation in human umbilical vein endothelial cells (HUVEC). After 4 hours, pre-incubation of HUVEC with RiV-PP before stimulation with TNF-alpha significantly reduced ICAM-1 (65.5+/-10.3%) and VCAM-1 (71.1+/-12.3%) mRNA expression compared to TNF-alpha-treated cells (100%, n=7). ICAM-1 surface expression was significantly albeit marginally reduced in RiV/TNF-alpha- treated cells (92.0+/-5.6%, n=4). No significant effect was observed on VCAM-1 surface expression. In RiV/TNF-alpha-treated cells (n=4), NF-kappaB subunits p50 (85.7+/-4.1%) and p65 (85.0+/-1.8%) nuclear translocation was significantly reduced. RiV-PP may exert an anti-inflammatory effect in HUVEC by reducing CAM mRNA expression via attenuation of p50 and p65 translocation.

Fatigue and gene expression in human leukocytes: Increased NF-κB and decreased glucocorticoid signaling in breast cancer survivors with persistent fatigue

Science.gov (United States)

Bower, Julienne E.; Ganz, Patricia A.; Irwin, Michael R.; Arevalo, Jesusa M.G.; Cole, Steve W.

2013-01-01

Fatigue is highly prevalent in the general population and is one of the most common side effects of cancer treatment. There is growing evidence that pro-inflammatory cytokines play a role in cancer-related fatigue, although the molecular mechanisms for chronic inflammation and fatigue have not been determined. The current study utilized genome-wide expression microarrays to identify differences in gene expression and associated alterations in transcriptional activity in leukocytes from breast cancer survivors with persistent fatigue (n = 11) and non-fatigued controls (n = 10). We focused on transcription of inflammation-related genes, particularly those responsive to the pro-inflammatory NF-κB transcription control pathway. Further, given the role of glucocorticoids as key regulators of inflammatory processes, we examined transcription of glucocorticoid-responsive genes indicative of potential glucocorticoid receptor (GR) desensitization. Plasma levels of cortisol were also assessed. Consistent with hypotheses, results showed increased expression of transcripts with response elements for NF-κB, and reduced expression of transcripts with response elements for glucocorticoids (p < .05) in fatigued breast cancer survivors. No differences in plasma levels of cortisol were observed. These data indicate that increased activity of pro-inflammatory transcription factors may contribute to persistent cancer-related fatigue and provide insight into potential mechanisms for tonic increases in NF-κB activity, specifically decreased expression of GR anti-inflammatory transcription factors. PMID:20854893

Tuning crystal phase of NiS_x through electro-oxidized nickel foam: A novel route for preparing efficient electrocatalysts for oxygen evolution reaction

International Nuclear Information System (INIS)

Li, Xiao; Shang, Xiao; Rao, Yi; Dong, Bin; Han, Guan-Qun; Hu, Wen-Hui; Liu, Yan-Ru; Yan, Kai-Li; Chi, Jing-Qi; Chai, Yong-Ming; Liu, Chen-Guang

2017-01-01

Highlights: • Electro-oxidized nickel foam as a support has been used to prepare NiS_x phases. • Ni(OH)_2 layer on electro-oxidized NF is responsible for the growth of β-NiS. • NiS_x/NF(Ox) composed of β-NiS and Ni_3S_2 has enhanced electrocatalytic activity. • The growth mechanisms of mixed NiS_x phases of NiS_x/NF(Ox) have been discussed. - Abstract: A facile solvothermal sulfurization using electro-oxidized nickel foam (NF(Ox)) as support has been applied to prepare NiS_x/NF(Ox) electrocatalyst with highly efficient activity for oxygen evolution reaction (OER). XRD patterns confirm the composition of NiS_x/NF(Ox): two kinds of crystal phase including β-NiS and Ni_3S_2. While using bare NF as support under identical conditions, only Ni_3S_2 phase can be detected. SEM images reveal two kinds of morphologies of NiS_x/NF(Ox) including pyramids structure of β-NiS and nanorod-like structure of Ni_3S_2, which implies the tuning effect of electro-pretreatment of NF on the selective preparation of NiS_x crystal phase. It can be speculated that Ni(OH)_2 layer derived from electro-oxidized NF is responsible for the growth of β-NiS while metallic Ni is transformed into Ni_2S_3 during sulfurization. Electrochemical measurements for OER indicate the enhanced electrocatalytic activity of NiS_x/NF(Ox) with a small overpotential of 72 mV to reach 10 mA cm"−"2 compared with Ni_3S_2/NF, which may be ascribed to the improved electron-transfer kinetics relating to the unique atomic configurations and crystalline structures of β-NiS. The electro-oxidation pretreatment of nickel foam provides a simple and convenient method by tuning different NiS_x crystal phases for preparing excellent OER eletrocatalysts.

Roles of Pannexin-1 Channels in Inflammatory Response through the TLRs/NF-Kappa B Signaling Pathway Following Experimental Subarachnoid Hemorrhage in Rats

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Ling-Yun Wu

2017-06-01

Full Text Available Background: Accumulating evidence suggests that neuroinflammation plays a critical role in early brain injury after subarachnoid hemorrhage (SAH. Pannexin-1 channels, as a member of gap junction proteins located on the plasma membrane, releases ATP, ions, second messengers, neurotransmitters, and molecules up to 1 kD into the extracellular space, when activated. Previous studies identified that the opening of Pannexin-1 channels is essential for cellular migration, apoptosis and especially inflammation, but its effects on inflammatory response in SAH model have not been explored yet.Methods: Adult male Sprague-Dawley rats were divided into six groups: sham group (n = 20, SAH group (n = 20, SAH + LV-Scramble-ShRNA group (n = 20, SAH + LV-ShRNA-Panx1 group (n = 20, SAH + LV-NC group (n = 20, and SAH + LV-Panx1-EGFP group (n = 20. The rat SAH model was induced by injection of 0.3 ml fresh arterial, non-heparinized blood into the prechiasmatic cistern in 20 s. In SAH + LV-ShRNA-Panx1 group and SAH + LV-Panx1-EGFP group, lentivirus was administered via intracerebroventricular injection (i.c.v. at 72 h before the induction of SAH. The Quantitative real-time polymerase chain reaction, electrophoretic mobility shift assay, enzyme-linked immunosorbent assay, immunofluorescence staining, and western blotting were performed to explore the potential interactive mechanism between Pannexin-1 channels and TLR2/TLR4/NF-κB-mediated signaling pathway. Cognitive and memory changes were investigated by the Morris water maze test.Results: Administration with LV-ShRNA-Panx1 markedly decreased the expression levels of TLR2/4/NF-κB pathway-related agents in the brain cortex and significantly ameliorated neurological cognitive and memory deficits in this SAH model. On the contrary, administration of LV-Panx1-EGFP elevated the expressions of TLR2/4/NF-κB pathway-related agents, which correlated with augmented neuronal apoptosis.Conclusion: Pannexin-1 channels may

Per a 10 protease activity modulates CD40 expression on dendritic cell surface by nuclear factor-kappaB pathway.

Science.gov (United States)

Goel, C; Kalra, N; Dwarakanath, B S; Gaur, S N; Arora, N

2015-05-01

Serine protease activity of Per a 10 from Periplaneta americana modulates dendritic cell (DC) functions by a mechanism(s) that remains unclear. In the present study, Per a 10 protease activity on CD40 expression and downstream signalling was evaluated in DCs. Monocyte-derived DCs from cockroach-allergic patients were treated with proteolytically active/heat-inactivated Per a 10. Stimulation with active Per a 10 demonstrated low CD40 expression on DCs surface (P Per a 10, suggesting cleavage of CD40. Per a 10 activity reduced the interleukin (IL)-12 and interferon (IFN)-γ secretion by DCs (P Per a 10, indicating that low CD40 expression is associated with low levels of IL-12 secretion. Active Per a 10 stimulation caused low nuclear factor-kappa B (NF-κB) activation in DCs compared to heat-inactivated Per a 10. Inhibition of the NF-κB pathway suppressed the CD40 expression and IL-12 secretion by DCs, further indicating that NF-κB is required for CD40 up-regulation. CD40 expression activated the tumour necrosis factor (TNF) receptor-associated factor 6 (TRAF6), thereby suggesting its involvement in NF-κB activation. Protease activity of Per a 10 induced p38 mitogen-activated protein kinase (MAPK) activation that showed no significant effect on CD40 expression by DCs. However, inhibiting p38 MAPK or NF-κB suppressed the secretion of IL-12, IFN-γ, IL-6 and TNF-α by DCs. Such DCs further reduced the secretion of IL-4, IL-6, IL-12 and TNF-α by CD4(+) T cells. In conclusion, protease activity of Per a 10 reduces CD40 expression on DCs. CD40 down-regulation leads to low NF-κB levels, thereby modulating DC-mediated immune responses. © 2014 British Society for Immunology.

Gelam honey attenuates carrageenan-induced rat paw inflammation via NF-κB pathway.

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Saba Zuhair Hussein

Full Text Available The activation of nuclear factor kappa B (NF-κB plays a major role in the pathogenesis of a number of inflammatory diseases. In this study, we investigated the anti-inflammatory mechanism of Gelam honey in inflammation induced rats via NF-κB signalling pathway. Rats paw edema was induced by subplantar injection of 1% carrageenan into the right hind paw. Rats were pre-treated with Gelam honey at different doses (1 or 2 g/kg, p.o. and NSAID Indomethacin (10 mg/kg, p.o., in two time points (1 and 7 days. Our results showed that Gelam honey at both concentrations suppressed the gene expressions of NF-κB (p65 & p50 and IκBα in inflamed rats paw tissues. In addition, Gelam honey inhibited the nuclear translocation and activation of NF-κB and decreased the cytosolic degradation of IκBα dose dependently in inflamed rats paw tissues. The immunohistochemical expressions of pro-inflammatory mediators COX-2 and TNF-α were also decreased in inflamed rats paw tissues when treated with Gelam honey. The results of our findings suggest that Gelam honey exhibits its inhibitory effects by attenuating NF-κB translocation to the nucleus and inhibiting IκBα degradation, with subsequent decrease of inflammatory mediators COX-2 and TNF-α.

Wilson loops in 5d $\\mathcal{N}=1$ theories and S-duality arXiv

CERN Document Server

Assel, Benjamin

We study the action of S-duality on half-BPS Wilson loop operators in 5d $\\mathcal{N}=1$ theories. The duality is the statement that different massive deformations of a single 5d SCFT are described by different gauge theories, or equivalently that the SCFT points in parameter space of two gauge theories coincide. The pairs of dual theories that we study are realized by brane webs in type IIB string theory that are S-dual to each other. We focus on $SU(2)$ SQCD theories with $N_f \\le 4$ flavors, which are self-dual, and on $SU(3)$ SQCD theories, which are dual to $SU(2)^2$ quiver theories. From string theory engineering we predict that Wilson loops are mapped to dual Wilson loops under S-duality. We confirm the predictions with exact computations of Wilson loop VEVs, which we extract from the 5d half-index in the presence of auxiliary loop operators (also known as higher qq-characters) sourced by D3 branes placed in the brane webs. A special role is played by Wilson loops in tensor products of the (anti)fundam...

FeS2-doped MoS2 nanoflower with the dominant 1T-MoS2 phase as an excellent electrocatalyst for high-performance hydrogen evolution

International Nuclear Information System (INIS)

Zhao, Xue; Ma, Xiao; Lu, Qingqing; Li, Qun; Han, Ce; Xing, Zhicai; Yang, Xiurong

2017-01-01

Well-established methods to improve the hydrogen evolution reaction (HER) performances include, but are not limited to, tailoring the morphology and electronic structure of transition metal dichalcogenides (TMDs), and doping of earth abundant chemicals such as iron pyrite FeS 2 into existing TMDs. In this work, MoS 2 nanoflowers with the majority being octahedral MoS 2 (1T-MoS 2 ) and doped with FeS 2 were prepared and applied to HER. The as-prepared catalysts were characterized by X-ray absorption fine structure at the K-edge of Mo, S, and Fe to probe the local electronic structures. The resulting nanomaterial was identified to be FeS 2 doped MoS 2 nanoflower (denoted as Fe-MoS 2 NF) with 66% 1T-MoS 2 which was the metallic phase and could drastically boost the HER properties. The Fe-MoS 2 NF exhibited high HER performance with a Tafel slope of 82 mV dec −1 and it needs 136 mV to achieve a current density of 10 mA cm −2 . The synthesis of Fe-MoS 2 NF with refined morphology and active electronic structure is expected to open a new era for improving the catalytic activity and stability of MoS 2 .

Electron velocity of 6 × 10{sup 7 }cm/s at 300 K in stress engineered InAlN/GaN nano-channel high-electron-mobility transistors

Energy Technology Data Exchange (ETDEWEB)

Arulkumaran, S., E-mail: SArulkumaran@pmail.ntu.edu.sg; Manoj Kumar, C. M.; Ranjan, K.; Teo, K. L. [Temasek Laboratories@NTU, Nanyang Technological University, Research Techno Plaza, 50 Nanyang Drive, Singapore 637553 (Singapore); Ng, G. I., E-mail: eging@ntu.edu.sg [School of Electrical and Electronics Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798 (Singapore); Shoron, O. F.; Rajan, S. [Electrical and Computer Engineering Department, The Ohio State University, Columbus, Ohio 43210 (United States); Bin Dolmanan, S.; Tripathy, S. [Institute of Materials Research and Engineering, A*STAR (Agency for Science, Technology, and Research), 3 Research Link, Singapore 117602 (Singapore)

2015-02-02

A stress engineered three dimensional (3D) Triple T-gate (TT-gate) on lattice matched In{sub 0.17}Al{sub 0.83}N/GaN nano-channel (NC) Fin-High-Electron-Mobility Transistor (Fin-HEMT) with significantly enhanced device performance was achieved that is promising for high-speed device applications. The Fin-HEMT with 200-nm effective fin-width (W{sub eff}) exhibited a very high I{sub Dmax} of 3940 mA/mm and a highest g{sub m} of 1417 mS/mm. This dramatic increase of I{sub D} and g{sub m} in the 3D TT-gate In{sub 0.17}Al{sub 0.83}N/GaN NC Fin-HEMT translated to an extracted highest electron velocity (v{sub e}) of 6.0 × 10{sup 7 }cm/s, which is ∼1.89× higher than that of the conventional In{sub 0.17}Al{sub 0.83}N/GaN HEMT (3.17 × 10{sup 7 }cm/s). The v{sub e} in the conventional III-nitride transistors are typically limited by highly efficient optical-phonon emission. However, the unusually high v{sub e} at 300 K in the 3D TT-gate In{sub 0.17}Al{sub 0.83}N/GaN NC Fin-HEMT is attributed to the increase of in-plane tensile stress component by SiN passivation in the formed NC which is also verified by micro-photoluminescence (0.47 ± 0.02 GPa) and micro-Raman spectroscopy (0.39 ± 0.12 GPa) measurements. The ability to reach the v{sub e} = 6 × 10{sup 7 }cm/s at 300 K by a stress engineered 3D TT-gate lattice-matched In{sub 0.17}Al{sub 0.83}N/GaN NC Fin-HEMTs shows they are promising for next-generation ultra-scaled high-speed device applications.

Trichomonas vaginalis Induces SiHa Cell Apoptosis by NF-κB Inactivation via Reactive Oxygen Species

Science.gov (United States)

Quan, Juan-Hua; Kang, Byung-Hun; Yang, Jung-Bo; Rhee, Yun-Ee; Noh, Heung-Tae; Choi, In-Wook; Cha, Guang-Ho; Yuk, Jae-Min

2017-01-01

Trichomonas vaginalis induces apoptosis in host cells through various mechanisms; however, little is known about the relationship between apoptosis, reactive oxygen species (ROS), and NF-κB signaling pathways in the cervical mucosal epithelium. Here, we evaluated apoptotic events, ROS production, and NF-κB activity in T. vaginalis-treated cervical mucosal epithelial SiHa cells, with or without specific inhibitors, using fluorescence microscopy, DNA fragmentation assays, subcellular fractionation, western blotting, and luciferase reporter assay. SiHa cells treated with live T. vaginalis at a multiplicity of infection of 5 (MOI 5) for 4 h produced intracellular and mitochondrial ROS in a parasite-load-dependent manner. Incubation with T. vaginalis caused DNA fragmentation, cleavage of caspase 3 and PARP, and release of cytochrome c into the cytoplasm. T. vaginalis-treated SiHa cells showed transient early NF-κB p65 nuclear translocation, which dramatically dropped at 4 h after treatment. Suppression of NF-κB activity was dependent on parasite burden. However, treatment with the ROS scavenger, N-acetyl-C-cysteine (NAC), reversed the effect of T. vaginalis on apoptosis and NF-κB inactivation in SiHa cells. Taken together, T. vaginalis induces apoptosis in human cervical mucosal epithelial cells by parasite-dose-dependent ROS production through an NF-κB-regulated, mitochondria-mediated pathway. PMID:29410962

Trichomonas vaginalis Induces SiHa Cell Apoptosis by NF-κB Inactivation via Reactive Oxygen Species

Directory of Open Access Journals (Sweden)

Juan-Hua Quan

2017-01-01

Full Text Available Trichomonas vaginalis induces apoptosis in host cells through various mechanisms; however, little is known about the relationship between apoptosis, reactive oxygen species (ROS, and NF-κB signaling pathways in the cervical mucosal epithelium. Here, we evaluated apoptotic events, ROS production, and NF-κB activity in T. vaginalis-treated cervical mucosal epithelial SiHa cells, with or without specific inhibitors, using fluorescence microscopy, DNA fragmentation assays, subcellular fractionation, western blotting, and luciferase reporter assay. SiHa cells treated with live T. vaginalis at a multiplicity of infection of 5 (MOI 5 for 4 h produced intracellular and mitochondrial ROS in a parasite-load-dependent manner. Incubation with T. vaginalis caused DNA fragmentation, cleavage of caspase 3 and PARP, and release of cytochrome c into the cytoplasm. T. vaginalis-treated SiHa cells showed transient early NF-κB p65 nuclear translocation, which dramatically dropped at 4 h after treatment. Suppression of NF-κB activity was dependent on parasite burden. However, treatment with the ROS scavenger, N-acetyl-C-cysteine (NAC, reversed the effect of T. vaginalis on apoptosis and NF-κB inactivation in SiHa cells. Taken together, T. vaginalis induces apoptosis in human cervical mucosal epithelial cells by parasite-dose-dependent ROS production through an NF-κB-regulated, mitochondria-mediated pathway.

Effect of light on N2 fixation and net nitrogen release of Trichodesmium in a field study

Science.gov (United States)

Lu, Yangyang; Wen, Zuozhu; Shi, Dalin; Chen, Mingming; Zhang, Yao; Bonnet, Sophie; Li, Yuhang; Tian, Jiwei; Kao, Shuh-Ji

2018-01-01

Dinitrogen fixation (NF) by marine cyanobacteria is an important pathway to replenish the oceanic bioavailable nitrogen inventory. Light is the key to modulating NF; however, field studies investigating the light response curve (NF-I curve) of NF rate and the effect of light on diazotroph-derived nitrogen (DDN) net release are relatively sparse in the literature, hampering prediction using models. A dissolution method was applied using uncontaminated 15N2 gas to examine how the light changes may influence the NF intensity and DDN net release in the oligotrophic ocean. Experiments were conducted at stations with diazotrophs dominated by filamentous cyanobacterium Trichodesmium spp. in the western Pacific and the South China Sea. The effect of light on carbon fixation (CF) was measured in parallel using the 13C tracer method specifically for a station characterized by Trichodesmium bloom. Both NF-I and CF-I curves showed a Ik (light saturation coefficient) range of 193 to 315 µE m-2 s-1, with light saturation at around 400 µE m-2 s-1. The proportion of DDN net release ranged from ˜ 6 to ˜ 50 %, suggesting an increasing trend as the light intensity decreased. At the Trichodesmium bloom station, we found that the CF / NF ratio was light-dependent and the ratio started to increase as light was lower than the carbon compensation point of 200 µE m-2 s-1. Under low-light stress, Trichodesmium physiologically preferred to allocate more energy for CF to alleviate the intensive carbon consumption by respiration; thus, there is a metabolism tradeoff between CF and NF pathways. Results showed that short-term ( energy associated with the variation in light intensity would be helpful for prediction of the global biogeochemical cycle of N by models involving Trichodesmium blooms.

The Infrared Fixed Points of 3d $\\mathcal{N}=4$ $USp(2N)$ SQCD Theories arXiv

CERN Document Server

Assel, Benjamin

We derive the algebraic description of the Coulomb branch of 3d $\\mathcal{N}=4$ $USp(2N)$ SQCD theories with $N_f$ fundamental hypermultiplets and determine their low energy physics in any vacuum from the local geometry of the moduli space, identifying the interacting SCFTs which arise at singularities and possible extra free sectors. The SCFT with the largest moduli space arises at the most singular locus on the Coulomb branch. For $N_f>2N$ (good theories) it sits at the origin of the conical variety as expected. For $N_f =2N$ we find two separate most singular points, from which the two isomorphic components of the Higgs branch of the UV theory emanate. The SCFTs sitting at any of these two vacua have only odd dimensional Coulomb branch generators, which transform under an accidental $SU(2)$ global symmetry. We provide a direct derivation of their moduli spaces of vacua, and propose a Lagrangian mirror theory for these fixed points. For $2 \\le N_f < 2N$ the most singular locus has one or two extended com...

Expression of the tumor suppressor genes NF2, 4.1B, and TSLC1 in canine meningiomas.

Science.gov (United States)

Dickinson, P J; Surace, E I; Cambell, M; Higgins, R J; Leutenegger, C M; Bollen, A W; LeCouteur, R A; Gutmann, D H

2009-09-01

Meningiomas are common primary brain tumors in dogs; however, little is known about the molecular genetic mechanisms involved in their tumorigenesis. Several tumor suppressor genes have been implicated in meningioma pathogenesis in humans, including the neurofibromatosis 2 (NF2), protein 4.1B (4.1 B), and tumor suppressor in lung cancer-1 (TSLC1) genes. We investigated the expression of these tumor suppressor genes in a series of spontaneous canine meningiomas using quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) (NF2; n = 25) and western blotting (NF2/merlin, 4.1B, TSLC1; n = 30). Decreased expression of 4.1B and TSLC1 expression on western blotting was seen in 6/30 (20%) and in 15/30 (50%) tumors, respectively, with 18/30 (60%) of meningiomas having decreased or absent expression of one or both proteins. NF2 gene expression assessed by western blotting and RT-PCR varied considerably between individual tumors. Complete loss of NF2 protein on western blotting was not seen, unlike 4.1B and TSLC1. Incidence of TSLC1 abnormalities was similar to that seen in human meningiomas, while perturbation of NF2 and 4.1B appeared to be less common than reported for human tumors. No association was observed between tumor grade, subtype, or location and tumor suppressor gene expression based on western blot or RT-PCR. These results suggest that loss of these tumor suppressor genes is a frequent occurrence in canine meningiomas and may be an early event in tumorigenesis in some cases. In addition, it is likely that other, as yet unidentified, genes play an important role in canine meningioma formation and growth.

GeNF - Experimental report 2007

Energy Technology Data Exchange (ETDEWEB)

Pranzas, P K; Schreyer, A; Willumeit, R [GKSS-Forschungszentrum Geesthacht GmbH (Germany). Inst. fuer Materialforschung

2008-11-05

At the Geesthacht Neutron Facility GeNF about 203 experiments were performed in 2007 by GKSS and by or for external users, partners or contractors. In most cases the measurements were performed and analysed in cooperation by the guests and by the GKSS staff or by the permanent external user group staff. The activities, which are based on a proposal procedure and on the in house R and D program, are reported in 70 contributions in the present annual experimental report for the year 2007. The contributions may contain one or also several combined experiments. During 2007 the GKSS research reactor FRG-1 achieved an operation time of 204 days at the full 5 MW reactor power providing a neutron flux of ca. 1.4 x 10{sup 14} thermal neutrons/cm{sup 2}s. In May/June 2007 the FRG-1 was upgraded with a new cold neutron source yielding a flux increase at the five instruments using cold neutrons of up to 40 %. The focus of the in house R and D work at GeNF instruments in 2007 was the characterisation of nano-structures in engineering materials, the analysis of stresses and textures in welds and technical structures at SANS-2, DCD, ARES-2 and TEX-2, the structural investigation of hydrogen containing substances such as polymers, colloids and biological macromolecules at SANS-1 as well as the characterisation of magnetic thin films at NeRo, PNR, POLDI and ROeDI. The modern experiment control hardware and software based on LabView was continuously improved on all instruments. In the appendices I and II the experimental reports of the GKSS outstation at the FRM II are attached as well as of the GKSS outstation at DESY. At the neutron reflectometer REFSANS at FRM II measurements are possible using a broad range of the scattering vector with reflectivities up to 10{sup -7}. Three reports show the activities of GKSS in the field of texture measurement at the instrument STRESS-SPEC. The instrument HARWI II at DESY is accepted very well by the community and is overbooked in all fields

GeNF - Experimental report 2007

International Nuclear Information System (INIS)

Pranzas, P.K.; Schreyer, A.; Willumeit, R.

2008-01-01

At the Geesthacht Neutron Facility GeNF about 203 experiments were performed in 2007 by GKSS and by or for external users, partners or contractors. In most cases the measurements were performed and analysed in cooperation by the guests and by the GKSS staff or by the permanent external user group staff. The activities, which are based on a proposal procedure and on the in house R and D program, are reported in 70 contributions in the present annual experimental report for the year 2007. The contributions may contain one or also several combined experiments. During 2007 the GKSS research reactor FRG-1 achieved an operation time of 204 days at the full 5 MW reactor power providing a neutron flux of ca. 1.4 x 10 14 thermal neutrons/cm 2 s. In May/June 2007 the FRG-1 was upgraded with a new cold neutron source yielding a flux increase at the five instruments using cold neutrons of up to 40 %. The focus of the in house R and D work at GeNF instruments in 2007 was the characterisation of nano-structures in engineering materials, the analysis of stresses and textures in welds and technical structures at SANS-2, DCD, ARES-2 and TEX-2, the structural investigation of hydrogen containing substances such as polymers, colloids and biological macromolecules at SANS-1 as well as the characterisation of magnetic thin films at NeRo, PNR, POLDI and ROeDI. The modern experiment control hardware and software based on LabView was continuously improved on all instruments. In the appendices I and II the experimental reports of the GKSS outstation at the FRM II are attached as well as of the GKSS outstation at DESY. At the neutron reflectometer REFSANS at FRM II measurements are possible using a broad range of the scattering vector with reflectivities up to 10 -7 . Three reports show the activities of GKSS in the field of texture measurement at the instrument STRESS-SPEC. The instrument HARWI II at DESY is accepted very well by the community and is overbooked in all fields (tomography

Effects of vitamin E on the NF-κB pathway in rats treated with the peroxisome proliferator, ciprofibrate

International Nuclear Information System (INIS)

Calfee-Mason, Karen G.; Spear, Brett T.; Glauert, Howard P.

2004-01-01

Peroxisome proliferators (PPs) are a diverse group of nongenotoxic compounds, which induce hepatic tumors in rodents. The mechanisms leading to hepatic tumors have not been elucidated, but oxidative stress may play a role in the process. Previous studies in our laboratory have shown that peroxisome proliferators activate the transcription factor nuclear factor-kappa B (NF-κB) and that this activation is mediated at least in part by oxidative stress. We therefore hypothesized that increased dietary vitamin E would decrease NF-κB DNA binding in rodents treated with ciprofibrate (CIP). In this study, 36 male Sprague-Dawley rats were fed a purified diet containing varying levels of vitamin E (10, 50, 250 ppm α-tocopherol acetate). After 28 days on the purified diet, seven animals per vitamin E group received 0.01% CIP in the diet for 10 days. Electrophoretic mobility shift assays (EMSAs) showed that CIP treatment increased DNA binding of NF-κB. Increased dietary α-tocopherol acetate inhibited CIP-induced NF-κB DNA binding. Because NF-κB translocates to the nucleus upon the phosphorylation and degradation of inhibitor of IκB, we also used Western blots to measure cytosolic protein levels of IκBα and IκBβ, and the IκB kinases, IKKα and IKKβ. IκBα protein levels were decreased in all three CIP-treated groups, with the 10 ppm vitamin E diet also decreasing IκBα levels in control rats. No difference in IκBβ protein levels was observed among any of the groups. The CIP-treated rats generally had lower protein levels of IKKα and IKKβ. This study supports our working hypothesis that an increased antioxidant environment can inhibit CIP-mediated NF-κB induction

Aberrant activation of NF-κB signaling in mammary epithelium leads to abnormal growth and ductal carcinoma in situ

International Nuclear Information System (INIS)

Barham, Whitney; Chen, Lianyi; Tikhomirov, Oleg; Onishko, Halina; Gleaves, Linda; Stricker, Thomas P.; Blackwell, Timothy S.; Yull, Fiona E.

2015-01-01

activated ductal tissue. These results indicate that aberrant NF-κB activation within mammary epithelium can lead to molecular and morphological changes consistent with the earliest stages of breast cancer. Thus, inhibition of NF-κB signaling following acute inflammation or the initial signs of hyperplastic ductal growth could represent an important opportunity for breast cancer prevention. The online version of this article (doi:10.1186/s12885-015-1652-8) contains supplementary material, which is available to authorized users

Drug Response and Resistance in Advanced NF-1-Associated Cancers

Science.gov (United States)

2015-07-01

Neurofibromatosis 1: closing the GAP between mice and men. Current opinion in genetics & development. 2003;13(1):20-7. 3. Maris JM, Wiersma SR, Mahgoub N...13. Side L, Taylor B, Cayouette M, Conner E, Thompson P, Luce M, Shannon K. Homozygous inactivation of the NF1 gene in bone marrow cells from children...1998;7(8):1261-8. 54. Bollag G, Adler F, elMasry N, McCabe PC, Conner E, Thompson P, McCormick F, Shannon K. Biochemical characterization of a novel KRAS

Sulfasalazine inhibits inflammation and fibrogenesis in pancreas via NF-κB signaling pathway in rats with oxidative stress-induced pancreatic injury

Directory of Open Access Journals (Sweden)

Wang YR

2016-05-01

Full Text Available Ya-Ru Wang,1,* Fei-Long Tian,2,* Ming-Xian Yan,1 Jin-Hua Fan,1 Li-Yun Wang,1 Rong-Guang Kuang,1 Yan-Qing Li3 1Department of Gastroenterology, Shandong Qianfoshan Hospital, Shandong University, 2Shandong University School of Medicine, 3Department of Gastroenterology, Qilu Hospital, Shandong University, Ji’nan, Shandong Province, People’s Republic of China *These authors contributed equally to this work Background: Pathogenesis and effective therapeutics of chronic pancreatic inflammation and fibrosis remain uncertain.Purpose: To investigate the effects of sulfasalazine (SF on pancreatic inflammation and fibrogenesis.Methods: Chronic pancreatic injury in rats was induced by diethyldithiocarbamate (DDC and interfered by SF through intraperitoneal injection. The rats were divided into five groups: group N, normal control group, rats were treated with dilated water only; group DS1, rats received SF (10 mg/kg 2 hours before DDC treatment; group DS2, rats were treated with DDC and then SF (100 mg/kg, twice a week; group DS3, rats were treated with DDC, then SF (100 mg/kg, thrice a week; and group DDC, rats were treated with DDC only. Pancreatic inflammation and fibrosis were determined by hematoxylin and eosin staining and Sirius red staining. The genes and proteins related to NF-κB pathway and fibrogenesis including NF-κB/p65, TNF-α, ICAM-1, α-SMA, and Con 1 were detected by immunohistochemical staining, reverse transcription polymerase chain reaction, and Western blotting.Results: Rats in the DDC and DS1 groups showed the highest histological scores after DDC treatment, but the scores of DS2 and DS3 groups decreased significantly when compared with the DDC group. Sirius red staining showed collagen formation clearly in DDC and DS1 rats rather than in DS2 and DS3 rats. NF-κB/p65, ICAM-1, and α-SMA were strongly expressed in DDC and DS1 rats, while DS2 and DS3 rats showed mild to moderate expression by immunohistochemistry. Reverse tran

Carbachol ameliorates lipopolysaccharide-induced intestinal epithelial tight junction damage by down-regulating NF-{kappa}{beta} and myosin light-chain kinase pathways

Energy Technology Data Exchange (ETDEWEB)

Zhang, Ying [Department of Anesthesia, Critical Care Medicine and Emergency Medicine Center, Zhongnan Hospital, Wuhan University, Wuhan 430071, Hubei Province, People' s Republic of China (China); Li, Jianguo, E-mail: 2010lijianguo@sina.cn [Department of Anesthesia, Critical Care Medicine and Emergency Medicine Center, Zhongnan Hospital, Wuhan University, Wuhan 430071, Hubei Province, People' s Republic of China (China)

2012-11-16

Highlights: Black-Right-Pointing-Pointer Carbachol reduced the lipopolysaccharide-induced intestinal barrier breakdown. Black-Right-Pointing-Pointer Carbachol ameliorated the lipopolysaccharide-induced ileal tight junction damage. Black-Right-Pointing-Pointer Carbachol prevented the LPS-induced NF-{kappa}{beta} and myosin light-chain kinase activation. Black-Right-Pointing-Pointer Carbachol exerted its beneficial effects in an {alpha}7 nicotinic receptor-dependent manner. -- Abstract: Carbachol is a cholinergic agonist that protects the intestines after trauma or burn injury. The present study determines the beneficial effects of carbachol and the mechanisms by which it ameliorates the lipopolysaccharide (LPS)-induced intestinal barrier breakdown. Rats were injected intraperitoneally with 10 mg/kg LPS. Results showed that the gut barrier permeability was reduced, the ultrastructural disruption of tight junctions (TJs) was prevented, the redistribution of zonula occludens-1 and claudin-2 proteins was partially reversed, and the nuclear factor-kappa beta (NF-{kappa}{beta}) and myosin light-chain kinase (MLCK) activation in the intestinal epithelium were suppressed after carbachol administration in LPS-exposed rats. Pretreatment with the {alpha}7 nicotinic acetylcholine receptor ({alpha}7nAchR) antagonist {alpha}-bungarotoxin blocked the protective action of carbachol. These results suggested that carbachol treatment can protect LPS-induced intestinal barrier dysfunction. Carbachol exerts its beneficial effect on the amelioration of the TJ damage by inhibiting the NF-{kappa}{beta} and MLCK pathways in an {alpha}7nAchR-dependent manner.

Tools to Ensure Safe Medicines: New Monograph Tests in USP-NF

Directory of Open Access Journals (Sweden)

Catherine Sheehan

2010-06-01

Full Text Available This paper describes USP-NF compendial updates to six ‘high-priority” excipient monographs: Glycerin, Propylene Glycol, Sorbitol Solution, Sorbitol Sorbitan Solution, Noncrystallizing Sorbitol Solution and Maltitol Solution. The USP-NF revisions arose from the Food and Drug Administration’s (FDA’s requests to include, as part of each monograph’s Identification test, a limit test to detect the presence of Diethylene Glycol (DEG, a toxic adulterant. These revisions align with the 2007 FDA Guidance for Industry: Testing of Glycerin for Diethylene Glycol (1, that drug product manufacturers perform a specific identity test for DEG on all containers of all lots of glycerin before glycerin is used in the manufacture and preparation of drug products. This paper describes several risk factors due to a complex global excipient supply chain, nonspecific specifications, inadequate supply chain qualification, and poor understanding of regulations. Strengthening and conformance to compendial specifications is one of the tools necessary to mitigate risk and help prevent the next DEG adulteration that is part of USP’s efforts to ensure safe medicines.

Genetic Factors that Affect Tumorigenesis in NF1

National Research Council Canada - National Science Library

Stephens, Karen

2003-01-01

...) that flank the NF1 gene. We identified recombination hotspots where 69% of NF1 microdeletions occur and developed robust and sensitive assays to detect microdeletions in a patient blood sample...

Genetic Factors that Affect Tumorigenesis in NF1

National Research Council Canada - National Science Library

Stephens, Karen G

2004-01-01

...) that flank the NF1 gene. We identified recombination hotspots where 69% of NF1 microdeletions occur and developed robust and sensitive assays to detect microdeletions in a patient blood sample...

S100a8/NF-κB signal pathway is involved in the 800-nm diode laser-induced skin collagen remodeling.

Science.gov (United States)

Ren, Xiaolin; Ge, Minggai; Qin, Xiaofeng; Xu, Peng; Zhu, Pingya; Dang, Yongyan; Gu, Jun; Ye, Xiyun

2016-05-01

The 800-nm diode laser is widely used for hair removal and also promotes collagen synthesis, but the molecular mechanism by which dermis responses to the thermal damage induced by the 800-nm diode laser is still unclear. Ten 2-month-old mice were irradiated with the 800-nm diode laser at 20, 40, and 60 J/cm(2), respectively. Skin samples were taken for PCR, Western blot analysis, and histological study at day 3 or 30 after laser irradiation. The expression of S100a8 and its two receptors (advanced glycosylation end product-specific receptor, RAGE and toll-like receptor 4, TRL4) was upregulated at day 3 after laser treatments. P-p65 levels were also elevated, causing the increase of cytokine (tumor necrosis factor, TNF-α and interleukin 6, IL-6) and MMPs (MMP1a, MMP9). At day 30, PCR and Western blot analysis showed significant increase of type I and III procollagen in the dermis treated with laser. Importantly, skin structure was markedly improved in the laser-irradiated skin compared with the control. Thus, it seemed that S100a8 upregulation triggered NF-κB signal pathway through RAGE and TLR4, responding to laser-induced dermis wound healing. The involvement of the NF-κB pathway in MMP gene transcription promoted the turnover of collagen in the skin, accelerating new collagen synthesis.

Final report on bilateral comparison EURAMET.M.T-S3: Torque wrenches (10 N m - 1 kN m)

Science.gov (United States)

Röske, Dirk; Medina, Nieves

2011-01-01

A bilateral comparison from 10 N m up to 1000 N m has been carried out between Physikalisch-Technische Bundesanstalt (PTB) and Centro Español de Metrología (CEM) for reference torque wrenches calibrated according to DKD-R 3-7. The transfer standards have been two reference torque wrenches, 10 N m and 1000 N m respectively, that have been measured between November and December 2010. The results presented here demonstrate the metrological equivalence, within the quoted uncertainties, of both participant laboratories. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by EURAMET, according to the provisions of the CIPM Mutual Recognition Arrangement (MRA).

The PTB thermal neutron reference field at GeNF

International Nuclear Information System (INIS)

Boettger, R.; Friedrich, H.; Janssen, H.

2004-01-01

The experimental setup and procedure for the characterization of the thermal neutron reference field established at the Geesthacht neutron facility (GeNF) of the GKSS is described. The neutron beam, free in air, with a maximum flux of 10 6 s -1 , can easily be reduced to less than 10 4 s -1 by using a diaphragm variable in size and without changing the beam divergence. Also, the spectral distribution with a mean energy of 45 meV, measured by time-of-flight over a 6.6 m long flight path, is independent of the beam current chosen. In the 2002/2003 experiments reported here, a 6 Li glass detector was employed to determine the absolute beam current and to calibrate the 3 He transmission beam monitor. In addition, activation measurements of gold foils were carried out at a reduced beam divergence. The results agree within ±2%. Furthermore, the beam is characterized by a low gamma background intensity and a negligible fraction of epithermal neutrons. Irradiations in combination with a scanner device to achieve a homogeneously illuminated scan field have shown that the thermal beam is well suited for dosemeter development and for the calibration of radiation protection instruments. (orig.)

The PTB thermal neutron reference field at GeNF

Energy Technology Data Exchange (ETDEWEB)

Boettger, R.; Friedrich, H.; Janssen, H.

2004-07-01

The experimental setup and procedure for the characterization of the thermal neutron reference field established at the Geesthacht neutron facility (GeNF) of the GKSS is described. The neutron beam, free in air, with a maximum flux of 10{sup 6} s{sup -1}, can easily be reduced to less than 10{sup 4} s{sup -1} by using a diaphragm variable in size and without changing the beam divergence. Also, the spectral distribution with a mean energy of 45 meV, measured by time-of-flight over a 6.6 m long flight path, is independent of the beam current chosen. In the 2002/2003 experiments reported here, a {sup 6}Li glass detector was employed to determine the absolute beam current and to calibrate the {sup 3}He transmission beam monitor. In addition, activation measurements of gold foils were carried out at a reduced beam divergence. The results agree within {+-}2%. Furthermore, the beam is characterized by a low gamma background intensity and a negligible fraction of epithermal neutrons. Irradiations in combination with a scanner device to achieve a homogeneously illuminated scan field have shown that the thermal beam is well suited for dosemeter development and for the calibration of radiation protection instruments. (orig.)

Expression and significance of TRAIL and NF-kB in osteosarcoma

International Nuclear Information System (INIS)

Du Xiumin; You Murong; Qi Falian; Hu Chengjin

2005-01-01

To investigate the relationship between expressions of TRAIL, NF-kB and cell proliferation in human osteosarcomas, the expressions of TRAIL and NF-kB in 16 cases of osteosarcoma, 5 cases of giant cell tumor of bone and 6 cases of chondrosarcoma were studied by flow cytometry. The expressions of TRAIL and NF-kB in osteosarcomas of different differentiation states were higher than those in other two kinds of tumors significantly in our study(P 0.05). The expressions of TRAIL and NF-kB in chondrosarcoma and giant cell tumor of bone were not different significantly(P>0.05). The higher expression of TRAIL in osteosarcoma with different differentiation states could not induce apoptosis because of the higher expression of NF-kB. NF-kB may restrain the apoptosis of tumor cells by regulating the NF-kB- induced apoptosis path way in osteosarcoma. (authors)

Effects of Qingshen Granules on the Oxidative Stress-NF/kB Signal Pathway in Unilateral Ureteral Obstruction Rats.

Science.gov (United States)

Jin, Hua; Wang, Yiping; Wang, Dong; Zhang, Lei

2018-01-01

Background . The activation of NF-kappa B (NF/kB) signaling pathway plays an important role in the process of epithelial-mesenchymal transition (EMT) and renal interstitial fibrosis (RIF) in renal tubules. The process of oxidative stress reaction in kidney is via excessive reactive oxygen species (ROS) production to activate NF/kB signaling pathway. Qingshen Granule (QSG) is an effective Chinese formula utilized to treat chronic renal failure. Previous studies confirmed that QSG could inhibit RIF in unilateral ureteral obstruction (UUO) rats. In this study, we used UUO rats to investigate the effects of QSG on oxidative stress and the activation of NF/kB signaling. Seventy male Sprague-Dawley (SD) rats were randomly divided into a sham group, UUO model group, Qingshen Granules (QSG) high-dose, medium-dose, and low-dose groups, PDTC group, and candesartan group (10 rats in each group). Our study demonstrated that oxidative stress-NF/kB signal pathway contributed to the formation of UUO renal interstitial fibrosis. QSG may protect against RIF by inhibiting the oxidative stress-NF/kB signal pathway, reducing inflammation, and improving renal tubular EMT.

TNF-α decreases VEGF secretion in highly polarized RPE cells but increases it in non-polarized RPE cells related to crosstalk between JNK and NF-κB pathways.

Directory of Open Access Journals (Sweden)

Hiroto Terasaki

Full Text Available Asymmetrical secretion of vascular endothelial growth factor (VEGF by retinal pigment epithelial (RPE cells in situ is critical for maintaining the homeostasis of the retina and choroid. VEGF is also involved in the development and progression of age-related macular degeneration (AMD. We studied the effect of tumor necrosis factor-α (TNF-α on the secretion of VEGF in polarized and non-polarized RPE cells (P-RPE cells and N-RPE cells, respectively in culture and in situ in rats. A subretinal injection of TNF-α caused a decrease in VEGF expression and choroidal atrophy. Porcine RPE cells were seeded on Transwell™ filters, and their maturation and polarization were confirmed by the asymmetrical VEGF secretion and trans electrical resistance. Exposure to TNF-α decreased the VEGF secretion in P-RPE cells but increased it in N-RPE cells in culture. TNF-α inactivated JNK in P-RPE cells but activated it in N-RPE cells, and TNF-α activated NF-κB in P-RPE cells but not in N-RPE cells. Inhibition of NF-κB activated JNK in both types of RPE cells indicating crosstalk between JNK and NF-κB. TNF-α induced the inhibitory effects of NF-κB on JNK in P-RPE cells because NF-κB is continuously inactivated. In N-RPE cells, however, it was not evident because NF-κB was already activated. The basic activation pattern of JNK and NF-κB and their crosstalk led to opposing responses of RPE cells to TNF-α. These results suggest that VEGF secretion under inflammatory conditions depends on cellular polarization, and the TNF-α-induced VEGF down-regulation may result in choroidal atrophy in polarized physiological RPE cells. TNF-α-induced VEGF up-regulation may cause neovascularization by non-polarized or non-physiological RPE cells.

NF-kappa B activity in T cells stably expressing the Tax protein of human T cell lymphotropic virus type I

International Nuclear Information System (INIS)

Lacoste, J.; Cohen, L.; Hiscott, J.

1991-01-01

The effect of constitutive Tax expression on the interaction of NF-κ B with its recognition sequence and on NF-κ B-dependent gene expression was examined in T lymphoid Jurkat cell lines (19D and 9J) stably transformed with a Tax expression vector. Tax expressing T cell lines contained a constitutive level of NF-κ B binding activity, detectable by mobility shift assay and uv cross-linking using a palindromic NF-κ B probe homologous to the interferon beta PRDII site. In Jurkat and NC2.10 induction with phorbol esters resulted in the appearance of new DNA binding proteins of 85, 75, and 54 kDa, whereas in Tax expressing cells the 85-kDa protein and a 92-kDa DNA binding protein were constitutively induced. Expression of Tax protein in 19D and 9J resulted in transcription of the endogenous NF-kappa B-dependent granulocyte-macrophage colony stimulating factor gene and increased basal level expression of transfected NF-kappa B-regulated promoters. Nonetheless transcription of both the endogenous and the transfected gene was inducible by PMA treatment. Tax expression in Jurkat T cells may alter the stoichiometry of NF-kappa B DNA binding proteins and thus change the expression of NF-kappa B-regulated promoters

Control of NF-kB activity in human melanoma by bromodomain and extra-terminal protein inhibitor I-BET151.

Science.gov (United States)

Gallagher, Stuart J; Mijatov, Branka; Gunatilake, Dilini; Gowrishankar, Kavitha; Tiffen, Jessamy; James, Wilmott; Jin, Lei; Pupo, Gulietta; Cullinane, Carleen; McArthur, Grant A; Tummino, Peter J; Rizos, Helen; Hersey, Peter

2014-11-01

The transcription factor NF-kappaB (NF-kB) is a key regulator of cytokine and chemokine production in melanoma and is responsible for symptoms such as anorexia, fatigue, and weight loss. In addition, NF-kB is believed to contribute to progression of the disease by upregulation of cell cycle and anti-apoptotic genes and to contribute to resistance against targeted therapies and immunotherapy. In this study, we have examined the ability of the bromodomain and extra-terminal (BET) protein inhibitor I-BET151 to inhibit NF-kB in melanoma cells. We show that I-BET151 is a potent, selective inhibitor of a number of NF-kB target genes involved in induction of inflammation and cell cycle regulation and downregulates production of cytokines such as IL-6 and IL-8. SiRNA studies indicate that BRD2 is the main BET protein involved in regulation of NF-kB and that I-BET151 caused transcriptional downregulation of the NF-kB subunit p105/p50. These results suggest that BET inhibitors may have an important role in treatment of melanoma where activation of NF-kB may have a key pathogenic role. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Unirradiated cells rescue cells exposed to ionizing radiation: Activation of NF-κB pathway in irradiated cells

Energy Technology Data Exchange (ETDEWEB)

Lam, R.K.K. [Department of Physics and Materials Science, City University of Hong Kong (Hong Kong); Han, Wei [Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031 (China); Yu, K.N., E-mail: peter.yu@cityu.edu.hk [Department of Physics and Materials Science, City University of Hong Kong (Hong Kong); State Key Laboratory in Marine Pollution, City University of Hong Kong (Hong Kong)

2015-12-15

Highlights: • Rescue effect was observed in both irradiated and HeLa and NIH/3T3 cells. • Novel setup and procedures to separate the rescue signals and the bystander signals. • Confirmed activation of NF-κB pathway in rescue effect using activation inhibitor. • Confirmed activation of NF-κB pathway in rescue effect using anti-NF-κB p65 antibody. - Abstract: We studied the involvement of NF-κB pathway activation in the rescue effect in HeLa and NIH/3T3 cells irradiated by α particles. Firstly, upon irradiation by 5 cGy of α particles, for both cell lines, the numbers of 53BP1 foci/cell at 12 h post-irradiation were significantly smaller when only 2.5% of the cell population was irradiated as compared to 100% irradiation, which demonstrated the rescue effect. Secondly, we studied the effect of NF-κB on the rescue effect through the use of the NF-κB activation inhibitor BAY-11-7082. Novel experimental setup and procedures were designed to prepare the medium (CM) which had conditioned the bystander cells previously partnered with irradiated cells, to ensure physical separation between rescue and bystander signals. BAY-11-7082 itself did not inflict DNA damages in the cells or have effects on activation of the NF-κB response pathway in the irradiated cells through direct irradiation. The rescue effect was induced in both cell lines by the CM, which was abrogated if BAY-11-7082 was added to the CM. Thirdly, we studied the effect of NF-κB on the rescue effect through staining for phosphorylated NF-κB (p-NF-κB) expression using the anti-NF-κB p65 (phospho S536) antibody. When the fraction of irradiated cells dropped from 100% to 2.5%, the p-NF-κB expression in the cell nuclei of irradiated NIH/3T3 cells increased significantly, while that in the cell nuclei of irradiated HeLa cells also increased although not significantly. Moreover, the p-NF-κB expression in the cell nuclei of irradiated HeLa cells and NIH/3T3 cells treated with CM also increased

Development and Characterisation of a Novel NF-κB Reporter Cell Line for Investigation of Neuroinflammation

Directory of Open Access Journals (Sweden)

Marie-Theres Zeuner

2017-01-01

Full Text Available Aberrant activation of the transcription factor NF-κB, as well as uncontrolled inflammation, has been linked to autoimmune diseases, development and progression of cancer, and neurological disorders like Alzheimer’s disease. Reporter cell lines are a valuable state-of-the art tool for comparative analysis of in vitro drug screening. However, a reporter cell line for the investigation of NF-κB-driven neuroinflammation has not been available. Thus, we developed a stable neural NF-κB-reporter cell line to assess the potency of proinflammatory molecules and peptides, as well as anti-inflammatory pharmaceuticals. We used lentivirus to transduce the glioma cell line U251-MG with a tandem NF-κB reporter construct containing GFP and firefly luciferase allowing an assessment of NF-κB activity via fluorescence microscopy, flow cytometry, and luminometry. We observed a robust activation of NF-κB after exposure of the reporter cell line to tumour necrosis factor alpha (TNFα and amyloid-β peptide [1-42] as well as to LPS derived from Salmonella minnesota and Escherichia coli. Finally, we demonstrate that the U251-NF-κB-GFP-Luc reporter cells can be used for assessing the anti-inflammatory potential of pharmaceutical compounds using Bay11-7082 and IMD0354. In summary, our newly generated cell line is a robust and cost-efficient tool to study pro- and anti-inflammatory potential of drugs and biologics in neural cells.

Recombinant human brain natriuretic peptide attenuates trauma-/haemorrhagic shock-induced acute lung injury through inhibiting oxidative stress and the NF-κB-dependent inflammatory/MMP-9 pathway.

Science.gov (United States)

Song, Zhi; Zhao, Xiu; Liu, Martin; Jin, Hongxu; Wang, Ling; Hou, Mingxiao; Gao, Yan

2015-12-01

Acute lung injury (ALI) is one of the most serious complications in traumatic patients and is an important part of multiple organ dysfunction syndrome (MODS). Recombinant human brain natriuretic peptide (rhBNP) is a peptide with a wide range of biological activity. In this study, we investigated local changes in oxidative stress and the NF-κB-dependent matrix metalloproteinase-9 (MMP-9) pathway in rats with trauma/haemorrhagic shock (TH/S)-induced ALI and evaluated the effects of pretreatment with rhBNP. Forty-eight rats were randomly divided into four groups: sham operation group, model group, low-dosage rhBNP group and high-dosage rhBNP group (n = 12 for each group). Oxidative stress and MPO activity were measured by ELISA kits. MMP-9 activity was detected by zymography analysis. NF-κB activity was determined using Western blot assay. With rhBNP pretreatment, TH/S-induced protein leakage, increased MPO activity, lipid peroxidation and metalloproteinase (MMP)-9 activity were inhibited. Activation of antioxidative enzymes was reversed. The phosphorylation of NF-κB and the degradation of its inhibitor IκB were suppressed. The results suggested that the protection mechanism of rhBNP is possibly mediated through upregulation of anti-oxidative enzymes and inhibition of NF-κB activation. More studies are needed to further evaluate whether rhBNP is a suitable candidate as an effective inhaling drug to reduce the incidence of TH/S-induced ALI. © 2016 The Authors. International Journal of Experimental Pathology © 2016 International Journal of Experimental Pathology.

(Bipyridine-κ2N,N′chlorido[N-(2-hydroxyethyl-N-isopropyldithiocarbamato-κ2S,S′]zinc(II

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Fatin Allia Mohamad

2012-07-01

Full Text Available The ZnII atom in the title compound, [Zn(C6H12NOS2Cl(C10H8N2], is coordinated by a chelating N-2-hydroxyethyl-N-isopropyldithiocarbamate ligand, a 2,2′-bipyridine ligand and a Cl atom. The resulting ClN2S2 donor set defines a distorted square-pyramidal coordination geometry. Helical supramolecular chains sustained by O—H...S hydrogen bonds and propagating along the b axis feature in the crystal packing. A three-dimensional architecture is stabilized by C—H...O, C—H...S and C—H...Cl interactions.

The reciprocal interaction of sympathetic nervous system and cAMP-PKA-NF-kB pathway in immune suppression after experimental stroke.

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Zuo, Lei; Shi, Luhang; Yan, Fuling

2016-08-03

Sympathetic nervous system(SNS) is involved in the mechanism of immune suppression after stroke. Furthermore, as the pro-inflammatory effect of nuclear factor kappa B(NF-kB) is inhibited after stroke, which is regulated by cyclic adenosine monophosphate(cAMP) and proteinkinase A(PKA). The cAMP-PKA-NF-kB pathway might play an important role in noradrenergic-mediated immune dysfunction. The purpose of our research is to analyze how SNS interfere with the immune system after acute stroke and the underlying mechanism of cAMP-PKA-NF-kB pathway in regulating the inflammation. 32 healthy male Sprague-Dawley rats were divided into 4 groups equally and randomly (1) Sham operation group; (2) middle cerebral artery occlusion; (MCAO) control group; (3) propranolol MCAO group; (4) isopropylarterenol sham group. 72h later after MCAO or sham operation, tumor necrosis factor-α(TNF-α)and interleukine-10(IL-10) in serum as well as cAMP, PKA and NF-kB in spleen cells were tested. TNF-α decreased while IL-10 increased in serum after acute ischemia stroke (pkB was inhibited (pkB is down-regulated. Since the pro-inflammatory effect of NF-kB slacked, the immune system may be inhibited after stroke. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

La receta Penal Después de la llegada de la Ley N ° 12.234 / 10 , y su relación con las funciones de protección del Estado

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Anelise Coelho Nunes

2016-06-01

Full Text Available Los cambios introducidos por la promulgación de la Ley n° 12.234 /10 trajeron una cierta controversia con respecto a una posible prescripción de la extinción (en forma retroactivo. En este sentido, el texto permite establecer un parámetro de la discusión, con la garantía de que el legislador optó por dar efecto ex tunc a la prescripción de la pretensión punitiva, en base a la sanción específica, sólo desde la recepción de la queja o reclamación. Por lo tanto, este estudio es necesario para tratar sobre el deber fundamental de la protección del Estado, que, por ley, acto administrativo o acciones de hecho, está obligado a actuar positivamente para evitar prácticas aceras sean perjudiciales para los derechos fundamentales.

Tuning crystal phase of NiS{sub x} through electro-oxidized nickel foam: A novel route for preparing efficient electrocatalysts for oxygen evolution reaction

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Li, Xiao; Shang, Xiao [State Key Laboratory of Heavy Oil Processing, China University of Petroleum (East China), Qingdao 266580 (China); Rao, Yi [State Key Laboratory of Heavy Oil Processing, China University of Petroleum (East China), Qingdao 266580 (China); College of Science, China University of Petroleum (East China), Qingdao 266580, PR China (China); Dong, Bin, E-mail: dongbin@upc.edu.cn [State Key Laboratory of Heavy Oil Processing, China University of Petroleum (East China), Qingdao 266580 (China); College of Science, China University of Petroleum (East China), Qingdao 266580, PR China (China); Han, Guan-Qun [State Key Laboratory of Heavy Oil Processing, China University of Petroleum (East China), Qingdao 266580 (China); College of Science, China University of Petroleum (East China), Qingdao 266580, PR China (China); Hu, Wen-Hui; Liu, Yan-Ru; Yan, Kai-Li; Chi, Jing-Qi; Chai, Yong-Ming [State Key Laboratory of Heavy Oil Processing, China University of Petroleum (East China), Qingdao 266580 (China); Liu, Chen-Guang, E-mail: cgliu@upc.edu.cn [State Key Laboratory of Heavy Oil Processing, China University of Petroleum (East China), Qingdao 266580 (China)

2017-02-28

Highlights: • Electro-oxidized nickel foam as a support has been used to prepare NiS{sub x} phases. • Ni(OH){sub 2} layer on electro-oxidized NF is responsible for the growth of β-NiS. • NiS{sub x}/NF(Ox) composed of β-NiS and Ni{sub 3}S{sub 2} has enhanced electrocatalytic activity. • The growth mechanisms of mixed NiS{sub x} phases of NiS{sub x}/NF(Ox) have been discussed. - Abstract: A facile solvothermal sulfurization using electro-oxidized nickel foam (NF(Ox)) as support has been applied to prepare NiS{sub x}/NF(Ox) electrocatalyst with highly efficient activity for oxygen evolution reaction (OER). XRD patterns confirm the composition of NiS{sub x}/NF(Ox): two kinds of crystal phase including β-NiS and Ni{sub 3}S{sub 2}. While using bare NF as support under identical conditions, only Ni{sub 3}S{sub 2} phase can be detected. SEM images reveal two kinds of morphologies of NiS{sub x}/NF(Ox) including pyramids structure of β-NiS and nanorod-like structure of Ni{sub 3}S{sub 2}, which implies the tuning effect of electro-pretreatment of NF on the selective preparation of NiS{sub x} crystal phase. It can be speculated that Ni(OH){sub 2} layer derived from electro-oxidized NF is responsible for the growth of β-NiS while metallic Ni is transformed into Ni{sub 2}S{sub 3} during sulfurization. Electrochemical measurements for OER indicate the enhanced electrocatalytic activity of NiS{sub x}/NF(Ox) with a small overpotential of 72 mV to reach 10 mA cm{sup −2} compared with Ni{sub 3}S{sub 2}/NF, which may be ascribed to the improved electron-transfer kinetics relating to the unique atomic configurations and crystalline structures of β-NiS. The electro-oxidation pretreatment of nickel foam provides a simple and convenient method by tuning different NiS{sub x} crystal phases for preparing excellent OER eletrocatalysts.

Comparison of NF membrane fouling and cleaning by two pretreatment strategies for the advanced treatment of antibiotic production wastewater.

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Wang, Jianxing; Li, Kun; Yu, Dawei; Zhang, Junya; Wei, Yuansong; Chen, Meixue; Shan, Baoqing

2016-01-01

The nanofiltration (NF) membrane fouling characteristics and cleaning strategies were investigated and compared for treating membrane bioreactor (MBR) effluent and MBR-granular activated carbon (GAC) effluent of an antibiotic production wastewater by DK membrane. Results showed that the fouling of treating MBR effluent was more severe than that of treating MBR-GAC effluent. After filtering for 216 h, the difference of membrane flux decline was obvious between MBR effluent and MBR-GAC effluent, with 14.9% and 10.3% flux decline, respectively. Further study showed that organic fouling is the main NF membrane fouling in the advanced treatment of antibiotic production wastewater for both of the two different effluents. Soluble microbial by-product like and tyrosine-like substances were the dominant components in the foulants, whereas humic-like substances existing in the effluents had little contribution to the NF membrane fouling. A satisfactory efficiency of NF chemical cleaning could be obtained using combination of acid (HCl, pH 2.0-2.5) and alkali (NaOH + 0.3 wt% NaDS, pH 10.0-10.5). The favorable cleaning strategy is acid-alkali for treating the MBR-GAC effluent, while it is alkali-acid for treating the MBR effluent.

Carrageenan-Induced Colonic Inflammation Is Reduced in Bcl10 Null Mice and Increased in IL-10-Deficient Mice

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Sumit Bhattacharyya

2013-01-01

Full Text Available The common food additive carrageenan is a known activator of inflammation in mammalian tissues and stimulates both the canonical and noncanonical pathways of NF-κB activation. Exposure to low concentrations of carrageenan (10 μg/mL in the water supply has produced glucose intolerance, insulin resistance, and impaired insulin signaling in C57BL/6 mice. B-cell leukemia/lymphoma 10 (Bcl10 is a mediator of inflammatory signals from Toll-like receptor (TLR 4 in myeloid and epithelial cells. Since the TLR4 signaling pathway is activated in diabetes and by carrageenan, we addressed systemic and intestinal inflammatory responses following carrageenan exposure in Bcl10 wild type, heterozygous, and null mice. Fecal calprotectin and circulating keratinocyte chemokine (KC, nuclear RelA and RelB, phospho(Thr559-NF-κB-inducing kinase (NIK, and phospho(Ser36-IκBα in the colonic epithelial cells were significantly less (P<0.001 in the carrageenan-treated Bcl10 null mice than in controls. IL-10-deficient mice exposed to carrageenan in a germ-free environment showed an increase in activation of the canonical pathway of NF-κB (RelA activation, but without increase in RelB or phospho-Bcl10, and exogenous IL-10 inhibited only the canonical pathway of NF-κB activation in cultured colonic cells. These findings demonstrate a Bcl10 requirement for maximum development of carrageenan-induced inflammation and lack of complete suppression by IL-10 of carrageenan-induced inflammation.

Neurofibromatosis tipo I con manifestaciones en el periodonto y lengua: presentación de un caso Type I neurofibromatosis with periodontal and lingual manifestations: a case report

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M.C. Negreiros Lyrio

2008-06-01

Full Text Available La enfermedad de Von Recklinghausen o Neurofibromatosis Tipo I (NF1 es una condición autosómica dominante que presenta una variada expresión clínica, con manifestaciones que van desde manchas tipo café con leche en piel a severas complicaciones estéticas y funcionales afectando los tejidos óseos y nerviosos. Las manifestaciones orales de la NF1 son comunes, afectando aproximadamente al 72% de los pacientes. Presentamos un caso de NF1 con lesiones neurofibromatosas afectando al reborde alveolar inferior y lengua, con indicación de excisión quirúrgica debido a la dificultad de higiene local.Von Recklinghausen’s disease, or type I neurofibromatosis (NF-1, is an autosomal dominant condition with a varied clinical expression. Disease manifestations may range from café au lait spots of the skin to severe cosmetic and functional complications that affect bone and nervous tissues. Oral manifestations of NF-1 are common, affecting approximately 72% of patients. We report a case of NF-1 with neurofibromatous lesions of the lower alveolar bridge and tongue. Resection was indicated due to the difficulty of maintaining oral hygiene.

Porcine arterivirus activates the NF-κB pathway through IκB degradation

International Nuclear Information System (INIS)

Lee, Sang-Myeong; Kleiboeker, Steven B.

2005-01-01

Nuclear factor-kappaB (NF-κB) is a critical regulator of innate and adaptive immune function as well as cell proliferation and survival. The present study demonstrated for the first time that a virus belonging to the Arteriviridae family activates NF-κB in MARC-145 cells and alveolar macrophages. In porcine reproductive and respiratory syndrome virus (PRRSV)-infected cells, NF-κB activation was characterized by translocation of NF-κB from the cytoplasm to the nucleus, increased DNA binding activity, and NF-κB-regulated gene expression. NF-κB activation was increased as PRRSV infection progressed and in a viral dose-dependent manner. UV-inactivation of PRRSV significantly reduced the level of NF-κB activation. Degradation of IκB protein was detected late in PRRSV infection, and overexpression of the dominant negative form of IκBα (IκBαDN) significantly suppressed NF-κB activation induced by PRRSV. However, IκBαDN did not affect viral replication and viral cytopathic effect. PRRSV infection induced oxidative stress in cells by generating reactive oxygen species (ROS), and antioxidants inhibited NF-κB DNA binding activity in PRRSV-infected cells, suggesting ROS as a mechanism by which NF-κB was activated by PRRSV infection. Moreover, NF-κB-dependent expression of matrix metalloproteinase (MMP)-2 and MMP-9 was observed in PRRSV-infected cells, an observation which implies that NF-κB activation is a biologically significant aspect of PRRSV pathogenesis. The results presented here provide a basis for understanding molecular pathways of pathology and immune evasion associated with disease caused by PRRSV

Cocrystals of 6-propyl-2-thiouracil: N-H···O versus N-H···S hydrogen bonds.

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Tutughamiarso, Maya; Egert, Ernst

2011-11-01

In order to investigate the relative stability of N-H···O and N-H···S hydrogen bonds, we cocrystallized the antithyroid drug 6-propyl-2-thiouracil with two complementary heterocycles. In the cocrystal pyrimidin-2-amine-6-propyl-2-thiouracil (1/2), C(4)H(5)N(3)·2C(7)H(10)N(2)OS, (I), the `base pair' is connected by one N-H···S and one N-H···N hydrogen bond. Homodimers of 6-propyl-2-thiouracil linked by two N-H···S hydrogen bonds are observed in the cocrystal N-(6-acetamidopyridin-2-yl)acetamide-6-propyl-2-thiouracil (1/2), C(9)H(11)N(3)O(2)·2C(7)H(10)N(2)OS, (II). The crystal structure of 6-propyl-2-thiouracil itself, C(7)H(10)N(2)OS, (III), is stabilized by pairwise N-H···O and N-H···S hydrogen bonds. In all three structures, N-H···S hydrogen bonds occur only within R(2)(2)(8) patterns, whereas N-H···O hydrogen bonds tend to connect the homo- and heterodimers into extended networks. In agreement with related structures, the hydrogen-bonding capability of C=O and C=S groups seems to be comparable.

Heterologous SUMO-2/3-ubiquitin chains optimize IκBα degradation and NF-κB activity.

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Fabienne Aillet

Full Text Available The NF-κB pathway is regulated by SUMOylation at least at three levels: the inhibitory molecule IκBα, the IKK subunit γ/NEMO and the p52 precursor p100. Here we investigate the role of SUMO-2/3 in the degradation of IκBα and activation of NF-κB mediated by TNFα. We found that under conditions of deficient SUMOylation, an important delay in both TNFα-mediated proteolysis of IκBα and NF-κB dependent transcription occurs. In vitro and ex vivo approaches, including the use of ubiquitin-traps (TUBEs, revealed the formation of chains on IκBα containing SUMO-2/3 and ubiquitin after TNFα stimulation. The integration of SUMO-2/3 appears to promote the formation of ubiquitin chains on IκBα after activation of the TNFα signalling pathway. Furthermore, heterologous chains of SUMO-2/3 and ubiquitin promote a more efficient degradation of IκBα by the 26S proteasome in vitro compared to chains of either SUMO-2/3 or ubiquitin alone. Consistently, Ubc9 silencing reduced the capture of IκBα modified with SUMO-ubiquitin hybrid chains that display a defective proteasome-mediated degradation. Thus, hybrid SUMO-2/3-ubiquitin chains increase the susceptibility of modified IκBα to the action of 26S proteasome, contributing to the optimal control of NF-κB activity after TNFα-stimulation.

Transcription Factor NF-κB: An Update on Intervention Strategies.

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Panday, Arvind; Inda, Maria Eugenia; Bagam, Prathyusha; Sahoo, Malaya K; Osorio, Diana; Batra, Sanjay

2016-12-01

The nuclear factor (NF)-κB family of transcription factors are ubiquitous and pleiotropic molecules that regulate the expression of more than 150 genes involved in a broad range of processes including inflammation, immunity, cell proliferation, differentiation, and survival. The chronic activation or dysregulation of NF-κB signaling is the central cause of pathogenesis in many disease conditions and, therefore, NF-κB is a major focus of therapeutic intervention. Because of this, understanding the relationship between NF-κB and the induction of various downstream signaling molecules is imperative. In this review, we provide an updated synopsis of the role of NF-κB in DNA repair and in various ailments including cardiovascular diseases, HIV infection, asthma, herpes simplex virus infection, chronic obstructive pulmonary disease, and cancer. Furthermore, we also discuss the specific targets for selective inhibitors and future therapeutic strategies.

Motor dysfunction in NF1: Mediated by attention deficit or inherent to the disorder?

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Haas-Lude, Karin; Heimgärtner, Magdalena; Winter, Sarah; Mautner, Victor-Felix; Krägeloh-Mann, Ingeborg; Lidzba, Karen

2018-01-01

Attention deficit and compromised motor skills are both prevalent in Neurofibromatosis type 1 (NF1), but the relationship is unclear. We investigated motor function in children with NF1 and in children with Attention Deficit/Hyperactivity Disorder (ADHD), and explored if, in patients with NF1, attention deficit influences motor performance. Motor performance was measured using the Movement Assessment Battery for Children (M-ABC) in 71 children (26 with NF1 plus ADHD, 14 with NF1 without ADHD, and 31 with ADHD without NF1) aged 6-12 years. There was a significant effect of group on motor performance. Both NF1 groups scored below children with ADHD without NF1. Attention performance mediated motor performance in children with ADHD without NF1, but not in children with NF1. Motor function is not mediated by attention performance in children with NF1. While in ADHD, attention deficit influences motor performance, motor problems in NF1 seem to be independent from attention deficit. This argues for different pathomechanisms in these two groups of developmental disorders. Copyright © 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Signal Transduction Pathways (MAPKs, NF-κB, and C/EBP) Regulating COX-2 Expression in Nasal Fibroblasts from Asthma Patients with Aspirin Intolerance

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Garcia-Garcia, Francesc Josep; Mullol, Joaquim; Perez-Gonzalez, Maria; Pujols, Laura; Alobid, Isam

2012-01-01

Background Recent studies have revealed that cyclooxygenase-2 (COX-2) expression is down-regulated in aspirin-induced asthma (AIA). Various signal pathways (MAPKs, NF-κB and C/EBP) are involved in COX-2 regulation. Objective To investigate the regulation of COX-2 expression through MAP-kinase pathway activation and nuclear factor translocation in aspirin-induced asthma (AIA). Methods Fibroblasts were isolated from specimens of nasal mucosa (NM, N = 5) and nasal polyps (NP, N = 5). After IL-1β (1 ng/ml) incubation, COX-2 and phosphorylated forms of ERK, JNK and p38 MAPK were measured by Western blot. MAPK’s role in IL-1β-induced COX-2 expression was assessed by treating cells with ERK (PD98059), JNK (SP600125) and p38 MAPK (SB203580) inhibitors (0.1–10 µM) prior to IL-1β exposure. NF-κB and C/EBP nuclear translocation was measured by Western blot and TransAM® after IL-1β (10 ng/ml) exposure. Results No differences were observed in the MAPK phosphorylation time-course between NM and NP-AIA fibroblasts. The p38 MAPK inhibitor at 10 µM significantly reduced IL-1β-induced COX-2 expression in NM fibroblasts (85%). In NP-AIA fibroblasts the COX-2 inhibition (65%) at 1 and 10 µM was not statistically significant compared to non-treated cells. ERK and JNK inhibitors had no significant effect in either the NM or NP-AIA cultures. The effect of IL-1β on NF-κB and C/EBP subunits’ nuclear translocation was similar between NM and NP-AIA fibroblasts. Conclusions These results suggest that p38 MAPK is the only MAPK involved in IL-1β-induced COX-2 expression. NM and NP-AIA fibroblasts have similar MAPK phosphorylation dynamics and nuclear factor translocation (NF-κB and C/EBP). COX-2 downregulation observed in AIA patients appears not to be caused by differences in MAPK dynamics or transcription factor translocation. PMID:23240010

Redox-Regulated Pathway of Tyrosine Phosphorylation Underlies NF-κB Induction by an Atypical Pathway Independent of the 26S Proteasome

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Cullen, Sarah; Ponnappan, Subramaniam; Ponnappan, Usha

2015-01-01

Alternative redox stimuli such as pervanadate or hypoxia/reoxygenation, induce transcription factor NF-κB by phospho-tyrosine-dependent and proteasome-independent mechanisms. While considerable attention has been paid to the absence of proteasomal regulation of tyrosine phosphorylated IκBα, there is a paucity of information regarding proteasomal regulation of signaling events distinct from tyrosine phosphorylation of IκBα. To delineate roles for the ubiquitin-proteasome pathway in the phospho-tyrosine dependent mechanism of NF-κB induction, we employed the proteasome inhibitor, Aclacinomycin, and the phosphotyrosine phosphatase inhibitor, pervanadate (PV). Results from these studies demonstrate that phospho-IκBα (Tyr-42) is not subject to proteasomal degradation in a murine stromal epithelial cell line, confirming results previously reported. Correspondingly, proteasome inhibition had no discernable effect on the key signaling intermediaries, Src and ERK1/2, involved in the phospho-tyrosine mechanisms regulating PV-mediated activation of NF-κB. Consistent with previous reports, a significant redox imbalance leading to the activation of tyrosine kinases, as occurs with pervanadate, is required for the induction of NF-κB. Strikingly, our studies demonstrate that proteasome inhibition can potentiate oxidative stress associated with PV-stimulation without impacting kinase activation, however, other cellular implications for this increase in intracellular oxidation remain to be fully delineated. PMID:25671697

Altholactone Inhibits NF-κB and STAT3 Activation and Induces Reactive Oxygen Species-Mediated Apoptosis in Prostate Cancer DU145 Cells

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Chunwa Jiang

2017-02-01

Full Text Available Altholactone, a natural compound isolated from Goniothalamus spp., has demonstrated anti-inflammatory and anticancer activities, but its molecular mechanisms are still not fully defined. Nuclear factor kappa B (NF-κB and signal transducer and activator of transcription 3 (STAT3 play pivotal roles in the cell survival of many human tumors. The objective of this study was to elucidate the mechanism of action of altholactone against prostate cancer DU145 cells and to evaluate whether its effects are mediated by inhibition of NF-κB and STAT3 activity. Altholactone inhibited proliferation of DU145 cells and induced cell cycle arrest in S phase and triggered apoptosis. Reporter assays revealed that altholactone repressed p65- and TNF-α-enhanced NF-κB transcriptional activity and also inhibited both constitutive and IL-6-induced transcriptional activity of STAT3. Consistent with this, altholactone down-regulated phosphorylation of STAT3 and moreover, decreased constitutively active mutant of STAT3 (STAT3C-induced transcriptional activity. Altholactone treatment also results in down-regulation of STAT3 target genes such as survivin, and Bcl-2 followed by up regulation of pro-apoptotic Bax protein. However, pre-treatment with the antioxidant N-acetylcysteine (NAC significantly inhibited the activation of Bax and prevented down-regulation of STAT3 target genes. Collectively, our findings suggest that altholactone induces DU145 cells death through inhibition of NF-κB and STAT3 activity.

A non-perturbative exploration of the high energy regime in Nf=3 QCD. ALPHA Collaboration

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Dalla Brida, Mattia; Fritzsch, Patrick; Korzec, Tomasz; Ramos, Alberto; Sint, Stefan; Sommer, Rainer

2018-05-01

Using continuum extrapolated lattice data we trace a family of running couplings in three-flavour QCD over a large range of scales from about 4 to 128 GeV. The scale is set by the finite space time volume so that recursive finite size techniques can be applied, and Schrödinger functional (SF) boundary conditions enable direct simulations in the chiral limit. Compared to earlier studies we have improved on both statistical and systematic errors. Using the SF coupling to implicitly define a reference scale 1/L_0≈ 4 GeV through \\bar{g}^2(L_0) =2.012, we quote L_0 Λ ^{N_f=3}_{{\\overline{MS}}} =0.0791(21). This error is dominated by statistics; in particular, the remnant perturbative uncertainty is negligible and very well controlled, by connecting to infinite renormalization scale from different scales 2^n/L_0 for n=0,1,\\ldots ,5. An intermediate step in this connection may involve any member of a one-parameter family of SF couplings. This provides an excellent opportunity for tests of perturbation theory some of which have been published in a letter (ALPHA collaboration, M. Dalla Brida et al. in Phys Rev Lett 117(18):182001, 2016). The results indicate that for our target precision of 3 per cent in L_0 Λ ^{N_f=3}_{{\\overline{MS}}}, a reliable estimate of the truncation error requires non-perturbative data for a sufficiently large range of values of α _s=\\bar{g}^2/(4π ). In the present work we reach this precision by studying scales that vary by a factor 2^5= 32, reaching down to α _s≈ 0.1. We here provide the details of our analysis and an extended discussion.

[Effect of NF-κB on the expression of interleukin-6 induced by lipopolysaccharides of Porphyromonas endodontalis in MC3T3-E1 cells].

Science.gov (United States)

Yu, Ya-qiong; Guo, Jia-jie; Qiu, Li-hong; Lv, You; Jia, Ge; Guo, Yan

2013-08-01

To investigate the effect of NF-κB signaling on the expression of interleukin-6(IL-6) induced by lipopolysaccharides(LPS) extracted from Porphyromonas endodontalis(P.e) in MC3T3-El cells. MC3T3-E1 cells were pretreated with BAY-117082 for 1 h, and then were treated with 10 mg/L P.e-LPS for different times. The translocation of NF-κB was observed by immunofluorescence. The expression of IL-6 was detected by reverse transcription polymerse chain reaction (RT-PCR) and enzyme-linked immuno sorbent assay (ELISA). Statistical analysis was performed using multi-way ANOVA and Dunnett's t test with SPSS 13.0 software package. The staining of NF-κB was mostly in cytoplasm in untreated cells. Rapid translocation of NF-κB into nucleus was observed in the cells stimulated for 30 min and mostly relocalization of NF-κB from nucleus to cytoplasm was observed after 60 min. Pretreatment with 10 μmol/L BAY-117082 for 1h significantly inhibited P.e-LPS-induced translocation of NF-κB .The mRNA and proteins of IL-6 decreased significantly after pretreatment with 10 μmol/L BAY-117082 and the expression of IL-6 proteins was reduced from (774.983±6.585) ng/L to (377.384±14.620) ng/L (P<0.01). The group of treatment with BAY-117082 alone had no significant difference from the blank control group. P.e-LPS can induce translocation of NF-κB in mouse osteoblast MC3T3-El, and P.e-LPS may induce the expression of IL-6 in mouse osteoblast through the signaling of NF-κB.

Nf1 Loss and Ras Hyperactivation in Oligodendrocytes Induce NOS-Driven Defects in Myelin and Vasculature

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Debra A. Mayes

2013-09-01

Full Text Available Patients with neurofibromatosis type 1 (NF1 and Costello syndrome Rasopathy have behavioral deficits. In NF1 patients, these may correlate with white matter enlargement and aberrant myelin. To model these features, we induced Nf1 loss or HRas hyperactivation in mouse oligodendrocytes. Enlarged brain white matter tracts correlated with myelin decompaction, downregulation of claudin-11, and mislocalization of connexin-32. Surprisingly, non-cell-autonomous defects in perivascular astrocytes and the blood-brain barrier (BBB developed, implicating a soluble mediator. Nitric oxide (NO can disrupt tight junctions and gap junctions, and NO and NO synthases (NOS1–NOS3 were upregulated in mutant white matter. Treating mice with the NOS inhibitor NG-nitro-L-arginine methyl ester or the antioxidant N-acetyl cysteine corrected cellular phenotypes. CNP-HRasG12V mice also displayed locomotor hyperactivity, which could be rescued by antioxidant treatment. We conclude that Nf1/Ras regulates oligodendrocyte NOS and that dysregulated NO signaling in oligodendrocytes can alter the surrounding vasculature. The data suggest that antioxidants may improve some behavioral deficits in Rasopathy patients.

Role of monoubiquitylation on the control of IκBα degradation and NF-κB activity.

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Elisa Da Silva-Ferrada

Full Text Available The NF-κB pathway is regulated by multiple post-translational modifications including phosphorylation, ubiquitylation and SUMOylation. Many of these modifications act on the natural inhibitor IκBα modulating its capacity to control signal-mediated NF-κB activity. While the canonical pathway involving the phosphorylation and polyubiquitylation of IκBα has been well characterized, the role of these post-translational modifications in the control of basal NF-κB activity has not been deeply explored. Using the recently developed Tandem-repeated Ubiquitin Binding Entities (also known as ubiquitin traps to capture ubiquitylated proteins, we identified monoubiquitylated forms of IκBα from multiple rat organs and cell types. The identification of these forms was demonstrated through different procedures such as immunoprecipitations with specific ubiquitin antibodies or His6-Ubiquitin pull downs. Monoubiquitylated forms of IκBα are resistant to TNFα-mediated degradation and can be captured using TUBEs, even after proteasome inhibitors treatment. As it occurs for monoSUMOylation, monoubiquitylation is not dependent of the phosphorylation of IκBα on the serines 32/36 and is not optimally degraded after TNFα stimulation. A ubiquitin-IκBα fusion exhibits phosphorylation defects and resistance to TNFα mediated degradation similar to the ones observed for endogenous monoubiquitylated IκBα. The N-terminal attachment of a single ubiquitin moiety on the IκBα fusion results in a deficient binding to the IKKβ kinase and recruitment of the SCF ligase component βTrCP, promoting a negative impact on the NF-κB activity. Altogether, our results suggest the existence of a reservoir of monoubiquitylated IκBα resistant to TNFα-induced proteolysis, which is able to interact and repress DNA binding and NF-κB transcriptional activity. Such pool of IκBα may play an important role in the control of basal and signal-mediated NF-κB activity.

Inhibition of NF-κB activity in the hypothalamic paraventricular nucleus attenuates hypertension and cardiac hypertrophy by modulating cytokines and attenuating oxidative stress

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Yu, Xiao-Jing [Department of Physiology and Pathophysiology, Xi' an Jiaotong University School of Basic Medical Sciences, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University Health Science Center, Xi' an 710061 (China); Zhang, Dong-Mei [Department of Physiology, Dalian Medical University, Dalian 116044 (China); Jia, Lin-Lin; Qi, Jie; Song, Xin-Ai; Tan, Hong [Department of Physiology and Pathophysiology, Xi' an Jiaotong University School of Basic Medical Sciences, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University Health Science Center, Xi' an 710061 (China); Cui, Wei [Department of Endocrinology and Metabolism, First Affiliated Hospital of Xi' an Jiaotong University, Xi' an Jiaotong University Health Science Center, Xi' an 710061 (China); Chen, Wensheng [Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi' an 710032 (China); Zhu, Guo-Qing [Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing 210029 (China); Qin, Da-Nian, E-mail: dnqin@stu.edu.cn [Department of Physiology, Shantou University Medical College, Shantou 515041 (China); Kang, Yu-Ming, E-mail: ykang@mail.xjtu.edu.cn [Department of Physiology and Pathophysiology, Xi' an Jiaotong University School of Basic Medical Sciences, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University Health Science Center, Xi' an 710061 (China)

2015-05-01

We hypothesized that chronic inhibition of NF-κB activity in the hypothalamic paraventricular nucleus (PVN) delays the progression of hypertension and attenuates cardiac hypertrophy by up-regulating anti-inflammatory cytokines, reducing pro-inflammatory cytokines (PICs), attenuating nuclear factor-κB (NF-κB) p65 and NAD(P)H oxidase in the PVN of young spontaneously hypertensive rats (SHR). Young normotensive Wistar–Kyoto (WKY) and SHR rats received bilateral PVN infusions with NF–κB inhibitor pyrrolidine dithiocarbamate (PDTC) or vehicle for 4 weeks. SHR rats had higher mean arterial pressure and cardiac hypertrophy as indicated by increased whole heart weight/body weight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, cardiomyocyte diameters of the left cardiac ventricle, and mRNA expressions of cardiac atrial natriuretic peptide (ANP) and beta-myosin heavy chain (β-MHC). These SHR rats had higher PVN levels of proinflammatory cytokines (PICs), reactive oxygen species (ROS), the chemokine monocyte chemoattractant protein-1 (MCP-1), NAD(P)H oxidase activity, mRNA expression of NOX-2 and NOX-4, and lower PVN IL-10, and higher plasma levels of PICs and NE, and lower plasma IL-10. PVN infusion of NF-κB inhibitor PDTC attenuated all these changes. These findings suggest that NF-κB activation in the PVN increases sympathoexcitation and hypertensive response, which are associated with the increases of PICs and oxidative stress in the PVN; PVN inhibition of NF-κB activity attenuates PICs and oxidative stress in the PVN, thereby attenuates hypertension and cardiac hypertrophy. - Highlights: • Spontaneously hypertensive rats exhibit neurohormonal excitation in the PVN. • PVN inhibition of NF-κB attenuates hypertension-induced cardiac hypertrophy. • PVN inhibition of NF-κB attenuates hypertension-induced neurohormonal excitation. • PVN inhibition of NF-κB attenuates hypertension-induced imbalance of cytokines

Bifidobacterium animalis AHC7 protects against pathogen-induced NF-kappaB activation in vivo

LENUS (Irish Health Repository)

O'Mahony, David

2010-12-22

Abstract Background Bifidobacteria and lactobacilli are among the early and important colonizers of the gastrointestinal tract and are generally considered to be part of a normal, healthy microbiota. It is believed that specific strains within the microbiota can influence host immune-reactivity and may play a role in protection from infection and aberrant inflammatory activity. One such strain, Bifidobacterium animalis AHC7, has been previously shown to protect against Salmonella typhimurium infection in mice and helps resolve acute idiopathic diarrhea in dogs. The aim of this study was to investigate the potential molecular and cellular mechanisms underpinning the Bifidobacterium animalis AHC7 protective effect. Results Following 4 hours of infection with Salmonella typhimurium, NF-κB activation was significantly elevated in vivo in placebo and Enterococcus faecium-fed animals while Bifidobacterium animalis AHC7 consumption significantly attenuated the NF-κB response. In vitro anti-CD3\\/CD28 stimulated Peyer\\'s patch cells secreted significantly less TNF-α and IFN-γ following Bifidobacterium animalis AHC7 consumption. Stimulated cells released more IL-12p70 but this difference did not reach statistical significance. No alteration in mucosal IL-6, IL-10 or MCP-1 levels were observed. No statistically significant change in the cytokine profile of mesenteric lymph node cells was noted. In vitro, Bifidobacterium animalis AHC7 was bound by dendritic cells and induced secretion of both IL-10 and IL-12p70. In addition, co-culture of CD4+ T cells with Bifidobacterium animalis AHC7-stimulated dendritic cells resulted in a significant increase in CD25+Foxp3+ T cell numbers. Conclusion Bifidobacterium animalis AHC7 exerts an anti-inflammatory effect via the attenuation of pro-inflammatory transcription factor activation in response to an infectious insult associated with modulation of pro-inflammatory cytokine production within the mucosa. The cellular mechanism

The handwriting performance of children with NF1.

Science.gov (United States)

Gilboa, Yafit; Josman, Naomi; Fattal-Valevski, Aviva; Toledano-Alhadef, Hagit; Rosenblum, Sara

2010-01-01

The objective of this study was to analyze the process and product of handwriting among children with Neurofibromatosis Type 1 (NF1) in comparison to those of Typically Developing (TD) children. Children with NF1 are at risk for some cognitive deficits, a wide range of deficits in perceptual skills and, motor and visual-motor integration skills which may interfere with handwriting competency, which is an essential ingredient for success at school. Participants were 30 NF1 children and 30 age and gender matched TD children, between the ages 8 and 16.08. The handwriting performance of children with NF1 was evaluated with the Beery-Buktenica Developmental Test of Visual-Motor Integration (VMI), for copying text and free style writing tasks, using: (1) Computerized Penmanship Evaluation Tool (ComPET) to assess mechanical aspects of the writing process. (2) The Hebrew Handwriting Evaluation (HHE) to examine product legibility. (3) The Six-Trait Writing Model to judge the quality of the written product. Significant differences between the NF1 children and the control group were found in the process and product measures. Significant correlations were found between the VMI, the ComPET, the HHE and the Six-Trait Writing Model variables for both groups. We suggest a possible relationship between executive dysfunction and poor performance in handwriting.

NF1 Signal Transduction and Vascular Dysfunction

Science.gov (United States)

2015-05-01

microenvironment that promotes much of the pathology associated with the disease . Moreover we hypothesize that a mechanistic consequence of the loss...obliteration of the normal red pulp architecture. In addition, we found significant peri-aveolar and peri-vascular inflammatory infiltrates in the lung...the mouse model of NF1 disease in the endothelium we proposed and have done experiments investigating the loss of endothelial NF1 in the adult

Epipolythiodiketopiperazines from the Marine Derived Fungus Dichotomomyces cejpii with NF-κB Inhibitory Potential

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Henrik Harms

2015-08-01

Full Text Available The Ascomycota Dichotomomyces cejpii was isolated from the marine sponge Callyspongia cf. C. flammea. A new gliotoxin derivative, 6-acetylmonodethiogliotoxin (1 was obtained from fungal extracts. Compounds 2 and 3, methylthio-gliotoxin derivatives were formerly only known as semi-synthetic compounds and are here described as natural products. Additionally the polyketide heveadride (4 was isolated. Compounds 1, 2 and 4 dose-dependently down-regulated TNFα-induced NF-κB activity in human chronic myeloid leukemia cells with IC50s of 38.5 ± 1.2 µM, 65.7 ± 2.0 µM and 82.7 ± 11.3 µM, respectively. The molecular mechanism was studied with the most potent compound 1 and results indicate downstream inhibitory effects targeting binding of NF-κB to DNA. Compound 1 thus demonstrates potential of epimonothiodiketopiperazine-derived compounds for the development of NF-κB inhibitors.

Withaferin A disrupts ubiquitin-based NEMO reorganization induced by canonical NF-κB signaling

Energy Technology Data Exchange (ETDEWEB)

Jackson, Shawn S. [McArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin-Madison, 6159 Wisconsin Institute for Medical Research, 1111 Highland Avenue, Madison, WI 53705 (United States); Medical Scientist Training Program, University of Wisconsin-Madison, 1111 Highland Avenue, Madison, WI 53705 (United States); Cellular and Molecular Biology Program, University of Wisconsin-Madison, 1111 Highland Avenue, Madison, WI 53705 (United States); Oberley, Christopher [McArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin-Madison, 6159 Wisconsin Institute for Medical Research, 1111 Highland Avenue, Madison, WI 53705 (United States); Hooper, Christopher P. [McArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin-Madison, 6159 Wisconsin Institute for Medical Research, 1111 Highland Avenue, Madison, WI 53705 (United States); Cellular and Molecular Biology Program, University of Wisconsin-Madison, 1111 Highland Avenue, Madison, WI 53705 (United States); Grindle, Kreg [Department of Medicine, Division of Hematology and Oncology, University of Wisconsin-Madison, 1111 Highland Avenue, Madison, WI 53705 (United States); Wuerzberger-Davis, Shelly [McArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin-Madison, 6159 Wisconsin Institute for Medical Research, 1111 Highland Avenue, Madison, WI 53705 (United States); Wolff, Jared [Department of Medicine, Division of Hematology and Oncology, University of Wisconsin-Madison, 1111 Highland Avenue, Madison, WI 53705 (United States); and others

2015-02-01

The NF-κB family of transcription factors regulates numerous cellular processes, including cell proliferation and survival responses. The constitutive activation of NF-κB has also emerged as an important oncogenic driver in many malignancies, such as activated B-cell like diffuse large B cell lymphoma, among others. In this study, we investigated the impact and mechanisms of action of Withaferin A, a naturally produced steroidal lactone, against both signal-inducible as well as constitutive NF-κB activities. We found that Withaferin A is a robust inhibitor of canonical and constitutive NF-κB activities, leading to apoptosis of certain lymphoma lines. In the canonical pathway induced by TNF, Withaferin A did not disrupt RIP1 polyubiquitination or NEMO–IKKβ interaction and was a poor direct IKKβ inhibitor, but prevented the formation of TNF-induced NEMO foci which colocalized with TNF ligand. While GFP-NEMO efficiently formed TNF-induced foci, a GFP-NEMO{sup Y308S} mutant that is defective in binding to polyubiquitin chains did not form foci. Our study reveals that Withaferin A is a novel type of IKK inhibitor which acts by disrupting NEMO reorganization into ubiquitin-based signaling structures in vivo. - Highlights: • Withaferin A, a NF-κB inhibitor, disrupts signaling induced NEMO localization, a novel point of inhibition. • NEMO can be localized to distinct signaling foci after treatment with TNF. • ABC-type DLCBL cells can be sensitized to apoptosis after treatment with Withaferin A.

Infección por el virus de la Lengua azul: activación de señales celulares que inducen apoptosis Bluetongue virus infection: signaling pathway activated during apoptosis

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E. Mortola

2009-09-01

Full Text Available El virus de la Lengua azul (VLA es un ARN virus de doble cadena que induce apoptosis tanto en cultivos celulares como en tejidos blanco. Con el fin de dilucidar el mecanismo de apoptosis en la infección por el VLA, en el presente trabajo examinamos en detalle, por la técnica de Western blot, las señales celulares de caspasas, Bax, citocromo c, Smac/DIABLO y factor nuclear kappa B (NF-kB que se activan en la infección viral. Hemos comprobado que luego de la infección in vitro con el VLA, se detectó la activación de la caspasa 8 y con ello el mecanismo extrínseco de la apoptosis. También detectamos por primera vez no sólo la activación de miembros de la familia Bcl-2 (Bax, sino también la liberación del citocromo c y la proteína Smac/DIABLO, confirmando que en la infección por el VLA está involucrado el mecanismo secuencial intrínseco de la apoptosis. Asimismo, demostramos que la infección por el VLA activa el NF-kB y que la apoptosis es sustancialmente reducida mediante la inhibición del mismo. La activación de las señales celulares tales como Bax, citocromo c, Smac/DIABLO y NF-kB presentados en este trabajo, esclarecen los mecanismos apoptóticos durante la infección por el VLA para una mayor comprensión del papel primario que juega la apoptosis en la patogénesis del virus.Bluetongue (BTV is a double-stranded RNA virus that induces apoptosis both in mammalian cell cultures and in target tissues. To elucidate the apoptosis pathways in BTV infection, we have examined in detail the apoptosis mechanism by examination of caspases, Bax, cytochrome c, Smac/DIABLO and NF-kB signalling pathways. In this report, after cell infection with BTV, the activation of caspase 8 was detected, proving the extrinsic receptor binding apoptotic pathway. Apoptosis followed a sequential pathway involving the detection of activated Bcl-2 family members. Furthermore, its translocation to the mitochondria, as well as the release of cytochrome c and

Neurofibromatosis tipo I: Mutación de splicing detectada por MLPA y secuenciación en la Argentina

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Sergio Laurito

2015-04-01

Full Text Available La neurofibromatosis tipo 1 (NF1 es un desorden genético autosómico dominante, con una prevalencia de 1 en 2500-3000 nacidos vivos. La dificultad diagnóstica se debe al tamaño extenso del gen NF1 con pocos sitios hot-spot, la ausencia de una clara relación genotipo-fenotipo y rasgos clínicos con un espectro muy heterogéneo. Un caso sospechoso de NF1 procedente de la provincia de Jujuy fue analizado por MLPA (multiplex ligation-dependent probe amplification en nuestro laboratorio. Mujer, adolescente mestiza (Amerindia/Europea, con un osteoma maxilar, lordosis lumbar, neurofibromas cutáneos y manchas café con leche. Por MLPA se detectó una alteración en el exón 13 del gen NF1. Por secuenciación del exón 13 se identificó una mutación "missense" en la posición 1466 del ARNm (NM_000267.3:c.1466A>G que introduce un sitio de splicing aberrante. La patogenicidad de la mutación fue corroborada en la base de datos de variantes clínicas del National Center for Biotechnology Information. En nuestro conocimiento, este es el primer registro de una mutación NF1 en un paciente proveniente de poblaciones mestizas del Noroeste Argentino. La alteración ha sido reportada en individuos de otras poblaciones de origen muy disímil al del caso presentado, como la europea, sugiriendo que el sitio podría considerarse un sitio hot-spot del gen. Donde exista baja disponibilidad de diagnósticos moleculares, como en nuestro caso, se puede aplicar un algoritmo que comience por el estudio del gen NF1 por MLPA, metodología relativamente sencilla y de costo accesible. Con ella se evita enviar muestras al extranjero para análisis genéticos.

Involvement of NF-κBIZ and related cytokines in age-associated renal fibrosis.

Science.gov (United States)

Chung, Ki Wung; Jeong, Hyeong Oh; Lee, Bonggi; Park, Daeui; Kim, Dae Hyun; Choi, Yeun Ja; Lee, Eun Kyeong; Kim, Kyung Mok; Park, June Whoun; Yu, Byung Pal; Chung, Hae Young

2017-01-31

Chronic inflammation is a major contributor to age-related nephropathic changes, including renal fibrosis. In this study, various experimental paradigms were designed to delineate the role played by NF-κBIZ (also known as IκBζ) in age-associated renal fibrosis. Analyses based on RNA-sequencing findings obtained by next generation sequencing (NGS) revealed the upregulations of NF-κBIZ and of IL-6 and MCP-1 (both known to be regulated by NF-κBIZ) during aging. The up-regulation of NF-κBIZ in aged rat kidneys coincided with increased macrophage infiltration. In LPS-treated macrophages, oxidative stress was found to play a pivotal role in NF-κBIZ expression, suggesting age-related oxidative stress is associated with NF-κBIZ activation. Furthermore, these in vitro findings were confirmed in LPS-treated old rats, which showed higher levels of oxidative stress and NF-κBIZ in kidneys than LPS-treated young rats. Additional in vitro experiments using macrophages and kidney fibroblasts demonstrated NF-κBIZ and related cytokines participate in fibrosis. In particular, increased levels of NF-κBIZ-associated cytokines in macrophages significantly up-regulated TGF-β induced kidney fibroblast activation. Moreover, experiments with NF-κBIZ knocked down macrophages showed reduced TGF-β-induced kidney fibroblast activation. The findings of the present study provide evidence regarding an involvement of NF-κBIZ in age-associated progressive renal fibrosis and provides potential targets for its prevention.

Microstructural evolution of NF709 (20Cr–25Ni–1.5MoNbTiN) under neutron irradiation

Energy Technology Data Exchange (ETDEWEB)

Kim, B.K. [Oak Ridge National Laboratory, Oak Ridge, TN 37831 (United States); Tan, L., E-mail: tanl@ornl.gov [Oak Ridge National Laboratory, Oak Ridge, TN 37831 (United States); Xu, C. [University of Florida, Gainesville, FL 32611 (United States); Yang, Y., E-mail: yongyang@ufl.edu [University of Florida, Gainesville, FL 32611 (United States); Zhang, X. [Argonne National Laboratory, Lemont, IL 60439 (United States); Li, M., E-mail: mli@anl.gov [Argonne National Laboratory, Lemont, IL 60439 (United States)

2016-03-15

Because of its superior creep and corrosion resistance as compared with general austenitic stainless steels, NF709 has emerged as a candidate structural material for advanced nuclear reactors. To obtain fundamental information about the radiation resistance of this material, this study examined the microstructural evolution of NF709 subjected to neutron irradiation to 3 displacements per atom at 500 °C. Transmission electron microscopy, scanning electron microscopy, and high-energy x-ray diffraction were employed to characterize radiation-induced segregation, Frank loops, voids, as well as the formation and reduction of precipitates. Radiation hardening of ∼76% was estimated by nanoindentation, approximately consistent with the calculation according to the dispersed barrier-hardening model, suggesting Frank loops as the primary hardening source.

Alteration in Inflammation-related miR-146a Expression in NF-KB Signaling Pathway in Diabetic Rat Hippocampus.

Science.gov (United States)

Habibi, Fatemeh; Ghadiri Soufi, Farhad; Ghiasi, Rafighe; Khamaneh, Amir Mahdi; Alipour, Mohammad Reza

2016-03-01

The purpose of the present study is to evaluate the expression of miR-146a gene, its adaptor genes (TRAF6, NF-KB, and IRAK1), and possible changes in the cellular signaling pathway in diabetic hippocampus tissue. Male Sprague-Dawley rats are randomly selected and divided into control and diabetic (n=6) groups. Diabetes induced by the single-dose injection of nicotinamide [110 mg/kg, (i.p.)], 15 min before streptozotocin (50 mg/kg; i.p.) in 12-h fasted rats. The rats are kept at the laboratory for two months. After anaesthetization, hippocampus of the rats was removed in order to measure the expression of miR-146a, NFK-B, IRAK1, and TRAF6 genes using real-time PCR and activity of NF-KB as well as amount of apoptosis rate using ELISA. The results indicated a reduction in expression of miR-146a and an increase in expression of IRAK1, NF-KB, and TRAF6 genes in the hippocampus of diabetic rats compared to control. Also it reveals an increase in the activity of NF-KB and apoptosis rate in the hippocampus of diabetic rats. Our results report the probability that reduction of miR-146a expression in the negative feedback loop between miR-146a and NF-KB increases NF-kB expression and thus intensifies inflammation and apoptosis in hippocampus.

The feasibility of nanofiltration membrane bioreactor (NF-MBR)+reverse osmosis (RO) process for water reclamation: Comparison with ultrafiltration membrane bioreactor (UF-MBR)+RO process.

Science.gov (United States)

Tay, Ming Feng; Liu, Chang; Cornelissen, Emile R; Wu, Bing; Chong, Tzyy Haur

2018-02-01

This study examines the feasibility of a novel nanofiltration membrane bioreactor (NF-MBR) followed by reverse osmosis (RO) process for water reclamation at 90% recovery and using an ultrafiltration MBR (UF-MBR)+RO as baseline for comparison. Both MBRs adopted the same external hollow fiber membrane configurations and operating conditions. The collected permeates of the MBRs were subsequently fed to the respective RO systems. The results showed that the NF-MBR (operated at a constant flux of 10 L/m 2 h) achieved superior MBR permeate quality due to enhanced biodegradation and high rejection capacity of the NF membrane, leading to lower RO fouling rates (∼3.3 times) as compared to the UF-MBR. Further analysis indicated that the cake layer fouling that caused the cake-enhanced osmotic pressure (CEOP) effect contributed predominantly to the transmembrane pressure (TMP) increase in the NF-MBR, while irreversible pore fouling was the major reason for UF membrane fouling. Furthermore, it was found that the biopolymers (i.e., organics with MW > 10 kDa) were the main components present in the foulants of the NF/UF membranes and RO membranes. The analysis indicated that the NF-MBR + RO system at recovery of 90% has comparable energy consumption as the UF-MBR + RO system at recovery of 75%. Our findings proved the feasibility of the NF-MBR + RO for water reclamation at a high recovery rate. Copyright © 2017 Elsevier Ltd. All rights reserved.

Fish oil suppresses cell growth and metastatic potential by regulating PTEN and NF-κB signaling in colorectal cancer.

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Shevali Kansal

Full Text Available Homeostasis in eukaryotic tissues is tightly regulated by an intricate balance of the prosurvival and antisurvival signals. The tumor suppressor PTEN (phosphatase and tensin homolog deleted on chromosome 10, a dual-specificity phosphatase, plays a functional role in cell cycle arrest and apoptosis. NF-κB and its downstream regulators (such as VEGF play a central role in prevention of apoptosis, promotion of inflammation and tumor growth. Therefore, we thought to estimate the expression of PTEN, Poly-ADP-ribose polymerase (PARP, NF-κBp50, NF-κBp65 and VEGF to evaluate the effect of supplementation of fish oil on apoptotic and inflammatory signaling in colon carcinoma. Male wistar rats in Group I received purified diet while Group II and III received modified diet supplemented with FO∶CO(1∶1&FO∶CO(2.5∶1 respectively. These were further subdivided into controls receiving ethylenediamine-tetra acetic-acid and treated groups received dimethylhydrazine-dihydrochloride (DMH/week for 4 weeks. Animals sacrificed 48 hours after last injection constituted initiation phase and that sacrificed after 16 weeks constituted post-initiation phase. We have analysed expression of PTEN, NF-κBp50, NF-κBp65 by flowcytometer and nuclear localization of NF-κB by immunofluorescence. PARP and VEGF were assessed by immunohistochemistry. In the initiation phase, animals receiving DMH have shown increased % of apoptotic cells, PTEN, PARP, NF-κBp50, NF-κBp65 and VEGF however in post-initiation phase no significant alteration in apoptosis with decreased PTEN and increased PARP, NF-κBp50, NF-κBp65 and VEGF were observed as compared to control animals. On treatment with both ratios of fish oil in both the phases, augmentation in % of apoptotic cells, decreased PTEN, PARP, NF-κBp50, NF-κBp65 and VEGF were documented with respect to DMH treated animals with effect being more exerted with higher ration in post-initiation phase. Hence, fish oil activates

Treatment of low level radioactive wastewater by means of NF process

Energy Technology Data Exchange (ETDEWEB)

Chen, Ding; Zhao, Xuan, E-mail: zhxinet@tsinghua.edu.cn; Li, Fuzhi

2014-10-15

Highlights: • Nanofiltration can offer one of the approaches in optimizing membrane system. • Operation parameters especially the pressure affect nuclides’ removal efficiency. • Organic polyamide membrane shows radiation resistance. • A summary of DF and flux values can be taken as reference in designing the membrane system for LLRWs treatment. - Abstract: Membrane technology has been proved as an effective technology in the treatment of low level radioactive wastewaters (LLRWs). As ‘loose reverse osmosis’, nanofiltration can be integrated with RO and offers the high permeate flux at low pressure without obvious loss of decontamination efficiency. In the paper, three kinds of commercially available NF membrane materials were investigated by lab-scale experiment with respect to the nuclide rejection. The results demonstrate the efficient elimination. The membrane flux can be improved by the elevation of temperature and cross-flow velocity within the ranges of 20–30 °C and 0.4–1.0 m s{sup −1}. The radiation resistance test demonstrates no obvious loss of flux and nuclide rejection after a long term operation in the radioactive circumstance. A brief comparison of LLRWs treatment methods shows that NF can perform the pre-treatment of RO and optimize the entire membrane system with high flux and low pressure. In the paper, decontamination factor and flux values of the tested membranes at different operation condition are summarized as the reference for membrane selection and system design.

Zinc regulates Nox1 expression through a NF-κB and mitochondrial ROS dependent mechanism to induce senescence of vascular smooth muscle cells.

Science.gov (United States)

Salazar, G; Huang, J; Feresin, R G; Zhao, Y; Griendling, K K

2017-07-01

The role of oxidative stress and inflammation in the development and progression of cardiovascular diseases (CVD) is well established. Increases in oxidative stress can further exacerbate the inflammatory response and lead to cellular senescence. We previously reported that angiotensin II (Ang II) and zinc increase reactive oxygen species (ROS) and cause senescence of vascular smooth muscle cells (VSMCs) and that senescence induced by Ang II is a zinc-dependent process. Zinc stimulated NADPH oxidase (Nox) activity; however, the role of Nox isoforms in zinc effects was not determined. Here, we show that downregulation of Nox1, but not Nox4, by siRNA prevented both Ang II- and zinc-induced senescence in VSMCs. On the other hand, overexpression of Nox1 induced senescence, which was associated with reduced proliferation, reduced expression of telomerase and increased DNA damage. Zinc increased Nox1 protein expression, which was inhibited by chelation of zinc with TPEN and by overexpression of the zinc exporters ZnT3 and ZnT10. These transporters work to reduce cytosolic zinc, suggesting that increased cytosolic zinc mediates Nox1 upregulation. Other metals including copper, iron, cobalt and manganese failed to upregulate Nox1, suggesting that this pathway is zinc specific. Nox1 upregulation was inhibited by actinomycin D (ACD), an inhibitor of transcription, by inhibition of NF-κB, a known Nox1 transcriptional regulator and by N-acetyl cysteine (NAC) and MitoTEMPO, suggesting that NF-κB and mitochondrial ROS mediate zinc effects. Supporting this idea, we found that zinc increased NF-κB activation in the cytosol, stimulated the translocation of the p65 subunit to the nucleus, and that zinc accumulated in mitochondria increasing mitochondrial ROS, measured using MitoSox. Further, zinc-induced senescence was reduced by inhibition of NF-κB or reduction of mitochondrial ROS with MitoTEMPO. NF-κB activity was also reduced by MitoTEMPO, suggesting that mitochondrial ROS

Ethanol Decreases Inflammatory Response in Human Lung Epithelial Cells by Inhibiting the Canonical NF-kB-Pathway.

Science.gov (United States)

Mörs, Katharina; Hörauf, Jason-Alexander; Kany, Shinwan; Wagner, Nils; Sturm, Ramona; Woschek, Mathias; Perl, Mario; Marzi, Ingo; Relja, Borna

2017-01-01

Alcohol (ethanol, EtOH) as significant contributor to traumatic injury is linked to suppressed inflammatory response, thereby influencing clinical outcomes. Alcohol-induced immune-suppression during acute inflammation (trauma) was linked to nuclear factor-kappaB (NF-ĸB). Here, we analyzed alcohol`s effects and mechanisms underlying its influence on NF-ĸB-signaling during acute inflammation in human lung epithelial cells. A549-cells were stimulated with interleukin (IL)-1β, or sera from trauma patients (TP) or healthy volunteers, with positive/negative blood alcohol concentrations (BAC), and subsequently exposed to EtOH (170 Mm, 1h). IL-6-release and neutrophil adhesion to A549 were analyzed. Specific siRNA-NIK mediated downregulation of non-canonical, and IKK-NBD-inhibition of canonical NF-ĸB signaling were performed. Nuclear levels of activated p50 and p52 NF-ĸB-subunits were detected using TransAm ELISA. Both stimuli significantly induced IL-6-release (39.79±4.70 vs. 0.58±0.8 pg/ml) and neutrophil adhesion (132.30±8.80 vs. 100% control, p<0.05) to A549-cells. EtOH significantly decreased IL-6-release (22.90±5.40, p<0.05) and neutrophil adherence vs. controls (105.40±14.5%, p<0.05). IL-1β-induced significant activation of canonical/p50 and non-canonical/p52 pathways. EtOH significantly reduced p50 (34.90±23.70 vs. 197.70±36.43, p<0.05) not p52 activation. Inhibition of canonical pathway was further increased by EtOH (less p50-activation), while p52 remained unaltered. Inhibition of non-canonical pathway was unchanged by EtOH. Here, alcohol`s anti-inflammatory effects are mediated via decreasing nuclear levels of activated p50-subunit and canonical NF-ĸB signaling pathway. © 2017 The Author(s). Published by S. Karger AG, Basel.

A complex relationship between TRAF3 and non-canonical NF-κB2 activation in B lymphocytes

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Wai Wai Lin

2013-12-01

Full Text Available The adaptor protein TRAF3 restrains BAFF receptor (BAFFR and CD40-mediated activation of the NF-κB2 pathway in B cells. Mice lacking TRAF3 specifically in B cells revealed the critical role of TRAF3 in restraining homeostatic B cell survival. Furthermore, loss- of-function mutations of the traf3 gene have been associated with human B cell malignancies, especially multiple myeloma (MM. It has been proposed that receptor-induced TRAF3 degradation leads to stabilization of the NF-B inducing kinase NIK, and subsequent NF-κB2 activation. However, it is unclear how receptor-mediated TRAF3 degradation or loss of function contributes to B cell-specific NF-κB2 activation. In the current study, we employed two complementary models to address this question. One utilized a mutant traf3 gene found in a human MM-derived cell line called LP1. The LP1 mutant TRAF3 protein lacks the TRAF-N and TRAF-C domains. Consistent with the paradigm described, expression of LP1 TRAF3 in B cells promoted higher basal levels of NF-κB2 activation compared to Wt TRAF3. However, LP1 did not associate with TRAF2, CD40, or BAFFR, and no LP1 degradation was observed following receptor engagement. Interestingly, LP1 showed enhanced NIK association. Thus, TRAF3 degradation becomes dispensable to activate NF-κB2 when it is unable to associate with TRAF2. In a second model, we examined several mutant forms of BAFFR that are unable to induce NF-κB2 activation in B cells. Signaling to B cells by each of these BAFFR mutants, however, induced levels of TRAF3 degradation similar to those induced by Wt BAFFR. Thus, in B cells, receptor-mediated TRAF3 degradation is not sufficient to promote NF-B2 activation. We thus conclude that there is not a simple linear relationship in B lymphocytes between relative levels of cellular TRAF3, induced TRAF3 degradation, NIK activation and NF-B2 activation.

AUTOMATIZACIÓN DE OFICINAS S.A.

Directory of Open Access Journals (Sweden)

Luis Carlos Diaz Osorio

1998-01-01

Full Text Available El caso muestra la situación de Automatización de Oficinas S.A., una empresa de gran trayectoria nacional, orientada a la comercialización de muebles y equipos para oficina. A principios de la década pasada, comenzó a comercializar microcomputadoras y elementos de conectividad de redes, manejando grandes márgenes por ser monopolio, aprovechando los beneficios de importación que le otorgaba el ser exportador de muebles. En el momento en que se abren las importaciones, más de doscientas empresas entran a competir en el mercado de los microcomputadores, llegando incluso a manejar márgenes de hasta el 10%. Las ventas de la empresa han bajado a niveles alarmantes, incluso se cree que únicamente compran empresas allegadas a los directivos o personas que no conocen nada del tema de los computadores. La situación puntual es la toma de decisión de las estrategias para ser competitivos o decidir salir del mercado de los PC. La orientación que hemos decidido darle al caso es “fijación de precios”.

Corneal NF-kappaB activity is necessary for the retention of transparency in the cornea of UV-B-exposed transgenic reporter mice.

Science.gov (United States)

Alexander, George; Carlsen, Harald; Blomhoff, Rune

2006-04-01

To determine the dynamics of Nuclear Factor-kappaB (NF-kappaB) in murine corneal pathology and the role of NF-kappaB in maintaining corneal clarity after ultraviolet B radiation insult, transgenic mice containing NF-kappaB-luciferase reporter were exposed to LPS (bacterial lipopolysaccharide), TNF-alpha (Tumor Necrosis Factor-alpha) or 4 kJ m(-2) UV-B radiation. NF-kappaB decoy oligonucleotides were also administered in some of the UV-B experiments. Following various exposure times, the mice were sacrificed and whole eyes or corneal tissues were obtained. Whole eyes were examined for scattering using a point-source optical imaging technique. Tissue homogenates were examined for luciferase activity using a luminometer. TNF-alpha and LPS-injected NF-kappaB-luciferase transgenic mice demonstrated 3-10-fold increases in cornea NF-kappaB with peak activities at 4 and 6 hr post-injection, respectively. Mice exposed to 4 kJ m(-2) UV-B exhibited a 3-fold increase in NF-kappaB activity 4 hr post-exposure. The administration of NF-kappaB-decoy oligonucleotides to mice had the effect of reducing UV-B-induced NF-kappaB activity in the cornea and significantly increasing the amount of light scattering in UV-B exposed corneas 7 days post-UV-B exposure when compared to sham injected mice. These results indicate that NF-kappaB is activated in cornea in pathologies that involves increased plasma levels of LPS and TNF-alpha, as well as direct UV-B exposure, and suggest that NF-kappaB activation play an essential part in the corneal healing process.

NF-1 Dependent Gene Regulation in Drosophila Melanogaster

Science.gov (United States)

2004-04-01

standard cornmeal medium at 25oC in a humidified incubator. Flies were collected and frozen in liquid nitrogen at the same time of day to minimize...melanogaster media, strains and heat-shock conditions Flies were raised at room temperature (22–248C) on standard cornmeal medium. The Nf1 mutants Nf1P1 and

How the projection domains of NF-L and alpha-internexin determine the conformations of NF-M and NF-H in neurofilaments

NARCIS (Netherlands)

Leermakers, F.A.M.; Zhulina, E.B.

2010-01-01

Making use of a numerical self-consistent field method and polymer brush concepts, we model the solvated corona of neurofilaments (NF) composed of projection domains (unstructured tails) of constituent proteins. Projections are modeled with amino acid resolution. We focus on the importance of the

NF-kappaB mediates FGF signal regulation of msx-1 expression.

Science.gov (United States)

Bushdid, P B; Chen, C L; Brantley, D M; Yull, F; Raghow, R; Kerr, L D; Barnett, J V

2001-09-01

The nuclear factor-kappaB (NF-kappaB) family of transcription factors is involved in proliferation, differentiation, and apoptosis in a stage- and cell-dependent manner. Recent evidence has shown that NF-kappaB activity is necessary for both chicken and mouse limb development. We report here that the NF-kappaB family member c-rel and the homeodomain gene msx-1 have partially overlapping expression patterns in the developing chick limb. In addition, inhibition of NF-kappaB activity resulted in a decrease in msx-1 mRNA expression. Sequence analysis of the msx-1 promoter revealed three potential kappaB-binding sites similar to the interferon-gamma (IFN-gamma) kappaB-binding site. These sites bound to c-Rel, as shown by electrophoretic mobility shift assay (EMSA). Furthermore, inhibition of NF-kappaB activity significantly reduced transactivation of the msx-1 promoter in response to FGF-2/-4, known stimulators of msx-1 expression. These results suggest that NF-kappaB mediates the FGF-2/-4 signal regulation of msx-1 gene expression. Copyright 2001 Academic Press.

Acrolein, an I-κBα-independent downregulator of NF-κB activity, causes the decrease in nitric oxide production in human malignant keratinocytes.

Science.gov (United States)

Moon, Ki-Young

2011-05-01

Acrolein, a reactive electrophilic α, β-unsaturated aldehyde, is known to be an alkylating chemical carcinogen. The effect of acrolein on the activation of NF-κB in human malignant epidermal keratinocytes was examined to elucidate the molecular mechanism associated with this NF-κB-acrolein regulation and its consecutive sequence, nitric oxide (NO) production. Acrolein significantly downregulated the cellular NF-κB activity up to 60% compared with control as well as the lipopolysaccharide (LPS)-induced NO production in a dose response manner at concentrations of 10~30 μM. To investigate the regulatory mechanism associated with this NF-κB-acrolein downregulation, the relative level of phosphorylation of I-κBα (serines-32 and -36), a principle regulator of NF-κB activation, represented by acrolein, was quantified. Acrolein inhibited NF-κB activity without altering cellular levels of the phosphorylated and nonphosphorylated forms of I-κBα, implying that the downregulatory effect of acrolein on cellular NF-κB activity in human skin cells is an I-κBα-independent activation pathway. The results suggests that acrolein causes the decrease in nitric oxide production as an I-κBα-independent downregulator of NF-κB activity in human malignant keratinocytes, and acrolein-induced carcinogenesis may be associated with the modulation of cellular NF-κB activity.

Hydrocortisone fails to abolish NF-κB1 protein nuclear translocation in deletion allele carriers of the NFKB1 promoter polymorphism (-94ins/delATTG and is associated with increased 30-day mortality in septic shock.

Directory of Open Access Journals (Sweden)

Simon T Schäfer

Full Text Available BACKGROUND: Previous investigations and meta-analyses on the effect of glucocorticoids on mortality in septic shock revealed mixed results. This heterogeneity might be evoked by genetic variations. Such candidate is a promoter polymorphism (-94ins/delATTG of the gene encoding the ubiquitous transcription-factor nuclear-factor-κB (NF-κB which binds to recognition elements in the promoter of several genes encoding for the innate immune-system. In turn, hydrocortisone inhibits NF-κB nuclear translocation and thus transcription of key immune-response regulators. Accordingly, we tested the hypotheses that hydrocortisone has a NFKB1 genotype dependent effect on 1 NF-κB1 nuclear translocation evoked by lipopolysaccharide (LPS in monocytes in vitro, and 2 mortality in septic shock. METHODS: Monocytes of volunteers with the homozygous insertion (II; n = 5 or deletion (DD; n = 6 NFKB1 genotype were incubated with 10 µgml-1 LPS ± hydrocortisone (10-5M, and NF-κB1 nuclear translocation was assessed (immunofluorescence. Furthermore, we analyzed 30-day-mortality in 160 patients with septic shock stratified for both genotype and hydrocortisone therapy. RESULTS: Hydrocortisone inhibited LPS induced nuclear translocation of NF-κB1 in II (25%±11;p = 0.0001 but not in DD genotypes (51%±15;p = n.s.. Onehundredandfour of 160 patients with septic shock received hydrocortisone, at the discretion of the intensivist. NFKB1 deletion allele carriers (ID/DD receiving hydrocortisone had a much greater 30-day-mortality (57.6% than II genotypes (24.4%; HR:3.18, 95%-CI:1.61-6.28;p = 0.001. In contrast, 30-day mortality was 22.2% in ID/DD and 25.0% in II genotypes without hydrocortisone therapy. Results were similar when using propensity score matching to account for possible bias in the intensivists' decision to administer hydrocortisone. CONCLUSION: Hydrocortisone fails to inhibit LPS induced nuclear NF-κB1 translocation in deletion allele

Hydrocortisone Fails to Abolish NF-κB1 Protein Nuclear Translocation in Deletion Allele Carriers of the NFKB1 Promoter Polymorphism (-94ins/delATTG) and Is Associated with Increased 30-Day Mortality in Septic Shock

Science.gov (United States)

Schäfer, Simon T.; Gessner, Sophia; Scherag, André; Rump, Katharina; Frey, Ulrich H.; Siffert, Winfried; Westendorf, Astrid M.; Steinmann, Jörg; Peters, Jürgen; Adamzik, Michael

2014-01-01

Background Previous investigations and meta-analyses on the effect of glucocorticoids on mortality in septic shock revealed mixed results. This heterogeneity might be evoked by genetic variations. Such candidate is a promoter polymorphism (-94ins/delATTG) of the gene encoding the ubiquitous transcription-factor nuclear-factor-κB (NF-κB) which binds to recognition elements in the promoter of several genes encoding for the innate immune-system. In turn, hydrocortisone inhibits NF-κB nuclear translocation and thus transcription of key immune-response regulators. Accordingly, we tested the hypotheses that hydrocortisone has a NFKB1 genotype dependent effect on 1) NF-κB1 nuclear translocation evoked by lipopolysaccharide (LPS) in monocytes in vitro, and 2) mortality in septic shock. Methods Monocytes of volunteers with the homozygous insertion (II; n = 5) or deletion (DD; n = 6) NFKB1 genotype were incubated with 10 µgml-1 LPS ± hydrocortisone (10-5M), and NF-κB1 nuclear translocation was assessed (immunofluorescence). Furthermore, we analyzed 30-day-mortality in 160 patients with septic shock stratified for both genotype and hydrocortisone therapy. Results Hydrocortisone inhibited LPS induced nuclear translocation of NF-κB1 in II (25%±11;p = 0.0001) but not in DD genotypes (51%±15;p = n.s.). Onehundredandfour of 160 patients with septic shock received hydrocortisone, at the discretion of the intensivist. NFKB1 deletion allele carriers (ID/DD) receiving hydrocortisone had a much greater 30-day-mortality (57.6%) than II genotypes (24.4%; HR:3.18, 95%-CI:1.61-6.28;p = 0.001). In contrast, 30-day mortality was 22.2% in ID/DD and 25.0% in II genotypes without hydrocortisone therapy. Results were similar when using propensity score matching to account for possible bias in the intensivists' decision to administer hydrocortisone. Conclusion Hydrocortisone fails to inhibit LPS induced nuclear NF-κB1 translocation in deletion allele carriers of the

Anti-inflammatory properties of clovamide and Theobroma cacao phenolic extracts in human monocytes: evaluation of respiratory burst, cytokine release, NF-κB activation, and PPARγ modulation.

Science.gov (United States)

Zeng, Huawu; Locatelli, Monica; Bardelli, Claudio; Amoruso, Angela; Coisson, Jean Daniel; Travaglia, Fabiano; Arlorio, Marco; Brunelleschi, Sandra

2011-05-25

There is a great interest in the potential health benefits of biologically active phenolic compounds in cocoa (Theobroma cacao) and dark chocolate. We investigated the anti-inflammatory potential of clovamide (a N-phenylpropenoyl-L-amino acid amide present in cocoa beans) and two phenolic extracts from unroasted and roasted cocoa beans, by evaluating superoxide anion (O(2)(-)) production, cytokine release, and NF-κB activation in human monocytes stimulated by phorbol 12-myristate 13-acetate (PMA). The effects of rosmarinic acid are shown for comparison. Clovamide and rosmarinic acid inhibited PMA-induced O(2)(-) production and cytokine release (with a bell-shaped curve and maximal inhibition at 10-100 nM), as well as PMA-induced NF-κB activation; the two cocoa extracts were less effective. In all tests, clovamide was the most potent compound and also enhanced peroxisome proliferator-activated receptor-γ (PPARγ) activity, which may exert anti-inflammatory effects. These findings indicate clovamide as a possible bioactive compound with anti-inflammatory activity in human cells.

Electrophysical properties of nCdS/pCdTe heterosystem

International Nuclear Information System (INIS)

Muzafarova, S.A.

2006-01-01

Full text: In this work results of research of electrophysical properties n CdS/pCdTe heterostructure are given. It is shown that at density of current 10 -8 -10 -5 A.cm -2 vol tamper characteristics in hetero system CdTe/CdS is described by thermo ionic law, and in the range 10 -4 -10 -2 A .cm -2 the current in heterostructure is limited by recombination in electronic neutral part of high-resistance of solid structure CdTe 1-x S x . Certain life time τ p and length of diffusion L p of non basic current carriers in solid structure CdTe 1-x S x , as well as superficial recombination rate v R on border of section between CdS and solid structures were considered at influence of irradiation and γ-quanta on the mechanism of current in n CdS/pCdTe heterostructure. From the analysis of dependence doze of sites the direct volt-ampere characteristics were obtained. It is shown that monotonous increase of doze of irradiation and γ-quanta leads to nonmonotonous change of micro parameters of nCdS/pCdTe heterostructure, superficial recombination rate - v R , values of both τ p and lengths of diffusion L p of non basic carriers of potential barrier - qφ B . On border of CdTe 1-x S x there is CdS-solid structure. (author)

Towards continuous global measurements and optimal emission estimates of NF3

Science.gov (United States)

Arnold, T.; Muhle, J.; Salameh, P.; Harth, C.; Ivy, D. J.; Weiss, R. F.

2011-12-01

We present an analytical method for the continuous in situ measurement of nitrogen trifluoride (NF3) - an anthropogenic gas with a global warming potential of ~16800 over a 100 year time horizon. NF3 is not included in national reporting emissions inventories under the United Nations Framework Convention on Climate Change (UNFCCC). However, it is a rapidly emerging greenhouse gas due to emission from a growing number of manufacturing facilities with increasing output and modern end-use applications, namely in microcircuit etching, and in production of flat panel displays and thin-film photovoltaic cells. Despite success in measuring the most volatile long lived halogenated species such as CF4, the Medusa preconcentration GC/MS system of Miller et al. (2008) is unable to detect NF3 under remote operation. Using altered techniques of gas separation and chromatography after initial preconcentration, we are now able to make continuous atmospheric measurements of NF3 with average precisions NF3 produced. Emission factors are shown to have reduced over the last decade; however, rising production and end-use have caused the average global atmospheric concentration to double between 2005 and 2011 i.e. half the atmospheric NF3 present today originates from emissions after 2005. Finally we show the first continuous in situ measurements from La Jolla, California, illustrating how global deployment of our technique could improve the temporal and spatial scale of NF3 'top-down' emission estimates over the coming years. These measurements will be important for independent verification of emissions should NF3 be regulated under a new climate treaty.

Human Papillomavirus type 16 E6 and E 7 proteins alter NF-kB in cultured cervical epithelial cells and inhibition of NF-kB promotes cell growth and immortalization

Science.gov (United States)

Vandermark, Erik R.; Deluca, Krysta A.; Gardner, Courtney R.; Marker, Daniel F.; Schreiner, Cynthia N.; Strickland, David A.; Wilton, Katelynn M.; Mondal, Sumona; Woodworth, Craig D.

2012-01-01

The NF-kB family of transcription factors regulates important biological functions including cell growth, survival and the immune response. We found that Human Papillomavirus type 16 (HPV-16) E7 and E6/E7 proteins inhibited basal and TNF-alpha-inducible NF-kB activity in human epithelial cells cultured from the cervical transformation zone, the anatomic region where most cervical cancers develop. In contrast, HPV-16 E6 regulated NF-kB in a cell type- and cell growth-dependent manner. NF-kB influenced immortalization of cervical cells by HPV16. Inhibition of NF-kB by an IkB alpha repressor mutant increased colony formation and immortalization by HPV-16. In contrast, activation of NF-kB by constitutive expression of p65 inhibited proliferation and immortalization. Our results suggest that inhibition of NF-kB by HPV-16 E6/E7 contributes to immortalization of cells from the cervical transformation zone. PMID:22284893

Role and molecular mechanism of HO-1-mediated NF-κB modulation in fibrosis progression of nonalcoholic steatohepatitis

Directory of Open Access Journals (Sweden)

NAN Yuemin

2013-05-01

Full Text Available ObjectiveTo investigate the potential effects and molecular mechanisms of heme oxygenase-1 (HO-1-mediated modulation of nuclear factor-kappa B (NF-κB, and its downstream activation of intercellular adhesion molecule 1 (ICAM-1 and platelet derived growth factor (PDGF, in fibrosis progression of non-alcoholic steatohepatitis (NASH using the methionine and choline deficient (MCD mouse model of NASH. Methods Forty C57BL/6J male mice (18-20 g were randomly divided into four groups (n=10 each: NASH model group, administered the MCD diet; HO-1 agonist group, administered the MCD diet with intraperitoneal (ip injections of hemin (30 μmol/kg every other day; HO-1 inhibitor group, administered the MCD diet with ip injections of zinc protoporphyrin (ZnPP-IX; 20 μmol/kg every other day; and control group, administered a methionine and choline sufficient (MCS diet, without agonist nor inhibitor injections. After eight weeks, the mice were sacrificed and resected liver tissues used to assess successful model establishment by histological analysis (hematoxylin-eosin and Masson staining and the differential mRNA expression of HO-1, NF-κB, ICAM-1, and PDGF by real-time quantitative PCR (GAPDH normalized and protein expression of HO-1 and PDGF by western blotting ( β-actin normalized. Significance of an intergroup difference was assessed by single-factor analysis of variance test, and the Student-Newman-Keuls test was used for pairwise comparisons. ResultsThe NASH model group showed the appropriate histologic features of hepatic steatosis, necroinflammation and fibrogenesis, while the control group showed normal lobular architecture. In addition, the NASH model group showed significantly higher expression of HO-1, NF-κB, ICAM-1 and PDGF mRNA (all P＜0.05, and concomitant increases in HO-1 and PDGF protein. The group treated with HO-1 agonist showed significant down-regulation of the NASH-induced NF-κB, ICAM-1 and PDGF expressions, while the opposite

Sulfasalazine inhibits inflammation and fibrogenesis in pancreas via NF-κB signaling pathway in rats with oxidative stress-induced pancreatic injury.

Science.gov (United States)

Wang, Ya-Ru; Tian, Fei-Long; Yan, Ming-Xian; Fan, Jin-Hua; Wang, Li-Yun; Kuang, Rong-Guang; Li, Yan-Qing

2016-01-01

Pathogenesis and effective therapeutics of chronic pancreatic inflammation and fibrosis remain uncertain. To investigate the effects of sulfasalazine (SF) on pancreatic inflammation and fibrogenesis. Chronic pancreatic injury in rats was induced by diethyldithiocarbamate (DDC) and interfered by SF through intraperitoneal injection. The rats were divided into five groups: group N, normal control group, rats were treated with dilated water only; group DS1, rats received SF (10 mg/kg) 2 hours before DDC treatment; group DS2, rats were treated with DDC and then SF (100 mg/kg, twice a week); group DS3, rats were treated with DDC, then SF (100 mg/kg, thrice a week); and group DDC, rats were treated with DDC only. Pancreatic inflammation and fibrosis were determined by hematoxylin and eosin staining and Sirius red staining. The genes and proteins related to NF-κB pathway and fibrogenesis including NF-κB/p65, TNF-α, ICAM-1, α-SMA, and Con 1 were detected by immunohistochemical staining, reverse transcription polymerase chain reaction, and Western blotting. Rats in the DDC and DS1 groups showed the highest histological scores after DDC treatment, but the scores of DS2 and DS3 groups decreased significantly when compared with the DDC group. Sirius red staining showed collagen formation clearly in DDC and DS1 rats rather than in DS2 and DS3 rats. NF-κB/p65, ICAM-1, and α-SMA were strongly expressed in DDC and DS1 rats, while DS2 and DS3 rats showed mild to moderate expression by immunohistochemistry. Reverse transcription polymerase chain reaction showed increased levels of NF-κB/p65, ICAM-1, TNF-α, α-SMA, and Con 1 mRNA in DDC and DS1 rats in comparison to normal controls. The mRNA levels of these molecules in DS2 and DS3 rats were significantly lower than those in DS1 and DDC rats. Western blotting demonstrated that the NF-κB/p65, ICAM-1, and α-SMA expressions in pancreatic tissues of the rats of the DDC group were more clear than those of the normal control, DS2

FY13 Summary Report on the Augmentation of the Spent Fuel Composition Dataset for Nuclear Forensics: SFCOMPO/NF

Energy Technology Data Exchange (ETDEWEB)

Brady Raap, Michaele C.; Lyons, Jennifer A.; Collins, Brian A.; Livingston, James V.

2014-03-31

This report documents the FY13 efforts to enhance a dataset of spent nuclear fuel isotopic composition data for use in developing intrinsic signatures for nuclear forensics. A review and collection of data from the open literature was performed in FY10. In FY11, the Spent Fuel COMPOsition (SFCOMPO) excel-based dataset for nuclear forensics (NF), SFCOMPO/NF was established and measured data for graphite production reactors, Boiling Water Reactors (BWRs) and Pressurized Water Reactors (PWRs) were added to the dataset and expanded to include a consistent set of data simulated by calculations. A test was performed to determine whether the SFCOMPO/NF dataset will be useful for the analysis and identification of reactor types from isotopic ratios observed in interdicted samples.

TEffect of nf-kappa B on diabetic retinopathy%NF-κB对糖尿病视网膜病变的影响

Institute of Scientific and Technical Information of China (English)

王爽; 宋子宣

2015-01-01

目的 研究和探讨核因子κB (NF-κ B)在糖尿病视网膜病变中的作用.方法 首先建立糖尿病视网膜病变(DR,diabetic retinopathy)动物模型,雄性SD大鼠,链脲佐菌素(streptozotocin,STZ) 60 mg/kg腹腔注射形成糖尿病模型,1.5个月后SD大鼠玻璃体内行血管内皮生长因子(VEGF)注射造成增殖型的糖尿病视网膜病变模型.视网膜铺片使用ADP酶染色视网膜血管,实时定量PCR检测NF-κ B表达量的变化,以及凋亡信号的检测.结果 视网膜血管染色的增殖面积造模给水组为(12.0±4.1)％,而视网膜血管染色的无灌注区面积造模给NF-κ B拮抗剂组为(37.9±3.9)％.正常组大鼠的NF-κ B蛋白的灰度值为(194.2890±3.8900),而造模给水组的NF-κB蛋白的灰度值为(74.4300±4.4900),凋亡实验结果显示正常组大鼠的凋亡信号个数平均为(32.2±3.1),而造模给水组的凋亡信号个数平均为(7.4±4.2).结论 NF-κB主要是通过引起细胞凋亡而减少糖尿病视网膜病变患者视网膜血管的增殖.%Objective To study the effect of nuclear factor kappa B (nf-kappa B) on diabetic retinopathy.Methods Diabetic retinopathy (DR,diabetic retinopathy) animal models were established.The SD rats intraperitoneal injected 60 cephalosporins (STZ streptozotocin) mg/kg to form diabetes models; 1.5 months from then,the SD rats were vitreously injected vascular endothelial growth factor (VEGF) to build models of proliferative diabetic retinopathy[l].Retinal blood vessels stained by ADP enzyme were used as retinal pave pieces.Real-time quantitative PCR was used to detect the e change of nf-kappa B expression quantity and apoptosis signal.Results The proliferation area of dyed retinal vessels of the model-buildingwith-water group was (12.0±4.1)％.The area without perfusion of dyed retinal blood vessels of the modelbuilding-with-nf-kappa-B-antagonist group was (37.9 ± 3.9)％.The gray value of nf-kappa B protein was (194.2890 ± 3.8900) in the

Activation of NF-κB is involved in 6-hydroxydopamine-but not MPP+-induced dopaminergic neuronal cell death: its potential role as a survival determinant

International Nuclear Information System (INIS)

Park, Seong H.; Choi, Won-Seok; Yoon, So-Young; Ahn, Young Soo; Oh, Young J.

2004-01-01

The nuclear factor-kappaB (NF-κB) family plays an important role in the control of the apoptotic response. Its activation has been demonstrated in both neurons and glial cells in many neurological disorders. In the present study, we specifically examined whether and to what extent NF-κB activation is involved in culture models of Parkinson's disease following exposure of MN9D dopaminergic neuronal cells to 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenyl-4-phenylpyridinium ion (MPP + ). Both analysis by immunocytochemistry and of immunoblots revealed that NF-κB-p65 was translocated into the nuclei following 6-OHDA but not MPP + -treatment. A time-dependent activation of NF-κB induced by 6-OHDA but not MPP + was also demonstrated by an electrophoretic mobility shift assay. A competition assay indicated that not only NF-κB-p65 but also -p50 is involved in 6-OHDA-induced NF-κB activity. Co-treatment with an antioxidant, N-acetyl-L-cysteine, blocked 6-OHDA-induced activation of NF-κB signaling. In the presence of an NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC), 6-OHDA-induced cell death was accelerated while PDTC did not affect MPP + -induced cell death. Our data may point to a drug-specific activation of NF-κB as a survival determinant for dopaminergic neurons

Oridonin stabilizes retinoic acid receptor alpha through ROS-activated NF-κB signaling.

Science.gov (United States)

Cao, Yang; Wei, Wei; Zhang, Nan; Yu, Qing; Xu, Wen-Bin; Yu, Wen-Jun; Chen, Guo-Qiang; Wu, Ying-Li; Yan, Hua

2015-04-10

Retinoic acid receptor alpha (RARα) plays an essential role in the regulation of many biological processes, such as hematopoietic cell differentiation, while abnormal RARα function contributes to the pathogenesis of certain diseases including cancers, especially acute promyelocytic leukemia (APL). Recently, oridonin, a natural diterpenoid isolated from Rabdosia rubescens, was demonstrated to regulate RARα by increasing its protein level. However, the underlying molecular mechanism for this action has not been fully elucidated. In the APL cell line, NB4, the effect of oridonin on RARα protein was analyzed by western blot and real-time quantitative RT-PCR analyses. Flow cytometry was performed to detect intracellular levels of reactive oxygen species (ROS). The association between nuclear factor-kappa B (NF-κB) signaling and the effect of oridonin was assessed using specific inhibitors, shRNA gene knockdown, and immunofluorescence assays. In addition, primary leukemia cells were treated with oridonin and analyzed by western blot in this study. RARα possesses transcriptional activity in the presence of its ligand, all-trans retinoic acid (ATRA). Oridonin remarkably stabilized the RARα protein, which retained transcriptional activity. Oridonin also moderately increased intracellular ROS levels, while pretreatment with the ROS scavenger, N-acetyl-l-cysteine (NAC), dramatically abrogated RARα stabilization by oridonin. More intriguingly, direct exposure to low concentrations of H2O2 also increased RARα protein but not mRNA levels, suggesting a role for ROS in oridonin stabilization of RARα protein. Further investigations showed that NAC antagonized oridonin-induced activation of NF-κB signaling, while the NF-κB signaling inhibitor, Bay 11-7082, effectively blocked the oridonin increase in RARα protein levels. In line with this, over-expression of IκΒα (A32/36), a super-repressor form of IκΒα, or NF-κB-p65 knockdown inhibited oridonin or H2O2-induced

A requirement for NF-κB in developmental and plasticity-associated synaptogenesis

Science.gov (United States)

Boersma, Matthew C. H.; Dresselhaus, Erica C.; De Biase, Lindsay M.; Mihalas, Anca B.; Bergles, Dwight E.

2011-01-01

Structural plasticity of dendritic spines and synapses is a fundamental mechanism governing neuronal circuits and may form an enduring basis for information storage in the brain. We find that the p65 subunit of the NF-κB transcription factor, which is required for learning and memory, controls excitatory synapse and dendritic spine formation and morphology in murine hippocampal neurons. Endogenous NF-κB activity is elevated by excitatory transmission during periods of rapid spine and synapse development. During in-vitro synaptogenesis, NF-κB enhances dendritic spine and excitatory synapse density and loss of endogenous p65 decreases spine density and spine head volume. Cell-autonomous function of NF-κB within the postsynaptic neuron is sufficient to regulate the formation of both pre- and post-synaptic elements. During synapse development in-vivo, loss of NF-κB similarly reduces spine density and also diminishes the amplitude of synaptic responses. In contrast, after developmental synaptogenesis has plateaued, endogenous NF-κB activity is low and p65-deficiency no longer attenuates basal spine density. Instead, NF-κB in mature neurons is activated by stimuli that induce demand for new synapses, including estrogen and short-term bicuculline, and is essential for upregulating spine density in response to these stimuli. p65 is enriched in dendritic spines making local protein-protein interactions possible; however, the effects of NF-κB on spine density require transcription and the NF-κB-dependent regulation of PSD-95, a critical postsynaptic component. Collectively, our data define a distinct role for NF-κB in imparting transcriptional regulation required for the induction of changes to, but not maintenance of, excitatory synapse and spine density. PMID:21471377

Rosiglitazone attenuates NF-κB-dependent ICAM-1 and TNF-α production caused by homocysteine via inhibiting ERK1/2/p38MAPK activation

International Nuclear Information System (INIS)

Bai, Yong-Ping; Liu, Yu-Hui; Chen, Jia; Song, Tao; You, Yu; Tang, Zhen-Yan; Li, Yuan-Jian; Zhang, Guo-Gang

2007-01-01

Previous studies demonstrated an important interaction between nuclear factor-kappaB (NF-κB) activation and homocysteine (Hcy)-induced cytokines expression in endothelial cells and vascular smooth muscle cells. However, the underlying mechanism remains illusive. In this study, we investigated the effects of Hcy on NF-κB-mediated sICAM-1, TNF-α production and the possible involvement of ERK 1/2 /p38MAPK pathway. The effects of rosiglitazone intervention were also examined. Our results show that Hcy increased the levels of sICAM-1 and TNF-α in cultured human umbilical vein endothelial cells (HUVECs) in a time- and concentration-dependent manner. This effect was significantly depressed by rosiglitazone and different inhibitors (PDTC, NF-κB inhibitor; PD98059, MEK inhibitor; SB203580, p38MAPK specific inhibitor; and staurosporine, PKC inhibitor). Next, we investigated the effect of Hcy on ERK 1/2 /p38MAPK pathway and NF-κB activity in HUVECs. The results show that Hcy activated both ERK 1/2 /p38MAPK pathway and NF-κB-DNA-binding activity. These effects were markedly inhibited by rosiglitazone as well as other inhibitors (SB203580, PD98059, and PDTC). Further, the pretreatment of staurosporine abrogated ERK 1/2 /p38MAPK phosphorylation, suggesting that Hcy-induced ERK 1/2 /p38MAPK activation is associated with PKC activity. Our results provide evidence that Hcy-induced NF-κB activation was mediated by activation of ERK 1/2 /p38MAPK pathway involving PKC activity. Rosiglitazone reduces the NF-κB-mediated sICAM-1 and TNF-α production induced by Hcy via inhibition of ERK 1/2 /p38MAPK pathway

Aralia elata inhibits neurodegeneration by downregulating O-GlcNAcylation of NF-κB in diabetic mice

Directory of Open Access Journals (Sweden)

Seong-Jae Kim

2017-08-01

Full Text Available AIM: To investigate the role of O-GlcNAcylation of nuclear factor-kappa B (NF-κB in retinal ganglion cell (RGC death and analysedthe effect of Aralia elata (AE on neurodegeneration in diabetic mice. METHODS: C57BL/6mice with streptozotocin-induced diabetes were fed daily with AE extract or control (CTL diet at the onset of diabetes mellitus (DM. Two months after injection of streptozotocin or saline, the degree of cell death and the expression of O-GlcNAc transferase (OGT, N-acetyl-b-D-glucosaminidase (OGA, O-GlcNAcylated proteins, and O-GlcNAcylation of NF-κB were examined. RESULTS: AE did not affect the metabolic status of diabetic mice. The decrease in the inner retinal thickness (P<0.001 vs CTL, P<0.01 vs DM and increases in RGCs with terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (P<0.001 vs CTL, P<0.0001 vs DM, glial activation, and active caspase-3 (P<0.0001 vs CTL, P<0.0001 vs DM were blocked in diabetic retinas of AE extract-fed mice. Expression levels of protein O-GlcNAcylation and OGT were increased in diabetic retinas (P<0.0001 vs CTL, and the level of O-GlcNAcylation of the NF-κB p65 subunit was higher in diabetic retinas than in controls (P<0.0001 vs CTL. AE extract downregulated O-GlcNAcylation of NF-κB and prevented neurodegeneration induced by hyperglycemia (P<0.0001 vs DM. CONCLUSION: O-GlcNAcylation of NF-κB is concerned in neuronal degeneration and that AE prevents diabetes-induced RGC apoptosis via downregulation of NF-κB O-GlcNAcylation. Hence, O-GlcNAcylation may be a new object for the treatment of DR, and AE may have therapeutic possibility to prevent diabetes-induced neurodegeneration.

Repetitive DNAs highlight the role of chromosomal fusions in the karyotype evolution of Dascyllus species (Pomacentridae, Perciformes).

Science.gov (United States)

Getlekha, Nuntaporn; Molina, Wagner Franco; de Bello Cioffi, Marcelo; Yano, Cassia Fernanda; Maneechot, Nuntiya; Bertollo, Luiz Antonio Carlos; Supiwong, Weerayuth; Tanomtong, Alongklod

2016-04-01

The Dascyllus genus consists of 11 species spread over vast regions of the Indo-Pacific, showing remarkable reductions in the diploid chromosome numbers (2n). The present study analyzed the karyotypes and other chromosomal characteristics of D. trimaculatus (2n = 48; 2st + 46a; NF = 50), D. carneus (2n = 48; 2st + 46a; NF = 50) and D. aruanus (2n = 30; 18m + 2st + 10a; NF = 50) from the Thailand Gulf (Pacific Ocean) and D. melanurus (2n = 48; 2st + 46a; NF = 50) from the Andaman Sea (Indian Ocean), employing conventional cytogenetic analyses and the chromosomal mapping of repetitive DNAs, using 18S and 5S rDNA, telomeric sequences and (CA)15, (GA)15, and (CAA)10 microsatellites as probes. The C-positive heterochromatin was found in the centromeric regions of most chromosomal pairs and 18S rDNA phenotypes were single in all species. However, in D. aruanus (2n = 30), which harbors nine metacentric pairs; the 5S rDNA sites were located in the centromeric region of the shortest one. The mapping of the telomeric sequences in D. aruanus revealed the presence of interstitial telomeric sites (ITS) in the centromeric region of four metacentric pairs, with one of these pairs also displaying an additional ITS in the long arms. Distinct chromosomal markers confirmed the reduction of the 2n by chromosomal fusions, highlighting the precise characterization of these rearrangements by the cytogenetic mapping of the repetitive DNAs.

10 Gb/s operation of photonic crystal silicon optical modulators.

Science.gov (United States)

Nguyen, Hong C; Sakai, Yuya; Shinkawa, Mizuki; Ishikura, Norihiro; Baba, Toshihiko

2011-07-04

We report the first experimental demonstration of 10 Gb/s modulation in a photonic crystal silicon optical modulator. The device consists of a 200 μm-long SiO2-clad photonic crystal waveguide, with an embedded p-n junction, incorporated into an asymmetric Mach-Zehnder interferometer. The device is integrated on a SOI chip and fabricated by CMOS-compatible processes. With the bias voltage set at 0 V, we measure a V(π)L pseudo-random bit sequence signal. An open eye pattern is observed at bitrates of 10 Gb/s and 2 Gb/s, with and without pre-emphasis of the drive signal, respectively.

The glutaredoxin/S-glutathionylation axis regulates interleukin-17A-induced proinflammatory responses in lung epithelial cells in association with S-glutathionylation of nuclear factor κB family proteins.

Science.gov (United States)

Nolin, James D; Tully, Jane E; Hoffman, Sidra M; Guala, Amy S; van der Velden, Jos L; Poynter, Matthew E; van der Vliet, Albert; Anathy, Vikas; Janssen-Heininger, Yvonne M W

2014-08-01

Interleukin-17A (IL-17A) is a newly emerging player in the pathogenesis of chronic lung diseases that amplifies inflammatory responses and promotes tissue remodeling. Stimulation of lung epithelial cells with IL-17A leads to activation of the transcription factor nuclear factor κB (NF-κB), a key player in the orchestration of lung inflammation. We have previously demonstrated the importance of the redox-dependent posttranslational modification S-glutathionylation in limiting activation of NF-κB and downstream gene induction. Under physiological conditions, the enzyme glutaredoxin 1 (Grx1) acts to deglutathionylate NF-κB proteins, which restores functional activity. In this study, we sought to determine the impact of S-glutathionylation on IL-17A-induced NF-κB activation and expression of proinflammatory mediators. C10 mouse lung alveolar epithelial cells or primary mouse tracheal epithelial cells exposed to IL-17A show rapid activation of NF-κB and the induction of proinflammatory genes. Upon IL-17A exposure, sulfenic acid formation and S-glutathionylated proteins increased. Assessment of S-glutathionylation of NF-κB pathway components revealed S-glutathionylation of RelA (RelA-SSG) and inhibitory κB kinase α (IKKα-SSG) after stimulation with IL-17A. SiRNA-mediated ablation of Grx1 increased both RelA-SSG and IKKα-SSG and acutely increased nuclear content of RelA and tended to decrease nuclear RelB. SiRNA-mediated ablation or genetic ablation of Glrx1 decreased the expression of the NF-κB-regulated genes KC and CCL20 in response to IL-17A, but conversely increased the expression of IL-6. Last, siRNA-mediated ablation of IKKα attenuated nuclear RelA and RelB content and decreased expression of KC and CCL20 in response to IL-17A. Together, these data demonstrate a critical role for the S-glutathionylation/Grx1 redox axis in regulating IKKα and RelA S-glutathionylation and the responsiveness of epithelial cells to IL-17A. Copyright © 2014 Elsevier Inc

Relationship between child epilepsy and MRI findings in von Recklinghausen Neurofibromatosis (NF 1)

International Nuclear Information System (INIS)

Yasujima, Hidehiro; Komatsu, Mikio; Sakurai, Takashi; Kodama, Soichi

1994-01-01

Fourteen children meeting the NIH consensus diagnostic criteria for NF 1 were evaluated at the Department of Pediatrics, Himeji Red Cross Hospital. MRI and EEG were examined in all patients, respectively. Four of 14 patients had a history of epilepsy, two had suffered West syndrome, one had complex partial seizures and one had secondary generalized partial epilepsy. Seven (50%) of 14 patients showed abnormal MRI; three (75%) of 4 patients with epilepsy and four (40%) of 10 patients with epilepsy showed low intensity on T 1 -weighted images and hyperintensity on T 2 -weighted images in the globus pallidus and brain stem. These results suggest that children with NF 1 have a spectrum of MRI abnormalities, irrespective of existence of epilepsy. (author)

RPAP3 enhances cytotoxicity of doxorubicin by impairing NF-kappa B pathway

International Nuclear Information System (INIS)

Shimada, Kana; Saeki, Makio; Egusa, Hiroshi; Fukuyasu, Sho; Yura, Yoshiaki; Iwai, Kazuhiro; Kamisaki, Yoshinori

2011-01-01

Research highlights: → RNA polymerase II-associated protein 3 (RPAP3) possesses an activity to bind with NEMO and to inhibit the ubiquitination of NEMO. → RPAP3 enhances doxorubicin-induced cell death in breast cancer cell line T-47D through the marked impairment of NF-κB pathway. → RPAP3 is a novel modulator of NF-κB pathway in apoptosis induced by anti-cancer chemotherapeutic agents. -- Abstract: Activation of anti-apoptotic gene transcription by NF-κB (nuclear factor-kappa B) has been reported to be linked with a resistance of cancer cells against chemotherapy. NEMO (NF-κB essential modulator) interacts with a number of proteins and modulates the activity of NF-κB pathway. In this study, we revealed that RPAP3 (RNA polymerase II-associated protein 3) possesses an activity to bind with NEMO and to inhibit the ubiquitination of NEMO and that RPAP3 enhances doxorubicin-induced cell death in breast cancer cell line T-47D through the marked impairment of NF-κB pathway. These results indicate that RPAP3 may be a novel modulator of NF-κB pathway in apoptosis induced by anti-cancer chemotherapeutic agents.

Asthmatic airway smooth muscle CXCL10 production: mitogen-activated protein kinase JNK involvement

Science.gov (United States)

Alrashdan, Yazan A.; Alkhouri, Hatem; Chen, Emily; Lalor, Daniel J.; Poniris, Maree; Henness, Sheridan; Brightling, Christopher E.; Burgess, Janette K.; Armour, Carol L.; Ammit, Alaina J.

2012-01-01

CXCL10 (IP10) is involved in mast cell migration to airway smooth muscle (ASM) bundles in asthma. We aimed to investigate the role of cytokine-induced MAPK activation in CXCL10 production by ASM cells from people with and without asthma. Confluent growth-arrested ASM cells were treated with inhibitors of the MAPKs ERK, p38, and JNK and transcription factor NF-κB, or vehicle, and stimulated with IL-1β, TNF-α, or IFN-γ, alone or combined (cytomix). CXCL10 mRNA and protein, JNK, NF-κB p65 phosphorylation, and Iκ-Bα protein degradation were assessed using real-time PCR, ELISA, and immunoblotting, respectively. Cytomix, IL-1β, and TNF-α induced CXCL10 mRNA expression more rapidly in asthmatic than nonasthmatic ASM cells. IL-1β and/or TNF-α combined with IFN-γ synergistically increased asthmatic ASM cell CXCL10 release. Inhibitor effects were similar in asthmatic and nonasthmatic cells, but cytomix-induced release was least affected, with only JNK and NF-κB inhibitors halving it. Notably, JNK phosphorylation was markedly less in asthmatic compared with nonasthmatic cells. However, in both, the JNK inhibitor SP600125 reduced JNK phosphorylation and CXCL10 mRNA levels but did not affect CXCL10 mRNA stability or Iκ-Bα degradation. Together, the JNK and NF-κB inhibitors completely inhibited their CXCL10 release. We concluded that, in asthmatic compared with nonasthmatic ASM cells, JNK activation was reduced and CXCL10 gene expression was more rapid following cytomix stimulation. However, in both, JNK activation did not regulate early events leading to NF-κB activation. Thus JNK and NF-κB provide independent therapeutic targets for limiting CXCL10 production and mast cell migration to the ASM in asthma. PMID:22387292

A Functional Genomic Analysis of NF1-Associated Learning Disabilities

National Research Council Canada - National Science Library

Tang, Shao-Jun

2008-01-01

Learning disabilities severely deteriorate the life of many NF1 patients. However, the pathogenic process for NF1-associated learning disabilities has not been fully understood and an effective therapy is not available...

A Functional Genomic Analysis of NF1-Associated Learning Disabilities

National Research Council Canada - National Science Library

Tang, Shao-Jun

2007-01-01

Learning disabilities severely deteriorate the life of many NF1 patients. However, the pathogenic process for NF1-associated learning disabilities has not been fully understood and an effective therapy is not available...

Interactions among oscillatory pathways in NF-kappa B signaling

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White Michael RH

2011-02-01

Full Text Available Abstract Background Sustained stimulation with tumour necrosis factor alpha (TNF-alpha induces substantial oscillations—observed at both the single cell and population levels—in the nuclear factor kappa B (NF-kappa B system. Although the mechanism has not yet been elucidated fully, a core system has been identified consisting of a negative feedback loop involving NF-kappa B (RelA:p50 hetero-dimer and its inhibitor I-kappa B-alpha. Many authors have suggested that this core oscillator should couple to other oscillatory pathways. Results First we analyse single-cell data from experiments in which the NF-kappa B system is forced by short trains of strong pulses of TNF-alpha. Power spectra of the ratio of nuclear-to-cytoplasmic concentration of NF-kappa B suggest that the cells' responses are entrained by the pulsing frequency. Using a recent model of the NF-kappa B system due to Caroline Horton, we carried out extensive numerical simulations to analyze the response frequencies induced by trains of pulses of TNF-alpha stimulation having a wide range of frequencies and amplitudes. These studies suggest that for sufficiently weak stimulation, various nonlinear resonances should be observable. To explore further the possibility of probing alternative feedback mechanisms, we also coupled the model to sinusoidal signals with a wide range of strengths and frequencies. Our results show that, at least in simulation, frequencies other than those of the forcing and the main NF-kappa B oscillator can be excited via sub- and superharmonic resonance, producing quasiperiodic and even chaotic dynamics. Conclusions Our numerical results suggest that the entrainment phenomena observed in pulse-stimulated experiments is a consequence of the high intensity of the stimulation. Computational studies based on current models suggest that resonant interactions between periodic pulsatile forcing and the system's natural frequencies may become evident for sufficiently

A noncanonical Flt3ITD/NF-κB signaling pathway represses DAPK1 in acute myeloid leukemia.

Science.gov (United States)

Shanmugam, Rajasubramaniam; Gade, Padmaja; Wilson-Weekes, Annique; Sayar, Hamid; Suvannasankha, Attaya; Goswami, Chirayu; Li, Lang; Gupta, Sushil; Cardoso, Angelo A; Baghdadi, Tareq Al; Sargent, Katie J; Cripe, Larry D; Kalvakolanu, Dhananjaya V; Boswell, H Scott

2012-01-15

Death-associated protein kinase 1 (DAPK1), a tumor suppressor, is a rate-limiting effector in an endoplasmic reticulum (ER) stress-dependent apoptotic pathway. Its expression is epigenetically suppressed in several tumors. A mechanistic basis for epigenetic/transcriptional repression of DAPK1 was investigated in certain forms of acute myeloid leukemia (AML) with poor prognosis, which lacked ER stress-induced apoptosis. Heterogeneous primary AMLs were screened to identify a subgroup with Flt3ITD in which repression of DAPK1, among NF-κB-and c-Jun-responsive genes, was studied. RNA interference knockdown studies were carried out in an Flt3ITD(+) cell line, MV-4-11, to establish genetic epistasis in the pathway Flt3ITD-TAK1-DAPK1 repression, and chromatin immunoprecipitations were carried out to identify proximate effector proteins, including TAK1-activated p52NF-κB, at the DAPK1 locus. AMLs characterized by normal karyotype with Flt3ITD were found to have 10- to 100-fold lower DAPK1 transcripts normalized to the expression of c-Jun, a transcriptional activator of DAPK1, as compared with a heterogeneous cytogenetic category. In addition, Meis1, a c-Jun-responsive adverse AML prognostic gene signature was measured as control. These Flt3ITD(+) AMLs overexpress relB, a transcriptional repressor, which forms active heterodimers with p52NF-κB. Chromatin immunoprecipitation assays identified p52NF-κB binding to the DAPK1 promoter together with histone deacetylase 2 (HDAC2) and HDAC6 in the Flt3ITD(+) human AML cell line MV-4-11. Knockdown of p52NF-κB or its upstream regulator, NF-κB-inducing kinase (NIK), de-repressed DAPK1. DAPK1-repressed primary Flt3ITD(+) AMLs had selective nuclear activation of p52NF-κB. Flt3ITD promotes a noncanonical pathway via TAK1 and p52NF-κB to suppress DAPK1 in association with HDACs, which explains DAPK1 repression in Flt3ITD(+) AML. ©2011 AACR.

A role for NF-κB–dependent gene transactivation in sunburn

Science.gov (United States)

Abeyama, Kazuhiro; Eng, William; Jester, James V.; Vink, Arie A.; Edelbaum, Dale; Cockerell, Clay J.; Bergstresser, Paul R.; Takashima, Akira

2000-01-01

Exposure of skin to ultraviolet (UV) radiation is known to induce NF-κB activation, but the functional role for this pathway in UV-induced cutaneous inflammation remains uncertain. In this study, we examined whether experimentally induced sunburn reactions in mice could be prevented by blocking UV-induced, NF-κB–dependent gene transactivation with oligodeoxynucleotides (ODNs) containing the NF-κB cis element (NF-κB decoy ODNs). UV-induced secretion of IL-1, IL-6, TNF-α, and VEGF by skin-derived cell lines was inhibited by the decoy ODNs, but not by the scrambled control ODNs. Systemic or local injection of NF-κB decoy ODNs also inhibited cutaneous swelling responses to UV irradiation. Moreover, local UV-induced inflammatory changes (swelling, leukocyte infiltration, epidermal hyperplasia, and accumulation of proinflammatory cytokines) were all inhibited specifically by topically applied decoy ODNs. Importantly, these ODNs had no effect on alternative types of cutaneous inflammation caused by irritant or allergic chemicals. These results indicate that sunburn reactions culminate from inflammatory events that are triggered by UV-activated transcription of NF-κB target genes, rather than from nonspecific changes associated with tissue damage. PMID:10862790

DNA-dependent protein kinase participates in the radiation activation of NF-kB

International Nuclear Information System (INIS)

Rosenzweig, Kenneth E.; Youmell, Matthew B.; Price, Brendan D.

1997-01-01

The NF-kB transcription factor is maintained in an inactive state by binding to the lkBa inhibitory protein. Activation requires phosphorylation and degradation of lkBa, releasing active NF-kB. NF-kB can be activated by cytokines, antigens, free radicals and X-ray irradiation. The protein kinase responsible for phosphorylation of lkBa in vivo has not been fully characterized. Here, we have examined the role of the DNA-dependent protein kinases (DNA-PK) in the radiation-activation of NF-kB. Wortmannin is an inhibitor of DNA-PK and related kinases. Exposure of SW480 cells to wortmannin inhibited the radioactivation of NF-kB DNA-binding. Analysis of lkBa levels by western blotting indicated that wortmannin blocked the radiation induced degradation of lkBa. In in vitro experiments, purified DNA-PK was able to efficiently phosphorylate lkBa, and this phosphorylation was inhibited by wortmannin. In contrast, the induction of NF-kB activity by TNFa was unaffected by wortmannin. The results suggest that DNA-PK may phosphorylate lkBa following irradiation, leading to degradation of lkBa and the release of active NF-kB. The inability of wortmannin to block TNFa activation of NF-kB indicates there may be more than one pathway for the activation of NF-kB

TRIM45 negatively regulates NF-κB-mediated transcription and suppresses cell proliferation

International Nuclear Information System (INIS)

Shibata, Mio; Sato, Tomonobu; Nukiwa, Ryota; Ariga, Tadashi; Hatakeyama, Shigetsugu

2012-01-01

Highlights: ► NF-κB plays an important role in cell survival and carcinogenesis. ► TRIM45 negatively regulates TNFα-induced NF-κB-mediated transcription. ► TRIM45 overexpression suppresses cell growth. ► TRIM45 acts as a repressor for the NF-κB signal and regulates cell growth. -- Abstract: The NF-κB signaling pathway plays an important role in cell survival, immunity, inflammation, carcinogenesis, and organogenesis. Activation of NF-κB is regulated by several posttranslational modifications including phosphorylation, neddylation and ubiquitination. The NF-κB signaling pathway is activated by two distinct signaling mechanisms and is strictly modulated by the ubiquitin–proteasome system. It has been reported that overexpression of TRIM45, one of the TRIM family ubiquitin ligases, suppresses transcriptional activities of Elk-1 and AP-1, which are targets of the MAPK signaling pathway. In this study, we showed that TRIM45 also negatively regulates TNFα-induced NF-κB-mediated transcription by a luciferase reporter assay and that TRIM45 lacking a RING domain also has an activity to inhibit the NF-κB signal. Moreover, we found that TRIM45 overexpression suppresses cell growth. These findings suggest that TRIM45 acts as a repressor for the NF-κB signal and regulates cell growth.

Genotype-Phenotype Correlation in NF1: Evidence for a More Severe Phenotype Associated with Missense Mutations Affecting NF1 Codons 844–848

NARCIS (Netherlands)

Koczkowska, M. (Magdalena); Chen, Y. (Yunjia); Callens, T. (Tom); Gomes, A. (Alicia); Sharp, A. (Angela); Johnson, S. (Sherrell); Hsiao, M.-C. (Meng-Chang); Chen, Z. (Zhenbin); Balasubramanian, M. (Meena); Barnett, C.P. (Christopher P.); Becker, T.A. (Troy A.); Ben-Shachar, S. (Shay); D.R. Bertola (Débora Romeo); J.O. Blakeley (Jaishri O.); Burkitt-Wright, E.M.M. (Emma M.M.); Callaway, A. (Alison); Crenshaw, M. (Melissa); Cunha, K.S. (Karin S.); Cunningham, M. (Mitch); M.D. D'Agostino (Maria Daniela); K. Dahan (Karin); De Luca, A. (Alessandro); A. Destrée (Anne); Dhamija, R. (Radhika); Eoli, M. (Marica); Evans, D.G.R. (D. Gareth R.); Galvin-Parton, P. (Patricia); George-Abraham, J.K. (Jaya K.); K.W. Gripp (Karen); Guevara-Campos, J. (Jose); Hanchard, N.A. (Neil A.); Hernández-Chico, C. (Concepcion); Immken, L. (LaDonna); S. Janssens (Sandra); K.J. Jones (Kristi); Keena, B.A. (Beth A.); Kochhar, A. (Aaina); Liebelt, J. (Jan); Martir-Negron, A. (Arelis); Mahoney, M.J. (Maurice J.); I. Maystadt (Isabelle); McDougall, C. (Carey); M. McEntagart (Meriel); N.J. Mendelsohn; Miller, D.T. (David T.); G. Mortier (Geert); J. Morton (Jenny); Pappas, J. (John); S.R. Plotkin (Scott R.); Pond, D. (Dinel); Rosenbaum, K. (Kenneth); Rubin, K. (Karol); Russell, L. (Laura); Rutledge, L.S. (Lane S.); Saletti, V. (Veronica); Schonberg, R. (Rhonda); Schreiber, A. (Allison); Seidel, M. (Meredith); Siqveland, E. (Elizabeth); D.W. Stockton (David); Trevisson, E. (Eva); N.J. Ullrich (Nicole J.); M. Upadhyaya (Meena); A.S. Thornton (Andrew); H. Verhelst (H.); M.R. Wallace (Margaret); Yap, Y.-S. (Yoon-Sim); Zackai, E. (Elaine); Zonana, J. (Jonathan); Zurcher, V. (Vickie); K. Claes (Kathleen); Martin, Y. (Yolanda); B. Korf (Bruce); E. Legius (Eric); L.M. Messiaen (Ludwine)

2018-01-01

textabstractNeurofibromatosis type 1 (NF1), a common genetic disorder with a birth incidence of 1:2,000–3,000, is characterized by a highly variable clinical presentation. To date, only two clinically relevant intragenic genotype-phenotype correlations have been reported for NF1 missense mutations

S.E.N.S.I.B. project

International Nuclear Information System (INIS)

2006-01-01

This report presents the state of progress of all the studies which constitute at present the S.E.N.S.I.B. project. The S.E.N.S.I.B. project receives a financial participation of the Ademe. The different chapters treat the following questions: the sensitivity of territories in the deposit; the sensitivity of grounds; the sensitivity of the banks of rivers; the sensitivity of the agricultural productions; the anthropological sensitivity of territories; comparative study of the global sensitivity of two sites; uncertainties, communication, perception and representation; assessment of the contributions to the S.E.N.S.I.B. project in 2005. (N.C.)

S N Hasan

Indian Academy of Sciences (India)

Home; Journals; Resonance – Journal of Science Education. S N Hasan. Articles written in Resonance – Journal of Science Education. Volume 12 Issue 3 March 2007 pp 13-26 General Article. Interactions and Mergers of Galaxies · S M Alladin S N Hasan · More Details Fulltext PDF ...

DESAIN DAN SINTESIS SENYAWA ACES (ANALOG CURCUMIN SERIES DENGAN METODE SOLID PHASE REACTION SEBAGAI SENYAWA ANTIKANKER POTEN DENGAN MEKANISME MENGHAMBAT PROTEIN NF-kB

Directory of Open Access Journals (Sweden)

Monica Sabrina Widiapranolo

2016-04-01

Full Text Available Abstract: Analog of curcumin in forms of enone and dienone aromatic is known for their activity as an NF-κB inhibitor. In this study, will be synthesize 2-(4'-N, N-dimethylamino benzilidine cyclohexane-1,3-dione as an analog that predicted has an activity as an NF-κB inhibitor. This research was conducted based on the crossed aldol condensation reaction by reacting 3 mmole pN,N-dimethylamino benzaldehide and 6 mmole cyclohexane-1,3-dione with hydrochloric acid as the catalyst using solid phase reaction method. Based on computational analysis, 2-(4'-N,Ndimethylamino benzilidine cyclohexane-1,3-dione showed a better interaction with NF-κB protein with PLANTSPLP score was -69,7895. The outcome of the reaction was yellow colored powder, no odor and soluble in hydrochloric acid 3N. The yield value was 78.8%. Liquid chromatography showed 100% purity. The melting point range was 237.5-240.3°C. The results of structure elucidation by 1H-NMR, infrared and mass spectroscopy tests indicated the compound was 2-(4-(dimetilaminobenzilidena-4-(3-oksosiklohex-1-enil sikloheksana-1,3-dion. Key words: 2-(4'-N, N-dimethylamino benzilidine cyclohexane-1,3-dione, crossed aldol condensation, solid phase reaction.

GeNF - Experimental report 2008

Energy Technology Data Exchange (ETDEWEB)

Pranzas, Philipp Klaus; Mueller, Martin; Willumeit, Regine; Schreyer, Andreas [GKSS-Forschungszentrum Geesthacht GmbH (Germany). Inst. fuer Materialforschung

2009-12-11

At the Geesthacht Neutron Facility GeNF about 182 experiments were performed in 2008 by GKSS and by or for external users, partners or contractors. In most cases the measurements were performed and analysed in cooperation by the guests, by GKSS staff or by the permanent external user group staff. The activities, which are based on a proposal procedure and on the in house R and D program, are reported in 76 contributions in the present annual experimental report for the year 2008. The contributions may contain several combined experiments. During 2008 the GKSS research reactor FRG-1 achieved an operation time of 175 days at the full 5 MW reactor power providing a neutron flux of ca. 1.4.10{sup 14} thermal neutrons/cm{sup 2} s. The focus of the in house R and D work at GeNF instruments in 2008 was the characterisation of nanostructures in engineering materials, the analysis of stresses and textures in welds and technical structures at SANS-2, DCD, ARES-2 and TEX-2, the structural investigation of hydrogen containing substances such as polymers, colloids and biological macromolecules at SANS-1 as well as the characterisation of magnetic thin films at NeRo, PNR, POLDI and ROeDI. The modern experiment control hardware (e.g. sample environments, like magnets, cryostats or furnaces) and software based on LabView was continuously improved on all instruments. In the appendices I and II the experimental reports of the GKSS outstation at the FRM II are attached as well as of the GKSS outstation at DESY. The massive activity at the FRM II outstation is documented by the increasing number of REFSANS reports, accumulated to nine. Three reports show the activities of GKSS in the field of texture measurement at the instrument STRESS-SPEC. The instrument HARWI II at the synchrotron storage ring DORIS III at DESY is accepted very well by the community and is heavily overbooked in all fields (tomography, diffraction, etc.). After an 8-month shutdown period for an upgrade in the frame

GeNF - Experimental report 2008

International Nuclear Information System (INIS)

Pranzas, Philipp Klaus; Mueller, Martin; Willumeit, Regine; Schreyer, Andreas

2009-01-01

At the Geesthacht Neutron Facility GeNF about 182 experiments were performed in 2008 by GKSS and by or for external users, partners or contractors. In most cases the measurements were performed and analysed in cooperation by the guests, by GKSS staff or by the permanent external user group staff. The activities, which are based on a proposal procedure and on the in house R and D program, are reported in 76 contributions in the present annual experimental report for the year 2008. The contributions may contain several combined experiments. During 2008 the GKSS research reactor FRG-1 achieved an operation time of 175 days at the full 5 MW reactor power providing a neutron flux of ca. 1.4.10 14 thermal neutrons/cm 2 s. The focus of the in house R and D work at GeNF instruments in 2008 was the characterisation of nanostructures in engineering materials, the analysis of stresses and textures in welds and technical structures at SANS-2, DCD, ARES-2 and TEX-2, the structural investigation of hydrogen containing substances such as polymers, colloids and biological macromolecules at SANS-1 as well as the characterisation of magnetic thin films at NeRo, PNR, POLDI and ROeDI. The modern experiment control hardware (e.g. sample environments, like magnets, cryostats or furnaces) and software based on LabView was continuously improved on all instruments. In the appendices I and II the experimental reports of the GKSS outstation at the FRM II are attached as well as of the GKSS outstation at DESY. The massive activity at the FRM II outstation is documented by the increasing number of REFSANS reports, accumulated to nine. Three reports show the activities of GKSS in the field of texture measurement at the instrument STRESS-SPEC. The instrument HARWI II at the synchrotron storage ring DORIS III at DESY is accepted very well by the community and is heavily overbooked in all fields (tomography, diffraction, etc.). After an 8-month shutdown period for an upgrade in the frame of the

THE ROLE OF NF-κB IN NEURONAL PLASTICITY AND NEURODEGENERATIVE DISEASES

OpenAIRE

Yağmur, Elif Nuran; Yıldız, Nazım; Adıgüzel, Serkan; Femir, Banu; Şenyer, Seray; Şen, Melis; Tüzün, Erdem; Küçükali, Cem İsmail

2018-01-01

NF-κB is a transcription factor emerged by the end of 20th century. At the beginning, NF-κB wasfound to be present in immune cells but following studies showed its presence in almost all cells inan organism. NF-κB takes part in the activation of almost 500 genes and have roles in mechanismsincluding immune response, cell cycle, cell survival, cell proliferation and development, as well asplasticity and memory formation. Long-term potentiation (LTP) of NF-κB in the central nervoussystem (CNS) ...

Torilin Inhibits Inflammation by Limiting TAK1-Mediated MAP Kinase and NF-κB Activation

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Mehari Endale

2017-01-01

Full Text Available Torilin, a sesquiterpene isolated from the fruits of Torilis japonica, has shown antimicrobial, anticancer, and anti-inflammatory properties. However, data on the mechanism of torilin action against inflammation is limited. This study aimed at determining the anti-inflammatory property of torilin in LPS-induced inflammation using in vitro model of inflammation. We examined torilin’s effect on expression levels of inflammatory mediators and cytokines in LPS-stimulated RAW 264.7 macrophages. The involvement of NF-kB and AP-1, MAP kinases, and adaptor proteins were assessed. Torilin strongly inhibited LPS-induced NO release, iNOS, PGE2, COX-2, NF-α, IL-1β, IL-6, and GM-CSF gene and protein expressions. In addition, MAPKs were also suppressed by torilin pretreatment. Involvement of ERK1/2, P38MAPK, and JNK1/2 was further confirmed by PD98059, SB203580, and SP600125 mediated suppression of iNOS and COX-2 proteins. Furthermore, torilin attenuated NF-kB and AP-1 translocation, DNA binding, and reporter gene transcription. Interestingly, torilin inhibited TAK1 kinase activation with the subsequent suppression of MAPK-mediated JNK, p38, ERK1/2, and AP-1 (ATF-2 and c-jun activation and IKK-mediated I-κBα degradation, p65/p50 activation, and translocation. Together, the results revealed the suppression of NF-κB and AP-1 regulated inflammatory mediator and cytokine expressions, suggesting the test compound’s potential as a candidate anti-inflammatory agent.

The inhibition of NF-kappaB activation pathways and the induction of apoptosis by dithiocarbamates in T cells are blocked by the glutathione precursor N-acetyl-L-cysteine

OpenAIRE

Fernandez, P C; Machado, J; Heussler, Volker; Botteron, C; Palmer, G H; Dobbelaere, D A

1999-01-01

Nuclear factor-kappaB regulates genes that control immune and inflammatory responses and are involved in the pathogenesis of several diseases, including AIDS and cancer. It has been proposed that reactive oxygen intermediates participate in NF-kappaB activation pathways, and compounds with putative antioxidant activity such as N-acetyl-L-cysteine (NAC) and pyrrolidine dithiocarbamate (PDTC) have been used interchangeably to demonstrate this point. We examined their effects, separately and com...

Effects of andrographolide on postoperative cognitive dysfunction and the association with NF-κB/MAPK pathway.

Science.gov (United States)

Ding, Yongbo; Shi, Cunxian; Chen, Linjing; Ma, Piliang; Li, Kezhong; Jin, Jin; Zhang, Qingfeng; Li, Aizhi

2017-12-01

The present study investigated the effects of andrographolide on postoperative cognitive dysfunction (POCD) in aged rats to gain insight of the underlying mechanism, which may provide theoretical basis for the clinical application of andrographolide to prevent POCD in older patients. Thirty aged male rats were randomly assigned to 3 groups: Control, model and andrographolide groups. The Morris water maze test was used to examine the spatial memory and learning ability of the rats postoperatively. The histological alterations of neuronal cells in the hippocampus were visualized by H&E staining. The serum levels of neuron-specific enolase (NSE), human soluble protein-100β (S-100β) and the inflammation factors of interluekin (IL)-1β, IL-6 and TNF-α involved in the nuclear factor κB (NF-κB)/mitogen-activated protein kinase (MAPK) signaling pathway were detected by ELISA. The NF-κB/MAPK signaling pathway-associated proteins in rat serum were detected by western blotting. Following andrographolide treatment, the rats significantly gained learning ability after surgery. Is it ameliorated hippocampal neuronal injury in rats following surgery. Andrographolide decreased NSE, S-100β, and the inflammation factors, IL-6, IL-1β and TNF-α in serum. Andrographolide reduced NF-κB/MAPK pathway-associated protein expression. Andrographolide ameliorated POCD in aged rats following surgery. The underlying mechanism may be associated with the downregulation the inflammatory factors and NF-κB/MAPK-associated protein expression.

Infrared Fixed Point Physics in ${\\rm SO}(N_c)$ and ${\\rm Sp}(N_c)$ Gauge Theories

DEFF Research Database (Denmark)

Ryttov, Thomas A.; Shrock, Robert

2017-01-01

We study properties of asymptotically free vectorial gauge theories with gauge groups $G={\\rm SO}(N_c)$ and $G={\\rm Sp}(N_c)$ and $N_f$ fermions in a representation $R$ of $G$, at an infrared (IR) zero of the beta function, $\\alpha_{IR}$, in the non-Abelian Coulomb phase. The fundamental, adjoint......_{\\bar\\psi\\psi,IR}$ increases monotonically with decreasing $N_f$ in the non-Abelian Coulomb phase. Using this property, we give a new estimate of the lower end of this phase for some specific realizations of these theories....

Post-Translational Modifications of RelB NF-κB Subunit and Associated Functions

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Véronique Baud

2016-05-01

Full Text Available The family of NF-κB transcription factors plays a key role in diverse biological processes, such as inflammatory and immune responses, cell survival and tumor development. Beyond the classical NF-κB activation pathway, a second NF-κB pathway has more recently been uncovered, the so-called alternative NF-κB activation pathway. It has been shown that this pathway mainly controls the activity of RelB, a member of the NF-κB family. Post-translational modifications, such as phosphorylation, acetylation, methylation, ubiquitination and SUMOylation, have recently emerged as a strategy for the fine-tuned regulation of NF-κB. Our review discusses recent progress in the understanding of RelB regulation by post-translational modifications and the associated functions in normal and pathological conditions.

NF-kappaB signaling: a tale of two pathways in skeletal myogenesis.

Science.gov (United States)

Bakkar, Nadine; Guttridge, Denis C

2010-04-01

NF-kappaB is a ubiquitiously expressed transcription factor that plays vital roles in innate immunity and other processes involving cellular survival, proliferation, and differentiation. Activation of NF-kappaB is controlled by an IkappaB kinase (IKK) complex that can direct either canonical (classical) NF-kappaB signaling by degrading the IkappaB inhibitor and releasing p65/p50 dimers to the nucleus, or causes p100 processing and nuclear translocation of RelB/p52 via a noncanonical (alternative) pathway. Under physiological conditions, NF-kappaB activity is transiently regulated, whereas constitutive activation of this transcription factor typically in the classical pathway is associated with a multitude of disease conditions, including those related to skeletal muscle. How NF-kappaB functions in muscle diseases is currently under intense investigation. Insight into this role of NF-kappaB may be gained by understanding at a more basic level how this transcription factor contributes to skeletal muscle cell differentiation. Recent data from knockout mice support that the classical NF-kappaB pathway functions as an inhibitor of skeletal myogenesis and muscle regeneration acting through multiple mechanisms. In contrast, alternative NF-kappaB signaling does not appear to be required for myofiber conversion, but instead functions in myotube homeostasis by regulating mitochondrial biogenesis. Additional knowledge of these signaling pathways in skeletal myogenesis should aid in the development of specific inhibitors that may be useful in treatments of muscle disorders.

Respiratory syncytial virus and TNFalpha induction of chemokine gene expression involves differential activation of Rel A and NF-kappaB1

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Roebuck Kenneth A

2002-03-01

Full Text Available Abstract Background Respiratory syncytial virus (RSV infection of airway epithelial cells stimulates the expression and secretion of a variety of cytokines including the chemotactic cytokines interleukin-8 (IL-8, monocyte chemoattractant protein-1 (MCP-1, and RANTES (regulated upon activation, normal T cell expressed and secreted. Chemokines are important chemoattractants for the recruitment of distinct sets of leukocytes to airway sites of inflammation. Results We have shown previously that chemokine expression is regulated in airway epithelial cells (A549 in a stimulus-specific manner in part through the redox-responsive transcription factors AP-1 and NF-κB. In this study, we examined the NF-κB-mediated effects of RSV and the proinflammatory cytokine TNFα on the induction of IL-8, MCP-1 and RANTES chemokine gene expression in A549 epithelial cells. The results demonstrate that RSV induces chemokine expression with distinct kinetics that is associated with a specific pattern of NF-κB binding activity. This distinction was further demonstrated by the differential effects of the NF-κB inhibitors dexamethasone (DEX and N-acetyl-L-cysteine (NAC. NAC preferentially inhibited RSV induced chemokine expression, whereas DEX preferentially inhibited TNFα induced chemokine expression. DNA binding studies using NF-κB subunit specific binding ELISA demonstrated that RSV and TNFα induced different NF-κB binding complexes containing Rel A (p65 and NF-κB1 (p50. Both TNFα and RSV strongly induced Rel A the activation subunit of NF-κB, whereas only TNFα was able to substantially induce the p50 subunit. Consistent with the expression studies, RSV but not TNFα induction of Rel A and p50 were markedly inhibited by NAC, providing a mechanism by which TNFα and RSV can differentially activate chemokine gene expression via NF-κB. Conclusions These data suggest that RSV induction of chemokine gene expression, in contrast to TNFα, involves redox

The order of the chiral transition in N_f=2 QCD

DEFF Research Database (Denmark)

D'Elia, M.; Di Giacomo, A.; Pica, Claudio

2004-01-01

A strategy is developed to investigate the order of the transition using finite size scaling and its relation to color confinement. An in-depth numerical investigation has been performed with KS fermions on lattices with N_t=4 and N_s=12,16,20,24,32 and quark masses am_q ranging from 0.01335 to 0...

Effects of age and sedentary lifestyle on skeletal muscle NF-kappaB signaling in men.

Science.gov (United States)

Buford, Thomas W; Cooke, Matthew B; Manini, Todd M; Leeuwenburgh, Christiaan; Willoughby, Darryn S

2010-05-01

Nuclear factor kappa B (NF-kappaB) is a critical signaling molecule of disuse-induced skeletal muscle atrophy. However, few studies have carefully investigated whether similar pathways are modulated with physical activity and age. The present study examined lean mass, maximal force production, and skeletal muscle NF-kappaB signaling in 41 men categorized as sedentary (OS, N = 13, 63.85 +/- 6.59 year), physically active (OA, N = 14, 60.71 +/- 5.54 year), or young and sedentary (YS, N = 14, 21.35 +/- 3.84 year). Muscle tissue from the vastus lateralis was assayed for messenger RNA (mRNA) expression of the beta subunit of IkB kinase (IKKbeta), cytosolic protein content of phosphorylated inhibitor of kappa B alpha (pIKBalpha), and nuclear content of NF-kappaB subunits p50 and p65. When compared with YS, OS demonstrated age-related muscle atrophy and reduced isokinetic knee extension torque. Physical activity in older individuals preserved maximal isokinetic knee extension torque. OS muscle contained 50% more pIKBalpha than OA and 61% more pIKBalpha than YS. Furthermore, nuclear p65 was significantly elevated in OS compared with YS. OS muscle did not differ from either of the other two groups for nuclear p50 or for mRNA expression of IKKbeta. These results indicate that skeletal muscle content of nuclear-bound p65 is elevated by age in humans. The elevation in nuclear-bound p65 appears to be at least partially due to significant increases in pIKBalpha. A sedentary lifestyle appears to play some role in increased IKBalpha; however, further research is needed to identify downstream effects of this increase.

Investigating the DNA-binding ability of GATA-1-N-terminal zinc finger

International Nuclear Information System (INIS)

Wong, R.; Newton, A.; Crossley, M.; Mackay, J.

2001-01-01

Erythroid transcription factor GATA-1 interacts with both DNA and other proteins through its zinc finger domains (ZnFs). While it has been known for me time that the C-terminal ZnF binds DNA at GATA sites, only recently has it been observed that the N-terminal finger (NF) is capable of interacting with GATC sites. Further, a number of naturally occurring mutations in NF (V205M, G208S, R216Q, D218G) that lead to anaemia and thrombocytopenia have been identified. We are interested in characterising the NF-DNA interaction and determining the effects of mutation upon this interaction. Using nuclear magnetic resonance (NMR) spectroscopy, we have observed an interaction between recombinant NF and a 16-mer DNA duplex containing a core GATC sequence. This result forms the basis from which residues in NF involved in DNA binding can be identified, and work is being carried out to improve the quality of the NMR data with the aim of determining the solution structure of the NF-DNA complex. The DNA-binding affinity of both wild-type and mutant NFs mentioned above is also being investigated using isothermal titration calorimetry. These data suggest that the strength of the interaction between NF and the 16-mer DNA duplex is in the sub-micromolar range, and comparisons between the DNA-binding affinities of the NF mutants are being made. Together, these studies will help us to understand how GATA-1 acts as a transcriptional regulator and how mutations in NF domain of GATA-1 may lead to blood disorders

Milföy Hamurunun Isıl Yayınım Katsayısının Sıcaklıkla Değişiminin Belirlenmesi

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Seher Kumcuoğlu

2015-02-01

Full Text Available Bu çalışmada milföy hamurunun ısıl yayınım katsayısı modifiye edilmiş Dickerson metodu kullanılarak -35 °C ile +10 °C sıcaklık aralığında deneysel olarak ölçülmüştür. Örneğin donmuş durumdaki ısıl yayınım katsayısının donmamış durumuna ait ısıl yayınım katsayısından daha yüksek olduğu ve sıcaklığın artmasıyla azaldığı tespit edilmiştir. Donmuş durum için elde edilen ölçüm sonuçlarına regresyon analizi uygulanarak milföy hamurunun ısıl yayınım katsayısının sıcaklıkla değişimini veren empirik denklem elde edilmiştir. Donmamış durumda, 3-10 °C sıcaklık aralığında örneğin ısıl yayınım katsayısı 1.08 x 10-7 m²/s olarak ölçülmüştür.

Ceftiofur impairs pro-inflammatory cytokine secretion through the inhibition of the activation of NF-κB and MAPK

International Nuclear Information System (INIS)

Ci Xinxin; Song Yu; Zeng Fanqin; Zhang Xuemei; Li Hongyu; Wang Xinrui; Cui Junqing; Deng Xuming

2008-01-01

Ceftiofur is a new broad-spectrum, third-generation cephalosporin antibiotic for veterinary use. Immunopharmacological studies can provide new information on the immunomodulatory activities of some drugs, including their effect on cytokine productions. For this reason, we investigated the effect of ceftiofur on cytokine productions in vitro. We found that ceftiofur can downregulate tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), but did not affect interleukin-10 (IL-10) production. We further investigated signal transduction mechanisms to determine how ceftiofur affects. RAW 264.7 cells were pretreated with 1, 5, or 10 mg/L of ceftiofur 1 h prior to treatment with 1 mg/L of LPS. Thirty minutes later, cells were harvested and mitogen activated protein kinases (MAPKs) activation was measured by Western blot. Alternatively, cells were fixed and nuclear factor-κB (NF-κB) activation was measured using immunocytochemical analysis. Signal transduction studies showed that ceftiofur significantly inhibited extracellular signal-regulated kinase (ERK), p38, and c-jun NH 2 -terminal kinase (JNK) phosphorylation protein expression. Ceftiofur also inhibited p65-NF-κB translocation into the nucleus. Therefore, ceftiofur may inhibit LPS-induced production of inflammatory cytokines by blocking NF-κB and MAPKs signaling in RAW264.7 cells

42 CFR 483.114 - Annual review of NF residents.

Science.gov (United States)

2010-10-01

... residents. (a) Individuals with mental illness. For each resident of a NF who has mental illness, the State... physical and mental condition, the resident requires— (1) The level of services provided by— (i) A NF; (ii... 65 or older; and (2) Specialized services for mental illness, as defined in § 483.120. (b...

The proinflammatory RAGE/NF-κB pathway is involved in neuronal damage and reactive gliosis in a model of sleep apnea by intermittent hypoxia.

Science.gov (United States)

Angelo, Maria Florencia; Aguirre, Alejandra; Avilés Reyes, Rolando X; Villarreal, Alejandro; Lukin, Jerónimo; Melendez, Matías; Vanasco, Virginia; Barker, Phil; Alvarez, Silvia; Epstein, Alberto; Jerusalinsky, Diana; Ramos, Alberto Javier

2014-01-01

Sleep apnea (SA) causes long-lasting changes in neuronal circuitry, which persist even in patients successfully treated for the acute effects of the disease. Evidence obtained from the intermittent hypoxia (IH) experimental model of SA has shown neuronal death, impairment in learning and memory and reactive gliosis that may account for cognitive and structural alterations observed in human patients. However, little is known about the mechanism controlling these deleterious effects that may be useful as therapeutic targets in SA. The Receptor for Advanced Glycation End products (RAGE) and its downstream effector Nuclear Factor Kappa B (NF-κB) have been related to neuronal death and astroglial conversion to the pro-inflammatory neurodegenerative phenotype. RAGE expression and its ligand S100B were shown to be increased in experimental models of SA. We here used dissociated mixed hippocampal cell cultures and male Wistar rats exposed to IH cycles and observed that NF-κB is activated in glial cells and neurons after IH. To disclose the relative contribution of the S100B/RAGE/NF-κB pathway to neuronal damage and reactive gliosis after IH we performed sequential loss of function studies using RAGE or S100B neutralizing antibodies, a herpes simplex virus (HSV)-derived amplicon vector that induces the expression of RAGEΔcyto (dominant negative RAGE) and a chemical blocker of NF-κB. Our results show that NF-κB activation peaks 3 days after IH exposure, and that RAGE or NF-κB blockage during this critical period significantly improves neuronal survival and reduces reactive gliosis. Both in vitro and in vivo, S100B blockage altered reactive gliosis but did not have significant effects on neuronal survival. We conclude that both RAGE and downstream NF-κB signaling are centrally involved in the neuronal alterations found in SA models, and that blockage of these pathways is a tempting strategy for preventing neuronal degeneration and reactive gliosis in SA.

The proinflammatory RAGE/NF-κB pathway is involved in neuronal damage and reactive gliosis in a model of sleep apnea by intermittent hypoxia.

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Maria Florencia Angelo

Full Text Available Sleep apnea (SA causes long-lasting changes in neuronal circuitry, which persist even in patients successfully treated for the acute effects of the disease. Evidence obtained from the intermittent hypoxia (IH experimental model of SA has shown neuronal death, impairment in learning and memory and reactive gliosis that may account for cognitive and structural alterations observed in human patients. However, little is known about the mechanism controlling these deleterious effects that may be useful as therapeutic targets in SA. The Receptor for Advanced Glycation End products (RAGE and its downstream effector Nuclear Factor Kappa B (NF-κB have been related to neuronal death and astroglial conversion to the pro-inflammatory neurodegenerative phenotype. RAGE expression and its ligand S100B were shown to be increased in experimental models of SA. We here used dissociated mixed hippocampal cell cultures and male Wistar rats exposed to IH cycles and observed that NF-κB is activated in glial cells and neurons after IH. To disclose the relative contribution of the S100B/RAGE/NF-κB pathway to neuronal damage and reactive gliosis after IH we performed sequential loss of function studies using RAGE or S100B neutralizing antibodies, a herpes simplex virus (HSV-derived amplicon vector that induces the expression of RAGEΔcyto (dominant negative RAGE and a chemical blocker of NF-κB. Our results show that NF-κB activation peaks 3 days after IH exposure, and that RAGE or NF-κB blockage during this critical period significantly improves neuronal survival and reduces reactive gliosis. Both in vitro and in vivo, S100B blockage altered reactive gliosis but did not have significant effects on neuronal survival. We conclude that both RAGE and downstream NF-κB signaling are centrally involved in the neuronal alterations found in SA models, and that blockage of these pathways is a tempting strategy for preventing neuronal degeneration and reactive gliosis in SA.

Regeneración miocárdica en Ambystoma mexicanum después de lesión quirúrgica

OpenAIRE

Vargas-González, Alvaro; Prado-Zayago, Esteban; León-Olea, Martha; Guarner-Lans, Verónica; Cano-Martínez, Agustina

2005-01-01

Se realizó resección ventricular en el corazón de Ambystoma mexicanum, se evaluó si la restitución del tejido resulta de hipertrofia o de hiperplasia. Por medio de una tinción tricrómica se encontró que 5 días después del daño en el espacio de la resección se encontró un coágulo rodeado de fibras de colágena (83 ± 6%), músculo (10 ± 3%) y zonas sin tejido (7 ± 2%). Una proporción de 50 ± 4 y 90 ± 2% correspondió a tejido muscular 10 y 30 días después de la lesión. La tinción con bis-Benzimida...

Kaempferol modulates pro-inflammatory NF-κB activation by suppressing advanced glycation endproducts-induced NADPH oxidase

Science.gov (United States)

Kim, Ji Min; Lee, Eun Kyeong; Kim, Dae Hyun; Yu, Byung Pal

2010-01-01

Advanced glycation endproducts (AGE) are oxidative products formed from the reaction between carbohydrates and a free amino group of proteins that are provoked by reactive species (RS). It is also known that AGE enhance the generation of RS and that the binding of AGE to a specific AGE receptor (RAGE) induces the activation of the redox-sensitive, pro-inflammatory transcription factor, nuclear factor-kappa B (NF-ĸB). In this current study, we investigated the anti-oxidative effects of short-term kaempferol supplementation on the age-related formation of AGE and the binding activity of RAGE in aged rat kidney. We further investigated the suppressive action of kaempferol against AGE's ability to stimulate activation of pro-inflammatory NF-ĸB and its molecular mechanisms. For this study, we utilized young (6 months old), old (24 months old), and kaempferol-fed (2 and 4 mg/kg/day for 10 days) old rats. In addition, for the molecular work, the rat endothelial cell line, YPEN-1 was used. The results show that AGE and RAGE were increased during aging and that these increases were blunted by kaempferol. In addition, dietary kaempferol reduced age-related increases in NF-κB activity and NF-ĸB-dependant pro-inflammatory gene activity. The most significant new finding from this study is that kaempferol supplementation prevented age-related NF-κB activation by suppressing AGE-induced nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase). Taken together, our results demonstrated that dietary kaempferol exerts its anti-oxidative and anti-inflammatory actions by modulating the age-related NF-κB signaling cascade and its pro-inflammatory genes by suppressing AGE-induced NADPH oxidase activation. Based on these data, dietary kaempferol is proposed as a possible anti-AGE agent that may have the potential for use in anti-inflammation therapies. PMID:20431987

Protein kinase Cη activates NF-κB in response to camptothecin-induced DNA damage

International Nuclear Information System (INIS)

Raveh-Amit, Hadas; Hai, Naama; Rotem-Dai, Noa; Shahaf, Galit; Gopas, Jacob; Livneh, Etta

2011-01-01

Highlights: → Protein kinase C-eta (PKCη) is an upstream regulator of the NF-κB signaling pathway. → PKCη activates NF-κB in non-stressed conditions and in response to DNA damage. → PKCη regulates NF-κB by activating IκB kinase (IKK) and inducing IκB degradation. -- Abstract: The nuclear factor κB (NF-κB) family of transcription factors participates in the regulation of genes involved in innate- and adaptive-immune responses, cell death and inflammation. The involvement of the Protein kinase C (PKC) family in the regulation of NF-κB in inflammation and immune-related signaling has been extensively studied. However, not much is known on the role of PKC in NF-κB regulation in response to DNA damage. Here we demonstrate for the first time that PKC-eta (PKCη) regulates NF-κB upstream signaling by activating the IκB kinase (IKK) and the degradation of IκB. Furthermore, PKCη enhances the nuclear translocation and transactivation of NF-κB under non-stressed conditions and in response to the anticancer drug camptothecin. We and others have previously shown that PKCη confers protection against DNA damage-induced apoptosis. Our present study suggests that PKCη is involved in NF-κB signaling leading to drug resistance.

About Learning Disabilities and NF

Science.gov (United States)

... complica- tions of NF1 include: • Learning disabilities: Although intelligence is usually within the normal range, 50-60% ... and the ability to access meaning from the printed word. 5 Recent findings suggest that a high ...

Caspase-10 Negatively Regulates Caspase-8-Mediated Cell Death, Switching the Response to CD95L in Favor of NF-κB Activation and Cell Survival

Directory of Open Access Journals (Sweden)

Sebastian Horn

2017-04-01

Full Text Available Formation of the death-inducing signaling complex (DISC initiates extrinsic apoptosis. Caspase-8 and its regulator cFLIP control death signaling by binding to death-receptor-bound FADD. By elucidating the function of the caspase-8 homolog, caspase-10, we discover that caspase-10 negatively regulates caspase-8-mediated cell death. Significantly, we reveal that caspase-10 reduces DISC association and activation of caspase-8. Furthermore, we extend our co-operative/hierarchical binding model of caspase-8/cFLIP and show that caspase-10 does not compete with caspase-8 for binding to FADD. Utilizing caspase-8-knockout cells, we demonstrate that caspase-8 is required upstream of both cFLIP and caspase-10 and that DISC formation critically depends on the scaffold function of caspase-8. We establish that caspase-10 rewires DISC signaling to NF-κB activation/cell survival and demonstrate that the catalytic activity of caspase-10, and caspase-8, is redundant in gene induction. Thus, our data are consistent with a model in which both caspase-10 and cFLIP coordinately regulate CD95L-mediated signaling for death or survival.

Dynamic activity of NF-κB in multiple trauma patients and protective effects of ulinastain

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LI Jun

2012-02-01

Full Text Available 【Abstract】Objective: To investigate the dynamic activity of NF-κB at the early stage of injury in multiple trauma patients and the protective effects of ulinastain. Methods: From January 2008 to May 2010, patients with multiple traumas admitted to our emergency department were enrolled in this study. Their age varied from 20-55 years. All enrolled patients were assigned randomly into control group (26 cases of multiple injury without ulinastain treatment, ulinastain group (25 cases of multiple injury with ulinastain treatment, and mild injury group (20 cases for basic control. The inclusion criteria for mild injury group were AIS-2005≤3, single wound, previously healthy inhospital patients without the history of surgical intervention. In addition to routine treatment, patients in ulinastain group were intravenously injected 200 000 IU of ulinastain dissolved in 100 ml of normal saline within 12 hours after injury and subsequently injected at the interval of every 8 hours for 7 days. NF-κB activity in monocytes and the level of TNF? IL-1, IL? in serum on admission (day 0, day 1, 2, 3, 4, and 7 were measured. Data were compared and analyzed between different groups. Results: NF-κB activity in monocytes and TNF? IL-1 and IL? of these patients reached peak levels at 24 hour after trauma, with gradual decrease to normal at 72 hour after trauma. NF-κB activity and levels of TNF? IL-1 and IL? were lower in ulinastain group than control one, without any significant difference between the two groups. The mean duration for systemic inflammatory response syndrome and multiple organ dysfunction syndrome was 7 d?.1 d and 10 d?.5 d in ulinastain group and control group respectively, and showed a significant difference. Conclusions: NF-κB activity in monocytes and the levels of inflammatory cytokines in multiply injured patients increased transiently at the early stage of trauma. Ulinastain may shorten the duration of systemic inflammatory

NF-κB2 mutation targets survival, proliferation and differentiation pathways in the pathogenesis of plasma cell tumors

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McCarthy Brian A

2012-05-01

Full Text Available Abstract Background Abnormal NF-κB2 activation has been implicated in the pathogenesis of multiple myeloma, a cancer of plasma cells. However, a causal role for aberrant NF-κB2 signaling in the development of plasma cell tumors has not been established. Also unclear is the molecular mechanism that drives the tumorigenic process. We investigated these questions by using a transgenic mouse model with lymphocyte-targeted expression of p80HT, a lymphoma-associated NF-κB2 mutant, and human multiple myeloma cell lines. Methods We conducted a detailed histopathological characterization of lymphomas developed in p80HT transgenic mice and microarray gene expression profiling of p80HT B cells with the goal of identifying genes that drive plasma cell tumor development. We further verified the significance of our findings in human multiple myeloma cell lines. Results Approximately 40% of p80HT mice showed elevated levels of monoclonal immunoglobulin (M-protein in the serum and developed plasma cell tumors. Some of these mice displayed key features of human multiple myeloma with accumulation of plasma cells in the bone marrow, osteolytic bone lesions and/or diffuse osteoporosis. Gene expression profiling of B cells from M-protein-positive p80HT mice revealed aberrant expression of genes known to be important in the pathogenesis of multiple myeloma, including cyclin D1, cyclin D2, Blimp1, survivin, IL-10 and IL-15. In vitro assays demonstrated a critical role of Stat3, a key downstream component of IL-10 signaling, in the survival of human multiple myeloma cells. Conclusions These findings provide a mouse model for human multiple myeloma with aberrant NF-κB2 activation and suggest a molecular mechanism for NF-κB2 signaling in the pathogenesis of plasma cell tumors by coordinated regulation of plasma cell generation, proliferation and survival.

cis-Bis[N′-(4-bromobenzoyl-N,N-dimethylthioureato-κ2O,S]copper(II

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Gün Binzet

2011-05-01

Full Text Available The asymmetric unit of the title compound, [Cu(C10H10BrN2OS2], contains two independent complex molecules with almost identical conformations. Two S and two O atoms form the coordination environment of the Cu atom, resulting in a slightly distorted square-planar coordination. The S atoms are in a cis configuration. The crystal structure is stabilized by weak intermolecular C—H...Br hydrogen-bonding interactions.

Comprehensive RNA Analysis of the NF1 Gene in Classically Affected NF1 Affected Individuals Meeting NIH Criteria has High Sensitivity and Mutation Negative Testing is Reassuring in Isolated Cases With Pigmentary Features Only

Directory of Open Access Journals (Sweden)

D.G. Evans

2016-05-01

Interpretation: RNA analysis in individuals with presumed NF1 has high sensitivity and includes a small subset with DNET without an NF1 variant. Furthermore negative analysis for NF1/SPRED1 provides strong reassurance to children with ≥6 CAL that they are unlikely to have NF1.

Double-edged swords as cancer therapeutics: novel, orally active, small molecules simultaneously inhibit p53-MDM2 interaction and the NF-κB pathway.

Science.gov (United States)

Zhuang, Chunlin; Miao, Zhenyuan; Wu, Yuelin; Guo, Zizhao; Li, Jin; Yao, Jianzhong; Xing, Chengguo; Sheng, Chunquan; Zhang, Wannian

2014-02-13

Simultaneous inactivation of p53 and hyperactivation of nuclear factor-κB (NF-κB) is a common occurrence in human cancer. Currently, antitumor agents are being designed to selectively activate p53 or inhibit NF-κB. However, there is no concerted effort yet to deliberately design inhibitors that can simultaneously do both. This paper provided a proof-of-concept study that p53-MDM2 interaction and NF-κB pathway can be simultaneously targeted by a small-molecule inhibitor. A series of pyrrolo[3,4-c]pyrazole derivatives were rationally designed and synthesized as the first-in-class inhibitors of p53-MDM2 interaction and NF-κB pathway. Most of the compounds were identified to possess nanomolar p53-MDM2 inhibitory activity. Compounds 5q and 5s suppressed NF-κB activation through inhibition of IκBα phosphorylation and elevation of the cytoplasmic levels of p65 and phosphorylated IKKα/β. Biochemical assay for the kinases also supported the fact that pyrrolo[3,4-c]pyrazole compounds directly targeted the NF-κB pathway. In addition, four compounds (5j, 5q, 5s, and 5u) effectively inhibited tumor growth in the A549 xenograft model. Further pharmacokinetic study revealed that compound 5q exhibited excellent oral bioavailability (72.9%).

Neutron-scattering studies of the S=2 antiferromagnetic chain MnCl3(C10D8N2)

International Nuclear Information System (INIS)

Granroth, G.E.; Nagler, S.E.; Coldea, R.; Eccleston, R.S.; Ward, B.H.; Talham, D.R.; Meisel, M.W.

2002-01-01

Quasi-elastic and inelastic neutron scattering studies of the quasi-one-dimensional S=2 antiferromagnet MnCl 3 (C 10 D 8 N 2 ) are reported. The quasi-elastic measurements exhibit a broad peak at Q∼0.69 A -1 , which is consistent with short-range antiferromagnetic coupling between neighboring Mn 3+ ions. Inelastic experiments, at 150 mK and Q=0.70 A -1 , reveal decreased magnetic scattering at energies less than 0.2 meV when compared to similar studies at 20 K. These results provide microscopic evidence for the presence of a Haldane gap and are consistent with the bulk magnetization measurements of Granroth et al. (orig.)

Vinpocetine Ameliorates Acetic Acid-Induced Colitis by Inhibiting NF-κB Activation in Mice.

Science.gov (United States)

Colombo, Bárbara B; Fattori, Victor; Guazelli, Carla F S; Zaninelli, Tiago H; Carvalho, Thacyana T; Ferraz, Camila R; Bussmann, Allan J C; Ruiz-Miyazawa, Kenji W; Baracat, Marcela M; Casagrande, Rúbia; Verri, Waldiceu A

2018-04-10

The idiopathic inflammatory bowel diseases (IBD) comprise two types of chronic intestinal disorders: Crohn's disease and ulcerative colitis. Recruited neutrophils and macrophages contribute to intestinal tissue damage via production of ROS and NF-κB-dependent pro-inflammatory cytokines. The introduction of anti-TNF-α therapies in the treatment of IBD patients was a seminal advance. This therapy is often limited by a loss of efficacy due to the development of adaptive immune response, underscoring the need for novel therapies targeting similar pathways. Vinpocetine is a nootropic drug and in addition to its antioxidant effect, it is known to have anti-inflammatory and analgesic properties, partly by inhibition of NF-κB and downstream cytokines. Therefore, the present study evaluated the effect of the vinpocetine in a model of acid acetic-induced colitis in mice. Treatment with vinpocetine reduced edema, MPO activity, microscopic score and macroscopic damage, and visceral mechanical hyperalgesia. Vinpocetine prevented the reduction of colonic levels of GSH, ABTS radical scavenging ability, and normalized levels of anti-inflammatory cytokine IL-10. Moreover, vinpocetine reduced NF-κB activation and thereby NF-κB-dependent pro-inflammatory cytokines IL-1β, TNF-α, and IL-33 in the colon. Thus, we demonstrate for the first time that vinpocetine has anti-inflammatory, antioxidant, and analgesic effects in a model of acid acetic-induced colitis in mice and deserves further screening to address its suitability as an approach for the treatment of IBD.

Modulation of the NF-kappaB pathway by Bordetella pertussis filamentous hemagglutinin.

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Tzvia Abramson

Full Text Available Filamentous hemagglutinin (FHA is a cell-associated and secreted adhesin produced by Bordetella pertussis with pro-apoptotic and pro-inflammatory activity in host cells. Given the importance of the NF-kappaB transcription factor family in these host cell responses, we examined the effect of FHA on NF-kappaB activation in macrophages and bronchial epithelial cells, both of which are relevant cell types during natural infection.Exposure to FHA of primary human monocytes and transformed U-937 macrophages, but not BEAS-2B epithelial cells, resulted in early activation of the NF-kappaB pathway, as manifested by the degradation of cytosolic IkappaB alpha, by NF-kappaB DNA binding, and by the subsequent secretion of NF-kappaB-regulated inflammatory cytokines. However, exposure of macrophages and human monocytes to FHA for two hours or more resulted in the accumulation of cytosolic IkappaB alpha, and the failure of TNF-alpha to activate NF-kappaB. Proteasome activity was attenuated following exposure of cells to FHA for 2 hours, as was the nuclear translocation of RelA in BEAS-2B cells.These results reveal a complex temporal dynamic, and suggest that despite short term effects to the contrary, longer exposures of host cells to this secreted adhesin may block NF-kappaB activation, and perhaps lead to a compromised immune response to this bacterial pathogen.

A new nonsense mutation in the NF1 gene with neurofibromatosis-Noonan syndrome phenotype.

Science.gov (United States)

Yimenicioğlu, Sevgi; Yakut, Ayten; Karaer, Kadri; Zenker, Martin; Ekici, Arzu; Carman, Kürşat Bora

2012-12-01

Neurofibromatosis-Noonan syndrome is a rare autosomal dominant disorder which combines neurofibromatosis type 1 (NF1) features with Noonan syndrome. NF1 gene mutations are reported in the majority of these patients. Sequence analysis of the established genes for Noonan syndrome revealed no mutation; a heterozygous NF1 point mutation c.7549C>T in exon 51, creating a premature stop codon (p.R2517X), had been demonstrated. Neurofibromatosis-Noonan syndrome recently has been considered a subtype of NF1 and caused by different NF1 mutations. We report the case of a 14-year-old boy with neurofibromatosis type 1 with Noonan-like features, who complained of headache with triventricular hydrocephaly and a heterozygous NF1 point mutation c.7549C>T in exon 51.

Overexpression of StNF-YB3.1 reduces photosynthetic capacity and tuber production, and promotes ABA-mediated stomatal closure in potato (Solanum tuberosum L.).

Science.gov (United States)

Xuanyuan, Guochao; Lu, Congming; Zhang, Ruofang; Jiang, Jiming

2017-08-01

Nuclear factor Y (NF-Y) is one of the most ubiquitous transcription factors (TFs), comprising NF-YA, NF-YB and NF-YC subunits, and has been identified and reported in various aspects of development for plants and animals. In this work, StNF-YB3.1, a putative potato NF-YB subunit encoding gene, was isolated from Solanum tuberosum by rapid amplification of cDNA ends (RACE). Overexpression of StNF-YB3.1 in potato (cv. Atlantic) resulted in accelerated onset of flowering, and significant increase in leaf chlorophyll content in field trials. However, transgenic potato plants overexpressing StNF-YB3.1 (OEYB3.1) showed significant decreases in photosynthetic rate and stomatal conductance both at tuber initiation and bulking stages. OEYB3.1 lines were associated with significantly fewer tuber numbers and yield reduction. Guard cell size and stomatal density were not changed in OEYB3.1 plants, whereas ABA-mediated stomatal closure was accelerated compared to that of wild type plants because of the up-regulation of genes for ABA signaling, such as StCPK10-like, StSnRK2.6/OST1-like, StSnRK2.7-like and StSLAC1-like. We speculate that the acceleration of stomatal closure was a possible reason for the significantly decreased stomatal conductance and photosynthetic rate. Copyright © 2017 Elsevier B.V. All rights reserved.

Genome mining of Streptomyces scabrisporus NF3 reveals symbiotic features including genes related to plant interactions

Science.gov (United States)

Rodríguez-Luna, Stefany Daniela; Cruz Vázquez, Angélica Patricia; Jiménez Suárez, Verónica; Rodríguez-Sanoja, Romina; Alvarez-Buylla, Elena R.; Sánchez, Sergio

2018-01-01

Endophytic bacteria are wide-spread and associated with plant physiological benefits, yet their genomes and secondary metabolites remain largely unidentified. In this study, we explored the genome of the endophyte Streptomyces scabrisporus NF3 for discovery of potential novel molecules as well as genes and metabolites involved in host interactions. The complete genomes of seven Streptomyces and three other more distantly related bacteria were used to define the functional landscape of this unique microbe. The S. scabrisporus NF3 genome is larger than the average Streptomyces genome and not structured for an obligate endosymbiotic lifestyle; this and the fact that can grow in R2YE media implies that it could include a soil-living stage. The genome displays an enrichment of genes associated with amino acid production, protein secretion, secondary metabolite and antioxidants production and xenobiotic degradation, indicating that S. scabrisporus NF3 could contribute to the metabolic enrichment of soil microbial communities and of its hosts. Importantly, besides its metabolic advantages, the genome showed evidence for differential functional specificity and diversification of plant interaction molecules, including genes for the production of plant hormones, stress resistance molecules, chitinases, antibiotics and siderophores. Given the diversity of S. scabrisporus mechanisms for host upkeep, we propose that these strategies were necessary for its adaptation to plant hosts and to face changes in environmental conditions. PMID:29447216

Genome mining of Streptomyces scabrisporus NF3 reveals symbiotic features including genes related to plant interactions.

Directory of Open Access Journals (Sweden)

Corina Diana Ceapă

Full Text Available Endophytic bacteria are wide-spread and associated with plant physiological benefits, yet their genomes and secondary metabolites remain largely unidentified. In this study, we explored the genome of the endophyte Streptomyces scabrisporus NF3 for discovery of potential novel molecules as well as genes and metabolites involved in host interactions. The complete genomes of seven Streptomyces and three other more distantly related bacteria were used to define the functional landscape of this unique microbe. The S. scabrisporus NF3 genome is larger than the average Streptomyces genome and not structured for an obligate endosymbiotic lifestyle; this and the fact that can grow in R2YE media implies that it could include a soil-living stage. The genome displays an enrichment of genes associated with amino acid production, protein secretion, secondary metabolite and antioxidants production and xenobiotic degradation, indicating that S. scabrisporus NF3 could contribute to the metabolic enrichment of soil microbial communities and of its hosts. Importantly, besides its metabolic advantages, the genome showed evidence for differential functional specificity and diversification of plant interaction molecules, including genes for the production of plant hormones, stress resistance molecules, chitinases, antibiotics and siderophores. Given the diversity of S. scabrisporus mechanisms for host upkeep, we propose that these strategies were necessary for its adaptation to plant hosts and to face changes in environmental conditions.

Overexpression of the transcription factor NF-YC9 confers abscisic acid hypersensitivity in Arabidopsis.

Science.gov (United States)

Bi, Chao; Ma, Yu; Wang, Xiao-Fang; Zhang, Da-Peng

2017-11-01

Nuclear factor Y (NF-Y) family proteins are involved in many developmental processes and responses to environmental cues in plants, but whether and how they regulate phytohormone abscisic acid (ABA) signaling need further studies. In the present study, we showed that over-expression of the NF-YC9 gene confers ABA hypersensitivity in both the early seedling growth and stomatal response, while down-regulation of NF-YC9 does not affect ABA response in these processes. We also showed that over-expression of the NF-YC9 gene confers salt and osmotic hypersensitivity in early seedling growth, which is likely to be directly associated with the ABA hypersensitivity. Further, we observed that NF-YC9 physically interacts with the ABA-responsive bZIP transcription factor ABA-INSENSITIVE5 (ABI5), and facilitates the function of ABI5 to bind and activate the promoter of a target gene EM6. Additionally, NF-YC9 up-regulates expression of the ABI5 gene in response to ABA. These findings show that NF-YC9 may be involved in ABA signaling as a positive regulator and likely functions redundantly together with other NF-YC members, and support the model that the NF-YC9 mediates ABA signaling via targeting to and aiding the ABA-responsive transcription factors such as ABI5.

Semipolar MOVPE AlGaN on (10 anti 10) m-plane sapphire; MOVPE von semipolarem AlGaN auf (10 anti 10) m-plane Saphir

Energy Technology Data Exchange (ETDEWEB)

Mehnke, Frank; Stellmach, Joachim; Frentrup, Martin; Kusch, Gunnar; Wernicke, Tim; Pristovsek, Markus; Kneissl, Michael [Technische Universitaet Berlin, Institut fuer Festkoerperphysik, Hardenbergstr. 36, 10623 Berlin (Germany)

2011-07-01

The energy gap of AlGaN varies between 3.4 eV and 6.2 eV and allows light emitting diodes (LED) in the ultraviolet spectral region. The authors studied semipolar (11 anti 22) AlGaN layers that were deposited on (10 anti 10) m-plane sapphire using MOVPE (metalorganic vapor phase epitaxy) without nucleation layer with a substrate temperature below 1100 C in H2 atmosphere. The layers are preferably (11 anti 22) oriented. The sample show a surface roughness between 15 and 2 nm. The Al content of the smoothest samples is about 60% determined by transmission experiments. Below 60% Al content a triangular morphology was observed, the opening angle increased with decreasing Al content. The absorption edge was 0.05 eV (GaN) to 0.35 eV (AlN) below the band edge of (0001) oriented AlGaN layers. Further investigations of semipolar AlGaN layers to study the applicability for UV LEDs are under preparation.

N S Vasanthi

Indian Academy of Sciences (India)

Home; Journals; Resonance – Journal of Science Education. N S Vasanthi. Articles written in Resonance – Journal of Science Education. Volume 11 Issue 11 November 2006 pp 48-55 General Article. Cancer Vaccines: The New Fight Against Cancer · N S Vasanthi · More Details Fulltext PDF ...

Soyasaponins can blunt inflammation by inhibiting the reactive oxygen species-mediated activation of PI3K/Akt/NF-kB pathway.

Science.gov (United States)

Zha, Longying; Chen, Jiading; Sun, Suxia; Mao, Limei; Chu, Xinwei; Deng, Hong; Cai, Junwei; Li, Xuefeng; Liu, Zhenqi; Cao, Wenhong

2014-01-01

We and others have recently shown that soyasaponins abundant in soybeans can decrease inflammation by suppressing the nuclear factor kappa B (NF-kB)-mediated inflammation. However, the exact molecular mechanisms by which soyasaponins inhibit the NF-kB pathway have not been established. In this study in macrophages, soyasaponins (A1, A2 and I) inhibited the lipopolysaccharide (LPS)-induced release of inflammatory marker prostaglandin E2 (PGE2) to a similar extent as the NF-kB inhibitor (BAY117082). Soyasaponins (A1, A2 and I) also suppressed the LPS-induced expression of cyclooxygenase 2 (COX-2), another inflammatory marker, in a dose-dependent manner by inhibiting NF-kB activation. In defining the associated mechanisms, we found that soyasaponins (A1, A2 and I) blunted the LPS-induced IKKα/β phosphorylation, IkB phosphorylation and degradation, and NF-kB p65 phosphorylation and nuclear translocation. In studying the upstream targets of soyasaponins on the NF-kB pathway, we found that soyasaponins (A1, A2 and I) suppressed the LPS-induced activation of PI3K/Akt similarly as the PI3K inhibitor LY294002, which alone blocked the LPS-induced activation of NF-kB. Additionally, soyasaponins (A1, A2 and I) reduced the LPS-induced production of reactive oxygen species (ROS) to the same extent as the anti-oxidant N-acetyl-L-cysteine, which alone inhibited the LPS-induced phosphorylation of Akt, IKKα/β, IkBα, and p65, transactivity of NF-kB, PGE2 production, and malondialdehyde production. Finally, our results show that soyasaponins (A1, A2 and I) elevated SOD activity and the GSH/GSSG ratio. Together, these results show that soyasaponins (A1, A2 and I) can blunt inflammation by inhibiting the ROS-mediated activation of the PI3K/Akt/NF-kB pathway.

A 10 nN resolution thrust-stand for micro-propulsion devices

Energy Technology Data Exchange (ETDEWEB)

Chakraborty, Subha; Courtney, Daniel G.; Shea, Herbert, E-mail: herbert.shea@epfl.ch [Microsystems for Space Technologies Laboratory (LMTS), Ecole Polytechnique Federale de Lausanne (EPFL), Neuchatel (Switzerland)

2015-11-15

We report on the development of a nano-Newton thrust-stand that can measure up to 100 μN thrust from different types of microthrusters with 10 nN resolution. The compact thrust-stand measures the impingement force of the particles emitted from a microthruster onto a suspended plate of size 45 mm × 45 mm and with a natural frequency over 50 Hz. Using a homodyne (lock-in) readout provides strong immunity to facility vibrations, which historically has been a major challenge for nano-Newton thrust-stands. A cold-gas thruster generating up to 50 μN thrust in air was first used to validate the thrust-stand. Better than 10 nN resolution and a minimum detectable thrust of 10 nN were achieved. Thrust from a miniature electrospray propulsion system generating up to 3 μN of thrust was measured with our thrust-stand in vacuum, and the thrust was compared with that computed from beam diagnostics, obtaining agreement within 50 nN to 150 nN. The 10 nN resolution obtained from this thrust-stand matches that from state-of-the-art nano-Newton thrust-stands, which measure thrust directly from the thruster by mounting it on a moving arm (but whose natural frequency is well below 1 Hz). The thrust-stand is the first of its kind to demonstrate less than 3 μN resolution by measuring the impingement force, making it capable of measuring thrust from different types of microthrusters, with the potential of easy upscaling for thrust measurement at much higher levels, simply by replacing the force sensor with other force sensors.

Constitutive overexpression of the TaNF-YB4 gene in transgenic wheat significantly improves grain yield.

Science.gov (United States)

Yadav, Dinesh; Shavrukov, Yuri; Bazanova, Natalia; Chirkova, Larissa; Borisjuk, Nikolai; Kovalchuk, Nataliya; Ismagul, Ainur; Parent, Boris; Langridge, Peter; Hrmova, Maria; Lopato, Sergiy

2015-11-01

Heterotrimeric nuclear factors Y (NF-Ys) are involved in regulation of various vital functions in all eukaryotic organisms. Although a number of NF-Y subunits have been characterized in model plants, only a few have been functionally evaluated in crops. In this work, a number of genes encoding NF-YB and NF-YC subunits were isolated from drought-tolerant wheat (Triticum aestivum L. cv. RAC875), and the impact of the overexpression of TaNF-YB4 in the Australian wheat cultivar Gladius was investigated. TaNF-YB4 was isolated as a result of two consecutive yeast two-hybrid (Y2H) screens, where ZmNF-YB2a was used as a starting bait. A new NF-YC subunit, designated TaNF-YC15, was isolated in the first Y2H screen and used as bait in a second screen, which identified two wheat NF-YB subunits, TaNF-YB2 and TaNF-YB4. Three-dimensional modelling of a TaNF-YB2/TaNF-YC15 dimer revealed structural determinants that may underlie interaction selectivity. The TaNF-YB4 gene was placed under the control of the strong constitutive polyubiquitin promoter from maize and introduced into wheat by biolistic bombardment. The growth and yield components of several independent transgenic lines with up-regulated levels of TaNF-YB4 were evaluated under well-watered conditions (T1-T3 generations) and under mild drought (T2 generation). Analysis of T2 plants was performed in large deep containers in conditions close to field trials. Under optimal watering conditions, transgenic wheat plants produced significantly more spikes but other yield components did not change. This resulted in a 20-30% increased grain yield compared with untransformed control plants. Under water-limited conditions transgenic lines maintained parity in yield performance. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Motivations for AdS/QCD from 10D supergravity solutions

International Nuclear Information System (INIS)

De Paula, Wayne

2016-01-01

We discuss some attempts for the construction of gravity duals of QCD-like theories. It is analysed some properties of solutions of 10D Type IIB supergravity theory that attempt to be dual to N= 1 gauge theories, in particular the solutions that belong to Papadoulos-Tseytlin ansatz. We argue that one could obtain 5D effective theories from 10d solutions and it motivates the use of phenomenological AdS/QCD models. (paper)

MicroRNAs control transcription factor NF-kB (p65) expression in human ovarian cells.

Science.gov (United States)

Sirotkin, Alexander V; Alexa, Richard; Kišová, Gabriela; Harrath, Abdel Halim; Alwasel, Saleh; Ovcharenko, Dmitriy; Mlynček, Miloš

2015-05-01

MicroRNAs (miRNAs) are known to influence ovarian cell proliferation, apoptosis and hormone release, but it remains unknown whether miRNAs affect ovarian functions via transcription factors. We examined the effect of miRNAs on nuclear factor-κappaB (NF-kB) (p65) expression in human ovarian luteinized granulosa cells. We transfected cultured primary human ovarian luteinized granulosa cells with 80 different constructs encoding human pre-miRNAs and then evaluated NF-kB (p65) expression (percentage of cells containing p65) by immunocytochemistry. We found that 21 of the constructs stimulated NF-kB (p65) expression and 18 of the constructs inhibited NF-kB (p65) expression. This is the first direct demonstration that miRNAs affect NF-kB (p65) expression and the first genome-scale miRNA screen to identify upregulation and downregulation of NF-kB accumulation by miRNAs in the ovary. Novel miRNAs that affect the NF-kB signalling pathway could be useful for the control of NF-kB-dependent reproductive processes and the treatment of NF-kB-dependent reproductive disorders.

Imaging MOSS tomographic system for H-1NF

International Nuclear Information System (INIS)

Glass, F.; Howard, J.

1999-01-01

A tomographic diagnostic utilising the Modulated Optical Solid-State spectrometer (MOSS) is planned for the H-1NF stellarator at the ANU. It is designed to create two-dimensional temperature or velocity maps of a poloidal cross-section of the high temperature plasma of H-1NF. The introduction of the MOSS spectrometers has enabled the development of several diagnostics to be used on the H-1NF stellerator. The MOSS spectrometer allows calculations of the plasma temperature and bulk velocity based on a line-integrated measurement of light emitted from electronic transitions within the plasma. A tomographic system utilising a rotatable multi-view ring apparatus and spatial multiplexing through a MOSS spectrometer is currently being developed. The ring apparatus is placed inside the H-1NF vessel and encircles the plasma. Multiple line-of-sight views collect light through a poloidal cross-section of the plasma and the emitted light is coupled into large core optical fibres. The transmitted light, via the optical fibre bundle, is then imaged through a large aperture MOSS spectrometer and onto another optical fibre array. Each fibre is then fed into a photomultiplier tube for signal detection. Characterisation of the properties of the lithium niobate (LiNbO 3 ) crystal used for modulation in the MOSS spectrometer is being undertaken to account for ray divergence in the imaging system. Tomographic techniques enable the construction of a temperature or velocity map of the poloidal cross-section. Rotating the ring apparatus to a new viewing position for the next pulse of plasma should allow an accurate picture to be built up based on the reproducibility of the plasma pulses. It is expected that initial testing of the system will begin in May when H-1NF begins operations at 0.5 Telsa field strength

Effects of Age and Sedentary Lifestyle on Skeletal Muscle NF-κB Signaling in Men

Science.gov (United States)

Buford, Thomas W.; Cooke, Matthew B.; Manini, Todd M.; Leeuwenburgh, Christiaan

2010-01-01

Background. Nuclear factor kappa B (NF-κB) is a critical signaling molecule of disuse-induced skeletal muscle atrophy. However, few studies have carefully investigated whether similar pathways are modulated with physical activity and age. Methods. The present study examined lean mass, maximal force production, and skeletal muscle NF-κB signaling in 41 men categorized as sedentary (OS, N = 13, 63.85 ± 6.59 year), physically active (OA, N = 14, 60.71 ± 5.54 year), or young and sedentary (YS, N = 14, 21.35 ± 3.84 year). Muscle tissue from the vastus lateralis was assayed for messenger RNA (mRNA) expression of the β subunit of IkB kinase (IKKβ), cytosolic protein content of phosphorylated inhibitor of kappa B alpha (pIKBα), and nuclear content of NF-κB subunits p50 and p65. Results. When compared with YS, OS demonstrated age-related muscle atrophy and reduced isokinetic knee extension torque. Physical activity in older individuals preserved maximal isokinetic knee extension torque. OS muscle contained 50% more pIKBα than OA and 61% more pIKBα than YS. Furthermore, nuclear p65 was significantly elevated in OS compared with YS. OS muscle did not differ from either of the other two groups for nuclear p50 or for mRNA expression of IKKβ. Conclusions. These results indicate that skeletal muscle content of nuclear-bound p65 is elevated by age in humans. The elevation in nuclear-bound p65 appears to be at least partially due to significant increases in pIKBα. A sedentary lifestyle appears to play some role in increased IKBα; however, further research is needed to identify downstream effects of this increase. PMID:20045871

NF-κB activation impairs somatic cell reprogramming in ageing.

Science.gov (United States)

Soria-Valles, Clara; Osorio, Fernando G; Gutiérrez-Fernández, Ana; De Los Angeles, Alejandro; Bueno, Clara; Menéndez, Pablo; Martín-Subero, José I; Daley, George Q; Freije, José M P; López-Otín, Carlos

2015-08-01

Ageing constitutes a critical impediment to somatic cell reprogramming. We have explored the regulatory mechanisms that constitute age-associated barriers, through derivation of induced pluripotent stem cells (iPSCs) from individuals with premature or physiological ageing. We demonstrate that NF-κB activation blocks the generation of iPSCs in ageing. We also show that NF-κB repression occurs during cell reprogramming towards a pluripotent state. Conversely, ageing-associated NF-κB hyperactivation impairs the generation of iPSCs by eliciting the reprogramming repressor DOT1L, which reinforces senescence signals and downregulates pluripotency genes. Genetic and pharmacological NF-κB inhibitory strategies significantly increase the reprogramming efficiency of fibroblasts from Néstor-Guillermo progeria syndrome and Hutchinson-Gilford progeria syndrome patients, as well as from normal aged donors. Finally, we demonstrate that DOT1L inhibition in vivo extends lifespan and ameliorates the accelerated ageing phenotype of progeroid mice, supporting the interest of studying age-associated molecular impairments to identify targets of rejuvenation strategies.

Resveratrol reduces senescence-associated secretory phenotype by SIRT1/NF-κB pathway in gut of the annual fish Nothobranchius guentheri.

Science.gov (United States)

Liu, Shan; Zheng, Zhaodi; Ji, Shuhua; Liu, Tingting; Hou, Yanhan; Li, Shasha; Li, Guorong

2018-06-13

Senescent cells display a senescence-associated secretory phenotype (SASP), which contributes to aging. Resveratrol, an activator of SIRT1, has anti-aging, anti-inflammatory, anti-oxidant, anti-free radical and other pharmacological effects. The genus of the annual fish Nothobranchius has become an emerging animal model for studying aging. However, the underlying mechanism for resveratrol to delay aging by SASP regulation has not been elucidated in vertebrates. In this study, the annual fish N. guentheri were fed with resveratrol for long-term treatment. The results showed that resveratrol reversed intensive senescence-associated β-galactosidase activity with aging process, down-regulated levels of SASP-associated proinflammatory cytokines IL-8 and TNFα, and up-regulated expression of anti-inflammatory cytokine IL-10 in gut of the fish. Resveratrol increased SIRT1 expression, and inhibited NF-κB by decreasing RelA/p65, Ac-RelA/p65 and p-IκBα levels and by increasing the interaction between SIRT1 and RelA/p65. Moreover, resveratrol reversed the decline of intestinal epithelial cells (IECs) and intestinal stem cells (ISCs) caused by aging in gut of the fish. Together, our results implied that resveratrol inhibited SASP through SIRT1/NF-κB signaling pathway and delayed aging of the annual fish N. guentheri. Copyright © 2018. Published by Elsevier Ltd.

Single Hind Limb Burn Injury to Mice Alters NF Kappa B (NF-κB) Expression and [18F] 2-Fluoro-2-Deoxy-d-Glucose (FDG) Uptake

OpenAIRE

Carter, Edward A.; Hamrahi, Victoria; Paul, Kasie; Bonab, Ali A.; Jung, Walter; Tompkins, Ronald G.; Fischman, Alan J.

2014-01-01

Burn trauma to the extremities can produce marked systemic effects in mice1, 6, 7. Burn injury to the dorsal surface of mice is also associated with changes in glucose metabolism (18FDG uptake) by brown adipose tissue (BAT) and NF-κB activity in a number of tissues including skeletal muscle. This study examined the effect of a single hindlimb burn in mice on 18FDG uptake by in vivo, NF-κB activity in vivo, and blood flow determined by laser Doppler techniques. Male mice NF-κB luciferase repor...

Functional Analysis of Drosophila NF1

National Research Council Canada - National Science Library

Bernards, Andre

2005-01-01

...) for Ras, yet homozygous loss of a highly conserved Drosophila NF1 ortholog results in several phenotypes that are insensitive to manipulating Ras signal transduction, but rescued by increasing...

Spontaneous NF-κB activation by autocrine TNFα signaling: a computational analysis.

Directory of Open Access Journals (Sweden)

Jakub Pękalski

Full Text Available NF-κB is a key transcription factor that regulates innate immune response. Its activity is tightly controlled by numerous feedback loops, including two negative loops mediated by NF-κB inducible inhibitors, IκBα and A20, which assure oscillatory responses, and by positive feedback loops arising due to the paracrine and autocrine regulation via TNFα, IL-1 and other cytokines. We study the NF-κB system of interlinked negative and positive feedback loops, combining bifurcation analysis of the deterministic approximation with stochastic numerical modeling. Positive feedback assures the existence of limit cycle oscillations in unstimulated wild-type cells and introduces bistability in A20-deficient cells. We demonstrated that cells of significant autocrine potential, i.e., cells characterized by high secretion of TNFα and its receptor TNFR1, may exhibit sustained cytoplasmic-nuclear NF-κB oscillations which start spontaneously due to stochastic fluctuations. In A20-deficient cells even a small TNFα expression rate qualitatively influences system kinetics, leading to long-lasting NF-κB activation in response to a short-pulsed TNFα stimulation. As a consequence, cells with impaired A20 expression or increased TNFα secretion rate are expected to have elevated NF-κB activity even in the absence of stimulation. This may lead to chronic inflammation and promote cancer due to the persistent activation of antiapoptotic genes induced by NF-κB. There is growing evidence that A20 mutations correlate with several types of lymphomas and elevated TNFα secretion is characteristic of many cancers. Interestingly, A20 loss or dysfunction also leaves the organism vulnerable to septic shock and massive apoptosis triggered by the uncontrolled TNFα secretion, which at high levels overcomes the antiapoptotic action of NF-κB. It is thus tempting to speculate that some cancers of deregulated NF-κB signaling may be prone to the pathogen-induced apoptosis.

TLR4 activates NF-{kappa}B in human ovarian granulosa tumor cells

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Woods, Dori C., E-mail: dwoods2@partners.org [Vincent Center for Reproductive Biology, Vincent Obstetrics and Gynecology Service, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02114 (United States); White, Yvonne A.R. [Vincent Center for Reproductive Biology, Vincent Obstetrics and Gynecology Service, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02114 (United States); Dau, Caroline [University of California, San Francisco, School of Dentistry, San Francisco, CA 94143 (United States); Johnson, A.L. [Center for Reproductive Biology and Health, The Pennsylvania State University, University Park, PA 16802 (United States)

2011-06-17

Highlights: {yields} TLR4 is expressed in human ovarian granulosa tumor cells. {yields} Acting through TLR4, LPS and HSP60 induce a NF{kappa}B signaling cascade in human ovarian granulosa tumor cells. {yields} NF{kappa}B activation or inhibition did not alter chemosensitivity to TRAIL or cisplatin. -- Abstract: Previous studies have demonstrated expression of Toll-like receptors (TLRs) in the surface epithelium of normal ovaries (OSE) and in epithelial ovarian tumors. Most notably, OSE-derived cancers express TLR4, which activates the nuclear factor-kappa B (NF-{kappa}B) signaling cascade as a mediator of inflammatory response. Currently, there is considerable interest in elucidating the role of TLR-mediated signaling in cancers. Nevertheless, the expression of TLRs in granulosa cell tumors (GCTs) of the ovary, and the extent to which GCT expression of TLRs may influence cell-signaling pathways and/or modulate the efficacy of chemotherapeutics, has yet to be determined. In the present study, human GCT lines (COV434 and KGN) were utilized to evaluate expression of functional TLR4. TLR4 is expressed in GCT cell lines and ligation of TLR4 with bacterial lipopolysaccharide (LPS) led to I{kappa}B degradation and activation of NF-{kappa}B. NF-{kappa}B activation was confirmed by nuclear localization of NF-{kappa}B p65 following treatment with LPS and the naturally occurring ligand, HSP60. Notably, immunoneutralization of TLR4 blocked nuclear localization, and inhibition of NF-{kappa}B signaling attenuated LPS-induced TNF{alpha} plus increased doubling time in both cell lines. Contradictory to reports using human OSE cell lines, inhibition of NF-{kappa}B signaling failed to sensitize GCT lines to TRAIL or cisplatin. In summary, findings herein are the first to demonstrate a functional TLR-signaling pathway specifically in GCTs, and indicate that in contrast to OSE-derived cancers, inhibition of NF-{kappa}B does not sensitize GCTs to TRAIL or cisplatin.

Nuclear factor kB (NF-KB): signalosoma and its importance in cancer and inflammatories diseases

International Nuclear Information System (INIS)

Echeverri, Nancy P; Mockus, Ismena S

2008-01-01

The nuclear factor B (NF- B) is a dimer conformed by Rel family. NF- B is found in cytoplasm bound to inhibitor proteins (I B). I B are phosphorylated by different kinases who are part of signalosome as IeB kinases (IKK , IKK and NF- B essential modulator or NEMO), the mitogenic activated protein kinase (MAPK or p38) and NF-eB inducer kinase (NIK). These kinases are activated by different cytokines and ultraviolet light, I B phosphorylated induce their ubiquitination and proteosome degradation subsequently NF- B release and nucleus translocation. Nowadays, the NF- B activation by oxidative stress, genotoxic stress and DNA damage pathways. In contrast with the classical pathway, in this pathway there are a SUMOilation and nuclear translocation of NEMO. In nucleus NEMO interact with ataxia telangiectasia muted which is activated by chromatin changes and DNA damage. The complex ATM/NEMO is later translocated to cytoplasm where IKK is phosphorylated by ATM bringing to ubiquitination and thus NF- B releasing which is translocated to nucleus. NF- B induces survival rising antioxidants enzymes as superoxide dismutase, catalase and glutathione. These enzymes act in the control of oxidative species levels in the cell. NF- B over expression is related with inflammation and cancer. Nowadays, is development a pharmacological search which can act inhibiting NF- B signalosome molecules, not only to inflammatory disease whereas to radiotherapy and chemotherapy cancer resistance.

Reaction Characteristics of Andrographolide and its Analogue AL-1 with GSH, as a Simple Chemical Simulation of NF-κB Inhibition

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Yuqiang Wang

2012-01-01

Full Text Available 14-α-Lipoic acid-3,19-dihydroxyandrographolide (AL-1, 2 is an analogue of andrographolide (Andro, 1 coupled to α-lipoic acid (LA, 4. AL-1 was at least 10-fold more potent than the natural parent compound Andro in inhibiting nuclear factor (NF-κB activation in RIN-m cells. In the present study, glutathione (GSH, 3 was used as a simple chemical model molecule of NF-κB with cysteine 62. The characteristics of the reaction between AL-1 or Andro and GSH were investigated to trace some possible elucidation for the inhibitive mechanism and stronger inhibition of AL-1 to NF-κB activation. The results showed that the main reaction products of AL-1 and Andro were identical, sulfhydryl adduct and amino adduct. AL-1 reacted much faster than Andro with GSH. The product yield of AL-1 was much higher than that of Andro. It was speculated that AL-1 might inhibit NF-κB by the same mechanism as Andro. And the faster reaction rate and higher yield may account for the stronger NF-κB inhibition of AL-1 when compared with Andro.

4d N=1 from 6d (1,0)

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Razamat, Shlomo S. [Physics Department, Technion,Haifa, 32000 (Israel); Vafa, Cumrun [Jefferson Physical Laboratory, Harvard University,Cambridge, MA 02138 (United States); Zafrir, Gabi [Physics Department, Technion,Haifa, 32000 (Israel); Kavli IPMU (WPI), UTIAS, the University of Tokyo,Kashiwa, Chiba 277-8583 (Japan)

2017-04-11

We study the geometry of 4d N=1 SCFT’s arising from compactification of 6d (1,0) SCFT’s on a Riemann surface. We show that the conformal manifold of the resulting theory is characterized, in addition to moduli of complex structure of the Riemann surface, by the choice of a connection for a vector bundle on the surface arising from flavor symmetries in 6d. We exemplify this by considering the case of 4d N=1 SCFT’s arising from M5 branes probing ℤ{sub k} singularity compactified on a Riemann surface. In particular, we study in detail the four dimensional theories arising in the case of two M5 branes on ℤ{sub 2} singularity. We compute the conformal anomalies and indices of such theories in 4d and find that they are consistent with expectations based on anomaly and the moduli structure derived from the 6 dimensional perspective.

Thiazolidinediones inhibit airway smooth muscle release of the chemokine CXCL10: in vitro comparison with current asthma therapies.

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Seidel, Petra; Alkhouri, Hatem; Lalor, Daniel J; Burgess, Janette K; Armour, Carol L; Hughes, J Margaret

2012-10-04

Activated mast cells are present within airway smooth muscle (ASM) bundles in eosinophilic asthma. ASM production of the chemokine CXCL10 plays a role in their recruitment. Thus the effects of glucocorticoids (fluticasone, budesonide), long-acting β2-agonists (salmeterol, formoterol) and thiazolidinediones (ciglitazone, rosiglitazone) on CXCL10 production by ASM cells (ASMC) from people with and without asthma were investigated in vitro. Confluent serum-deprived cells were treated with the agents before and during cytokine stimulation for 0-24 h. CXCL10 protein/mRNA, IκB-α levels and p65 activity were measured using ELISA, RT PCR, immunoblotting and p65 activity assays respectively. Data were analysed using ANOVA followed by Fisher's post-hoc test. Fluticasone and/or salmeterol at 1 and 100 nM inhibited CXCL10 release induced by IL-1β and TNF-α, but not IFNγ or all three cytokines (cytomix). The latter was also not affected by budesonide and formoterol. In asthmatic ASMC low salmeterol, but not formoterol, concentrations increased cytomix-induced CXCL10 release and at 0.01 nM enhanced NF-κB activity. Salmeterol 0.1 nM together with fluticasone 0.1 and 10 nM still increased CXCL10 release. The thiazolidinediones ciglitazone and rosiglitazone (at 25 and 100 μM) inhibited cytomix-induced CXCL10 release but these inhibitory effects were not prevented by the PPAR-g antagonist GW9662. Ciglitazone did not affect early NF-κB activity and CXCL10 mRNA production. Thus the thiazolidinediones inhibited asthmatic ASMC CXCL10 release under conditions when common asthma therapies were ineffective or enhanced it. They may provide an alternative strategy to reduce mast cell-ASM interactions and restore normal airway physiology in asthma.

In silico identification of NF-kappaB-regulated genes in pancreatic beta-cells

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Eizirik Decio L

2007-02-01

Full Text Available Abstract Background Pancreatic beta-cells are the target of an autoimmune attack in type 1 diabetes mellitus (T1DM. This is mediated in part by cytokines, such as interleukin (IL-1β and interferon (IFN-γ. These cytokines modify the expression of hundreds of genes, leading to beta-cell dysfunction and death by apoptosis. Several of these cytokine-induced genes are potentially regulated by the IL-1β-activated transcription factor (TF nuclear factor (NF-κB, and previous studies by our group have shown that cytokine-induced NF-κB activation is pro-apoptotic in beta-cells. To identify NF-κB-regulated gene networks in beta-cells we presently used a discriminant analysis-based approach to predict NF-κB responding genes on the basis of putative regulatory elements. Results The performance of linear and quadratic discriminant analysis (LDA, QDA in identifying NF-κB-responding genes was examined on a dataset of 240 positive and negative examples of NF-κB regulation, using stratified cross-validation with an internal leave-one-out cross-validation (LOOCV loop for automated feature selection and noise reduction. LDA performed slightly better than QDA, achieving 61% sensitivity, 91% specificity and 87% positive predictive value, and allowing the identification of 231, 251 and 580 NF-κB putative target genes in insulin-producing INS-1E cells, primary rat beta-cells and human pancreatic islets, respectively. Predicted NF-κB targets had a significant enrichment in genes regulated by cytokines (IL-1β or IL-1β + IFN-γ and double stranded RNA (dsRNA, as compared to genes not regulated by these NF-κB-dependent stimuli. We increased the confidence of the predictions by selecting only evolutionary stable genes, i.e. genes with homologs predicted as NF-κB targets in rat, mouse, human and chimpanzee. Conclusion The present in silico analysis allowed us to identify novel regulatory targets of NF-κB using a supervised classification method based on

Commensal-induced regulatory T cells mediate protection against pathogen-stimulated NF-kappaB activation.

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Caitlin O'Mahony

Full Text Available Host defence against infection requires a range of innate and adaptive immune responses that may lead to tissue damage. Such immune-mediated pathologies can be controlled with appropriate T regulatory (Treg activity. The aim of the present study was to determine the influence of gut microbiota composition on Treg cellular activity and NF-kappaB activation associated with infection. Mice consumed the commensal microbe Bifidobacterium infantis 35624 followed by infection with Salmonella typhimurium or injection with LPS. In vivo NF-kappaB activation was quantified using biophotonic imaging. CD4+CD25+Foxp3+ T cell phenotypes and cytokine levels were assessed using flow cytometry while CD4+ T cells were isolated using magnetic beads for adoptive transfer to naïve animals. In vivo imaging revealed profound inhibition of infection and LPS induced NF-kappaB activity that preceded a reduction in S. typhimurium numbers and murine sickness behaviour scores in B. infantis-fed mice. In addition, pro-inflammatory cytokine secretion, T cell proliferation, and dendritic cell co-stimulatory molecule expression were significantly reduced. In contrast, CD4+CD25+Foxp3+ T cell numbers were significantly increased in the mucosa and spleen of mice fed B. infantis. Adoptive transfer of CD4+CD25+ T cells transferred the NF-kappaB inhibitory activity. Consumption of a single commensal micro-organism drives the generation and function of Treg cells which control excessive NF-kappaB activation in vivo. These cellular interactions provide the basis for a more complete understanding of the commensal-host-pathogen trilogue that contribute to host homeostatic mechanisms underpinning protection against aberrant activation of the innate immune system in response to a translocating pathogen or systemic LPS.

Splenectomy following MCAO inhibits the TLR4-NF-κB signaling pathway and protects the brain from neurodegeneration in rats.

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Belinga, Victor Fabrice; Wu, Guan-Jin; Yan, Fu-Ling; Limbenga, Erica Audrey

2016-04-15

The Toll-like receptor 4(TLR4)/nuclear factor kappa B NF-κB inflammatory pathway contributes to secondary inflammation in many diseases including stroke. Moreover, the neuroprotective effect of splenectomy in stroke is supported by a vast body of experimental evidence. Nevertheless, the underlying mechanism(s) by which splenectomy enhance neuroprotection in stroke is still poorly understood. Our study aimed to investigate whether post-ischemic splenectomy modulate the TLR4/NF-κB inflammatory pathway in stroke. Immunohistochemistry was used to evaluate the levels of TLR4 and NF-κB expression in brain areas (parietal lobe, hippocampus and striatum) of rats that underwent: MCAO-splenectomy surgery (MS ); MCAO surgery without splenectomy (MCAO control or MC); Sham MCAO and splenectomy surgery (sham control group or SC group respectively. Apoptosis in these areas was assessed by TUNEL detection technique. The levels of TLR4 and NF-κB expression were significantly reduced in splenectomized rats relative to the MS group (Psplenectomy in ischemic stroke. Our results suggest that such an effect might be due to the inhibition of theTLR4/NF-κB inflammatory pathway. Copyright © 2016 Elsevier B.V. All rights reserved.

Effect of apple extracts on NF-kappaB activation in human umbilical vein endothelial cells

Czech Academy of Sciences Publication Activity Database

Davis, P.A.; Polagruto, J.A.; Valacchi, G.; Phung, A.; Souček, Karel; Keen, C.L.; Gershwin, M.E.

2006-01-01

Roč. 231, č. 5 (2006), s. 594-598 ISSN 1535-3702 Institutional research plan: CEZ:AV0Z50040507 Keywords : human umbilical vascular endothelial cells * NF-kappaB * antioxidants Subject RIV: BO - Biophysics Impact factor: 2.845, year: 2006

Stevia and stevioside protect against cisplatin nephrotoxicity through inhibition of ERK1/2, STAT3, and NF-κB activation.

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Potočnjak, Iva; Broznić, Dalibor; Kindl, Marija; Kropek, Matija; Vladimir-Knežević, Sanda; Domitrović, Robert

2017-09-01

We investigated the effect of natural sweetener Stevia rebaudiana and its constituent stevioside in cisplatin (CP)-induced kidney injury. Male BALB/cN mice were orally administered 10, 20, and 50 mg/kg body weight of Stevia rebaudiana ethanol extract (SE) or stevioside 50 mg/kg, 48 h after intraperitoneal administration of CP (13 mg/kg). Two days later, CP treatment resulted in histopathological changes showing kidney injury. Increased expression of 4-hydroxynonenal (4-HNE), 3-nitrotyrosine (3-NT), and heme oxygenase-1 (HO-1) in mice kidneys suggested oxidative stress. CP treatment also increased renal expression of nuclear factor-kappaB (NF-κB) p65 subunit and phosphorylated inhibitor of NF-κB (IκBα), as well as expression of pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α). Induction of apoptosis and inhibition of the cell cycle in kidneys was evidenced by increased expression of p53, Bax, caspase-9, and p21, proteolytic cleavage of poly (ADP-ribose) polymerase (PARP), with concomitant suppression of Bcl-2 and cyclin D1 expression. The number of apoptotic cells in kidneys was also assessed. CP administration resulted in activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and signal transducer and activator of transcription 3 (STAT3). Both SE and stevioside attenuated CP nephrotoxicity by suppressing oxidative stress, inflammation, and apoptosis through mechanism involving ERK1/2, STAT3, and NF-κB suppression. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hypoxia and Inflammation in Cancer, Focus on HIF and NF-κB

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Laura D’Ignazio

2017-05-01

Full Text Available Cancer is often characterised by the presence of hypoxia and inflammation. Paramount to the mechanisms controlling cellular responses under such stress stimuli, are the transcription factor families of Hypoxia Inducible Factor (HIF and Nuclear Factor of κ-light-chain-enhancer of activated B cells (NF-κB. Although, a detailed understating of how these transcription factors respond to their cognate stimulus is well established, it is now appreciated that HIF and NF-κB undergo extensive crosstalk, in particular in pathological situations such as cancer. Here, we focus on the current knowledge on how HIF is activated by inflammation and how NF-κB is modulated by hypoxia. We summarise the evidence for the possible mechanism behind this activation and how HIF and NF-κB function impacts cancer, focusing on colorectal, breast and lung cancer. We discuss possible new points of therapeutic intervention aiming to harness the current understanding of the HIF-NF-κB crosstalk.

The D. melanogaster capa-1 neuropeptide activates renal NF-kB signaling.

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Terhzaz, Selim; Overend, Gayle; Sebastian, Sujith; Dow, Julian A T; Davies, Shireen-A

2014-03-01

The capa peptide family exists in a very wide range of insects including species of medical, veterinary and agricultural importance. Capa peptides act via a cognate G-protein coupled receptor (capaR) and have a diuretic action on the Malpighian tubules of Dipteran and Lepidopteran species. Capa signaling is critical for fluid homeostasis and has been associated with desiccation tolerance in the fly, Drosophila melanogaster. The mode of capa signaling is highly complex, affecting calcium, nitric oxide and cyclic GMP pathways. Such complex physiological regulation by cell signaling pathways may occur ultimately for optimal organismal stress tolerance to multiple stressors. Here we show that D. melanogaster capa-1 (Drome-capa-1) acts via the Nuclear Factor kappa B (NF-kB) stress signaling network. Human PCR gene arrays of capaR-transfected Human Embryonic Kidney (HEK) 293 cells showed that Drome-capa-1 increases expression of NF-kB, NF-kB regulated genes including IL8, TNF and PTGS2, and NF-kB pathway-associated transcription factors i.e. EGR1, FOS, cJUN. Furthermore, desiccated HEK293 cells show increased EGR1, EGR3 and PTGS2 - but not IL8, expression. CapaR-transfected NF-kB reporter cells showed that Drome-capa-1 increased NF-kB promoter activity via increased calcium. In Malpighian tubules, both Drome-capa-1 stimulation and desiccation result in increased gene expression of the D. melanogaster NF-kB orthologue, Relish; as well as EGR-like stripe and klumpfuss. Drome-capa-1 also induces Relish translocation in tubule principal cells. Targeted knockdown of Relish in only tubule principal cells reduces desiccation stress tolerance of adult flies. Together, these data suggest that Drome-capa-1 acts in desiccation stress tolerance, by activating NF-kB signaling. Copyright © 2013 Elsevier Inc. All rights reserved.

Novel Serine 176 Phosphorylation of YBX1 Activates NF-κB in Colon Cancer.

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Martin, Matthew; Hua, Laiqing; Wang, Benlian; Wei, Han; Prabhu, Lakshmi; Hartley, Antja-Voy; Jiang, Guanglong; Liu, Yunlong; Lu, Tao

2017-02-24

Y box protein 1 (YBX1) is a well known oncoprotein that has tumor-promoting functions. YBX1 is widely considered to be an attractive therapeutic target in cancer. To develop novel therapeutics to target YBX1, it is of great importance to understand how YBX1 is finely regulated in cancer. Previously, we have shown that YBX1 could function as a tumor promoter through phosphorylation of its Ser-165 residue, leading to the activation of the NF-κB signaling pathway (1). In this study, using mass spectrometry analysis, we discovered a distinct phosphorylation site, Ser-176, on YBX1. Overexpression of the YBX1-S176A (serine-to-alanine) mutant in either HEK293 cells or colon cancer HT29 cells showed dramatically reduced NF-κB-activating ability compared with that of WT-YBX1, confirming that Ser-176 phosphorylation is critical for the activation of NF-κB by YBX1. Importantly, the mutant of Ser-176 and the previously reported Ser-165 sites regulate distinct groups of NF-κB target genes, suggesting the unique and irreplaceable function of each of these two phosphorylated serine residues. Our important findings could provide a novel cancer therapy strategy by blocking either Ser-176 or Ser-165 phosphorylation or both of YBX1 in colon cancer. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Effects of different doses of atorvastatin on NF-κB, inflammatory factors and insulin resistance in elderly patients with early diabetic nephropathy

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Ying Liu

2016-01-01

Full Text Available Objective: To explore the effects of different doses of atorvastatin on NF-κB, inflammatory factors and insulin resistance in elderly patients with early diabetic nephropathy. Methods: A total of 150 cases with elderly early diabetic nephropathy were randomly divided into two groups according to the random number table method. Group A (n=75 was treated with atorvastatin tablets at a dose of 10 mg/d, while group B (n=75 was treated at a dose of 20 mg/d. The NF-κB, inflammatory factors and insulin resistance were detected and compared between the two groups. Results: After treatment, UAER (52.87±7.78 μg/min, SCr (70.43±6.76 μmol/L and BUN (4.04±0.40 mmol/L of group B were significantly decreased compared with before treatment and post-treated group A (P<0.05; phosphorylation level of NF-κB p65 after treatment was (0.80±0.17 μg/min in the peripheral blood of patients from group B, which was significantly reduced compared with before treatment and post-treated group A (P<0.05; inflammatory factors including TNF-α (52.80±7.78 ng/L, IL-6 (70.43±6.76 ng/L and Hs-CRP (4.04±0.40 mg/L of group B after treatment also declined significantly compared with before treatment and post-treated group A (P<0.05; while HbAlc and FBG were not significantly changed after treatment in both groups, and there was no significant difference in each group before and after treatment; FINS (9.88±0.85 mU/L and HOMA-IR (3.36±0.33 of group B after treatment were significantly lowered compared with before treatment and posttreated group A (P<0.05. Conclusions: High dose atorvastatin can inhibit the activity of NF- κB p65 and levels of inflammation, and improve renal function and insulin resistance in elderly patients with early diabetic nephropathy, making it a promising means for clinical application.

NF-κB Directly Regulates Fas Transcription to Modulate Fas-mediated Apoptosis and Tumor Suppression*

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Liu, Feiyan; Bardhan, Kankana; Yang, Dafeng; Thangaraju, Muthusamy; Ganapathy, Vadivel; Waller, Jennifer L.; Liles, Georgia B.; Lee, Jeffrey R.; Liu, Kebin

2012-01-01

Fas is a member of the death receptor family. Stimulation of Fas leads to induction of apoptotic signals, such as caspase 8 activation, as well as “non-apoptotic” cellular responses, notably NF-κB activation. Convincing experimental data have identified NF-κB as a critical promoter of cancer development, creating a solid rationale for the development of antitumor therapy that suppresses NF-κB activity. On the other hand, compelling data have also shown that NF-κB activity enhances tumor cell sensitivity to apoptosis and senescence. Furthermore, although stimulation of Fas activates NF-κB, the function of NF-κB in the Fas-mediated apoptosis pathway remains largely undefined. In this study, we observed that deficiency of either Fas or FasL resulted in significantly increased incidence of 3-methylcholanthrene-induced spontaneous sarcoma development in mice. Furthermore, Fas-deficient mice also exhibited significantly greater incidence of azoxymethane and dextran sodium sulfate-induced colon carcinoma. In addition, human colorectal cancer patients with high Fas protein in their tumor cells had a longer time before recurrence occurred. Engagement of Fas with FasL triggered NF-κB activation. Interestingly, canonical NF-κB was found to directly bind to the FAS promoter. Blocking canonical NF-κB activation diminished Fas expression, whereas blocking alternate NF-κB increased Fas expression in human carcinoma cells. Moreover, although canonical NF-κB protected mouse embryo fibroblast (MEF) cells from TNFα-induced apoptosis, knocking out p65 diminished Fas expression in MEF cells, resulting in inhibition of FasL-induced caspase 8 activation and apoptosis. In contrast, knocking out p52 increased Fas expression in MEF cells. Our observations suggest that canonical NF-κB is a Fas transcription activator and alternate NF-κB is a Fas transcription repressor, and Fas functions as a suppressor of spontaneous sarcoma and colon carcinoma. PMID:22669972

Hinokitiol, a tropolone derivative, inhibits mouse melanoma (B16-F10) cell migration and in vivo tumor formation.

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Huang, Chien-Hsun; Lu, Shing-Hwa; Chang, Chao-Chien; Thomas, Philip Aloysius; Jayakumar, Thanasekaran; Sheu, Joen-Rong

2015-01-05

Invasion and metastasis are the major causes of treatment failure in patients with cancer. Hinokitiol, a natural bioactive compound found in Chamacyparis taiwanensis, has been used in hair tonics, cosmetics, and food as an antimicrobial agent. In this study, we investigated the effects and possible mechanisms of action of hinokitiol on migration by the metastatic melanoma cell line, B16-F10, in which matrix metalloproteinase-1 (MMP-1) is found to be highly- expressed. Treatment with hinokitiol revealed a concentration-dependent inhibition of migration of B16-F10 melanoma cells. Hinokitiol appeared to achieve this effect by reducing the expression of MMP-1 and by suppressing the phosphorylation of mitogen- activated protein kinase (MAPK) signaling molecules such as extracellular signal-regulated kinase (ERK) 1/2, p38 MAPK and c-Jun N-terminal kinases (JNK). On the other hand, hinokitiol treatment reversed IκB-α degradation and inhibited the phosphorylation of p65 nuclear factor kappa B (NF-κB) and cJun in B16-F10 cells. In addition, hinokitiol suppressed the translocation of p65 NF-κB from the cytosol to the nucleus, suggesting reduced NF-κB activation. Consistent with these in vitro findings, our in vivo study demonstrated that hinokitiol treatment significantly reduced the total number of mouse lung metastatic nodules and improved histological alterations in B16-F10 injected C57BL/6 mice. These findings suggest that treatment of B16-F10 cells with hinokitiol significantly inhibits metastasis, possibly by blocking MMP-1 activation, MAPK signaling pathways and inhibition of the transcription factors, NF-κB and c-Jun, involved in cancer cell migration. These results may accelerate the development of novel therapeutic agents for the treatment of malignant cancers. Copyright © 2014 Elsevier B.V. All rights reserved.

Nuclear NF-κB Expression Correlates With Outcome Among Patients With Head and Neck Squamous Cell Carcinoma Treated With Primary Chemoradiation Therapy

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Balermpas, Panagiotis [Department of Radiation Therapy and Oncology, J. W. Goethe – University Frankfurt am Main, Frankfurt (Germany); Michel, Yvonne [Senckenberg Institute of Pathology, J. W. Goethe – University Frankfurt am Main, Frankfurt (Germany); Wagenblast, Jens [Department of Otorhinolaryngology, J. W. Goethe – University Frankfurt am Main, Frankfurt (Germany); Seitz, Oliver [Department of Maxillofacial Surgery, J. W. Goethe – University Frankfurt am Main, Frankfurt (Germany); Sipek, Florian; Rödel, Franz; Rödel, Claus [Department of Radiation Therapy and Oncology, J. W. Goethe – University Frankfurt am Main, Frankfurt (Germany); Fokas, Emmanouil, E-mail: emmanouil.fokas@kgu.de [Department of Radiation Therapy and Oncology, J. W. Goethe – University Frankfurt am Main, Frankfurt (Germany)

2013-07-15

Background: To examine whether nuclear NF-κB expression correlates with outcome in patients with head and neck squamous cell carcinoma (HNSCC) treated with primary chemoradiation therapy (CRT). Methods and Materials: Between 2007 and 2010, 101 patients with locally advanced primary HNSCC were treated with definitive simultaneous CRT. Pretreatment biopsy specimens were analyzed for NF-κB p65 (RelA) nuclear immunoreactivity. A sample was assigned to be positive with more than 5% positive nuclear expression. The predictive relevance of NF-κB and clinicopathologic factors for overall survival (OS), progression-free survival (PFS), local progression-free survival (LPFS), and metastasis-free survival (DMFS) was examined by univariate and multivariate analysis. Results: No significant differences between the groups were observed with regard to age, sex, total radiation dose, fractionation mode, total chemotherapy applied, T stage or grading. Patients with p65 nuclear positive biopsy specimens showed significantly a higher rate of lymph node metastasis (cN2c or cN3 status, P=.034). Within a mean follow-up time of 25 months (range, 2.33-62.96 months) OS, PFS, and DMFS were significantly poorer in the p65 nuclear positive group (P=.008, P=.027, and P=.008, respectively). These correlations remained significant in multivariate analysis. Conclusion: NF-κB/p65 nuclear expression is associated with increased lymphatic and hematogenous tumor dissemination and decreased survival in HNSCC patients treated with primary CRT. Our results may foster further investigation of a predictive relevance of NF-κB/p65 and its role as a suitable target for a molecular-based targeted therapy in HNSCC cancer.

1,25-Dihydroxyvitamin D3 induces biphasic NF-κB responses during HL-60 leukemia cells differentiation through protein induction and PI3K/Akt-dependent phosphorylation/degradation of IκB

International Nuclear Information System (INIS)

Tse, A.K.-W.; Wan, C.-K.; Shen, X.-L.; Zhu, G.-Y.; Cheung, H.-Y.; Yang, M.; Fong, W.-F.

2007-01-01

1,25-Dihydroxyvitamin D 3 (VD 3 ) induces differentiation in a number of leukemia cell lines and under various conditions is able to either stimulate or inhibit nuclear factor kappa B (NF-κB) activity. Here we report a time-dependent biphasic regulation of NF-κB in VD 3 -treated HL-60 leukemia cells. After VD 3 treatment there was an early ∼ 4 h suppression and a late 8-72 h prolonged reactivation of NF-κB. The reactivation of NF-κB was concomitant with increased IKK activities, IKK-mediated IκBα phosphorylation, p65 phosphorylation at residues S276 and S536, p65 nuclear translocation and p65 recruitment to the NF-κB/vitamin D responsive element promoters. In parallel with NF-κB stimulation, there was an up-regulation of NF-κB controlled inflammatory and anti-apoptotic genes such as TNFα, IL-1β and Bcl-xL. VD 3 -triggered reactivation of NF-κB was associated with PI3K/Akt phosphorylation. PI3K/Akt antagonists suppressed VD 3 -stimulated IκBα phosphorylation as well as NF-κB-controlled gene expression. The early ∼ 4 h VD 3 -mediated NF-κB suppression coincided with a prolonged increase of IκBα protein which require de novo protein synthesis, lasted for as least 72 h and was insensitive to MAPK, IKK or PI3K/Akt inhibitors. Our data suggest a novel biphasic regulation of NF-κB in VD 3 -treated leukemia cells and our results may have provided the first molecular explanation for the contradictory observations reported on VD 3 -mediated immune-regulation

Baicalin Inhibits Lipopolysaccharide-Induced Inflammation Through Signaling NF-κB Pathway in HBE16 Airway Epithelial Cells.

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Dong, Shou-jin; Zhong, Yun-qing; Lu, Wen-ting; Li, Guan-hong; Jiang, Hong-li; Mao, Bing

2015-08-01

Baicalin, a flavonoid monomer derived from Scutellaria baicalensis called Huangqin in mandarin, is the main active ingredient contributing to S. baicalensis' efficacy. It is known in China that baicalin has potential therapeutic effects on inflammatory diseases. However, its anti-inflammatory mechanism has still not been fully interpreted. We aim to investigate the anti-inflammatory effect of baicalin on lipopolysaccharide (LPS)-induced inflammation in HBE16 airway epithelial cells and also to explore the underlying signaling mechanisms. The anti-inflammatory action of baicalin was evaluated in human airway epithelial cells HBE16 treated with LPS. Airway epithelial cells HBE16 were pretreated with a range of concentrations of baicalin for 30 min and then stimulated with 10 μg/ml LPS. The secretions of interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) in cell culture supernatants were quantified by enzyme-linked immunosorbent assay (ELISA). The messenger RNA (mRNA) expressions of IL-6, IL-8, and TNF-α were tested by quantitative real-time polymerase chain reaction (real-time RT-PCR). Furthermore, Western blotting was used to determine whether the signaling pathway NF-κB was involved in the anti-inflammatory action of baicalin. The inflammatory cell model was successfully built with 10 μg/ml LPS for 24 h in our in vitro experiments. Both the secretions and the mRNA expressions of IL-6, IL-8, and TNF-α were significantly inhibited by baicalin. Moreover, the expression levels of phospho-IKKα/β and phospho-NF-κB p65 were downregulated, and the phospho-IκB-α level was upregulated by baicalin. These findings suggest that the anti-inflammatory properties of baicalin may be resulted from the inhibition of IL-6, IL-8, and TNF-α expression via preventing signaling NF-κB pathway in HBE16 airway epithelial cells. In addition, this study provides evidence to understand the therapeutic effects of baicalin on inflammatory diseases in

NF-kB as a mediator of brain inflammation in AD.

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Hong, Jin Tae

2017-08-07

Alzheimer's disease is the most common form of dementia. It is characterized by beta-amyloid peptide fibrils which are extracellular deposition of a specific protein, and is accompanied by extensive neuroinflammation. Various studies show the presence of a number of inflammation markers in the AD brain: elevated inflammatory cytokines and chemokines, and an accumulation of activated microglia in the damaged regions. NF-kB is a redox of transcriptional factors, and it is known to be located in the genes involved in amyloidogenesis and inflammation. Epidemiological studies have shown that NF-kB is elevated in the AD patient brain, and long-term use of non-steroidal anti-inflammatory drugs suppresses the progression of AD and delays its onset, suggesting that there is a close correlation between NF-kB and AD pathogenesis. This study is (1) to assess the association between NF-kB activity and AD through discussion of a variety of experimental and clinical studies on AD and (2) to review treatment strategies designed to treat or prevent AD with NF-kB inhibitors. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

An Update on Neurofibromatosis Type 1: Not Just Café-au-Lait Spots and Freckling. Part II. Other Skin Manifestations Characteristic of NF1. NF1 and Cancer.

Science.gov (United States)

Hernández-Martín, A; Duat-Rodríguez, A

2016-01-01

Neurofibromatosis type 1 (NF1) is the most common neurocutaneous syndrome and probably the one best known to dermatologists. Although the genetic locus of NF1 was identified on chromosome 17 in 1987, diagnosis of the disease is still based primarily on clinical observations. The 7 diagnostic criteria of the National Institutes of Health, which were established in 1988, include 3 skin manifestations (café-au-lait spots, freckling on flexural areas, and cutaneous neurofibromas). The age at which these diagnostic lesions appear is variable: onset can be late in some patients while others never develop certain symptoms. Definitive diagnosis may therefore be delayed by years. Although the appearance of the characteristic café-au-lait spots and freckling in the early years of childhood are very suggestive of the disease, these signs are not pathognomonic and, in isolation, do not constitute sufficient evidence to establish a definitive diagnosis. Thus, other diagnoses should be considered in patients whose only symptoms are café-au-lait spots and freckling. By contrast, the presence of multiple cutaneous neurofibromas or at least 1 plexiform neurofibroma is a very specific indication of NF1. Identification of the different types of neurofibroma allows us to confirm the diagnosis and initiate appropriate management. Copyright © 2016 AEDV. Published by Elsevier España, S.L.U. All rights reserved.

Sphingosine 1-phosphate (S1P)/S1P receptor 1 signaling regulates receptor activator of NF-κB ligand (RANKL) expression in rheumatoid arthritis

International Nuclear Information System (INIS)

Takeshita, Harunori; Kitano, Masayasu; Iwasaki, Tsuyoshi; Kitano, Sachie; Tsunemi, Sachi; Sato, Chieri; Sekiguchi, Masahiro; Azuma, Naoto; Miyazawa, Keiji; Hla, Timothy; Sano, Hajime

2012-01-01

Highlights: ► MH7A cells and CD4 + T cells expressed S1P1 and RANKL. ► S1P increased RANKL expression in MH7A cells and CD4 + T cells. ► The effect of S1P in MH7A cells was inhibited by specific Gi/Go inhibitors. -- Abstract: Sphingosine 1-phosphate (S1P)/S1P receptor 1 (S1P1) signaling plays an important role in synovial cell proliferation and inflammatory gene expression by rheumatoid arthritis (RA) synoviocytes. The purpose of this study is to clarify the role of S1P/S1P1 signaling in the expression of receptor activator of NF-κB ligand (RANKL) in RA synoviocytes and CD4 + T cells. We demonstrated MH7A cells, a human RA synovial cell line, and CD4 + T cells expressed S1P1 and RANKL. Surprisingly, S1P increased RANKL expression in MH7A cells and CD4 + T cells in a dose-dependent manner. Moreover, S1P enhanced RANKL expression induced by stimulation with TNF-α in MH7A cells and CD4 + T cells. These effects of S1P in MH7A cells were inhibited by pretreatment with PTX, a specific Gi/Go inhibitor. These findings suggest that S1P/S1P1 signaling may play an important role in RANKL expression by MH7A cells and CD4 + T cells. S1P/S1P1 signaling of RA synoviocytes is closely connected with synovial hyperplasia, inflammation, and RANKL-induced osteoclastogenesis in RA. Thus, regulation of S1P/S1P1 signaling may become a novel therapeutic target for RA.

Sphingosine 1-phosphate (S1P)/S1P receptor 1 signaling regulates receptor activator of NF-{kappa}B ligand (RANKL) expression in rheumatoid arthritis

Energy Technology Data Exchange (ETDEWEB)

Takeshita, Harunori [Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan); Kitano, Masayasu, E-mail: mkitano6@hyo-med.ac.jp [Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan); Iwasaki, Tsuyoshi [Department of Pharmacy, Hyogo University of Health Sciences, 1-3-6 Minatojima Kobe, Hyogo 650-8530 (Japan); Kitano, Sachie; Tsunemi, Sachi; Sato, Chieri; Sekiguchi, Masahiro; Azuma, Naoto [Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan); Miyazawa, Keiji [Discovery Research III, Research and Development, Kissei Pharmaceutical Company, 4365-1 Hodakakashiwara, Azumino, Nagano 399-8304 (Japan); Hla, Timothy [Center for Vascular Biology, Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, 1300 York Avenue, Box 69, NY 10065 (United States); Sano, Hajime [Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan)

2012-03-09

Highlights: Black-Right-Pointing-Pointer MH7A cells and CD4{sup +} T cells expressed S1P1 and RANKL. Black-Right-Pointing-Pointer S1P increased RANKL expression in MH7A cells and CD4{sup +} T cells. Black-Right-Pointing-Pointer The effect of S1P in MH7A cells was inhibited by specific Gi/Go inhibitors. -- Abstract: Sphingosine 1-phosphate (S1P)/S1P receptor 1 (S1P1) signaling plays an important role in synovial cell proliferation and inflammatory gene expression by rheumatoid arthritis (RA) synoviocytes. The purpose of this study is to clarify the role of S1P/S1P1 signaling in the expression of receptor activator of NF-{kappa}B ligand (RANKL) in RA synoviocytes and CD4{sup +} T cells. We demonstrated MH7A cells, a human RA synovial cell line, and CD4{sup +} T cells expressed S1P1 and RANKL. Surprisingly, S1P increased RANKL expression in MH7A cells and CD4{sup +} T cells in a dose-dependent manner. Moreover, S1P enhanced RANKL expression induced by stimulation with TNF-{alpha} in MH7A cells and CD4{sup +} T cells. These effects of S1P in MH7A cells were inhibited by pretreatment with PTX, a specific Gi/Go inhibitor. These findings suggest that S1P/S1P1 signaling may play an important role in RANKL expression by MH7A cells and CD4{sup +} T cells. S1P/S1P1 signaling of RA synoviocytes is closely connected with synovial hyperplasia, inflammation, and RANKL-induced osteoclastogenesis in RA. Thus, regulation of S1P/S1P1 signaling may become a novel therapeutic target for RA.

The apoptogenic toxin AIP56 is a metalloprotease A-B toxin that cleaves NF-κb P65.

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Daniela S Silva

2013-02-01

Full Text Available AIP56 (apoptosis-inducing protein of 56 kDa is a major virulence factor of Photobacterium damselae piscicida (Phdp, a Gram-negative pathogen that causes septicemic infections, which are among the most threatening diseases in mariculture. The toxin triggers apoptosis of host macrophages and neutrophils through a process that, in vivo, culminates with secondary necrosis of the apoptotic cells contributing to the necrotic lesions observed in the diseased animals. Here, we show that AIP56 is a NF-κB p65-cleaving zinc-metalloprotease whose catalytic activity is required for the apoptogenic effect. Most of the bacterial effectors known to target NF-κB are type III secreted effectors. In contrast, we demonstrate that AIP56 is an A-B toxin capable of acting at distance, without requiring contact of the bacteria with the target cell. We also show that the N-terminal domain cleaves NF-κB at the Cys(39-Glu(40 peptide bond and that the C-terminal domain is involved in binding and internalization into the cytosol.

Polycystin-1 promotes PKCα-mediated NF-κB activation in kidney cells

International Nuclear Information System (INIS)

Banzi, Manuela; Aguiari, Gianluca; Trimi, Viky; Mangolini, Alessandra; Pinton, Paolo; Witzgall, Ralph; Rizzuto, Rosario; Senno, Laura del

2006-01-01

Polycystin-1 (PC1), the PKD1 gene product, is a membrane receptor which regulates many cell functions, including cell proliferation and apoptosis, both typically increased in cyst lining cells in autosomal dominant polycystic kidney disease. Here we show that PC1 upregulates the NF-κB signalling pathway in kidney cells to prevent cell death. Human embryonic kidney cell lines (HEK293 CTT ), stably expressing a PC1 cytoplasmic terminal tail (CTT), presented increased NF-κB nuclear levels and NF-κB-mediated luciferase promoter activity. This, consistently, was reduced in HEK293 cells in which the endogenous PC1 was depleted by RNA interference. CTT-dependent NF-κB promoter activation was mediated by PKCα because it was blocked by its specific inhibitor Ro-320432. Furthermore, it was observed that apoptosis, which was increased in PC1-depleted cells, was reduced in HEK293 CTT cells and in porcine kidney LtTA cells expressing a doxycycline-regulated CTT. Staurosporine, a PKC inhibitor, and parthenolide, a NF-κB inhibitor, significantly reduced the CTT-dependent antiapoptotic effect. These data reveal, therefore, a novel pathway by which polycystin-1 activates a PKCα-mediated NF-κB signalling and cell survival

RAC1b overexpression stimulates proliferation and NF-kB-mediated anti-apoptotic signaling in thyroid cancer cells.

Science.gov (United States)

Faria, Márcia; Matos, Paulo; Pereira, Teresa; Cabrera, Rafael; Cardoso, Bruno A; Bugalho, Maria João; Silva, Ana Luísa

2017-01-01

Overexpression of tumor-associated RAC1b has been recently highlighted as one of the most promising targets for therapeutic intervention in colon, breast, lung and pancreatic cancer. RAC1b is a hyperactive variant of the small GTPase RAC1 and has been recently shown to be overexpressed in a subset of papillary thyroid carcinomas associated with unfavorable outcome. Using the K1 PTC derived cell line as an in vitro model, we observed that both RAC1 and RAC1b were able to induce a significant increase on NF-kB and cyclin D1 reporter activity. A clear p65 nuclear localization was found in cells transfected with RAC1b-WT, confirming NF-kB canonical pathway activation. Consistently, we observed a RAC1b-mediated decrease in IκBα (NF-kB inhibitor) protein levels. Moreover, we show that RAC1b overexpression stimulates G1/S progression and protects thyroid cells against induced apoptosis, the latter through a process involving the NF-kB pathway. Present data support previous findings suggesting an important role for RAC1b in the development of follicular cell-derived thyroid malignancies and point out NF-kB activation as one of the molecular mechanisms associated with the pro-tumorigenic advantage of RAC1b overexpression in thyroid carcinomas.

Reorganización del Sistema Nacional de Salud, una gran transformación Ley 10 de 1990

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Ricardo Galán Morera

1990-04-01

Full Text Available RESUMEN El sistema Nacional de Salud Colombiano  se creó a través del Decreto No 056 de 1975 y constituyó un hito histórico de especial relevancia Nacional. Después de 14 años de funcionamiento, el Gobierno Nacional, consideró urgente y necesario efectuar su restructuración, para ponerlo acorde con la descentralización política, administrativa  y fiscal y con las políticas  gubernamentales de “Erradicación de la pobreza Absoluta”, “Plan Nacional  de Rehabilitación”, “Participación Comunitaria” y “Participación Ciudadana”. El presente artículo señala, a manera de “flash”, las principales  características de la ley 10 de 1990, mediante la cual se “Reorganiza el Sistema Nacional de salud y se dictan otras disposiciones”.

Ozone Enhances Diesel Exhaust Particles (DEP-Induced Interleukin-8 (IL-8 Gene Expression in Human Airway Epithelial Cells through Activation of Nuclear Factors- κB (NF-κB and IL-6 (NF-IL6

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James Kelley

2005-12-01

Full Text Available Ozone, a highly reactive oxidant gas is a major component of photochemical smog. As an inhaled toxicant, ozone induces its adverse effects mainly on the lung. Inhalation of particulate matter has been reported to cause airway inflammation in humans and animals. Furthermore, epidemiological evidence has indicated that exposure to particulate matter (PM2.5-10, including diesel exhaust particles (DEP has been correlated with increased acute and chronic respiratory morbidity and exacerbation of asthma. Previously, exposure to ozone or particulate matter and their effect on the lung have been addressed as separate environmental problems. Ozone and particulate matter may be chemically coupled in the ambient air. In the present study we determined whether ozone exposure enhances DEP effect on interleukin-8 (IL-8 gene expression in human airway epithelial cells. We report that ozone exposure (0.5 ppm x 1 hr significantly increased DEP-induced IL-8 gene expression in A549 cells (117 ± 19 pg/ml, n = 6, p < 0.05 as compared to cultures treated with DEP (100 μg/ml x 4 hr alone (31 ± 3 pg/ml, n = 6, or cultures exposed to purified air (24 ± 6 pg/ml, n = 6. The increased DEP-induced IL-8 gene expression following ozone exposure was attributed to ozone-induced increase in the activity of the transcription factors NF-κB and NF-IL6. The results of the present study indicate that ozone exposure enhances the toxicity of DEP in human airway epithelial cells by augmenting IL-8 gene expression, a potent chemoattractant of neutrophils in the lung.

Ultraviyole a ışığının oluşturduğu oksidatif koenszim q10 ve alfa lipoik asit’in koruyucu etkisi

OpenAIRE

Yüksel, Mehtap

2013-01-01

UVA ışınlarına maruz kalan hücrelerde oluşan reaktif oksijen ürünleri (ROS) lipid, protein ve nükleik asitlerde hasar oluşturabilirler. Antioksidanlar bu hasardan koruma ve iyileştirmede yararlı olabilirler. Bu çalışmada UVA ışınına maruz bıraktığımız sıçanların deri, kan ve karaciğerinde MDA, GSH ve KAT düzeylerini tespit ederken diğer yandan da bu parametreler üzerinde CoQ10 ve ALA’nın etkisini inceledik. Bunun için sıçanlar kontrol, UVA, UVA+mısır yağı, UVA+CoQ10, UVA+ALA ve UVA+CoQ10+ALA ...

Eukaryotic Initiation Factor 4H Is under Transcriptional Control of p65/NF-κB

Science.gov (United States)

Fiume, Giuseppe; Rossi, Annalisa; de Laurentiis, Annamaria; Falcone, Cristina; Pisano, Antonio; Vecchio, Eleonora; Pontoriero, Marilena; Scala, Iris; Scialdone, Annarita; Masci, Francesca Fasanella; Mimmi, Selena; Palmieri, Camillo; Scala, Giuseppe; Quinto, Ileana

2013-01-01

Protein synthesis is mainly regulated at the initiation step, allowing the fast, reversible and spatial control of gene expression. Initiation of protein synthesis requires at least 13 translation initiation factors to assemble the 80S ribosomal initiation complex. Loss of translation control may result in cell malignant transformation. Here, we asked whether translational initiation factors could be regulated by NF-κB transcription factor, a major regulator of genes involved in cell proliferation, survival, and inflammatory response. We show that the p65 subunit of NF-κB activates the transcription of eIF4H gene, which is the regulatory subunit of eIF4A, the most relevant RNA helicase in translation initiation. The p65-dependent transcriptional activation of eIF4H increased the eIF4H protein content augmenting the rate of global protein synthesis. In this context, our results provide novel insights into protein synthesis regulation in response to NF-κB activation signalling, suggesting a transcription-translation coupled mechanism of control. PMID:23776612

Extraction of the 1S0 neutron-neutron scattering length from a kinematically-complete n-d breakup experiment at TUNL

International Nuclear Information System (INIS)

Gonzalez Trotter, D. E.; Tornow, W.; Howell, C. R.; Salinas, F.; Walter, R. L.; Witalea, H.

1999-01-01

The 1 S 0 neutron-neutron (nn) scattering length's currently accepted value (a nn =-18.6±0.3 fm) is derived exclusively from two π - -d capture-reaction experiments, in disagreement with the average -16.7±0.5 fm extracted from kinematically-complete nd breakup experiments. This discrepancy may be due to deficiencies in the analyses of n-d breakup data and/or three-nucleon force (3NF) effects. A kinematically-complete n+d→n 1 +n 2 +p breakup experiment at an incident neutron energy of 13.0 MeV was performed recently at TUNL. The value of a nn was extracted from the direct comparison of experimental and rigorously-calculated theoretical nd breakup differential cross sections at four production angles of the nn pair. Using modern nucleon-nucleon potential models in the three-nucleon cross-section calculations we obtained a nn =-18.7±0.6 fm, in agreement with the π - -d result. We found no significant effect due to 3NFs on our a nn value

Curcumin inhibits interferon-α induced NF-κB and COX-2 in human A549 non-small cell lung cancer cells

International Nuclear Information System (INIS)

Lee, Jeeyun; Im, Young-Hyuck; Jung, Hae Hyun; Kim, Joo Hyun; Park, Joon Oh; Kim, Kihyun; Kim, Won Seog; Ahn, Jin Seok; Jung, Chul Won; Park, Young Suk; Kang, Won Ki; Park, Keunchil

2005-01-01

The A549 cells, non-small cell lung cancer cell line from human, were resistant to interferon (IFN)-α treatment. The IFN-α-treated A549 cells showed increase in protein expression levels of NF-κB and COX-2. IFN-α induced NF-κB binding activity within 30 min and this increased binding activity was markedly suppressed with inclusion of curcumin. Curcumin also inhibited IFN-α-induced COX-2 expression in A549 cells. Within 10 min, IFN-α rapidly induced the binding activity of a γ- 32 P-labeled consensus GAS oligonucleotide probe, which was profoundly reversed by curcumin. Taken together, IFN-α-induced activations of NF-κB and COX-2 were inhibited by the addition of curcumin in A549 cells

DNA Binding and Phosphorylation Regulate the Core Structure of the NF-κB p50 Transcription Factor.

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Vonderach, Matthias; Byrne, Dominic P; Barran, Perdita E; Eyers, Patrick A; Eyers, Claire E

2018-06-05

The NF-κB transcription factors are known to be extensively phosphorylated, with dynamic site-specific modification regulating their ability to dimerize and interact with DNA. p50, the proteolytic product of p105 (NF-κB1), forms homodimers that bind DNA but lack intrinsic transactivation function, functioning as repressors of transcription from κB promoters. Here, we examine the roles of specific phosphorylation events catalysed by either protein kinase A (PKA c ) or Chk1, in regulating the functions of p50 homodimers. LC-MS/MS analysis of proteolysed p50 following in vitro phosphorylation allows us to define Ser328 and Ser337 as PKA c - and Chk1-mediated modifications, and pinpoint an additional four Chk1 phosphosites: Ser65, Thr152, Ser242 and Ser248. Native mass spectrometry (MS) reveals Chk1- and PKA c -regulated disruption of p50 homodimer formation through Ser337. Additionally, we characterise the Chk1-mediated phosphosite, Ser242, as a regulator of DNA binding, with a S242D p50 phosphomimetic exhibiting a > 10-fold reduction in DNA binding affinity. Conformational dynamics of phosphomimetic p50 variants, including S242D, are further explored using ion-mobility MS (IM-MS). Finally, comparative theoretical modelling with experimentally observed p50 conformers, in the absence and presence of DNA, reveals that the p50 homodimer undergoes conformational contraction during electrospray ionisation that is stabilised by complex formation with κB DNA. Graphical Abstract ᅟ.

Antitumor Activity of Tenacissoside H on Esophageal Cancer through Arresting Cell Cycle and Regulating PI3K/Akt-NF-κB Transduction Cascade

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Yong-sen Jia

2015-01-01

Full Text Available Objective. The purpose of the study was to elucidate the molecular mechanism of tenacissoside H (TDH inhibiting esophageal carcinoma infiltration and proliferation. Methods. In vitro, EC9706 cells were treated with TDH. Cells proliferation and cell cycle were assayed. PI3K and NF-κB mRNAs expression were determined by real time PCR. In vivo, model of nude mice with tumor was established. Mice were treated with TDH. Inhibition ratio of tumor volume was calculated. PCNA expression was examined. Protein expression in PI3K/Akt-NF-κB signaling pathway was determined. Results. In vitro, TDH significantly inhibited cells proliferation in a time-and-dose-dependent manner. TDH arrested the cell cycle in S phase and significantly inhibited PI3K and NF-κB mRNA expression, compared with blank controlled group (P<0.05. In vivo, TDH strongly inhibits tumor growth and volume. PCNA expression was significantly decreased after treatment of TDH. TDH downregulated proteins expression in PI3K/Akt-NF-κB transduction cascade (P<0.05. Conclusion. TDH inhibited esophageal carcinoma infiltration and proliferation both in vitro and in vivo. The anticancer activity has relation to arresting the cell cycle at the S phase, inhibited the PCNA expression of transplanted tumors in nude mice, and regulated the protein expression in the PI3K/Akt-NF-κB transduction cascade.

Variations in 5S rDNAs in diploid and tetraploid offspring of red crucian carp × common carp.

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Ye, Lihai; Zhang, Chun; Tang, Xiaojun; Chen, Yiyi; Liu, Shaojun

2017-08-08

The allotetraploid hybrid fish (4nAT) that was created in a previous study through an intergeneric cross between red crucian carp (Carassius auratus red var., ♀) and common carp (Cyprinus carpio L., ♂) provided an excellent platform to investigate the effect of hybridization and polyploidization on the evolution of 5S rDNA. The 5S rDNAs of paternal common carp were made up of a coding sequence (CDS) and a non-transcribed spacer (NTS) unit, and while the 5S rDNAs of maternal red crucian carp contained a CDS and a NTS unit, they also contained a variable number of interposed regions (IPRs). The CDSs of the 5S rDNAs in both parental fishes were conserved, while their NTS units seemed to have been subjected to rapid evolution. The diploid hybrid 2nF 1 inherited all the types of 5S rDNAs in both progenitors and there were no signs of homeologous recombination in the 5S rDNAs of 2nF 1 by sequencing of PCR products. We obtained two segments of 5S rDNA with a total length of 16,457 bp from allotetraploid offspring 4nAT through bacterial artificial chromosome (BAC) sequencing. Using this sequence together with the 5S rDNA sequences amplified from the genomic DNA of 4nAT, we deduced that the 5S rDNAs of 4nAT might be inherited from the maternal progenitor red crucian carp. Additionally, the IPRs in the 5S rDNAs of 4nAT contained A-repeats and TA-repeats, which was not the case for the IPRs in the 5S rDNAs of 2nF 1 . We also detected two signals of a 200-bp fragment of 5S rDNA in the chromosomes of parental progenitors and hybrid progenies by fluorescence in situ hybridization (FISH). We deduced that during the evolution of 5S rDNAs in different ploidy hybrid fishes, interlocus gene conversion events and tandem repeat insertion events might occurred in the process of polyploidization. This study provided new insights into the relationship among the evolution of 5S rDNAs, hybridization and polyploidization, which were significant in clarifying the genome evolution of

S.E.N.S.I.B. project. Progress report 2006

International Nuclear Information System (INIS)

2007-01-01

This report presents the state of progress of all the studies which establish at present the S.E.N.S.I.B. project. For year 2006, the progress of the project is globally in compliance with the general schedule of realization of the S.E.N.S.I.B. project and with the perspectives announced in 2005. Factors of sensitivity were identified in diverse circles ( thematic studies) and methods and specific tools of the project are developed. 14 publications (reviews and congress) and 9 I.R.S.N. reports were produced. An international work group was launched to the I.R.S.N. initiative. The web site of S.E.N.S.I.B. on the I.R.S.N. scientific site was built. The S.E.N.S.I.B. project receives a financial participation of the Ademe. (N.C.)

An NF-Y-dependent switch of positive and negative histone methyl marks on CCAAT promoters.

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Giacomo Donati

Full Text Available BACKGROUND: Histone tails have a plethora of different post-translational modifications, which are located differently in "open" and "closed" parts of genomes. H3K4me3/H3K79me2 and H4K20me3 are among the histone marks associated with the early establishment of active and inactive chromatin, respectively. One of the most widespread promoter elements is the CCAAT box, bound by the NF-Y trimer. Two of NF-Y subunits have an H2A-H2B-like structure. PRINCIPAL FINDINGS: We established the causal relationship between NF-Y binding and positioning of methyl marks, by ChIP analysis of mouse and human cells infected with a dominant negative NF-YA: a parallel decrease in NF-Y binding, H3K4me3, H3K79me2 and transcription was observed in promoters that are dependent upon NF-Y. On the contrary, changes in the levels of H3K9-14ac were more subtle. Components of the H3K4 methylating MLL complex are not recruited in the absence of NF-Y. As for repressed promoters, NF-Y removal leads to a decrease in the H4K20me3 mark and deposition of H3K4me3. CONCLUSIONS: Two relevant findings are reported: (i NF-Y gains access to its genomic locations independently from the presence of methyl histone marks, either positive or negative; (ii NF-Y binding has profound positive or negative consequences on the deposition of histone methyl marks. Therefore NF-Y is a fundamental switch at the heart of decision between gene activation and repression in CCAAT regulated genes.

Determinación de la condición saturada y seca superficialmente (S.S.S. de agregados orgánicos para hormigón ligero

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Jaime Salazar Contreras

1988-01-01

Full Text Available Como parte del provecto de grado titulado "DOSIFICACION DE HORMIGONES LIGEROS UTILIZANDO COMO ARIDO LA CASCARILLA DE CAFE II PARTE", se desarrolló un procedimiento para determinar la condición saturada y seca superficialmente (S.S.S. de la cascarilla de café debido a que no existe ninguna literatura técnica que establezca los pasos a seguir para hallar la condición s.s.s de agregados ligeros, como si la hay para los agregados tradicionales del hormigón. Puesto que los agregados orgánicos presentan una elevada absorción, se hace necesario determinar un procedimiento de ensaya que permita obtener la condición s.s.s., del agregado de una manera precisa y más confiable que la obtenida mediante la inspección visual, procedimiento éste utilizado hasta ahora en el diseño de mezclas para los agregados ligeros de naturaleza orgánica. El ensayo consiste básicamente en someter a un proceso de secado una muestra de cascarilla saturada hasta que desaparece el agua libre contenida en ella, hecho que se manifiesta por la variación de la temperatura del bulbo húmedo medida por un termómetro colocado en el centro de la muestra; la humedad determinada en este momento corresponde a la condición s.s.s. de la cascarilla, valor éste que se utilizará posteriormente para determinar las propiedades físicas requeridas para el diseño y en especial para establecer con gran aproximación la relación agua-cemento (A/c parámetro fundamental que rige la resistencia del hormigón. Estos ensayos se realizaron en el laboratorio de Ingeniería Agrícola de la Universidad Nacional de Bogotá

’n Retoriese analise van Romeine 9:1–10:4

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A.H. (Andries Snyman

2015-06-01

Full Text Available Die artikel is ’n poging om Paulus se retoriese strategie uit die teks self te rekonstrueer, eerder as om ’n klassieke of moderne retoriese model op die teks toe te pas. ’n Voorstel virso ’n teksgesentreerde benadering word kortliks opgesom, gevolg deur ’n beskrywing van die retoriese situasie wat Paulus in die brief wil ondersoek. Daar word geargumenteer dat Romeine 9:1–10:4 ’n integrale deel van Paulus se retoriese strategie vorm met die doel om sy gehoor te oortuig om sy siening van God se verlossingsplan, asook sy beoogde sending na Spanje te steun. In die proses van oorreding gebruik hy verskillende soorte argumente en retoriese tegnieke om die trefkrag van sy kommunikasie te verhoog. Die gevolgtrekkingis dat ’n teksgesentreerde benadering (met fokus op die funksionele aspekte van die teks ’n beter alternatief as die bestaande benaderings (met fokus op die formele aspekte van die teks bied. A rhetorical analysis of Romans 9:1-10:4. This article is an attempt to reconstruct Paul’s rhetorical strategy from the text itself, rather than applying ancient or modern rhetorical models to his letters. A proposal for such a text-centred approach is briefly summarised, followed by a discussion of the rhetorical situation that Paul wants to address in this letter. It is argued that Romans 9:1–10:4 forms an integral part of his rhetorical strategy, aimed at persuading his audience in Rome to support his view on God’s plan of salvationas well as his forthcoming mission to Spain. In the process of persuasion Paul uses various types of argument and rhetorical techniques to enhance the impact of his communication.The conclusion is that a text-centred approach (with its focus on the functional aspects of the text provides a better alternative to existing approaches (which focus on the formal aspects of the text.

Enrichment of 15N and 10B isotopes by chemical exchange process

International Nuclear Information System (INIS)

D'Souza, A.B.; Sonwalkar, A.S.; Subrahmanyam, B.V.; Valladares, B.A.

1994-01-01

Many processes are available for separation of stable isotopes like distillation, chemical exchange, thermal diffusion, gaseous diffusion, centrifuge etc. Chemical exchange process is eminently suitable for separation of isotopes of light elements. Work done on separation and enrichment of two of the stable isotopes viz. 15 N and 10 B in Chemical Engineering Division is presented. 15 N is widely used as a tracer in agricultural research and 10 B is used in nuclear industry as control rod material, soluble reactor poison, neutron detector etc. The work on 15 N isotope resulted in a pilot plant, which was the only source of this material in the country for many years and later it was translated into a production plant as M/s. RCF Ltd. The work done on the ion-exchange process for enrichment of 10 B isotope which is basically a chemical exchange process, is now being updated into a pilot plant to produce enriched 10 B to be used as soluble reactor poison. (author)

Difluoro-lambda(5)-phosphinonitrile F(2)P[triple bond]N: matrix isolation and photoisomerization into FP=NF.

Science.gov (United States)

Zeng, Xiaoqing; Beckers, Helmut; Willner, Helge

2009-01-01

Splendid isolation: Monomeric phosphazene F(2)PN ((1)A(1)) was prepared for the first time through irradiation of F(2)PN(3) in an argon matrix with an ArF excimer laser (lambda=193 nm). Upon subsequent irradiation with a high-pressure mercury arc lamp (lambda=255 nm), F(2)PN undergoes a 1,2-fluorine shift to give iminophosphane cis-FP=NF.

Late-phase synthesis of I��B�� insulates the TLR4-activated canonical NF-��B pathway from noncanonical NF-��B signaling in macrophages

OpenAIRE

Chatterjee, Budhaditya; Banoth, Balaji; Mukherjee, Tapas; Taye, Nandaraj; Vijayaragavan, Bharath; Chattopadhyay, Samit; Gomes, James; Basak, Soumen

2016-01-01

The nuclear factor ��B (NF-��B) transcription factors coordinate the inflammatory immune response during microbial infection. Pathogenic substances engage canonical NF-��B signaling through the heterodimer RelA:p50, which is subjected to rapid negative feedback by inhibitor of ��B�� (I��B��). The noncanonical NF-��B pathway is required for the differentiation of immune cells; however, crosstalk between both pathways can occur. Concomitantly activated noncanonical signaling generates p52 from ...

Classical NF-κB Metabolically Reprograms Sarcoma Cells Through Regulation of Hexokinase 2

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Priya Londhe

2018-04-01

Full Text Available BackgroundMetabolic reprogramming has emerged as a cancer hallmark, and one of the well-known cancer-associated metabolic alterations is the increase in the rate of glycolysis. Recent reports have shown that both the classical and alternative signaling pathways of nuclear factor κB (NF-κB play important roles in controlling the metabolic profiles of normal cells and cancer cells. However, how these signaling pathways affect the metabolism of sarcomas, specifically rhabdomyosarcoma (RMS and osteosarcoma (OS, has not been characterized.MethodsClassical NF-κB activity was inhibited through overexpression of the IκBα super repressor of NF-κB in RMS and OS cells. Global gene expression analysis was performed using Affymetrix GeneChip Human Transcriptome Array 2.0, and data were interpreted using gene set enrichment analysis. Seahorse Bioscience XFe24 was used to analyze oxygen consumption rate as a measure of aerobic respiration.ResultsInhibition of classical NF-κB activity in sarcoma cell lines restored alternative signaling as well as an increased oxidative respiratory metabolic phenotype in vitro. In addition, microarray analysis indicated that inhibition of NF-κB in sarcoma cells reduced glycolysis. We showed that a glycolytic gene, hexokinase (HK 2, is a direct NF-κB transcriptional target. Knockdown of HK2 shifted the metabolic profile in sarcoma cells away from aerobic glycolysis, and re-expression of HK2 rescued the metabolic shift induced by inhibition of NF-κB activity in OS cells.ConclusionThese findings suggest that classical signaling of NF-κB plays a crucial role in the metabolic profile of pediatric sarcomas potentially through the regulation of HK2.

Spironolactone induces apoptosis and inhibits NF-kappaB independent of the mineralocorticoid receptor

DEFF Research Database (Denmark)

Sønder, Søren Ulrik Salling; Woetmann, Anders; Odum, Niels

2006-01-01

mononuclear cells (MNC). To elucidate the mechanism behind SPIR's apoptotic effect, we investigated the relation between apoptosis and cytokine suppression for SPIR along with the apoptosis-inducing and antiinflammatory drug sulfasalazine (SFZ). Using human MNC, we found that SPIR and SFZ, at concentrations...... 10 and 1000 muM, respectively, significantly increased both apoptosis and cell death. Production of inflammatory cytokines was significantly reduced by 3 to 30 muM SPIR and by 300 to 1000 muM SFZ. We also found that 0.4 muM SPIR and 300 muM SFZ significantly reduced the activity of NF......-kappaB, a transcription factor involved in both apoptosis and immunoinflammation. ALDO, the MR antagonist, eplerenone, and the SPIR metabolite, 7alpha-thiomethyl-spironolactone, slightly reduced NF-kappaB activity, but they did not interfere with SPIR's effect, showing that MR binding is not involved in SPIR...

Salicortin inhibits osteoclast differentiation and bone resorption by down-regulating JNK and NF-κB/NFATc1 signaling pathways

Energy Technology Data Exchange (ETDEWEB)

Nie, Shaobo [Department of Orthopaedics, PLA General Hospital, Beijing 100853 (China); Xu, Jiawei [Department of Orthopaedics, Shanghai Ninth People' s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011 (China); Zhang, Chenghua [Department of Orthopaedics, Changle County Hospital of Traditional Chinese Medicine, Weifang 262400 (China); Xu, Chen [Department of Orthopaedics, Shanghai Ninth People' s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011 (China); Liu, Ming, E-mail: ming_li4717@sina.com [Department of Orthopaedics, Shanghai Ninth People' s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011 (China); Yu, Degang, E-mail: ydg163@126.com [Department of Orthopaedics, Shanghai Ninth People' s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011 (China)

2016-01-29

Receptor activator of nuclear factor (NF)-κB ligand (RANKL)-activated signaling is essential for osteoclast differentiation, activation, and survival. Salicortin is a phenolic glycoside that has been isolated from many plants such as Populus and Salix species, and has been shown to have anti-amnesic and anti-adipogenic effects. In this study, we investigated the effect of salicortin on RANKL-induced osteoclasts formation, bone resorption, and activation of osteoclast-related signaling pathways. Salicortin suppressed RANKL-induced osteoclastogenesis in bone marrow macrophage cultures in a dose-dependent manner, and inhibited osteoclastic bone resorption activity without any cytotoxicity. Salicortin inhibited RANKL-induced c-Jun N-terminal kinase and NF-κB activation, concomitant with retarded IκBα phosphorylation and inhibition of p65 nuclear translocation, leading to impaired transcription of nuclear factor of activated T cells c1 (NFATc1) and expression of osteoclastic-specific genes. Taken together, our findings demonstrate that salicortin inhibits NF-κB and NFATc1 activation, leading to attenuation of osteoclastogenesis and bone resorption. Thus, salicortin may be of interest in developments of treatment for osteoclast related diseases. - Highlights: • Salicortin suppresses osteoclastogenesis in vitro. • Salicortin impairs the JNK and NF-κB/NFATc1 signaling pathway. • Salicortin may be of interest in developments of osteoporosis treatment.

Salicortin inhibits osteoclast differentiation and bone resorption by down-regulating JNK and NF-κB/NFATc1 signaling pathways

International Nuclear Information System (INIS)

Nie, Shaobo; Xu, Jiawei; Zhang, Chenghua; Xu, Chen; Liu, Ming; Yu, Degang

2016-01-01

Receptor activator of nuclear factor (NF)-κB ligand (RANKL)-activated signaling is essential for osteoclast differentiation, activation, and survival. Salicortin is a phenolic glycoside that has been isolated from many plants such as Populus and Salix species, and has been shown to have anti-amnesic and anti-adipogenic effects. In this study, we investigated the effect of salicortin on RANKL-induced osteoclasts formation, bone resorption, and activation of osteoclast-related signaling pathways. Salicortin suppressed RANKL-induced osteoclastogenesis in bone marrow macrophage cultures in a dose-dependent manner, and inhibited osteoclastic bone resorption activity without any cytotoxicity. Salicortin inhibited RANKL-induced c-Jun N-terminal kinase and NF-κB activation, concomitant with retarded IκBα phosphorylation and inhibition of p65 nuclear translocation, leading to impaired transcription of nuclear factor of activated T cells c1 (NFATc1) and expression of osteoclastic-specific genes. Taken together, our findings demonstrate that salicortin inhibits NF-κB and NFATc1 activation, leading to attenuation of osteoclastogenesis and bone resorption. Thus, salicortin may be of interest in developments of treatment for osteoclast related diseases. - Highlights: • Salicortin suppresses osteoclastogenesis in vitro. • Salicortin impairs the JNK and NF-κB/NFATc1 signaling pathway. • Salicortin may be of interest in developments of osteoporosis treatment.

Mycobacterium leprae induces NF-κB-dependent transcription repression in human Schwann cells

International Nuclear Information System (INIS)

Pereira, Renata M.S.; Calegari-Silva, Teresa Cristina; Hernandez, Maristela O.; Saliba, Alessandra M.; Redner, Paulo; Pessolani, Maria Cristina V.; Sarno, Euzenir N.; Sampaio, Elizabeth P.; Lopes, Ulisses G.

2005-01-01

Mycobacterium leprae, the causative agent of leprosy, invades peripheral nerve Schwann cells, resulting in deformities associated with this disease. NF-κB is an important transcription factor involved in the regulation of host immune antimicrobial responses. We aimed in this work to investigate NF-κB signaling pathways in the human ST88-14 Schwannoma cell line infected with M. leprae. Gel shift and supershift assays indicate that two NF-κB dimers, p65/p50 and p50/p50, translocate to the nucleus in Schwann cells treated with lethally irradiated M. leprae. Consistent with p65/p50 and p50/p50 activation, we observed IκB-α degradation and reduction of p105 levels. The nuclear translocation of p50/p50 complex due to M. leprae treatment correlated with repression of NF-κB-driven transcription induced by TNF-α. Moreover, thalidomide inhibited p50 homodimer nuclear translocation induced by M. leprae and consequently rescues Schwann cells from NF-κB-dependent transcriptional repression. Here, we report for the first time that M. leprae induces NF-κB activation in Schwann cells and thalidomide is able to modulate this activation

Substances released from probiotic Lactobacillus rhamnosus GR-1 potentiate NF-κB activity in Escherichia coli-stimulated urinary bladder cells.

Science.gov (United States)

Karlsson, Mattias; Scherbak, Nikolai; Khalaf, Hazem; Olsson, Per-Erik; Jass, Jana

2012-11-01

Lactobacillus rhamnosus GR-1 is a probiotic bacterium used to maintain urogenital health. The putative mechanism for its probiotic effect is by modulating the host immunity. Urinary tract infections (UTI) are often caused by uropathogenic Escherichia coli that frequently evade or suppress immune responses in the bladder and can target pathways, including nuclear factor-kappaB (NF-κB). We evaluated the role of L. rhamnosus GR-1 on NF-κB activation in E. coli-stimulated bladder cells. Viable L. rhamnosus GR-1 was found to potentiate NF-κB activity in E. coli-stimulated T24 bladder cells, whereas heat-killed lactobacilli demonstrated a marginal increase in NF-κB activity. Surface components released by trypsin- or LiCl treatment, or the resultant heat-killed shaved lactobacilli, had no effect on NF-κB activity. Isolation of released products from L. rhamnosus GR-1 demonstrated that the induction of NF-κB activity was owing to released product(s) with a relatively large native size. Several putative immunomodulatory proteins were identified, namely GroEL, elongation factor Tu and NLP/P60. GroEL and elongation factor Tu have previously been shown to elicit immune responses from human cells. Isolating and using immune-augmenting substances produced by lactobacilli is a novel strategy for the prevention or treatment of UTI caused by immune-evading E. coli. © 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

Ultrasound surface treatment of Kh18N10T steel with different structural state. Ul'trazvukovaya poverkhnostnaya obrabotka stali Kh18N10T s razlichnym strukturnym sostoyaniem

Energy Technology Data Exchange (ETDEWEB)

Aksenov, V K; Danilov, P A; Mats, A V; Netesov, V M; Yaes, A A [AN Ukrainskoj SSR, Kharkov (Ukrainian SSR). Fiziko-Tekhnicheskij Inst.

1989-09-01

Ultrasound surface treatment (USST) is studied for its effect on the structure and mechanical-and-physical properties of Kh18N10T steel with different prehistory. It is shown that surface treatment may both increase and decrease steel microhardness.

Effect of N-Feruloylserotonin and Methotrexate on Severity of Experimental Arthritis and on Messenger RNA Expression of Key Proinflammatory Markers in Liver

Directory of Open Access Journals (Sweden)

Ľudmila Pašková

2016-01-01

Full Text Available Rheumatoid arthritis (RA is a chronic inflammatory disease, leading to progressive destruction of joints and extra-articular tissues, including organs such as liver and spleen. The purpose of this study was to compare the effects of a potential immunomodulator, natural polyphenol N-feruloylserotonin (N-f-5HT, with methotrexate (MTX, the standard in RA therapy, in the chronic phase of adjuvant-induced arthritis (AA in male Lewis rats. The experiment included healthy controls (CO, arthritic animals (AA, AA given N-f-5HT (AA-N-f-5HT, and AA given MTX (AA-MTX. N-f-5HT did not affect the body weight change and clinical parameters until the 14th experimental day. Its positive effect was rising during the 28-day experiment, indicating a delayed onset of N-f-5HT action. Administration of either N-f-5HT or MTX caused reduction of inflammation measured as the level of CRP in plasma and the activity of LOX in the liver. mRNA transcription of TNF-α and iNOS in the liver was significantly attenuated in both MTX and N-f-5HT treated groups of arthritic rats. Interestingly, in contrast to MTX, N-f-5HT significantly lowered the level of IL-1β in plasma and IL-1β mRNA expression in the liver and spleen of arthritic rats. This speaks for future investigations of N-f-5HT as an agent in the treatment of RA in combination therapy with MTX.

Chemisorption-induced n-doping of MoS2 by oxygen

International Nuclear Information System (INIS)

Qi, Long; Wang, Ying; Wu, Yihong; Shen, Lei

2016-01-01

Both chemisorption and physisorption affect the electronic properties of two-dimensional materials, such as MoS 2 , but it remains a challenge to probe their respective roles experimentally. Through repeated in-situ electrical measurements of few-layer MoS 2 field-effect transistors in an ultrahigh vacuum system with well-controlled oxygen partial pressure (6 × 10 −8 mbar–3 × 10 −7 mbar), we were able to study the effect of chemisorption on surface defects separately from physically adsorbed oxygen molecules. It is found that chemisorption of oxygen results in n-doping in the channel but negligible effect on mobility and on/off ratio of the MoS 2 transistors. These results are in disagreement with the previous reports on p-doping and degradation of the device's performance when both chemisorption and physisorption are present. Through the analysis of adsorption-desorption kinetics and the first-principles calculations of electronic properties, we show that the experimentally observed n-doping effect originates from dissociative adsorption of oxygen at the surface defects of MoS 2 , which lowers the conduction band edge locally and makes the MoS 2 channel more n-type-like as compared to the as-fabricated devices

Transforming growth factor-beta 1 (TGF-beta1) promotes IL-2 mRNA expression through the up-regulation of NF-kappaB, AP-1 and NF-AT in EL4 cells.

Science.gov (United States)

Han, S H; Yea, S S; Jeon, Y J; Yang, K H; Kaminski, N E

1998-12-01

Transforming growth factor beta1 (TGF-beta1) has been previously shown to modulate interleukin 2 (IL-2) secretion by activated T-cells. In the present studies, we determined that TGF-beta1 induced IL-2 mRNA expression in the murine T-cell line EL4, in the absence of other stimuli. IL-2 mRNA expression was significantly induced by TGF-beta1 (0.1-1 ng/ml) over a relatively narrow concentration range, which led to the induction of IL-2 secretion. Under identical condition, we examined the effect of TGF-beta1 on the activity of nuclear factor AT (NF-AT), nuclear factor kappaB (NF-kappaB), activator protein-1 (AP-1) and octamer, all of which contribute to the regulation of IL-2 gene expression. Electrophoretic mobility shift assays showed that TGF-beta1 markedly increased NF-AT, NF-kappaB and AP-1 binding to their respective cognate DNA binding sites, whereas octamer binding remained constant, as compared with untreated cells. Employing a reporter gene expression system with p(NF-kappaB)3-CAT, p(NF-AT)3-CAT and p(AP-1)3-CAT, TGF-beta1 treatment of transfected EL4 cells induced a dose-related increase in chloramphenicol acetyltransferase activity that correlated well with the DNA binding profile found in the electrophoretic mobility shift assay studies. These results show that TGF-beta1, in the absence of any additional stimuli, up-regulates the activity of key transcription factors involved in IL-2 gene expression, including NF-AT, NF-kappaB and AP-1, to help promote IL-2 mRNA expression by EL4 cells.

Ethanol Decreases Inflammatory Response in Human Lung Epithelial Cells by Inhibiting the Canonical NF-kB-Pathway

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Katharina Mörs

2017-08-01

Full Text Available Background/Aims: Alcohol (ethanol, EtOH as significant contributor to traumatic injury is linked to suppressed inflammatory response, thereby influencing clinical outcomes. Alcohol-induced immune-suppression during acute inflammation (trauma was linked to nuclear factor-kappaB (NF-ĸB. Here, we analyzed alcohol`s effects and mechanisms underlying its influence on NF-ĸB-signaling during acute inflammation in human lung epithelial cells. Methods: A549-cells were stimulated with interleukin (IL-1β, or sera from trauma patients (TP or healthy volunteers, with positive/negative blood alcohol concentrations (BAC, and subsequently exposed to EtOH (170 Mm, 1h. IL-6-release and neutrophil adhesion to A549 were analyzed. Specific siRNA-NIK mediated downregulation of non-canonical, and IKK-NBD-inhibition of canonical NF-ĸB signaling were performed. Nuclear levels of activated p50 and p52 NF-ĸB-subunits were detected using TransAm ELISA. Results: Both stimuli significantly induced IL-6-release (39.79±4.70 vs. 0.58±0.8 pg/ml and neutrophil adhesion (132.30±8.80 vs. 100% control, p<0.05 to A549-cells. EtOH significantly decreased IL-6-release (22.90±5.40, p<0.05 and neutrophil adherence vs. controls (105.40±14.5%, p<0.05. IL-1β-induced significant activation of canonical/p50 and non-canonical/p52 pathways. EtOH significantly reduced p50 (34.90±23.70 vs. 197.70±36.43, p<0.05 not p52 activation. Inhibition of canonical pathway was further increased by EtOH (less p50-activation, while p52 remained unaltered. Inhibition of non-canonical pathway was unchanged by EtOH. Conclusion: Here, alcohol`s anti-inflammatory effects are mediated via decreasing nuclear levels of activated p50-subunit and canonical NF-ĸB signaling pathway.

Síndrome de microdeleción en la neurofibromatosis tipo- 1: presentación de un caso Microdeletion syndrome in neurofibromatosis type-1: a case report